Douglas College Human Anatomy and Physiology I

Preface

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Preface2

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01_01ab_Gross_and_Microscopic_Anatomy

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101_Levels_of_Org_in_Body

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102_Organ_Systems_of_BodyPage2

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102_Organ_Systems_of_BodyPage1

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103_Metabolism

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metabolic

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01_05_Marathon_Runners

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01_06_Extreme_Heat

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01_07_Harsh_Conditions

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105_Negative_Feedback_Loops

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H2Ocon

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106_Pregnancy-Positive_Feedback

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107_Regions_of_Human_Body_new

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108_Directional_Terms

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109_Planes_of_Body

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110_Dorsal_Ventral_Body_Cavities

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111_Abdominal_Quadrant_Regions

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112_Serous_Membrane_new

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Print

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Print

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Figure_10_05_03

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Print

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Print

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Figure_10_06_02a

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Figure_10_06_03a

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Figure_10_06_04a

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Figure_10_06_05a

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Figure_10_06_06a

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Figure_10_06_07a

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Figure_10_06_08a

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Figure_10_06_09a

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Figure_10_06_10a

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Figure_10_06_11a

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Figure_10_06_12a

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Figure_10_06_13a

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200_DNA_Double_Helix-02

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201_Elements_of_the_Human_Body-01

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202_Two_Models_of_Atomic_Structure

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203_Periodic_Table-02

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ptable

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204_Isotopes_of_Hydrogen-01

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206_Electron_Shells-01

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electenergy

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207_Ionic_Bonding-01

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208_Covalent_Bonding-01

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209_Polar_Covalent_Bonds_in_a_Water_Molecule

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210_Hydrogen_Bonds_Between_Water_Molecules-01

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213_Dehydration_Synthesis_and_Hydrolysis-01

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214_Dissociation_of_Sodium_Chloride_in_Water-01

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215_Acids_and_Bases-01

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216_pH_Scale-01

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217_Five_Important_Monosaccharides-01

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218_Three_Important_Disaccharides-01

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219_Three_Important_Polysaccharides-01

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disaccharide

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220_Triglycerides-01

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221_Fatty_Acids_Shapes-01

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222_Other_Important_Lipids-01

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223_Structure_of_an_Amino_Acid-01

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224_Peptide_Bond-01

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225_Peptide_Bond-01

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227_Steps_in_an_Enzymatic_Reaction-01

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228_Nucleotides-01

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229_Nucleotides-01

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230_Structure_of_Adenosine_Triphosphate_ATP-01

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0300_Flourescence_Stained_new

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0301_Phospholipid_Structure

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0302_Phospholipid_Bilayer

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0303_Lipid_Bilayer_With_Various_Components

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diffusion

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0305_Simple_Diffusion_Across_Plasma_Membrane

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0306_Facilitated_Diffusion

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0307_Osmosis

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0346_Concentration_of_Solutions

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0308_Sodium_Potassium_Pump

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0309_Three_Forms_of_Endocytosis

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0310_Exocytosis

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pcells

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0311_Pancreatic_Cells_Micrograph

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0312_Animal_Cell_and_Components

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0313_Endoplasmic_Reticulum

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0314_Golgi_Apparatus

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endomembrane1

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0315_Mitochondrion_new

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0318_Nucleus

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0319_Multinucleate_Muscle_Tissue_Micrograph

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0320_RBC_Extruding_Nucleus_Micrograph

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0321_DNA_Macrostructure

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0322_DNA_Nucleotides

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0324_DNA_Translation_and_Codons

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0325_Transcription

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0326_Splicing

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0327_Translation

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0328_Transcription-translation_Summary

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ribosome

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0329_Cell_Cycle

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0330_Homologous_Pair_of_Chromosomes

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0331_Stages_of-_Mitosis_and_Cytokinesis-e1459277007217

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0332_Cell_Cycle_With_Cyclins_and_Checkpoints

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mitosis

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0337_Hematopoiesis_new

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0338_RNA_Polymerase_Binding

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422_Feature_Stem_Cell_new

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401_Types_of_Tissue

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419_420_421_Table_04_01_updated

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413_Types_of_Membranes

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402_Types_of_Cell_Junctions_new

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403_Epithelial_Tissue

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404_Goblet_Cell_new

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404b_Goblet_Cell_new

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423_Table_04_02_Summary_of_Epithelial_Tissue_CellsN

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etissues

barkerj1 — Sun, 16 Apr 2017 00:11:08 +0000

406_Types_of_Glands

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405_Modes_of_Secretion_by_Glands_updated

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407_Sebaceous_Glands

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408_Connective_Tissue

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409_Adipose_Tissue

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410_Reticular_Tissue

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411_Reg_Dense-Irregular_Dense

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412_Types_of_Cartilage-new

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424_Blood_A_Fluid_Connective_Tissue-new

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cardiovascular_new

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10quiz

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414_Skeletal_Smooth_Cardiac

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musctissue

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415_Neuron

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416_Nervous_Tissue-new

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layers

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501_Structure_of_the_skin

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502ab_Thin_Skin_versus_Thick_Skin

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503_Epidermis

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Epidermis

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502_Layers_of_epidermis

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505_Cells_of_the_Epidermis

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basal

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506_Layers_of_the_Dermis

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504_Melanocytes

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508_Moles

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506_Hair

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511_Hair_Follicle

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follicle

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507_Nails

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nails

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508_Figure_5.08_Eccrine_gland

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sweating

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514_Light_Micrograph_of_a_Meissner_Corpuscle

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515_Thermoregulation

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600_Child_Looking_at_Bones

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617_Bone_Support_Movement

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618_Bones_Protect_Brain

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619_Red_and_Yellow_Bone_Marrow

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601_Bone_Classification

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603_Anatomy_of_a_Long_Bone

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607_Periosteum_and_Endosteum

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621_Anatomy_of_a_Flat_Bone

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602_Bone_Markings

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604_Bone_cells

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624_Diagram_of_Compact_Bone-new

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606_Spongy_Bone

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610_Feature_Pagets_Disease

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609_Body_Supply_to_the_Bone

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microbone

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611_Intramembraneous_Ossification

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608_Endochrondal_Ossification

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622_Longitudinal_Bone_Growth

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623_Epiphyseal_Plate-Line

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612_Types_of_Fractures

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613_Stages_of_Fracture_Repair

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fracturequiz

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700_Lateral_View_of_Skull-01

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701_Axial_Skeleton-01

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703_Parts_of_Skull-01

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skull1

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704_Skull-01

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705_Lateral_View_of_Skull-01

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708_Temporal_Bone

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730_Posterior_View_Skull

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711_Maxilla

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726_Mandible

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712_Hyoid_Bone

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715_Vertebral_Column

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718_Vertebra

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716_Intervertebral_Disk

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723_Cervical_Vertebrae

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719_Thoracic_Vertebra

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732_Thoracic_Vertebra_and_Rib

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725_Lumbar_Vertebrae

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720_Sacrum_and_Coccyx

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diskslip

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728_Herniated_Disk

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721_Rib_Cage

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702_Newborn_Skull-01

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skullbones

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800_Dancer

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801_Appendicular_Skeleton

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802_Pectoral_Girdle

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803_The_Scapula

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804_Humerus_and_Elbow

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805_Ulna_and_Radius

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fractures

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806_Hand_and_Wrist

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814_Radiograph_of_Hand

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815_The_Carpal_Tunnel

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816_Hand_Gripping

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handbone

barkerj1 — Sun, 16 Apr 2017 00:13:00 +0000

807_Pelvis

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808_Hip_Bone

barkerj1 — Sun, 16 Apr 2017 00:13:03 +0000

809_Male_Female_Pelvic_Girdle

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810_Femur_and_Patella

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midfemur

barkerj1 — Sun, 16 Apr 2017 00:13:05 +0000

kneesurgery

barkerj1 — Sun, 16 Apr 2017 00:13:06 +0000

818_Femur_Q_Angle

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811_Tibia_and_fibula

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812_Bones_of_the_Foot

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footbones

barkerj1 — Sun, 16 Apr 2017 00:13:11 +0000

bunion

barkerj1 — Sun, 16 Apr 2017 00:13:12 +0000

819_Embryo_at_Seven_Weeks

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limbbuds

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900_Girl_Kayaking

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901_Skull_Sutures

barkerj1 — Sun, 16 Apr 2017 00:13:18 +0000

902_Intervertebral_Disk-02

barkerj1 — Sun, 16 Apr 2017 00:13:19 +0000

903_Multiaxial_Joint

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904_Fibrous_Joints

barkerj1 — Sun, 16 Apr 2017 00:13:22 +0000

905_The_Newborn_Skull

barkerj1 — Sun, 16 Apr 2017 00:13:23 +0000

906_Cartiliginous_Joints

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childhand

barkerj1 — Sun, 16 Apr 2017 00:13:26 +0000

907_Synovial_Joints

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908_Bursa

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909_Types_of_Synovial_Joints

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synjoints

barkerj1 — Sun, 16 Apr 2017 00:13:33 +0000

0910_Oateoarthritis_Hip

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gout

barkerj1 — Sun, 16 Apr 2017 00:13:36 +0000

hipreplace

barkerj1 — Sun, 16 Apr 2017 00:13:37 +0000

rheuarthritis

barkerj1 — Sun, 16 Apr 2017 00:13:38 +0000

anatomical

barkerj1 — Sun, 16 Apr 2017 00:13:39 +0000

911_Body_MovementsPage-1-865x1024

barkerj1 — Sun, 16 Apr 2017 00:13:41 +0000

911_Body_MovementsPage-2-948x1024

barkerj1 — Sun, 16 Apr 2017 00:13:42 +0000

917_Knee_Joint

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flexext

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kneejoint1

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1000_Tennis_Player

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414_Skeletal_Smooth_Cardiac-1

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1007_Muscle_Fibes_large

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1022_Muscle_Fibers_small

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micromacro

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1003_Thick_and_Thin_Filaments

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skelmuscfiber

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1009_Motor_End_Plate_and_Innervation

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1023_T-tubule

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1010a_Contraction_new

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1010b_Relaxation_new

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calciumrole

barkerj1 — Sun, 16 Apr 2017 00:14:00 +0000

1006_Sliding_Filament_Model_of_Muscle_Contraction

barkerj1 — Sun, 16 Apr 2017 00:14:01 +0000

1008_Skeletal_Muscle_Contraction

barkerj1 — Sun, 16 Apr 2017 00:14:02 +0000

1016_Muscle_Metabolism

barkerj1 — Sun, 16 Apr 2017 00:14:04 +0000

1015_Types_of_Contraction_new

barkerj1 — Sun, 16 Apr 2017 00:14:05 +0000

1011_Muscle_Length_and_Tension

barkerj1 — Sun, 16 Apr 2017 00:14:06 +0000

1026_Marathoners

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1027_Hypertrophy

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1025_Atrophy

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1100_Body_in_Motion

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1101_Biceps_Muscle

barkerj1 — Sun, 16 Apr 2017 00:14:11 +0000

29218000742_8a42528d49_b

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29039288310_d592e23e18_b

barkerj1 — Sun, 16 Apr 2017 00:14:12 +0000

29294217976_3129be3d8a_b

barkerj1 — Sun, 16 Apr 2017 00:14:12 +0000

29249539951_42cc9f05bb_b

barkerj1 — Sun, 16 Apr 2017 00:14:13 +0000

29395645875_780905eb76_b

barkerj1 — Sun, 16 Apr 2017 00:14:13 +0000

29377723362_de29812d45_b

barkerj1 — Sun, 16 Apr 2017 00:14:13 +0000

1105_Anterior_and_Posterior_Views_of_Muscles

barkerj1 — Sun, 16 Apr 2017 00:14:16 +0000

1126_Understand_A_Muscle_from_the_Latin

barkerj1 — Sun, 16 Apr 2017 00:14:18 +0000

1111_Posterior_and_Side_Views_of_the_Neck

barkerj1 — Sun, 16 Apr 2017 00:14:20 +0000

1117_Muscles_of_the_Neck_and_Back

barkerj1 — Sun, 16 Apr 2017 00:14:22 +0000

1112_Muscles_of_the_Abdomen

barkerj1 — Sun, 16 Apr 2017 00:14:24 +0000

1113_The_Diaphragm

barkerj1 — Sun, 16 Apr 2017 00:14:26 +0000

1114_Thorax

barkerj1 — Sun, 16 Apr 2017 00:14:28 +0000

1118_Muscles_that_Position_the_Pectoral_Girdle

barkerj1 — Sun, 16 Apr 2017 00:14:30 +0000

1119_Muscles_that_Move_the_Humerus

barkerj1 — Sun, 16 Apr 2017 00:14:32 +0000

1129_Muscles_that_Moves_the_Humerus

barkerj1 — Sun, 16 Apr 2017 00:14:34 +0000

1120_Muscles_that_Move_the_Forearm

barkerj1 — Sun, 16 Apr 2017 00:14:36 +0000

1130_Muscles_that_Move_the_Forearm

barkerj1 — Sun, 16 Apr 2017 00:14:39 +0000

1122_Gluteal_Muscles_that_Move_the_Femur

barkerj1 — Sun, 16 Apr 2017 00:14:41 +0000

1132_Gluteal_Region_Muscles_that_Move_the_Femur

barkerj1 — Sun, 16 Apr 2017 00:14:45 +0000

1133_Thigh_Muscles_that_Moves_the_Femur_Tibia_and_Fibula

barkerj1 — Sun, 16 Apr 2017 00:14:49 +0000

1123_Muscles_of_the_Leg_that_Move_the_Foot_and_Toes

barkerj1 — Sun, 16 Apr 2017 00:14:51 +0000

1134_Muscles_that_Moves_the_Feet_and_Toes

barkerj1 — Sun, 16 Apr 2017 00:14:53 +0000

1900_Blood_cells

barkerj1 — Sun, 16 Apr 2017 00:14:56 +0000

1901_Composition_of_Blood

barkerj1 — Sun, 16 Apr 2017 00:14:58 +0000

normallevels

barkerj1 — Sun, 16 Apr 2017 00:14:58 +0000

1915_Table_19_01_Major_Blood_Components

barkerj1 — Sun, 16 Apr 2017 00:15:00 +0000

1902_Hemopoiesis

barkerj1 — Sun, 16 Apr 2017 00:15:01 +0000

1914_Table_19_3_1

barkerj1 — Sun, 16 Apr 2017 00:15:04 +0000

1903_Shape_of_Red_Blood_Cells

barkerj1 — Sun, 16 Apr 2017 00:15:07 +0000

1904_Hemoglobin

barkerj1 — Sun, 16 Apr 2017 00:15:08 +0000

1905_Erythrocyte_Life_Cycle

barkerj1 — Sun, 16 Apr 2017 00:15:10 +0000

1911_Sickle_Cells

barkerj1 — Sun, 16 Apr 2017 00:15:13 +0000

1906_Emigration

barkerj1 — Sun, 16 Apr 2017 00:15:15 +0000

1907_Granular_Leukocytes

barkerj1 — Sun, 16 Apr 2017 00:15:17 +0000

1908_Platelet_Development

barkerj1 — Sun, 16 Apr 2017 00:15:18 +0000

bloodslidesMG

barkerj1 — Sun, 16 Apr 2017 00:15:19 +0000

1916_Leukocyte_Key

barkerj1 — Sun, 16 Apr 2017 00:15:21 +0000

1909_Blood_Clotting

barkerj1 — Sun, 16 Apr 2017 00:15:22 +0000

coagulation

barkerj1 — Sun, 16 Apr 2017 00:15:24 +0000

1910_Erythroblastosis_Fetalis

barkerj1 — Sun, 16 Apr 2017 00:15:26 +0000

1912_Cross_Matching_Blood_Types

barkerj1 — Sun, 16 Apr 2017 00:15:28 +0000

1913_ABO_Blood_Groups

barkerj1 — Sun, 16 Apr 2017 00:15:30 +0000

2000_Human_Heart_Photo

barkerj1 — Sun, 16 Apr 2017 00:15:32 +0000

2001_Heart_Position_in_ThoraxN

barkerj1 — Sun, 16 Apr 2017 00:15:33 +0000

2003_Dual_System_of_Human_Circulation

barkerj1 — Sun, 16 Apr 2017 00:15:36 +0000

2004_Heart_Wall

barkerj1 — Sun, 16 Apr 2017 00:15:38 +0000

2005_Surface_Anatomy_of_the_Heart

barkerj1 — Sun, 16 Apr 2017 00:15:40 +0000

2006_Heart_Musculature

barkerj1 — Sun, 16 Apr 2017 00:15:42 +0000

2007_Ventricular_Muscle_Thickness

barkerj1 — Sun, 16 Apr 2017 00:15:44 +0000

2008_Internal_Anatomy_of_the_HeartN

barkerj1 — Sun, 16 Apr 2017 00:15:45 +0000

2010_Chordae_Tendinae_Papillary_Muscles

barkerj1 — Sun, 16 Apr 2017 00:15:47 +0000

2011_Heart_Valves

barkerj1 — Sun, 16 Apr 2017 00:15:49 +0000

2012_Blood_Flow_Relaxed_Ventricles

barkerj1 — Sun, 16 Apr 2017 00:15:50 +0000

2013_Blood_Flow_Contracted_Ventricles

barkerj1 — Sun, 16 Apr 2017 00:15:53 +0000

heartvalve

barkerj1 — Sun, 16 Apr 2017 00:15:54 +0000

2014ab_Coronary_Blood_Vessels

barkerj1 — Sun, 16 Apr 2017 00:15:56 +0000

2017abc_Cardiac_Muscle

barkerj1 — Sun, 16 Apr 2017 00:15:59 +0000

2018_Conduction_System_of_Heart

barkerj1 — Sun, 16 Apr 2017 00:16:02 +0000

2019_Cardiac_ConductionN

barkerj1 — Sun, 16 Apr 2017 00:16:04 +0000

2020_SA_Node_Tracing

barkerj1 — Sun, 16 Apr 2017 00:16:05 +0000

2026_Action_Potential_Heart_Contraction

barkerj1 — Sun, 16 Apr 2017 00:16:07 +0000

2021_ECG_Placement_of_Electrodes

barkerj1 — Sun, 16 Apr 2017 00:16:09 +0000

ECG

barkerj1 — Sun, 16 Apr 2017 00:16:10 +0000

2022_Electrocardiogram

barkerj1 — Sun, 16 Apr 2017 00:16:11 +0000

2023_ECG_Tracing_with_Heart_ContractionN

barkerj1 — Sun, 16 Apr 2017 00:16:13 +0000

2024_Cardiac_Arrhythmias

barkerj1 — Sun, 16 Apr 2017 00:16:16 +0000

abnormalECG-150x150

barkerj1 — Sun, 16 Apr 2017 00:16:17 +0000

2027_Phases_of_the_Cardiac_Cycle

barkerj1 — Sun, 16 Apr 2017 00:16:18 +0000

2028_Cardiac_Cycle_vs_Electrocardiogram

barkerj1 — Sun, 16 Apr 2017 00:16:20 +0000

2029_Cardiac_Cycle_vs_Heart_Sounds

barkerj1 — Sun, 16 Apr 2017 00:16:21 +0000

2030_Stethoscope_Placement

barkerj1 — Sun, 16 Apr 2017 00:16:23 +0000

2031_Factors_in_Cardiac_Output

barkerj1 — Sun, 16 Apr 2017 00:16:24 +0000

2032_Automatic_Innervation

barkerj1 — Sun, 16 Apr 2017 00:16:26 +0000

2033_Depolarization_in_Sinus_Rhythm

barkerj1 — Sun, 16 Apr 2017 00:16:27 +0000

2035_Factors_in_Stroke_Volume

barkerj1 — Sun, 16 Apr 2017 00:16:29 +0000

2036_Summary_of_Factors_in_Cardiac_Output

barkerj1 — Sun, 16 Apr 2017 00:16:31 +0000

2100_Arm_with_Bulging_Veins

barkerj1 — Sun, 16 Apr 2017 00:16:33 +0000

2101_Blood_Flow_Through_the_Heart

barkerj1 — Sun, 16 Apr 2017 00:16:35 +0000

2102_Comparison_of_Artery_and_Vein

barkerj1 — Sun, 16 Apr 2017 00:16:37 +0000

2103_Muscular_and_Elastic_Artery_Arteriole

barkerj1 — Sun, 16 Apr 2017 00:16:39 +0000

2104_Three_Major_Capillary_Types

barkerj1 — Sun, 16 Apr 2017 00:16:40 +0000

2105_Capillary_Bed

barkerj1 — Sun, 16 Apr 2017 00:16:41 +0000

2106_Large_Medium_Vein_Venule

barkerj1 — Sun, 16 Apr 2017 00:16:43 +0000

2142_Distribution_of_Blood_Flow

barkerj1 — Sun, 16 Apr 2017 00:16:44 +0000

2109_Systemic_Blood_Pressure

barkerj1 — Sun, 16 Apr 2017 00:16:46 +0000

2110_Pulse_Sites

barkerj1 — Sun, 16 Apr 2017 00:16:47 +0000

2111_Blood_Pressure_Graph

barkerj1 — Sun, 16 Apr 2017 00:16:49 +0000

2112_Vessel_Blood_Pressure_Relationships

barkerj1 — Sun, 16 Apr 2017 00:16:50 +0000

2114_Skeletal_Muscle_Vein_Pump

barkerj1 — Sun, 16 Apr 2017 00:16:52 +0000

2108_Capillary_ExchangeN

barkerj1 — Sun, 16 Apr 2017 00:16:53 +0000

2115_Vascular_Homeostasis_Flow_Art

barkerj1 — Sun, 16 Apr 2017 00:16:55 +0000

2116_Baroreceptor_Reflex_Flow_Art

barkerj1 — Sun, 16 Apr 2017 00:16:57 +0000

2117_Renin_Angiotensin_Aldosterone_Pathway

barkerj1 — Sun, 16 Apr 2017 00:16:59 +0000

2143_Mechanism_Regulating_Arteries_and_Veins

barkerj1 — Sun, 16 Apr 2017 00:17:01 +0000

CDCpodcast

barkerj1 — Sun, 16 Apr 2017 00:17:03 +0000

2118_Blood_Volume_Loss_and_Homeostasis

barkerj1 — Sun, 16 Apr 2017 00:17:04 +0000

2141_CircSyst_vs_OtherSystemsN

barkerj1 — Sun, 16 Apr 2017 00:17:06 +0000

arts1

barkerj1 — Sun, 16 Apr 2017 00:17:08 +0000

2119_Pulmonary_Circuit

barkerj1 — Sun, 16 Apr 2017 00:17:10 +0000

2120_Major_Systemic_Artery

barkerj1 — Sun, 16 Apr 2017 00:17:11 +0000

2121_Aorta

barkerj1 — Sun, 16 Apr 2017 00:17:13 +0000

2122_Common_Carotid_Artery

barkerj1 — Sun, 16 Apr 2017 00:17:15 +0000

2123_Arteries_of_the_Brain

barkerj1 — Sun, 16 Apr 2017 00:17:17 +0000

2124_Thoracic_Abdominal_Arteries

barkerj1 — Sun, 16 Apr 2017 00:17:18 +0000

2125_Thoracic_Abdominal_Arteries_Chart

barkerj1 — Sun, 16 Apr 2017 00:17:20 +0000

2126_Iliac_Artery_Branches_Chart

barkerj1 — Sun, 16 Apr 2017 00:17:23 +0000

2127_Thoracic_Upper_Limb_Arteries

barkerj1 — Sun, 16 Apr 2017 00:17:24 +0000

2128_Thoracic_Upper_Limb_Arteries_Chart

barkerj1 — Sun, 16 Apr 2017 00:17:26 +0000

2129ab_Lower_Limb_Arteries_Anterior_Posterior

barkerj1 — Sun, 16 Apr 2017 00:17:28 +0000

2130_Lower_Limb_Arteries_Chart

barkerj1 — Sun, 16 Apr 2017 00:17:30 +0000

veinsum

barkerj1 — Sun, 16 Apr 2017 00:17:32 +0000

2131_Major_Systematic_Veins

barkerj1 — Sun, 16 Apr 2017 00:17:34 +0000

2132_Thoracic_Abdominal_Veins

barkerj1 — Sun, 16 Apr 2017 00:17:36 +0000

2133_Head_and_Neck_Veins

barkerj1 — Sun, 16 Apr 2017 00:17:38 +0000

2134_Thoracic_Upper_Limb_Veins

barkerj1 — Sun, 16 Apr 2017 00:17:40 +0000

2135_Veins_Draining_into_Superior_Vena_Cava_Chart

barkerj1 — Sun, 16 Apr 2017 00:17:42 +0000

2140_FlowChart_Veins_into_VenaCava

barkerj1 — Sun, 16 Apr 2017 00:17:44 +0000

2136ab_Lower_Limb_Veins_Anterior_Posterior

barkerj1 — Sun, 16 Apr 2017 00:17:47 +0000

2137_Lower_Limb_Veins_Chart

barkerj1 — Sun, 16 Apr 2017 00:17:49 +0000

2138_Hepatic_Portal_Vein_System

barkerj1 — Sun, 16 Apr 2017 00:17:51 +0000

2200_The_Worldwide_AIDS_Epidemic

barkerj1 — Sun, 16 Apr 2017 00:17:52 +0000

lymphsystem

barkerj1 — Sun, 16 Apr 2017 00:17:53 +0000

2201_Anatomy_of_the_Lymphatic_System

barkerj1 — Sun, 16 Apr 2017 00:17:55 +0000

2202_Lymphatic_Capillaries

barkerj1 — Sun, 16 Apr 2017 00:17:56 +0000

2203_Lymphatic_Trunks_and_Ducts_System

barkerj1 — Sun, 16 Apr 2017 00:17:57 +0000

2204_The_Hematopoietic_System_of_the_Bone_Marrow_new

barkerj1 — Sun, 16 Apr 2017 00:17:58 +0000

immunecells

barkerj1 — Sun, 16 Apr 2017 00:18:00 +0000

2205_Bone_Marrow

barkerj1 — Sun, 16 Apr 2017 00:18:01 +0000

2206_The_Location_Structure_and_Histology_of_the_Thymus

barkerj1 — Sun, 16 Apr 2017 00:18:02 +0000

thymusMG

barkerj1 — Sun, 16 Apr 2017 00:18:03 +0000

2207_Structure_and_Histology_of_a_Lymph_Node

barkerj1 — Sun, 16 Apr 2017 00:18:05 +0000

lymphnodeMG

barkerj1 — Sun, 16 Apr 2017 00:18:05 +0000

2208_Spleen

barkerj1 — Sun, 16 Apr 2017 00:18:07 +0000

2209_Location_and_History_of_Tonsils

barkerj1 — Sun, 16 Apr 2017 00:18:08 +0000

tonsilMG

barkerj1 — Sun, 16 Apr 2017 00:18:09 +0000

2210_Mucosa_Associated_Lymphoid_Tissue_MALT_Nodule

barkerj1 — Sun, 16 Apr 2017 00:18:11 +0000

2215_Alpha-Beta_T_Cell_Receptor

barkerj1 — Sun, 16 Apr 2017 00:18:12 +0000

2214_Antigenic_Determinants

barkerj1 — Sun, 16 Apr 2017 00:18:12 +0000

2216_Antigen_Processing_and_Presentation

barkerj1 — Sun, 16 Apr 2017 00:18:13 +0000

2217_Differentiation_of_T_Cells_Within_the_Thymus

barkerj1 — Sun, 16 Apr 2017 00:18:15 +0000

2218_Clonal_Selection_and_Expansion_of_T_Lymphocytes

barkerj1 — Sun, 16 Apr 2017 00:18:16 +0000

2219_Pathogen_Presentation

barkerj1 — Sun, 16 Apr 2017 00:18:17 +0000

2220_Four_Chain_Structure_of_a_Generic_Antibody-IgG2-Structures

barkerj1 — Sun, 16 Apr 2017 00:18:18 +0000

2221_Five_Classes_of_Antibodies_new

barkerj1 — Sun, 16 Apr 2017 00:18:19 +0000

2222_Clonal_Selection_of_B_Cells

barkerj1 — Sun, 16 Apr 2017 00:18:21 +0000

2223_Primary_and_Secondary_Antibody_Respons_new

barkerj1 — Sun, 16 Apr 2017 00:18:22 +0000

immunity

barkerj1 — Sun, 16 Apr 2017 00:18:23 +0000

2224_T_and_B_Cell_Binding

barkerj1 — Sun, 16 Apr 2017 00:18:24 +0000

2225_HIV_Disease_Progression

barkerj1 — Sun, 16 Apr 2017 00:18:25 +0000

2226_IgA_Immunity

barkerj1 — Sun, 16 Apr 2017 00:18:26 +0000

2228_Immune_Hypersensitivity_new

barkerj1 — Sun, 16 Apr 2017 00:18:28 +0000

2229_Autoimmune_Disorders_Rheumatoid_Arthritis_and_Lupus

barkerj1 — Sun, 16 Apr 2017 00:18:34 +0000

2230_Erythroblastosis_Fetalis

barkerj1 — Sun, 16 Apr 2017 00:18:35 +0000

2231_Kaposis_Sacroma_Lesions

barkerj1 — Sun, 16 Apr 2017 00:18:37 +0000

2300_Mountain_Climbers

barkerj1 — Sun, 16 Apr 2017 00:18:38 +0000

2301_Major_Respiratory_Organs

barkerj1 — Sun, 16 Apr 2017 00:18:40 +0000

2302_External_Nose

barkerj1 — Sun, 16 Apr 2017 00:18:42 +0000

2303_Anatomy_of_Nose-Pharynx-Mouth-Larynx

barkerj1 — Sun, 16 Apr 2017 00:18:44 +0000

2304_Pseudostratified_Epithelium

barkerj1 — Sun, 16 Apr 2017 00:18:46 +0000

pseudoMG

barkerj1 — Sun, 16 Apr 2017 00:18:47 +0000

2305_Divisions_of_the_Pharynx

barkerj1 — Sun, 16 Apr 2017 00:18:48 +0000

2306_The_Larynx

barkerj1 — Sun, 16 Apr 2017 00:18:51 +0000

2307_Cartilages_of_the_Larynx

barkerj1 — Sun, 16 Apr 2017 00:18:52 +0000

2308_The_Trachea

barkerj1 — Sun, 16 Apr 2017 00:18:54 +0000

2309_The_Respiratory_Zone

barkerj1 — Sun, 16 Apr 2017 00:18:56 +0000

2310_Structures_of_the_Respiratory_Zone

barkerj1 — Sun, 16 Apr 2017 00:18:58 +0000

2312_Gross_Anatomy_of_the_Lungs

barkerj1 — Sun, 16 Apr 2017 00:19:00 +0000

2313_The_Lung_Pleurea

barkerj1 — Sun, 16 Apr 2017 00:19:01 +0000

2314_Boyles_Law

barkerj1 — Sun, 16 Apr 2017 00:19:03 +0000

2315_Intrapulmonary_and_Intrapleural_Pressure

barkerj1 — Sun, 16 Apr 2017 00:19:05 +0000

2316_Inspiration_and_Expiration

barkerj1 — Sun, 16 Apr 2017 00:19:06 +0000

2317_Spirometry_and_Respiratory_Volumes

barkerj1 — Sun, 16 Apr 2017 00:19:08 +0000

2329_Pulmonary_Function_TestingN

barkerj1 — Sun, 16 Apr 2017 00:19:09 +0000

spirometers

barkerj1 — Sun, 16 Apr 2017 00:19:10 +0000

2327_Respiratory_Centers_of_the_Brain

barkerj1 — Sun, 16 Apr 2017 00:19:12 +0000

2319_Fig_23.19

barkerj1 — Sun, 16 Apr 2017 00:19:15 +0000

2320_Fig_23.20_NEW_KGX

barkerj1 — Sun, 16 Apr 2017 00:19:16 +0000

2322_Fig_23.22-a

barkerj1 — Sun, 16 Apr 2017 00:19:17 +0000

2323_Oxygen-hemoglobin_Dissociation-a

barkerj1 — Sun, 16 Apr 2017 00:19:19 +0000

image385

barkerj1 — Wed, 19 Apr 2017 00:29:15 +0000

Gray410

barkerj1 — Wed, 19 Apr 2017 00:29:15 +0000

image409

barkerj1 — Wed, 19 Apr 2017 00:29:16 +0000

image411

barkerj1 — Wed, 19 Apr 2017 00:29:16 +0000

image397

barkerj1 — Wed, 19 Apr 2017 00:29:17 +0000

image430

barkerj1 — Wed, 19 Apr 2017 00:29:17 +0000

image434

barkerj1 — Wed, 19 Apr 2017 00:29:17 +0000

image389

barkerj1 — Wed, 19 Apr 2017 00:29:18 +0000

image437

barkerj1 — Wed, 19 Apr 2017 00:29:18 +0000

image438

barkerj1 — Wed, 19 Apr 2017 00:29:19 +0000

01_01ab_Gross_and_Microscopic_Anatomy-3

barkerj1 — Wed, 30 Aug 2017 18:36:04 +0000

101_Levels_of_Org_in_Body-3

barkerj1 — Wed, 30 Aug 2017 18:36:04 +0000

102_Organ_Systems_of_BodyPage2-3

barkerj1 — Wed, 30 Aug 2017 18:36:05 +0000

102_Organ_Systems_of_BodyPage1-3

barkerj1 — Wed, 30 Aug 2017 18:36:06 +0000

103_Metabolism-3

barkerj1 — Wed, 30 Aug 2017 18:36:07 +0000

1.3-300x300

barkerj1 — Wed, 30 Aug 2017 18:36:07 +0000

metabolic-3

barkerj1 — Wed, 30 Aug 2017 18:36:07 +0000

01_05_Marathon_Runners-3

barkerj1 — Wed, 30 Aug 2017 18:36:08 +0000

01_06_Extreme_Heat-3

barkerj1 — Wed, 30 Aug 2017 18:36:08 +0000

01_07_Harsh_Conditions-3

barkerj1 — Wed, 30 Aug 2017 18:36:08 +0000

105_Negative_Feedback_Loops-3

barkerj1 — Wed, 30 Aug 2017 18:36:09 +0000

H2Ocon-3

barkerj1 — Wed, 30 Aug 2017 18:36:09 +0000

1.5-300x300

barkerj1 — Wed, 30 Aug 2017 18:36:10 +0000

106_Pregnancy-Positive_Feedback-3

barkerj1 — Wed, 30 Aug 2017 18:36:10 +0000

107_Regions_of_Human_Body_new-3

barkerj1 — Wed, 30 Aug 2017 18:36:10 +0000

108_Directional_Terms-3

barkerj1 — Wed, 30 Aug 2017 18:36:11 +0000

109_Planes_of_Body-3

barkerj1 — Wed, 30 Aug 2017 18:36:11 +0000

110_Dorsal_Ventral_Body_Cavities-3

barkerj1 — Wed, 30 Aug 2017 18:36:12 +0000

111_Abdominal_Quadrant_Regions-3

barkerj1 — Wed, 30 Aug 2017 18:36:12 +0000

112_Serous_Membrane_new-3

barkerj1 — Wed, 30 Aug 2017 18:36:12 +0000

200_DNA_Double_Helix-02-3

barkerj1 — Wed, 30 Aug 2017 18:36:13 +0000

201_Elements_of_the_Human_Body-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:14 +0000

202_Two_Models_of_Atomic_Structure-3

barkerj1 — Wed, 30 Aug 2017 18:36:15 +0000

203_Periodic_Table-02-3

barkerj1 — Wed, 30 Aug 2017 18:36:16 +0000

ptable-3

barkerj1 — Wed, 30 Aug 2017 18:36:17 +0000

204_Isotopes_of_Hydrogen-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:18 +0000

206_Electron_Shells-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:19 +0000

electenergy-3

barkerj1 — Wed, 30 Aug 2017 18:36:20 +0000

207_Ionic_Bonding-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:21 +0000

208_Covalent_Bonding-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:22 +0000

209_Polar_Covalent_Bonds_in_a_Water_Molecule-3

barkerj1 — Wed, 30 Aug 2017 18:36:23 +0000

210_Hydrogen_Bonds_Between_Water_Molecules-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:24 +0000

2.2-scishow-150x150

barkerj1 — Wed, 30 Aug 2017 18:36:24 +0000

2.2-crashcourse-150x150

barkerj1 — Wed, 30 Aug 2017 18:36:24 +0000

213_Dehydration_Synthesis_and_Hydrolysis-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:24 +0000

2.4-amoeba-150x150

barkerj1 — Wed, 30 Aug 2017 18:36:25 +0000

2.4-water-150x150

barkerj1 — Wed, 30 Aug 2017 18:36:25 +0000

214_Dissociation_of_Sodium_Chloride_in_Water-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:25 +0000

215_Acids_and_Bases-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:26 +0000

216_pH_Scale-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:27 +0000

2.4-buffer-150x150

barkerj1 — Wed, 30 Aug 2017 18:36:28 +0000

217_Five_Important_Monosaccharides-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:28 +0000

218_Three_Important_Disaccharides-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:29 +0000

219_Three_Important_Polysaccharides-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:30 +0000

220_Triglycerides-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:31 +0000

221_Fatty_Acids_Shapes-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:31 +0000

222_Other_Important_Lipids-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:32 +0000

223_Structure_of_an_Amino_Acid-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:33 +0000

224_Peptide_Bond-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:34 +0000

225_Peptide_Bond-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:34 +0000

227_Steps_in_an_Enzymatic_Reaction-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:35 +0000

228_Nucleotides-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:36 +0000

229_Nucleotides-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:37 +0000

230_Structure_of_Adenosine_Triphosphate_ATP-01-3

barkerj1 — Wed, 30 Aug 2017 18:36:38 +0000

2.5-amoeba-biomolecules-150x150

barkerj1 — Wed, 30 Aug 2017 18:36:38 +0000

0300_Flourescence_Stained_new-3

barkerj1 — Wed, 30 Aug 2017 18:36:38 +0000

3.0-amoeba-cell-intro-150x150

barkerj1 — Wed, 30 Aug 2017 18:36:39 +0000

0301_Phospholipid_Structure-3

barkerj1 — Wed, 30 Aug 2017 18:36:39 +0000

0302_Phospholipid_Bilayer-3

barkerj1 — Wed, 30 Aug 2017 18:36:39 +0000

0303_Lipid_Bilayer_With_Various_Components-3

barkerj1 — Wed, 30 Aug 2017 18:36:39 +0000

0305_Simple_Diffusion_Across_Plasma_Membrane-3

barkerj1 — Wed, 30 Aug 2017 18:36:39 +0000

0306_Facilitated_Diffusion-3

barkerj1 — Wed, 30 Aug 2017 18:36:40 +0000

0307_Osmosis-3

barkerj1 — Wed, 30 Aug 2017 18:36:40 +0000

0346_Concentration_of_Solutions-3

barkerj1 — Wed, 30 Aug 2017 18:36:40 +0000

0308_Sodium_Potassium_Pump-3

barkerj1 — Wed, 30 Aug 2017 18:36:40 +0000

0309_Three_Forms_of_Endocytosis-3

barkerj1 — Wed, 30 Aug 2017 18:36:41 +0000

3.1-amoeba-cell-transport-150x150

barkerj1 — Wed, 30 Aug 2017 18:36:41 +0000

3.1-crashcourse-150x150

barkerj1 — Wed, 30 Aug 2017 18:36:41 +0000

3.1-khan-150x150

barkerj1 — Wed, 30 Aug 2017 18:36:41 +0000

0310_Exocytosis-3

barkerj1 — Wed, 30 Aug 2017 18:36:41 +0000

0311_Pancreatic_Cells_Micrograph-3

barkerj1 — Wed, 30 Aug 2017 18:36:41 +0000

0312_Animal_Cell_and_Components-3

barkerj1 — Wed, 30 Aug 2017 18:36:42 +0000

0313_Endoplasmic_Reticulum-3

barkerj1 — Wed, 30 Aug 2017 18:36:42 +0000

0314_Golgi_Apparatus-3

barkerj1 — Wed, 30 Aug 2017 18:36:43 +0000

0315_Mitochondrion_new-3

barkerj1 — Wed, 30 Aug 2017 18:36:43 +0000

0318_Nucleus-3

barkerj1 — Wed, 30 Aug 2017 18:36:44 +0000

0319_Multinucleate_Muscle_Tissue_Micrograph-3

barkerj1 — Wed, 30 Aug 2017 18:36:44 +0000

0320_RBC_Extruding_Nucleus_Micrograph-3

barkerj1 — Wed, 30 Aug 2017 18:36:44 +0000

0321_DNA_Macrostructure-3

barkerj1 — Wed, 30 Aug 2017 18:36:45 +0000

0322_DNA_Nucleotides-3

barkerj1 — Wed, 30 Aug 2017 18:36:45 +0000

0324_DNA_Translation_and_Codons-3

barkerj1 — Wed, 30 Aug 2017 18:36:45 +0000

0325_Transcription-3

barkerj1 — Wed, 30 Aug 2017 18:36:45 +0000

0326_Splicing-3

barkerj1 — Wed, 30 Aug 2017 18:36:46 +0000

0327_Translation-3

barkerj1 — Wed, 30 Aug 2017 18:36:46 +0000

0328_Transcription-translation_Summary-3

barkerj1 — Wed, 30 Aug 2017 18:36:46 +0000

0329_Cell_Cycle-3

barkerj1 — Wed, 30 Aug 2017 18:36:46 +0000

0330_Homologous_Pair_of_Chromosomes-3

barkerj1 — Wed, 30 Aug 2017 18:36:47 +0000

0331_Stages_of-_Mitosis_and_Cytokinesis-e1459277007217-3

barkerj1 — Wed, 30 Aug 2017 18:36:47 +0000

0332_Cell_Cycle_With_Cyclins_and_Checkpoints-3

barkerj1 — Wed, 30 Aug 2017 18:36:47 +0000

3.5-amoeba-150x150

barkerj1 — Wed, 30 Aug 2017 18:36:47 +0000

3.5-amoeba-meiosis-150x150

barkerj1 — Wed, 30 Aug 2017 18:36:47 +0000

3.5-150x150

barkerj1 — Wed, 30 Aug 2017 18:36:47 +0000

0337_Hematopoiesis_new-3

barkerj1 — Wed, 30 Aug 2017 18:36:47 +0000

0338_RNA_Polymerase_Binding-3

barkerj1 — Wed, 30 Aug 2017 18:36:49 +0000

422_Feature_Stem_Cell_new-3

barkerj1 — Wed, 30 Aug 2017 18:36:49 +0000

3.6-amoeba-how-specialized-150x150

barkerj1 — Wed, 30 Aug 2017 18:36:50 +0000

3.6-amoeba-specialized-examples-150x150

barkerj1 — Wed, 30 Aug 2017 18:36:50 +0000

400_Micrograph_of_Cervical_Tissue_updated-3

barkerj1 — Wed, 30 Aug 2017 18:36:50 +0000

401_Types_of_Tissue-3

barkerj1 — Wed, 30 Aug 2017 18:36:51 +0000

419_420_421_Table_04_01_updated-3

barkerj1 — Wed, 30 Aug 2017 18:36:52 +0000

413_Types_of_Membranes-3

barkerj1 — Wed, 30 Aug 2017 18:36:53 +0000

402_Types_of_Cell_Junctions_new-3

barkerj1 — Wed, 30 Aug 2017 18:36:54 +0000

403_Epithelial_Tissue-3

barkerj1 — Wed, 30 Aug 2017 18:36:59 +0000

404_Goblet_Cell_new-3

barkerj1 — Wed, 30 Aug 2017 18:37:00 +0000

404b_Goblet_Cell_new-3

barkerj1 — Wed, 30 Aug 2017 18:37:02 +0000

423_Table_04_02_Summary_of_Epithelial_Tissue_CellsN-3

barkerj1 — Wed, 30 Aug 2017 18:37:04 +0000

4.2-150x150

barkerj1 — Wed, 30 Aug 2017 18:37:04 +0000

406_Types_of_Glands-3

barkerj1 — Wed, 30 Aug 2017 18:37:05 +0000

405_Modes_of_Secretion_by_Glands_updated-3

barkerj1 — Wed, 30 Aug 2017 18:37:05 +0000

407_Sebaceous_Glands-3

barkerj1 — Wed, 30 Aug 2017 18:37:06 +0000

408_Connective_Tissue-3

barkerj1 — Wed, 30 Aug 2017 18:37:07 +0000

409_Adipose_Tissue-3

barkerj1 — Wed, 30 Aug 2017 18:37:07 +0000

410_Reticular_Tissue-3

barkerj1 — Wed, 30 Aug 2017 18:37:08 +0000

411_Reg_Dense-Irregular_Dense-3

barkerj1 — Wed, 30 Aug 2017 18:37:09 +0000

412_Types_of_Cartilage-new-3

barkerj1 — Wed, 30 Aug 2017 18:37:10 +0000

424_Blood_A_Fluid_Connective_Tissue-new-3

barkerj1 — Wed, 30 Aug 2017 18:37:11 +0000

414_Skeletal_Smooth_Cardiac-4

barkerj1 — Wed, 30 Aug 2017 18:37:12 +0000

4.4-150x150

barkerj1 — Wed, 30 Aug 2017 18:37:12 +0000

415_Neuron-3

barkerj1 — Wed, 30 Aug 2017 18:37:12 +0000

416_Nervous_Tissue-new-3

barkerj1 — Wed, 30 Aug 2017 18:37:12 +0000

501_Structure_of_the_skin-3

barkerj1 — Wed, 30 Aug 2017 18:37:13 +0000

5.1-150x150

barkerj1 — Wed, 30 Aug 2017 18:37:14 +0000

502ab_Thin_Skin_versus_Thick_Skin-3

barkerj1 — Wed, 30 Aug 2017 18:37:14 +0000

503_Epidermis-3

barkerj1 — Wed, 30 Aug 2017 18:37:14 +0000

502_Layers_of_epidermis-3

barkerj1 — Wed, 30 Aug 2017 18:37:14 +0000

505_Cells_of_the_Epidermis-3

barkerj1 — Wed, 30 Aug 2017 18:37:15 +0000

basal-3

barkerj1 — Wed, 30 Aug 2017 18:37:16 +0000

506_Layers_of_the_Dermis-3

barkerj1 — Wed, 30 Aug 2017 18:37:16 +0000

504_Melanocytes-3

barkerj1 — Wed, 30 Aug 2017 18:37:17 +0000

508_Moles-3

barkerj1 — Wed, 30 Aug 2017 18:37:17 +0000

5.2-150x150

barkerj1 — Wed, 30 Aug 2017 18:37:18 +0000

506_Hair-3

barkerj1 — Wed, 30 Aug 2017 18:37:18 +0000

511_Hair_Follicle-3

barkerj1 — Wed, 30 Aug 2017 18:37:18 +0000

507_Nails-3

barkerj1 — Wed, 30 Aug 2017 18:37:18 +0000

508_Figure_5.08_Eccrine_gland

barkerj1 — Wed, 30 Aug 2017 18:37:18 +0000

514_Light_Micrograph_of_a_Meissner_Corpuscle-3

barkerj1 — Wed, 30 Aug 2017 18:37:19 +0000

515_Thermoregulation-3

barkerj1 — Wed, 30 Aug 2017 18:37:19 +0000

600_Child_Looking_at_Bones-3

barkerj1 — Wed, 30 Aug 2017 18:37:19 +0000

617_Bone_Support_Movement-3

barkerj1 — Wed, 30 Aug 2017 18:37:20 +0000

618_Bones_Protect_Brain-3

barkerj1 — Wed, 30 Aug 2017 18:37:20 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:20 +0000

601_Bone_Classification-3

barkerj1 — Wed, 30 Aug 2017 18:37:20 +0000

603_Anatomy_of_a_Long_Bone-3

barkerj1 — Wed, 30 Aug 2017 18:37:21 +0000

607_Periosteum_and_Endosteum-3

barkerj1 — Wed, 30 Aug 2017 18:37:22 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:22 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:22 +0000

604_Bone_cells-3

barkerj1 — Wed, 30 Aug 2017 18:37:23 +0000

624_Diagram_of_Compact_Bone-new-3

barkerj1 — Wed, 30 Aug 2017 18:37:23 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:24 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:24 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:25 +0000

611_Intramembraneous_Ossification-3

barkerj1 — Wed, 30 Aug 2017 18:37:26 +0000

608_Endochrondal_Ossification-3

barkerj1 — Wed, 30 Aug 2017 18:37:26 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:27 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:27 +0000

612_Types_of_Fractures-3

barkerj1 — Wed, 30 Aug 2017 18:37:28 +0000

613_Stages_of_Fracture_Repair-3

barkerj1 — Wed, 30 Aug 2017 18:37:28 +0000

700_Lateral_View_of_Skull-01-3

barkerj1 — Wed, 30 Aug 2017 18:37:29 +0000

701_Axial_Skeleton-01-3

barkerj1 — Wed, 30 Aug 2017 18:37:31 +0000

703_Parts_of_Skull-01-3

barkerj1 — Wed, 30 Aug 2017 18:37:32 +0000

704_Skull-01-3

barkerj1 — Wed, 30 Aug 2017 18:37:33 +0000

705_Lateral_View_of_Skull-01-3

barkerj1 — Wed, 30 Aug 2017 18:37:35 +0000

708_Temporal_Bone-3

barkerj1 — Wed, 30 Aug 2017 18:37:36 +0000

730_Posterior_View_Skull-3

barkerj1 — Wed, 30 Aug 2017 18:37:36 +0000

711_Maxilla-3

barkerj1 — Wed, 30 Aug 2017 18:37:37 +0000

726_Mandible-3

barkerj1 — Wed, 30 Aug 2017 18:37:37 +0000

712_Hyoid_Bone-3

barkerj1 — Wed, 30 Aug 2017 18:37:37 +0000

715_Vertebral_Column-3

barkerj1 — Wed, 30 Aug 2017 18:37:38 +0000

718_Vertebra-3

barkerj1 — Wed, 30 Aug 2017 18:37:38 +0000

716_Intervertebral_Disk-3

barkerj1 — Wed, 30 Aug 2017 18:37:38 +0000

723_Cervical_Vertebrae-3

barkerj1 — Wed, 30 Aug 2017 18:37:38 +0000

719_Thoracic_Vertebra-3

barkerj1 — Wed, 30 Aug 2017 18:37:39 +0000

732_Thoracic_Vertebra_and_Rib-3

barkerj1 — Wed, 30 Aug 2017 18:37:39 +0000

725_Lumbar_Vertebrae-3

barkerj1 — Wed, 30 Aug 2017 18:37:40 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:40 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:40 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:41 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:41 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:42 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:42 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:43 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:44 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:44 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:45 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:45 +0000

805_Ulna_and_Radius-3

barkerj1 — Wed, 30 Aug 2017 18:37:45 +0000

806_Hand_and_Wrist-3

barkerj1 — Wed, 30 Aug 2017 18:37:46 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:46 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:46 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:46 +0000

807_Pelvis-3

barkerj1 — Wed, 30 Aug 2017 18:37:47 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:47 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:47 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:48 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:48 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:49 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:49 +0000

footbones-3

barkerj1 — Wed, 30 Aug 2017 18:37:50 +0000

819_Embryo_at_Seven_Weeks-3

barkerj1 — Wed, 30 Aug 2017 18:37:50 +0000

900_Girl_Kayaking-3

barkerj1 — Wed, 30 Aug 2017 18:37:51 +0000

901_Skull_Sutures-3

barkerj1 — Wed, 30 Aug 2017 18:37:52 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:52 +0000

903_Multiaxial_Joint-3

barkerj1 — Wed, 30 Aug 2017 18:37:53 +0000

9.1-150x150

barkerj1 — Wed, 30 Aug 2017 18:37:53 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:54 +0000

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barkerj1 — Wed, 30 Aug 2017 18:37:54 +0000

906_Cartiliginous_Joints-3

barkerj1 — Wed, 30 Aug 2017 18:37:55 +0000

907_Synovial_Joints-3

barkerj1 — Wed, 30 Aug 2017 18:37:56 +0000

908_Bursa-3

barkerj1 — Wed, 30 Aug 2017 18:37:56 +0000

909_Types_of_Synovial_Joints-3

barkerj1 — Wed, 30 Aug 2017 18:37:57 +0000

synjoints-3

barkerj1 — Wed, 30 Aug 2017 18:37:59 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:00 +0000

gout-3

barkerj1 — Wed, 30 Aug 2017 18:38:00 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:01 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:02 +0000

911_Body_MovementsPage-2-948x1024-3

barkerj1 — Wed, 30 Aug 2017 18:38:03 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:04 +0000

flexext-3

barkerj1 — Wed, 30 Aug 2017 18:38:05 +0000

kneejoint1-3

barkerj1 — Wed, 30 Aug 2017 18:38:06 +0000

1000_Tennis_Player-3

barkerj1 — Wed, 30 Aug 2017 18:38:06 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:07 +0000

1007_Muscle_Fibes_large-3

barkerj1 — Wed, 30 Aug 2017 18:38:07 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:08 +0000

micromacro-3

barkerj1 — Wed, 30 Aug 2017 18:38:08 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:09 +0000

1003_Thick_and_Thin_Filaments-3

barkerj1 — Wed, 30 Aug 2017 18:38:09 +0000

skelmuscfiber-3

barkerj1 — Wed, 30 Aug 2017 18:38:09 +0000

1009_Motor_End_Plate_and_Innervation-3

barkerj1 — Wed, 30 Aug 2017 18:38:10 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:11 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:12 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:12 +0000

calciumrole-3

barkerj1 — Wed, 30 Aug 2017 18:38:13 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:14 +0000

1008_Skeletal_Muscle_Contraction-3

barkerj1 — Wed, 30 Aug 2017 18:38:14 +0000

1016_Muscle_Metabolism-3

barkerj1 — Wed, 30 Aug 2017 18:38:14 +0000

1015_Types_of_Contraction_new-3

barkerj1 — Wed, 30 Aug 2017 18:38:15 +0000

1011_Muscle_Length_and_Tension-3

barkerj1 — Wed, 30 Aug 2017 18:38:15 +0000

1026_Marathoners-3

barkerj1 — Wed, 30 Aug 2017 18:38:16 +0000

1027_Hypertrophy-3

barkerj1 — Wed, 30 Aug 2017 18:38:16 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:16 +0000

1100_Body_in_Motion-3

barkerj1 — Wed, 30 Aug 2017 18:38:17 +0000

1101_Biceps_Muscle-3

barkerj1 — Wed, 30 Aug 2017 18:38:17 +0000

29218000742_8a42528d49_b-3

barkerj1 — Wed, 30 Aug 2017 18:38:18 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:18 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:18 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:19 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:19 +0000

1126_Understand_A_Muscle_from_the_Latin-3

barkerj1 — Wed, 30 Aug 2017 18:38:20 +0000

1111_Posterior_and_Side_Views_of_the_Neck-3

barkerj1 — Wed, 30 Aug 2017 18:38:21 +0000

1117_Muscles_of_the_Neck_and_Back-3

barkerj1 — Wed, 30 Aug 2017 18:38:22 +0000

1112_Muscles_of_the_Abdomen-3

barkerj1 — Wed, 30 Aug 2017 18:38:24 +0000

1113_The_Diaphragm-3

barkerj1 — Wed, 30 Aug 2017 18:38:25 +0000

1114_Thorax-3

barkerj1 — Wed, 30 Aug 2017 18:38:26 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:27 +0000

1119_Muscles_that_Move_the_Humerus-3

barkerj1 — Wed, 30 Aug 2017 18:38:27 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:29 +0000

1120_Muscles_that_Move_the_Forearm-3

barkerj1 — Wed, 30 Aug 2017 18:38:31 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:33 +0000

1122_Gluteal_Muscles_that_Move_the_Femur-3

barkerj1 — Wed, 30 Aug 2017 18:38:34 +0000

1132_Gluteal_Region_Muscles_that_Move_the_Femur-3

barkerj1 — Wed, 30 Aug 2017 18:38:35 +0000

1133_Thigh_Muscles_that_Moves_the_Femur_Tibia_and_Fibula-3

barkerj1 — Wed, 30 Aug 2017 18:38:37 +0000

1123_Muscles_of_the_Leg_that_Move_the_Foot_and_Toes-3

barkerj1 — Wed, 30 Aug 2017 18:38:39 +0000

1134_Muscles_that_Moves_the_Feet_and_Toes-3

barkerj1 — Wed, 30 Aug 2017 18:38:40 +0000

1900_Blood_cells-3

barkerj1 — Wed, 30 Aug 2017 18:38:41 +0000

1901_Composition_of_Blood-3

barkerj1 — Wed, 30 Aug 2017 18:38:42 +0000

normallevels-3

barkerj1 — Wed, 30 Aug 2017 18:38:43 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:44 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:44 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:44 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:46 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:47 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:48 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:49 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:50 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:52 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:53 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:53 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:54 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:55 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:55 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:57 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:58 +0000

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barkerj1 — Wed, 30 Aug 2017 18:38:59 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:00 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:01 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:01 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:03 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:04 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:05 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:07 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:07 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:08 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:09 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:10 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:11 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:12 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:13 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:14 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:15 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:16 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:17 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:17 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:18 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:19 +0000

ECG-3

barkerj1 — Wed, 30 Aug 2017 18:39:20 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:21 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:21 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:23 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:24 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:24 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:25 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:26 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:27 +0000

2031_Factors_in_Cardiac_Output-3

barkerj1 — Wed, 30 Aug 2017 18:39:27 +0000

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barkerj1 — Wed, 30 Aug 2017 18:39:28 +0000

2033_Depolarization_in_Sinus_Rhythm-3

barkerj1 — Wed, 30 Aug 2017 18:39:29 +0000

2035_Factors_in_Stroke_Volume-3

barkerj1 — Wed, 30 Aug 2017 18:39:30 +0000

2036_Summary_of_Factors_in_Cardiac_Output-3

barkerj1 — Wed, 30 Aug 2017 18:39:31 +0000

2100_Arm_with_Bulging_Veins-3

barkerj1 — Wed, 30 Aug 2017 18:39:32 +0000

2101_Blood_Flow_Through_the_Heart-3

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1.1 Overview of Anatomy and Physiology

barkerj1 — Wed, 30 Aug 2017 18:36:04 +0000

Human anatomy is the scientific study of the body’s structures. Some of these structures are very small and can only be observed and analyzed with the assistance of a microscope. Other larger structures can readily be seen, manipulated, measured, and weighed. The word “anatomy” comes from a Greek root that means “to cut apart.” Human anatomy was first studied by observing the exterior of the body and observing the wounds of soldiers and other injuries. Later, physicians were allowed to dissect bodies of the dead to augment their knowledge. When a body is dissected, its structures are cut apart in order to observe their physical attributes and their relationships to one another. Dissection is still used in medical schools, anatomy courses, and in pathology labs. In order to observe structures in living people, however, a number of imaging techniques have been developed. These techniques allow clinicians to visualize structures inside the living body such as a cancerous tumor or a fractured bone.

Like most scientific disciplines, anatomy has areas of specialization. Gross anatomy is the study of the larger structures of the body, those visible without the aid of magnification (Figure 1a). Macro- means “large,” thus, gross anatomy is also referred to as macroscopic anatomy. In contrast, micro- means “small,” and microscopic anatomy is the study of structures that can be observed only with the use of a microscope or other magnification devices (Figure 1b). Microscopic anatomy includes cytology, the study of cells and histology, the study of tissues. As the technology of microscopes has advanced, anatomists have been able to observe smaller and smaller structures of the body, from slices of large structures like the heart, to the three-dimensional structures of large molecules in the body.

[caption id="" align="aligncenter" width="480"] Figure 1. Gross and Microscopic Anatomy. (a) Gross anatomy considers large structures such as the brain. (b) Microscopic anatomy can deal with the same structures, though at a different scale. This is a micrograph of nerve cells from the brain. LM × 1600. (credit a: “WriterHound”/Wikimedia Commons; credit b: Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption]

Anatomists take two general approaches to the study of the body’s structures: regional and systemic. Regional anatomy is the study of the interrelationships of all of the structures in a specific body region, such as the abdomen. Studying regional anatomy helps us appreciate the interrelationships of body structures, such as how muscles, nerves, blood vessels, and other structures work together to serve a particular body region. In contrast, systemic anatomy is the study of the structures that make up a discrete body system—that is, a group of structures that work together to perform a unique body function. For example, a systemic anatomical study of the muscular system would consider all of the skeletal muscles of the body.

Whereas anatomy is about structure, physiology is about function. Human physiology is the scientific study of the chemistry and physics of the structures of the body and the ways in which they work together to support the functions of life. Much of the study of physiology centers on the body’s tendency toward homeostasis. Homeostasis is the state of steady internal conditions maintained by living things. The study of physiology certainly includes observation, both with the naked eye and with microscopes, as well as manipulations and measurements. However, current advances in physiology usually depend on carefully designed laboratory experiments that reveal the functions of the many structures and chemical compounds that make up the human body.

Like anatomists, physiologists typically specialize in a particular branch of physiology. For example, neurophysiology is the study of the brain, spinal cord, and nerves and how these work together to perform functions as complex and diverse as vision, movement, and thinking. Physiologists may work from the organ level (exploring, for example, what different parts of the brain do) to the molecular level (such as exploring how an electrochemical signal travels along nerves).

Form is closely related to function in all living things. For example, the thin flap of your eyelid can snap down to clear away dust particles and almost instantaneously slide back up to allow you to see again. At the microscopic level, the arrangement and function of the nerves and muscles that serve the eyelid allow for its quick action and retreat. At a smaller level of analysis, the function of these nerves and muscles likewise relies on the interactions of specific molecules and ions. Even the three-dimensional structure of certain molecules is essential to their function.

Your study of anatomy and physiology will make more sense if you continually relate the form of the structures you are studying to their function. In fact, it can be somewhat frustrating to attempt to study anatomy without an understanding of the physiology that a body structure supports. Imagine, for example, trying to appreciate the unique arrangement of the bones of the human hand if you had no conception of the function of the hand. Fortunately, your understanding of how the human hand manipulates tools—from pens to cell phones—helps you appreciate the unique alignment of the thumb in opposition to the four fingers, making your hand a structure that allows you to pinch and grasp objects and type text messages.

1.2 Structural Organization of the Human Body

barkerj1 — Wed, 30 Aug 2017 18:36:07 +0000

Learning Objectives

By the end of this section, you will be able to:

Define the terms organ, organ system, and organism
Describe the chemical, cellular, tissue, organ, organ system, and organismal levels of structural organization in the body
Name the eleven organ systems of the human body, identifying the major organs found in each, and identify at least one major function of each

[caption id="" align="aligncenter" width="550"] Figure 1. Levels of Structural Organization of the Human Body. The organization of the body often is discussed in terms of six distinct levels of increasing complexity, from the smallest chemical building blocks to a unique human organism.[/caption] Before you begin to study the different structures and functions of the human body, it is helpful to consider its basic architecture; that is, how its smallest parts are assembled into larger structures. It is convenient to consider the structures of the body in terms of fundamental levels of organization that increase in complexity: subatomic particles, atoms, molecules, organelles, cells, tissues, organs, organ systems, organisms and biosphere (Figure 1).

The Levels of Organization

To study the chemical level of organization, scientists consider the simplest building blocks of matter: subatomic particles, atoms and molecules. All matter in the universe is composed of one or more unique pure substances called elements, familiar examples of which are hydrogen, oxygen, carbon, nitrogen, calcium, and iron. The smallest unit of any of these pure substances (elements) is an atom. Atoms are made up of subatomic particles such as the proton, electron and neutron. Two or more atoms combine to form a molecule, such as the water molecules, proteins, and sugars found in living things. Molecules are the chemical building blocks of all body structures. A cell is the smallest independently functioning unit of a living organism. Even bacteria, which are extremely small, independently-living organisms, have a cellular structure. Each bacterium is a single cell. All living structures of human anatomy contain cells, and almost all functions of human physiology are performed in cells or are initiated by cells. A human cell typically consists of flexible membranes that enclose cytoplasm, a water-based cellular fluid together with a variety of tiny functioning units called organelles. In humans, as in all organisms, cells perform all functions of life. A tissue is a group of many similar cells (though sometimes composed of a few related types) that work together to perform a specific function. An organ is an anatomically distinct structure of the body composed of two or more tissue types. Each organ performs one or more specific physiological functions. An organ system is a group of organs that work together to perform major functions or meet physiological needs of the body. [caption id="" align="aligncenter" width="500"] Figure 3. Organ Systems of the Human Body (continued). Organs that work together are grouped into organ systems.[/caption] [caption id="" align="aligncenter" width="500"] Figure 2. Organ Systems of the Human Body. Organs that work together are grouped into organ systems.[/caption] This book covers eleven distinct organ systems in the human body (Figure 2 and Figure 3). Assigning organs to organ systems can be imprecise since organs that “belong” to one system can also have functions integral to another system. In fact, most organs contribute to more than one system. The organism level is the highest level of organization. An organism is a living being that has a cellular structure and that can independently perform all physiologic functions necessary for life. In multicellular organisms, including humans, all cells, tissues, organs, and organ systems of the body work together to maintain the life and health of the organism.

1.3 Functions of Human Life

barkerj1 — Wed, 30 Aug 2017 18:36:08 +0000

Learning Objectives

By the end of this section, you will be able to:

Specify the characteristics associated with life
Explain why the cell is considered to be the basic unit of life
Explain what is meant by cellular metabolism
Distinguish between anabolism and catabolism
Describe the three processes that must occur at both a cellular and organismal level for a human body to develop from a fertilized egg to an adult

The different organ systems each have different functions and therefore unique roles to perform in physiology. These many functions can be summarized in terms of a few that we might consider definitive of human life: organization, metabolism, responsiveness, movement, development, and reproduction.

Organization

A human body consists of trillions of cells organized in a way that maintains distinct internal compartments. These compartments keep body cells separated from external environmental threats and keep the cells moist and nourished. They also separate internal body fluids from the countless microorganisms that grow on body surfaces, including the lining of certain tracts, or passageways. The intestinal tract, for example, is home to even more bacteria cells than the total of all human cells in the body, yet these bacteria are outside the body and cannot be allowed to circulate freely inside the body.

Cells, for example, have a cell membrane (also referred to as the plasma membrane) that keeps the intracellular environment—the fluids and organelles—separate from the extracellular environment. Blood vessels keep blood inside a closed circulatory system, and nerves and muscles are wrapped in connective tissue sheaths that separate them from surrounding structures. In the chest and abdomen, a variety of internal membranes keep major organs such as the lungs, heart, and kidneys separate from others.

The body’s largest organ system is the integumentary system, which includes the skin and its associated structures, such as hair and nails. The surface tissue of skin is a barrier that protects internal structures and fluids from potentially harmful microorganisms and other toxins.

Metabolism

The first law of thermodynamics holds that energy can neither be created nor destroyed—it can only change form. Your basic function as an organism is to consume (ingest) energy and molecules in the foods you eat, convert some of it into fuel for movement, sustain your body functions, and build and maintain your body structures. There are two types of reactions that accomplish this: anabolism and catabolism.

Anabolism is the process whereby smaller, simpler molecules are combined into larger, more complex substances. Your body can assemble, by utilizing energy, the complex chemicals it needs by combining small molecules derived from the foods you eat.
Catabolism is the process by which larger more complex substances are broken down into smaller simpler molecules. Catabolism releases energy. The complex molecules found in foods are broken down so the body can use their parts to assemble the structures and substances needed for life.

Taken together, these two processes are called metabolism. Metabolism is the sum of all anabolic and catabolic reactions that take place in the body (Figure 1). Both anabolism and catabolism occur simultaneously and continuously to keep you alive.

[caption id="" align="aligncenter" width="300"] Figure 1. Metabolism. Anabolic reactions are building reactions, and they consume energy. Catabolic reactions break materials down and release energy. Metabolism includes both anabolic and catabolic reactions.[/caption]

Every cell in your body makes use of a chemical compound, adenosine triphosphate (ATP), to store and release energy. The cell stores energy in the synthesis (anabolism) of ATP, then moves the ATP molecules to the location where energy is needed to fuel cellular activities. Then the ATP is broken down (catabolism) and a controlled amount of energy is released, which is used by the cell to perform a particular job.

[caption id="attachment_2943" align="aligncenter" width="123"] Watch this CrashCourse video to learn more about metabolism![/caption]

Exchange of Material

Organisms do not exist solely within their own boundaries, but interact with the external environment that surrounds them. One of the ways in which they do this is by exchanging materials with their external environment: taking in materials from their external environment and by expelling waste products out into their external environment. These materials and waste products may be anything from very small, relatively simple molecules (e.g. glucose, carbon dioxide) that must cross an individual cell's plasma membrane to whole cells or foodstuffs that were ingested but not fully digested and/or absorbed and so must be excreted from the organism.

Responsiveness

Responsiveness is the ability of an organism to adjust to changes in its internal and external environments. An example of responsiveness to external stimuli could include moving toward sources of food and water and away from perceived dangers. Changes in an organism’s internal environment, such as increased body temperature, can cause the responses of sweating and the dilation of blood vessels in the skin in order to decrease body temperature, as shown by the runners in Figure 2.

Movement

Human movement includes not only actions at the joints of the body, but also the motion of individual organs and even individual cells. As you read these words, red and white blood cells are moving throughout your body, muscle cells are contracting and relaxing to maintain your posture and to focus your vision, and glands are secreting chemicals to regulate body functions. Your body is coordinating the action of entire muscle groups to enable you to move air into and out of your lungs, to push blood throughout your body, and to propel the food you have eaten through your digestive tract. Consciously, of course, you contract your skeletal muscles to move the bones of your skeleton to get from one place to another (as the runners are doing in Figure 2), and to carry out all of the activities of your daily life.

[caption id="" align="aligncenter" width="480"] Figure 2. Marathon Runners. Runners demonstrate two characteristics of living humans—responsiveness and movement. Anatomic structures and physiological processes allow runners to coordinate the action of muscle groups and sweat in response to rising internal body temperature. (credit: Phil Roeder/flickr)[/caption]

Development, growth and reproduction

Development is all of the changes the body goes through in life. Development includes the process of differentiation, in which unspecialized cells become specialized in structure and function to perform certain tasks in the body. Development also includes the processes of growth and repair, both of which involve cell differentiation.

Growth is the increase in body size. Humans, like all multicellular organisms, grow by increasing the number of existing cells, increasing the amount of non-cellular material around cells (such as mineral deposits in bone), and, within very narrow limits, increasing the size of existing cells.

Reproduction is the formation of a new organism from parent organisms. In humans, reproduction is carried out by the male and female reproductive systems. Because death will come to all complex organisms, without reproduction, the line of organisms would end.

1.4 Requirements for Human Life

barkerj1 — Wed, 30 Aug 2017 18:36:09 +0000

Learning Objectives

By the end of this section, you will be able to:

Discuss the role of oxygen and nutrients in maintaining human survival
Explain why extreme heat and extreme cold threaten human survival
Explain how the pressure exerted by gases and fluids influences human survival

Humans have been adapting to life on Earth for at least the past 200,000 years. Earth and its atmosphere have provided us with air to breathe, water to drink, and food to eat, but these are not the only requirements for survival. Although you may rarely think about it, you also cannot live outside of a certain range of temperature and pressure that the surface of our planet and its atmosphere provides. The next sections explore these four requirements of life.

Oxygen

Atmospheric air is only about 20 percent oxygen, but that oxygen is a key component of the chemical reactions that keep the body alive, including the reactions that produce ATP. Brain cells are especially sensitive to lack of oxygen because of their requirement for a high-and-steady production of ATP. Brain damage is likely within five minutes without oxygen, and death is likely within ten minutes.

Nutrients

A nutrient is a substance in foods and beverages that is essential to human survival. The three basic classes of nutrients are water, the energy-yielding and body-building nutrients, and the micronutrients (vitamins and minerals).

The most critical nutrient is water. Depending on the environmental temperature and our state of health, we may be able to survive for only a few days without water. The body’s functional chemicals are dissolved and transported in water, and the chemical reactions of life take place in water. Moreover, water is the largest component of cells, blood, and the fluid between cells, and water makes up about 70 percent of an adult’s body mass. Water also helps regulate our internal temperature and cushions, protects, and lubricates joints and many other body structures.

The energy-yielding nutrients are primarily carbohydrates and lipids, while proteins mainly supply the amino acids that are the building blocks of the body itself. You ingest these in plant and animal foods and beverages, and the digestive system breaks them down into molecules small enough to be absorbed. The breakdown products of carbohydrates and lipids can then be used in the metabolic processes that convert them to ATP. Although you might feel as if you are starving after missing a single meal, you can survive without consuming the energy-yielding nutrients for at least several weeks.

Water and the energy-yielding nutrients are also referred to as macronutrients because the body needs them in large amounts. In contrast, micronutrients are vitamins and minerals. These elements and compounds participate in many essential chemical reactions and processes, such as nerve impulses, and some, such as calcium, also contribute to the body’s structure. Your body can store some of the micronutrients in its tissues, and draw on those reserves if you fail to consume them in your diet for a few days or weeks. Some others micronutrients, such as vitamin C and most of the B vitamins, are water-soluble and cannot be stored, so you need to consume them every day or two.

Narrow Range of Temperature

You have probably seen news stories about athletes who died of heat stroke, or hikers who died of exposure to cold. Such deaths occur because the chemical reactions upon which the body depends can only take place within a narrow range of body temperature, from just below to just above 37°C (98.6°F). When body temperature rises well above or drops well below normal, certain proteins (enzymes) that facilitate chemical reactions lose their normal structure and their ability to function and the chemical reactions of metabolism cannot proceed.

That said, the body can respond effectively to short-term exposure to heat (Figure 1) or cold. One of the body’s responses to heat is, of course, sweating. As sweat evaporates from skin, it removes some thermal energy from the body, cooling it. Adequate water (from the extracellular fluid in the body) is necessary to produce sweat, so adequate fluid intake is essential to balance that loss during the sweat response. Not surprisingly, the sweat response is much less effective in a humid environment because the air is already saturated with water. Thus, the sweat on the skin’s surface is not able to evaporate, and internal body temperature can get dangerously high.

[caption id="" align="aligncenter" width="420"] Figure 1. Extreme Heat. Humans adapt to some degree to repeated exposure to high temperatures. (credit: McKay Savage/flickr)[/caption]

The body can also respond effectively to short-term exposure to cold. One response to cold is shivering, which is random muscle movement that generates heat. Another response is increased breakdown of stored energy to generate heat. When that energy reserve is depleted, however, and the core temperature begins to drop significantly, red blood cells will lose their ability to give up oxygen, denying the brain of this critical component of ATP production. This lack of oxygen can cause confusion, lethargy, and eventually loss of consciousness and death. The body responds to cold by reducing blood circulation to the extremities, the hands and feet, in order to prevent blood from cooling there and so that the body’s core can stay warm. Even when core body temperature remains stable, however, tissues exposed to severe cold, especially the fingers and toes, can develop frostbite when blood flow to the extremities has been much reduced. This form of tissue damage can be permanent and lead to gangrene, requiring amputation of the affected region.

Narrow Range of Atmospheric Pressure

Pressure is a force exerted by a substance that is in contact with another substance. Atmospheric pressure is pressure exerted by the mixture of gases (primarily nitrogen and oxygen) in the Earth’s atmosphere. Although you may not perceive it, atmospheric pressure is constantly pressing down on your body. This pressure keeps gases within your body, such as the gaseous nitrogen in body fluids, dissolved. If you were suddenly ejected from a space ship above Earth’s atmosphere, you would go from a situation of normal pressure to one of very low pressure. The pressure of the nitrogen gas in your blood would be much higher than the pressure of nitrogen in the space surrounding your body. As a result, the nitrogen gas in your blood would expand, forming bubbles that could block blood vessels and even cause cells to break apart.

Atmospheric pressure does more than just keep blood gases dissolved. Your ability to breathe—that is, to take in oxygen and release carbon dioxide—also depends upon a precise atmospheric pressure. Altitude sickness occurs in part because the atmosphere at high altitudes exerts less pressure, reducing the exchange of these gases, and causing shortness of breath, confusion, headache, lethargy, and nausea. Mountain climbers carry oxygen to reduce the effects of both low oxygen levels and low barometric pressure at higher altitudes (Figure 2).

[caption id="" align="aligncenter" width="380"] Figure 2. Harsh Conditions. Climbers on Mount Everest must accommodate extreme cold, low oxygen levels, and low barometric pressure in an environment hostile to human life. (credit: Melanie Ko/flickr)[/caption]

1.5 Homeostasis

barkerj1 — Wed, 30 Aug 2017 18:36:10 +0000

Learning Objectives

By the end of this section, you will be able to:

Define the term "homeostasis"
Explain the importance of homeostasis
Specify the four main variables that must be regulated to maintain homeostasis
Define "internal environment" and explain its relationship to the following: extracellular fluid, intracellular fluid, plasma, interstitial fluid, lymph
Define the term "stressor" or "stimulus"
Provide two examples of internal stressors/stimuli
Provide two examples of an external stressors/stimuli
Define a feedback loop
Explain what is meant by negative and positive feedback systems and describe their role in homeostasis
Describe the role of the skin in monitoring body temperature as an example of a negative feedback system

Homeostasis refers to a relatively stable set of conditions within an organism's internal environment. Within the human body, maintaining a healthy environment for living cells requires maintaining appropriate conditions in the extracellular fluids - interstitial fluid and blood plasma - for each living cell to be able to function properly.

Maintaining homeostasis requires that the body continuously monitor its internal conditions. From body temperature to blood pressure to levels of certain nutrients, each physiological condition has a particular set point. A set point is the physiological value around which the normal range fluctuates. A normal range is the restricted set of values that is optimally healthful and stable. For example, the set point for normal human body temperature is approximately 37°C (98.6°F) Physiological parameters, such as body temperature and blood pressure, tend to fluctuate within a normal range a few degrees above and below that point. Control centers in the brain and other parts of the body monitor and react to deviations from homeostasis using negative feedback. Negative feedback is a mechanism that reverses a deviation from the set point. Therefore, negative feedback maintains body parameters within their normal range. The maintenance of homeostasis by negative feedback goes on throughout the body at all times, and an understanding of negative feedback is thus fundamental to an understanding of human physiology.

Negative Feedback

A negative feedback system has three basic components (Figure 1a). A sensor, also referred to a receptor, is a component of a feedback system that monitors a physiological value. This value is reported to the control center. The control center is the component in a feedback system that compares the value to the normal range. If the value deviates too much from the set point, then the control center activates an effector. An effector is the component in a feedback system that causes a change to reverse the situation and return the value to the normal range.

[caption id="" align="aligncenter" width="450"] Figure 1. Negative Feedback Loop. In a negative feedback loop, a stimulus—a deviation from a set point—is resisted through a physiological process that returns the body to homeostasis. (a) A negative feedback loop has four basic parts. (b) Body temperature is regulated by negative feedback.[/caption]

In order to set the system in motion, a stimulus must drive a physiological parameter beyond its normal range (that is, beyond homeostasis). This stimulus is “heard” by a specific sensor. For example, in the control of blood glucose, specific endocrine cells in the pancreas detect excess glucose (the stimulus) in the bloodstream. These pancreatic beta cells respond to the increased level of blood glucose by releasing the hormone insulin into the bloodstream. The insulin signals skeletal muscle fibers, fat cells (adipocytes), and liver cells to take up the excess glucose, removing it from the bloodstream. As glucose concentration in the bloodstream drops, the decrease in concentration—the actual negative feedback—is detected by pancreatic alpha cells, and insulin release stops. This prevents blood sugar levels from continuing to drop below the normal range.

Humans have a similar temperature regulation feedback system that works by promoting either heat loss or heat gain (Figure 1b). When the brain’s temperature regulation center receives data from the sensors indicating that the body’s temperature exceeds its normal range, it stimulates a cluster of brain cells referred to as the “heat-loss center.” This stimulation has three major effects:

Blood vessels in the skin begin to dilate allowing more blood from the body core to flow to the surface of the skin allowing the heat to radiate into the environment.
As blood flow to the skin increases, sweat glands are activated to increase their output. As the sweat evaporates from the skin surface into the surrounding air, it takes heat with it.
The depth of respiration increases, and a person may breathe through an open mouth instead of through the nasal passageways. This further increases heat loss from the lungs.

In contrast, activation of the brain’s heat-gain center by exposure to cold reduces blood flow to the skin, and blood returning from the limbs is diverted into a network of deep veins. This arrangement traps heat closer to the body core and restricts heat loss. If heat loss is severe, the brain triggers an increase in random signals to skeletal muscles, causing them to contract and producing shivering. The muscle contractions of shivering release heat while using up ATP. The brain triggers the thyroid gland in the endocrine system to release thyroid hormone, which increases metabolic activity and heat production in cells throughout the body. The brain also signals the adrenal glands to release epinephrine (adrenaline), a hormone that causes the breakdown of glycogen into glucose, which can be used as an energy source. The breakdown of glycogen into glucose also results in increased metabolism and heat production.

[caption id="attachment_2946" align="aligncenter" width="119"] Watch this CrashCourse video to learn more about homeostasis![/caption]

Positive Feedback

Positive feedback intensifies a change in the body’s physiological condition rather than reversing it. A deviation from the normal range results in more change, and the system moves farther away from the normal range. Positive feedback in the body is normal only when there is a definite end point. Childbirth and the body’s response to blood loss are two examples of positive feedback loops that are normal but are activated only when needed.

Childbirth at full term is an example of a situation in which the maintenance of the existing body state is not desired. Enormous changes in the mother’s body are required to expel the baby at the end of pregnancy. And the events of childbirth, once begun, must progress rapidly to a conclusion or the life of the mother and the baby are at risk. The extreme muscular work of labor and delivery are the result of a positive feedback system (Figure 2).

[caption id="" align="aligncenter" width="380"] Figure 2. Positive Feedback Loop. Normal childbirth is driven by a positive feedback loop. A positive feedback loop results in a change in the body’s status, rather than a return to homeostasis.[/caption] The first contractions of labor (the stimulus) push the baby toward the cervix (the lowest part of the uterus). The cervix contains stretch-sensitive nerve cells that monitor the degree of stretching (the sensors). These nerve cells send messages to the brain, which in turn causes the pituitary gland at the base of the brain to release the hormone oxytocin into the bloodstream. Oxytocin causes stronger contractions of the smooth muscles in of the uterus (the effectors), pushing the baby further down the birth canal. This causes even greater stretching of the cervix. The cycle of stretching, oxytocin release, and increasingly more forceful contractions stops only when the baby is born. At this point, the stretching of the cervix halts, stopping the release of oxytocin.

A second example of positive feedback centers on reversing extreme damage to the body. Following a penetrating wound, the most immediate threat is excessive blood loss. Less blood circulating means reduced blood pressure and reduced perfusion (penetration of blood) to the brain and other vital organs. If perfusion is severely reduced, vital organs will shut down and the person will die. The body responds to this potential catastrophe by releasing substances in the injured blood vessel wall that begin the process of blood clotting. As each step of clotting occurs, it stimulates the release of more clotting substances. This accelerates the processes of clotting and sealing off the damaged area. Clotting is contained in a local area based on the tightly controlled availability of clotting proteins. This is an adaptive, life-saving cascade of events.

1.6 Anatomical Terminology

barkerj1 — Wed, 30 Aug 2017 18:36:13 +0000

Learning Objectives

By the end of this section, you will be able to:

Define the anatomical position
Locate the anterior (ventral) and posterior (dorsal) surfaces for the human body, hands, and feet
Define the following terms as they relate to body directions:
- Superior and inferior
- Medial, laterla, and intermediate
- Peripheral and central
- Proximal and distal
- Deep, superficial, and median
- Parietal and visceral
- Anterior and posterior
Explain why a body or structure is often cut into sections before viewing
Define the following types of sections: sagittal section, frontal section, transverse section
Specify the five body cavities, the major organs contained in each cavity, and structures that separate the cavities

Anatomists and health care providers use terminology that can be bewildering to the uninitiated. However, the purpose of this language is not to confuse, but rather to increase precision and reduce medical errors. For example, is a scar “above the wrist” located on the forearm two or three inches away from the hand? Or is it at the base of the hand? Is it on the palm-side or back-side? By using precise anatomical terminology, we eliminate ambiguity. Anatomical terms derive from ancient Greek and Latin words. Because these languages are no longer used in everyday conversation, the meaning of their words does not change.

Anatomical terms are made up of roots, prefixes, and suffixes. The root of a term often refers to an organ, tissue, or condition, whereas the prefix or suffix often describes the root. For example, in the disorder hypertension, the prefix “hyper-” means “high” or “over,” and the root word “tension” refers to pressure, so the word “hypertension” refers to abnormally high blood pressure.

[caption id="" align="aligncenter" width="550"] Figure 1. Regions of the Human Body. The human body is shown in anatomical position in an (a) anterior view and a (b) posterior view. The regions of the body are labeled in boldface.[/caption]

Anatomical Position

To further increase precision, anatomists standardize the way in which they view the body. Just as maps are normally oriented with north at the top, the standard body “map,” or anatomical position, is that of the body standing upright, with the feet at shoulder width and parallel, toes forward. The upper limbs are held out to each side, and the palms of the hands face forward as illustrated in Figure 1. Using this standard position reduces confusion. It does not matter how the body being described is oriented, the terms are used as if it is in anatomical position. For example, a scar in the “anterior (front) carpal (wrist) region” would be present on the palm side of the wrist. The term “anterior” would be used even if the hand were palm down on a table.

A body that is lying down is described as either prone or supine. Prone describes a face-down orientation, and supine describes a face up orientation. These terms are sometimes used in describing the position of the body during specific physical examinations or surgical procedures.

Regional Terms

The human body’s numerous regions have specific terms to help increase precision (see Figure 1). Notice that the term “brachium” or “arm” is reserved for the “upper arm” and “antebrachium” or “forearm” is used rather than “lower arm.” Similarly, “femur” or “thigh” is correct, and “leg” or “crus” is reserved for the portion of the lower limb between the knee and the ankle. You will be able to describe the body’s regions using the terms from the figure.

Directional Terms

[caption id="" align="aligncenter" width="450"] Figure 2. Directional Terms Applied to the Human Body. Paired directional terms are shown as applied to the human body.[/caption] Certain directional anatomical terms appear throughout this and any other anatomy textbook (Figure 2). These terms are essential for describing the relative locations of different body structures. For instance, an anatomist might describe one band of tissue as “inferior to” another or a physician might describe a tumor as “superficial to” a deeper body structure. Commit these terms to memory to avoid confusion when you are studying or describing the locations of particular body parts.

Anterior (or ventral) Describes the front or direction toward the front of the body. The toes are anterior to the foot.
Posterior (or dorsal) Describes the back or direction toward the back of the body. The popliteus is posterior to the patella.
Superior (or cranial) describes a position above or higher than another part of the body proper. The orbits are superior to the oris.
Inferior (or caudal) describes a position below or lower than another part of the body proper; near or toward the tail (in humans, the coccyx, or lowest part of the spinal column). The pelvis is inferior to the abdomen.
Lateral describes the side or direction toward the side of the body. The thumb (pollex) is lateral to the digits.
Medial describes the middle or direction toward the middle of the body. The hallux is the medial toe.
Proximal describes a position in a limb that is nearer to the point of attachment or the trunk of the body. The brachium is proximal to the antebrachium.
Distal describes a position in a limb that is farther from the point of attachment or the trunk of the body. The crus is distal to the femur.
Central describes a position towards the middle (centre) of a structure or organ system. The central nervous system is contained within the skull and vertebral column.
Peripheral describes a position towards the outer edge (periphery) of a structure or organ system. The peripheral nervous system is found outside the skull and vertebral column.
Superficial describes a position closer to the surface of the body. The skin is superficial to the bones.
Deep describes a position farther from the surface of the body. The brain is deep to the skull.

Body Planes

[caption id="" align="alignleft" width="350"] Figure 3. Planes of the Body. The three planes most commonly used in anatomical and medical imaging are the sagittal, frontal (or coronal), and transverse plane.[/caption]

A section is a two-dimensional surface of a three-dimensional structure that has been cut. Modern medical imaging devices enable clinicians to obtain “virtual sections” of living bodies. We call these scans. Body sections and scans can be correctly interpreted, however, only if the viewer understands the plane along which the section was made. A plane is an imaginary two-dimensional surface that passes through the body. There are three planes commonly referred to in anatomy and medicine, as illustrated in Figure 3.

The sagittal plane is the plane that divides the body or an organ vertically into right and left sides. If this vertical plane runs directly down the middle of the body, it is called the midsagittal or median plane. If it divides the body into unequal right and left sides, it is called a parasagittal plane or less commonly a longitudinal section.
The frontal plane is the plane that divides the body or an organ into an anterior (front) portion and a posterior (rear) portion. The frontal plane is often referred to as a coronal plane. (“Corona” is Latin for “crown.”)
The transverse plane is the plane that divides the body or organ horizontally into upper and lower portions. Transverse planes produce images referred to as cross sections.

Body Cavities and Serous Membranes

The body maintains its internal organization by means of membranes, sheaths, and other structures that separate compartments. The dorsal (posterior) cavity and the ventral (anterior) cavity are the largest body compartments (Figure 4). These cavities contain and protect delicate internal organs, and the ventral cavity allows for significant changes in the size and shape of the organs as they perform their functions. The lungs, heart, stomach, and intestines, for example, can expand and contract without distorting other tissues or disrupting the activity of nearby organs.

[caption id="" align="aligncenter" width="550"] Figure 4. Dorsal and Ventral Body Cavities. The ventral cavity includes the thoracic and abdominopelvic cavities and their subdivisions. The dorsal cavity includes the cranial and spinal cavities.[/caption]

Subdivisions of the Posterior (Dorsal) and Anterior (Ventral) Cavities

The posterior (dorsal) and anterior (ventral) cavities are each subdivided into smaller cavities. In the posterior (dorsal) cavity, the cranial cavity houses the brain, and the spinal cavity (or vertebral cavity) encloses the spinal cord. Just as the brain and spinal cord make up a continuous, uninterrupted structure, the cranial and spinal cavities that house them are also continuous. The brain and spinal cord are protected by the bones of the skull and vertebral column and by cerebrospinal fluid, a colorless fluid produced by the brain, which cushions the brain and spinal cord within the posterior (dorsal) cavity.

The anterior (ventral) cavity has two main subdivisions: the thoracic cavity and the abdominopelvic cavity (see Figure 4). The thoracic cavity is the more superior subdivision of the anterior cavity, and it is enclosed by the rib cage. The thoracic cavity contains the lungs and the heart, which is located in the mediastinum. The diaphragm forms the floor of the thoracic cavity and separates it from the more inferior abdominopelvic cavity. The abdominopelvic cavity is the largest cavity in the body. Although no membrane physically divides the abdominopelvic cavity, it can be useful to distinguish between the abdominal cavity, the division that houses the digestive organs, and the pelvic cavity, the division that houses the organs of reproduction.

[caption id="" align="aligncenter" width="565"] Figure 5. Regions and Quadrants of the Peritoneal Cavity. There are (a) nine abdominal regions and (b) four abdominal quadrants in the peritoneal cavity.[/caption]

Abdominal Regions and Quadrants

To promote clear communication, for instance about the location of a patient’s abdominal pain or a suspicious mass, health care providers typically divide up the cavity into either nine regions or four quadrants (Figure 5).

The more detailed regional approach subdivides the cavity with one horizontal line immediately inferior to the ribs and one immediately superior to the pelvis, and two vertical lines drawn as if dropped from the midpoint of each clavicle (collarbone). There are nine resulting regions. The simpler quadrants approach, which is more commonly used in medicine, subdivides the cavity with one horizontal and one vertical line that intersect at the patient’s umbilicus (navel).

Membranes of the Anterior (Ventral) Body Cavity

A serous membrane (also referred to a serosa) is one of the thin membranes that cover the walls and organs in the thoracic and abdominopelvic cavities. The parietal layers of the membranes line the walls of the body cavity (pariet- refers to a cavity wall). The visceral layer of the membrane covers the organs (the viscera). Between the parietal and visceral layers is a very thin, fluid-filled serous space, or cavity (Figure 6).

[caption id="" align="alignright" width="420"] Figure 6. Serous Membrane. Serous membrane lines the pericardial cavity and reflects back to cover the heart—much the same way that an underinflated balloon would form two layers surrounding a fist.[/caption] There are three serous cavities and their associated membranes. The pleura is the serous membrane that surrounds the lungs in the pleural cavity; the pericardium is the serous membrane that surrounds the heart in the pericardial cavity; and the peritoneum is the serous membrane that surrounds several organs in the abdominopelvic cavity.The serous membranes form fluid-filled sacs, or cavities, that are meant to cushion and reduce friction on internal organs when they move, such as when the lungs inflate or the heart beats. Both the parietal and visceral serosa secrete the thin, slippery serous fluid located within the serous cavities. The pleural cavity reduces friction between the lungs and the body wall. Likewise, the pericardial cavity reduces friction between the heart and the wall of the pericardium. The peritoneal cavity reduces friction between the abdominal and pelvic organs and the body wall. Therefore, serous membranes provide additional protection to the viscera they enclose by reducing friction that could lead to inflammation of the organs.

Introduction

barkerj1 — Wed, 30 Aug 2017 18:36:14 +0000

[caption id="" align="aligncenter" width="358"] Figure 1. Human DNA. Human DNA is described as a double helix that resembles a molecular spiral staircase. In humans the DNA is organized into 46 chromosomes.[/caption] The smallest, most fundamental material components of the human body are chemical elements. All of the elements found in the human body — elements that include phosphorus, carbon, sodium, and calcium, to name a few — originated in stars. These elements, in turn, form both the inorganic and organic chemical compounds important to life, including, for example, water, glucose, and proteins. This chapter begins by examining elements and how the structures of atoms, the basic units of matter, determine the characteristics of elements by the number of protons, neutrons, and electrons in the atoms. The chapter then builds the framework of life from there.

2.1 Elements and Atoms: the Building Blocks of Matter

barkerj1 — Wed, 30 Aug 2017 18:36:20 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the nature of a chemical element
Specify the name and symbol for the four most common chemical elements in the body, and describe the importance of each
Distinguish between elements, molecules, and compounds
Describe the structure of an atom

The substance of the universe—from a grain of sand to a star—is called matter. Scientists define matter as anything that occupies space and has mass. An object’s mass and its weight are related concepts, but not quite the same. An object’s mass is the amount of matter contained in the object, and the object’s mass is the same whether that object is on Earth or in the zero-gravity environment of outer space. An object’s weight, on the other hand, is its mass as affected by the pull of gravity. Where gravity strongly pulls on an object’s mass its weight is greater than it is where gravity is less strong. An object of a certain mass weighs less on the moon, for example, than it does on Earth because the gravity of the moon is less than that of Earth. In other words, weight is variable, and is influenced by gravity. A piece of cheese that weighs a pound on Earth weighs only a few ounces on the moon.

Elements and Compounds

All matter in the natural world is composed of one or more of the 92 fundamental substances called elements. An element is a pure substance that is distinguished from all other matter by the fact that it cannot be created or broken down by ordinary chemical means. While your body can assemble many of the chemical compounds needed for life from their constituent elements, it cannot make elements. They must come from the environment.

A familiar example of an element that you must take in is calcium, in the form of calcium ions (Ca²⁺). Calcium is essential to the human body; it is absorbed and required for a number of processes including neurotransmitter release, muscle contraction, and strengthening bones. When you consume food your digestive system breaks down the food into components small enough to cross into the bloodstream. Among these is calcium, which, because it is an element, cannot be broken down further. The elemental calcium in cheese, therefore, is the same as the calcium that is found in your bones. Some other elements you might be familiar with are oxygen, sodium, and iron. The elements in the human body are shown in Figure 1, beginning with the four most abundant: oxygen (O), carbon (C), hydrogen (H), and nitrogen (N). Each element’s name can be replaced by a one- or two-letter symbol; you will become familiar with some of these during this course. All the elements in your body are derived from the foods you eat and the air you breathe.

[caption id="" align="aligncenter" width="585"] Figure 1. Elements of the Human Body. The main elements that compose the human body are shown from most abundant to least abundant.[/caption]

In nature, elements rarely occur alone. Instead, they combine to form compounds. A compound is a substance composed of two or more elements joined by chemical bonds. For example, the compound glucose is an important body fuel. It is always composed of the same three elements: carbon, hydrogen, and oxygen. Moreover, the elements that make up any given compound always occur in the same relative amounts. In glucose, there are always six carbon units and six oxygen units for every twelve hydrogen units. But what, exactly, are these “units” of elements?

Atoms and Subatomic Particles

An atom is the smallest quantity of an element that retains the unique properties of that element. In other words, an atom of hydrogen is a unit of hydrogen—the smallest amount of hydrogen that can possibly exist. As you might guess, atoms are almost unfathomably small. The period at the end of this sentence is millions of atoms wide.

Atomic Structure and Energy

Atoms are made up of even smaller subatomic particles, three types of which are important: the proton, neutron, and electron. The number of positively-charged protons and non-charged (“neutral”) neutrons, gives mass to the atom, and the number of each in the nucleus of the atom determine the element. The number of negatively-charged electrons that “spin” around the nucleus at close to the speed of light equals the number of protons. An electron has about 1/2000th the mass of a proton or neutron.

Figure 2 shows two models that can help you imagine the structure of an atom—in this case, helium (He). In the planetary model, helium’s two electrons are shown circling the nucleus in a fixed orbit depicted as a ring. Although this model is helpful in visualizing atomic structure, in reality, electrons do not travel in fixed orbits, but whiz around the nucleus erratically in a so-called electron cloud.

[caption id="" align="alignleft" width="285"] Figure 2. Two Models of Atomic Structure. (a) In the planetary model, the electrons of helium are shown in fixed orbits, depicted as rings, at a precise distance from the nucleus, somewhat like planets orbiting the sun. (b) In the electron cloud model, the electrons of carbon are shown in the variety of locations they would have at different distances from the nucleus over time.[/caption]

An atom’s protons and electrons carry electrical charges. Protons, with their positive charge, are designated p⁺. Electrons, which have a negative charge, are designated e^–. An atom’s neutrons have no charge: they are electrically neutral. Just as a magnet sticks to a steel refrigerator because their opposite charges attract, the positively charged protons attract the negatively charged electrons. This mutual attraction gives the atom some structural stability. The attraction by the positively charged nucleus helps keep electrons from straying far. The number of protons and electrons within a neutral atom are equal, thus, the atom’s overall charge is balanced.

Atomic Number and Mass Number

An atom of carbon is unique to carbon, but a proton of carbon is not. One proton is the same as another, whether it is found in an atom of carbon, sodium (Na), or iron (Fe). The same is true for neutrons and electrons. So, what gives an element its distinctive properties—what makes carbon so different from sodium or iron? The answer is the unique quantity of protons each contains. Carbon by definition is an element whose atoms contain six protons. No other element has exactly six protons in its atoms. Moreover, all atoms of carbon, whether found in your liver or in a lump of coal, contain six protons. Thus, the atomic number, which is the number of protons in the nucleus of the atom, identifies the element. Because an atom usually has the same number of electrons as protons, the atomic number identifies the usual number of electrons as well.

In their most common form, many elements also contain the same number of neutrons as protons. The most common form of carbon, for example, has six neutrons as well as six protons, for a total of 12 subatomic particles in its nucleus. An element’s mass number is the sum of the number of protons and neutrons in its nucleus. So the most common form of carbon’s mass number is 12. (Electrons have so little mass that they do not appreciably contribute to the mass of an atom.) Carbon is a relatively light element. Uranium (U), in contrast, has a mass number of 238 and is referred to as a heavy metal. Its atomic number is 92 (it has 92 protons) but it contains 146 neutrons; it has the most mass of all the naturally occurring elements.

The periodic table of the elements, shown below in Figure 3, is a chart identifying the 92 elements found in nature, as well as several larger, unstable elements discovered experimentally. The elements are arranged in order of their atomic number, with hydrogen and helium at the top of the table, and the more massive elements below. The periodic table is a useful device because for each element, it identifies the chemical symbol, the atomic number, and the mass number, while organizing elements according to their propensity to react with other elements. The number of protons and electrons in an element are equal. The number of protons and neutrons may be equal for some elements, but are not equal for all.

[caption id="" align="aligncenter" width="650"] Figure 3. The Periodic Table of the Elements. (credit: R.A. Dragoset, A. Musgrove, C.W. Clark, W.C. Martin)[/caption]

In the periodic table of the elements, elements in a single column have the same number of electrons that can participate in a chemical reaction. These electrons are known as “valence electrons.” For example, the elements in the first column all have a single valence electron, an electron that can be “donated” in a chemical reaction with another atom.

Isotopes

Although each element has a unique number of protons, it can exist as different isotopes. An isotope is one of the different forms of an element, distinguished from one another by different numbers of neutrons. The standard isotope of carbon is ¹²C, commonly called carbon twelve. ¹²C has six protons and six neutrons, for a mass number of twelve. All of the isotopes of carbon have the same number of protons; therefore,¹³C has seven neutrons, and ¹⁴C has eight neutrons. The different isotopes of an element can also be indicated with the mass number hyphenated (for example, C-12 instead of ¹²C). Hydrogen has three common isotopes, shown in Figure 4.

[caption id="" align="alignright" width="380"] Figure 4. Isotopes of Hydrogen. Protium, designated 1H, has one proton and no neutrons. It is by far the most abundant isotope of hydrogen in nature. Deuterium, designated 2H, has one proton and one neutron. Tritium, designated 3H, has two neutrons.[/caption]

An isotope that contains more than the usual number of neutrons is referred to as a heavy isotope. An example is ¹⁴C. Heavy isotopes tend to be unstable, and unstable isotopes are radioactive. A radioactive isotope is an isotope whose nucleus readily decays, giving off subatomic particles and electromagnetic energy. Different radioactive isotopes (also called radioisotopes) differ in their half-life, the time it takes for half of any size sample of an isotope to decay. For example, the half-life of tritium—a radioisotope of hydrogen—is about 12 years, indicating it takes 12 years for half of the tritium nuclei in a sample to decay. Excessive exposure to radioactive isotopes can damage human cells and even cause cancer and birth defects, but when exposure is controlled, some radioactive isotopes can be useful in medicine. For more information, see the Career Connections.

Radioisotopes emit subatomic particles that can be detected and tracked by imaging technologies. One of the most advanced uses of radioisotopes in medicine is the positron emission tomography (PET) scanner, which detects the activity in the body of a very small injection of radioactive glucose, the simple sugar that cells use for energy. The PET camera reveals to the medical team which of the patient’s tissues are taking up the most glucose. Thus, the most metabolically active tissues show up as bright “hot spots” on the images (Figure 5). PET can reveal some cancerous masses because cancer cells consume glucose at a high rate to fuel their rapid reproduction.

The Behavior of Electrons

In the human body, atoms do not exist as independent entities. Rather, they are constantly reacting with other atoms to form and to break down more complex substances. To fully understand anatomy and physiology you must grasp how atoms participate in such reactions. The key is understanding the behavior of electrons.

Although electrons do not follow rigid orbits a set distance away from the atom’s nucleus, they do tend to stay within certain regions of space called electron shells. An electron shell is a layer of electrons that encircle the nucleus at a distinct energy level.

The atoms of the elements found in the human body have from one to five electron shells, and all electron shells hold eight electrons except the first shell, which can only hold two. This configuration of electron shells is the same for all atoms. The precise number of shells depends on the number of electrons in the atom. Hydrogen and helium have just one and two electrons, respectively. If you take a look at the periodic table of the elements, you will notice that hydrogen and helium are placed alone on either sides of the top row; they are the only elements that have just one electron shell (Figure 6). A second shell is necessary to hold the electrons in all elements larger than hydrogen and helium.

Lithium (Li), whose atomic number is 3, has three electrons. Two of these fill the first electron shell, and the third spills over into a second shell. The second electron shell can accommodate as many as eight electrons. Carbon, with its six electrons, entirely fills its first shell, and half-fills its second. With ten electrons, neon (Ne) entirely fills its two electron shells. Again, a look at the periodic table reveals that all of the elements in the second row, from lithium to neon, have just two electron shells. Atoms with more than ten electrons require more than two shells. These elements occupy the third and subsequent rows of the periodic table.

[caption id="" align="alignright" width="420"] Figure 6. Electron Shells. Electrons orbit the atomic nucleus at distinct levels of energy called electron shells. (a) With one electron, hydrogen only half-fills its electron shell. Helium also has a single shell, but its two electrons completely fill it. (b) The electrons of carbon completely fill its first electron shell, but only half-fills its second. (c) Neon, an element that does not occur in the body, has 10 electrons, filling both of its electron shells.[/caption]

The factor that most strongly governs the tendency of an atom to participate in chemical reactions is the number of electrons in its valence shell. A valence shell is an atom’s outermost electron shell. If the valence shell is full, the atom is stable; meaning its electrons are unlikely to be pulled away from the nucleus by the electrical charge of other atoms. If the valence shell is not full, the atom is reactive; meaning it will tend to react with other atoms in ways that make the valence shell full. Consider hydrogen, with its one electron only half-filling its valence shell. This single electron is likely to be drawn into relationships with the atoms of other elements, so that hydrogen’s single valence shell can be stabilized.

All atoms (except hydrogen and helium with their single electron shells) are most stable when there are exactly eight electrons in their valence shell. This principle is referred to as the octet rule, and it states that an atom will give up, gain, or share electrons with another atom so that it ends up with eight electrons in its own valence shell. For example, oxygen, with six electrons in its valence shell, is likely to react with other atoms in a way that results in the addition of two electrons to oxygen’s valence shell, bringing the number to eight. When two hydrogen atoms each share their single electron with oxygen, covalent bonds are formed, resulting in a molecule of water, H₂O.

In nature, atoms of one element tend to join with atoms of other elements in characteristic ways. For example, carbon commonly fills its valence shell by linking up with four atoms of hydrogen. In so doing, the two elements form the simplest of organic molecules, methane, which also is one of the most abundant and stable carbon-containing compounds on Earth. As stated above, another example is water; oxygen needs two electrons to fill its valence shell. It commonly interacts with two atoms of hydrogen, forming H₂O. Incidentally, the name “hydrogen” reflects its contribution to water (hydro- = “water”; -gen = “maker”). Thus, hydrogen is the “water maker.”

2.2 Chemical Bonds

barkerj1 — Wed, 30 Aug 2017 18:36:24 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the formation of molecules and compounds
Describe the formation of ions and ionic bonds
Describe the formation of covalent bonds
Describe the chemical structure and chemical properties of water

Ions and Ionic Bonds

Recall that an atom typically has the same number of positively charged protons and negatively charged electrons. As long as this situation remains, the atom is electrically neutral. But when an atom participates in a chemical reaction that results in the donation or acceptance of one or more electrons, the atom will then become positively or negatively charged. This happens frequently for most atoms in order to have a full valence shell, as described previously. This can happen either by gaining electrons to fill a shell that is more than half-full, or by giving away electrons to empty a shell than is less than half-full, thereby leaving the next smaller electron shell as the new, full, valence shell. An atom that has an electrical charge—whether positive or negative—is an ion.

Potassium (K), for instance, is an important element in all body cells. Its atomic number is 19. It has just one electron in its valence shell. This characteristic makes potassium highly likely to participate in chemical reactions in which it donates one electron. (It is easier for potassium to donate one electron than to gain seven electrons.) The loss will cause the positive charge of potassium’s protons to be more influential than the negative charge of potassium’s electrons. In other words, the resulting potassium ion will be slightly positive. A potassium ion is written K⁺, indicating that it has lost a single electron. A positively charged ion is known as a cation.

Now consider fluorine (F), a component of bones and teeth. Its atomic number is nine, and it has seven electrons in its valence shell. Thus, it is highly likely to bond with other atoms in such a way that fluorine accepts one electron (it is easier for fluorine to gain one electron than to donate seven electrons). When it does, its electrons will outnumber its protons by one, and it will have an overall negative charge. The ionized form of fluorine is called fluoride, and is written as F^–. A negatively charged ion is known as an anion.

Atoms that have more than one electron to donate or accept will end up with stronger positive or negative charges. A cation that has donated two electrons has a net charge of +2. Using magnesium (Mg) as an example, this can be written Mg⁺⁺ or Mg²⁺. An anion that has accepted two electrons has a net charge of –2. The ionic form of selenium (Se), for example, is typically written Se^2–.

[caption id="" align="alignright" width="420"] Figure 1. Ionic Bonding. (a) Sodium readily donates the solitary electron in its valence shell to chlorine, which needs only one electron to have a full valence shell. (b) The opposite electrical charges of the resulting sodium cation and chloride anion result in the formation of a bond of attraction called an ionic bond. (c) The attraction of many sodium and chloride ions results in the formation of large groupings called crystals.[/caption]

The opposite charges of cations and anions exert a moderately strong mutual attraction that keeps the atoms in close proximity forming an ionic bond. An ionic bond is an ongoing, close association between ions of opposite charge. The table salt you sprinkle on your food owes its existence to ionic bonding. As shown in Figure 1, sodium commonly donates an electron to chlorine, becoming the cation Na⁺. When chlorine accepts the electron, it becomes the chloride anion, Cl^–. With their opposing charges, these two ions strongly attract each other.

Water is an essential component of life because it is able to break the ionic bonds in salts to free the ions. In fact, in biological fluids, most individual atoms exist as ions. These dissolved ions produce electrical charges within the body. The behavior of these ions produces the tracings of heart and brain function observed as waves on an electrocardiogram (EKG or ECG) or an electroencephalogram (EEG). The electrical activity that derives from the interactions of the charged ions is why they are also called electrolytes.

Covalent Bonds

Unlike ionic bonds formed by the attraction between a cation’s positive charge and an anion’s negative charge, molecules formed by a covalent bond share electrons in a mutually stabilizing relationship. Like next-door neighbors whose kids hang out first at one home and then at the other, the atoms do not lose or gain electrons permanently. Instead, the electrons move back and forth between the elements. Because of the close sharing of pairs of electrons (one electron from each of two atoms), covalent bonds are stronger than ionic bonds.

Nonpolar Covalent Bonds

Figure 2 shows several common types of covalent bonds. Notice that the two covalently bonded atoms typically share just one or two electron pairs, though larger sharings are possible. The important concept to take from this is that in covalent bonds, electrons in the outermost valence shell are shared to fill the valence shells of both atoms, ultimately stabilizing both of the atoms involved. In a single covalent bond, a single electron is shared between two atoms, while in a double covalent bond, two pairs of electrons are shared between two atoms. There even are triple covalent bonds, where three atoms are shared.

[caption id="" align="aligncenter" width="589"] Figure 2. Covalent Bonding.[/caption] You can see that the covalent bonds shown in Figure 2 are balanced. The sharing of the negative electrons is relatively equal, as is the electrical pull of the positive protons in the nucleus of the atoms involved. This is why covalently bonded molecules that are electrically balanced in this way are described as nonpolar; that is, no region of the molecule is either more positive or more negative than any other.

Polar Covalent Bonds

Groups of legislators with completely opposite views on a particular issue are often described as “polarized” by news writers. In chemistry, a polar molecule is a molecule that contains regions that have opposite electrical charges. Polar molecules occur when atoms share electrons unequally, in polar covalent bonds.

The most familiar example of a polar molecule is water (Figure 3). The molecule has three parts: one atom of oxygen, the nucleus of which contains eight protons, and two hydrogen atoms, whose nuclei each contain only one proton. Because every proton exerts an identical positive charge, a nucleus that contains eight protons exerts a charge eight times greater than a nucleus that contains one proton. This means that the negatively charged electrons present in the water molecule are more strongly attracted to the oxygen nucleus than to the hydrogen nuclei. Each hydrogen atom’s single negative electron therefore migrates toward the oxygen atom, making the oxygen end of their bond slightly more negative than the hydrogen end of their bond.

[caption id="" align="alignleft" width="380"] Figure 3. Polar Covalent Bonds in a Water Molecule.[/caption]

What is true for the bonds is true for the water molecule as a whole; that is, the oxygen region has a slightly negative charge and the regions of the hydrogen atoms have a slightly positive charge. These charges are often referred to as “partial charges” because the strength of the charge is less than one full electron, as would occur in an ionic bond. As shown in Figure 3, regions of weak polarity are indicated with the Greek letter delta (∂) and a plus (+) or minus (–) sign.

Even though a single water molecule is unimaginably tiny, it has mass, and the opposing electrical charges on the molecule pull that mass in such a way that it creates a shape somewhat like a triangular tent (see Figure 3b). The resulting dipole, with the positive charges at one end formed by the hydrogen atoms at the “bottom” of the tent and the negative charge at the opposite end (the oxygen atom at the “top” of the tent) makes the charged regions highly likely to interact with charged regions of other polar molecules. For human physiology, the resulting bond is one of the most important formed by water—the hydrogen bond.

Hydrogen Bonds

A hydrogen bond is formed when a weakly positive hydrogen atom already bonded to one electronegative atom (for example, the oxygen in the water molecule) is attracted to another electronegative atom from another molecule. In other words, hydrogen bonds always include hydrogen that is already part of a polar molecule.

The most common example of hydrogen bonding in the natural world occurs between molecules of water. It happens before your eyes whenever two raindrops merge into a larger bead, or a creek spills into a river. Hydrogen bonding occurs because the weakly negative oxygen atom in one water molecule is attracted to the weakly positive hydrogen atoms of two other water molecules (Figure 4).

[caption id="" align="alignright" width="280"] Figure 4. Hydrogen Bonds between Water Molecules. Notice that the bonds occur between the weakly positive charge on the hydrogen atoms and the weakly negative charge on the oxygen atoms. Hydrogen bonds are relatively weak, and therefore are indicated with a dotted (rather than a solid) line.[/caption]

Water molecules also strongly attract other types of charged molecules as well as ions. This explains why sodium chloride or “table salt,” for example, which consists of equal numbers of positively-charged sodium (Na⁺) and negatively-charged chloride (Cl^–), dissolves so readily in water. In this case dipole-ion bonds form between the water and the electrically-charged ions (electrolytes), allowing moving water molecules to pull the Na⁺ and Cl^– away from each other. Water molecules also repel molecules with nonpolar covalent bonds, like fats, lipids, and oils. You can demonstrate this with a simple kitchen experiment: pour a teaspoon of vegetable oil, a compound formed by nonpolar covalent bonds, into a glass of water. Instead of instantly dissolving in the water, the oil forms a distinct bead because the polar water molecules repel the nonpolar oil.

[caption id="attachment_2948" align="aligncenter" width="150"] Watch this SciShow video to learn more about electrostatic forces![/caption] [caption id="attachment_2949" align="aligncenter" width="150"] Watch this CrashCourse video to learn more bonding![/caption]

2.4 Inorganic Compounds Essential to Human Functioning

barkerj1 — Wed, 30 Aug 2017 18:36:28 +0000

Learning Objectives

By the end of this section, you will be able to:

Distinguish between organic and inorganic molecules
Specify the chemical and physical properties of water
Explain the biological importance of water

The concepts you have learned so far in this chapter govern all forms of matter, and would work as a foundation for geology as well as biology. This section of the chapter narrows the focus to the chemistry of human life; that is, the compounds important for the body’s structure and function. In general, these compounds are either inorganic or organic.

An inorganic compound is a substance that does not contain both carbon and hydrogen. A great many inorganic compounds do contain hydrogen atoms, such as water (H₂O) and the hydrochloric acid (HCl) produced by your stomach. In contrast, only a handful of inorganic compounds contain carbon atoms. Carbon dioxide (CO₂) is one of the few examples.
An organic compound, then, is a molecule that contains both carbon and hydrogen. Many organic compounds can be synthesized via covalent bonds within living organisms, including the human body. Recall that carbon and hydrogen are the second and third most abundant elements in your body. You will soon discover how these two elements combine in the foods you eat, in the compounds that make up your body structure, and in the chemicals that fuel your functioning.

The following section examines the three groups of inorganic compounds essential to life: water, salts, acids, and bases. Organic compounds are covered later in the chapter.

Water

As much as 70 percent of an adult’s body weight is water. This water is contained both within the cells and between the cells that make up tissues and organs. Its several roles make water indispensable to human functioning.

Water as a Lubricant and Cushion

Water is a major component of many of the body’s lubricating fluids. Just as oil lubricates the hinge on a door, water in synovial fluid lubricates the actions of body joints, and water in pleural fluid helps the lungs expand and recoil with breathing. Watery fluids help keep food flowing through the digestive tract, and ensure that the movement of adjacent abdominal organs is friction free.

Water also protects cells and organs from physical trauma, cushioning the brain within the skull, for example, and protecting the delicate nerve tissue of the eyes. Water cushions a developing fetus in the mother’s womb as well.

Water as a Heat Sink

A heat sink is a substance or object that absorbs and dissipates heat but does not experience a corresponding increase in temperature. In the body, water absorbs the heat generated by chemical reactions without greatly increasing in temperature. Moreover, when environmental temperature soars, the water stored in the body helps keep the body cool. This cooling effect happens as warm blood from the body’s core flows to the blood vessels just under the skin and is transferred out to the environment as radiant heat. At the same time, sweat glands release warm water in sweat. For evaporation of this water to occur, the hydrogen bonds between the water molecules must be broken, requiring a relatively high amount of energy that in part includes heat. This removal of heat by evaporation results in a cooling of the blood in the body's periphery, near the surface of the skin, which then circulates back to the body core and cools the body.

Water as a Component of Liquid Mixtures

A mixture is a combination of two or more substances, each of which maintains its own chemical identity. In other words, the constituent substances are not chemically bonded into a new, larger chemical compound. The concept is easy to imagine if you think of powdery substances such as flour and sugar; when you stir them together in a bowl, they obviously do not bond to form a new compound. The room air you breathe is a gaseous mixture, containing three discrete elements—nitrogen, oxygen, and argon—and one compound, carbon dioxide. There are three types of liquid mixtures, all of which contain water as a key component. These are solutions, colloids, and suspensions.

For cells in the body to survive, they must be kept moist in a water-based liquid called a solution. In chemistry, a liquid solution consists of a solvent that dissolves a substance called a solute. An important characteristic of solutions is that they are homogeneous; that is, the solute molecules are distributed evenly throughout the solution. If you were to stir a teaspoon of sugar into a glass of water, the sugar would dissolve into sugar molecules separated by water molecules. The ratio of sugar to water in the left side of the glass would be the same as the ratio of sugar to water in the right side of the glass. If you were to add more sugar, the ratio of sugar to water would change, but the distribution—provided you had stirred well—would still be even.

Water is considered the “universal solvent” and it is believed that life cannot exist without water because of this. Water is certainly the most abundant solvent in the body; essentially all of the body’s chemical reactions occur among compounds dissolved in water. Because water molecules are polar, with regions of positive and negative electrical charge, water readily dissolves ionic compounds and polar covalent compounds. Such compounds are referred to as hydrophilic, or “water-loving.” As mentioned above, sugar dissolves well in water. This is because sugar molecules contain regions of hydrogen-oxygen polar bonds, making it hydrophilic. Nonpolar molecules, which do not readily dissolve in water, are called hydrophobic, or “water-fearing.”

The Role of Water in Chemical Reactions

[caption id="" align="aligncenter" width="603"] Figure 1. Dehydration Synthesis and Hydrolysis. Monomers, the basic units for building larger molecules, form polymers (two or more chemically-bonded monomers). (a) In dehydration synthesis, two monomers are covalently bonded in a reaction in which one gives up a hydroxyl group and the other a hydrogen atom. A molecule of water is released as a byproduct during dehydration reactions. (b) In hydrolysis, the covalent bond between two monomers is split by the addition of a hydrogen atom to one and a hydroxyl group to the other, which requires the contribution of one molecule of water.[/caption]

Two types of chemical reactions involve the creation or the consumption of water: dehydration synthesis and hydrolysis.

In dehydration synthesis, one reactant gives up an atom of hydrogen and another reactant gives up a hydroxyl group (OH) in the synthesis of a new product. In the formation of their covalent bond, a molecule of water is released as a byproduct (Figure 1). This is also sometimes referred to as a condensation reaction.
In hydrolysis, a molecule of water disrupts a compound, breaking its bonds. The water is itself split into H and OH. One portion of the severed compound then bonds with the hydrogen atom, and the other portion bonds with the hydroxyl group.

These reactions are reversible, and play an important role in the chemistry of organic compounds (which will be discussed shortly).

[caption id="attachment_3037" align="aligncenter" width="150"] Watch this amoeba sisters video to learn more about the properties of water![/caption]

[caption id="attachment_2951" align="aligncenter" width="150"] Watch this CrashCourse video to learn more about the importance of water and its chemical properties.[/caption]

Salts

[caption id="" align="alignright" width="480"] Figure 2. Dissociation of Sodium Chloride in Water. Notice that the crystals of sodium chloride dissociate not into molecules of NaCl, but into Na+ cations and Cl– anions, each completely surrounded by water molecules.[/caption] Recall that salts are formed when ions form ionic bonds. In these reactions, one atom gives up one or more electrons, and thus becomes positively charged, whereas the other accepts one or more electrons and becomes negatively charged. You can now define a salt as a substance that, when dissolved in water, dissociates into ions other than H⁺ or OH^–. This fact is important in distinguishing salts from acids and bases, discussed next.

A typical salt, NaCl, dissociates completely in water (Figure 2). The positive and negative regions on the water molecule (the hydrogen and oxygen ends respectively) attract the negative chloride and positive sodium ions, pulling them away from each other. Again, whereas nonpolar and polar covalently bonded compounds break apart into molecules in solution, salts dissociate into ions. These ions are electrolytes; they are capable of conducting an electrical current in solution. This property is critical to the function of ions in transmitting nerve impulses and prompting muscle contraction.

Many other salts are important in the body. For example, bile salts produced by the liver help break apart dietary fats, and calcium phosphate salts form the mineral portion of teeth and bones.

2.5 Organic Compounds Essential to Human Functioning

barkerj1 — Wed, 30 Aug 2017 18:36:38 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the composition of organic molecules
Specify two characteristics of organic molecules that make them useful to living organisms
Name and describe specific examples of organic molecules
Specify the major elements that make up carbohydrate molecules
Describe three major groups of carbohydrates, using specific examples and specifying one function in the human body served by each group
Specify the major elements that make up lipid molecules
Specify a function for each of the following groups of lipids: triglycerides, phospholipids, and steroids
Describe the structural components of a typical phospholipid molecule
Distinguish between the polar "head" and non-polar "tail" ends of a phospholipid molecule
Distinguish between saturated, unsaturated, and polyunsaturated fats
Specify the major elements that make up protein molecules
Describe, using examples, eight major functional groups of proteins
Specify the major elements that make up nucleic acids
Describe the structure and function of the two types of nucleic acids
Describe the general structure and importance of adenosine triphosphate

Organic compounds typically consist of groups of carbon atoms covalently bonded to hydrogen, usually oxygen, and often other elements as well. Created by living things, they are found throughout the world, in soils and seas, commercial products, and every cell of the human body. The four types most important to human structure and function are carbohydrates, lipids, proteins, and nucleotides. Before exploring these compounds, you need to first understand the chemistry of carbon.

The Chemistry of Carbon

What makes organic compounds ubiquitous is the chemistry of their carbon core. Recall that carbon atoms have four electrons in their valence shell, and that the octet rule dictates that atoms tend to react in such a way as to complete their valence shell with eight electrons. Carbon atoms do not complete their valence shells by donating or accepting four electrons. Instead, they readily share electrons via covalent bonds.

Commonly, carbon atoms share with other carbon atoms, often forming a long carbon chain referred to as a carbon skeleton. When they do share, however, they do not share all their electrons exclusively with each other. Rather, carbon atoms tend to share electrons with a variety of other elements; in organic compounds, one of these elements is always hydrogen. Carbon and hydrogen groupings are called hydrocarbons. If you study the figures of organic compounds in the remainder of this chapter, you will see several with chains of hydrocarbons in one region of the compound.

Many combinations are possible to fill carbon’s four “vacancies.” Carbon may share electrons with oxygen or nitrogen or other atoms in a particular region of an organic compound. Moreover, the atoms to which carbon atoms bond may also be part of a functional group. A functional group is a group of atoms linked by strong covalent bonds and tending to function in chemical reactions as a single unit. You can think of functional groups as tightly knit “cliques” whose members are unlikely to be parted. Five functional groups are important in human physiology; these are the hydroxyl, carboxyl, amino, methyl and phosphate groups (Table 1).

Functional Groups Important in Human Physiology
Functional group	Structural formula	Importance
Hydroxyl	—O—H	Hydroxyl groups are polar. They are components of all four types of organic compounds discussed in this chapter. They are involved in dehydration synthesis and hydrolysis reactions.
Carboxyl	O—C—OH	Carboxyl groups are found within fatty acids, amino acids, and many other acids.
Amino	—N—H₂	Amino groups are found within amino acids, the building blocks of proteins.
Methyl	—C—H₃	Methyl groups are found within amino acids.
Phosphate	—P—O₄^2–	Phosphate groups are found within phospholipids and nucleotides.

Carbon’s affinity for covalent bonding means that many distinct and relatively stable organic molecules nevertheless readily form larger, more complex molecules. Any large molecule is referred to as macromolecule (macro- = “large”), and the organic compounds in this section all fit this description. However, some macromolecules are made up of several “copies” of single units called monomer (mono- = “one”; -mer = “part”). Like beads in a long necklace, these monomers link by covalent bonds to form long polymers (poly- = “many”). There are many examples of monomers and polymers among the organic compounds.

Monomers form polymers by engaging in dehydration synthesis (see Chapter 2.4 Figure 1). As was noted earlier, this reaction results in the release of a molecule of water. Each monomer contributes: One gives up a hydrogen atom and the other gives up a hydroxyl group. Polymers are split into monomers by hydrolysis (-lysis = “rupture”). The bonds between their monomers are broken, via the donation of a molecule of water, which contributes a hydrogen atom to one monomer and a hydroxyl group to the other.

The fact that organic molecules can be assembled into very large polymers with complex structures makes them useful to living cells in several ways. One results largely from the sheer size of the molecules; this allows them to be used as structural components of cells, such as the membranes of cells and the fibers of the cytoskeleton and extracellular matrix. Another is the result of the relative complexity of the molecules possible; the many different ways in which carbon atoms can bind to each other and to other elements allows for complex structures that allow molecules to interact with each other in unique ways. This for example allows proteins called enzymes to interact with other molecules to control the location and rate at which specific chemical reactions occur within cells. It also means that organic molecules may be hydrophobic or hydrophilic in nature, or a combination of the two, depending on their size and chemical composition. Again this makes them useful as structural components, as they can be used to make membranes that separate different aqueous fluid compartments from each other. Finally, the chemical energy present in the covalent bonds in many organic molecules can be transferred to other molecules, in the form of new bonds. For example, some of the energy contained in the bonds of a glucose molecule can be harvested and used by living cells to attach a phosphate group to a molecule of adenosine diphosphate, making the molecule adenosine triphosphate (ATP). The vital importance of ATP to the functioning of human cells is discussed later in this section, and in more detail elsewhere in this textbook. Carbohydrates

The term carbohydrate means “hydrated carbon.” Recall that the root hydro- indicates water. A carbohydrate is a molecule composed of carbon, hydrogen, and oxygen; in most carbohydrates, hydrogen and oxygen are found in the same two-to-one relative proportions they have in water. In fact, the chemical formula for a “generic” molecule of carbohydrate is (CH₂O)_n.

Carbohydrates are referred to as saccharides, a word meaning “sugars.” Three forms are important in the body. Monosaccharides are the monomers of carbohydrates. Disaccharides (di- = “two”) are made up of two monomers. Polysaccharides are the polymers, and can consist of hundreds to thousands of monomers.

[caption id="" align="alignleft" width="420"] Figure 1. Five Important Monosaccharides.[/caption]

Monosaccharides

A monosaccharide is a monomer of carbohydrates. Five monosaccharides are important in the body. Three of these are the hexose sugars, so called because they each contain six atoms of carbon. These are glucose, fructose, and galactose, shown in Figure 1a. The remaining monosaccharides are the two pentose sugars, each of which contains five atoms of carbon. They are ribose and deoxyribose, shown in Figure 2b.

Disaccharides

A disaccharide is a pair of monosaccharides. Disaccharides are formed via dehydration synthesis, and the bond linking them is referred to as a glycosidic bond (glyco- = “sugar”). Three disaccharides (shown in Figure 2) are important to humans. These are sucrose, commonly referred to as table sugar; lactose, or milk sugar; and maltose, or malt sugar. As you can tell from their common names, you consume these in your diet; however, your body cannot use them directly. Instead, in the digestive tract, they are split into their component monosaccharides via hydrolysis.

[caption id="" align="aligncenter" width="420"] Figure 2. Three Important Disaccharides. All three important disaccharides form by dehydration synthesis.[/caption]

Polysaccharides

Polysaccharides can contain a few to a thousand or more monosaccharides. Three are important to the body (Figure 3):

Starches are polymers of glucose. They occur in long chains called amylose or branched chains called amylopectin, both of which are stored in plant-based foods and are relatively easy to digest.
Glycogen is also a polymer of glucose, but it is stored in the tissues of animals, especially in the muscles and liver. It is not considered a dietary carbohydrate because very little glycogen remains in animal tissues after slaughter; however, the human body stores excess glucose as glycogen, again, in the muscles and liver.
Cellulose, a polysaccharide that is the primary component of the cell wall of green plants, is the component of plant food referred to as “fiber”. In humans, cellulose/fiber is not digestible; however, dietary fiber has many health benefits. It helps you feel full so you eat less, it promotes a healthy digestive tract, and a diet high in fiber is thought to reduce the risk of heart disease and possibly some forms of cancer.

[caption id="" align="aligncenter" width="412"] Figure 3. Three Important Polysaccharides. Three important polysaccharides are starches, glycogen, and fiber.[/caption]

Functions of Carbohydrates

The body obtains carbohydrates from plant-based foods. Grains, fruits, and legumes and other vegetables provide most of the carbohydrate in the human diet, although lactose is found in dairy products.

Although most body cells can break down other organic compounds for fuel, all body cells can use glucose. Moreover, nerve cells (neurons) in the brain, spinal cord, and through the peripheral nervous system, as well as red blood cells, can use only glucose for fuel. In the breakdown of glucose for energy, molecules of adenosine triphosphate, better known as ATP, are produced. Adenosine triphosphate (ATP) is composed of a ribose sugar, an adenine base, and three phosphate groups. ATP releases free energy when its phosphate bonds are broken, and thus supplies ready energy to the cell. More ATP is produced in the presence of oxygen (O₂) than in pathways that do not use oxygen. The overall reaction for the conversion of the energy in glucose to energy stored in ATP can be written:

C₆H₁₂O₆ + 6 O₂ → 6 CO₂ + 6 H₂O + ATP

In addition to being a critical fuel source, carbohydrates are used in small amounts as part of a cell's structure. For instance, some carbohydrate molecules bind with proteins to produce glycoproteins, and others combine with lipids to produce glycolipids, both of which are found in the membrane that encloses the contents of body cells. The carbohydrate chains protrude outward from the cell membrane, creating a structure known as the glycocalyx ("sugar coat") of a cell that is used in cell adhesion and recognition. Pentose sugars are critical structural components of ATP and the nucleotides that make up RNA and DNA.

Lipids

A lipid is one of a highly diverse group of compounds made up mostly of hydrocarbons. The few oxygen atoms they contain are often at the periphery of the molecule. Their nonpolar hydrocarbons make all lipids hydrophobic. In water, lipids do not form a true solution, but they may form an emulsion, which is the term for a mixture of solutions that do not mix well.

Triglycerides

A triglyceride is one of the most common dietary lipid groups, and the type found most abundantly in body tissues. This compound, which is commonly referred to as a fat, is formed from the synthesis of two types of molecules (Figure 4):

A glycerol backbone at the core of triglycerides, consists of three carbon atoms.
Three fatty acids, long chains of hydrocarbons with a carboxyl group and a methyl group at opposite ends, extend from each of the carbons of the glycerol.

[caption id="" align="alignleft" width="550"] Figure 4. Triglycerides. Triglycerides are composed of glycerol attached to three fatty acids via dehydration synthesis. Notice that glycerol gives up a hydrogen atom, and the carboxyl groups on the fatty acids each give up a hydroxyl group.[/caption]

Triglycerides form via dehydration synthesis. Glycerol gives up hydrogen atoms from its hydroxyl groups at each bond, and the carboxyl group on each fatty acid chain gives up a hydroxyl group. A total of three water molecules are thereby released.

Fatty acid chains that have no double carbon bonds anywhere along their length and therefore contain the maximum number of hydrogen atoms are called saturated fatty acids. These straight, rigid chains pack tightly together and are solid or semi-solid at room temperature (Figure 5a). Butter and lard are examples, as is the fat found on a steak or in your own body. In contrast, fatty acids with one double carbon bond are kinked at that bond (Figure 5b). These monounsaturated fatty acids are therefore unable to pack together tightly, and are liquid at room temperature. Polyunsaturated fatty acids contain two or more double carbon bonds, and are also liquid at room temperature. Plant oils such as olive oil typically contain both mono- and polyunsaturated fatty acids.

[caption id="" align="alignright" width="380"] Figure 5. Fatty Acid Shapes. The level of saturation of a fatty acid affects its shape. (a) Saturated fatty acid chains are straight. (b) Unsaturated fatty acid chains are kinked.[/caption]

Whereas a diet high in saturated fatty acids increases the risk of heart disease, a diet high in unsaturated fatty acids is thought to reduce the risk. This is especially true for the omega-3 unsaturated fatty acids found in cold-water fish such as salmon. These fatty acids have their first double carbon bond at the third hydrocarbon from the methyl group (referred to as the omega end of the molecule).

Finally, trans fatty acids found in some processed foods, including some stick and tub margarines, are thought to be even more harmful to the heart and blood vessels than saturated fatty acids. Trans fats are created from unsaturated fatty acids (such as corn oil) when chemically treated to produce partially hydrogenated fats.

As a group, triglycerides are a major fuel source for the body. When you are resting or asleep, a majority of the energy used to keep you alive is derived from triglycerides stored in your fat (adipose) tissues. Triglycerides also fuel long, slow physical activity such as gardening or hiking, and contribute a modest percentage of energy for vigorous physical activity. Dietary fat also assists the absorption and transport of the nonpolar fat-soluble vitamins A, D, E, and K. Additionally, stored body fat protects and cushions the body’s bones and internal organs, and acts as insulation to retain body heat.

Fatty acids are also components of glycolipids, which are sugar-fat compounds found in the cell membrane. Lipoproteins are compounds in which the hydrophobic triglycerides are packaged in protein envelopes for transport in body fluids.

Phospholipids

As its name suggests, a phospholipid is a bond between the glycerol component of a lipid and a phosphorous molecule. In fact, phospholipids are similar in structure to triglycerides. However, instead of having three fatty acids, a phospholipid is generated from a diglyceride, a glycerol with just two fatty acid chains (Figure 6). The third binding site on the glycerol is taken up by the phosphate group, which in turn is attached to a polar “head” region of the molecule. Recall that triglycerides are nonpolar and hydrophobic. This still holds for the fatty acid portion of a phospholipid compound. However, the head of a phospholipid contains charges on the phosphate groups, as well as on the nitrogen atom. These charges make the phospholipid head hydrophilic. Therefore, phospholipids are said to have hydrophobic tails, containing the neutral fatty acids, and hydrophilic heads, containing the charged phosphate groups and nitrogen atom.

[caption id="" align="aligncenter" width="600"] Figure 6. Other Important Lipids. (a) Phospholipids are composed of two fatty acids, glycerol, and a phosphate group. (b) Sterols are ring-shaped lipids. Shown here is cholesterol. (c) Prostaglandins are derived from unsaturated fatty acids. Prostaglandin E2 (PGE2) includes hydroxyl and carboxyl groups.[/caption]

Steroids

A steroid compound (referred to as a sterol) has as its foundation a set of four hydrocarbon rings bonded to a variety of other atoms and molecules (see Figure 6b). Although both plants and animals synthesize sterols, the type that makes the most important contribution to human structure and function is cholesterol, which is synthesized by the liver in humans and animals and is also present in most animal-based foods. Like other lipids, cholesterol’s hydrocarbons make it hydrophobic; however, it has a polar hydroxyl head that is hydrophilic. Cholesterol is an important component of bile acids, compounds that help emulsify dietary fats. In fact, the word root chole- refers to bile. Cholesterol is also a building block of many hormones, signaling molecules that the body releases to regulate processes at distant sites. Finally, like phospholipids, cholesterol molecules are found in the cell membrane, where their hydrophobic and hydrophilic regions help regulate the flow of substances into and out of the cell.

Prostaglandins

Like a hormone, a prostaglandin is one of a group of signaling molecules, but prostaglandins are derived from unsaturated fatty acids (see Figure 6c). One reason that the omega-3 fatty acids found in fish are beneficial is that they stimulate the production of certain prostaglandins that help regulate aspects of blood pressure and inflammation, and thereby reduce the risk for heart disease. Prostaglandins also sensitize nerves to pain. One class of pain-relieving medications called nonsteroidal anti-inflammatory drugs (NSAIDs) works by reducing the effects of prostaglandins.

Proteins

You might associate proteins with muscle tissue, but in fact, proteins are critical components of all tissues and organs. A protein is an organic molecule composed of amino acids linked by peptide bonds. Proteins include the keratin in the epidermis of skin that protects underlying tissues, the collagen found in the dermis of skin, in bones, and in the meninges that cover the brain and spinal cord. Proteins are also components of many of the body’s functional chemicals, including digestive enzymes in the digestive tract, antibodies, the neurotransmitters that neurons use to communicate with other cells, and the peptide-based hormones that regulate certain body functions (for instance, growth hormone). While carbohydrates and lipids are composed of hydrocarbons and oxygen, all proteins also contain nitrogen (N), and many contain sulfur (S), in addition to carbon, hydrogen, and oxygen.

Microstructure of Proteins

Proteins are polymers made up of nitrogen-containing monomers called amino acids. An amino acid is a molecule composed of an amino group and a carboxyl group, together with a variable side chain. Just 20 different amino acids contribute to nearly all of the thousands of different proteins important in human structure and function. Body proteins contain a unique combination of a few dozen to a few hundred of these 20 amino acid monomers. All 20 of these amino acids share a similar structure (Figure 7). All consist of a central carbon atom to which the following are bonded:

[caption id="" align="alignright" width="320"] Figure 8. Structure of an Amino Acid[/caption]

a hydrogen atom
an alkaline (basic) amino group NH₂ (see Table 1)
an acidic carboxyl group COOH (see Table 1)
a variable group

Notice that all amino acids contain both an acid (the carboxyl group) and a base (the amino group) (amine = “nitrogen-containing”). For this reason, they make excellent buffers, helping the body regulate acid–base balance. What distinguishes the 20 amino acids from one another is their variable group, which is referred to as a side chain or an R-group. This group can vary in size and can be polar or nonpolar, giving each amino acid its unique characteristics. For example, the side chains of two amino acids—cysteine and methionine—contain sulfur. Sulfur does not readily participate in hydrogen bonds, whereas all other amino acids do. This variation influences the way that proteins containing cysteine and methionine are assembled.

Amino acids join via dehydration synthesis to form protein polymers (Figure 8). The unique bond holding amino acids together is called a peptide bond. A peptide bond is a covalent bond between two amino acids that forms by dehydration synthesis. A peptide, in fact, is a very short chain of amino acids. Strands containing fewer than about 100 amino acids are generally referred to as polypeptides rather than proteins. [caption id="" align="alignright" width="280"] Figure 8.Peptide Bond. Different amino acids join together to form peptides, polypeptides, or proteins via dehydration synthesis. The bonds between the amino acids are peptide bonds.[/caption]

The body is able to synthesize most of the amino acids from components of other molecules; however, nine cannot be synthesized and have to be consumed in the diet. These are known as the essential amino acids.

Free amino acids available for protein construction are said to reside in the amino acid pool within cells. Structures within cells use these amino acids when assembling proteins. If a particular essential amino acid is not available in sufficient quantities in the amino acid pool, however, synthesis of proteins containing it can slow or even cease.

Shape of Proteins

Just as a fork cannot be used to eat soup and a spoon cannot be used to spear meat, a protein’s shape is essential to its function. A protein’s shape is determined, most fundamentally, by the sequence of amino acids of which it is made (Figure 9a).

The sequence is called the primary structure of the protein. [caption id="" align="aligncenter" width="480"] Figure 9. The Shape of Proteins. (a) The primary structure is the sequence of amino acids that make up the polypeptide chain. (b) The secondary structure, which can take the form of an alpha-helix or a beta-pleated sheet, is maintained by hydrogen bonds between amino acids in different regions of the original polypeptide strand. (c) The tertiary structure occurs as a result of further folding and bonding of the secondary structure. (d) The quaternary structure occurs as a result of interactions between two or more tertiary subunits. The example shown here is hemoglobin, a protein in red blood cells which transports oxygen to body tissues.[/caption]

Although some polypeptides exist as linear chains, most are twisted or folded into more complex secondary structures that form when bonding occurs between amino acids with different properties at different regions of the polypeptide. The most common secondary structure is a spiral called an alpha-helix. If you were to take a length of string and simply twist it into a spiral, it would not hold the shape. Similarly, a strand of amino acids could not maintain a stable spiral shape without the help of hydrogen bonds, which create bridges between different regions of the same strand (see Figure 9b). Less commonly, a polypeptide chain can form a beta-pleated sheet, in which hydrogen bonds form bridges between different regions of a single polypeptide that has folded back upon itself, or between two or more adjacent polypeptide chains.

The secondary structure of proteins further folds into a compact three-dimensional shape, referred to as the protein’s tertiary structure (see Figure 9c). In this configuration, amino acids that had been very distant in the primary chain can be brought quite close via hydrogen bonds or, in proteins containing cysteine, via disulfide bonds. A disulfide bond is a covalent bond between sulfur atoms in a polypeptide. Often, two or more separate polypeptides bond to form an even larger protein with a quaternary structure (see Figure 9d). The polypeptide subunits forming a quaternary structure can be identical or different. For instance, hemoglobin, the protein found in red blood cells is composed of four tertiary polypeptides, two of which are called alpha chains and two of which are called beta chains.

When they are exposed to extreme heat, acids, bases, and certain other substances, proteins will denature. Denaturation is a change in the structure of a molecule through physical or chemical means. Denatured proteins lose their functional shape and are no longer able to carry out their jobs. An everyday example of protein denaturation is the curdling of milk when acidic lemon juice is added.

The contribution of the shape of a protein to its function can hardly be exaggerated. For example, the long, slender shape of protein strands that make up muscle tissue is essential to their ability to contract (shorten) and relax (lengthen). As another example, bones contain long threads of a protein called collagen that acts as scaffolding upon which bone minerals are deposited. These elongated proteins, called fibrous proteins, are strong and durable and typically hydrophobic. Fibrous proteins are used for movement, from muscle cell contraction (actin and myosin) down to intracellular transport (e.g. actin). They are also used to provide a structural framework or mechanical support of connective tissues (e.g. collagen, keratin, elastin), individual cells (e.g. titin), and plasma membranes (e.g. spectrin, dystrophin).

In contrast, globular proteins are shaped like globes or spheres that tend to be highly reactive and are hydrophilic. Globular proteins are abundant throughout the body, playing critical roles in most body functions. Enzymes, introduced earlier as protein catalysts, are examples of this; the next section takes a closer look at the catalytic action of enzymes, but globular proteins serve many other functions in the human body as well.

Some globular proteins are used to transport specific molecules (e.g. hormones or gases) or ions (e.g. iron or calcium) in blood. The hemoglobin proteins packed into red blood cells for example (see Figure 9d) are used to transport the oxygen gas molecules from the lungs to other body cells. Others (e.g. albumin, hemoglobin) can help regulate body fluid pH by reversibly functioning as acids or bases, thus acting as buffers. Some globular proteins act as hormones to regulate metabolism, and are referred to as peptide hormones or protein hormones (e.g. insulin, growth hormone, oxytocin). Others are used to defend the body against foreign substances including invading pathogens and toxins (e.g. antibodies, complement proteins). Finally, some globular proteins known as molecular chaperones are essential to the production of other proteins and the appropriate breakdown of damaged proteins.

Proteins Function as Enzymes

If you were trying to type a paper, and every time you hit a key on your laptop there was a delay of six or seven minutes before you got a response, you would probably get a new laptop. In a similar way, without enzymes to catalyze chemical reactions, the human body would be nonfunctional. It functions only because enzymes function.

Enzymatic reactions—chemical reactions catalyzed by enzymes—begin when substrates bind to the enzyme. A substrate is a reactant in an enzymatic reaction. This occurs on regions of the enzyme known as active sites (Figure 10). Any given enzyme catalyzes just one type of chemical reaction. This characteristic, called specificity, is due to the fact that a substrate with a particular shape and electrical charge can bind only to an active site corresponding to that substrate.

[caption id="" align="aligncenter" width="520"] Figure 10. Steps in an Enzymatic Reaction. (a) Substrates approach active sites on enzyme. (b) Substrates bind to active sites, producing an enzyme–substrate complex. (c) Changes internal to the enzyme–substrate complex facilitate interaction of the substrates. (d) Products are released and the enzyme returns to its original form, ready to facilitate another enzymatic reaction.[/caption]

Binding of a substrate produces an enzyme–substrate complex. It is likely that enzymes speed up chemical reactions in part because the enzyme–substrate complex undergoes a set of temporary and reversible changes that cause the substrates to be oriented toward each other in an optimal position to facilitate their interaction. This promotes increased reaction speed. The enzyme then releases the product(s), and resumes its original shape. The enzyme is then free to engage in the process again, and will do so as long as substrate remains.

Other Functions of Proteins

Advertisements for protein bars, powders, and shakes all say that protein is important in building, repairing, and maintaining muscle tissue, but the truth is that proteins contribute to all body tissues, from the skin to the brain cells. Also, certain proteins act as hormones, chemical messengers that help regulate body functions, For example, growth hormone is important for skeletal growth, among other roles.

As was noted earlier, the basic and acidic components enable proteins to function as buffers in maintaining acid–base balance, but they also help regulate fluid–electrolyte balance. Proteins attract fluid, and a healthy concentration of proteins in the blood, the cells, and the spaces between cells helps ensure a balance of fluids in these various “compartments.” Moreover, proteins in the cell membrane help to transport electrolytes in and out of the cell, keeping these ions in a healthy balance. Like lipids, proteins can bind with carbohydrates. They can thereby produce glycoproteins or proteoglycans, both of which have many functions in the body.

The body can use proteins for energy when carbohydrate and fat intake is inadequate, and stores of glycogen and adipose tissue become depleted. However, since there is no storage site for protein except functional tissues, using protein for energy causes tissue breakdown, and results in body wasting.

Nucleotides

The fourth type of organic compound important to human structure and function are the nucleotides (Figure 11). A nucleotide is one of a class of organic compounds composed of three subunits:

one or more phosphate groups
a pentose sugar: either deoxyribose or ribose
a nitrogen-containing base: adenine, cytosine, guanine, thymine, or uracil

Nucleotides can be assembled into nucleic acids (DNA or RNA) or the energy compound adenosine triphosphate.

[caption id="" align="aligncenter" width="520"] Figure 11. Nucleotides. (a) The building blocks of all nucleotides are one or more phosphate groups, a pentose sugar, and a nitrogen-containing base. (b) The nitrogen-containing bases of nucleotides. (c) The two pentose sugars of DNA and RNA.[/caption]

Nucleic Acids

The nucleic acids differ in their type of pentose sugar. Deoxyribonucleic acid (DNA) is nucleotide that stores genetic information. DNA contains deoxyribose (so-called because it has one less atom of oxygen than ribose) plus one phosphate group and one nitrogen-containing base. The “choices” of base for DNA are adenine, cytosine, guanine, and thymine. Ribonucleic acid (RNA) is a ribose-containing nucleotide that helps manifest the genetic code as protein. RNA contains ribose, one phosphate group, and one nitrogen-containing base, but the “choices” of base for RNA are adenine, cytosine, guanine, and uracil.

The nitrogen-containing bases adenine and guanine are classified as purines. A purine is a nitrogen-containing molecule with a double ring structure, which accommodates several nitrogen atoms. The bases cytosine, thymine (found in DNA only) and uracil (found in RNA only) are pyramidines. A pyramidine is a nitrogen-containing base with a single ring structure

[caption id="" align="alignleft" width="320"] Figure 12. DNA. In the DNA double helix, two strands attach via hydrogen bonds between the bases of the component nucleotides.[/caption]

Bonds formed by dehydration synthesis between the pentose sugar of one nucleic acid monomer and the phosphate group of another form a “backbone,” from which the components’ nitrogen-containing bases protrude. In DNA, two such backbones attach at their protruding bases via hydrogen bonds. These twist to form a shape known as a double helix (Figure 12). The sequence of nitrogen-containing bases within a strand of DNA form the genes that act as a molecular code instructing cells in the assembly of amino acids into proteins. Humans have almost 22,000 genes in their DNA, locked up in the 46 chromosomes inside the nucleus of each cell (except red blood cells which lose their nuclei during development). These genes carry the genetic code to build one’s body, and are unique for each individual except identical twins.

In contrast, RNA consists of a single strand of sugar-phosphate backbone studded with bases. Messenger RNA (mRNA) is created during protein synthesis to carry the genetic instructions from the DNA to the cell’s protein manufacturing plants in the cytoplasm, the ribosomes.

Adenosine Triphosphate

[caption id="" align="alignright" width="420"] Figure 13. Structure of Adenosine Triphosphate (ATP).[/caption]

The nucleotide adenosine triphosphate (ATP), is composed of a ribose sugar, an adenine base, and three phosphate groups (Figure 13). ATP is classified as a high energy compound because the two covalent bonds linking its three phosphates store a significant amount of potential energy. In the body, the energy released from these high energy bonds helps fuel the body’s activities, from muscle contraction to the transport of substances in and out of cells to anabolic chemical reactions.

When a phosphate group is cleaved from ATP, the products are adenosine diphosphate (ADP) and inorganic phosphate (P_i). This hydrolysis reaction can be written:

ATP + H₂O → ADP + P_i + energy

Removal of a second phosphate leaves adenosine monophosphate (AMP) and two phosphate groups. Again, these reactions also liberate the energy that had been stored in the phosphate-phosphate bonds. They are reversible, too, as when ADP undergoes phosphorylation. Phosphorylation is the addition of a phosphate group to an organic compound, in this case, resulting in ATP. In such cases, the same level of energy that had been released during hydrolysis must be reinvested to power dehydration synthesis.

Cells can also transfer a phosphate group from ATP to another organic compound. For example, when glucose first enters a cell, a phosphate group is transferred from ATP, forming glucose phosphate (C₆H₁₂O₆—P) and ADP. Once glucose is phosphorylated in this way, it can be stored as glycogen or metabolized for immediate energy.

[caption id="attachment_3052" align="aligncenter" width="150"] Watch this amoeba sisters video to learn more about biomolecules![/caption]

Introduction

barkerj1 — Wed, 30 Aug 2017 18:36:39 +0000

[caption id="" align="aligncenter" width="356"] Figure 1. Fluorescence-stained Cell Undergoing Mitosis. A lung cell from a newt, commonly studied for its similarity to human lung cells, is stained with fluorescent dyes. The green stain reveals mitotic spindles, red is the cell membrane and part of the cytoplasm, and the structures that appear light blue are chromosomes. This cell is in anaphase of mitosis. (credit: “Mortadelo2005”/Wikimedia Commons)[/caption] You developed from a single fertilized egg cell into the complex organism containing trillions of cells that you see when you look in a mirror. During this developmental process, early, undifferentiated cells differentiate and become specialized in their structure and function. These different cell types form specialized tissues that work in concert to perform all of the functions necessary for the living organism. Cellular and developmental biologists study how the continued division of a single cell leads to such complexity and differentiation. Consider the difference between a structural cell in the skin and a nerve cell. A structural skin cell may be shaped like a flat plate (squamous) and live only for a short time before it is shed and replaced. Packed tightly into rows and sheets, the squamous skin cells provide a protective barrier for the cells and tissues that lie beneath. A nerve cell, on the other hand, may be shaped something like a star, sending out long processes up to a meter in length and may live for the entire lifetime of the organism. With their long winding appendages, nerve cells can communicate with one another and with other types of body cells and send rapid signals that inform the organism about its environment and allow it to interact with that environment. These differences illustrate one very important theme that is consistent at all organizational levels of biology: the form of a structure is optimally suited to perform particular functions assigned to that structure. Keep this theme in mind as you tour the inside of a cell and are introduced to the various types of cells in the body. A primary responsibility of each cell is to contribute to homeostasis. Homeostasis is a term used in biology that refers to a dynamic state of balance within parameters that are compatible with life. For example, living cells require a water-based environment to survive in, and there are various physical (anatomical) and physiological mechanisms that keep all of the trillions of living cells in the human body moist. This is one aspect of homeostasis. When a particular parameter, such as blood pressure or blood oxygen content, moves far enough out of homeostasis (generally becoming too high or too low), illness or disease—and sometimes death—inevitably results. The concept of a cell started with microscopic observations of dead cork tissue by scientist Robert Hooke in 1665. Without realizing their function or importance, Hook coined the term “cell” based on the resemblance of the small subdivisions in the cork to the rooms that monks inhabited, called cells. About ten years later, Antonie van Leeuwenhoek became the first person to observe living and moving cells under a microscope. In the century that followed, the theory that cells represented the basic unit of life would develop. These tiny fluid-filled sacs house components responsible for the thousands of biochemical reactions necessary for an organism to grow and survive. In this chapter, you will learn about the major components and functions of a prototypical, generalized cell and discover some of the different types of cells in the human body. [caption id="attachment_3048" align="aligncenter" width="150"] Watch this amoeba sisters video for an introduction to the cell![/caption]

3.1 The Cell Membrane

barkerj1 — Wed, 30 Aug 2017 18:36:42 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the structure and components of the cell membrane
Describe the function of the plasma membrane
Describe the "fluid mosaic" model of membrane structure
Describe how the structure of the cell membrane affects membrane permeability
Describe and explain the effects of placing erythrocytes in hypertonic, hypotonic, and isotonic solutions
Describe and clearly distinguish between the processes of diffusion and active transport
Describe and clearly distinguish between the processes of simple diffusion and facilitated diffusion
Describe the process of osmosis and explain how it differs from diffusion
Describe and clearly distinguish between the processes of phagocytosis and pinocytosis
Explain the importance of each of the above transport processes to the functioning of a cell

Despite differences in structure and function, all living cells in multicellular organisms have a surrounding cell membrane. As the outer layer of your skin separates your body from its environment, the cell membrane (also known as the plasma membrane) separates the inner contents of a cell from its exterior environment. This cell membrane provides a protective barrier around the cell and regulates which materials can pass in or out.

Structure and Composition of the Cell Membrane

The cell membrane is an extremely pliable structure composed primarily of back-to-back phospholipids (a “bilayer”). Cholesterol is also present, which contributes to the fluidity of the membrane, and there are various proteins embedded within the membrane that have a variety of functions.

[caption id="" align="alignleft" width="280"] Figure 1. Phospholipid Structure. A phospholipid molecule consists of a polar phosphate “head,” which is hydrophilic and a non-polar lipid “tail,” which is hydrophobic. Unsaturated fatty acids result in kinks in the hydrophobic tails.[/caption] A single phospholipid molecule has a phosphate group on one end, called the “head,” and two side-by-side chains of fatty acids that make up the lipid tails (Figure 1). The phosphate group is negatively charged, making the head polar and hydrophilic—or “water loving.” A hydrophilic molecule (or region of a molecule) is one that is attracted to water. The phosphate heads are thus attracted to the water molecules of both the extracellular and intracellular environments. The lipid tails, on the other hand, are uncharged, or nonpolar, and are hydrophobic—or “water fearing.” A hydrophobic molecule (or region of a molecule) repels and is repelled by water. Some lipid tails consist of saturated fatty acids and some contain unsaturated fatty acids. This combination adds to the fluidity of the tails that are constantly in motion. Phospholipids are thus amphipathic molecules. An amphipathic molecule is one that contains both a hydrophilic and a hydrophobic region. In fact, soap works to remove oil and grease stains because it has amphipathic properties. The hydrophilic portion can dissolve in water while the hydrophobic portion can trap grease in micelles that then can be washed away.

[caption id="" align="alignright" width="280"] Figure 2. Phospolipid Bilayer. The phospholipid bilayer consists of two adjacent sheets of phospholipids, arranged tail to tail. The hydrophobic tails associate with one another, forming the interior of the membrane. The polar heads contact the fluid inside and outside of the cell.[/caption] The cell membrane consists of two adjacent layers of phospholipids. The lipid tails of one layer face the lipid tails of the other layer, meeting at the interface of the two layers. The phospholipid heads face outward, one layer exposed to the interior of the cell and one layer exposed to the exterior (Figure 2). Because the phosphate groups are polar and hydrophilic, they are attracted to water in the intracellular fluid. Intracellular fluid (ICF) is the fluid interior of the cell. The phosphate groups are also attracted to the extracellular fluid. Extracellular fluid (ECF) is the fluid environment outside the enclosure of the cell membrane. Interstitial fluid (IF) is the term given to extracellular fluid not contained within blood vessels. Because the lipid tails are hydrophobic, they meet in the inner region of the membrane, excluding watery intracellular and extracellular fluid from this space. The cell membrane has many proteins, as well as other lipids (such as cholesterol), that are associated with the phospholipid bilayer. An important feature of the membrane is that it remains fluid; the lipids and proteins in the cell membrane are not rigidly locked in place.

Membrane Proteins

The lipid bilayer forms the basis of the cell membrane, but it is peppered throughout with various proteins. Two different types of proteins that are commonly associated with the cell membrane are the integral proteins and peripheral protein (Figure 3). As its name suggests, an integral protein is a protein that is embedded in the membrane. A channel protein is an example of an integral protein that selectively allows particular materials, such as certain ions, to pass into or out of the cell.

[caption id="" align="aligncenter" width="495"] Figure 3. Cell Membrane. The cell membrane of the cell is a phospholipid bilayer containing many different molecular components, including proteins and cholesterol, some with carbohydrate groups attached.[/caption]

Another important group of integral proteins are cell recognition proteins, which serve to mark a cell’s identity so that it can be recognized by other cells. A receptor is a type of recognition protein that can selectively bind a specific molecule outside the cell, and this binding induces a chemical reaction within the cell. A ligand is the specific molecule that binds to and activates a receptor. Some integral proteins serve dual roles as both a receptor and an ion channel. One example of a receptor-ligand interaction is the receptors on nerve cells that bind neurotransmitters, such as dopamine. When a dopamine molecule binds to a dopamine receptor protein, a channel within the transmembrane protein opens to allow certain ions to flow into the cell.

Some integral membrane proteins are glycoproteins. A glycoprotein is a protein that has carbohydrate molecules attached, which extend into the extracellular matrix. The attached carbohydrate tags on glycoproteins aid in cell recognition. The carbohydrates that extend from membrane proteins and even from some membrane lipids collectively form the glycocalyx. The glycocalyx is a fuzzy-appearing coating around the cell formed from glycoproteins and other carbohydrates attached to the cell membrane. The glycocalyx can have various roles. For example, it may have molecules that allow the cell to bind to another cell, it may contain receptors for hormones, or it might have enzymes to break down nutrients. The glycocalyces found in a person’s body are products of that person’s genetic makeup. They give each of the individual’s trillions of cells the “identity” of belonging in the person’s body. This identity is the primary way that a person’s immune defense cells “know” not to attack the person’s own body cells, but it also is the reason organs donated by another person might be rejected.

Peripheral proteins are typically found on the inner or outer surface of the lipid bilayer but can also be attached to the internal or external surface of an integral protein. These proteins typically perform a specific function for the cell. Some peripheral proteins on the surface of intestinal cells, for example, act as digestive enzymes to break down nutrients to sizes that can pass through the cells and into the bloodstream.

Transport across the Cell Membrane

One of the great wonders of the cell membrane is its ability to regulate the concentration of substances inside the cell. These substances include ions such as Ca⁺⁺, Na⁺, K⁺, and Cl^–; nutrients including sugars, fatty acids, and amino acids; and waste products, particularly carbon dioxide (CO₂), which must leave the cell.

The membrane’s lipid bilayer structure provides the first level of control. The phospholipids are tightly packed together, and the membrane has a hydrophobic interior. This structure causes the membrane to be selectively permeable. A membrane that has selective permeability allows only substances meeting certain criteria to pass through it unaided. In the case of the cell membrane, only relatively small, nonpolar materials can move through the lipid bilayer (remember, the lipid tails of the membrane are nonpolar). Some examples of these are other lipids, oxygen and carbon dioxide gases, and alcohol. However, water-soluble materials—like glucose, amino acids, and electrolytes—need some assistance to cross the membrane because they are repelled by the hydrophobic tails of the phospholipid bilayer. All substances that move through the membrane do so by one of two general methods, which are categorized based on whether or not energy is required. Passive transport is the movement of substances across the membrane using their own kinetic energy, without the expenditure of chemical energy. In contrast, active transport is the movement of substances across the membrane using energy from the hydrolysis of adenosine triphosphate (ATP).

Passive Transport

In order to understand how substances move passively across a cell membrane, it is necessary to understand concentration gradients and diffusion. A concentration gradient is the difference in concentration of a substance across a space. Molecules (or ions) will spread/diffuse from where they are more concentrated to where they are less concentrated until they are equally distributed in that space. (When molecules move in this way, they are said to move down their concentration gradient.) Diffusion is the movement of particles from an area of higher concentration to an area of lower concentration. A couple of common examples will help to illustrate this concept. Imagine being inside a closed bathroom. If a bottle of perfume were sprayed, the scent molecules would naturally diffuse from the spot where they left the bottle to all corners of the bathroom, and this diffusion would go on until no more concentration gradient remains. Another example is a spoonful of sugar placed in a cup of tea. Eventually the sugar will diffuse throughout the tea until no concentration gradient remains. In both cases, if the room is warmer or the tea hotter, diffusion occurs even faster as the molecules are bumping into each other and spreading out faster than at cooler temperatures. Having an internal body temperature around 98.6^°F thus also aids in diffusion of particles within the body.

Whenever a substance exists in greater concentration on one side of a semipermeable membrane than on the other side, such as the cell membranes, any substance that can move down its concentration gradient across the membrane will do so. Consider substances that can easily diffuse through the lipid bilayer of the cell membrane, such as the gases oxygen (O₂) and CO₂. O₂ generally diffuses into cells because it is more concentrated outside of them, and CO₂ typically diffuses out of cells because it is more concentrated inside of them. In both these examples the molecules rely on their own kinetic energy to move, so neither of these examples requires any chemical energy output from the cell. The movement of molecules across a cell membrane without the expenditure of cellular energy is referred to as passive transport, or diffusion.

[caption id="" align="alignright" width="380"] Figure 4. Simple Diffusion across the Cell (Plasma) Membrane. The structure of the lipid bilayer allows small, uncharged substances such as oxygen and carbon dioxide, and hydrophobic molecules such as lipids, to pass through the cell membrane, down their concentration gradient, by simple diffusion.[/caption] Before moving on, you need to review the gases that can diffuse across a cell membrane. Because cells rapidly use up oxygen during metabolism, there is typically a lower concentration of O₂ inside the cell than outside. As a result, oxygen will diffuse from the interstitial fluid into the cytoplasm within the cell. On the other hand, because cells produce CO₂ as a byproduct of metabolism, CO₂ concentrations rise within the cytoplasm; therefore, CO₂ will move from the cell into the interstitial fluid, where its concentration is lower. Both these molecules are small and nonpolar, which means they can easily interact with the hydrophobic core of a lipid bilayer and move between the molecules to get from one side to the other. This mechanism of small, nonpolar molecules slipping between the lipid tails of a cell membrane from the side where they are more concentrated to the side where they are less concentrated is a form of passive transport called simple diffusion (Figure 4). [caption id="" align="alignright" width="300"] Figure 5. Facilitated Diffusion. (a) Facilitated diffusion of substances crossing the cell (plasma) membrane takes place with the help of proteins such as channel proteins and carrier proteins. Channel proteins are less selective than carrier proteins, and usually mildly discriminate between their cargo based on size and charge. (b) Carrier proteins are more selective, often only allowing one particular type of molecule to cross.[/caption] Large polar or ionic molecules, which are hydrophilic, cannot easily cross the phospholipid bilayer. Charged atoms or molecules of any size cannot cross the cell membrane via simple diffusion as the charges are repelled by the hydrophobic tails in the interior of the phospholipid bilayer. Solutes dissolved in water on either side of the cell membrane will tend to diffuse down their concentration gradients, but because most substances cannot pass freely through the lipid bilayer of the cell membrane, their movement is restricted to protein channels and specialized transport mechanisms in the membrane. Facilitated diffusion is the diffusion process used for those substances that cannot cross the lipid bilayer due to their size, charge, and/or polarity (Figure 5). A common example of facilitated diffusion is the movement of glucose into the cell, where it is used to make ATP. Although glucose can be more concentrated outside of a cell, it cannot cross the lipid bilayer via simple diffusion because it is both large and polar. To resolve this, a specialized carrier protein called the glucose transporter will transfer glucose molecules into the cell to facilitate its inward diffusion. Glucose and other relatively large polar molecules typically bind to transport proteins that change shape to allow the molecules into the cell by a process known as carrier-mediated facilitated diffusion.

As an example, even though sodium ions (Na⁺) are highly concentrated outside of cells, these electrolytes are charged and cannot pass through the nonpolar lipid bilayer of the membrane. Their diffusion is facilitated by membrane proteins that form sodium channels (or “pores”), so that Na⁺ ions can move down their concentration gradient from outside the cells to inside the cells. The use of a protein that acts as a channel through which an ion or small polar molecule can move down its concentration gradient is referred to as channel-mediated facilitated diffusion.

There are many other solutes that must undergo facilitated diffusion to move into a cell, such as amino acids, or to move out of a cell, such as wastes. Because facilitated diffusion is a passive process, it does not require chemical energy expenditure by the cell. [caption id="" align="alignleft" width="280"] Figure 6. Osmosis. Osmosis is the diffusion of water through a semipermeable membrane down its concentration gradient. If a membrane is permeable to water, though not to a solute, water will equalize its own concentration by diffusing to the side of lower water concentration (and thus the side of higher solute concentration). In the beaker on the left, the solution on the right side of the membrane is hypertonic relative to the solution on the left side of the membrane.[/caption] Very small polar molecules, including water, can cross a phospholipid bilayer via simple diffusion due to their small size. The rate at which water can move across cell membranes is increased by the presence of membrane proteins called aquaporins that form channels through which water molecules (but not solutes) can pass. Osmosis refers to the passive movement of water across a semipermeable membrane (Figure 6). Osmosis across a cell membrane therefore includes the movement of water molecules by either simple diffusion or facilitated diffusion or both.

The movement of water across a cell membrane cannot be directly determined by cells, so it is important that cells are exposed to an environment in which the concentration of solutes outside of the cells (in the extracellular fluid) is equal to the concentration of solutes inside the cells (in the cytoplasm). Two solutions that have the same concentration of solutes are said to be isotonic (equal tension). When cells and their extracellular environments are isotonic, the concentration of water molecules is the same outside and inside the cells, and the cells maintain their normal shape (and function).

[caption id="" align="alignright" width="280"] Figure 7. Concentration of Solutions. A hypertonic solution has a solute concentration higher than another solution. An isotonic solution has a solute concentration equal to another solution. A hypotonic solution has a solute concentration lower than another solution.[/caption] Osmosis occurs when there is an imbalance of solutes outside of a cell versus inside the cell. A solution that has a higher concentration of solutes than another solution is said to be hypertonic, and water molecules tend to diffuse into a hypertonic solution (Figure 7). Cells in a hypertonic solution will shrivel as water leaves the cell via osmosis. In contrast, a solution that has a lower concentration of solutes than another solution is said to be hypotonic, and water molecules tend to diffuse out of a hypotonic solution. Cells in a hypotonic solution will take on too much water and swell, with the risk of eventually bursting. A critical aspect of homeostasis in living things is to create an internal environment in which all of the body’s cells are in an isotonic solution. Various organ systems, particularly the kidneys, work to maintain this homeostasis.

Another mechanism besides diffusion to passively transport materials between compartments is filtration. Unlike diffusion of a substance from where it is more concentrated to less concentrated, filtration uses a hydrostatic pressure gradient that pushes the fluid—and the solutes within it—from a higher pressure area to a lower pressure area. Filtration is an extremely important process in the body. For example, the circulatory system uses filtration to move plasma and substances across the endothelial lining of capillaries and into surrounding tissues, supplying cells with the nutrients. Filtration pressure in the kidneys provides the mechanism to remove wastes from the bloodstream.

Active Transport

For all of the transport methods described above, the cell does not need to use chemical energy. Membrane proteins that aid in the passive transport of substances do so without the use of ATP. During active transport, ATP is required to move a substance across a membrane, often with the help of carrier proteins, and usually against the concentration gradient of the substance being moved.

One of the most common types of active transport involves proteins that serve as pumps. The word “pump” probably conjures up thoughts of using energy to pump up the tire of a bicycle or a basketball. Similarly, chemical energy from ATP is required for these membrane proteins to transport substances—molecules or ions—across the membrane, usually against their concentration gradients (from an area of low concentration to an area of high concentration).

The sodium-potassium pump, which is also called Na⁺/K⁺ ATPase, transports sodium out of a cell while moving potassium into the cell. The Na⁺/K⁺ pump is an important ion pump found in the membranes of many types of cells. These pumps are particularly abundant in nerve cells, which are constantly pumping out sodium ions and pulling in potassium ions to maintain an electrical gradient across their cell membranes. An electrical gradient is a difference in electrical charge across a space. In the case of nerve cells, for example, the electrical gradient exists between the inside and outside of the cell, with the inside being negatively-charged (at around -70 mV) relative to the outside. The negative electrical gradient is maintained because each Na⁺/K⁺ pump moves three Na⁺ ions out of the cell and two K⁺ ions into the cell for each ATP molecule that is used (Figure 8). This process is so important for nerve cells that it accounts for the majority of their ATP usage.

[caption id="" align="aligncenter" width="550"] Figure 8. Sodium-Potassium Pump. The sodium-potassium pump is found in many cell (plasma) membranes. Powered by ATP, the pump moves sodium and potassium ions in opposite directions, each against its concentration gradient. In a single cycle of the pump, three sodium ions are extruded from and two potassium ions are imported into the cell.[/caption]

Active transport pumps can also work together with other active or passive transport systems to move substances across the membrane. For example, the sodium-potassium pump maintains a high concentration of sodium ions outside of the cell. Therefore, if the cell needs sodium ions, all it has to do is open a passive sodium channel, as the concentration gradient of the sodium ions will drive them to diffuse into the cell. In this way, the action of an active transport pump (the sodium-potassium pump) powers the passive transport of sodium ions by creating a concentration gradient. When active transport of one substance is used to power the transport of another substance in this way, it is called secondary active transport, to distinguish it from primary active transport mechanisms that use the chemical energy in ATP to directly drive the movement of an ion or molecule.

Symporters are secondary active transporters that move two substances in the same direction. For example, the sodium-glucose symporter uses sodium ions to “pull” glucose molecules into the cell. Because cells store glucose for energy, glucose is typically at a higher concentration inside of the cell than outside. However, due to the action of the sodium-potassium pump, sodium ions will easily diffuse into the cell when the symporter is opened. The flood of sodium ions through the symporter provides the energy that allows glucose to move through the symporter and into the cell, against its concentration gradient.

Conversely, antiporters are secondary active transport systems that transport substances in opposite directions. For example, the sodium-hydrogen ion antiporter uses the energy from the inward flood of sodium ions to move hydrogen ions (H+) out of the cell. The sodium-hydrogen antiporter is used to maintain the pH of the cell's interior.

[caption id="" align="alignleft" width="380"] Figure 9. Three Forms of Endocytosis. Endocytosis is a form of active transport in which a cell envelopes extracellular materials using its cell membrane. (a) In phagocytosis, which is relatively nonselective, the cell takes in a large particle. (b) In pinocytosis, the cell takes in small particles in fluid. (c) In contrast, receptor-mediated endocytosis is quite selective. When external receptors bind a specific ligand, the cell responds by endocytosing the ligand.[/caption] Other forms of active transport do not involve membrane carriers. Endocytosis (bringing “into the cell”) is the process of a cell ingesting material by enveloping it in a portion of its cell membrane, and then pinching off that portion of membrane (Figure 9). Once pinched off, the portion of membrane and its contents becomes an independent, intracellular vesicle. A vesicle is a membranous sac—a spherical and hollow organelle bounded by a lipid bilayer membrane. Endocytosis often brings materials into the cell that must to be broken down or digested. Phagocytosis (“cell eating”) is the endocytosis of large particles. Many immune cells engage in phagocytosis of invading pathogens. Like little Pac-men, their job is to patrol body tissues for unwanted matter, such as invading bacterial cells, phagocytize them, and digest them. In contrast to phagocytosis, pinocytosis (“cell drinking”) brings fluid containing dissolved substances into a cell through membrane vesicles.

Phagocytosis and pinocytosis take in large portions of extracellular material, and they are typically not highly selective in the substances they bring in. Cells regulate the endocytosis of specific substances via receptor-mediated endocytosis. Receptor-mediated endocytosis is endocytosis by a portion of the cell membrane that contains many receptors that are specific for a certain substance. Once the surface receptors have bound sufficient amounts of the specific substance (the receptor’s ligand), the cell will endocytose the part of the cell membrane containing the receptor-ligand complexes. Iron, a required component of hemoglobin, is endocytosed by red blood cells in this way. Iron is bound to a protein called transferrin in the blood. Specific transferrin receptors on red blood cell surfaces bind the iron-transferrin molecules, and the cell endocytoses the receptor-ligand complexes.

[caption id="" align="aligncenter" width="242"] Figure 10. Exocytosis. Exocytosis is much like endocytosis in reverse. Material destined for export is packaged into a vesicle inside the cell. The membrane of the vesicle fuses with the cell membrane, and the contents are released into the extracellular space.[/caption]

In contrast with endocytosis, exocytosis (taking “out of the cell”) is the process of a cell exporting material using vesicular transport (Figure 10). Many cells manufacture substances that must be secreted, like a factory manufacturing a product for export. These substances are typically packaged into membrane-bound vesicles within the cell. When the vesicle membrane fuses with the cell membrane, the vesicle releases it contents into the interstitial fluid. The vesicle membrane then becomes part of the cell membrane. Cells of the stomach and pancreas produce and secrete digestive enzymes through exocytosis (Figure 11). Endocrine cells produce and secrete hormones that are sent throughout the body, and certain immune cells produce and secrete large amounts of histamine, a chemical important for immune responses.

[caption id="" align="aligncenter" width="370"] Figure 11. Pancreatic Cells' Enzyme Products. The pancreatic acinar cells produce and secrete many enzymes that digest food. The tiny black granules in this electron micrograph are secretory vesicles filled with enzymes that will be exported from the cells via exocytosis. LM × 2900. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption]

[caption id="attachment_3050" align="aligncenter" width="150"] Watch this amoeba sisters video to learn more about cell transport![/caption]

[caption id="attachment_2954" align="aligncenter" width="150"] Watch this CrashCourse video on membranes and transport![/caption] [caption id="attachment_2955" align="aligncenter" width="150"] Check out the Khan Academy membranes and transport section to find out more[/caption]

3.2 The Cytoplasm and Cellular Organelles

barkerj1 — Wed, 30 Aug 2017 18:36:44 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the structure and function of the cellular organelles associated with the endomembrane system, including the endoplasmic reticulum, Golgi apparatus, vesicles, and lysosomes
Describe the structure and function of ribosomes
Describe the structure and function of mitochondria

[caption id="" align="aligncenter" width="450"] Figure 1. Prototypical Human Cell. While this image is not indicative of any one particular human cell, it is a prototypical example of a cell containing the primary organelles and internal structures.[/caption] Now that you have learned that the cell membrane surrounds all cells, you can dive inside of a prototypical human cell to learn about its internal components and their functions. All living cells in multicellular organisms contain an internal cytoplasmic compartment, and a nucleus within the cytoplasm. Cytosol, the jelly-like substance within the cell, provides the fluid medium necessary for biochemical reactions. Eukaryotic cells, including all animal cells, also contain various cellular organelles. An organelle (“little organ”) is one of several different types of membrane-enclosed bodies in the cell, each performing a unique function. Just as the various bodily organs work together in harmony to perform all of a human’s functions, the many different cellular organelles work together to keep the cell healthy and performing all of its important functions. The organelles and cytosol, taken together, compose the cell’s cytoplasm. The nucleus is a cell’s central organelle, which contains the cell’s DNA (Figure 1).

Organelles of the Endomembrane System

A set of three major organelles together form a system within the cell called the endomembrane system. These organelles work together to perform various cellular jobs, including the task of producing, packaging, and exporting certain cellular products. The organelles of the endomembrane system include the endoplasmic reticulum, Golgi apparatus, and vesicles.

Endoplasmic Reticulum

The endoplasmic reticulum (ER) is a system of channels that is continuous with the nuclear membrane (or “envelope”) covering the nucleus and composed of the same lipid bilayer material. The ER can be thought of as a series of winding thoroughfares similar to the waterway canals in Venice. The ER provides passages throughout much of the cell that function in transporting, synthesizing, and storing materials. The winding structure of the ER results in a large membranous surface area that supports its many functions (Figure 2).

[caption id="" align="aligncenter" width="550"] Figure 2. Endoplasmic Reticulum (ER). (a) The ER is a winding network of thin membranous sacs found in close association with the cell nucleus. The smooth and rough endoplasmic reticula are very different in appearance and function (source: mouse tissue). (b) Rough ER is studded with numerous ribosomes, which are sites of protein synthesis (source: mouse tissue). EM × 110,000. (c) Smooth ER synthesizes phospholipids, steroid hormones, regulates the concentration of cellular Ca²⁺,metabolizes some carbohydrates, and breaks down certain toxins (source: mouse tissue). EM × 110,510. (Micrographs provided by the Regents of University of Michigan Medical School © 2012)[/caption]

Endoplasmic reticulum can exist in two forms: rough ER and smooth ER. These two types of ER perform some very different functions and can be found in very different amounts depending on the type of cell. Rough ER (RER) is so-called because its membrane is dotted with embedded granules—organelles called ribosomes, giving the RER a bumpy appearance. A ribosome is an organelle that serves as the site of protein synthesis. It is composed of two ribosomal RNA subunits that wrap around mRNA to start the process of translation, followed by protein synthesis. Smooth ER (SER) lacks these ribosomes.

One of the main functions of the smooth ER is in the synthesis of lipids. The smooth ER synthesizes phospholipids, the main component of biological membranes, as well as steroid hormones. For this reason, cells that produce large quantities of such hormones, such as those of the female ovaries and male testes, contain large amounts of smooth ER. In addition to lipid synthesis, the smooth ER also sequesters (i.e., stores) and regulates the concentration of cellular Ca²⁺, a function extremely important in cells of the nervous system where Ca²⁺ is the trigger for neurotransmitter release. The smooth ER additionally metabolizes some carbohydrates and performs a detoxification role, breaking down certain toxins.

In contrast with the smooth ER, the primary job of the rough ER is the synthesis and modification of proteins destined for the cell membrane or for export from the cell. For this protein synthesis, many ribosomes attach to the ER (giving it the studded appearance of rough ER). Typically, a protein is synthesized within the ribosome and released inside the channel of the rough ER, where sugars can be added to it (by a process called glycosylation) before it is transported within a vesicle to the next stage in the packaging and shipping process: the Golgi apparatus.

The Golgi Apparatus

The Golgi apparatus is responsible for sorting, modifying, and shipping off the products that come from the rough ER, much like a post-office. The Golgi apparatus looks like stacked flattened discs, almost like stacks of oddly shaped pancakes. Like the ER, these discs are membranous. The Golgi apparatus has two distinct sides, each with a different role. One side of the apparatus receives products in vesicles. These products are sorted through the apparatus, and then they are released from the opposite side after being repackaged into new vesicles. If the product is to be exported from the cell, the vesicle migrates to the cell surface and fuses to the cell membrane, and the cargo is secreted (Figure 3). [caption id="" align="aligncenter" width="550"] Figure 3. Golgi Apparatus. (a) The Golgi apparatus manipulates products from the rough ER, and also produces new organelles called lysosomes. Proteins and other products of the ER are sent to the Golgi apparatus, which organizes, modifies, packages, and tags them. Some of these products are transported to other areas of the cell and some are exported from the cell through exocytosis. Enzymatic proteins are packaged as new lysosomes (or packaged and sent for fusion with existing lysosomes). (b) An electron micrograph of the Golgi apparatus.[/caption]

Lysosomes

Some of the protein products packaged by the Golgi include digestive enzymes that are meant to remain inside the cell for use in breaking down certain materials. The enzyme-containing vesicles released by the Golgi may form new lysosomes, or fuse with existing, lysosomes. A lysosome is an organelle that contains enzymes that break down and digest unneeded cellular components, such as a damaged organelle. (A lysosome is similar to a wrecking crew that takes down old and unsound buildings in a neighborhood.) Autophagy (“self-eating”) is the process of a cell digesting its own structures. Lysosomes are also important for breaking down foreign material. For example, when certain immune defense cells (white blood cells) phagocytize bacteria, the bacterial cell is transported into a lysosome and digested by the enzymes inside. As one might imagine, such phagocytic defense cells contain large numbers of lysosomes.

Under certain circumstances, lysosomes perform a more grand and dire function. In the case of damaged or unhealthy cells, lysosomes can be triggered to open up and release their digestive enzymes into the cytoplasm of the cell, killing the cell. This “self-destruct” mechanism is called autolysis, and makes the process of cell death controlled (a mechanism called “apoptosis”).

Watch this Khan Academy video to learn more about the endomembrane system

Organelles for Energy Production

In addition to the jobs performed by the endomembrane system, the cell has many other important functions. Just as you must consume nutrients to provide yourself with energy, so must each of your cells take in nutrient molecules whose chemical energy can be harvested to power biochemical reactions.

Mitochondria

[caption id="" align="aligncenter" width="520"] Figure 4. Mitochondrion. The mitochondria are the energy-conversion factories of the cell. (a) A mitochondrion is composed of two separate lipid bilayer membranes. Along the inner membrane are various molecules that work together to produce ATP, the cell’s major energy currency. (b) An electron micrograph of mitochondria. EM × 236,000. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption]

A mitochondrion (plural = mitochondria) is a membranous, bean-shaped organelle that is the “energy transformer” of the cell. Mitochondria consist of an outer lipid bilayer membrane as well as an additional inner lipid bilayer membrane (Figure 4). The inner membrane is highly folded into winding structures with a great deal of surface area, called cristae. It is along this inner membrane that a series of proteins, enzymes, and other molecules perform the biochemical reactions of cellular respiration. These reactions convert energy stored in nutrient molecules (such as glucose) into adenosine triphosphate (ATP), which provides usable cellular energy to the cell. Cells use ATP constantly, and so the mitochondria are constantly at work. Oxygen molecules are required during cellular respiration, which is why you must constantly breathe it in. One of the organ systems in the body that uses huge amounts of ATP is the muscular system because ATP is required to sustain muscle contraction. As a result, muscle cells are packed full of mitochondria. Nerve cells also need large quantities of ATP to run their sodium-potassium pumps. Therefore, an individual neuron will be loaded with over a thousand mitochondria. On the other hand, a bone cell, which is not nearly as metabolically-active, might only have a couple hundred mitochondria.

3.3 The Nucleus

barkerj1 — Wed, 30 Aug 2017 18:36:45 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the structure and features of the nuclear membrane
Describe the structure and function of the nucleolus
Describe the structure and function of chromosomes

[caption id="" align="alignright" width="382"] Figure 1. The Nucleus. The nucleus is the control center of the cell. The nucleus of living cells contains the genetic material that determines the entire structure and function of that cell.[/caption] The nucleus is the largest and most prominent of a cell’s organelles (Figure 1). The nucleus is generally considered the control center of the cell because it stores all of the genetic instructions for manufacturing proteins. Interestingly, some cells in the body, such as muscle cells, contain more than one nucleus (Figure 2), which is known as multinucleated. Other cells, such as mammalian red blood cells (RBCs), do not contain nuclei at all. RBCs eject their nuclei as they mature, making space for the large numbers of hemoglobin molecules that carry oxygen throughout the body (Figure 3). Without nuclei, the life span of RBCs is short, and so the body must produce new ones constantly.

[caption id="" align="alignleft" width="345"] Figure 2. Multinucleate Muscle Cell. Unlike cardiac muscle cells and smooth muscle cells, which have a single nucleus, a skeletal muscle cell contains many nuclei, and is referred to as “multinucleated.” These muscle cells are long and fibrous (often referred to as muscle fibers). During development, many smaller cells fuse to form a mature muscle fiber. The nuclei of the fused cells are conserved in the mature cell, thus imparting a multinucleate characteristic to mature muscle cells. LM × 104.3. Visit the University of Michigan MedScope to view the sample further. http://141.214.65.171/Histology/Basic%20Tissues/Muscle/058thin_HISTO_83X.svs/view.apml (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption]

[caption id="" align="alignright" width="317"] Figure 3. Red Blood Cell Extruding Its Nucleus. Mature red blood cells lack a nucleus. As they mature, erythroblasts extrude their nucleus, making room for more hemoglobin. The two panels here show an erythroblast before and after ejecting its nucleus, respectively.[/caption]

Inside the nucleus lies the blueprint that dictates everything a cell will do and all of the products it will make. This information is stored within DNA. The nucleus sends “commands” to the cell via molecular messengers that translate the information from DNA. Each cell in your body (with the exception of germ cells) contains the complete set of your DNA. When a cell divides, the DNA must be duplicated so that the each new cell receives a full complement of DNA. The following section will explore the structure of the nucleus and its contents, as well as the process of DNA replication.

Organization of the Nucleus and Its DNA

Like most other cellular organelles, the nucleus is surrounded by a membrane called the nuclear envelope. This membranous covering consists of two adjacent lipid bilayers with a thin fluid space in between them. Spanning these two bilayers are nuclear pores. A nuclear pore is a tiny passageway for the passage of proteins, RNA, and solutes between the nucleus and the cytoplasm. Proteins called pore complexes lining the nuclear pores regulate the passage of materials into and out of the nucleus.

[caption id="" align="aligncenter" width="420"] Figure 4. DNA Macrostructure. Strands of DNA are wrapped around supporting histones. These proteins are increasingly bundled and condensed into chromatin, which is packed tightly into chromosomes when the cell is ready to divide.[/caption] Inside the nuclear envelope is a gel-like nucleoplasm with solutes that include the building blocks of nucleic acids. There also can be a dark-staining mass often visible under a simple light microscope, called a nucleolus (plural = nucleoli). The nucleolus is a region of the nucleus that is responsible for manufacturing the RNA necessary for construction of ribosomes. Once synthesized, newly made ribosomal subunits exit the cell’s nucleus through the nuclear pores.

The genetic instructions that are used to build and maintain an organism are arranged in an orderly manner in strands of DNA. Within the nucleus are threads of chromatin composed of DNA and associated proteins (Figure 4). Along the chromatin threads, the DNA is wrapped around a set of histone proteins. A nucleosome is a single, wrapped DNA-histone complex. Multiple nucleosomes along the entire molecule of DNA appear like a beaded necklace, in which the string is the DNA and the beads are the associated histones. When a cell is in the process of division, the chromatin condenses into chromosomes, so that the DNA can be safely transported to the “daughter cells.” The chromosome is composed of DNA and proteins; it is the condensed form of chromatin. It is estimated that humans have almost 22,000 genes distributed on 46 chromosomes.

[caption id="" align="aligncenter" width="450"] Figure 5. Molecular Structure of DNA. The DNA double helix is composed of two complementary strands. The strands are bonded together via their nitrogenous base pairs using hydrogen bonds.[/caption]

3.4 Protein Synthesis

barkerj1 — Wed, 30 Aug 2017 18:36:46 +0000

Learning Objectives

By the end of this section, you will be able to:

Explain how the genetic code stored within DNA determines the protein that will form
Describe the process of transcription
Describe the process of translation
Discuss the function of ribosomes

It was mentioned earlier that DNA provides a “blueprint” for the cell structure and physiology. This refers to the fact that DNA contains the information necessary for the cell to build one very important type of molecule: the protein. Most structural components of the cell are made up, at least in part, by proteins and virtually all the functions that a cell carries out are completed with the help of proteins. One of the most important classes of proteins is enzymes, which help speed up necessary biochemical reactions that take place inside the cell. Some of these critical biochemical reactions include building larger molecules from smaller components (such as occurs during DNA replication or synthesis of microtubules) and breaking down larger molecules into smaller components (such as when harvesting chemical energy from nutrient molecules). Whatever the cellular process may be, it is almost sure to involve proteins. Just as the cell’s genome describes its full complement of DNA, a cell’s proteome is its full complement of proteins. Protein synthesis begins with genes. A gene is a functional segment of DNA that provides the genetic information necessary to build a protein. Each particular gene provides the code necessary to construct a particular protein. Gene expression, which transforms the information coded in a gene to a final gene product, ultimately dictates the structure and function of a cell by determining which proteins are made.

The interpretation of genes works in the following way. Recall that proteins are polymers, or chains, of many amino acid building blocks. The sequence of bases in a gene (that is, its sequence of A, T, C, G nucleotides) translates to an amino acid sequence. A triplet is a section of three DNA bases in a row that codes for a specific amino acid. Similar to the way in which the three-letter code d-o-g signals the image of a dog, the three-letter DNA base code signals the use of a particular amino acid. For example, the DNA triplet CAC (cytosine, adenine, and cytosine) specifies the amino acid valine. Therefore, a gene, which is composed of multiple triplets in a unique sequence, provides the code to build an entire protein, with multiple amino acids in the proper sequence (Figure 1). The mechanism by which cells turn the DNA code into a protein product is a two-step process, with an RNA molecule as the intermediate.

[caption id="" align="aligncenter" width="400"] Figure 1. The Genetic Code. DNA holds all of the genetic information necessary to build a cell’s proteins. The nucleotide sequence of a gene is ultimately translated into an amino acid sequence of the gene’s corresponding protein.[/caption]

From DNA to RNA: Transcription

DNA is housed within the nucleus, and protein synthesis takes place in the cytoplasm, thus there must be some sort of intermediate messenger that leaves the nucleus and manages protein synthesis. This intermediate messenger is messenger RNA (mRNA), a single-stranded nucleic acid that carries a copy of the genetic code for a single gene out of the nucleus and into the cytoplasm where it is used to produce proteins.

There are several different types of RNA, each having different functions in the cell. The structure of RNA is similar to DNA with a few small exceptions. For one thing, unlike DNA, most types of RNA, including mRNA, are single-stranded and contain no complementary strand. Second, the ribose sugar in RNA contains an additional oxygen atom compared with DNA. Finally, instead of the base thymine, RNA contains the base uracil. This means that adenine will always pair up with uracil during the protein synthesis process.

Gene expression begins with the process called transcription, which is the synthesis of a strand of mRNA that is complementary to the gene of interest. This process is called transcription because the mRNA is like a transcript, or copy, of the gene’s DNA code. Transcription begins in a fashion somewhat like DNA replication, in that a region of DNA unwinds and the two strands separate, however, only that small portion of the DNA will be split apart. The triplets within the gene on this section of the DNA molecule are used as the template to transcribe the complementary strand of RNA (Figure 2). A codon is a three-base sequence of mRNA, so-called because they directly encode amino acids. Like DNA replication, there are three stages to transcription: initiation, elongation, and termination.

[caption id="" align="aligncenter" width="550"] Figure 2. Transcription: from DNA to mRNA. In the first of the two stages of making protein from DNA, a gene on the DNA molecule is transcribed into a complementary mRNA molecule.[/caption]

Stage 1: Initiation. A region at the beginning of the gene called a promoter—a particular sequence of nucleotides—triggers the start of transcription.

Stage 2: Elongation. Transcription starts when RNA polymerase unwinds the DNA segment. One strand, referred to as the coding strand, becomes the template with the genes to be coded. The polymerase then aligns the correct nucleic acid (A, C, G, or U) with its complementary base on the coding strand of DNA. RNA polymerase is an enzyme that adds new nucleotides to a growing strand of RNA. This process builds a strand of mRNA.

Stage 3: Termination. When the polymerase has reached the end of the gene, one of three specific triplets (UAA, UAG, or UGA) codes a “stop” signal, which triggers the enzymes to terminate transcription and release the mRNA transcript.

Before the mRNA molecule leaves the nucleus and proceeds to protein synthesis, it is modified in a number of ways. For this reason, it is often called a pre-mRNA at this stage. For example, your DNA, and thus complementary mRNA, contains long regions called non-coding regions that do not code for amino acids. Their function is still a mystery, but the process called splicing removes these non-coding regions from the pre-mRNA transcript (Figure 3). A spliceosome—a structure composed of various proteins and other molecules—attaches to the mRNA and “splices” or cuts out the non-coding regions. The removed segment of the transcript is called an intron. The remaining exons are pasted together. An exon is a segment of RNA that remains after splicing. Interestingly, some introns that are removed from mRNA are not always non-coding. When different coding regions of mRNA are spliced out, different variations of the protein will eventually result, with differences in structure and function. This process results in a much larger variety of possible proteins and protein functions. When the mRNA transcript is ready, it travels out of the nucleus and into the cytoplasm.

[caption id="" align="aligncenter" width="320"] Figure 3. Splicing DNA. In the nucleus, a structure called a spliceosome cuts out introns (noncoding regions) within a pre-mRNA transcript and reconnects the exons.[/caption]

From RNA to Protein: Translation

Like translating a book from one language into another, the codons on a strand of mRNA must be translated into the amino acid alphabet of proteins. Translation is the process of synthesizing a chain of amino acids called a polypeptide. Translation requires two major aids: first, a “translator,” the molecule that will conduct the translation, and second, a substrate on which the mRNA strand is translated into a new protein, like the translator’s “desk.” Both of these requirements are fulfilled by other types of RNA. The substrate on which translation takes place is the ribosome.

Remember that many of a cell’s ribosomes are found associated with the rough ER, and carry out the synthesis of proteins destined for the Golgi apparatus. Ribosomal RNA (rRNA) is a type of RNA that, together with proteins, composes the structure of the ribosome. Ribosomes exist in the cytoplasm as two distinct components, a small and a large subunit. When an mRNA molecule is ready to be translated, the two subunits come together and attach to the mRNA. The ribosome provides a substrate for translation, bringing together and aligning the mRNA molecule with the molecular “translators” that must decipher its code.

The other major requirement for protein synthesis is the translator molecules that physically “read” the mRNA codons. Transfer RNA (tRNA) is a type of RNA that ferries the appropriate corresponding amino acids to the ribosome, and attaches each new amino acid to the last, building the polypeptide chain one-by-one. Thus tRNA transfers specific amino acids from the cytoplasm to a growing polypeptide. The tRNA molecules must be able to recognize the codons on mRNA and match them with the correct amino acid. The tRNA is modified for this function. On one end of its structure is a binding site for a specific amino acid. On the other end is a base sequence that matches the codon specifying its particular amino acid. This sequence of three bases on the tRNA molecule is called an anticodon. For example, a tRNA responsible for shuttling the amino acid glycine contains a binding site for glycine on one end. On the other end it contains an anticodon that complements the glycine codon (GGA is a codon for glycine, and so the tRNAs anticodon would read CCU). Equipped with its particular cargo and matching anticodon, a tRNA molecule can read its recognized mRNA codon and bring the corresponding amino acid to the growing chain (Figure 4).

[caption id="" align="aligncenter" width="280"] Figure 4. Translation from RNA to Protein. During translation, the mRNA transcript is “read” by a functional complex consisting of the ribosome and tRNA molecules. tRNAs bring the appropriate amino acids in sequence to the growing polypeptide chain by matching their anti-codons with codons on the mRNA strand.[/caption]

Much like the processes of DNA replication and transcription, translation consists of three main stages: initiation, elongation, and termination. Initiation takes place with the binding of a ribosome to an mRNA transcript. The elongation stage involves the recognition of a tRNA anticodon with the next mRNA codon in the sequence. Once the anticodon and codon sequences are bound (remember, they are complementary base pairs), the tRNA presents its amino acid cargo and the growing polypeptide strand is attached to this next amino acid. This attachment takes place with the assistance of various enzymes and requires energy. The tRNA molecule then releases the mRNA strand, the mRNA strand shifts one codon over in the ribosome, and the next appropriate tRNA arrives with its matching anticodon. This process continues until the final codon on the mRNA is reached which provides a “stop” message that signals termination of translation and triggers the release of the complete, newly synthesized protein. Thus, a gene within the DNA molecule is transcribed into mRNA, which is then translated into a protein product (Figure 5).

[caption id="" align="aligncenter" width="280"] Figure 5. From DNA to Protein: Transcription through Translation. Transcription within the cell nucleus produces an mRNA molecule, which is modified and then sent into the cytoplasm for translation. The transcript is decoded into a protein with the help of a ribosome and tRNA molecules.[/caption]

Commonly, an mRNA transcription will be translated simultaneously by several adjacent ribosomes. This increases the efficiency of protein synthesis. A single ribosome might translate an mRNA molecule in approximately one minute; so multiple ribosomes aboard a single transcript could produce multiple times the number of the same protein in the same minute. A polyribosome is a string of ribosomes translating a single mRNA strand.

Check out the Khan Academy nucleus and ribosomes section to find out more!

3.5 Cell Growth and Division

barkerj1 — Wed, 30 Aug 2017 18:36:47 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the importance of cellular division in the growth of a human body from a fertilized egg
Describe the importance of cellular growth in the growth of a human body from a fertilized egg

While there are a few cells in the body that do not undergo cell division (such as gametes, red blood cells, most neurons, and some muscle cells), most somatic cells divide regularly. A somatic cell is a general term for a body cell, and all human cells, except for the cells that produce eggs and sperm (which are referred to as germ cells), are somatic cells. Somatic cells contain two copies of each of their chromosomes (one copy received from each parent). A homologous pair of chromosomes is the two copies of a single chromosome found in each somatic cell. The human is a diploid organism, having 23 homologous pairs of chromosomes in each of the somatic cells. The condition of having pairs of chromosomes is known as diploidy.

Cells in the body replace themselves over the lifetime of a person. For example, the cells lining the gastrointestinal tract must be frequently replaced when constantly “worn off” by the movement of food through the gut. But what triggers a cell to divide, and how does it prepare for and complete cell division? The cell cycle is the sequence of events in the life of the cell from the moment it is created at the end of a previous cycle of cell division until it then divides itself, generating two new cells.

The Cell Cycle

One “turn” or cycle of the cell cycle consists of two general phases: interphase, followed by mitosis and cytokinesis. Interphase is the period of the cell cycle during which the cell is not dividing. The majority of cells are in interphase most of the time. Mitosis is the division of genetic material, during which the cell nucleus breaks down and two new, fully functional, nuclei are formed. Cytokinesis divides the cytoplasm into two distinctive cells.

Interphase

A cell grows and carries out all normal metabolic functions and processes in a period called G₁ (Figure 1). G₁ phase (gap 1 phase) is the first gap, or growth phase in the cell cycle. For cells that will divide again, G₁ is followed by replication of the DNA, during the S phase. The S phase (synthesis phase) is period during which a cell replicates its DNA.

[caption id="" align="aligncenter" width="280"] Figure 1. Cell Cycle. The two major phases of the cell cycle include mitosis (cell division), and interphase, when the cell grows and performs all of its normal functions. Interphase is further subdivided into G1, S, and G2 phases.[/caption]

After the synthesis phase, the cell proceeds through the G₂ phase. The G₂ phase is a second gap phase, during which the cell continues to grow and makes the necessary preparations for mitosis. Between G₁, S, and G₂ phases, cells will vary the most in their duration of the G1 phase. It is here that a cell might spend a couple of hours, or many days. The S phase typically lasts between 8-10 hours and the G₂ phase approximately 5 hours. In contrast to these phases, the G₀ phase is a resting phase of the cell cycle. Cells that have temporarily stopped dividing and are resting (a common condition) and cells that have permanently ceased dividing (like nerve cells) are said to be in G₀.

Mitosis and Cytokinesis

The mitotic phase of the cell typically takes between 1 and 2 hours. During this phase, a cell undergoes two major processes. First, it completes mitosis, during which the contents of the nucleus are equitably pulled apart and distributed between its two halves. Cytokinesis then occurs, dividing the cytoplasm and cell body into two new cells. Mitosis is divided into four major stages that take place after interphase (Figure 3) and in the following order: prophase, metaphase, anaphase, and telophase. The process is then followed by cytokinesis.

[caption id="attachment_1512" align="aligncenter" width="600"] Figure 3. Cell Division: Mitosis Followed by Cytokinesis. The stages of cell division oversee the separation of identical genetic material into two new nuclei, followed by the division of the cytoplasm.[/caption]

Imagine a cell that completed mitosis but never underwent cytokinesis. In some cases, a cell may divide its genetic material and grow in size, but fail to undergo cytokinesis. This results in larger cells with more than one nucleus. Usually this is an unwanted aberration and can be a sign of cancerous cells.

[caption id="attachment_3039" align="aligncenter" width="150"] Watch this amoeba sisters video to learn more about mitosis![/caption] [caption id="attachment_3040" align="aligncenter" width="150"] Watch this amoeba sisters video to learn about the process of meiosis![/caption]

[caption id="attachment_2957" align="aligncenter" width="150"] Watch this CrashCourse video to learn more about mitosis![/caption] The life of cell consists of stages that make up the cell cycle. After a cell is born, it passes through an interphase before it is ready to replicate itself and produce daughter cells. This interphase includes two gap phases (G₁ and G₂), as well as an S phase, during which its DNA is replicated in preparation for cell division. The cell cycle is under precise regulation by chemical messengers both inside and outside the cell that provide “stop” and “go” signals for movement from one phase to the next. Failures of these signals can result in cells that continue to divide uncontrollably, which can lead to cancer.

Once a cell has completed interphase and is ready for cell division, it proceeds through four separate stages of mitosis (prophase, metaphase, anaphase, and telophase). Telophase is followed by the division of the cytoplasm (cytokinesis), which generates two daughter cells. This process takes place in all normally dividing cells of the body except for the germ cells that produce eggs and sperm.

3.6 Cellular Differentiation

barkerj1 — Wed, 30 Aug 2017 18:36:50 +0000

Learning Objectives

By the end of this section, you will be able to:

Define cell specialization and describe its importance to an organism
Describe the importance of cellular differentiation in the growth of a human body from a fertilized egg

How does a complex organism such as a human develop from a single cell—a fertilized egg—into the vast array of cell types such as nerve cells, muscle cells, and epithelial cells that characterize the adult? Throughout development and adulthood, the process of cellular differentiation leads cells to assume their final morphology and physiology. Differentiation is the process by which unspecialized cells become specialized to carry out distinct functions.

Stem Cells

A stem cell is an unspecialized cell that can divide without limit as needed and can, under specific conditions, differentiate into specialized cells (Figure 3). Stem cells are divided into several categories according to their potential to differentiate.

The first embryonic cells that arise from the division of the zygote are the ultimate stem cells; these stems cells are described as totipotent because they have the potential to differentiate into any of the cells needed to enable an organism to grow and develop.

The embryonic cells that develop from totipotent stem cells and are precursors to the fundamental tissue layers of the embryo are classified as pluripotent. A pluripotent stem cell is one that has the potential to differentiate into any type of human tissue but cannot support the full development of an organism. These cells then become slightly more specialized, and are referred to as multipotent cells.

A multipotent stem cell has the potential to differentiate into different types of cells within a given cell lineage or small number of lineages, such as a red blood cell or white blood cell.

Finally, multipotent cells can become further specialized oligopotent cells. An oligopotent stem cell is limited to becoming one of a few different cell types. In contrast, a unipotent cell is fully specialized and can only reproduce to generate more of its own specific cell type.

Stem cells are unique in that they can also continually divide and regenerate new stem cells instead of further specializing. There are different stem cells present at different stages of a human’s life. They include the embryonic stem cells of the embryo, fetal stem cells of the fetus, and adult stem cells in the adult. One type of adult stem cell is the epithelial stem cell, which gives rise to the keratinocytes in the multiple layers of epithelial cells in the epidermis of skin. Adult bone marrow has three distinct types of stem cells: hematopoietic stem cells, which give rise to red blood cells, white blood cells, and platelets (Figure 1); endothelial stem cells, which give rise to the endothelial cell types that line blood and lymph vessels; and mesenchymal stem cells, which give rise to the different types of muscle cells.

[caption id="" align="aligncenter" width="600"] Figure 1. Hematopoiesis. The process of hematopoiesis involves the differentiation of multipotent cells into blood and immune cells. The multipotent hematopoietic stem cells give rise to many different cell types, including the cells of the immune system and red blood cells.[/caption]

Mature Cells

The morphology (structure) of a mature cell is closely related to the function it is specialized to serve. Muscle fibers for example are far removed in structure and function from the zygote that they ultimately arose from: they are long, slender structures that are well-suited to contracting to produce macroscopic movements over relatively long distances. Some neurons (nerve cells) are exceptionally long and slender in shape, again to act over relatively long distances, although in this case their function is to transmit information rather than move body structures directly. Erythrocytes (red blood cells) are used to transport oxygen in the blood; their tiny size and lack of a nucleus make them well-suited to squeezing through the smallest of capillaries, and their lack of mitochondria mean they do not themselves use up the oxygen they are supposed to be delivering to other cells. Leucocytes (white blood cells) on the other hand are typically noticeably larger than erythrocytes, and do have mitochondria. The large size of macrophages, for example, means they are capable of physically engulfing relatively large particles or whole cells such as bacteria by phagocytosis, and their mitochondria allow them access to the chemical energy required to move themselves through body tissues towards invading pathogens.

Differentiation

When a cell differentiates (becomes more specialized), it may undertake major changes in its size, shape, metabolic activity, and overall function. Because all cells in the body, beginning with the fertilized egg, contain the same DNA, how do the different cell types come to be so different? The answer is analogous to a movie script. The different actors in a movie all read from the same script, however, they are each only reading their own part of the script. Similarly, all cells contain the same full complement of DNA, but each type of cell only “reads” the portions of DNA that are relevant to its own function. In biology, this is referred to as the unique genetic expression of each cell.

In order for a cell to differentiate into its specialized form and function, it need only manipulate those genes (and thus those proteins) that will be expressed, and not those that will remain silent. The primary mechanism by which genes are turned “on” or “off” is through transcription factors. A transcription factor is one of a class of proteins that bind to specific genes on the DNA molecule and either promote or inhibit their transcription (Figure 2).

[caption id="" align="aligncenter" width="525"] Figure 2. Transcription Factors Regulate Gene Expression. While each body cell contains the organism’s entire genome, different cells regulate gene expression with the use of various transcription factors. Transcription factors are proteins that affect the binding of RNA polymerase to a particular gene on the DNA molecule.[/caption]

[caption id="" align="aligncenter" width="500"] Figure 3. Stem Cells. The capacity of stem cells to differentiate into specialized cells make them potentially valuable in therapeutic applications designed to replace damaged cells of different body tissues.[/caption]

In contrast, adult stem cells isolated from a patient are not seen as foreign by the body, but they have a limited range of differentiation. Some individuals bank the cord blood or deciduous teeth of their child, storing away those sources of stem cells for future use, should their child need it. Induced pluripotent stem cells are considered a promising advance in the field because using them avoids the legal, ethical, and immunological pitfalls of embryonic stem cells.

[caption id="attachment_3042" align="aligncenter" width="150"] Watch this amoeba sisters video to learn more about how cells become specialized![/caption] [caption id="attachment_3043" align="aligncenter" width="150"] Watch this amoeba sisters video for some examples of specialized cells![/caption]

Introduction

barkerj1 — Wed, 30 Aug 2017 18:36:51 +0000

[caption id="" align="aligncenter" width="600"] Figure 1. Micrograph of Cervical Tissue. This figure is a view of the regular architecture of normal tissue contrasted with the irregular arrangement of cancerous cells. (credit: “Haymanj”/Wikimedia Commons)[/caption]

Learning Objectives

By the end of this chapter, you will be able to:

Describe the general characteristics of each of the following cell types, and relate their characteristics to their function: neuron, muscle fiber, erythrocyte, leukocyte

The body contains at least 200 distinct cell types. These cells contain essentially the same internal structures yet they vary enormously in shape and function. The different types of cells are not randomly distributed throughout the body; rather they occur in organized layers, a level of organization referred to as tissue. The micrograph that opens this chapter shows the high degree of organization among different types of cells in the tissue of the cervix. You can also see how that organization breaks down when cancer takes over the regular mitotic functioning of a cell. The variety in shape reflects the many different roles that cells fulfill in your body. The human body starts as a single cell at fertilization. As this fertilized egg divides, it gives rise to trillions of cells, each built from the same blueprint, but organizing into tissues and becoming irreversibly committed to a developmental pathway.

4.1 Types of Tissues

barkerj1 — Wed, 30 Aug 2017 18:36:54 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the structure and function of epithelial, connective, muscle, and nervous tissue

The term tissue is used to describe a group of cells found together in the body. The cells within a tissue share a common embryonic origin. Microscopic observation reveals that the cells in a tissue share morphological features and are arranged in an orderly pattern that achieves the tissue’s functions. From the evolutionary perspective, tissues appear in more complex organisms. For example, multicellular protists, ancient eukaryotes, do not have cells organized into tissues.

Although there are many types of cells in the human body, they are organized into four broad categories of tissues: epithelial, connective, muscle, and nervous. Each of these categories is characterized by specific functions that contribute to the overall health and maintenance of the body. A disruption of the structure is a sign of injury or disease. Such changes can be detected through histology, the microscopic study of tissue appearance, organization, and function.

The Four Types of Tissues

[caption id="" align="alignleft" width="500"] Figure 1. Four Types of Tissue: Body. The four types of tissues are exemplified in nervous tissue, stratified squamous epithelial tissue, cardiac muscle tissue, and connective tissue in small intestine. Clockwise from nervous tissue, LM × 872, LM × 282, LM × 460, LM × 800. (Micrographs provided by the Regents of University of Michigan Medical School © 2012)[/caption]

Epithelial tissue, also referred to as epithelium, refers to the sheets of cells that cover exterior surfaces of the body, lines internal cavities and passageways, and forms certain glands. Connective tissue, as its name implies, binds the cells and organs of the body together and functions in the protection, support, and integration of all parts of the body. Muscle tissue is excitable, responding to stimulation and contracting to provide movement, and occurs as three major types: skeletal (voluntary) muscle, smooth muscle, and cardiac muscle in the heart. Nervous tissue is also excitable, allowing the propagation of electrochemical signals in the form of nerve impulses that communicate between different regions of the body (Figure 1).

The next level of organization is the organ, where several types of tissues come together to form a working unit. Just as knowing the structure and function of cells helps you in your study of tissues, knowledge of tissues will help you understand how organs function. The epithelial and connective tissues are discussed in detail in this chapter. Muscle and nervous tissues will be discussed only briefly in this chapter.

Embryonic Origin of Tissues

[caption id="" align="alignright" width="520"] Figure 2. Embryonic Origin of Tissues and Major Organs[/caption]

The zygote, or fertilized egg, is a single cell formed by the fusion of an egg and sperm. After fertilization the zygote gives rise to rapid mitotic cycles, generating many cells to form the embryo. The first embryonic cells generated have the ability to differentiate into any type of cell in the body and, as such, are called totipotent, meaning each has the capacity to divide, differentiate, and develop into a new organism. As cell proliferation progresses, three major cell lineages are established within the embryo. Each of these lineages of embryonic cells forms the distinct germ layers from which all the tissues and organs of the human body eventually form. Each germ layer is identified by its relative position: ectoderm (ecto- = “outer”), mesoderm (meso- = “middle”), and endoderm (endo- = “inner”). Figure 2 shows the types of tissues and organs associated with the each of the three germ layers. Note that epithelial tissue originates in all three layers, whereas nervous tissue derives primarily from the ectoderm and muscle tissue from mesoderm.

Tissue Membranes

[caption id="" align="alignright" width="420"] Figure 3. Tissue Membranes. The two broad categories of tissue membranes in the body are (1) connective tissue membranes, which include synovial membranes, and (2) epithelial membranes, which include mucous membranes, serous membranes, and the cutaneous membrane, in other words, the skin.[/caption]

A tissue membrane is a thin layer or sheet of cells that covers the outside of the body (for example, skin), the organs (for example, pericardium), internal passageways that lead to the exterior of the body (for example, abdominal mesenteries), and the lining of the moveable joint cavities. There are two basic types of tissue membranes: connective tissue and epithelial membranes (Figure 3).

Connective Tissue Membranes

The connective tissue membrane is formed solely from connective tissue. These membranes encapsulate organs, such as the kidneys, and line our movable joints. A synovial membrane is a type of connective tissue membrane that lines the cavity of a freely movable joint. For example, synovial membranes surround the joints of the shoulder, elbow, and knee. Fibroblasts in the inner layer of the synovial membrane release hyaluronan into the joint cavity. The hyaluronan effectively traps available water to form the synovial fluid, a natural lubricant that enables the bones of a joint to move freely against one another without much friction. This synovial fluid readily exchanges water and nutrients with blood, as do all body fluids.

Epithelial Membranes

The epithelial membrane is composed of epithelium attached to a layer of connective tissue, for example, your skin. The mucous membrane is also a composite of connective and epithelial tissues. Sometimes called mucosae, these epithelial membranes line the body cavities and hollow passageways that open to the external environment, and include the digestive, respiratory, excretory, and reproductive tracts. Mucous, produced by the epithelial exocrine glands, covers the epithelial layer. The underlying connective tissue, called the lamina propria (literally “own layer”), help support the fragile epithelial layer.

A serous membrane is an epithelial membrane composed of mesodermally derived epithelium called the mesothelium that is supported by connective tissue. These membranes line the coelomic cavities of the body, that is, those cavities that do not open to the outside, and they cover the organs located within those cavities. They are essentially membranous bags, with mesothelium lining the inside and connective tissue on the outside. Serous fluid secreted by the cells of the thin squamous mesothelium lubricates the membrane and reduces abrasion and friction between organs. Serous membranes are identified according locations. Three serous membranes line the thoracic cavity; the two pleura that cover the lungs and the pericardium that covers the heart. A fourth, the peritoneum, is the serous membrane in the abdominal cavity that covers abdominal organs and forms double sheets of mesenteries that suspend many of the digestive organs.

The skin is an epithelial membrane also called the cutaneous membrane. It is a stratified squamous epithelial membrane resting on top of connective tissue. The apical surface of this membrane is exposed to the external environment and is covered with dead, keratinized cells that help protect the body from desiccation and pathogens.

4.2 Epithelial Tissue

barkerj1 — Wed, 30 Aug 2017 18:37:07 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the structure and function of epithelial tissue

Most epithelial tissues are essentially large sheets of cells covering all the surfaces of the body exposed to the outside world and lining the outside of organs. Epithelium also forms much of the glandular tissue of the body. Skin is not the only area of the body exposed to the outside. Other areas include the airways, the digestive tract, as well as the urinary and reproductive systems, all of which are lined by an epithelium. Hollow organs and body cavities that do not connect to the exterior of the body, which includes, blood vessels and serous membranes, are lined by endothelium (plural = endothelia), which is a type of epithelium.

Epithelial cells derive from all three major embryonic layers. The epithelia lining the skin, parts of the mouth and nose, and the anus develop from the ectoderm. Cells lining the airways and most of the digestive system originate in the endoderm. The epithelium that lines vessels in the lymphatic and cardiovascular system derives from the mesoderm and is called an endothelium.

All epithelia share some important structural and functional features. This tissue is highly cellular, with little or no extracellular material present between cells. Adjoining cells form a specialized intercellular connection between their cell membranes called a cell junction. The epithelial cells exhibit polarity with differences in structure and function between the exposed or apical facing surface of the cell and the basal surface close to the underlying body structures. The basal lamina, a mixture of glycoproteins and collagen, provides an attachment site for the epithelium, separating it from underlying connective tissue. The basal lamina attaches to a reticular lamina, which is secreted by the underlying connective tissue, forming a basement membrane that helps hold it all together.

Epithelial tissues are nearly completely avascular. For instance, no blood vessels cross the basement membrane to enter the tissue, and nutrients must come by diffusion or absorption from underlying tissues or the surface. Many epithelial tissues are capable of rapidly replacing damaged and dead cells. Sloughing off of damaged or dead cells is a characteristic of surface epithelium and allows our airways and digestive tracts to rapidly replace damaged cells with new cells.

Generalized Functions of Epithelial Tissue

Epithelial tissues provide the body’s first line of protection from physical, chemical, and biological wear and tear. The cells of an epithelium act as gatekeepers of the body controlling permeability and allowing selective transfer of materials across a physical barrier. All substances that enter the body must cross an epithelium. Some epithelia often include structural features that allow the selective transport of molecules and ions across their cell membranes.

Many epithelial cells are capable of secretion and release mucous and specific chemical compounds onto their apical surfaces. The epithelium of the small intestine releases digestive enzymes, for example. Cells lining the respiratory tract secrete mucous that traps incoming microorganisms and particles. A glandular epithelium contains many secretory cells.

The Epithelial Cell

Epithelial cells are typically characterized by the polarized distribution of organelles and membrane-bound proteins between their basal and apical surfaces. Particular structures found in some epithelial cells are an adaptation to specific functions. Certain organelles are segregated to the basal sides, whereas other organelles and extensions, such as cilia, when present, are on the apical surface.

Cilia are microscopic extensions of the apical cell membrane that are supported by microtubules. They beat in unison and move fluids as well as trapped particles. Ciliated epithelium lines the ventricles of the brain where it helps circulate the cerebrospinal fluid. The ciliated epithelium of your airway forms a mucociliary escalator that sweeps particles of dust and pathogens trapped in the secreted mucous toward the throat. It is called an escalator because it continuously pushes mucous with trapped particles upward. In contrast, nasal cilia sweep the mucous blanket down towards your throat. In both cases, the transported materials are usually swallowed, and end up in the acidic environment of your stomach.

Cell to Cell Junctions

[caption id="" align="alignright" width="500"] Figure 1. Types of Cell Junctions. The three basic types of cell-to-cell junctions are tight junctions, gap junctions, and anchoring junctions.[/caption]

Cells of epithelia are closely connected and are not separated by intracellular material. Three basic types of connections allow varying degrees of interaction between the cells: tight junctions, anchoring junctions, and gap junctions (Figure 1).

At one end of the spectrum is the tight junction, which separates the cells into apical and basal compartments. An anchoring junction includes several types of cell junctions that help stabilize epithelial tissues. Anchoring junctions are common on the lateral and basal surfaces of cells where they provide strong and flexible connections. There are three types of anchoring junctions: desmosomes, hemidesmosomes, and adherens. Desmosomes occur in patches on the membranes of cells. The patches are structural proteins on the inner surface of the cell’s membrane. The adhesion molecule, cadherin, is embedded in these patches and projects through the cell membrane to link with the cadherin molecules of adjacent cells. These connections are especially important in holding cells together. Hemidesmosomes, which look like half a desmosome, link cells to the extracellular matrix, for example, the basal lamina. While similar in appearance to desmosomes, they include the adhesion proteins called integrins rather than cadherins. Adherens junctions use either cadherins or integrins depending on whether they are linking to other cells or matrix. The junctions are characterized by the presence of the contractile protein actin located on the cytoplasmic surface of the cell membrane. The actin can connect isolated patches or form a belt-like structure inside the cell. These junctions influence the shape and folding of the epithelial tissue.

In contrast with the tight and anchoring junctions, a gap junction forms an intercellular passageway between the membranes of adjacent cells to facilitate the movement of small molecules and ions between the cytoplasm of adjacent cells. These junctions allow electrical and metabolic coupling of adjacent cells, which coordinates function in large groups of cells.

Classification of Epithelial Tissues

[caption id="" align="alignright" width="520"] Figure 2. Cells of Epithelial Tissue. Simple epithelial tissue is organized as a single layer of cells and stratified epithelial tissue is formed by several layers of cells.[/caption]

Epithelial tissues are classified according to the shape of the cells and number of the cell layers formed (Figure 2). Cell shapes can be squamous (flattened and thin), cuboidal (boxy, as wide as it is tall), or columnar (rectangular, taller than it is wide). Similarly, the number of cell layers in the tissue can be one—where every cell rests on the basal lamina—which is a simple epithelium, or more than one, which is a stratified epithelium and only the basal layer of cells rests on the basal lamina. Pseudostratified (pseudo- = “false”) describes tissue with a single layer of irregularly shaped cells that give the appearance of more than one layer. Transitional describes a form of specialized stratified epithelium in which the shape of the cells can vary.

Simple Epithelium

The shape of the cells in the single cell layer of simple epithelium reflects the functioning of those cells. The cells in simple squamous epithelium have the appearance of thin scales. Squamous cell nuclei tend to be flat, horizontal, and elliptical, mirroring the form of the cell. The endothelium is the epithelial tissue that lines vessels of the lymphatic and cardiovascular system, and it is made up of a single layer of squamous cells. Simple squamous epithelium, because of the thinness of the cell, is present where rapid passage of chemical compounds is observed. The alveoli of lungs where gases diffuse, segments of kidney tubules, and the lining of capillaries are also made of simple squamous epithelial tissue. The mesothelium is a simple squamous epithelium that forms the surface layer of the serous membrane that lines body cavities and internal organs. Its primary function is to provide a smooth and protective surface. Mesothelial cells are squamous epithelial cells that secrete a fluid that lubricates the mesothelium.

In simple cuboidal epithelium, the nucleus of the box-like cells appears round and is generally located near the center of the cell. These epithelia are active in the secretion and absorptions of molecules. Simple cuboidal epithelia are observed in the lining of the kidney tubules and in the ducts of glands.

[caption id="" align="alignleft" width="250"] Figure 3. Goblet Cell. (a) In the lining of the small intestine, columnar epithelium cells are interspersed with goblet cells. (b) The arrows in this micrograph point to the mucous-secreting goblet cells. LM × 1600. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption]

In simple columnar epithelium, the nucleus of the tall column-like cells tends to be elongated and located in the basal end of the cells. Like the cuboidal epithelia, this epithelium is active in the absorption and secretion of molecules. Simple columnar epithelium forms the lining of some sections of the digestive system and parts of the female reproductive tract. Ciliated columnar epithelium is composed of simple columnar epithelial cells with cilia on their apical surfaces. These epithelial cells are found in the lining of the fallopian tubes and parts of the respiratory system, where the beating of the cilia helps remove particulate matter.

Pseudostratified columnar epithelium is a type of epithelium that appears to be stratified but instead consists of a single layer of irregularly shaped and differently sized columnar cells. In pseudostratified epithelium, nuclei of neighboring cells appear at different levels rather than clustered in the basal end. The arrangement gives the appearance of stratification; but in fact all the cells are in contact with the basal lamina, although some do not reach the apical surface. Pseudostratified columnar epithelium is found in the respiratory tract, where some of these cells have cilia.

Both simple and pseudostratified columnar epithelia are heterogeneous epithelia because they include additional types of cells interspersed among the epithelial cells. For example, a goblet cell is a mucous-secreting unicellular “gland” interspersed between the columnar epithelial cells of mucous membranes (Figure 3).

Stratified Epithelium

[caption id="" align="aligncenter" width="500"] Figure 4. Summary of Epithelial Tissue Cells.[/caption]

A stratified epithelium consists of several stacked layers of cells. This epithelium protects against physical and chemical wear and tear. The stratified epithelium is named by the shape of the most apical layer of cells, closest to the free space. Stratified squamous epithelium is the most common type of stratified epithelium in the human body. The apical cells are squamous, whereas the basal layer contains either columnar or cuboidal cells. The top layer may be covered with dead cells filled with keratin. Mammalian skin is an example of this dry, keratinized, stratified squamous epithelium. The lining of the mouth cavity is an example of an unkeratinized, stratified squamous epithelium. Stratified cuboidal epithelium and stratified columnar epithelium can also be found in certain glands and ducts, but are uncommon in the human body.

Another kind of stratified epithelium is transitional epithelium, so-called because of the gradual changes in the shapes of the apical cells as the bladder fills with urine. It is found only in the urinary system, specifically the ureters and urinary bladder. When the bladder is empty, this epithelium is convoluted and has cuboidal apical cells with convex, umbrella shaped, apical surfaces. As the bladder fills with urine, this epithelium loses its convolutions and the apical cells transition from cuboidal to squamous. It appears thicker and more multi-layered when the bladder is empty, and more stretched out and less stratified when the bladder is full and distended. Figure 4 summarizes the different categories of epithelial cell tissue cells. [caption id="attachment_2959" align="aligncenter" width="150"] Watch this CrashCourse video to learn more about epithelial histology.[/caption]

Glandular Epithelium

A gland is a structure made up of one or more cells modified to synthesize and secrete chemical substances. Most glands consist of groups of epithelial cells. A gland can be classified as an endocrine gland, a ductless gland that releases secretions directly into surrounding tissues and fluids (endo- = “inside”), or an exocrine gland whose secretions leave through a duct that opens directly, or indirectly, to the external environment (exo- = “outside”).

Endocrine Glands

The secretions of endocrine glands are called hormones. Hormones are released into the interstitial fluid, diffused into the bloodstream, and delivered to targets, in other words, cells that have receptors to bind the hormones. The endocrine system is part of a major regulatory system coordinating the regulation and integration of body responses. A few examples of endocrine glands include the anterior pituitary, thymus, adrenal cortex, and gonads.

Exocrine Glands

Exocrine glands release their contents through a duct that leads to the epithelial surface. Mucous, sweat, saliva, and breast milk are all examples of secretions from exocrine glands. They are all discharged through tubular ducts. Secretions into the lumen of the gastrointestinal tract, technically outside of the body, are of the exocrine category.

Glandular Structure

[caption id="" align="alignright" width="550"] Figure 5. Types of Exocrine Glands. Exocrine glands are classified by their structure.[/caption]

Exocrine glands are classified as either unicellular or multicellular. The unicellular glands are scattered single cells, such as goblet cells, found in the mucous membranes of the small and large intestine.

The multicellular exocrine glands known as serous glands develop from simple epithelium to form a secretory surface that secretes directly into an inner cavity. These glands line the internal cavities of the abdomen and chest and release their secretions directly into the cavities. Other multicellular exocrine glands release their contents through a tubular duct. The duct is single in a simple gland but in compound glands is divided into one or more branches (Figure 5). In tubular glands, the ducts can be straight or coiled, whereas tubes that form pockets are alveolar (acinar), such as the exocrine portion of the pancreas. Combinations of tubes and pockets are known as tubuloalveolar (tubuloacinar) compound glands. In a branched gland, a duct is connected to more than one secretory group of cells.

Methods and Types of Secretion

[caption id="" align="alignleft" width="400"] Figure 6. Modes of Glandular Secretion. (a) In merocrine secretion, the cell remains intact. (b) In apocrine secretion, the apical portion of the cell is released, as well. (c) In holocrine secretion, the cell is destroyed as it releases its product and the cell itself becomes part of the secretion.[/caption]

Exocrine glands can be classified by their mode of secretion and the nature of the substances released, as well as by the structure of the glands and shape of ducts (Figure 6). Merocrine secretion is the most common type of exocrine secretion. The secretions are enclosed in vesicles that move to the apical surface of the cell where the contents are released by exocytosis. For example, watery mucous containing the glycoprotein mucin, a lubricant that offers some pathogen protection is a merocrine secretion. The eccrine glands that produce and secrete sweat are another example.

Apocrine secretion accumulates near the apical portion of the cell. That portion of the cell and its secretory contents pinch off from the cell and are released. The sweat glands of the armpit are classified as apocrine glands. Both merocrine and apocrine glands continue to produce and secrete their contents with little damage caused to the cell because the nucleus and golgi regions remain intact after secretion.

In contrast, the process of holocrine secretion involves the rupture and destruction of the entire gland cell. The cell accumulates its secretory products and releases them only when it bursts. New gland cells differentiate from cells in the surrounding tissue to replace those lost by secretion. The sebaceous glands that produce the oils on the skin and hair are holocrine glands/cells (Figure 7).

[caption id="" align="alignright" width="520"] Figure 7. Sebaceous Glands. These glands secrete oils that lubricate and protect the skin. They are holocrine glands and they are destroyed after releasing their contents. New glandular cells form to replace the cells that are lost. LM × 400. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption]

Glands are also named after the products they produce. The serous gland produces watery, blood-plasma-like secretions rich in enzymes such as alpha amylase, whereas the mucous gland releases watery to viscous products rich in the glycoprotein mucin. Both serous and mucous glands are common in the salivary glands of the mouth. Mixed exocrine glands contain both serous and mucous glands and release both types of secretions.

4.3 Connective Tissue Supports and Protects

barkerj1 — Wed, 30 Aug 2017 18:37:12 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the general characteristics of an erythrocyte and a leukocyte, and relate those characteristics to their functions
Describe the structure and function of connective tissue
Describe the characteristics and function of cartilage
Describe ligaments and tendons

As may be obvious from its name, one of the major functions of connective tissue is to connect tissues and organs. Unlike epithelial tissue, which is composed of cells closely packed with little or no extracellular space in between, connective tissue cells are dispersed in a matrix. The matrix usually includes a large amount of extracellular material produced by the connective tissue cells that are embedded within it. The matrix plays a major role in the functioning of this tissue. The major component of the matrix is a ground substance often crisscrossed by protein fibers. This ground substance is usually a fluid, but it can also be mineralized and solid, as in bones. Connective tissues come in a vast variety of forms, yet they typically have in common three characteristic components: cells, large amounts of amorphous ground substance, and protein fibers. The amount and structure of each component correlates with the function of the tissue, from the rigid ground substance in bones supporting the body to the inclusion of specialized cells; for example, a phagocytic cell that engulfs pathogens and also rids tissue of cellular debris.

Functions of Connective Tissues

Connective tissues perform many functions in the body, but most importantly, they support and connect other tissues; from the connective tissue sheath that surrounds muscle cells, to the tendons that attach muscles to bones, and to the skeleton that supports the positions of the body. Protection is another major function of connective tissue, in the form of fibrous capsules and bones that protect delicate organs and, of course, the skeletal system. Specialized cells in connective tissue defend the body from microorganisms that enter the body. Transport of fluid, nutrients, waste, and chemical messengers is ensured by specialized fluid connective tissues, such as blood and lymph. Adipose cells store surplus energy in the form of fat and contribute to the thermal insulation of the body.

Embryonic Connective Tissue

All connective tissues derive from the mesodermal layer of the embryo (see Chapter 4.1 Figure 2). The first connective tissue to develop in the embryo is mesenchyme, the stem cell line from which all connective tissues are later derived. Clusters of mesenchymal cells are scattered throughout adult tissue and supply the cells needed for replacement and repair after a connective tissue injury. A second type of embryonic connective tissue forms in the umbilical cord, called mucous connective tissue or Wharton’s jelly. This tissue is no longer present after birth, leaving only scattered mesenchymal cells throughout the body.

Classification of Connective Tissues

The three broad categories of connective tissue are classified according to the characteristics of their ground substance and the types of fibers found within the matrix (Table 1). Connective tissue proper includes loose connective tissue and dense connective tissue. Both tissues have a variety of cell types and protein fibers suspended in a viscous ground substance. Dense connective tissue is reinforced by bundles of fibers that provide tensile strength, elasticity, and protection. In loose connective tissue, the fibers are loosely organized, leaving large spaces in between. Supportive connective tissue—bone and cartilage—provide structure and strength to the body and protect soft tissues. A few distinct cell types and densely packed fibers in a matrix characterize these tissues. In bone, the matrix is rigid and described as calcified because of the deposited calcium salts. In fluid connective tissue, in other words, lymph and blood, various specialized cells circulate in a watery fluid containing salts, nutrients, and dissolved proteins.

Connective Tissue Examples (Table 1)
Connective tissue proper	Supportive connective tissue	Fluid connective tissue
Loose connective tissue Areolar Adipose Reticular	Cartilage Hyaline Fibrocartilage Elastic	Blood
Dense connective tissue Regular elastic Irregular elastic	Bones Compact bone Cancellous bone	Lymph

Connective Tissue Proper

Fibroblasts are present in all connective tissue proper (Figure 1). Fibrocytes, adipocytes, and mesenchymal cells are fixed cells, which means they remain within the connective tissue. Other cells move in and out of the connective tissue in response to chemical signals. Macrophages, mast cells, lymphocytes, plasma cells, and phagocytic cells are found in connective tissue proper but are actually part of the immune system protecting the body.

[caption id="" align="aligncenter" width="650"] Figure 1. Connective Tissue Proper. Fibroblasts produce this fibrous tissue. Connective tissue proper includes the fixed cells fibrocytes, adipocytes, and mesenchymal cells. LM × 400. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption]

Cell Types

The most abundant cell in connective tissue proper is the fibroblast. Polysaccharides and proteins secreted by fibroblasts combine with extra-cellular fluids to produce a viscous ground substance that, with embedded fibrous proteins, forms the extra-cellular matrix. As you might expect, a fibrocyte, a less active form of fibroblast, is the second most common cell type in connective tissue proper.

Adipocytes are cells that store lipids as droplets that fill most of the cytoplasm. There are two basic types of adipocytes: white and brown. The brown adipocytes store lipids as many droplets, and have high metabolic activity. In contrast, white fat adipocytes store lipids as a single large drop and are metabolically less active. Their effectiveness at storing large amounts of fat is witnessed in obese individuals. The number and type of adipocytes depends on the tissue and location, and vary among individuals in the population. The mesenchymal cell is a multipotent adult stem cell. These cells can differentiate into any type of connective tissue cells needed for repair and healing of damaged tissue.

The macrophage is a large cell derived from a monocyte, a type of blood cell, which enters the connective tissue matrix from the blood vessels. The macrophage cells are an essential component of the immune system, which is the body’s defense against potential pathogens and degraded host cells. When stimulated, macrophages release cytokines, small proteins that act as chemical messengers. Cytokines recruit other cells of the immune system to infected sites and stimulate their activities. Roaming, or free, macrophages move rapidly by amoeboid movement, engulfing infectious agents and cellular debris. In contrast, fixed macrophages are permanent residents of their tissues.

The mast cell, found in connective tissue proper, has many cytoplasmic granules. These granules contain the chemical signals histamine and heparin. When irritated or damaged, mast cells release histamine, an inflammatory mediator, which causes vasodilation and increased blood flow at a site of injury or infection, along with itching, swelling, and redness you recognize as an allergic response. Like blood cells, mast cells are derived from hematopoietic stem cells and are part of the immune system.

Connective Tissue Fibers and Ground Substance

Three main types of fibers are secreted by fibroblasts: collagen fibers, elastic fibers, and reticular fibers. Collagen fiber is made from fibrous protein subunits linked together to form a long and straight fiber. Collagen fibers, while flexible, have great tensile strength, resist stretching, and give ligaments and tendons their characteristic resilience and strength. These fibers hold connective tissues together, even during the movement of the body.

Elastic fiber contains the protein elastin along with lesser amounts of other proteins and glycoproteins. The main property of elastin is that after being stretched or compressed, it will return to its original shape. Elastic fibers are prominent in elastic tissues found in skin and the elastic ligaments of the vertebral column.

Reticular fiber is also formed from the same protein subunits as collagen fibers; however, these fibers remain narrow and are arrayed in a branching network. They are found throughout the body, but are most abundant in the reticular tissue of soft organs, such as liver and spleen, where they anchor and provide structural support to the parenchyma (the functional cells, blood vessels, and nerves of the organ).

All of these fiber types are embedded in ground substance. Secreted by fibroblasts, ground substance is made of polysaccharides, specifically hyaluronic acid, and proteins. These combine to form a proteoglycan with a protein core and polysaccharide branches. The proteoglycan attracts and traps available moisture forming the clear, viscous, colorless matrix you now know as ground substance.

Loose Connective Tissue

Loose connective tissue is found between many organs where it acts both to absorb shock and bind tissues together. It allows water, salts, and various nutrients to diffuse through to adjacent or imbedded cells and tissues.

[caption id="" align="alignright" width="500"] Figure 2. Adipose Tissue. This is a loose connective tissue that consists of fat cells with little extracellular matrix. It stores fat for energy and provides insulation. LM × 800. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption] Adipose tissue consists mostly of fat storage cells, with little extracellular matrix (Figure 2). A large number of capillaries allow rapid storage and mobilization of lipid molecules. White adipose tissue is most abundant. It can appear yellow and owes its color to carotene and related pigments from plant food. White fat contributes mostly to lipid storage and can serve as insulation from cold temperatures and mechanical injuries. White adipose tissue can be found protecting the kidneys and cushioning the back of the eye. Brown adipose tissue is more common in infants, hence the term “baby fat.” In adults, there is a reduced amount of brown fat and it is found mainly in the neck and clavicular regions of the body. The many mitochondria in the cytoplasm of brown adipose tissue help explain its efficiency at metabolizing stored fat. Brown adipose tissue is thermogenic, meaning that as it breaks down fats, it releases metabolic heat, rather than producing adenosine triphosphate (ATP), a key molecule used in metabolism.

Areolar tissue shows little specialization. It contains all the cell types and fibers previously described and is distributed in a random, web-like fashion. It fills the spaces between muscle fibers, surrounds blood and lymph vessels, and supports organs in the abdominal cavity. Areolar tissue underlies most epithelia and represents the connective tissue component of epithelial membranes, which are described further in a later section.

[caption id="" align="alignleft" width="476"] Figure 3. Reticular Tissue. This is a loose connective tissue made up of a network of reticular fibers that provides a supportive framework for soft organs. LM × 1600. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption] Reticular tissue is a mesh-like, supportive framework for soft organs such as lymphatic tissue, the spleen, and the liver (Figure 3). Reticular cells produce the reticular fibers that form the network onto which other cells attach. It derives its name from the Latin reticulus, which means “little net.”

Dense Connective Tissue

Dense connective tissue contains more collagen fibers than does loose connective tissue. As a consequence, it displays greater resistance to stretching. There are two major categories of dense connective tissue: regular and irregular. Dense regular connective tissue fibers are parallel to each other, enhancing tensile strength and resistance to stretching in the direction of the fiber orientations. Ligaments and tendons are made of dense regular connective tissue, but in ligaments not all fibers are parallel. Dense regular elastic tissue contains elastin fibers in addition to collagen fibers, which allows the ligament to return to its original length after stretching. The ligaments in the vocal folds and between the vertebrae in the vertebral column are elastic. [caption id="" align="alignright" width="500"] Figure 4. Dense Connective Tissue. (a) Dense regular connective tissue consists of collagenous fibers packed into parallel bundles. (b) Dense irregular connective tissue consists of collagenous fibers interwoven into a mesh-like network. From top, LM × 1000, LM × 200. (Micrographs provided by the Regents of University of Michigan Medical School © 2012)[/caption] In dense irregular connective tissue, the direction of fibers is random. This arrangement gives the tissue greater strength in all directions and less strength in one particular direction. In some tissues, fibers crisscross and form a mesh. In other tissues, stretching in several directions is achieved by alternating layers where fibers run in the same orientation in each layer, and it is the layers themselves that are stacked at an angle. The dermis of the skin is an example of dense irregular connective tissue rich in collagen fibers. Dense irregular elastic tissues give arterial walls the strength and the ability to regain original shape after stretching (Figure 4).

Supportive Connective Tissues

Two major forms of supportive connective tissue, cartilage and bone, allow the body to maintain its posture and protect internal organs.

Cartilage

The distinctive appearance of cartilage is due to polysaccharides called chondroitin sulfates, which bind with ground substance proteins to form proteoglycans. Embedded within the cartilage matrix are chondrocytes, or cartilage cells, and the space they occupy are called lacunae (singular = lacuna). A layer of dense irregular connective tissue, the perichondrium, encapsulates the cartilage. Cartilaginous tissue is avascular, thus all nutrients need to diffuse through the matrix to reach the chondrocytes. This is a factor contributing to the very slow healing of cartilaginous tissues.

[caption id="" align="alignright" width="480"] Figure 5. Types of Cartilage. Cartilage is a connective tissue consisting of collagenous fibers embedded in a firm matrix of chondroitin sulfates. (a) Hyaline cartilage provides support with some flexibility. The example is from dog tissue. (b) Fibrocartilage provides some compressibility and can absorb pressure. (c) Elastic cartilage provides firm but elastic support. From top, LM × 300, LM × 1200, LM × 1016. (Micrographs provided by the Regents of University of Michigan Medical School © 2012)[/caption] The three main types of cartilage tissue are hyaline cartilage, fibrocartilage, and elastic cartilage (Figure 5). Hyaline cartilage, the most common type of cartilage in the body, consists of short and dispersed collagen fibers and contains large amounts of proteoglycans. Under the microscope, tissue samples appear clear. The surface of hyaline cartilage is smooth. Both strong and flexible, it is found in the rib cage and nose and covers bones where they meet to form moveable joints. It makes up a template of the embryonic skeleton before bone formation. A plate of hyaline cartilage at the ends of bone allows continued growth until adulthood. Fibrocartilage is tough because it has thick bundles of collagen fibers dispersed through its matrix. The knee and jaw joints and the the intervertebral discs are examples of fibrocartilage. Elastic cartilage contains elastic fibers as well as collagen and proteoglycans. This tissue gives rigid support as well as elasticity. Tug gently at your ear lobes, and notice that the lobes return to their initial shape. The external ear contains elastic cartilage.

Bone

Bone is the hardest connective tissue. It provides protection to internal organs and supports the body. Bone’s rigid extracellular matrix contains mostly collagen fibers embedded in a mineralized ground substance containing hydroxyapatite, a form of calcium phosphate. Both components of the matrix, organic and inorganic, contribute to the unusual properties of bone. Without collagen, bones would be brittle and shatter easily. Without mineral crystals, bones would flex and provide little support. Osteocytes, bone cells like chondrocytes, are located within lacunae. The histology of transverse tissue from long bone shows a typical arrangement of osteocytes in concentric circles around a central canal. Bone is a highly vascularized tissue. Unlike cartilage, bone tissue can recover from injuries in a relatively short time. Cancellous bone ("trabecular bone" or "spongy bone") looks like a sponge under the microscope and contains empty spaces between trabeculae, or arches of bone proper. It is lighter than compact bone and found in the interior of some bones and at the end of long bones. Compact bone is solid and has greater structural strength.

Fluid Connective Tissue

Blood and lymph are fluid connective tissues. Cells circulate in a liquid extracellular matrix. The formed elements circulating in blood are all derived from hematopoietic stem cells located in bone marrow (Figure 6). Erythrocytes, red blood cells, transport oxygen and some carbon dioxide. Leukocytes, white blood cells, are responsible for defending against potentially harmful microorganisms or molecules. Platelets are cell fragments involved in blood clotting. Some white blood cells have the ability to cross the endothelial layer that lines blood vessels and enter adjacent tissues. Nutrients, salts, and wastes are dissolved in the liquid matrix and transported through the body.

[caption id="" align="alignright" width="420"] Figure 6. Blood: A Fluid Connective Tissue. Blood is a fluid connective tissue containing erythrocytes and various types of leukocytes that circulate in a liquid extracellular matrix. LM × 1600. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption] Lymph contains a liquid matrix and white blood cells. Lymphatic capillaries are extremely permeable, allowing larger molecules and excess fluid from interstitial spaces to enter the lymphatic vessels. Lymph drains into blood vessels, delivering molecules to the blood that could not otherwise directly enter the bloodstream. In this way, specialized lymphatic capillaries transport absorbed fats away from the intestine and deliver these molecules to the blood.

4.4 Muscle Tissue and Motion

barkerj1 — Wed, 30 Aug 2017 18:37:12 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the general characteristics of a muscle fiber, and relate those characteristics to its function
Describe the structure and function of muscle tissue

Muscle tissue is characterized by properties that allow movement. Muscle cells are excitable; they respond to a stimulus. They are contractile, meaning they can shorten and generate a pulling force. When attached between two movable objects, in other words, bones, contractions of the muscles cause the bones to move. Some muscle movement is voluntary, which means it is under conscious control. For example, a person decides to open a book and read a chapter on anatomy. Other movements are involuntary, meaning they are not under conscious control, such as the contraction of your pupil in bright light. Muscle tissue is classified into three types according to structure and function: skeletal, cardiac, and smooth (Table 1).

Comparison of Structure and Properties of Muscle Tissue Types (Table 1)
Tissue	Histology	Function	Location
Skeletal	Long cylindrical fiber, striated, many peripherally located nuclei	Voluntary movement, produces heat, protects organs	Attached to bones and around entrance points to body (e.g., mouth, anus)
Cardiac	Short, branched, striated, single central nucleus	Contracts to pump blood	Heart
Smooth	Short, spindle-shaped, no evident striation, single nucleus in each fiber	Involuntary movement, moves food, involuntary control of respiration, moves secretions, regulates flow of blood in arteries by contraction	Walls of major organs and passageways

[caption id="" align="alignright" width="280"] Figure 1. Muscle Tissue. (a) Skeletal muscle cells have prominent striation and nuclei on their periphery. (b) Smooth muscle cells have a single nucleus and no visible striations. (c) Cardiac muscle cells appear striated and have a single nucleus. From top, LM × 1600, LM × 1600, LM × 1600. (Micrographs provided by the Regents of University of Michigan Medical School © 2012)[/caption] Skeletal muscle is attached to bones and its contraction makes possible locomotion, facial expressions, posture, and other voluntary movements of the body. Forty percent of your body mass is made up of skeletal muscle. Skeletal muscles generate heat as a byproduct of their contraction and thus participate in thermal homeostasis. Shivering is an involuntary contraction of skeletal muscles in response to perceived lower than normal body temperature. The muscle cell, or myocyte, develops from myoblasts derived from the mesoderm. Myocytes and their numbers remain relatively constant throughout life. Skeletal muscle tissue is arranged in bundles surrounded by connective tissue. Under the light microscope, muscle cells appear striated with many nuclei squeezed along the membranes. The striation is due to the regular alternation of the contractile proteins actin and myosin, along with the structural proteins that couple the contractile proteins to connective tissues. The cells are multinucleated as a result of the fusion of the many myoblasts that fuse to form each long muscle fiber.

Cardiac muscle forms the contractile walls of the heart. The cells of cardiac muscle, known as cardiomyocytes, also appear striated under the microscope. Unlike skeletal muscle fibers, cardiomyocytes are single cells typically with a single centrally located nucleus. A principal characteristic of cardiomyocytes is that they contract on their own intrinsic rhythms without any external stimulation. Cardiomyocyte attach to one another with specialized cell junctions called intercalated discs. Intercalated discs have both anchoring junctions and gap junctions. Attached cells form long, branching cardiac muscle fibers that are, essentially, a mechanical and electrochemical syncytium allowing the cells to synchronize their actions. The cardiac muscle pumps blood through the body and is under involuntary control. The attachment junctions hold adjacent cells together across the dynamic pressures changes of the cardiac cycle.

Smooth muscle tissue contraction is responsible for involuntary movements in the internal organs. It forms the contractile component of the digestive, urinary, and reproductive systems as well as the airways and arteries. Each cell is spindle shaped with a single nucleus and no visible striations (Figure 1).

[caption id="attachment_2961" align="aligncenter" width="150"] Watch this CrashCourse video on tissues to learn more about muscle tissue.[/caption]

4.5 Nervous Tissue Mediates Perception and Response

barkerj1 — Wed, 30 Aug 2017 18:37:13 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the general characteristics of a neuron, and relate those characteristics to its function
Describe the structure and function of nervous tissue

[caption id="" align="alignright" width="480"] Figure 1. The Neuron. The cell body of a neuron, also called the soma, contains the nucleus and mitochondria. The dendrites transfer the nerve impulse to the soma. The axon carries the action potential away to another excitable cell. LM × 1600. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption]

Nervous tissue is characterized as being excitable and capable of sending and receiving electrochemical signals that provide the body with information. Two main classes of cells make up nervous tissue: the neuron and neuroglia (Figure 1). Neurons propagate information via electrochemical impulses, called action potentials, which are biochemically linked to the release of chemical signals. Neuroglia play an essential role in supporting neurons and modulating their information propagation.

Neurons display distinctive morphology, well suited to their role as conducting cells, with three main parts. The cell body includes most of the cytoplasm, the organelles, and the nucleus. Dendrites branch off the cell body and appear as thin extensions. A long “tail,” the axon, extends from the neuron body and can be wrapped in an insulating layer known as myelin, which is formed by accessory cells. The synapse is the gap between nerve cells, or between a nerve cell and its target, for example, a muscle or a gland, across which the impulse is transmitted by chemical compounds known as neurotransmitters. Neurons categorized as multipolar neurons have several dendrites and a single prominent axon. Bipolar neurons possess a single dendrite and axon with the cell body, while unipolar neurons have only a single process extending out from the cell body, which divides into a functional dendrite and into a functional axon. When a neuron is sufficiently stimulated, it generates an action potential that propagates down the axon towards the synapse. If enough neurotransmitters are released at the synapse to stimulate the next neuron or target, a response is generated.

[caption id="" align="alignleft" width="550"] Figure 2. Nervous Tissue. Nervous tissue is made up of neurons and neuroglia. The cells of nervous tissue are specialized to transmit and receive impulses. LM × 872. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption]

The second class of neural cells comprises the neuroglia or glial cells, which have been characterized as having a simple support role. The word “glia” comes from the Greek word for glue. Recent research is shedding light on the more complex role of neuroglia in the function of the brain and nervous system. Astrocyte cells, named for their distinctive star shape, are abundant in the central nervous system. The astrocytes have many functions, including regulation of ion concentration in the intercellular space, uptake and/or breakdown of some neurotransmitters, and formation of the blood-brain barrier, the membrane that separates the circulatory system from the brain. Microglia protect the nervous system against infection but are not nervous tissue because they are related to macrophages. Oligodendrocyte cells produce myelin in the central nervous system (brain and spinal cord) while the Schwann cell produces myelin in the peripheral nervous system (Figure 2).

As appropriate to its role as a conductor of information, nervous tissue is found throughout the body. Nervous tissue is divided into different subsystems or divisions based primarily on its specific function. It is organized into two broad systems: the central nervous system (CNS) and the peripheral nervous system. The CNS includes the brain and the spinal cord and is responsible for integrating, and generating a response to, information from the peripheral nervous system. The peripheral nervous system is the part of the nervous system outside the CNS and is responsible for relaying information from other body tissues to the CNS, and for relaying commands from the CNS out to other body tissues. The peripheral nervous system includes a sensory or afferent division, and a motor or efferent division. The sensory division carries information to the CNS and includes receptors found in the skin, skeletal muscles and joints as well as their associated nerve fibres in visceral organs and skeletal muscles. The motor division conducts information away from the CNS to skeletal muscles (somatic or voluntary nervous system) or to the heart, glands and muscles involved with the movement of materials throughout the body (autonomic or involuntary nervous system). The autonomic system includes the sympathetic nervous system that is activated during stress (“flight or fight”) and the parasympathetic nervous system that maintains body functions during rest (“rest and digest”). The presence of the nervous system throughout the body and its organization allow it to receive, integrate and provide information to the entire body. This ensures that appropriate responses can occur among all body systems within an intact organism, both under normal conditions as well as during times of stress.

Introduction

barkerj1 — Wed, 30 Aug 2017 18:37:13 +0000

[caption id="" align="aligncenter" width="600"] Figure 1. Your skin is a vital part of your life and appearance (a–d). Some people choose to embellish it with tattoos (a), makeup (b), and even piercings (c). (credit a: Steve Teo; credit b: “spaceodissey”/flickr; credit c: Mark/flickr; credit d: Lisa Schaffer)[/caption] What do you think when you look at your skin in the mirror? Do you think about covering it with makeup, adding a tattoo, or maybe a body piercing? Or do you think about the fact that the skin belongs to one of the body’s most essential and dynamic systems: the integumentary system? The integumentary system refers to the skin and its accessory structures, and it is responsible for much more than simply lending to your outward appearance. In the adult human body, the skin makes up about 16 percent of body weight and covers an area of 1.5 to 2 m². In fact, the skin and accessory structures are the largest organ system in the human body. As such, the skin protects your inner organs and it is in need of daily care and protection to maintain its health. This chapter will introduce the structure and functions of the integumentary system, as well as some of the diseases, disorders, and injuries that can affect this system.

5.1 Layers of the Skin

barkerj1 — Wed, 30 Aug 2017 18:37:18 +0000

Learning Objectives

By the end of this section, you will be able to:

Specify the components of the integumentary system
Identify and describe the two layers of the skin
Identify and describe the two layers of the dermis
Explain why the skin is considered to be an organ
Identify and describe the five layers of the epidermis of the skin
Specify the function of keratinocytes
Specify the function of melanocytes

[caption id="" align="alignright" width="500"] Figure 1. Layers of Skin. The skin is composed of two main layers: the epidermis, made of closely packed epithelial cells, and the dermis, made of dense, irregular connective tissue that houses blood vessels, hair follicles, sweat glands, and other structures. Beneath the dermis lies the hypodermis, which is composed mainly of loose connective and fatty tissues.[/caption] Although you may not typically think of the skin as an organ, it is in fact made of tissues that work together as a single structure to perform unique and critical functions. The skin and its accessory structures make up the integumentary system, which provides the body with overall protection. The skin is made of multiple layers of cells and tissues, which are held to underlying structures by connective tissue (Figure 1). The deeper layer of skin is well vascularized (has numerous blood vessels). It also has numerous sensory, and autonomic and sympathetic nerve fibers ensuring communication to and from the brain. [caption id="attachment_2963" align="aligncenter" width="150"] Watch this CrashCourse video to learn more about the integumentary system.[/caption]

[caption id="" align="alignleft" width="280"] Figure 2. Thin Skin versus Thick Skin. These slides show cross-sections of the epidermis and dermis of (a) thin and (b) thick skin. Note the significant difference in the thickness of the epithelial layer of the thick skin. From top, LM × 40, LM × 40. (Micrographs provided by the Regents of University of Michigan Medical School © 2012)[/caption]

The Epidermis

The epidermis is composed of keratinized, stratified squamous epithelium. It is made of four or five layers of epithelial cells, depending on its location in the body. It does not have any blood vessels within it (i.e., it is avascular). Skin that has four layers of cells is referred to as “thin skin.” From deep to superficial, these layers are the stratum basale, stratum spinosum, stratum granulosum, and stratum corneum. Most of the skin can be classified as thin skin. “Thick skin” is found only on the palms of the hands and the soles of the feet. It has a fifth layer, called the stratum lucidum, located between the stratum corneum and the stratum granulosum (Figure 2).

[caption id="" align="alignright" width="280"] Figure 3. Epidermis. The epidermis is epithelium composed of multiple layers of cells. The basal layer consists of cuboidal cells, whereas the outer layers are squamous, keratinized cells, so the whole epithelium is often described as being keratinized stratified squamous epithelium. LM × 40. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption] The cells in all of the layers except the stratum basale are called keratinocytes. A keratinocyte is a cell that manufactures and stores the protein keratin. Keratin is an intracellular fibrous protein that gives hair, nails, and skin their hardness and water-resistant properties. The keratinocytes in the stratum corneum are dead and regularly slough away, being replaced by cells from the deeper layers (Figure 3).

Stratum Basale

The stratum basale (also called the stratum germinativum) is the deepest epidermal layer and attaches the epidermis to the basal lamina, below which lie the layers of the dermis. The cells in the stratum basale bond to the dermis via intertwining collagen fibers, referred to as the basement membrane. A finger-like projection, or fold, known as the dermal papilla (plural = dermal papillae) is found in the superficial portion of the dermis. Dermal papillae increase the strength of the connection between the epidermis and dermis; the greater the folding, the stronger the connections made (Figure 4).

[caption id="" align="aligncenter" width="500"] Figure 4. Layers of the Epidermis. The epidermis of thick skin has five layers: stratum basale, stratum spinosum, stratum granulosum, stratum lucidum, and stratum corneum.[/caption]

The stratum basale is a single layer of cells primarily made of basal cells. A basal cell is a cuboidal-shaped stem cell that is a precursor of the keratinocytes of the epidermis. All of the keratinocytes are produced from this single layer of cells, which are constantly going through mitosis to produce new cells. As new cells are formed, the existing cells are pushed superficially away from the stratum basale. Two other cell types are found dispersed among the basal cells in the stratum basale. The first is a Merkel cell, which functions as a receptor and is responsible for stimulating sensory nerves that the brain perceives as touch. These cells are especially abundant on the surfaces of the hands and feet. The second is a melanocyte, a cell that produces the pigment melanin. Melanin gives hair and skin its color, and also helps protect the living cells of the epidermis from ultraviolet (UV) radiation damage.

In a growing fetus, fingerprints form where the cells of the stratum basale meet the papillae of the underlying dermal layer (papillary layer), resulting in the formation of the ridges on your fingers that you recognize as fingerprints. Fingerprints are unique to each individual and are used for forensic analyses because the patterns do not change with the growth and aging processes.

[caption id="" align="aligncenter" width="500"] Figure 5. Cells of the Epidermis. The cells in the different layers of the epidermis originate from basal cells located in the stratum basale, yet the cells of each layer are distinctively different. EM × 2700. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption]

Stratum Spinosum

As the name suggests, the stratum spinosum is spiny in appearance due to the protruding cell processes that join the cells via a structure called a desmosome. The desmosomes interlock with each other and strengthen the bond between the cells. It is interesting to note that the “spiny” nature of this layer is an artifact of the staining process. Unstained epidermis samples do not exhibit this characteristic appearance. The stratum spinosum is composed of eight to 10 layers of keratinocytes, formed as a result of cell division in the stratum basale (Figure 5). Interspersed among the keratinocytes of this layer is a type of dendritic cell called the Langerhans cell, which functions as a macrophage by engulfing bacteria, foreign particles, and damaged cells that occur in this layer. The keratinocytes in the stratum spinosum begin the synthesis of keratin and release a water-repelling glycolipid that helps prevent water loss from the body, making the skin relatively waterproof. As new keratinocytes are produced atop the stratum basale, the keratinocytes of the stratum spinosum are pushed into the stratum granulosum.

Stratum Granulosum

The stratum granulosum has a grainy appearance due to further changes to the keratinocytes as they are pushed from the stratum spinosum. The cells (three to five layers deep) become flatter, their cell membranes thicken, and they generate large amounts of the proteins keratin, which is fibrous, and keratohyalin, which accumulates as lamellar granules within the cells (see Figure 4). These two proteins make up the bulk of the keratinocyte mass in the stratum granulosum and give the layer its grainy appearance. The nuclei and other cell organelles disintegrate as the cells die, leaving behind the keratin, keratohyalin, and cell membranes that will form the stratum lucidum, the stratum corneum, and the accessory structures of hair and nails.

Stratum Lucidum

The stratum lucidum is a smooth, seemingly translucent layer of the epidermis located just above the stratum granulosum and below the stratum corneum. This thin layer of cells is found only in the thick skin of the palms, soles, and digits. The keratinocytes that compose the stratum lucidum are dead and flattened (see Figure 4). These cells are densely packed with eleiden, a clear protein rich in lipids, derived from keratohyalin, which gives these cells their transparent (i.e., lucid) appearance and provides a barrier to water.

Stratum Corneum

The stratum corneum is the most superficial layer of the epidermis and is the layer exposed to the outside environment (see Figure 4). The increased keratinization (also called cornification) of the cells in this layer gives it its name. There are usually 15 to 30 layers of cells in the stratum corneum. This dry, dead layer helps prevent the penetration of microbes and the dehydration of underlying tissues, and provides a mechanical protection against abrasion for the more delicate, underlying layers. Cells in this layer are shed periodically and are replaced by cells pushed up from the stratum granulosum (or stratum lucidum in the case of the palms and soles of feet). The entire layer is replaced during a period of about 4 weeks. Cosmetic procedures, such as microdermabrasion, help remove some of the dry, upper layer and aim to keep the skin looking “fresh” and healthy.

[caption id="" align="alignleft" width="320"] Figure 6. Layers of the Dermis. This stained slide shows the two components of the dermis—the papillary layer and the reticular layer. Both are made of connective tissue with fibers of collagen extending from one to the other, making the border between the two somewhat indistinct. The dermal papillae extending into the epidermis belong to the papillary layer, whereas the dense collagen fiber bundles below belong to the reticular layer. LM × 10. (credit: modification of work by “kilbad”/Wikimedia Commons)[/caption]

Dermis

The dermis might be considered the “core” of the integumentary system (derma- = “skin”), as distinct from the epidermis (epi- = “upon” or “over”) and hypodermis (hypo- = “below”). It contains blood and lymph vessels, nerves, and other structures, such as hair follicles and sweat glands. The dermis is made of two layers of connective tissue that compose an interconnected mesh of elastin and collagenous fibers, produced by fibroblasts (Figure 6).

Papillary Layer

The papillary layer is made of loose, areolar connective tissue, which means the collagen and elastin fibers of this layer form a loose mesh. This superficial layer of the dermis projects into the stratum basale of the epidermis to form finger-like dermal papillae (see Figure 6). Within the papillary layer are fibroblasts, a small number of fat cells (adipocytes), and an abundance of small blood vessels. In addition, the papillary layer contains phagocytes, defensive cells that help fight bacteria or other infections that have breached the skin. This layer also contains lymphatic capillaries, nerve fibers, and touch receptors called the Meissner corpuscles.

Reticular Layer

Underlying the papillary layer is the much thicker reticular layer, composed of dense, irregular connective tissue. This layer is well vascularized and has a rich sensory and sympathetic nerve supply. The reticular layer appears reticulated (net-like) due to a tight meshwork of fibers. Elastin fibers provide some elasticity to the skin, enabling movement. Collagen fibers provide structure and tensile strength, with strands of collagen extending into both the papillary layer and the hypodermis. In addition, collagen binds water to keep the skin hydrated. Collagen injections and Retin-A creams help restore skin turgor by either introducing collagen externally or stimulating blood flow and repair of the dermis, respectively.

Hypodermis

The hypodermis (also called the subcutaneous layer or superficial fascia) is a layer directly below the dermis and serves to connect the skin to the underlying fascia (fibrous tissue) of the bones and muscles. It is not strictly a part of the skin, although the border between the hypodermis and dermis can be difficult to distinguish. The hypodermis consists of well-vascularized, loose, areolar connective tissue and adipose tissue, which functions as a mode of fat storage and provides insulation and cushioning for the integument.

Pigmentation

The color of skin is influenced by a number of pigments, including melanin, carotene, and hemoglobin. Recall that melanin is produced by cells called melanocytes, which are found scattered throughout the stratum basale of the epidermis. The melanin is transferred into the keratinocytes via a cellular vesicle called a melanosome (Figure 7).

[caption id="" align="aligncenter" width="550"] Figure 7. Skin Pigmentation. The relative coloration of the skin depends of the amount of melanin produced by melanocytes in the stratum basale and taken up by keratinocytes.[/caption]

Melanin occurs in two primary forms. Eumelanin exists as black and brown, whereas pheomelanin provides a red color. Dark-skinned individuals produce more melanin than those with pale skin. Exposure to the UV rays of the sun or a tanning salon causes melanin to be manufactured and built up in keratinocytes, as sun exposure stimulates keratinocytes to secrete chemicals that stimulate melanocytes. The accumulation of melanin in keratinocytes results in the darkening of the skin, or a tan. This increased melanin accumulation protects the DNA of epidermal cells from UV ray damage and the breakdown of folic acid, a nutrient necessary for our health and well-being. In contrast, too much melanin can interfere with the production of vitamin D, an important nutrient involved in calcium absorption. Thus, the amount of melanin present in our skin is dependent on a balance between available sunlight and folic acid destruction, and protection from UV radiation and vitamin D production.

It requires about 10 days after initial sun exposure for melanin synthesis to peak, which is why pale-skinned individuals tend to suffer sunburns of the epidermis initially. Dark-skinned individuals can also get sunburns, but are more protected than are pale-skinned individuals. Melanosomes are temporary structures that are eventually destroyed by fusion with lysosomes; this fact, along with melanin-filled keratinocytes in the stratum corneum sloughing off, makes tanning impermanent.

Too much sun exposure can eventually lead to wrinkling due to the destruction of the cellular structure of the skin, and in severe cases, can cause sufficient DNA damage to result in skin cancer. When there is an irregular accumulation of melanocytes in the skin, freckles appear. Moles are larger masses of melanocytes, and although most are benign, they should be monitored for changes that might indicate the presence of cancer (Figure 8).

[caption id="" align="aligncenter" width="380"] Figure 8. Moles. Moles range from benign accumulations of melanocytes to melanomas. These structures populate the landscape of our skin. (credit: the National Cancer Institute)[/caption]

5.2 Accessory Structures of the Skin

barkerj1 — Wed, 30 Aug 2017 18:37:19 +0000

Learning Objectives

By the end of this section, you will be able to:

Specify the functions of hair, sebaceous glands, sudoriferous glands, ceruminous glands, and nails

Accessory structures of the skin include hair, nails, sweat glands, and sebaceous glands. These structures embryologically originate from the epidermis and can extend down through the dermis into the hypodermis.

[caption id="attachment_2965" align="aligncenter" width="150"] Watch this CrashCourse video to learn more about the accessory structures![/caption]

[caption id="" align="alignright" width="300"] Figure 1. Hair. Hair follicles originate in the epidermis and have many different parts.[/caption]

Hair

Hair is a keratinous filament growing out of the epidermis. It is primarily made of dead, keratinized cells. Strands of hair originate in an epidermal penetration of the dermis called the hair follicle. The hair shaft is the part of the hair not anchored to the follicle, and much of this is exposed at the skin’s surface. The rest of the hair, which is anchored in the follicle, lies below the surface of the skin and is referred to as the hair root. The hair root ends deep in the dermis at the hair bulb, and includes a layer of mitotically active basal cells called the hair matrix. The hair bulb surrounds the hair papilla, which is made of connective tissue and contains blood capillaries and nerve endings from the dermis (Figure 1).

Just as the basal layer of the epidermis forms the layers of epidermis that get pushed to the surface as the dead skin on the surface sheds, the basal cells of the hair bulb divide and push cells outward in the hair root and shaft as the hair grows. The medulla forms the central core of the hair, which is surrounded by the cortex, a layer of compressed, keratinized cells that is covered by an outer layer of very hard, keratinized cells known as the cuticle. These layers are depicted in a longitudinal cross-section of the hair follicle (Figure 2), although not all hair has a medullary layer. [caption id="" align="alignleft" width="380"] Figure 2. Hair Follicle. The slide shows a cross-section of a hair follicle. Basal cells of the hair matrix in the center differentiate into cells of the inner root sheath. Basal cells at the base of the hair root form the outer root sheath. LM × 4. (credit: modification of work by “kilbad”/Wikimedia Commons)[/caption] Hair texture (straight, curly) is determined by the shape and structure of the cortex, and to the extent that it is present, the medulla. The shape and structure of these layers are, in turn, determined by the shape of the hair follicle. Hair growth begins with the production of keratinocytes by the basal cells of the hair bulb. As new cells are deposited at the hair bulb, the hair shaft is pushed through the follicle toward the surface. Keratinization is completed as the cells are pushed to the skin surface to form the shaft of hair that is externally visible. The external hair is completely dead and composed entirely of keratin. For this reason, our hair does not have sensation. Furthermore, you can cut your hair or shave without damaging the hair structure because the cut is superficial. Most chemical hair removers also act superficially; however, electrolysis and yanking both attempt to destroy the hair bulb so hair cannot grow. The wall of the hair follicle is made of three concentric layers of cells. The cells of the internal root sheath surround the root of the growing hair and extend just up to the hair shaft. They are derived from the basal cells of the hair matrix. The external root sheath, which is an extension of the epidermis, encloses the hair root. It is made of basal cells at the base of the hair root and tends to be more keratinous in the upper regions. The glassy membrane is a thick, clear connective tissue sheath covering the hair root, connecting it to the tissue of the dermis.

Hair serves a variety of functions, including protection, sensory input, thermoregulation, and communication. For example, hair on the head protects the skull from the sun. The hair in the nose and ears, and around the eyes (eyelashes) defends the body by trapping and excluding dust particles that may contain allergens and microbes. Hair of the eyebrows prevents sweat and other particles from dripping into and bothering the eyes. Hair also has a sensory function due to sensory innervation by a hair root plexus surrounding the base of each hair follicle. Hair is extremely sensitive to air movement or other disturbances in the environment, much more so than the skin surface. This feature is also useful for the detection of the presence of insects or other potentially damaging substances on the skin surface. Each hair root is connected to a smooth muscle called the arrector pili that contracts in response to nerve signals from the sympathetic nervous system, making the external hair shaft “stand up.” The primary purpose for this is to trap a layer of air to add insulation. This is visible in humans as goose bumps and even more obvious in animals, such as when a frightened cat raises its fur. Of course, this is much more obvious in organisms with a heavier coat than most humans, such as dogs and cats.

Hair Growth

Hair grows and is eventually shed and replaced by new hair. This occurs in three phases. The first is the anagen phase, during which cells divide rapidly at the root of the hair, pushing the hair shaft up and out. The length of this phase is measured in years, typically from 2 to 7 years. The catagen phase lasts only 2 to 3 weeks, and marks a transition from the hair follicle’s active growth. Finally, during the telogen phase, the hair follicle is at rest and no new growth occurs. At the end of this phase, which lasts about 2 to 4 months, another anagen phase begins. The basal cells in the hair matrix then produce a new hair follicle, which pushes the old hair out as the growth cycle repeats itself. Hair typically grows at the rate of 0.3 mm per day during the anagen phase. On average, 50 hairs are lost and replaced per day. Hair loss occurs if there is more hair shed than what is replaced and can happen due to hormonal or dietary changes. Hair loss can also result from the aging process, or the influence of hormones.

Hair Color

Similar to the skin, hair gets its color from the pigment melanin, produced by melanocytes in the hair papilla. Different hair color results from differences in the type of melanin, which is genetically determined. As a person ages, the melanin production decreases, and hair tends to lose its color and becomes gray and/or white.

Nails

[caption id="" align="alignright" width="520"] Figure 3. Nails. The nail is an accessory structure of the integumentary system.[/caption] The nail bed is a specialized structure of the epidermis that is found at the tips of our fingers and toes. The nail body is formed on the nail bed, and protects the tips of our fingers and toes as they are the farthest extremities and the parts of the body that experience the maximum mechanical stress (Figure 3). In addition, the nail body forms a back-support for picking up small objects with the fingers. The nail body is composed of densely packed dead keratinocytes. The epidermis in this part of the body has evolved a specialized structure upon which nails can form. The nail body forms at the nail root, which has a matrix of proliferating cells from the stratum basale that enables the nail to grow continuously. The lateral nail fold overlaps the nail on the sides, helping to anchor the nail body. The nail fold that meets the proximal end of the nail body forms the nail cuticle, also called the eponychium. The nail bed is rich in blood vessels, making it appear pink, except at the base, where a thick layer of epithelium over the nail matrix forms a crescent-shaped region called the lunula (the “little moon”). The area beneath the free edge of the nail, furthest from the cuticle, is called the hyponychium. It consists of a thickened layer of stratum corneum.

[caption id="" align="alignleft" width="350"] Figure 4. Eccrine Gland. Eccrine glands are coiled glands in the dermis that release sweat that is mostly water.[/caption]

Sweat Glands

When the body becomes warm, sudoriferous glands produce sweat to cool the body. Sweat glands develop from epidermal projections into the dermis and are classified as merocrine glands; that is, the secretions are excreted by exocytosis through a duct without affecting the cells of the gland. There are two main types of sweat glands, each secreting slightly different products.

An eccrine sweat gland is type of gland that produces a hypotonic sweat for thermoregulation. These glands are found all over the skin’s surface, but are especially abundant on the palms of the hand, the soles of the feet, and the forehead (Figure 4). They are coiled glands lying deep in the dermis, with the duct rising up to a pore on the skin surface, where the sweat is released. This type of sweat, released by exocytosis, is hypotonic and composed mostly of water, with some salt, antibodies, traces of metabolic waste, and dermicidin, an antimicrobial peptide. Eccrine glands are a primary component of thermoregulation in humans and thus help to maintain homeostasis.

An apocrine sweat gland is usually associated with hair follicles in densely hairy areas, such as armpits and genital regions. Apocrine sweat glands are larger than eccrine sweat glands and lie deeper in the dermis, sometimes even reaching the hypodermis, with the duct normally emptying into the hair follicle. In addition to water and salts, apocrine sweat includes organic compounds that make the sweat thicker and subject to bacterial decomposition and subsequent smell. The release of this sweat is under both nervous and hormonal control, and plays a role in the poorly understood human pheromone response. Most commercial antiperspirants use an aluminum-based compound as their primary active ingredient to stop sweat. When the antiperspirant enters the sweat gland duct, the aluminum-based compounds precipitate due to a change in pH and form a physical block in the duct, which prevents sweat from coming out of the pore. There are several different types of modified apocrine glands that have become specialized to serve particular functions. One example is the mammary gland, which in mammals produces and secretes milk: a mixture of water, salt, and organic compounds in appropriate concentrations to nourish growing offspring. Another example is the ceruminous gland, which is found in the external auditory meatus (ear canal) and secretes cerumen: a pigmented mixture of lipids and proteins that combines with the sebum secreted from sebaceous glands (see below) and dead keratinocytes to form earwax. This sticky substance is used to trap small foreign bodies (e.g. dirt, small insects) and help prevent damage to the tympanic membrane (eardrum).

Sebaceous Glands

A sebaceous gland is a type of oil gland that is found all over the body and helps to lubricate and waterproof the skin and hair. Most sebaceous glands are associated with hair follicles. They generate and excrete sebum, a mixture of lipids, onto the skin surface, thereby naturally lubricating the dry and dead layer of keratinized cells of the stratum corneum, keeping it pliable. The fatty acids of sebum also have antibacterial properties, and prevent water loss from the skin in low-humidity environments. The secretion of sebum is stimulated by hormones, many of which do not become active until puberty. Thus, sebaceous glands are relatively inactive during childhood.

5.3 Functions of the Integumentary System

barkerj1 — Wed, 30 Aug 2017 18:37:19 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe six major functions of the integumentary system
Describe the role of the skin in monitoring body temperature as an example of a negative feedback system

The skin and accessory structures perform a variety of essential functions, such as protecting the body from invasion by microorganisms, chemicals, and other environmental factors; preventing dehydration; acting as a sensory organ; modulating body temperature and electrolyte balance; and synthesizing vitamin D. The underlying hypodermis has important roles in storing fats, forming a “cushion” over underlying structures, and providing insulation from cold temperatures.

Protection

The skin protects the rest of the body from the basic elements of nature such as wind, water, and UV sunlight. It acts as a protective barrier against water loss, due to the presence of layers of keratin and glycolipids in the stratum corneum. It also is the first line of defense against abrasive activity due to contact with grit, microbes, or harmful chemicals. Sweat excreted from sweat glands deters microbes from over-colonizing the skin surface by generating dermicidin, which has antibiotic properties.

[caption id="" align="alignright" width="380"] Figure 1. Light Micrograph of a Meissner Corpuscle. In this micrograph of a skin cross-section, you can see a Meissner corpuscle (arrow), a type of touch receptor located in a dermal papilla adjacent to the basement membrane and stratum basale of the overlying epidermis. LM × 100. (credit: “Wbensmith”/Wikimedia Commons)[/caption]

Sensory Function

The fact that you can feel an ant crawling on your skin, allowing you to flick it off before it bites, is because the skin, and especially the hairs projecting from hair follicles in the skin, can sense changes in the environment. The hair root plexus surrounding the base of the hair follicle senses a disturbance, and then transmits the information to the central nervous system (brain and spinal cord), which can then respond by activating the skeletal muscles of your eyes to see the ant and the skeletal muscles of the body to act against the ant.

The skin acts as a sense organ because the epidermis, dermis, and the hypodermis contain specialized sensory nerve structures that detect touch, surface temperature, and pain. These receptors are more concentrated on the tips of the fingers, which are most sensitive to touch, especially the Meissner corpuscle (tactile corpuscle) (Figure 1), which responds to light touch, and the Pacinian corpuscle (lamellated corpuscle), which responds to vibration. Merkel cells, seen scattered in the stratum basale, are also touch receptors. In addition to these specialized receptors, there are sensory nerves connected to each hair follicle, pain and temperature receptors scattered throughout the skin, and motor nerves innervate the arrector pili muscles and glands. This rich innervation helps us sense our environment and react accordingly.

[caption id="" align="aligncenter" width="550"] Figure 2. Thermoregulation. During strenuous physical activities, such as skiing (a) or running (c), the dermal blood vessels dilate and sweat secretion increases (b). These mechanisms prevent the body from overheating. In contrast, the dermal blood vessels constrict to minimize heat loss in response to low temperatures (b). (credit a: “Trysil”/flickr; credit c: Ralph Daily)[/caption]

Thermoregulation

The integumentary system helps regulate body temperature through its tight association with the sympathetic nervous system, the division of the nervous system involved in our fight-or-flight responses. The sympathetic nervous system is continuously monitoring body temperature and initiating appropriate motor responses. Recall that sweat glands, accessory structures to the skin, secrete water, salt, and other substances to cool the body when it becomes warm. Even when the body does not appear to be noticeably sweating, approximately 500 mL of sweat (insensible perspiration) are secreted a day. If the body becomes excessively warm due to high temperatures, vigorous activity (Figure 2ac), or a combination of the two, sweat glands will be stimulated by the sympathetic nervous system to produce large amounts of sweat, as much as 0.7 to 1.5 L per hour for an active person. When the sweat evaporates from the skin surface, the body is cooled as body heat is dissipated.

In addition to sweating, arterioles in the dermis dilate so that excess heat carried by the blood can dissipate through the skin and into the surrounding environment (Figure 2b). This accounts for the skin redness that many people experience when exercising.

When body temperatures drop, the arterioles constrict to minimize heat loss, particularly in the ends of the digits and tip of the nose. This reduced circulation can result in the skin taking on a whitish hue. Although the temperature of the skin drops as a result, passive heat loss is prevented, and internal organs and structures remain warm. If the temperature of the skin drops too much (such as environmental temperatures below freezing), the conservation of body core heat can result in the skin actually freezing, a condition called frostbite.

Other Functions of the Skin

The epidermal layer of human skin synthesizes vitamin D when exposed to UV radiation. In the presence of sunlight, a form of vitamin D₃ called cholecalciferol is synthesized from a derivative of the steroid cholesterol in the skin. The liver then converts cholecalciferol to calcidiol, which is then converted to calcitriol (the active chemical form of the vitamin) in the kidneys. In present day society, vitamin D is added as a supplement to many foods, including milk and orange juice, compensating for the need for sun exposure. (The physiological roles of vitamin D are discussed elsewhere, in the "Nutrition and Diet" chapter of the subsequent volume of this textbook.)The skin is also a minor component of the excretory system, which is used to remove metabolic waste products from the body. Most metabolic waste products are removed from the body via the urinary and respiratory systems. However, the skin does release in sweat some of the metabolic waste products that are found in blood plasma, albeit at relatively low concentrations. (The urinary and respiratory systems are discussed in more detail elsewhere in this textbook and the subsequent volume.)

Introduction

barkerj1 — Wed, 30 Aug 2017 18:37:20 +0000

[caption id="" align="aligncenter" width="392"] Figure 1. Child Looking at Bones. Bone is a living tissue. Unlike the bones of a fossil made inert by a process of mineralization, a child’s bones will continue to grow and develop while contributing to the support and function of other body systems. (credit: James Emery)[/caption] Bones make good fossils. While the soft tissue of a once living organism will decay and fall away over time, bone tissue will, under the right conditions, undergo a process of mineralization, effectively turning the bone to stone. A well-preserved fossil skeleton can give us a good sense of the size and shape of an organism, just as your skeleton helps to define your size and shape. Unlike a fossil skeleton, however, your skeleton is a structure of living tissue that grows, repairs, and renews itself. The bones within it are dynamic and complex organs that serve a number of important functions, including some necessary to maintain homeostasis.

6.1 The Functions of the Skeletal System

barkerj1 — Wed, 30 Aug 2017 18:37:20 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the basic structure and histology of the skeletal system

Bone, or osseous tissue, is a hard, dense connective tissue that forms most of the adult skeleton, the support structure of the body. In the areas of the skeleton where bones move (for example, the ribcage and joints), cartilage, a semi-rigid form of connective tissue, provides flexibility and smooth surfaces for movement. The skeletal system is the body system composed of bones and cartilage and performs the following critical functions for the human body:

supports the body
facilitates movement
protects internal organs
produces blood cells
stores and releases minerals and fat

[caption id="" align="alignleft" width="290"] Figure 1. Bones Support Movement. Bones act as levers when muscles span a joint and contract. (credit: Benjamin J. DeLong)[/caption] [caption id="" align="alignright" width="250"] Figure 2. Bones Protect Brain. The cranium completely surrounds and protects the brain from non-traumatic injury.[/caption]

Support, Movement, and Protection

The most apparent functions of the skeletal system are the gross functions—those visible by observation. Simply by looking at a person, you can see how the bones support, facilitate movement, and protect the human body.

Just as the steel beams of a building provide a scaffold to support its weight, the bones and cartilage of your skeletal system compose the scaffold that supports the rest of your body. Without the skeletal system, you would be a limp mass of organs, muscle, and skin.

Bones also facilitate movement by serving as points of attachment for your muscles. While some bones only serve as a support for the muscles, others also transmit the forces produced when your muscles contract. From a mechanical point of view, bones act as levers and joints serve as fulcrums (Figure 1). Unless a muscle spans a joint and contracts, a bone is not going to move.

Bones also protect internal organs from injury by covering or surrounding them. For example, your ribs protect your lungs and heart, the bones of your vertebral column (spine) protect your spinal cord, and the bones of your cranium (skull) protect your brain (Figure 2).

Mineral Storage, Energy Storage, and Hematopoiesis

[caption id="" align="alignright" width="380"] Figure 4. Head of Femur Showing Red and Yellow Marrow. The head of the femur contains both yellow and red marrow. Yellow marrow stores fat. Red marrow is responsible for hematopoiesis. (credit: modification of work by “stevenfruitsmaak”/Wikimedia Commons)[/caption] On a metabolic level, bone tissue performs several critical functions. For one, the bone matrix acts as a reservoir for a number of minerals important to the functioning of the body, especially calcium, and phosphorus. These minerals, incorporated into bone tissue, can be released back into the bloodstream to maintain levels needed to support physiological processes. Calcium ions, for example, are essential for muscle contractions and controlling the flow of other ions involved in the transmission of nerve impulses.

Bone also serves as a site for fat storage and blood cell production. The softer connective tissue that fills the interior of most bone is referred to as bone marrow (Figure 4). There are two types of bone marrow: yellow marrow and red marrow. Yellow marrow contains adipose tissue; the triglycerides stored in the adipocytes of the tissue can serve as a source of energy. Red marrow is where hematopoiesis—the production of blood cells—takes place. Red blood cells, white blood cells, and platelets are all produced in the red marrow.

6.2 Bone Classification

barkerj1 — Wed, 30 Aug 2017 18:37:21 +0000

Learning Objectives

By the end of this section, you will be able to:

Specify the major types of bones found in the human skeleton

The 206 bones that compose the adult skeleton can be divided into five categories based on their shapes (Figure 1). Their shapes and their functions are related such that each categorical shape of bone has a distinct function.

[caption id="" align="aligncenter" width="600"] Figure 1. Classifications of Bones. Bones are classified according to their shape.[/caption]

Long Bones

A long bone is one that is cylindrical in shape, being longer than it is wide. Keep in mind, however, that the term describes the shape of a bone, not its size. Long bones are found in the arms (humerus, ulna, radius) and legs (femur, tibia, fibula), as well as in the fingers (metacarpals, phalanges) and toes (metatarsals, phalanges). Long bones function as levers; they move when muscles contract.

Short Bones

A short bone is one that is cube-like in shape, being approximately equal in length, width, and thickness. The only short bones in the human skeleton are in the carpals of the wrists and the tarsals of the ankles. Short bones provide stability and support as well as some limited motion.

Flat Bones

The term “flat bone” is somewhat of a misnomer because, although a flat bone is typically thin, it is also often curved. Examples include the cranial bones of the skull (neurocranium or braincase), the scapulae (shoulder blades), the sternum (breastbone), and the ribs. Flat bones serve as points of attachment for muscles and often protect internal organs.

Irregular Bones

An irregular bone is one that does not have any easily characterized shape and therefore does not fit any other classification. These bones tend to have more complex shapes, like the vertebrae that support the spinal cord and protect it from compressive forces. Many facial bones, particularly the ones containing sinuses, are classified as irregular bones.

Sesamoid Bones

A sesamoid bone is a small, round bone that, as the name suggests, is shaped like a sesame seed. These bones form in tendons (the sheaths of tissue that connect bones to muscles) where a great deal of pressure is generated in a joint. The sesamoid bones protect tendons by helping them overcome compressive forces. Sesamoid bones vary in number and placement from person to person but are typically found in tendons associated with the feet, hands, and knees. The patellae (singular = patella) are the only sesamoid bones found in common with every person. Table 1 reviews bone classifications with their associated features, functions, and examples.

Bone Classifications (Table 1)
Bone classification	Features	Function(s)	Examples
Long	Cylinder-like shape, longer than it is wide	Leverage	Femur, tibia, fibula, metatarsals, humerus, ulna, radius, metacarpals, phalanges
Short	Cube-like shape, approximately equal in length, width, and thickness	Provide stability, support, while allowing for some motion	Carpals, tarsals
Flat	Thin and curved	Points of attachment for muscles; protectors of internal organs	Sternum, ribs, scapulae, cranial bones
Irregular	Complex shape	Protect internal organs	Vertebrae, facial bones
Sesamoid	Small and round; embedded in tendons	Protect tendons from compressive forces	Patellae

6.3 Bone Structure

barkerj1 — Wed, 30 Aug 2017 18:37:25 +0000

Learning Objectives

By the end of this section, you will be able to:

Define and identify the following parts of a long bone: diaphysis, epiphysis, metaphysis, articular cartilage, periosteum, medullary cavity, endosteum
Compare the composition and function of compact bone versus spongy bone

Bone tissue (osseous tissue) differs greatly from other tissues in the body. Bone is hard and many of its functions depend on that characteristic hardness. Later discussions in this chapter will show that bone is also dynamic in that its shape adjusts to accommodate stresses. This section will examine the gross anatomy of bone first and then move on to its histology.

Gross Anatomy of Bone

The structure of a long bone allows for the best visualization of all of the parts of a bone (Figure 1). A long bone has two parts: the diaphysis and the epiphysis. The diaphysis is the tubular shaft that runs between the proximal and distal ends of the bone. The hollow region in the diaphysis is called the medullary cavity, which is filled with yellow marrow. The walls of the diaphysis are composed of dense and hard compact bone.

[caption id="" align="alignright" width="320"] Figure 1. Anatomy of a Long Bone. A typical long bone shows the gross anatomical characteristics of bone.[/caption]

The wider section at each end of the bone is called the epiphysis (plural = epiphyses), which is filled with spongy bone. Red marrow fills the spaces in the spongy bone. Each epiphysis meets the diaphysis at the metaphysis, the narrow area that contains the epiphyseal plate (growth plate), a layer of hyaline (transparent) cartilage in a growing bone. When the bone stops growing in early adulthood (approximately 18–21 years), the cartilage is replaced by osseous tissue and the epiphyseal plate becomes an epiphyseal line.

The medullary cavity has a delicate membranous lining called the endosteum (end- = “inside”; oste- = “bone”), where bone growth, repair, and remodeling occur. The outer surface of the bone is covered with a fibrous membrane called the periosteum (peri- = “around” or “surrounding”). The periosteum contains blood vessels, nerves, and lymphatic vessels that nourish compact bone. Tendons and ligaments also attach to bones at the periosteum. The periosteum covers the entire outer surface except where the epiphyses meet other bones to form joints (Figure 2). In this region, the epiphyses are covered with articular cartilage, a thin layer of cartilage that reduces friction and acts as a shock absorber.

[caption id="" align="aligncenter" width="480"] Figure 2. Periosteum and Endosteum. The periosteum forms the outer surface of bone, and the endosteum lines the medullary cavity.[/caption] Flat bones, like those of the cranium, consist of a layer of diploë (spongy bone), lined on either side by a layer of compact bone (Figure 3). The two layers of compact bone and the interior spongy bone work together to protect the internal organs. If the outer layer of a cranial bone fractures, the brain is still protected by the intact inner layer.

[caption id="" align="aligncenter" width="420"] Figure 3. Anatomy of a Flat Bone. This cross-section of a flat bone shows the spongy bone (diploë) lined on either side by a layer of compact bone.[/caption]

Bone Markings

The surface features of bones vary considerably, depending on the function and location in the body. Table 2 describes the bone markings, which are illustrated in (Figure 4). There are three general classes of bone markings: (1) articulations, (2) projections, and (3) holes. As the name implies, an articulation is where two bone surfaces come together (articulus = “joint”). These surfaces tend to conform to one another, such as one being rounded and the other cupped, to facilitate the function of the articulation. A projection is an area of a bone that projects above the surface of the bone. These are the attachment points for tendons and ligaments. In general, their size and shape is an indication of the forces exerted through the attachment to the bone. A hole is an opening or groove in the bone that allows blood vessels and nerves to enter the bone. As with the other markings, their size and shape reflect the size of the vessels and nerves that penetrate the bone at these points.

Bone Markings (Table 2)
Marking	Description	Example
Articulations	Where two bones meet	Knee joint
Head	Prominent rounded surface	Head of femur
Facet	Flat surface	Vertebrae
Condyle	Rounded surface	Occipital condyles
Projections	Raised markings	Spinous process of the vertebrae
Protuberance	Protruding	Chin
Process	Prominence feature	Transverse process of vertebra
Spine	Sharp process	Ischial spine
Tubercle	Small, rounded process	Tubercle of humerus
Tuberosity	Rough surface	Deltoid tuberosity
Line	Slight, elongated ridge	Temporal lines of the parietal bones
Crest	Ridge	Iliac crest
Holes	Holes and depressions	Foramen (holes through which blood vessels can pass through)
Fossa	Elongated basin	Mandibular fossa
Fovea	Small pit	Fovea capitis on the head of the femur
Sulcus	Groove	Sigmoid sulcus of the temporal bones
Canal	Passage in bone	Auditory canal
Fissure	Slit through bone	Auricular fissure
Foramen	Hole through bone	Foramen magnum in the occipital bone
Meatus	Opening into canal	External auditory meatus
Sinus	Air-filled space in bone	Nasal sinus

[caption id="" align="aligncenter" width="500"] Figure 4. Bone Features. The surface features of bones depend on their function, location, attachment of ligaments and tendons, or the penetration of blood vessels and nerves.[/caption]

Bone Cells and Tissue

Bone contains a relatively small number of cells entrenched in a matrix of collagen fibers that provide a surface for inorganic salt crystals to adhere. These salt crystals form when calcium phosphate and calcium carbonate combine to create hydroxyapatite, which incorporates other inorganic salts like magnesium hydroxide, fluoride, and sulfate as it crystallizes, or calcifies, on the collagen fibers. The hydroxyapatite crystals give bones their hardness and strength, while the collagen fibers give them flexibility so that they are not brittle.

Although bone cells compose a small amount of the bone volume, they are crucial to the function of bones. Four types of cells are found within bone tissue: osteoblasts, osteocytes, osteogenic cells, and osteoclasts (Figure 5).

[caption id="" align="aligncenter" width="395"] Figure 5. Bone Cells. Four types of cells are found within bone tissue. Osteogenic cells are undifferentiated and develop into osteoblasts. When osteoblasts get trapped within the calcified matrix, their structure and function changes, and they become osteocytes. Osteoclasts develop from monocytes and macrophages and differ in appearance from other bone cells.[/caption]

The osteoblast is the bone cell responsible for forming new bone and is found in the growing portions of bone, including the periosteum and endosteum. Osteoblasts, which do not divide, synthesize and secrete the collagen matrix and calcium salts. As the secreted matrix surrounding the osteoblast calcifies, the osteoblast become trapped within it; as a result, it changes in structure and becomes an osteocyte, the primary cell of mature bone and the most common type of bone cell. Each osteocyte is located in a space called a lacuna and is surrounded by bone tissue. Osteocytes maintain the mineral concentration of the matrix via the secretion of enzymes. Like osteoblasts, osteocytes lack mitotic activity. They can communicate with each other and receive nutrients via long cytoplasmic processes that extend through canaliculi (singular = canaliculus), channels within the bone matrix.

If osteoblasts and osteocytes are incapable of mitosis, then how are they replenished when old ones die? The answer lies in the properties of a third category of bone cells—the osteogenic cell. These osteogenic cells are undifferentiated with high mitotic activity and they are the only bone cells that divide. Immature osteogenic cells are found in the deep layers of the periosteum and the marrow. They differentiate and develop into osteoblasts.

The dynamic nature of bone means that new tissue is constantly formed, and old, injured, or unnecessary bone is dissolved for repair or for calcium release. The cell responsible for bone resorption, or breakdown, is the osteoclast. They are found on bone surfaces, are multinucleated, and originate from monocytes and macrophages, two types of white blood cells, not from osteogenic cells. Osteoclasts are continually breaking down old bone while osteoblasts are continually forming new bone. The ongoing balance between osteoblasts and osteoclasts is responsible for the constant but subtle reshaping of bone. Table 3 reviews the bone cells, their functions, and locations.

Bone Cells (Table 3)
Cell type	Function	Location
Osteogenic cells	Develop into osteoblasts	Deep layers of the periosteum and the marrow
Osteoblasts	Bone formation	Growing portions of bone, including periosteum and endosteum
Osteocytes	Maintain mineral concentration of matrix	Entrapped in matrix
Osteoclasts	Bone resorption	Bone surfaces and at sites of old, injured, or unneeded bone

Compact and Spongy Bone

The differences between compact and spongy bone are best explored via their histology. Most bones contain compact and spongy osseous tissue, but their distribution and concentration vary based on the bone’s overall function. Compact bone is dense so that it can withstand compressive forces, while spongy (cancellous) bone has open spaces and supports shifts in weight distribution.

Compact Bone

Compact bone is the denser, stronger of the two types of bone tissue (Figure 6). It can be found under the periosteum and in the diaphyses of long bones, where it provides support and protection.

[caption id="" align="aligncenter" width="480"] Figure 6. Diagram of Compact Bone. (a) This cross-sectional view of compact bone shows the basic structural unit, the osteon. (b) In this micrograph of the osteon, you can clearly see the concentric lamellae and central canals. LM × 40. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption]

The microscopic structural unit of compact bone is called an osteon, or Haversian system. Each osteon is composed of concentric rings of calcified matrix called lamellae (singular = lamella). Running down the center of each osteon is the central canal, or Haversian canal, which contains blood vessels, nerves, and lymphatic vessels. These vessels and nerves branch off at right angles through a perforating canal, also known as Volkmann’s canals, to extend to the periosteum and endosteum.

The osteocytes are located inside spaces called lacunae (singular = lacuna), found at the borders of adjacent lamellae. As described earlier, canaliculi connect with the canaliculi of other lacunae and eventually with the central canal. This system allows nutrients to be transported to the osteocytes and wastes to be removed from them.

Spongy (Cancellous) Bone

Like compact bone, spongy bone, also known as cancellous bone, contains osteocytes housed in lacunae, but they are not arranged in concentric circles. Instead, the lacunae and osteocytes are found in a lattice-like network of matrix spikes called trabeculae (singular = trabecula) (Figure 7). The trabeculae may appear to be a random network, but each trabecula forms along lines of stress to provide strength to the bone. The spaces of the trabeculated network provide balance to the dense and heavy compact bone by making bones lighter so that muscles can move them more easily. In addition, the spaces in some spongy bones contain red marrow, protected by the trabeculae, where hematopoiesis occurs.

[caption id="" align="aligncenter" width="480"] Figure 7. Diagram of Spongy Bone. Spongy bone is composed of trabeculae that contain the osteocytes. Red marrow fills the spaces in some bones.[/caption]

Aging and the…

Skeletal System: Paget’s Disease Paget’s disease usually occurs in adults over age 40. It is a disorder of the bone remodeling process that begins with overactive osteoclasts. This means more bone is resorbed than is laid down. The osteoblasts try to compensate but the new bone they lay down is weak and brittle and therefore prone to fracture.

While some people with Paget’s disease have no symptoms, others experience pain, bone fractures, and bone deformities (Figure 8). Bones of the pelvis, skull, spine, and legs are the most commonly affected. When occurring in the skull, Paget’s disease can cause headaches and hearing loss.

[caption id="" align="aligncenter" width="300"] Figure 8. Paget's Disease. Normal leg bones are relatively straight, but those affected by Paget’s disease are porous and curved.[/caption] What causes the osteoclasts to become overactive? The answer is still unknown, but hereditary factors seem to play a role. Some scientists believe Paget’s disease is due to an as-yet-unidentified virus. Paget’s disease is diagnosed via imaging studies and lab tests. X-rays may show bone deformities or areas of bone resorption. Bone scans are also useful. In these studies, a dye containing a radioactive ion is injected into the body. Areas of bone resorption have an affinity for the ion, so they will light up on the scan if the ions are absorbed. In addition, blood levels of an enzyme called alkaline phosphatase are typically elevated in people with Paget’s disease. Bisphosphonates, drugs that decrease the activity of osteoclasts, are often used in the treatment of Paget’s disease. However, in a small percentage of cases, bisphosphonates themselves have been linked to an increased risk of fractures because the old bone that is left after bisphosphonates are administered becomes worn out and brittle. Still, most doctors feel that the benefits of bisphosphonates more than outweigh the risk; the medical professional has to weigh the benefits and risks on a case-by-case basis. Bisphosphonate treatment can reduce the overall risk of deformities or fractures, which in turn reduces the risk of surgical repair and its associated risks and complications.

Blood and Nerve Supply

The spongy bone and medullary cavity receive nourishment from arteries that pass through the compact bone. The arteries enter through the nutrient foramen (plural = foramina), small openings in the diaphysis (Figure 9). The osteocytes in spongy bone are nourished by blood vessels of the periosteum that penetrate spongy bone and blood that circulates in the marrow cavities. As the blood passes through the marrow cavities, it is collected by veins, which then pass out of the bone through the foramina.

In addition to the blood vessels, nerves follow the same paths into the bone where they tend to concentrate in the more metabolically active regions of the bone. The nerves sense pain, and it appears the nerves also play roles in regulating blood supplies and in bone growth, hence their concentrations in metabolically active sites of the bone. [caption id="" align="alignleft" width="280"] Figure 9. Diagram of Blood and Nerve Supply to Bone.Blood vessels and nerves enter the bone through the nutrient foramen.[/caption]

6.4 Bone Formation and Development

barkerj1 — Wed, 30 Aug 2017 18:37:27 +0000

Learning Objectives

By the end of this section, you will be able to:

Define ossification
Compare intramembranous ossification with endochondral ossification
Specify three factors which affect the rate of ossification
Describe how a long bone grows in length
Describe how a long bone grows in girth

In the early stages of embryonic development, the embryo’s skeleton consists of fibrous membranes and hyaline cartilage. By the sixth or seventh week of embryonic life, the actual process of bone development, ossification (osteogenesis), begins. There are two osteogenic pathways—intramembranous ossification and endochondral ossification—but bone is the same regardless of the pathway that produces it.

Cartilage Templates

Bone is a replacement tissue; that is, it uses a model tissue on which to lay down its mineral matrix. For skeletal development, the most common template is cartilage. During fetal development, a framework is laid down that determines where bones will form. This framework is a flexible, semi-solid matrix produced by chondroblasts and consists of hyaluronic acid, chondroitin sulfate, collagen fibers, and water. As the matrix surrounds and isolates chondroblasts, they are called chondrocytes. Unlike most connective tissues, cartilage is avascular, meaning that it has no blood vessels supplying nutrients and removing metabolic wastes. All of these functions are carried on by diffusion through the matrix. This is why damaged cartilage does not repair itself as readily as most tissues do.

Throughout fetal development and into childhood growth and development, bone forms on the cartilaginous matrix. By the time a fetus is born, most of the cartilage has been replaced with bone. Some additional cartilage will be replaced throughout childhood, and some cartilage remains in the adult skeleton.

[caption id="" align="aligncenter" width="550"] Figure 1. Intramembranous Ossification. Intramembranous ossification follows four steps. (a) Mesenchymal cells group into clusters, and ossification centers form. (b) Secreted osteoid traps osteoblasts, which then become osteocytes. (c) Trabecular matrix and periosteum form. (d) Compact bone develops superficial to the trabecular bone, and crowded blood vessels condense into red marrow.[/caption]

Intramembranous Ossification

During intramembranous ossification, compact and spongy bone develops directly from sheets of mesenchymal (undifferentiated) connective tissue. The flat bones of the face, most of the cranial bones, and the clavicles (collarbones) are formed via intramembranous ossification.

The process begins when mesenchymal cells in the embryonic skeleton gather together and begin to differentiate into specialized cells (Figure 1a). Some of these cells will differentiate into capillaries, while others will become osteogenic cells and then osteoblasts. Although they will ultimately be spread out by the formation of bone tissue, early osteoblasts appear in a cluster called an ossification center.

The osteoblasts secrete osteoid, uncalcified matrix, which calcifies (hardens) within a few days as mineral salts are deposited on it, thereby entrapping the osteoblasts within. Once entrapped, the osteoblasts become osteocytes (Figure 1b). As osteoblasts transform into osteocytes, osteogenic cells in the surrounding connective tissue differentiate into new osteoblasts.

Osteoid (unmineralized bone matrix) secreted around the capillaries results in a trabecular matrix, while osteoblasts on the surface of the spongy bone become the periosteum (Figure 1c). The periosteum then creates a protective layer of compact bone superficial to the trabecular bone. The trabecular bone crowds nearby blood vessels, which eventually condense into red marrow (Figure 1d).

Intramembranous ossification begins in utero during fetal development and continues on into adolescence. At birth, the skull and clavicles are not fully ossified nor are the sutures of the skull closed. This allows the skull and shoulders to deform during passage through the birth canal. The last bones to ossify via intramembranous ossification are the flat bones of the face, which reach their adult size at the end of the adolescent growth spurt.

[caption id="" align="aligncenter" width="600"] Figure 2. Endochondral Ossification. Endochondral ossification follows five steps. (a) Mesenchymal cells differentiate into chondrocytes. (b) The cartilage model of the future bony skeleton and the perichondrium form. (c) Capillaries penetrate cartilage. Perichondrium transforms into periosteum. Periosteal collar develops. Primary ossification center develops. (d) Cartilage and chondrocytes continue to grow at ends of the bone. (e) Secondary ossification centers develop. (f) Cartilage remains at epiphyseal (growth) plate and at joint surface as articular cartilage.[/caption]

Endochondral Ossification

In endochondral ossification, bone develops by replacing hyaline cartilage. Cartilage does not become bone. Instead, cartilage serves as a template to be completely replaced by new bone. Endochondral ossification takes much longer than intramembranous ossification. Bones at the base of the skull and long bones form via endochondral ossification.

In a long bone, for example, at about 6 to 8 weeks after conception, some of the mesenchymal cells differentiate into chondrocytes (cartilage cells) that form the cartilaginous skeletal precursor of the bones (Figure 2a). Soon after, the perichondrium, a membrane that covers the cartilage, appears Figure 2b).

As more matrix is produced, the chondrocytes in the center of the cartilaginous model grow in size. As the matrix calcifies, nutrients can no longer reach the chondrocytes. This results in their death and the disintegration of the surrounding cartilage. Blood vessels invade the resulting spaces, not only enlarging the cavities but also carrying osteogenic cells with them, many of which will become osteoblasts. These enlarging spaces eventually combine to become the medullary cavity.

As the cartilage grows, capillaries penetrate it. This penetration initiates the transformation of the perichondrium into the bone-producing periosteum. Here, the osteoblasts form a periosteal collar of compact bone around the cartilage of the diaphysis. By the second or third month of fetal life, bone cell development and ossification ramps up and creates the primary ossification center, a region deep in the periosteal collar where ossification begins (Figure 2c).

While these deep changes are occurring, chondrocytes and cartilage continue to grow at the ends of the bone (the future epiphyses), which increases the bone’s length at the same time bone is replacing cartilage in the diaphyses. By the time the fetal skeleton is fully formed, cartilage only remains at the joint surface as articular cartilage and between the diaphysis and epiphysis as the epiphyseal plate, the latter of which is responsible for the longitudinal growth of bones. After birth, this same sequence of events (matrix mineralization, death of chondrocytes, invasion of blood vessels from the periosteum, and seeding with osteogenic cells that become osteoblasts) occurs in the epiphyseal regions, and each of these centers of activity is referred to as a secondary ossification center (Figure 2e).

How Bones Grow in Length

The epiphyseal plate is the area of growth in a long bone. It is a layer of hyaline cartilage where ossification occurs in immature bones. On the epiphyseal side of the epiphyseal plate, cartilage is formed. On the diaphyseal side, cartilage is ossified, and the diaphysis grows in length. The epiphyseal plate is composed of four zones of cells and activity (Figure 3). The reserve zone is the region closest to the epiphyseal end of the plate and contains small chondrocytes within the matrix. These chondrocytes do not participate in bone growth but secure the epiphyseal plate to the osseous tissue of the epiphysis.

[caption id="" align="alignright" width="350"] Figure 3. Longitudinal Bone Growth. The epiphyseal plate is responsible for longitudinal bone growth.[/caption] The proliferative zone is the next layer toward the diaphysis and contains stacks of slightly larger chondrocytes. It makes new chondrocytes (via mitosis) to replace those that die at the diaphyseal end of the plate. Chondrocytes in the next layer, the zone of maturation and hypertrophy, are older and larger than those in the proliferative zone. The more mature cells are situated closer to the diaphyseal end of the plate. The longitudinal growth of bone is a result of cellular division in the proliferative zone and the maturation of cells in the zone of maturation and hypertrophy.

Most of the chondrocytes in the zone of calcified matrix, the zone closest to the diaphysis, are dead because the matrix around them has calcified. Capillaries and osteoblasts from the diaphysis penetrate this zone, and the osteoblasts secrete bone tissue on the remaining calcified cartilage. Thus, the zone of calcified matrix connects the epiphyseal plate to the diaphysis. A bone grows in length when osseous tissue is added to the diaphysis.

Bones continue to grow in length until early adulthood. The rate of growth is controlled by hormones, which will be discussed later. When the chondrocytes in the epiphyseal plate cease their proliferation and bone replaces the cartilage, longitudinal growth stops. All that remains of the epiphyseal plate is the epiphyseal line (Figure 4).

[caption id="" align="alignleft" width="380"] Figure 4. Progression from Epiphyseal Plate to Epiphyseal Line. As a bone matures, the epiphyseal plate progresses to an epiphyseal line. (a) Epiphyseal plates are visible in a growing bone. (b) Epiphyseal lines are the remnants of epiphyseal plates in a mature bone.[/caption]

How Bones Grow in Diameter

While bones are increasing in length, they are also increasing in diameter; growth in diameter can continue even after longitudinal growth ceases. This is called appositional growth. Osteoclasts resorb old bone that lines the medullary cavity, while osteoblasts, via intramembranous ossification, produce new bone tissue beneath the periosteum. The erosion of old bone along the medullary cavity and the deposition of new bone beneath the periosteum not only increase the diameter of the diaphysis but also increase the diameter of the medullary cavity. This process is called modeling.

Bone Remodeling

The process in which matrix is resorbed on one surface of a bone and deposited on another is known as bone modeling. Modeling primarily takes place during a bone’s growth. However, in adult life, bone undergoes remodeling, in which resorption of old or damaged bone takes place on the same surface where osteoblasts lay new bone to replace that which is resorbed. Injury, exercise, and other activities lead to remodeling. Those influences are discussed later in the chapter, but even without injury or exercise, about 5 to 10 percent of the skeleton is remodeled annually just by destroying old bone and renewing it with fresh bone.

6.5 Fractures: Bone Repair

barkerj1 — Wed, 30 Aug 2017 18:37:28 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe four types of bone fractures, and explain how the frequencies of these fractures change with age

A fracture is a broken bone. It will heal whether or not a physician resets it in its anatomical position. If the bone is not reset correctly, the healing process will keep the bone in its deformed position.

When a broken bone is manipulated and set into its natural position without surgery, the procedure is called a closed reduction. Open reduction requires surgery to expose the fracture and reset the bone. While some fractures can be minor, others are quite severe and result in grave complications. For example, a fractured diaphysis of the femur has the potential to release fat globules into the bloodstream. These can become lodged in the capillary beds of the lungs, leading to respiratory distress and if not treated quickly, death.

Types of Fractures

Fractures are classified by their complexity, location, and other features (Figure 1). Table 4 outlines common types of fractures. Some fractures may be described using more than one term because it may have the features of more than one type (e.g., an open transverse fracture). [caption id="" align="aligncenter" width="395"] Figure 1. Types of Fractures. Compare healthy bone with different types of fractures: (a) closed fracture, (b) open fracture, (c) transverse fracture, (d) spiral fracture, (e) comminuted fracture, (f) impacted fracture, (g) greenstick fracture, and (h) oblique fracture.[/caption]

Types of Fractures (Table 4)
Type of fracture	Description
Transverse	Occurs straight across the long axis of the bone
Oblique	Occurs at an angle that is not 90 degrees
Spiral	Bone segments are pulled apart as a result of a twisting motion
Comminuted	Several breaks result in many small pieces between two large segments
Impacted	One fragment is driven into the other, usually as a result of compression
Greenstick	A partial fracture in which only one side of the bone is broken
Open (or compound)	A fracture in which at least one end of the broken bone tears through the skin; carries a high risk of infection
Closed (or simple)	A fracture in which the skin remains intact

Bone Repair

When a bone breaks, blood flows from any vessel torn by the fracture. These vessels could be in the periosteum, osteons, and/or medullary cavity. The blood begins to clot, and about six to eight hours after the fracture, the clotting blood has formed a fracture hematoma (Figure 2a). The disruption of blood flow to the bone results in the death of bone cells around the fracture.

[caption id="" align="aligncenter" width="485"] Figure 2. Stages in Fracture Repair. The healing of a bone fracture follows a series of progressive steps: (a) A fracture hematoma forms. (b) Internal and external calli form. (c) Cartilage of the calli is replaced by trabecular bone. (d) Remodeling occurs.[/caption]

Within about 48 hours after the fracture, chondrocytes from the endosteum have created an internal callus (plural = calli) by secreting a fibrocartilaginous matrix between the two ends of the broken bone, while the periosteal chondrocytes and osteoblasts create an external callus of hyaline cartilage and bone, respectively, around the outside of the break (Figure 2b). This stabilizes the fracture.

Over the next several weeks, osteoclasts resorb the dead bone; osteogenic cells become active, divide, and differentiate into osteoblasts. The cartilage in the calli is replaced by trabecular bone via endochondral ossification (Figure 2c).

Eventually, the internal and external calli unite, compact bone replaces spongy bone at the outer margins of the fracture, and healing is complete. A slight swelling may remain on the outer surface of the bone, but quite often, that region undergoes remodeling (Figure 2d), and no external evidence of the fracture remains...

Introduction

barkerj1 — Wed, 30 Aug 2017 18:37:30 +0000

[caption id="" align="aligncenter" width="250"] Figure 1. Lateral View of the Human Skull.[/caption] The skeletal system forms the rigid internal framework of the body. It consists of the bones, cartilages, and ligaments. Bones support the weight of the body, allow for body movements, and protect internal organs. Cartilage provides flexible strength and support for body structures such as the thoracic cage, the external ear, and the trachea and larynx. At joints of the body, cartilage can also unite adjacent bones or provide cushioning between them. Ligaments are the strong connective tissue bands that hold the bones at a moveable joint together and serve to prevent excessive movements of the joint that would result in injury. Providing movement of the skeleton are the muscles of the body, which are firmly attached to the skeleton via connective tissue structures called tendons. As muscles contract, they pull on the bones to produce movements of the body. Thus, without a skeleton, you would not be able to stand, run, or even feed yourself! Each bone of the body serves a particular function, and therefore bones vary in size, shape, and strength based on these functions. For example, the bones of the lower back and lower limb are thick and strong to support your body weight. Similarly, the size of a bony landmark that serves as a muscle attachment site on an individual bone is related to the strength of this muscle. Muscles can apply very strong pulling forces to the bones of the skeleton. To resist these forces, bones have enlarged bony landmarks at sites where powerful muscles attach. This means that not only the size of a bone, but also its shape, is related to its function. For this reason, the identification of bony landmarks is important during your study of the skeletal system. Bones are also dynamic organs that can modify their strength and thickness in response to changes in muscle strength or body weight. Thus, muscle attachment sites on bones will thicken if you begin a workout program that increases muscle strength. Similarly, the walls of weight-bearing bones will thicken if you gain body weight or begin pounding the pavement as part of a new running regimen. In contrast, a reduction in muscle strength or body weight will cause bones to become thinner. This may happen during a prolonged hospital stay, following limb immobilization in a cast, or going into the weightlessness of outer space. Even a change in diet, such as eating only soft food due to the loss of teeth, will result in a noticeable decrease in the size and thickness of the jaw bones.

7.1 Divisions of the Skeletal System

barkerj1 — Wed, 30 Aug 2017 18:37:32 +0000

Learning Objectives

By the end of this section, you will be able to:

Specify the components of the axial and appendicular skeletons
Describe the general function of the axial skeleton
Describe the general function of the appendicular skeleton

The skeletal system includes all of the bones, cartilages, and ligaments of the body that support and give shape to the body and body structures. The skeleton consists of the bones of the body. For adults, there are 206 bones in the skeleton. Younger individuals have higher numbers of bones because some bones fuse together during childhood and adolescence to form an adult bone. The primary functions of the skeleton are to provide a rigid, internal structure that can support the weight of the body against the force of gravity, and to provide a structure upon which muscles can act to produce movements of the body. The lower portion of the skeleton is specialized for stability during walking or running. In contrast, the upper skeleton has greater mobility and ranges of motion, features that allow you to lift and carry objects or turn your head and trunk.

In addition to providing for support and movements of the body, the skeleton has protective and storage functions. It protects the internal organs, including the brain, spinal cord, heart, lungs, and pelvic organs. The bones of the skeleton serve as the primary storage site for important minerals such as calcium and phosphate. The bone marrow found within bones stores fat and houses the blood-cell producing tissue of the body.

The skeleton is subdivided into two major divisions—the axial and appendicular.

The Axial Skeleton

The skeleton is subdivided into two major divisions—the axial and appendicular. The axial skeleton forms the vertical, central axis of the body and includes all bones of the head, neck, chest, and back (Figure 1). It serves to protect the brain, spinal cord, heart, and lungs. It also serves as the attachment site for muscles that move the head, neck, and back, and for muscles that act across the shoulder and hip joints to move their corresponding limbs.

The axial skeleton of the adult consists of 80 bones, including the skull, the vertebral column, and the thoracic cage. The skull is formed by 22 bones. Also associated with the head are an additional seven bones, including the hyoid bone and the ear ossicles (three small bones found in each middle ear). The vertebral column consists of 24 bones, each called a vertebra, plus the sacrum and coccyx. The thoracic cage includes the 12 pairs of ribs, and the sternum, the flattened bone of the anterior chest.

[caption id="" align="aligncenter" width="500"] Figure 1. Axial and Appendicular Skeleton. The axial skeleton supports the head, neck, back, and chest and thus forms the vertical axis of the body. It consists of the skull, vertebral column (including the sacrum and coccyx), and the thoracic cage, formed by the ribs and sternum. The appendicular skeleton is made up of all bones of the upper and lower limbs.[/caption]

The Appendicular Skeleton

The appendicular skeleton includes all bones of the upper and lower limbs, plus the bones that attach each limb to the axial skeleton. There are 126 bones in the appendicular skeleton of an adult. The bones of the appendicular skeleton are covered in a separate chapter.

7.2 The Skull

barkerj1 — Wed, 30 Aug 2017 18:37:37 +0000

Learning Objectives

By the end of this section, you will be able to:

Name and describe the principle components of the skull

The cranium (skull) is the skeletal structure of the head that supports the face and protects the brain. It is subdivided into the facial bones and the brain case, or cranial vault (Figure 1). The facial bones underlie the facial structures, form the nasal cavity, enclose the eyeballs, and support the teeth of the upper and lower jaws. The rounded brain case surrounds and protects the brain and houses the middle and inner ear structures.

In the adult, the skull consists of 22 individual bones, 21 of which are immobile and united into a single unit. The 22nd bone is the mandible (lower jaw), which is the only moveable bone of the skull.

[caption id="" align="aligncenter" width="380"] Figure 1. Parts of the Skull. The skull consists of the rounded brain case that houses the brain and the facial bones that form the upper and lower jaws, nose, orbits, and other facial structures.[/caption]

Anterior View of Skull

The anterior skull consists of the facial bones and provides the bony support for the eyes and structures of the face. This view of the skull is dominated by the openings of the orbits and the nasal cavity. Also seen are the upper and lower jaws, with their respective teeth (Figure 2).

The orbit is the bony socket that houses the eyeball and muscles that move the eyeball or open the upper eyelid. The upper margin of the anterior orbit is the supraorbital margin. Located near the midpoint of the supraorbital margin is a small opening called the supraorbital foramen. This provides for passage of a sensory nerve to the skin of the forehead. Below the orbit is the infraorbital foramen, which is the point of emergence for a sensory nerve that supplies the anterior face below the orbit.

[caption id="" align="aligncenter" width="480"] Figure 2. Anterior View of Skull. An anterior view of the skull shows the bones that form the forehead, orbits (eye sockets), nasal cavity, nasal septum, and upper and lower jaws.[/caption]

Inside the nasal area of the skull, the nasal cavity is divided into halves by the nasal septum. The upper portion of the nasal septum is formed by the perpendicular plate of the ethmoid bone and the lower portion is the vomer bone. Each side of the nasal cavity is triangular in shape, with a broad inferior space that narrows superiorly. When looking into the nasal cavity from the front of the skull, two bony plates are seen projecting from each lateral wall. The larger of these is the inferior nasal concha, an independent bone of the skull. Located just above the inferior concha is the middle nasal concha, which is part of the ethmoid bone. A third bony plate, also part of the ethmoid bone, is the superior nasal concha. It is much smaller and out of sight, above the middle concha. The superior nasal concha is located just lateral to the perpendicular plate, in the upper nasal cavity.

Lateral View of Skull

A view of the lateral skull is dominated by the large, rounded brain case above and the upper and lower jaws with their teeth below (Figure 3). Separating these areas is the bridge of bone called the zygomatic arch. The zygomatic arch is the bony arch on the side of skull that spans from the area of the cheek to just above the ear canal. It is formed by the junction of two bony processes: a short anterior component, the temporal process of the zygomatic bone (the cheekbone) and a longer posterior portion, the zygomatic process of the temporal bone, extending forward from the temporal bone. Thus the temporal process (anteriorly) and the zygomatic process (posteriorly) join together, like the two ends of a drawbridge, to form the zygomatic arch. One of the major muscles that pulls the mandible upward during biting and chewing arises from the zygomatic arch.

On the lateral side of the brain case, above the level of the zygomatic arch, is a shallow space called the temporal fossa. Below the level of the zygomatic arch and deep to the vertical portion of the mandible is another space called the infratemporal fossa. Both the temporal fossa and infratemporal fossa contain muscles that act on the mandible during chewing.

[caption id="" align="aligncenter" width="480"] Figure 3. Lateral View of Skull. The lateral skull shows the large rounded brain case, zygomatic arch, and the upper and lower jaws. The zygomatic arch is formed jointly by the zygomatic process of the temporal bone and the temporal process of the zygomatic bone. The shallow space above the zygomatic arch is the temporal fossa. The space inferior to the zygomatic arch and deep to the posterior mandible is the infratemporal fossa.[/caption]

Bones of the Brain Case

The brain case contains and protects the brain. The interior space that is almost completely occupied by the brain is called the cranial cavity. This cavity is bounded superiorly by the rounded top of the skull, which is called the calvaria (skullcap), and the lateral and posterior sides of the skull. The bones that form the top and sides of the brain case are usually referred to as the “flat” bones of the skull.

The floor of the brain case is referred to as the base of the skull. This is a complex area that varies in depth and has numerous openings for the passage of cranial nerves, blood vessels, and the spinal cord. Inside the skull, the base is subdivided into three large spaces, called the anterior cranial fossa, middle cranial fossa, and posterior cranial fossa (fossa = “trench or ditch”) (Figure 4). From anterior to posterior, the fossae increase in depth. The shape and depth of each fossa corresponds to the shape and size of the brain region that each houses. The boundaries and openings of the cranial fossae (singular = fossa) will be described in a later section.

The brain case consists of eight bones. These include the paired parietal and temporal bones, plus the unpaired frontal, occipital, sphenoid, and ethmoid bones.

Parietal Bone

The parietal bone forms most of the upper lateral side of the skull (see Figure 3). These are paired bones, with the right and left parietal bones joining together at the top of the skull. Each parietal bone is also bounded anteriorly by the frontal bone, inferiorly by the temporal bone, and posteriorly by the occipital bone.

Temporal Bone

The temporal bone forms the lower lateral side of the skull (see Figure 3). Common wisdom has it that the temporal bone (temporal = “time”) is so named because this area of the head (the temple) is where hair typically first turns gray, indicating the passage of time.

The temporal bone is subdivided into several regions (Figure 5). The flattened, upper portion is the squamous portion of the temporal bone. Below this area and projecting anteriorly is the zygomatic process of the temporal bone, which forms the posterior portion of the zygomatic arch. Posteriorly is the mastoid portion of the temporal bone. Projecting inferiorly from this region is a large prominence, the mastoid process, which serves as a muscle attachment site. The mastoid process can easily be felt on the side of the head just behind your earlobe. On the interior of the skull, the petrous portion of each temporal bone forms the prominent, diagonally oriented petrous ridge in the floor of the cranial cavity. Located inside each petrous ridge are small cavities that house the structures of the middle and inner ears.

[caption id="" align="aligncenter" width="450"] Figure 5. Temporal Bone. A lateral view of the isolated temporal bone shows the squamous, mastoid, and zygomatic portions of the temporal bone.[/caption]

Frontal Bone

The frontal bone is the single bone that forms the forehead. At its anterior midline, between the eyebrows, there is a slight depression called the glabella (see Figure 3). The frontal bone also forms the supraorbital margin of the orbit. Near the middle of this margin, is the supraorbital foramen, the opening that provides passage for a sensory nerve to the forehead. The frontal bone is thickened just above each supraorbital margin, forming rounded brow ridges. These are located just behind your eyebrows and vary in size among individuals, although they are generally larger in males. Inside the cranial cavity, the frontal bone extends posteriorly. This flattened region forms both the roof of the orbit below and the floor of the anterior cranial cavity above (see Figure 6b).

Occipital Bone

The occipital bone is the single bone that forms the posterior skull and posterior base of the cranial cavity (Figure 7; see also Figure 6). On its outside surface, at the posterior midline, is a small protrusion called the external occipital protuberance, which serves as an attachment site for a ligament of the posterior neck. Lateral to either side of this bump is a superior nuchal line (nuchal = “nape” or “posterior neck”). The nuchal lines represent the most superior point at which muscles of the neck attach to the skull, with only the scalp covering the skull above these lines. On the base of the skull, the occipital bone contains the large opening of the foramen magnum, which allows for passage of the spinal cord as it exits the skull. On either side of the foramen magnum is an oval-shaped occipital condyle. These condyles form joints with the first cervical vertebra and thus support the skull on top of the vertebral column.

[caption id="" align="aligncenter" width="420"] Figure 7. Posterior View of Skull. This view of the posterior skull shows attachment sites for muscles and joints that support the skull.[/caption]

Sutures of the Skull

A suture is an immobile joint between adjacent bones of the skull. The narrow gap between the bones is filled with dense, fibrous connective tissue that unites the bones. The long sutures located between the bones of the brain case are not straight, but instead follow irregular, tightly twisting paths. These twisting lines serve to tightly interlock the adjacent bones, thus adding strength to the skull for brain protection.

The two suture lines seen on the top of the skull are the coronal and sagittal sutures. The coronal suture runs from side to side across the skull, within the coronal plane of section (see Figure 3). It joins the frontal bone to the right and left parietal bones. The sagittal suture extends posteriorly from the coronal suture, running along the midline at the top of the skull in the sagittal plane of section (see Figure 7). It unites the right and left parietal bones. On the posterior skull, the sagittal suture terminates by joining the lambdoid suture. The lambdoid suture extends downward and laterally to either side away from its junction with the sagittal suture. The lambdoid suture joins the occipital bone to the right and left parietal and temporal bones. This suture is named for its upside-down "V" shape, which resembles the capital letter version of the Greek letter lambda (Λ). The squamous suture is located on the lateral skull. It unites the squamous portion of the temporal bone with the parietal bone (see Figure 3). At the intersection of four bones is the pterion, a small, capital-H-shaped suture line region that unites the frontal bone, parietal bone, squamous portion of the temporal bone, and greater wing of the sphenoid bone. It is the weakest part of the skull. The pterion is located approximately two finger widths above the zygomatic arch and a thumb’s width posterior to the upward portion of the zygomatic bone.

Facial Bones of the Skull

The facial bones of the skull form the upper and lower jaws, the nose, nasal cavity and nasal septum, and the orbit. The facial bones include 14 bones, with six paired bones and two unpaired bones. The paired bones are the maxilla, palatine, zygomatic, nasal, lacrimal, and inferior nasal conchae bones. The unpaired bones are the vomer and mandible bones. Although classified with the brain-case bones, the ethmoid bone also contributes to the nasal septum and the walls of the nasal cavity and orbit.

Maxillary Bone

The maxillary bone, often referred to simply as the maxilla (plural = maxillae), is one of a pair that together form the upper jaw, much of the hard palate, the medial floor of the orbit, and the lateral base of the nose (see Figure 2). The curved, inferior margin of the maxillary bone that forms the upper jaw and contains the upper teeth is the alveolar process of the maxilla (Figure 12). Each tooth is anchored into a deep socket called an alveolus. On the anterior maxilla, just below the orbit, is the infraorbital foramen. This is the point of exit for a sensory nerve that supplies the nose, upper lip, and anterior cheek. On the inferior skull, the palatine process from each maxillary bone can be seen joining together at the midline to form the anterior three-quarters of the hard palate (see Figure 6a). The hard palate is the bony plate that forms the roof of the mouth and floor of the nasal cavity, separating the oral and nasal cavities.

[caption id="" align="aligncenter" width="420"] Figure 12. Maxillary Bone. The maxillary bone forms the upper jaw and supports the upper teeth. Each maxilla also forms the lateral floor of each orbit and the majority of the hard palate.[/caption]

Mandible

The mandible forms the lower jaw and is the only moveable bone of the skull. At the time of birth, the mandible consists of paired right and left bones, but these fuse together during the first year to form the single U-shaped mandible of the adult skull. Each side of the mandible consists of a horizontal body and posteriorly, a vertically oriented ramus of the mandible (ramus = “branch”). The outside margin of the mandible, where the body and ramus come together is called the angle of the mandible (Figure 13).

The ramus on each side of the mandible has two upward-going bony projections. The more anterior projection is the flattened coronoid process of the mandible, which provides attachment for one of the biting muscles. The posterior projection is the condylar process of the mandible, which is topped by the oval-shaped condyle. The condyle of the mandible articulates (joins) with the mandibular fossa and articular tubercle of the temporal bone. Together these articulations form the temporomandibular joint, which allows for opening and closing of the mouth (see Figure 3). The broad U-shaped curve located between the coronoid and condylar processes is the mandibular notch.

[caption id="" align="aligncenter" width="420"] Figure 13. Isolated Mandible. The mandible is the only moveable bone of the skull.[/caption]

Hyoid Bone

The hyoid bone is an independent bone that does not contact any other bone and thus is not part of the skull (Figure 17). It is a small U-shaped bone located in the upper neck near the level of the inferior mandible, with the tips of the “U” pointing posteriorly. The hyoid serves as the base for the tongue above, and is attached to the larynx below and the pharynx posteriorly. The hyoid is held in position by a series of small muscles that attach to it either from above or below. These muscles act to move the hyoid up/down or forward/back. Movements of the hyoid are coordinated with movements of the tongue, larynx, and pharynx during swallowing and speaking.

[caption id="" align="aligncenter" width="300"] Figure 17. Hyoid Bone. The hyoid bone is located in the upper neck and does not join with any other bone. It provides attachments for muscles that act on the tongue, larynx, and pharynx.[/caption]

7.3 The Vertebral Column

barkerj1 — Wed, 30 Aug 2017 18:37:41 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the structure and function of a typical vertebra
Explain how the structure and function of the atlas and axis differ from those of a typical vertebra

The vertebral column is also known as the spinal column or spine (Figure 1). It consists of a sequence of vertebrae (singular = vertebra), each of which is separated and united by an intervertebral disc. Together, the vertebrae and intervertebral discs form the vertebral column. It is a flexible column that supports the head, neck, and body and allows for their movements. It also protects the spinal cord, which passes down the back through openings in the vertebrae.

[caption id="" align="aligncenter" width="480"] Figure 1. Vertebral Column. The adult vertebral column consists of 24 vertebrae, plus the sacrum and coccyx. The vertebrae are divided into three regions: cervical C1–C7 vertebrae, thoracic T1–T12 vertebrae, and lumbar L1–L5 vertebrae. The vertebral column is curved, with two primary curvatures (thoracic and sacrococcygeal curves) and two secondary curvatures (cervical and lumbar curves).[/caption]

Regions of the Vertebral Column

The vertebral column originally develops as a series of 33 vertebrae, but this number is eventually reduced to 24 vertebrae, plus the sacrum and coccyx. The vertebral column is subdivided into five regions, with the vertebrae in each area named for that region and numbered in descending order. In the neck, there are seven cervical vertebrae, each designated with the letter “C” followed by its number. Superiorly, the C1 vertebra articulates (forms a joint) with the occipital condyles of the skull. Inferiorly, C1 articulates with the C2 vertebra, and so on. Below these are the 12 thoracic vertebrae, designated T1–T12. The lower back contains the L1–L5 lumbar vertebrae. The single sacrum, which is also part of the pelvis, is formed by the fusion of five sacral vertebrae. Similarly, the coccyx, or tailbone, results from the fusion of four small coccygeal vertebrae. However, the sacral and coccygeal fusions do not start until age 20 and are not completed until middle age.

An interesting anatomical fact is that almost all mammals have seven cervical vertebrae, regardless of body size. This means that there are large variations in the size of cervical vertebrae, ranging from the very small cervical vertebrae of a shrew to the greatly elongated vertebrae in the neck of a giraffe. In a full-grown giraffe, each cervical vertebra is 11 inches tall.

Curvatures of the Vertebral Column

The adult vertebral column does not form a straight line, but instead has four curvatures along its length (see Figure 1). These curves increase the vertebral column’s strength, flexibility, and ability to absorb shock. When the load on the spine is increased, by carrying a heavy backpack for example, the curvatures increase in depth (become more curved) to accommodate the extra weight. They then spring back when the weight is removed. The four adult curvatures are classified as either primary or secondary curvatures. Primary curves are retained from the original fetal curvature, while secondary curvatures develop after birth.

During fetal development, the body is flexed anteriorly into the fetal position, giving the entire vertebral column a single curvature that is concave anteriorly. In the adult, this fetal curvature is retained in two regions of the vertebral column as the thoracic curve, which involves the thoracic vertebrae, and the sacrococcygeal curve, formed by the sacrum and coccyx. Each of these is thus called a primary curve because they are retained from the original fetal curvature of the vertebral column.

A secondary curve develops gradually after birth as the child learns to sit upright, stand, and walk. Secondary curves are concave posteriorly, opposite in direction to the original fetal curvature. The cervical curve of the neck region develops as the infant begins to hold their head upright when sitting. Later, as the child begins to stand and then to walk, the lumbar curve of the lower back develops. In adults, the lumbar curve is generally deeper in females.

Disorders associated with the curvature of the spine include kyphosis (an excessive posterior curvature of the thoracic region), lordosis (an excessive anterior curvature of the lumbar region), and scoliosis (an abnormal, lateral curvature, accompanied by twisting of the vertebral column).

General Structure of a Vertebra

Within the different regions of the vertebral column, vertebrae vary in size and shape, but they all follow a similar structural pattern. A typical vertebra will consist of a body, a vertebral arch, and seven processes (Figure 4).

The body is the anterior portion of each vertebra and is the part that supports the body weight. Because of this, the vertebral bodies progressively increase in size and thickness going down the vertebral column. The bodies of adjacent vertebrae are separated and strongly united by an intervertebral disc.

The vertebral arch forms the posterior portion of each vertebra. It consists of four parts, the right and left pedicles and the right and left laminae. Each pedicle forms one of the lateral sides of the vertebral arch. The pedicles are anchored to the posterior side of the vertebral body. Each lamina forms part of the posterior roof of the vertebral arch. The large opening between the vertebral arch and body is the vertebral foramen, which contains the spinal cord. In the intact vertebral column, the vertebral foramina of all of the vertebrae align to form the vertebral (spinal) canal, which serves as the bony protection and passageway for the spinal cord down the back. When the vertebrae are aligned together in the vertebral column, notches in the margins of the pedicles of adjacent vertebrae together form an intervertebral foramen, the opening through which a spinal nerve exits from the vertebral column (Figure 5).

Seven processes arise from the vertebral arch. Each paired transverse process projects laterally and arises from the junction point between the pedicle and lamina. The single spinous process (vertebral spine) projects posteriorly at the midline of the back. The vertebral spines can easily be felt as a series of bumps just under the skin down the middle of the back. The transverse and spinous processes serve as important muscle attachment sites. A superior articular process extends or faces upward, and an inferior articular process faces or projects downward on each side of a vertebrae. The paired superior articular processes of one vertebra join with the corresponding paired inferior articular processes from the next higher vertebra. These junctions form slightly moveable joints between the adjacent vertebrae. The shape and orientation of the articular processes vary in different regions of the vertebral column and play a major role in determining the type and range of motion available in each region.

[caption id="" align="aligncenter" width="550"] Figure 4. Parts of a Typical Vertebra. A typical vertebra consists of a body and a vertebral arch. The arch is formed by the paired pedicles and paired laminae. Arising from the vertebral arch are the transverse, spinous, superior articular, and inferior articular processes. The vertebral foramen provides for passage of the spinal cord. Each spinal nerve exits through an intervertebral foramen, located between adjacent vertebrae. Intervertebral discs unite the bodies of adjacent vertebrae.[/caption]

[caption id="" align="aligncenter" width="480"] Figure 5. Intervertebral Disc. The bodies of adjacent vertebrae are separated and united by an intervertebral disc, which provides padding and allows for movements between adjacent vertebrae. The disc consists of a fibrous outer layer called the anulus fibrosus and a gel-like center called the nucleus pulposus. The intervertebral foramen is the opening formed between adjacent vertebrae for the exit of a spinal nerve.[/caption]

Regional Modifications of Vertebrae

In addition to the general characteristics of a typical vertebra described above, vertebrae also display characteristic size and structural features that vary between the different vertebral column regions. Thus, cervical vertebrae are smaller than lumbar vertebrae due to differences in the proportion of body weight that each supports. Thoracic vertebrae have sites for rib attachment, and the vertebrae that give rise to the sacrum and coccyx have fused together into single bones.

Cervical Vertebrae

Typical cervical vertebrae, such as C4 or C5, have several characteristic features that differentiate them from thoracic or lumbar vertebrae (Figure 6). Cervical vertebrae have a small body, reflecting the fact that they carry the least amount of body weight. Cervical vertebrae usually have a bifid (Y-shaped) spinous process. The spinous processes of the C3–C6 vertebrae are short, but the spine of C7 is much longer. You can find these vertebrae by running your finger down the midline of the posterior neck until you encounter the prominent C7 spine located at the base of the neck. The transverse processes of the cervical vertebrae are sharply curved (U-shaped) to allow for passage of the cervical spinal nerves. Each transverse process also has an opening called the transverse foramen. An important artery that supplies the brain ascends up the neck by passing through these openings. The superior and inferior articular processes of the cervical vertebrae are flattened and largely face upward or downward, respectively.

The first and second cervical vertebrae are further modified, giving each a distinctive appearance. The first cervical (C1) vertebra is also called the atlas, because this is the vertebra that supports the skull on top of the vertebral column (in Greek mythology, Atlas was the god who supported the heavens on his shoulders). The C1 vertebra does not have a body or spinous process. Instead, it is ring-shaped, consisting of an anterior arch and a posterior arch. The transverse processes of the atlas are longer and extend more laterally than do the transverse processes of any other cervical vertebrae. The superior articular processes face upward and are deeply curved for articulation with the occipital condyles on the base of the skull. The inferior articular processes are flat and face downward to join with the superior articular processes of the C2 vertebra.

The second cervical (C2) vertebra is called the axis, because it serves as the axis for rotation when turning the head toward the right or left. The axis resembles typical cervical vertebrae in most respects, but is easily distinguished by the dens (odontoid process), a bony projection that extends upward from the vertebral body. The dens joins with the inner aspect of the anterior arch of the atlas, where it is held in place by transverse ligament.

[caption id="" align="aligncenter" width="550"] Figure 6. Cervical Vertebrae. A typical cervical vertebra has a small body, a bifid spinous process, transverse processes that have a transverse foramen and are curved for spinal nerve passage. The atlas (C1 vertebra) does not have a body or spinous process. It consists of an anterior and a posterior arch and elongated transverse processes. The axis (C2 vertebra) has the upward projecting dens, which articulates with the anterior arch of the atlas.[/caption]

Thoracic Vertebrae

The bodies of the thoracic vertebrae are larger than those of cervical vertebrae (Figure 7). The characteristic feature for a typical midthoracic vertebra is the spinous process, which is long and has a pronounced downward angle that causes it to overlap the next inferior vertebra. The superior articular processes of thoracic vertebrae face anteriorly and the inferior processes face posteriorly. These orientations are important determinants for the type and range of movements available to the thoracic region of the vertebral column.

Thoracic vertebrae have several additional articulation sites, each of which is called a facet, where a rib is attached. Most thoracic vertebrae have two facets located on the lateral sides of the body, each of which is called a costal facet (costal = “rib”). These are for articulation with the head (end) of a rib. An additional facet is located on the transverse process for articulation with the tubercle of a rib.

[caption id="" align="aligncenter" width="450"] Figure 7. Thoracic Vertebrae. A typical thoracic vertebra is distinguished by the spinous process, which is long and projects downward to overlap the next inferior vertebra. It also has articulation sites (facets) on the vertebral body and a transverse process for rib attachment.[/caption]

[caption id="" align="aligncenter" width="380"] Figure 8. Rib Articulation in Thoracic Vertebrae. Thoracic vertebrae have superior and inferior articular facets on the vertebral body for articulation with the head of a rib, and a transverse process facet for articulation with the rib tubercle.[/caption]

Lumbar Vertebrae

Lumbar vertebrae carry the greatest amount of body weight and are thus characterized by the large size and thickness of the vertebral body (Figure 9). They have short transverse processes and a short, blunt spinous process that projects posteriorly. The articular processes are large, with the superior process facing backward and the inferior facing forward.

[caption id="" align="aligncenter" width="350"] Figure 9. Lumbar Vertebrae. Lumbar vertebrae are characterized by having a large, thick body and a short, rounded spinous process.[/caption]

Sacrum and Coccyx

The sacrum is a triangular-shaped bone that is thick and wide across its superior base where it is weight bearing and then tapers down to an inferior, non-weight bearing apex (Figure 10). It is formed by the fusion of five sacral vertebrae, a process that does not begin until after the age of 20. On the anterior surface of the older adult sacrum, the lines of vertebral fusion can be seen as four transverse ridges. On the posterior surface, running down the midline, is the median sacral crest, a bumpy ridge that is the remnant of the fused spinous processes (median = “midline”; while medial = “toward, but not necessarily at, the midline”). Similarly, the fused transverse processes of the sacral vertebrae form the lateral sacral crest.

The sacral promontory is the anterior lip of the superior base of the sacrum. Lateral to this is the roughened auricular surface, which joins with the ilium portion of the hipbone to form the immobile sacroiliac joints of the pelvis. Passing inferiorly through the sacrum is a bony tunnel called the sacral canal, which terminates at the sacral hiatus near the inferior tip of the sacrum. The anterior and posterior surfaces of the sacrum have a series of paired openings called sacral foramina (singular = foramen) that connect to the sacral canal. Each of these openings is called a posterior (dorsal) sacral foramen or anterior (ventral) sacral foramen. These openings allow for the anterior and posterior branches of the sacral spinal nerves to exit the sacrum. The superior articular process of the sacrum, one of which is found on either side of the superior opening of the sacral canal, articulates with the inferior articular processes from the L5 vertebra.

The coccyx, or tailbone, is derived from the fusion of four very small coccygeal vertebrae (see Figure 10). It articulates with the inferior tip of the sacrum. It is not weight bearing in the standing position, but may receive some body weight when sitting.

[caption id="" align="aligncenter" width="550"] Figure 10. Sacrum and Coccyx. The sacrum is formed from the fusion of five sacral vertebrae, whose lines of fusion are indicated by the transverse ridges. The fused spinous processes form the median sacral crest, while the lateral sacral crest arises from the fused transverse processes. The coccyx is formed by the fusion of four small coccygeal vertebrae.[/caption]

Intervertebral Discs and Ligaments of the Vertebral Column

The bodies of adjacent vertebrae are strongly anchored to each other by an intervertebral disc. This structure provides padding between the bones during weight bearing, and because it can change shape, also allows for movement between the vertebrae. Although the total amount of movement available between any two adjacent vertebrae is small, when these movements are summed together along the entire length of the vertebral column, large body movements can be produced. Ligaments that extend along the length of the vertebral column also contribute to its overall support and stability.

Intervertebral Disc

An intervertebral disc is a fibrocartilaginous pad that fills the gap between adjacent vertebral bodies (see Figure 5). Each disc is anchored to the bodies of its adjacent vertebrae, thus strongly uniting these. The discs also provide padding between vertebrae during weight bearing. Because of this, intervertebral discs are thin in the cervical region and thickest in the lumbar region, which carries the most body weight. In total, the intervertebral discs account for approximately 25 percent of your body height between the top of the pelvis and the base of the skull. Intervertebral discs are also flexible and can change shape to allow for movements of the vertebral column.

Each intervertebral disc consists of two parts. The anulus fibrosus is the tough, fibrous outer layer of the disc. It forms a circle (anulus = “ring” or “circle”) and is firmly anchored to the outer margins of the adjacent vertebral bodies. Inside is the nucleus pulposus, consisting of a softer, more gel-like material. It has a high water content that serves to resist compression and thus is important for weight bearing. With increasing age, the water content of the nucleus pulposus gradually declines. This causes the disc to become thinner, decreasing total body height somewhat, and reduces the flexibility and range of motion of the disc, making bending more difficult.

The gel-like nature of the nucleus pulposus also allows the intervertebral disc to change shape as one vertebra rocks side to side or forward and back in relation to its neighbors during movements of the vertebral column. Thus, bending forward causes compression of the anterior portion of the disc but expansion of the posterior disc. If the posterior anulus fibrosus is weakened due to injury or increasing age, the pressure exerted on the disc when bending forward and lifting a heavy object can cause the nucleus pulposus to protrude posteriorly through the anulus fibrosus, resulting in a herniated disc (“ruptured” or “slipped” disc) (Figure 11). The posterior bulging of the nucleus pulposus can cause compression of a spinal nerve at the point where it exits through the intervertebral foramen, with resulting pain and/or muscle weakness in those body regions supplied by that nerve. The most common sites for disc herniation are the L4/L5 or L5/S1 intervertebral discs, which can cause sciatica, a widespread pain that radiates from the lower back down the thigh and into the leg. Similar injuries of the C5/C6 or C6/C7 intervertebral discs, following forcible hyperflexion of the neck from a collision accident or football injury, can produce pain in the neck, shoulder, and upper limb.

[caption id="" align="aligncenter" width="450"] Figure 11. Herniated Intervertebral Disc. Weakening of the anulus fibrosus can result in herniation (protrusion) of the nucleus pulposus and compression of a spinal nerve, resulting in pain and/or muscle weakness in the body regions supplied by that nerve.[/caption]

7.4 The Thoracic Cage

barkerj1 — Wed, 30 Aug 2017 18:37:41 +0000

Learning Objectives

By the end of this section, you will be able to:

Name and describe the principle components of the thoracic cage

The thoracic cage (rib cage) forms the thorax (chest) portion of the body. It consists of the 12 pairs of ribs with their costal cartilages and the sternum (Figure 1). The ribs are anchored posteriorly to the 12 thoracic vertebrae (T1–T12). The thoracic cage protects the heart and lungs.

[caption id="" align="aligncenter" width="550"] Figure 1. Thoracic Cage. The thoracic cage is formed by the (a) sternum and (b) 12 pairs of ribs with their costal cartilages. The ribs are anchored posteriorly to the 12 thoracic vertebrae. The sternum consists of the manubrium, body, and xiphoid process. The ribs are classified as true ribs (1–7) and false ribs (8–12). The last two pairs of false ribs are also known as floating ribs (11–12).[/caption]

Sternum

The sternum is the elongated bony structure that anchors the anterior thoracic cage. It consists of three parts: the manubrium, body, and xiphoid process. The manubrium is the wider, superior portion of the sternum. The top of the manubrium has a shallow, U-shaped border called the jugular (suprasternal) notch. This can be easily felt at the anterior base of the neck, between the medial ends of the clavicles. The clavicular notch is the shallow depression located on either side at the superior-lateral margins of the manubrium. This is the site of the sternoclavicular joint, between the sternum and clavicle. The first ribs also attach to the manubrium.

The elongated, central portion of the sternum is the body. The manubrium and body join together at the sternal angle, so called because the junction between these two components is not flat, but forms a slight bend. The second rib attaches to the sternum at the sternal angle. Since the first rib is hidden behind the clavicle, the second rib is the highest rib that can be identified by palpation. Thus, the sternal angle and second rib are important landmarks for the identification and counting of the lower ribs. Ribs 3–7 attach to the sternal body.

The inferior tip of the sternum is the xiphoid process. This small structure is cartilaginous early in life, but gradually becomes ossified starting during middle age.

Ribs

Each rib is a curved, flattened bone that contributes to the wall of the thorax. The ribs articulate posteriorly with the T1–T12 thoracic vertebrae, and most attach anteriorly via their costal cartilages to the sternum. There are 12 pairs of ribs. The ribs are numbered 1–12 in accordance with the thoracic vertebrae.

Parts of a Typical Rib

The posterior end of a typical rib is called the head of the rib (see Chapter 7.3 Figure 8). This region articulates primarily with the costal facet located on the body of the same numbered thoracic vertebra and to a lesser degree, with the costal facet located on the body of the next higher vertebra. Lateral to the head is the narrowed neck of the rib. A small bump on the posterior rib surface is the tubercle of the rib, which articulates with the facet located on the transverse process of the same numbered vertebra. The remainder of the rib is the body of the rib (shaft). Just lateral to the tubercle is the angle of the rib, the point at which the rib has its greatest degree of curvature. The angles of the ribs form the most posterior extent of the thoracic cage. In the anatomical position, the angles align with the medial border of the scapula. A shallow costal groove for the passage of blood vessels and a nerve is found along the inferior margin of each rib.

Rib Classifications

The bony ribs do not extend anteriorly completely around to the sternum. Instead, each rib ends in a costal cartilage. These cartilages are made of hyaline cartilage and can extend for several inches. Most ribs are then attached, either directly or indirectly, to the sternum via their costal cartilage (see Figure 1). The ribs are classified into three groups based on their relationship to the sternum.

Ribs 1–7 are classified as true ribs (vertebrosternal ribs). The costal cartilage from each of these ribs attaches directly to the sternum. Ribs 8–12 are called false ribs (vertebrochondral ribs). The costal cartilages from these ribs do not attach directly to the sternum. For ribs 8–10, the costal cartilages are attached to the cartilage of the next higher rib. Thus, the cartilage of rib 10 attaches to the cartilage of rib 9, rib 9 then attaches to rib 8, and rib 8 is attached to rib 7. The last two false ribs (11–12) are also called floating ribs (vertebral ribs). These are short ribs that do not attach to the sternum at all. Instead, their small costal cartilages terminate within the musculature of the lateral abdominal wall.1.

7.5 Embryonic Development of the Axial Skeleton

barkerj1 — Wed, 30 Aug 2017 18:37:43 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the major differences between the axial skeleton of a baby and that of an adult

The axial skeleton begins to form during early embryonic development. However, growth, remodeling, and ossification (bone formation) continue for several decades after birth before the adult skeleton is fully formed. Knowledge of the developmental processes that give rise to the skeleton is important for understanding the abnormalities that may arise in skeletal structures.

Development of the Skull

The bones of the skull arise from mesenchyme during embryonic development in two different ways. The first mechanism produces the bones that form the top and sides of the brain case. This involves the local accumulation of mesenchymal cells at the site of the future bone. These cells then differentiate directly into bone producing cells, which form the skull bones through the process of intramembranous ossification. As the brain case bones grow in the fetal skull, they remain separated from each other by large areas of dense connective tissue, each of which is called a fontanelle (Figure 1). The fontanelles are the soft spots on an infant’s head. They are important during birth because these areas allow the skull to change shape as it squeezes through the birth canal. After birth, the fontanelles allow for continued growth and expansion of the skull as the brain enlarges. The largest fontanelle is located on the anterior head, at the junction of the frontal and parietal bones. The fontanelles decrease in size and disappear by age 2. However, the skull bones remained separated from each other at the sutures, which contain dense fibrous connective tissue that unites the adjacent bones. The connective tissue of the sutures allows for continued growth of the skull bones as the brain enlarges during childhood growth. This structure also means that, although the size of the cranium increases from birth to adulthood, proportionately it does so less than other parts of the skeleton; the relative size of the cranium in proportion to the rest of the body therefore decreases with age from birth to adulthood.

The second mechanism for bone development in the skull produces the facial bones and floor of the brain case. This also begins with the localized accumulation of mesenchymal cells. However, these cells differentiate into cartilage cells, which produce a hyaline cartilage model of the future bone. As this cartilage model grows, it is gradually converted into bone through the process of endochondral ossification. This is a slow process and the cartilage is not completely converted to bone until the skull achieves its full adult size.

At birth, the brain case and orbits of the skull are disproportionally large compared to the bones of the jaws and lower face. This reflects the relative underdevelopment of the maxilla and mandible, which lack teeth, and the small sizes of the paranasal sinuses and nasal cavity. During early childhood, the mastoid process enlarges, the two halves of the mandible and frontal bone fuse together to form single bones, and the paranasal sinuses enlarge. The jaws also expand as the teeth begin to appear. These changes all contribute to the rapid growth and enlargement of the face during childhood.

[caption id="" align="aligncenter" width="550"] Figure 1. Newborn Skull. The bones of the newborn skull are not fully ossified and are separated by large areas called fontanelles, which are filled with fibrous connective tissue. The fontanelles allow for continued growth of the skull after birth. At the time of birth, the facial bones are small and underdeveloped, and the mastoid process has not yet formed.[/caption]

Development of the Vertebral Column and Thoracic cage

Development of the vertebrae begins with the accumulation of mesenchyme cells from each sclerotome around the notochord. These cells differentiate into a hyaline cartilage model for each vertebra, which then grow and eventually ossify into bone through the process of endochondral ossification. As the developing vertebrae grow, the notochord largely disappears. However, small areas of notochord tissue persist between the adjacent vertebrae and this contributes to the formation of each intervertebral disc.

[caption id="" align="alignright" width="120"] View this video to review the two processes that give rise to the bones of the skull and body.[/caption] The ribs and sternum also develop from mesenchyme. The ribs initially develop as part of the cartilage model for each vertebra, but in the thorax region, the rib portion separates from the vertebra by the eighth week. The cartilage model of the rib then ossifies, except for the anterior portion, which remains as the costal cartilage. The sternum initially forms as paired hyaline cartilage models on either side of the anterior midline, beginning during the fifth week of development. The cartilage models of the ribs become attached to the lateral sides of the developing sternum. Eventually, the two halves of the cartilaginous sternum fuse together along the midline and then ossify into bone. The manubrium and body of the sternum are converted into bone first, with the xiphoid process remaining as cartilage until late in life.

Introduction

barkerj1 — Wed, 30 Aug 2017 18:37:43 +0000

[caption id="" align="aligncenter" width="500"] Figure 1. Dancer. The appendicular skeleton consists of the upper and lower limb bones, the bones of the hands and feet, and the bones that anchor the limbs to the axial skeleton. (credit: Melissa Dooley/flickr)[/caption] Your skeleton provides the internal supporting structure of the body. The adult axial skeleton consists of 80 bones that form the head and body trunk. Attached to this are the limbs, whose 126 bones constitute the appendicular skeleton. These bones are divided into two groups: the bones that are located within the limbs themselves, and the girdle bones that attach the limbs to the axial skeleton. The bones of the shoulder region form the pectoral girdle, which anchors the upper limb to the thoracic cage of the axial skeleton. The lower limb is attached to the vertebral column by the pelvic girdle. Because of our upright stance, different functional demands are placed upon the upper and lower limbs. Thus, the bones of the lower limbs are adapted for weight-bearing support and stability, as well as for body locomotion via walking or running. In contrast, our upper limbs are not required for these functions. Instead, our upper limbs are highly mobile and can be utilized for a wide variety of activities. The large range of upper limb movements, coupled with the ability to easily manipulate objects with our hands and opposable thumbs, has allowed humans to construct the modern world in which we live.

8.1 The Pectoral Girdle

barkerj1 — Wed, 30 Aug 2017 18:37:45 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the components and functions of the pectoral girdle

The appendicular skeleton includes all of the limb bones, plus the bones that unite each limb with the axial skeleton (Figure 1). The bones that attach each upper limb to the axial skeleton form the pectoral girdle (shoulder girdle). This consists of two bones, the scapula and clavicle (Figure 2). The clavicle (collarbone) is an S-shaped bone located on the anterior side of the shoulder. It is attached on its medial end to the sternum of the thoracic cage, which is part of the axial skeleton. The lateral end of the clavicle articulates (joins) with the scapula just above the shoulder joint. You can easily palpate, or feel with your fingers, the entire length of your clavicle.

[caption id="" align="aligncenter" width="600"] Figure 1. Axial and Appendicular Skeletons. The axial skeleton forms the central axis of the body and consists of the skull, vertebral column, and thoracic cage. The appendicular skeleton consists of the pectoral and pelvic girdles, the limb bones, and the bones of the hands and feet.[/caption]

[caption id="" align="aligncenter" width="450"] Figure 2. Pectoral Girdle. The pectoral girdle consists of the clavicle and the scapula, which serve to attach the upper limb to the sternum of the axial skeleton.[/caption]

The scapula (shoulder blade) lies on the posterior aspect of the shoulder. It is supported by the clavicle, which also articulates with the humerus (arm bone) to form the shoulder joint. The scapula is a flat, triangular-shaped bone with a prominent ridge running across its posterior surface. This ridge extends out laterally, where it forms the bony tip of the shoulder and joins with the lateral end of the clavicle. By following along the clavicle, you can palpate out to the bony tip of the shoulder, and from there, you can move back across your posterior shoulder to follow the ridge of the scapula. Move your shoulder around and feel how the clavicle and scapula move together as a unit. Both of these bones serve as important attachment sites for muscles that aid with movements of the shoulder and arm.

The right and left pectoral girdles are not joined to each other, allowing each to operate independently. In addition, the clavicle of each pectoral girdle is anchored to the axial skeleton by a single, highly mobile joint. This allows for the extensive mobility of the entire pectoral girdle, which in turn enhances movements of the shoulder and upper limb.

Clavicle

The clavicle is the only long bone that lies in a horizontal position in the body (see Figure 2). The clavicle has several important functions. First, anchored by muscles from above, it serves as a strut that extends laterally to support the scapula. This in turn holds the shoulder joint superiorly and laterally from the body trunk, allowing for maximal freedom of motion for the upper limb. The clavicle also transmits forces acting on the upper limb to the sternum and axial skeleton. Finally, it serves to protect the underlying nerves and blood vessels as they pass between the trunk of the body and the upper limb.

The clavicle has three regions: the medial end, the lateral end, and the shaft. The medial end, known as the sternal end of the clavicle, has a triangular shape and articulates with the manubrium portion of the sternum. This forms the sternoclavicular joint, which is the only bony articulation between the pectoral girdle of the upper limb and the axial skeleton. This joint allows considerable mobility, enabling the clavicle and scapula to move in upward/downward and anterior/posterior directions during shoulder movements. The sternoclavicular joint is indirectly supported by the costoclavicular ligament (costo- = “rib”), which spans the sternal end of the clavicle and the underlying first rib. The lateral or acromial end of the clavicle articulates with the acromion of the scapula, the portion of the scapula that forms the bony tip of the shoulder. There are some sex differences in the morphology of the clavicle. In women, the clavicle tends to be shorter, thinner, and less curved. In men, the clavicle is heavier and longer, and has a greater curvature and rougher surfaces where muscles attach, features that are more pronounced in manual workers.

The clavicle is the most commonly fractured bone in the body. Such breaks often occur because of the force exerted on the clavicle when a person falls onto his or her outstretched arms, or when the lateral shoulder receives a strong blow. Because the sternoclavicular joint is strong and rarely dislocated, excessive force results in the breaking of the clavicle, usually between the middle and lateral portions of the bone. If the fracture is complete, the shoulder and lateral clavicle fragment will drop due to the weight of the upper limb, causing the person to support the sagging limb with their other hand. Muscles acting across the shoulder will also pull the shoulder and lateral clavicle anteriorly and medially, causing the clavicle fragments to override. The clavicle overlies many important blood vessels and nerves for the upper limb, but fortunately, due to the anterior displacement of a broken clavicle, these structures are rarely affected when the clavicle is fractured.

Scapula

The scapula is also part of the pectoral girdle and thus plays an important role in anchoring the upper limb to the body. The scapula is located on the posterior side of the shoulder. It is surrounded by muscles on both its anterior (deep) and posterior (superficial) sides, and thus does not articulate with the ribs of the thoracic cage.

The scapula has several important landmarks (Figure 3). The three margins or borders of the scapula, named for their positions within the body, are the superior border of the scapula, the medial border of the scapula, and the lateral border of the scapula. The suprascapular notch is located lateral to the midpoint of the superior border. The corners of the triangular scapula, at either end of the medial border, are the superior angle of the scapula, located between the medial and superior borders, and the inferior angle of the scapula, located between the medial and lateral borders. The inferior angle is the most inferior portion of the scapula, and is particularly important because it serves as the attachment point for several powerful muscles involved in shoulder and upper limb movements. The remaining corner of the scapula, between the superior and lateral borders, is the location of the glenoid cavity (glenoid fossa). This shallow depression articulates with the humerus bone of the arm to form the glenohumeral joint (shoulder joint). The small bony bumps located immediately above and below the glenoid cavity are the supraglenoid tubercle and the infraglenoid tubercle, respectively. These provide attachments for muscles of the arm.

[caption id="" align="aligncenter" width="450"] Figure 3. Scapula. The isolated scapula is shown here from its anterior (deep) side and its posterior (superficial) side.[/caption]

The scapula also has two prominent projections. Toward the lateral end of the superior border, between the suprascapular notch and glenoid cavity, is the hook-like coracoid process (coracoid = “shaped like a crow’s beak”). This process projects anteriorly and curves laterally. At the shoulder, the coracoid process is located inferior to the lateral end of the clavicle. It is anchored to the clavicle by a strong ligament, and serves as the attachment site for muscles of the anterior chest and arm. On the posterior aspect, the spine of the scapula is a long and prominent ridge that runs across its upper portion. Extending laterally from the spine is a flattened and expanded region called the acromion or acromial process. The acromion forms the bony tip of the superior shoulder region and articulates with the lateral end of the clavicle, forming the acromioclavicular joint (see Figure 2). Together, the clavicle, acromion, and spine of the scapula form a V-shaped bony line that provides for the attachment of neck and back muscles that act on the shoulder, as well as muscles that pass across the shoulder joint to act on the arm.

The scapula has three depressions, each of which is called a fossa (plural = fossae). Two of these are found on the posterior scapula, above and below the scapular spine. Superior to the spine is the narrow supraspinous fossa, and inferior to the spine is the broad infraspinous fossa. The anterior (deep) surface of the scapula forms the broad subscapular fossa. All of these fossae provide large surface areas for the attachment of muscles that cross the shoulder joint to act on the humerus.

The acromioclavicular joint transmits forces from the upper limb to the clavicle. The ligaments around this joint are relatively weak. A hard fall onto the elbow or outstretched hand can stretch or tear the acromioclavicular ligaments, resulting in a moderate injury to the joint. However, the primary support for the acromioclavicular joint comes from a very strong ligament called the coracoclavicular ligament (see Figure 2). This connective tissue band anchors the coracoid process of the scapula to the inferior surface of the acromial end of the clavicle and thus provides important indirect support for the acromioclavicular joint. Following a strong blow to the lateral shoulder, such as when a hockey player is driven into the boards, a complete dislocation of the acromioclavicular joint can result. In this case, the acromion is thrust under the acromial end of the clavicle, resulting in ruptures of both the acromioclavicular and coracoclavicular ligaments. The scapula then separates from the clavicle, with the weight of the upper limb pulling the shoulder downward. This dislocation injury of the acromioclavicular joint is known as a “shoulder separation” and is common in contact sports such as hockey, football, or martial arts.

8.2 Bones of the Upper Limb

barkerj1 — Wed, 30 Aug 2017 18:37:47 +0000

Learning Objectives

By the end of this section, you will be able to:

Specify the components of the upper limb

The upper limb is divided into three regions. These consist of the arm, located between the shoulder and elbow joints; the forearm, which is between the elbow and wrist joints; and the hand, which is located distal to the wrist. There are 30 bones in each upper limb (see Chapter 8.1 Figure 1). The humerus is the single bone of the upper arm, and the ulna (medially) and the radius (laterally) are the paired bones of the forearm. The base of the hand contains eight bones, each called a carpal bone, and the palm of the hand is formed by five bones, each called a metacarpal bone. The fingers and thumb contain a total of 14 bones, each of which is a phalanx bone of the hand.

Humerus

The humerus is the single bone of the upper arm region (Figure 1). At its proximal end is the head of the humerus. This is the large, round, smooth region that faces medially. The head articulates with the glenoid cavity of the scapula to form the glenohumeral (shoulder) joint. The margin of the smooth area of the head is the anatomical neck of the humerus. Located on the lateral side of the proximal humerus is an expanded bony area called the greater tubercle. The smaller lesser tubercle of the humerus is found on the anterior aspect of the humerus. Both the greater and lesser tubercles serve as attachment sites for muscles that act across the shoulder joint. Passing between the greater and lesser tubercles is the narrow intertubercular groove (sulcus), which is also known as the bicipital groove because it provides passage for a tendon of the biceps brachii muscle. The surgical neck is located at the base of the expanded, proximal end of the humerus, where it joins the narrow shaft of the humerus. The surgical neck is a common site of arm fractures. The deltoid tuberosity is a roughened, V-shaped region located on the lateral side in the middle of the humerus shaft. As its name indicates, it is the site of attachment for the deltoid muscle.

[caption id="" align="aligncenter" width="350"] Figure 1. Humerus and Elbow Joint. The humerus is the single bone of the upper arm region. It articulates with the radius and ulna bones of the forearm to form the elbow joint.[/caption]

Distally, the humerus becomes flattened. The prominent bony projection on the medial side is the medial epicondyle of the humerus. The much smaller lateral epicondyle of the humerus is found on the lateral side of the distal humerus. The roughened ridge of bone above the lateral epicondyle is the lateral supracondylar ridge. All of these areas are attachment points for muscles that act on the forearm, wrist, and hand. The powerful grasping muscles of the anterior forearm arise from the medial epicondyle, which is thus larger and more robust than the lateral epicondyle that gives rise to the weaker posterior forearm muscles.

The distal end of the humerus has two articulation areas, which join the ulna and radius bones of the forearm to form the elbow joint. The more medial of these areas is the trochlea, a spindle- or pulley-shaped region (trochlea = “pulley”), which articulates with the ulna bone. Immediately lateral to the trochlea is the capitulum (“small head”), a knob-like structure located on the anterior surface of the distal humerus. The capitulum articulates with the radius bone of the forearm. Just above these bony areas are two small depressions. These spaces accommodate the forearm bones when the elbow is fully bent (flexed). Superior to the trochlea is the coronoid fossa, which receives the coronoid process of the ulna, and above the capitulum is the radial fossa, which receives the head of the radius when the elbow is flexed. Similarly, the posterior humerus has the olecranon fossa, a larger depression that receives the olecranon process of the ulna when the forearm is fully extended.

Ulna

The ulna is the medial bone of the forearm. It runs parallel to the radius, which is the lateral bone of the forearm (Figure 2). The proximal end of the ulna resembles a crescent wrench with its large, C-shaped trochlear notch. This region articulates with the trochlea of the humerus as part of the elbow joint. The inferior margin of the trochlear notch is formed by a prominent lip of bone called the coronoid process of the ulna. Just below this on the anterior ulna is a roughened area called the ulnar tuberosity. To the lateral side and slightly inferior to the trochlear notch is a small, smooth area called the radial notch of the ulna. This area is the site of articulation between the proximal radius and the ulna, forming the proximal radioulnar joint. The posterior and superior portions of the proximal ulna make up the olecranon process, which forms the bony tip of the elbow.

[caption id="" align="aligncenter" width="350"] Figure 2. Ulna and Radius. The ulna is located on the medial side of the forearm, and the radius is on the lateral side. These bones are attached to each other by an interosseous membrane.[/caption]

More distal is the shaft of the ulna. The lateral side of the shaft forms a ridge called the interosseous border of the ulna. This is the line of attachment for the interosseous membrane of the forearm, a sheet of dense connective tissue that unites the ulna and radius bones. The small, rounded area that forms the distal end is the head of the ulna. Projecting from the posterior side of the ulnar head is the styloid process of the ulna, a short bony projection. This serves as an attachment point for a connective tissue structure that unites the distal ends of the ulna and radius.

In the anatomical position, with the elbow fully extended and the palms facing forward, the arm and forearm do not form a straight line. Instead, the forearm deviates laterally by 5–15 degrees from the line of the arm. This deviation is called the carrying angle. It allows the forearm and hand to swing freely or to carry an object without hitting the hip. The carrying angle is larger in females to accommodate their wider pelvis.

Radius

The radius runs parallel to the ulna, on the lateral (thumb) side of the forearm (see Figure 2). The head of the radius is a disc-shaped structure that forms the proximal end. The small depression on the surface of the head articulates with the capitulum of the humerus as part of the elbow joint, whereas the smooth, outer margin of the head articulates with the radial notch of the ulna at the proximal radioulnar joint. The neck of the radius is the narrowed region immediately below the expanded head. Inferior to this point on the medial side is the radial tuberosity, an oval-shaped, bony protuberance that serves as a muscle attachment point. The shaft of the radius is slightly curved and has a small ridge along its medial side. This ridge forms the interosseous border of the radius, which, like the similar border of the ulna, is the line of attachment for the interosseous membrane that unites the two forearm bones. The distal end of the radius has a smooth surface for articulation with two carpal bones to form the radiocarpal joint or wrist joint (Figure 3 and Figure 4). On the medial side of the distal radius is the ulnar notch of the radius. This shallow depression articulates with the head of the ulna, which together form the distal radioulnar joint. The lateral end of the radius has a pointed projection called the styloid process of the radius. This provides attachment for ligaments that support the lateral side of the wrist joint. Compared to the styloid process of the ulna, the styloid process of the radius projects more distally, thereby limiting the range of movement for lateral deviations of the hand at the wrist joint.

Carpal Bones

The wrist and base of the hand are formed by a series of eight small carpal bones (see Figure 3). The carpal bones are arranged in two rows, forming a proximal row of four carpal bones and a distal row of four carpal bones. The bones in the proximal row, running from the lateral (thumb) side to the medial side, are the scaphoid (“boat-shaped”), lunate (“moon-shaped”), triquetrum (“three-cornered”), and pisiform (“pea-shaped”) bones. The small, rounded pisiform bone articulates with the anterior surface of the triquetrum bone. The pisiform thus projects anteriorly, where it forms the bony bump that can be felt at the medial base of your hand. The distal bones (lateral to medial) are the trapezium (“table”), trapezoid (“resembles a table”), capitate (“head-shaped”), and hamate (“hooked bone”) bones. The hamate bone is characterized by a prominent bony extension on its anterior side called the hook of the hamate bone.

A helpful mnemonic for remembering the arrangement of the carpal bones is “So Long To Pinky, Here Comes The Thumb.” This mnemonic starts on the lateral side and names the proximal bones from lateral to medial (scaphoid, lunate, triquetrum, pisiform), then makes a U-turn to name the distal bones from medial to lateral (hamate, capitate, trapezoid, trapezium). Thus, it starts and finishes on the lateral side.

[caption id="" align="aligncenter" width="480"] Figure 3. Bones of the Wrist and Hand. The eight carpal bones form the base of the hand. These are arranged into proximal and distal rows of four bones each. The metacarpal bones form the palm of the hand. The thumb and fingers consist of the phalanx bones.[/caption]

The carpal bones form the base of the hand. This can be seen in the radiograph (X-ray image) of the hand that shows the relationships of the hand bones to the skin creases of the hand (see Figure 4). Within the carpal bones, the four proximal bones are united to each other by ligaments to form a unit. Only three of these bones, the scaphoid, lunate, and triquetrum, contribute to the radiocarpal joint. The scaphoid and lunate bones articulate directly with the distal end of the radius, whereas the triquetrum bone articulates with a fibrocartilaginous pad that spans the radius and styloid process of the ulna. The distal end of the ulna thus does not directly articulate with any of the carpal bones.

The four distal carpal bones are also held together as a group by ligaments. The proximal and distal rows of carpal bones articulate with each other to form the midcarpal joint (see Figure 4). Together, the radiocarpal and midcarpal joints are responsible for all movements of the hand at the wrist. The distal carpal bones also articulate with the metacarpal bones of the hand.

[caption id="" align="aligncenter" width="480"] Figure 4. Bones of the Hand. This radiograph shows the position of the bones within the hand. Note the carpal bones that form the base of the hand. (credit: modification of work by Trace Meek)[/caption]

In the articulated hand, the carpal bones form a U-shaped grouping. A strong ligament called the flexor retinaculum spans the top of this U-shaped area to maintain this grouping of the carpal bones. The flexor retinaculum is attached laterally to the trapezium and scaphoid bones, and medially to the hamate and pisiform bones. Together, the carpal bones and the flexor retinaculum form a passageway called the carpal tunnel, with the carpal bones forming the walls and floor, and the flexor retinaculum forming the roof of this space (Figure 5). The tendons of nine muscles of the anterior forearm and an important nerve pass through this narrow tunnel to enter the hand. Overuse of the muscle tendons or wrist injury can produce inflammation and swelling within this space. This produces compression of the nerve, resulting in carpal tunnel syndrome, which is characterized by pain or numbness, and muscle weakness in those areas of the hand supplied by this nerve.

[caption id="" align="aligncenter" width="350"] Figure 5. Carpal Tunnel. The carpal tunnel is the passageway by which nine muscle tendons and a major nerve enter the hand from the anterior forearm. The walls and floor of the carpal tunnel are formed by the U-shaped grouping of the carpal bones, and the roof is formed by the flexor retinaculum, a strong ligament that anteriorly unites the bones.[/caption]

Metacarpal Bones

The palm of the hand contains five elongated metacarpal bones. These bones lie between the carpal bones of the wrist and the bones of the fingers and thumb (see Figure 3). The proximal end of each metacarpal bone articulates with one of the distal carpal bones. Each of these articulations is a carpometacarpal joint (see Figure 4). The expanded distal end of each metacarpal bone articulates at the metacarpophalangeal joint with the proximal phalanx bone of the thumb or one of the fingers. The distal end also forms the knuckles of the hand, at the base of the fingers. The metacarpal bones are numbered 1–5, beginning at the thumb.

The first metacarpal bone, at the base of the thumb, is separated from the other metacarpal bones. This allows it a freedom of motion that is independent of the other metacarpal bones, which is very important for thumb mobility. The remaining metacarpal bones are united together to form the palm of the hand. The second and third metacarpal bones are firmly anchored in place and are immobile. However, the fourth and fifth metacarpal bones have limited anterior-posterior mobility, a motion that is greater for the fifth bone. This mobility is important during power gripping with the hand (Figure 6). The anterior movement of these bones, particularly the fifth metacarpal bone, increases the strength of contact for the medial hand during gripping actions.

[caption id="" align="aligncenter" width="480"] Figure 6. Hand During Gripping. During tight gripping—compare (b) to (a)—the fourth and, particularly, the fifth metatarsal bones are pulled anteriorly. This increases the contact between the object and the medial side of the hand, thus improving the firmness of the grip.[/caption]

Phalanx Bones

The fingers and thumb contain 14 bones, each of which is called a phalanx bone (plural = phalanges), named after the ancient Greek phalanx (a rectangular block of soldiers). The thumb (pollex) is digit number 1 and has two phalanges, a proximal phalanx, and a distal phalanx bone (see Figure 3). Digits 2 (index finger) through 5 (little finger) have three phalanges each, called the proximal, middle, and distal phalanx bones. An interphalangeal joint is one of the articulations between adjacent phalanges of the digits (see Figure 4).

8.3 The Pelvic Girdle and Pelvis

barkerj1 — Wed, 30 Aug 2017 18:37:48 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the components and functions of the pelvic girdle
Describe the differences between the skeleton of a female and that of a male

The pelvic girdle (hip girdle) is formed by a single bone, the hip bone or coxal bone (coxal = “hip”), which serves as the attachment point for each lower limb. Each hip bone, in turn, is firmly joined to the axial skeleton via its attachment to the sacrum of the vertebral column. The right and left hip bones also converge anteriorly to attach to each other. The bony pelvis is the entire structure formed by the two hip bones, the sacrum, and, attached inferiorly to the sacrum, the coccyx (Figure 1).

Unlike the bones of the pectoral girdle, which are highly mobile to enhance the range of upper limb movements, the bones of the pelvis are strongly united to each other to form a largely immobile, weight-bearing structure. This is important for stability because it enables the weight of the body to be easily transferred laterally from the vertebral column, through the pelvic girdle and hip joints, and into either lower limb whenever the other limb is not bearing weight. Thus, the immobility of the pelvis provides a strong foundation for the upper body as it rests on top of the mobile lower limbs.

[caption id="" align="aligncenter" width="480"] Figure 1. Pelvis. The pelvic girdle is formed by a single hip bone. The hip bone attaches the lower limb to the axial skeleton through its articulation with the sacrum. The right and left hip bones, plus the sacrum and the coccyx, together form the pelvis.[/caption]

Hip Bone

The hip bone, or coxal bone, forms the pelvic girdle portion of the pelvis. The paired hip bones are the large, curved bones that form the lateral and anterior aspects of the pelvis. Each adult hip bone is formed by three separate bones that fuse together during the late teenage years. These bony components are the ilium, ischium, and pubis (Figure 2). These names are retained and used to define the three regions of the adult hip bone.

[caption id="" align="aligncenter" width="480"] Figure 2. The Hip Bone. The adult hip bone consists of three regions. The ilium forms the large, fan-shaped superior portion, the ischium forms the posteroinferior portion, and the pubis forms the anteromedial portion.[/caption]

The ilium is the fan-like, superior region that forms the largest part of the hip bone. It is firmly united to the sacrum at the largely immobile sacroiliac joint (see Figure 1). The ischium forms the posteroinferior region of each hip bone. It supports the body when sitting. The pubis forms the anterior portion of the hip bone. The pubis curves medially, where it joins to the pubis of the opposite hip bone at a specialized joint called the pubic symphysis.

Ilium

When you place your hands on your waist, you can feel the arching, superior margin of the ilium along your waistline (see Figure 2). This curved, superior margin of the ilium is the iliac crest. The rounded, anterior termination of the iliac crest is the anterior superior iliac spine. This important bony landmark can be felt at your anterolateral hip. Inferior to the anterior superior iliac spine is a rounded protuberance called the anterior inferior iliac spine. Both of these iliac spines serve as attachment points for muscles of the thigh. Posteriorly, the iliac crest curves downward to terminate as the posterior superior iliac spine. Muscles and ligaments surround but do not cover this bony landmark, thus sometimes producing a depression seen as a “dimple” located on the lower back. More inferiorly is the posterior inferior iliac spine. This is located at the inferior end of a large, roughened area called the auricular surface of the ilium. The auricular surface articulates with the auricular surface of the sacrum to form the sacroiliac joint. Both the posterior superior and posterior inferior iliac spines serve as attachment points for the muscles and very strong ligaments that support the sacroiliac joint.

The shallow depression located on the anteromedial (internal) surface of the upper ilium is called the iliac fossa. The inferior margin of this space is formed by the arcuate line of the ilium, the ridge formed by the pronounced change in curvature between the upper and lower portions of the ilium. The large, inverted U-shaped indentation located on the posterior margin of the lower ilium is called the greater sciatic notch.

Ischium

The ischium forms the posterolateral portion of the hip bone (see Figure 2). The large, roughened area of the inferior ischium is the ischial tuberosity. This serves as the attachment for the posterior thigh muscles and also carries the weight of the body when sitting. You can feel the ischial tuberosity if you wiggle your pelvis against the seat of a chair. Projecting superiorly and anteriorly from the ischial tuberosity is a narrow segment of bone called the ischial ramus. The slightly curved posterior margin of the ischium above the ischial tuberosity is the lesser sciatic notch. The bony projection separating the lesser sciatic notch and greater sciatic notch is the ischial spine.

Pubis

The pubis forms the anterior portion of the hip bone (see Figure 2). The enlarged medial portion of the pubis is the pubic body. Located superiorly on the pubic body is a small bump called the pubic tubercle. The superior pubic ramus is the segment of bone that passes laterally from the pubic body to join the ilium. The narrow ridge running along the superior margin of the superior pubic ramus is the pectineal line of the pubis.

The pubic body is joined to the pubic body of the opposite hip bone by the pubic symphysis. Extending downward and laterally from the body is the inferior pubic ramus. The pubic arch is the bony structure formed by the pubic symphysis, and the bodies and inferior pubic rami of the adjacent pubic bones. The inferior pubic ramus extends downward to join the ischial ramus. Together, these form the single ischiopubic ramus, which extends from the pubic body to the ischial tuberosity. The inverted V-shape formed as the ischiopubic rami from both sides come together at the pubic symphysis is called the subpubic angle.

Pelvis

The pelvis consists of four bones: the right and left hip bones, the sacrum, and the coccyx (see Figure 1). The pelvis has several important functions. Its primary role is to support the weight of the upper body when sitting and to transfer this weight to the lower limbs when standing. It serves as an attachment point for trunk and lower limb muscles, and also protects the internal pelvic organs. When standing in the anatomical position, the pelvis is tilted anteriorly. In this position, the anterior superior iliac spines and the pubic tubercles lie in the same vertical plane, and the anterior (internal) surface of the sacrum faces forward and downward.

The three areas of each hip bone, the ilium, pubis, and ischium, converge centrally to form a deep, cup-shaped cavity called the acetabulum. This is located on the lateral side of the hip bone and is part of the hip joint. The large opening in the anteroinferior hip bone between the ischium and pubis is the obturator foramen. This space is largely filled in by a layer of connective tissue and serves for the attachment of muscles on both its internal and external surfaces.

The space enclosed by the bony pelvis is divided into two regions (Figure 4). The broad, superior region, defined laterally by the large, fan-like portion of the upper hip bone, is called the greater pelvis (greater pelvic cavity; false pelvis). This broad area is occupied by portions of the small and large intestines, and because it is more closely associated with the abdominal cavity, it is sometimes referred to as the false pelvis. More inferiorly, the narrow, rounded space of the lesser pelvis (lesser pelvic cavity; true pelvis) contains the bladder and other pelvic organs, and thus is also known as the true pelvis. The pelvic brim (also known as the pelvic inlet) forms the superior margin of the lesser pelvis, separating it from the greater pelvis. The pelvic brim is defined by a line formed by the upper margin of the pubic symphysis anteriorly, and the pectineal line of the pubis, the arcuate line of the ilium, and the sacral promontory (the anterior margin of the superior sacrum) posteriorly. The inferior limit of the lesser pelvic cavity is called the pelvic outlet. This large opening is defined by the inferior margin of the pubic symphysis anteriorly, and the ischiopubic ramus, the ischial tuberosity, the sacrotuberous ligament, and the inferior tip of the coccyx posteriorly. Because of the anterior tilt of the pelvis, the lesser pelvis is also angled, giving it an anterosuperior (pelvic inlet) to posteroinferior (pelvic outlet) orientation.

[caption id="" align="aligncenter" width="480"] Figure 4. Male and Female Pelvis. The female pelvis is adapted for childbirth and is broader, with a larger subpubic angle, a rounder pelvic brim, and a wider and more shallow lesser pelvic cavity than the male pelvis.[/caption]

Comparison of the Female and Male Pelvis

The differences between the adult female and male pelvis relate to function and body size. In general, the bones of the male pelvis are thicker and heavier, adapted for support of the male’s heavier physical build and stronger muscles; this average size difference is generally true of other bones of the skeleton as well. The pelvis does show more robust differences between males and females due to its functional relationship to bipedal movement (requiring a relatively narrow pelvis) and birth of infants with large brains (requiring a relatively broad pelvis). Because the female pelvis is adapted for childbirth, it is wider than the male pelvis, as evidenced by the distance between the anterior superior iliac spines (see Figure 4). The ischial tuberosities of females are also farther apart, which increases the size of the pelvic outlet. Because of this increased pelvic width, the subpubic angle is larger in females (greater than 80 degrees) than it is in males (less than 70 degrees). The female sacrum is wider, shorter, and less curved, and the sacral promontory projects less into the pelvic cavity, thus giving the female pelvic inlet (pelvic brim) a more rounded or oval shape compared to males. The lesser pelvic cavity of females is also wider and more shallow than the narrower, deeper, and tapering lesser pelvis of males. The greater sciatic notch of the male hip bone is narrower and deeper than the broader notch of females. Because of the obvious differences between female and male hip bones, this is the one bone of the body that allows for the most accurate sex determination. Table 1 provides an overview of the general differences between the female and male pelvis.

Overview of Differences between the Female and Male Pelvis (Table 1)
	Female pelvis	Male pelvis
Pelvic weight	Bones of the pelvis are lighter and thinner	Bones of the pelvis are thicker and heavier
Pelvic inlet shape	Pelvic inlet has a round or oval shape	Pelvic inlet is heart-shaped
Lesser pelvic cavity shape	Lesser pelvic cavity is shorter and wider	Lesser pelvic cavity is longer and narrower
Subpubic angle	Subpubic angle is greater than 80 degrees	Subpubic angle is less than 70 degrees
Pelvic outlet shape	Pelvic outlet is rounded and larger	Pelvic outlet is smaller

8.4 Bones of the Lower Limb

barkerj1 — Wed, 30 Aug 2017 18:37:50 +0000

Learning Objectives

By the end of this section, you will be able to:

Specify the components of the lower limb

Like the upper limb, the lower limb is divided into three regions. The thigh is that portion of the lower limb located between the hip joint and knee joint. The leg is specifically the region between the knee joint and the ankle joint. Distal to the ankle is the foot. The lower limb contains 30 bones. These are the femur, patella, tibia, fibula, tarsal bones, metatarsal bones, and phalanges (see Chapter 8.1 Figure 1). The femur is the single bone of the thigh. The patella is the kneecap and articulates with the distal femur. The tibia is the larger, weight-bearing bone located on the medial side of the leg, and the fibula is the thin bone of the lateral leg. The bones of the foot are divided into three groups. The posterior portion of the foot is formed by a group of seven bones, each of which is known as a tarsal bone, whereas the mid-foot contains five elongated bones, each of which is a metatarsal bone. The toes contain 14 small bones, each of which is a phalanx bone of the foot.

Femur

The femur, or thigh bone, is the single bone of the thigh region (Figure 1). It is the longest and strongest bone of the body, and accounts for approximately one-quarter of a person’s total height. The rounded, proximal end is the head of the femur, which articulates with the acetabulum of the hip bone to form the hip joint. The fovea capitis is a minor indentation on the medial side of the femoral head that serves as the site of attachment for the ligament of the head of the femur. This ligament spans the femur and acetabulum, but is weak and provides little support for the hip joint. It does, however, carry an important artery that supplies the head of the femur.

[caption id="" align="aligncenter" width="380"] Figure 1. Femur and Patella. The femur is the single bone of the thigh region. It articulates superiorly with the hip bone at the hip joint, and inferiorly with the tibia at the knee joint. The patella only articulates with the distal end of the femur.[/caption]

The narrowed region below the head is the neck of the femur. This is a common area for fractures of the femur. The greater trochanter is the large, upward, bony projection located above the base of the neck. Multiple muscles that act across the hip joint attach to the greater trochanter, which, because of its projection from the femur, gives additional leverage to these muscles. The greater trochanter can be felt just under the skin on the lateral side of your upper thigh. The lesser trochanter is a small, bony prominence that lies on the medial aspect of the femur, just below the neck. A single, powerful muscle attaches to the lesser trochanter. Running between the greater and lesser trochanters on the anterior side of the femur is the roughened intertrochanteric line. The trochanters are also connected on the posterior side of the femur by the larger intertrochanteric crest.

The elongated shaft of the femur has a slight anterior bowing or curvature. At its proximal end, the posterior shaft has the gluteal tuberosity, a roughened area extending inferiorly from the greater trochanter. More inferiorly, the gluteal tuberosity becomes continuous with the linea aspera (“rough line”). This is the roughened ridge that passes distally along the posterior side of the mid-femur. Multiple muscles of the hip and thigh regions make long, thin attachments to the femur along the linea aspera.

The distal end of the femur has medial and lateral bony expansions. On the lateral side, the smooth portion that covers the distal and posterior aspects of the lateral expansion is the lateral condyle of the femur. The roughened area on the outer, lateral side of the condyle is the lateral epicondyle of the femur. Similarly, the smooth region of the distal and posterior medial femur is the medial condyle of the femur, and the irregular outer, medial side of this is the medial epicondyle of the femur. The lateral and medial condyles articulate with the tibia to form the knee joint. The epicondyles provide attachment for muscles and supporting ligaments of the knee. The adductor tubercle is a small bump located at the superior margin of the medial epicondyle. Posteriorly, the medial and lateral condyles are separated by a deep depression called the intercondylar fossa. Anteriorly, the smooth surfaces of the condyles join together to form a wide groove called the patellar surface, which provides for articulation with the patella bone. The combination of the medial and lateral condyles with the patellar surface gives the distal end of the femur a horseshoe (U) shape.

Patella

The patella (kneecap) is largest sesamoid bone of the body (see Figure 1). A sesamoid bone is a bone that is incorporated into the tendon of a muscle where that tendon crosses a joint. The sesamoid bone articulates with the underlying bones to prevent damage to the muscle tendon due to rubbing against the bones during movements of the joint. The patella is found in the tendon of the quadriceps femoris muscle, the large muscle of the anterior thigh that passes across the anterior knee to attach to the tibia. The patella articulates with the patellar surface of the femur and thus prevents rubbing of the muscle tendon against the distal femur. The patella also lifts the tendon away from the knee joint, which increases the leverage power of the quadriceps femoris muscle as it acts across the knee. The patella does not articulate with the tibia.

[caption id="" align="aligncenter" width="225"] Figure 2. The Q-Angle. The Q-angle is a measure of the amount of lateral deviation of the femur from the vertical line of the tibia. Adult females have a larger Q-angle due to their wider pelvis than adult males.[/caption]

Tibia

The tibia (shin bone) is the medial bone of the leg and is larger than the fibula, with which it is paired (Figure 3). The tibia is the main weight-bearing bone of the lower leg and the second longest bone of the body, after the femur. The medial side of the tibia is located immediately under the skin, allowing it to be easily palpated down the entire length of the medial leg.

[caption id="" align="aligncenter" width="400"] Figure 3. Tibia and Fibula. The tibia is the larger, weight-bearing bone located on the medial side of the leg. The fibula is the slender bone of the lateral side of the leg and does not bear weight.[/caption]

The proximal end of the tibia is greatly expanded. The two sides of this expansion form the medial condyle of the tibia and the lateral condyle of the tibia. The tibia does not have epicondyles. The top surface of each condyle is smooth and flattened. These areas articulate with the medial and lateral condyles of the femur to form the knee joint. Between the articulating surfaces of the tibial condyles is the intercondylar eminence, an irregular, elevated area that serves as the inferior attachment point for two supporting ligaments of the knee.

The tibial tuberosity is an elevated area on the anterior side of the tibia, near its proximal end. It is the final site of attachment for the muscle tendon associated with the patella. More inferiorly, the shaft of the tibia becomes triangular in shape. The anterior apex of this triangle forms the anterior border of the tibia, which begins at the tibial tuberosity and runs inferiorly along the length of the tibia. Both the anterior border and the medial side of the triangular shaft are located immediately under the skin and can be easily palpated along the entire length of the tibia. A small ridge running down the lateral side of the tibial shaft is the interosseous border of the tibia. This is for the attachment of the interosseous membrane of the leg, the sheet of dense connective tissue that unites the tibia and fibula bones. Located on the posterior side of the tibia is the soleal line, a diagonally running, roughened ridge that begins below the base of the lateral condyle, and runs down and medially across the proximal third of the posterior tibia. Muscles of the posterior leg attach to this line.

The large expansion found on the medial side of the distal tibia is the medial malleolus (“little hammer”). This forms the large bony bump found on the medial side of the ankle region. Both the smooth surface on the inside of the medial malleolus and the smooth area at the distal end of the tibia articulate with the talus bone of the foot as part of the ankle joint. On the lateral side of the distal tibia is a wide groove called the fibular notch. This area articulates with the distal end of the fibula, forming the distal tibiofibular joint.

Fibula

The fibula is the slender bone located on the lateral side of the leg (see Figure 3). The fibula does not bear weight. It serves primarily for muscle attachments and thus is largely surrounded by muscles. Only the proximal and distal ends of the fibula can be palpated.

The head of the fibula is the small, knob-like, proximal end of the fibula. It articulates with the inferior aspect of the lateral tibial condyle, forming the proximal tibiofibular joint. The thin shaft of the fibula has the interosseous border of the fibula, a narrow ridge running down its medial side for the attachment of the interosseous membrane that spans the fibula and tibia. The distal end of the fibula forms the lateral malleolus, which forms the easily palpated bony bump on the lateral side of the ankle. The deep (medial) side of the lateral malleolus articulates with the talus bone of the foot as part of the ankle joint. The distal fibula also articulates with the fibular notch of the tibia.

Tarsal Bones

The posterior half of the foot is formed by seven tarsal bones (Figure 4). The most superior bone is the talus. This has a relatively square-shaped, upper surface that articulates with the tibia and fibula to form the ankle joint. Three areas of articulation form the ankle joint: The superomedial surface of the talus bone articulates with the medial malleolus of the tibia, the top of the talus articulates with the distal end of the tibia, and the lateral side of the talus articulates with the lateral malleolus of the fibula. Inferiorly, the talus articulates with the calcaneus (heel bone), the largest bone of the foot, which forms the heel. Body weight is transferred from the tibia to the talus to the calcaneus, which rests on the ground. The medial calcaneus has a prominent bony extension called the sustentaculum tali (“support for the talus”) that supports the medial side of the talus bone.

[caption id="" align="aligncenter" width="600"] Figure 4. Bones of the Foot. The bones of the foot are divided into three groups. The posterior foot is formed by the seven tarsal bones. The mid-foot has the five metatarsal bones. The toes contain the phalanges.[/caption]

[caption id="" align="alignright" width="120"] Use this tutorial to review the bones of the foot.[/caption] The cuboid bone articulates with the anterior end of the calcaneus bone. The cuboid has a deep groove running across its inferior surface, which provides passage for a muscle tendon. The talus bone articulates anteriorly with the navicular bone, which in turn articulates anteriorly with the three cuneiform (“wedge-shaped”) bones. These bones are the medial cuneiform, the intermediate cuneiform, and the lateral cuneiform. Each of these bones has a broad superior surface and a narrow inferior surface, which together produce the transverse (medial-lateral) curvature of the foot. The navicular and lateral cuneiform bones also articulate with the medial side of the cuboid bone.

Metatarsal Bones

The anterior half of the foot is formed by the five metatarsal bones, which are located between the tarsal bones of the posterior foot and the phalanges of the toes (see Figure 4). These elongated bones are numbered 1–5, starting with the medial side of the foot. The first metatarsal bone is shorter and thicker than the others. The second metatarsal is the longest. The base of the metatarsal bone is the proximal end of each metatarsal bone. These articulate with the cuboid or cuneiform bones. The base of the fifth metatarsal has a large, lateral expansion that provides for muscle attachments. This expanded base of the fifth metatarsal can be felt as a bony bump at the midpoint along the lateral border of the foot. The expanded distal end of each metatarsal is the head of the metatarsal bone. Each metatarsal bone articulates with the proximal phalanx of a toe to form a metatarsophalangeal joint. The heads of the metatarsal bones also rest on the ground and form the ball (anterior end) of the foot.

Phalanges

The toes contain a total of 14 phalanx bones (phalanges), arranged in a similar manner as the phalanges of the fingers (see Figure 4). The toes are numbered 1–5, starting with the big toe (hallux). The big toe has two phalanx bones, the proximal and distal phalanges. The remaining toes all have proximal, middle, and distal phalanges. A joint between adjacent phalanx bones is called an interphalangeal joint.

8.5 Development of the Appendicular Skeleton

barkerj1 — Wed, 30 Aug 2017 18:37:51 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the major differences between the appendicular skeleton of a baby and that of an adult

Embryologically, the appendicular skeleton arises from mesenchyme, a type of embryonic tissue that can differentiate into many types of tissues, including bone or muscle tissue. Mesenchyme gives rise to the bones of the upper and lower limbs, as well as to the pectoral and pelvic girdles. Development of the limbs begins near the end of the fourth embryonic week, with the upper limbs appearing first. Thereafter, the development of the upper and lower limbs follows similar patterns, with the lower limbs lagging behind the upper limbs by a few days.

Limb Growth

Each upper and lower limb initially develops as a small bulge called a limb bud, which appears on the lateral side of the early embryo. The upper limb bud appears near the end of the fourth week of development, with the lower limb bud appearing shortly after (Figure 1).

[caption id="" align="aligncenter" width="280"] Figure 1. Embryo at Seven Weeks. Limb buds are visible in an embryo at the end of the seventh week of development (embryo derived from an ectopic pregnancy). (credit: Ed Uthman/flickr)[/caption] Initially, the limb buds consist of a core of mesenchyme covered by a layer of ectoderm. The ectoderm at the end of the limb bud thickens to form a narrow crest called the apical ectodermal ridge. This ridge stimulates the underlying mesenchyme to rapidly proliferate, producing the outgrowth of the developing limb. As the limb bud elongates, cells located farther from the apical ectodermal ridge slow their rates of cell division and begin to differentiate. In this way, the limb develops along a proximal-to-distal axis.

During the sixth week of development, the distal ends of the upper and lower limb buds expand and flatten into a paddle shape. This region will become the hand or foot. The wrist or ankle areas then appear as a constriction that develops at the base of the paddle. Shortly after this, a second constriction on the limb bud appears at the future site of the elbow or knee. Within the paddle, areas of tissue undergo cell death, producing separations between the growing fingers and toes. Also during the sixth week of development, mesenchyme within the limb buds begins to differentiate into hyaline cartilage that will form models of the future limb bones.

The early outgrowth of the upper and lower limb buds initially has the limbs positioned so that the regions that will become the palm of the hand or the bottom of the foot are facing medially toward the body, with the future thumb or big toe both oriented toward the head. During the seventh week of development, the upper limb rotates laterally by 90 degrees, so that the palm of the hand faces anteriorly and the thumb points laterally. In contrast, the lower limb undergoes a 90-degree medial rotation, thus bringing the big toe to the medial side of the foot.

Ossification of Appendicular Bones

All of the girdle and limb bones, except for the clavicle, develop by the process of endochondral ossification. This process begins as the mesenchyme within the limb bud differentiates into hyaline cartilage to form cartilage models for future bones. By the twelfth week, a primary ossification center will have appeared in the diaphysis (shaft) region of the long bones, initiating the process that converts the cartilage model into bone. A secondary ossification center will appear in each epiphysis (expanded end) of these bones at a later time, usually after birth. The primary and secondary ossification centers are separated by the epiphyseal plate, a layer of growing hyaline cartilage. This plate is located between the diaphysis and each epiphysis. It continues to grow and is responsible for the lengthening of the bone. The epiphyseal plate is retained for many years, until the bone reaches its final, adult size, at which time the epiphyseal plate disappears and the epiphysis fuses to the diaphysis. (Seek additional content on ossification in the chapter on bone tissue).

Small bones, such as the phalanges, will develop only one secondary ossification center and will thus have only a single epiphyseal plate. Large bones, such as the femur, will develop several secondary ossification centers, with an epiphyseal plate associated with each secondary center. Thus, ossification of the femur begins at the end of the seventh week with the appearance of the primary ossification center in the diaphysis, which rapidly expands to ossify the shaft of the bone prior to birth. Secondary ossification centers develop at later times. Ossification of the distal end of the femur, to form the condyles and epicondyles, begins shortly before birth. Secondary ossification centers also appear in the femoral head late in the first year after birth, in the greater trochanter during the fourth year, and in the lesser trochanter between the ages of 9 and 10 years. Once these areas have ossified, their fusion to the diaphysis and the disappearance of each epiphyseal plate follow a reversed sequence. Thus, the lesser trochanter is the first to fuse, doing so at the onset of puberty (around 11 years of age), followed by the greater trochanter approximately 1 year later. The femoral head fuses between the ages of 14–17 years, whereas the distal condyles of the femur are the last to fuse, between the ages of 16–19 years. Knowledge of the age at which different epiphyseal plates disappear is important when interpreting radiographs taken of children. Since the cartilage of an epiphyseal plate is less dense than bone, the plate will appear dark in a radiograph image. Thus, a normal epiphyseal plate may be mistaken for a bone fracture.

The clavicle is the one appendicular skeleton bone that does not develop via endochondral ossification. Instead, the clavicle develops through the process of intramembranous ossification. During this process, mesenchymal cells differentiate directly into bone-producing cells, which produce the clavicle directly, without first making a cartilage model. Because of this early production of bone, the clavicle is the first bone of the body to begin ossification, with ossification centers appearing during the fifth week of development. However, ossification of the clavicle is not complete until age 25.

Introduction

barkerj1 — Wed, 30 Aug 2017 18:37:51 +0000

[caption id="" align="aligncenter" width="600"] Figure 1. Girl Kayaking. Without joints, body movements would be impossible. (credit: Graham Richardson/flickr.com)[/caption] The adult human body has 206 bones, and with the exception of the hyoid bone in the neck, each bone is connected to at least one other bone. Joints are the location where bones come together. Many joints allow for movement between the bones. At these joints, the articulating surfaces of the adjacent bones can move smoothly against each other. However, the bones of other joints may be joined to each other by connective tissue or cartilage. These joints are designed for stability and provide for little or no movement. Importantly, joint stability and movement are related to each other. This means that stable joints allow for little or no mobility between the adjacent bones. Conversely, joints that provide the most movement between bones are the least stable. Understanding the relationship between joint structure and function will help to explain why particular types of joints are found in certain areas of the body. The articulating surfaces of bones at stable types of joints, with little or no mobility, are strongly united to each other. For example, most of the joints of the skull are held together by fibrous connective tissue and do not allow for movement between the adjacent bones. This lack of mobility is important, because the skull bones serve to protect the brain. Similarly, other joints united by fibrous connective tissue allow for very little movement, which provides stability and weight-bearing support for the body. For example, the tibia and fibula of the leg are tightly united to give stability to the body when standing. At other joints, the bones are held together by cartilage, which permits limited movements between the bones. Thus, the joints of the vertebral column only allow for small movements between adjacent vertebrae, but when added together, these movements provide the flexibility that allows your body to twist, or bend to the front, back, or side. In contrast, at joints that allow for wide ranges of motion, the articulating surfaces of the bones are not directly united to each other. Instead, these surfaces are enclosed within a space filled with lubricating fluid, which allows the bones to move smoothly against each other. These joints provide greater mobility, but since the bones are free to move in relation to each other, the joint is less stable. Most of the joints between the bones of the appendicular skeleton are this freely moveable type of joint. These joints allow the muscles of the body to pull on a bone and thereby produce movement of that body region. Your ability to kick a soccer ball, pick up a fork, and dance the tango depend on mobility at these types of joints.

9.1 Classification of Joints

barkerj1 — Wed, 30 Aug 2017 18:37:53 +0000

Learning Objectives

By the end of this section, you will be able to:

Explain what is meant by the terms synarthrotic, diarthrotic, and amphiarthrotic as descriptions of the functional classes of joints

A joint, also called an articulation, is any place where adjacent bones or bone and cartilage come together (articulate with each other) to form a connection. Joints are classified both structurally and functionally. Structural classifications of joints take into account whether the adjacent bones are strongly anchored to each other by fibrous connective tissue or cartilage, or whether the adjacent bones articulate with each other within a fluid-filled space called a joint cavity. Functional classifications describe the degree of movement available between the bones, ranging from immobile, to slightly mobile, to freely moveable joints. The amount of movement available at a particular joint of the body is related to the functional requirements for that joint. Thus immobile or slightly moveable joints serve to protect internal organs, give stability to the body, and allow for limited body movement. In contrast, freely moveable joints allow for much more extensive movements of the body and limbs.

Structural Classification of Joints

The structural classification of joints is based on whether the articulating surfaces of the adjacent bones are directly connected by fibrous connective tissue or cartilage, or whether the articulating surfaces contact each other within a fluid-filled joint cavity. These differences serve to divide the joints of the body into three structural classifications. A fibrous joint is where the adjacent bones are united by fibrous connective tissue. At a cartilaginous joint, the bones are joined by hyaline cartilage or fibrocartilage. At a synovial joint, the articulating surfaces of the bones are not directly connected, but instead come into contact with each other within a joint cavity that is filled with a lubricating fluid. Synovial joints allow for free movement between the bones and are the most common joints of the body.

Functional Classification of Joints

The functional classification of joints is determined by the amount of mobility found between the adjacent bones. Joints are thus functionally classified as a synarthrosis or immobile joint, an amphiarthrosis or slightly moveable joint, or as a diarthrosis, which is a freely moveable joint (arthroun = “to fasten by a joint”). Depending on their location, fibrous joints may be functionally classified as a synarthrosis (immobile joint) or an amphiarthrosis (slightly mobile joint). Cartilaginous joints are also functionally classified as either a synarthrosis or an amphiarthrosis joint. All synovial joints are functionally classified as a diarthrosis joint.

Synarthrosis

An immobile or nearly immobile joint is called a synarthrosis. The immobile nature of these joints provide for a strong union between the articulating bones. This is important at locations where the bones provide protection for internal organs. Examples include sutures, the fibrous joints between the bones of the skull that surround and protect the brain (Figure 1), and the manubriosternal joint, the cartilaginous joint that unites the manubrium and body of the sternum for protection of the heart.

[caption id="" align="aligncenter" width="340"] Figure 1. Suture Joints of Skull. The suture joints of the skull are an example of a synarthrosis, an immobile or essentially immobile joint.[/caption]

Amphiarthrosis

An amphiarthrosis is a joint that has limited mobility. An example of this type of joint is the cartilaginous joint that unites the bodies of adjacent vertebrae. Filling the gap between the vertebrae is a thick pad of fibrocartilage called an intervertebral disc (Figure 2). Each intervertebral disc strongly unites the vertebrae but still allows for a limited amount of movement between them. However, the small movements available between adjacent vertebrae can sum together along the length of the vertebral column to provide for large ranges of body movements.

Another example of an amphiarthrosis is the pubic symphysis of the pelvis. This is a cartilaginous joint in which the pubic regions of the right and left hip bones are strongly anchored to each other by fibrocartilage. This joint normally has very little mobility. The strength of the pubic symphysis is important in conferring weight-bearing stability to the pelvis.

[caption id="" align="aligncenter" width="330"] Figure 2. Intervertebral Disc. An intervertebral disc unites the bodies of adjacent vertebrae within the vertebral column. Each disc allows for limited movement between the vertebrae and thus functionally forms an amphiarthrosis type of joint. Intervertebral discs are made of fibrocartilage and thereby structurally form a symphysis type of cartilaginous joint.[/caption]

Diarthrosis

A freely mobile joint is classified as a diarthrosis. These types of joints include all synovial joints of the body, which provide the majority of body movements. Most diarthrotic joints are found in the appendicular skeleton and thus give the limbs a wide range of motion. These joints are divided into three categories, based on the number of axes of motion provided by each. An axis in anatomy is described as the movements in reference to the three anatomical planes: transverse, frontal, and sagittal. Thus, diarthroses are classified as uniaxial (for movement in one plane), biaxial (for movement in two planes), or multiaxial joints (for movement in all three anatomical planes).

A uniaxial joint only allows for a motion in a single plane (around a single axis). The elbow joint, which only allows for bending or straightening, is an example of a uniaxial joint. A biaxial joint allows for motions within two planes. An example of a biaxial joint is a metacarpophalangeal joint (knuckle joint) of the hand. The joint allows for movement along one axis to produce bending or straightening of the finger, and movement along a second axis, which allows for spreading of the fingers away from each other and bringing them together. A joint that allows for the several directions of movement is called a multiaxial joint (polyaxial or triaxial joint). This type of diarthrotic joint allows for movement along three axes (Figure 3). The shoulder and hip joints are multiaxial joints. They allow the upper or lower limb to move in an anterior-posterior direction and a medial-lateral direction. In addition, the limb can also be rotated around its long axis. This third movement results in rotation of the limb so that its anterior surface is moved either toward or away from the midline of the body.

[caption id="" align="aligncenter" width="450"] Figure 3. Multiaxial Joint. A multiaxial joint, such as the hip joint, allows for three types of movement: anterior-posterior, medial-lateral, and rotational.[/caption] [caption id="attachment_2967" align="aligncenter" width="150"] Watch this CrashCourse video to learn more about joints![/caption]

9.2 Fibrous Joints

barkerj1 — Wed, 30 Aug 2017 18:37:55 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the structure of a suture, a syndesmosis, and a gomphosis
Describe the movement allowed by a suture, a syndesmosis, and a gomphosis
Provide a specific example of a suture, a syndesmosis, and a gomphosis
Describe a ligament

At a fibrous joint, the adjacent bones are directly connected to each other by fibrous connective tissue, and thus the bones do not have a joint cavity between them (Figure 1). The gap between the bones may be narrow or wide. There are three types of fibrous joints. A suture is the narrow fibrous joint found between most bones of the skull. At a syndesmosis joint, the bones are more widely separated but are held together by a narrow band of fibrous connective tissue called a ligament or a wide sheet of connective tissue called an interosseous membrane. This type of fibrous joint is found between the shaft regions of the long bones in the forearm and in the leg. Lastly, a gomphosis is the narrow fibrous joint between the roots of a tooth and the bony socket in the jaw into which the tooth fits.

[caption id="" align="aligncenter" width="520"] Figure 1. Fibrous Joints. Fibrous joints form strong connections between bones. (a) Sutures join most bones of the skull. (b) An interosseous membrane forms a syndesmosis between the radius and ulna bones of the forearm. (c) A gomphosis is a specialized fibrous joint that anchors a tooth to its socket in the jaw.[/caption]

Suture

All the bones of the skull, except for the mandible, are joined to each other by a fibrous joint called a suture. The fibrous connective tissue found at a suture (“to bind or sew”) strongly unites the adjacent skull bones and thus helps to protect the brain and form the face. In adults, the skull bones are closely opposed and fibrous connective tissue fills the narrow gap between the bones. The suture is frequently convoluted, forming a tight union that prevents most movement between the bones. (See Figure 1a.) Thus, skull sutures are functionally classified as a synarthrosis, although some sutures may allow for slight movements between the cranial bones.

In newborns and infants, the areas of connective tissue between the bones are much wider, especially in those areas on the top and sides of the skull that will become the sagittal, coronal, squamous, and lambdoid sutures. These broad areas of connective tissue are called fontanelles (Figure 2). During birth, the fontanelles provide flexibility to the skull, allowing the bones to push closer together or to overlap slightly, thus aiding movement of the infant’s head through the birth canal. After birth, these expanded regions of connective tissue allow for rapid growth of the skull and enlargement of the brain. The fontanelles greatly decrease in width during the first year after birth as the skull bones enlarge. When the connective tissue between the adjacent bones is reduced to a narrow layer, these fibrous joints are now called sutures. At some sutures, the connective tissue will ossify and be converted into bone, causing the adjacent bones to fuse to each other. This fusion between bones is called a synostosis (“joined by bone”). Examples of synostosis fusions between cranial bones are found both early and late in life. At the time of birth, the frontal and maxillary bones consist of right and left halves joined together by sutures, which disappear by the eighth year as the halves fuse together to form a single bone. Late in life, the sagittal, coronal, and lambdoid sutures of the skull will begin to ossify and fuse, causing the suture line to gradually disappear.

[caption id="" align="aligncenter" width="380"] Figure 2. The Newborn Skull. The fontanelles of a newborn’s skull are broad areas of fibrous connective tissue that form fibrous joints between the bones of the skull.[/caption]

Syndesmosis

A syndesmosis (“fastened with a band”) is a type of fibrous joint in which two parallel bones are united to each other by fibrous connective tissue. The gap between the bones may be narrow, with the bones joined by ligaments, or the gap may be wide and filled in by a broad sheet of connective tissue called an interosseous membrane.

In the forearm, the wide gap between the shaft portions of the radius and ulna bones are strongly united by an interosseous membrane (see Figure 1b). Similarly, in the leg, the shafts of the tibia and fibula are also united by an interosseous membrane. In addition, at the distal tibiofibular joint, the articulating surfaces of the bones lack cartilage and the narrow gap between the bones is anchored by fibrous connective tissue and ligaments on both the anterior and posterior aspects of the joint. Together, the interosseous membrane and these ligaments form the tibiofibular syndesmosis.

The syndesmoses found in the forearm and leg serve to unite parallel bones and prevent their separation. However, a syndesmosis does not prevent all movement between the bones, and thus this type of fibrous joint is functionally classified as an amphiarthrosis. In the leg, the syndesmosis between the tibia and fibula strongly unites the bones, allows for little movement, and firmly locks the talus bone in place between the tibia and fibula at the ankle joint. This provides strength and stability to the leg and ankle, which are important during weight bearing. In the forearm, the interosseous membrane is flexible enough to allow for rotation of the radius bone during forearm movements. Thus in contrast to the stability provided by the tibiofibular syndesmosis, the flexibility of the antebrachial interosseous membrane allows for the much greater mobility of the forearm.

The interosseous membranes of the leg and forearm also provide areas for muscle attachment. Damage to a syndesmotic joint, which usually results from a fracture of the bone with an accompanying tear of the interosseous membrane, will produce pain, loss of stability of the bones, and may damage the muscles attached to the interosseous membrane. If the fracture site is not properly immobilized with a cast or splint, contractile activity by these muscles can cause improper alignment of the broken bones during healing.

Gomphosis

A gomphosis (“fastened with bolts”) is the specialized fibrous joint that anchors the root of a tooth into its bony socket within the maxillary bone (upper jaw) or mandible bone (lower jaw) of the skull. A gomphosis is also known as a peg-and-socket joint. Spanning between the bony walls of the socket and the root of the tooth are numerous short bands of dense connective tissue, each of which is called a periodontal ligament (see Figure 1c). Due to the immobility of a gomphosis, this type of joint is functionally classified as a synarthrosis.

Glossary

fontanelles: expanded areas of fibrous connective tissue that separate the braincase bones of the skull prior to birth and during the first year after birth

gomphosis: type of fibrous joint in which the root of a tooth is anchored into its bony jaw socket by strong periodontal ligaments

interosseous membrane: wide sheet of fibrous connective tissue that fills the gap between two parallel bones, forming a syndesmosis; found between the radius and ulna of the forearm and between the tibia and fibula of the leg

ligament: strong band of dense connective tissue spanning between bones

periodontal ligament: band of dense connective tissue that anchors the root of a tooth into the bony jaw socket

suture: fibrous joint that connects the bones of the skull (except the mandible); an immobile joint (synarthrosis)

syndesmosis: type of fibrous joint in which two separated, parallel bones are connected by an interosseous membrane

synostosis: site at which adjacent bones or bony components have fused together

9.3 Cartilaginous Joints

barkerj1 — Wed, 30 Aug 2017 18:37:56 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the structure of a synchondrosis and a symphysis
Describe the movement allowed by a synchondrosis and a symphysis
Provide a specific example of a synchondrosis and a symphysis

As the name indicates, at a cartilaginous joint, the adjacent bones are united by cartilage, a tough but flexible type of connective tissue. These types of joints lack a joint cavity and involve bones that are joined together by either hyaline cartilage or fibrocartilage (Figure 1). There are two types of cartilaginous joints. A synchondrosis is a cartilaginous joint where the bones are joined by hyaline cartilage. Also classified as a synchondrosis are places where bone is united to a cartilage structure, such as between the anterior end of a rib and the costal cartilage of the thoracic cage. The second type of cartilaginous joint is a symphysis, where the bones are joined by fibrocartilage.

[caption id="" align="aligncenter" width="520"] Figure 1. Cartiliginous Joints. At cartilaginous joints, bones are united by hyaline cartilage to form a synchondrosis or by fibrocartilage to form a symphysis. (a) The hyaline cartilage of the epiphyseal plate (growth plate) forms a synchondrosis that unites the shaft (diaphysis) and end (epiphysis) of a long bone and allows the bone to grow in length. (b) The pubic portions of the right and left hip bones of the pelvis are joined together by fibrocartilage, forming the pubic symphysis.[/caption]

Synchondrosis

A synchondrosis (“joined by cartilage”) is a cartilaginous joint where bones are joined together by hyaline cartilage, or where bone is united to hyaline cartilage. A synchondrosis may be temporary or permanent. A temporary synchondrosis is the epiphyseal plate (growth plate) of a growing long bone. The epiphyseal plate is the region of growing hyaline cartilage that unites the diaphysis (shaft) of the bone to the epiphysis (end of the bone). Bone lengthening involves growth of the epiphyseal plate cartilage and its replacement by bone, which adds to the diaphysis. For many years during childhood growth, the rates of cartilage growth and bone formation are equal and thus the epiphyseal plate does not change in overall thickness as the bone lengthens. During the late teens and early 20s, growth of the cartilage slows and eventually stops. The epiphyseal plate is then completely replaced by bone, and the diaphysis and epiphysis portions of the bone fuse together to form a single adult bone. This fusion of the diaphysis and epiphysis is a synostosis. Once this occurs, bone lengthening ceases. For this reason, the epiphyseal plate is considered to be a temporary synchondrosis. Because cartilage is softer than bone tissue, injury to a growing long bone can damage the epiphyseal plate cartilage, thus stopping bone growth and preventing additional bone lengthening.

Growing layers of cartilage also form synchondroses that join together the ilium, ischium, and pubic portions of the hip bone during childhood and adolescence. When body growth stops, the cartilage disappears and is replaced by bone, forming synostoses and fusing the bony components together into the single hip bone of the adult. Similarly, synostoses unite the sacral vertebrae that fuse together to form the adult sacrum.

Visit this website to view a radiograph (X-ray image) of a child’s hand and wrist. The growing bones of child have an epiphyseal plate that forms a synchondrosis between the shaft and end of a long bone. Being less dense than bone, the area of epiphyseal cartilage is seen on this radiograph as the dark epiphyseal gaps located near the ends of the long bones, including the radius, ulna, metacarpal, and phalanx bones. Which of the bones in this image do not show an epiphyseal plate (epiphyseal gap)?

Examples of permanent synchondroses are found in the thoracic cage. One example is the first sternocostal joint, where the first rib is anchored to the manubrium by its costal cartilage. (The articulations of the remaining costal cartilages to the sternum are all synovial joints.) Additional synchondroses are formed where the anterior end of the other 11 ribs is joined to its costal cartilage. Unlike the temporary synchondroses of the epiphyseal plate, these permanent synchondroses retain their hyaline cartilage and thus do not ossify with age. Due to the lack of movement between the bone and cartilage, both temporary and permanent synchondroses are functionally classified as a synarthrosis.

Symphysis

A cartilaginous joint where the bones are joined by fibrocartilage is called a symphysis (“growing together”). Fibrocartilage is very strong because it contains numerous bundles of thick collagen fibers, thus giving it a much greater ability to resist pulling and bending forces when compared with hyaline cartilage. This gives symphyses the ability to strongly unite the adjacent bones, but can still allow for limited movement to occur. Thus, a symphysis is functionally classified as an amphiarthrosis.

The gap separating the bones at a symphysis may be narrow or wide. Examples in which the gap between the bones is narrow include the pubic symphysis and the manubriosternal joint. At the pubic symphysis, the pubic portions of the right and left hip bones of the pelvis are joined together by fibrocartilage across a narrow gap. Similarly, at the manubriosternal joint, fibrocartilage unites the manubrium and body portions of the sternum.

The intervertebral symphysis is a wide symphysis located between the bodies of adjacent vertebrae of the vertebral column. Here a thick pad of fibrocartilage called an intervertebral disc strongly unites the adjacent vertebrae by filling the gap between them. The width of the intervertebral symphysis is important because it allows for small movements between the adjacent vertebrae. In addition, the thick intervertebral disc provides cushioning between the vertebrae, which is important when carrying heavy objects or during high-impact activities such as running or jumping.

9.4 Synovial Joints

barkerj1 — Wed, 30 Aug 2017 18:38:01 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the structure of a synovial joint
Describe the following types of synovial joints, including the movements allowed by each and providing a specific example of each:
- Gliding joint
- Hinge joint
- Pivot joint
- Condyloid (ellipsoidal) joint
- Saddle joint
- Ball and socket joint
Explain how the structure of a synovial joint can restrict what type of movement is allowed when a muscle contracts
Describe the following joint disorder:
- Osteoarthritis
- Rheumatoid arthritis
- Bursitis
- Tendonitis
- Dislocation

Synovial joints are the most common type of joint in the body (Figure 1). A key structural characteristic for a synovial joint that is not seen at fibrous or cartilaginous joints is the presence of a joint cavity. This fluid-filled space is the site at which the articulating surfaces of the bones contact each other. Also unlike fibrous or cartilaginous joints, the articulating bone surfaces at a synovial joint are not directly connected to each other with fibrous connective tissue or cartilage. This gives the bones of a synovial joint the ability to move smoothly against each other, allowing for increased joint mobility.

[caption id="" align="aligncenter" width="380"] Figure 1. Synovial Joints. Synovial joints allow for smooth movements between the adjacent bones. The joint is surrounded by an articular capsule that defines a joint cavity filled with synovial fluid. The articulating surfaces of the bones are covered by a thin layer of articular cartilage. Ligaments support the joint by holding the bones together and resisting excess or abnormal joint motions.[/caption]

Structural Features of Synovial Joints

Synovial joints are characterized by the presence of a joint cavity. The walls of this space are formed by the articular capsule, a fibrous connective tissue structure that is attached to each bone just outside the area of the bone’s articulating surface. The bones of the joint articulate with each other within the joint cavity.

Friction between the bones at a synovial joint is prevented by the presence of the articular cartilage, a thin layer of hyaline cartilage that covers the entire articulating surface of each bone. However, unlike at a cartilaginous joint, the articular cartilages of each bone are not continuous with each other. Instead, the articular cartilage acts like a Teflon^® coating over the bone surface, allowing the articulating bones to move smoothly against each other without damaging the underlying bone tissue. Lining the inner surface of the articular capsule is a thin synovial membrane. The cells of this membrane secrete synovial fluid (synovia = “a thick fluid”), a thick, slimy fluid that provides lubrication to further reduce friction between the bones of the joint. This fluid also provides nourishment to the articular cartilage, which does not contain blood vessels. The ability of the bones to move smoothly against each other within the joint cavity, and the freedom of joint movement this provides, means that each synovial joint is functionally classified as a diarthrosis.

Outside of their articulating surfaces, the bones are connected together by ligaments, which are strong bands of fibrous connective tissue. These strengthen and support the joint by anchoring the bones together and preventing their separation. Ligaments allow for normal movements at a joint, but limit the range of these motions, thus preventing excessive or abnormal joint movements. Ligaments are classified based on their relationship to the fibrous articular capsule. An extrinsic ligament is located outside of the articular capsule, an intrinsic ligament is fused to or incorporated into the wall of the articular capsule, and an intracapsular ligament is located inside of the articular capsule.

At many synovial joints, additional support is provided by the muscles and their tendons that act across the joint. A tendon is the dense connective tissue structure that attaches a muscle to bone. As forces acting on a joint increase, the body will automatically increase the overall strength of contraction of the muscles crossing that joint, thus allowing the muscle and its tendon to serve as a “dynamic ligament” to resist forces and support the joint. This type of indirect support by muscles is very important at the shoulder joint, for example, where the ligaments are relatively weak.

Additional Structures Associated with Synovial Joints

A few synovial joints of the body have a fibrocartilage structure located between the articulating bones. This is called an articular disc, which is generally small and oval-shaped, or a meniscus, which is larger and C-shaped. These structures can serve several functions, depending on the specific joint. In some places, an articular disc may act to strongly unite the bones of the joint to each other. Examples of this include the articular discs found at the sternoclavicular joint or between the distal ends of the radius and ulna bones. At other synovial joints, the disc can provide shock absorption and cushioning between the bones, which is the function of each meniscus within the knee joint. Finally, an articular disc can serve to smooth the movements between the articulating bones, as seen at the temporomandibular joint. Some synovial joints also have a fat pad, which can serve as a cushion between the bones.

Additional structures located outside of a synovial joint serve to prevent friction between the bones of the joint and the overlying muscle tendons or skin. A bursa (plural = bursae) is a thin connective tissue sac filled with lubricating liquid. They are located in regions where skin, ligaments, muscles, or muscle tendons can rub against each other, usually near a body joint (Figure 2). Bursae reduce friction by separating the adjacent structures, preventing them from rubbing directly against each other. Bursae are classified by their location. A subcutaneous bursa is located between the skin and an underlying bone. It allows skin to move smoothly over the bone. Examples include the prepatellar bursa located over the kneecap and the olecranon bursa at the tip of the elbow. A submuscular bursa is found between a muscle and an underlying bone, or between adjacent muscles. These prevent rubbing of the muscle during movements. A large submuscular bursa, the trochanteric bursa, is found at the lateral hip, between the greater trochanter of the femur and the overlying gluteus maximus muscle. A subtendinous bursa is found between a tendon and a bone. Examples include the subacromial bursa that protects the tendon of shoulder muscle as it passes under the acromion of the scapula, and the suprapatellar bursa that separates the tendon of the large anterior thigh muscle from the distal femur just above the knee.

[caption id="" align="aligncenter" width="380"] Figure 2. Bursae. Bursae are fluid-filled sacs that serve to prevent friction between skin, muscle, or tendon and an underlying bone. Three major bursae and a fat pad are part of the complex joint that unites the femur and tibia of the leg.[/caption]

A tendon sheath is similar in structure to a bursa, but smaller. It is a connective tissue sac that surrounds a muscle tendon at places where the tendon crosses a joint. It contains a lubricating fluid that allows for smooth motions of the tendon during muscle contraction and joint movements.

Bursitis is the inflammation of a bursa near a joint. This will cause pain, swelling, or tenderness of the bursa and surrounding area, and may also result in joint stiffness. Bursitis is most commonly associated with the bursae found at or near the shoulder, hip, knee, or elbow joints. At the shoulder, subacromial bursitis may occur in the bursa that separates the acromion of the scapula from the tendon of a shoulder muscle as it passes deep to the acromion. In the hip region, trochanteric bursitis can occur in the bursa that overlies the greater trochanter of the femur, just below the lateral side of the hip. Ischial bursitis occurs in the bursa that separates the skin from the ischial tuberosity of the pelvis, the bony structure that is weight bearing when sitting. At the knee, inflammation and swelling of the bursa located between the skin and patella bone is prepatellar bursitis (“housemaid’s knee”), a condition more commonly seen today in roofers or floor and carpet installers who do not use knee pads. At the elbow, olecranon bursitis is inflammation of the bursa between the skin and olecranon process of the ulna. The olecranon forms the bony tip of the elbow, and bursitis here is also known as “student’s elbow.”

Bursitis can be either acute (lasting only a few days) or chronic. It can arise from muscle overuse, trauma, excessive or prolonged pressure on the skin, rheumatoid arthritis, gout, or infection of the joint. Repeated acute episodes of bursitis can result in a chronic condition. Treatments for the disorder include antibiotics if the bursitis is caused by an infection, or anti-inflammatory agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids if the bursitis is due to trauma or overuse. Chronic bursitis may require that fluid be drained, but additional surgery is usually not required.

Types of Synovial Joints

Synovial joints are subdivided based on the shapes of the articulating surfaces of the bones that form each joint. The six types of synovial joints are pivot, hinge, condyloid, saddle, plane, and ball-and socket-joints (Figure 3).

[caption id="" align="aligncenter" width="600"] Figure 3. Types of Synovial Joints. The six types of synovial joints allow the body to move in a variety of ways. (a) Pivot joints allow for rotation around an axis, such as between the first and second cervical vertebrae, which allows for side-to-side rotation of the head. (b) The hinge joint of the elbow works like a door hinge. (c) The articulation between the trapezium carpal bone and the first metacarpal bone at the base of the thumb is a saddle joint. (d) Plane joints, such as those between the tarsal bones of the foot, allow for limited gliding movements between bones. (e) The radiocarpal joint of the wrist is a condyloid joint. (f) The hip and shoulder joints are the only ball-and-socket joints of the body.[/caption]

Pivot Joint

At a pivot joint, a rounded portion of a bone is enclosed within a ring formed partially by the articulation with another bone and partially by a ligament (see Figure 3a). The bone rotates within this ring. Since the rotation is around a single axis, pivot joints are functionally classified as a uniaxial diarthrosis type of joint. An example of a pivot joint is the atlantoaxial joint, found between the C1 (atlas) and C2 (axis) vertebrae. Here, the upward projecting dens of the axis articulates with the inner aspect of the atlas, where it is held in place by a ligament. Rotation at this joint allows you to turn your head from side to side. A second pivot joint is found at the proximal radioulnar joint. Here, the head of the radius is largely encircled by a ligament that holds it in place as it articulates with the radial notch of the ulna. Rotation of the radius allows for forearm movements.

Hinge Joint

In a hinge joint, the convex end of one bone articulates with the concave end of the adjoining bone (see Figure 3b). This type of joint allows only for bending and straightening motions along a single axis, and thus hinge joints are functionally classified as uniaxial joints. A good example is the elbow joint, with the articulation between the trochlea of the humerus and the trochlear notch of the ulna. Other hinge joints of the body include the knee, ankle, and interphalangeal joints between the phalanx bones of the fingers and toes.

Condyloid Joint

At a condyloid joint (ellipsoid joint), the shallow depression at the end of one bone articulates with a rounded structure from an adjacent bone or bones (see Figure 3e). The knuckle (metacarpophalangeal) joints of the hand between the distal end of a metacarpal bone and the proximal phalanx bone are condyloid joints. Another example is the radiocarpal joint of the wrist, between the shallow depression at the distal end of the radius bone and the rounded scaphoid, lunate, and triquetrum carpal bones. In this case, the articulation area has a more oval (elliptical) shape. Functionally, condyloid joints are biaxial joints that allow for two planes of movement. One movement involves the bending and straightening of the fingers or the anterior-posterior movements of the hand. The second movement is a side-to-side movement, which allows you to spread your fingers apart and bring them together, or to move your hand in a medial-going or lateral-going direction.

Saddle Joint

At a saddle joint, both of the articulating surfaces for the bones have a saddle shape, which is concave in one direction and convex in the other (see Figure 3c). This allows the two bones to fit together like a rider sitting on a saddle. Saddle joints are functionally classified as biaxial joints. The primary example is the first carpometacarpal joint, between the trapezium (a carpal bone) and the first metacarpal bone at the base of the thumb. This joint provides the thumb the ability to move away from the palm of the hand along two planes. Thus, the thumb can move within the same plane as the palm of the hand, or it can jut out anteriorly, perpendicular to the palm. This movement of the first carpometacarpal joint is what gives humans their distinctive “opposable” thumbs. The sternoclavicular joint is also classified as a saddle joint.

Plane Joint

At a plane joint (gliding joint), the articulating surfaces of the bones are flat or slightly curved and of approximately the same size, which allows the bones to slide against each other (see Figure 3d). The motion at this type of joint is usually small and tightly constrained by surrounding ligaments. Based only on their shape, plane joints can allow multiple movements, including rotation. Thus plane joints can be functionally classified as a multiaxial joint. However, not all of these movements are available to every plane joint due to limitations placed on it by ligaments or neighboring bones. Thus, depending upon the specific joint of the body, a plane joint may exhibit only a single type of movement or several movements. Plane joints are found between the carpal bones (intercarpal joints) of the wrist or tarsal bones (intertarsal joints) of the foot, between the clavicle and acromion of the scapula (acromioclavicular joint), and between the superior and inferior articular processes of adjacent vertebrae (zygapophysial joints).

Ball-and-Socket Joint

The joint with the greatest range of motion is the ball-and-socket joint. At these joints, the rounded head of one bone (the ball) fits into the concave articulation (the socket) of the adjacent bone (see Figure 3f). The hip joint and the glenohumeral (shoulder) joint are the only ball-and-socket joints of the body. At the hip joint, the head of the femur articulates with the acetabulum of the hip bone, and at the shoulder joint, the head of the humerus articulates with the glenoid cavity of the scapula.

[caption id="" align="alignright" width="120"] Watch this video to see an animation of synovial joints in action.[/caption]

Ball-and-socket joints are classified functionally as multiaxial joints. The femur and the humerus are able to move in both anterior-posterior and medial-lateral directions and they can also rotate around their long axis. The shallow socket formed by the glenoid cavity allows the shoulder joint an extensive range of motion. In contrast, the deep socket of the acetabulum and the strong supporting ligaments of the hip joint serve to constrain movements of the femur, reflecting the need for stability and weight-bearing ability at the hip.

Disorders of Synovial Joints

Arthritis is a common disorder of synovial joints that involves inflammation of the joint. This often results in significant joint pain, along with swelling, stiffness, and reduced joint mobility. There are more than 100 different forms of arthritis. Arthritis may arise from aging, damage to the articular cartilage, autoimmune diseases, bacterial or viral infections, or unknown (probably genetic) causes.

The most common type of arthritis is osteoarthritis, which is associated with aging and “wear and tear” of the articular cartilage (Figure 4). Risk factors that may lead to osteoarthritis later in life include injury to a joint; jobs that involve physical labor; sports with running, twisting, or throwing actions; and being overweight. These factors put stress on the articular cartilage that covers the surfaces of bones at synovial joints, causing the cartilage to gradually become thinner. As the articular cartilage layer wears down, more pressure is placed on the bones. The joint responds by increasing production of the lubricating synovial fluid, but this can lead to swelling of the joint cavity, causing pain and joint stiffness as the articular capsule is stretched. The bone tissue underlying the damaged articular cartilage also responds by thickening, producing irregularities and causing the articulating surface of the bone to become rough or bumpy. Joint movement then results in pain and inflammation. In its early stages, symptoms of osteoarthritis may be reduced by mild activity that “warms up” the joint, but the symptoms may worsen following exercise. In individuals with more advanced osteoarthritis, the affected joints can become more painful and therefore are difficult to use effectively, resulting in increased immobility. There is no cure for osteoarthritis, but several treatments can help alleviate the pain. Treatments may include lifestyle changes, such as weight loss and low-impact exercise, and over-the-counter or prescription medications that help to alleviate the pain and inflammation. For severe cases, joint replacement surgery (arthroplasty) may be required.

Joint replacement is a very invasive procedure, so other treatments are always tried before surgery. However arthroplasty can provide relief from chronic pain and can enhance mobility within a few months following the surgery. This type of surgery involves replacing the articular surfaces of the bones with prosthesis (artificial components). For example, in hip arthroplasty, the worn or damaged parts of the hip joint, including the head and neck of the femur and the acetabulum of the pelvis, are removed and replaced with artificial joint components. The replacement head for the femur consists of a rounded ball attached to the end of a shaft that is inserted inside the diaphysis of the femur. The acetabulum of the pelvis is reshaped and a replacement socket is fitted into its place. The parts, which are always built in advance of the surgery, are sometimes custom made to produce the best possible fit for a patient.

Gout is a form of arthritis that results from the deposition of uric acid crystals within a body joint. Usually only one or a few joints are affected, such as the big toe, knee, or ankle. The attack may only last a few days, but may return to the same or another joint. Gout occurs when the body makes too much uric acid or the kidneys do not properly excrete it. A diet with excessive fructose has been implicated in raising the chances of a susceptible individual developing gout.

Other forms of arthritis are associated with various autoimmune diseases, bacterial infections of the joint, or unknown genetic causes. Autoimmune diseases, including rheumatoid arthritis, scleroderma, or systemic lupus erythematosus, produce arthritis because the immune system of the body attacks the body joints. In rheumatoid arthritis, the joint capsule and synovial membrane become inflamed. As the disease progresses, the articular cartilage is severely damaged or destroyed, resulting in joint deformation, loss of movement, and severe disability. The most commonly involved joints are the hands, feet, and cervical spine, with corresponding joints on both sides of the body usually affected, though not always to the same extent. Rheumatoid arthritis is also associated with lung fibrosis, vasculitis (inflammation of blood vessels), coronary heart disease, and premature mortality. With no known cure, treatments are aimed at alleviating symptoms. Exercise, anti-inflammatory and pain medications, various specific disease-modifying anti-rheumatic drugs, or surgery are used to treat rheumatoid arthritis.

[caption id="" align="aligncenter" width="420"] Figure 4. Osteoarthritis. Osteoarthritis of a synovial joint results from aging or prolonged joint wear and tear. These cause erosion and loss of the articular cartilage covering the surfaces of the bones, resulting in inflammation that causes joint stiffness and pain.[/caption]

[caption id="" align="alignleft" width="120"] Visit this website to learn about a patient who arrives at the hospital with joint pain and weakness in his legs. What caused this patient’s weakness?[/caption]

Other joint disorders are the result of inflammation of the soft tissues near a joint, without bone tissue necessarily being involved directly. Bursitis refers to inflammation of a bursa, usually caused by a blow or friction. Bursitis of the prepatellar bursa ("water on the knee") can be caused by falling on one's knees or frequent "mini-traumas" associated with repeated kneeling. Bursitis can also be associated with other joint disorders, as it may also be caused by conditions such as osteoarthritis, rheumatoid arthritis, gouty arthritis, or pseudogout. Tendonitis, or inflammation of a tendon sheath, is more likely to be caused by excessive repetition of a particular movement over time. For example, medial epicondylitis ("golfer's elbow") can be caused by repeated flexion of the fingers or forearm pronation, and lateral epicondylitis ("tennis elbow") is commonly caused by repeated extension of the forearm.

9.5 Types of Body Movements

barkerj1 — Wed, 30 Aug 2017 18:38:03 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe, and provide a specific example of, each of the following movements allowed by synovial joints: gliding, angular movement, rotation, circumduction
Describe, using specific examples, 16 types of movements characteristic of skeletal muscle contractions

[caption id="" align="alignright" width="120"] Watch this video to learn about anatomical motions. What motions involve increasing or decreasing the angle of the foot at the ankle?[/caption]

Synovial joints allow the body a tremendous range of movements. Each movement at a synovial joint results from the contraction or relaxation of the muscles that are attached to the bones on either side of the articulation. The type of movement that can be produced at a synovial joint is determined by its structural type. While the ball-and-socket joint gives the greatest range of movement at an individual joint, in other regions of the body, several joints may work together to produce a particular movement. Overall, each type of synovial joint is necessary to provide the body with its great flexibility and mobility. There are many types of movement that can occur at synovial joints (Table 1). Movement types are generally paired, with one being the opposite of the other. Body movements are always described in relation to the anatomical position of the body: upright stance, with upper limbs to the side of body and palms facing forward.

[caption id="attachment_1604" align="aligncenter" width="600"] Figure 1. Movements of the Body, Part 1. Synovial joints give the body many ways in which to move. (a)–(b) Flexion and extension motions are in the sagittal (anterior–posterior) plane of motion. These movements take place at the shoulder, hip, elbow, knee, wrist, metacarpophalangeal, metatarsophalangeal, and interphalangeal joints. (c)–(d) Anterior bending of the head or vertebral column is flexion, while any posterior-going movement is extension. (e) Abduction and adduction are motions of the limbs, hand, fingers, or toes in the coronal (medial–lateral) plane of movement. Moving the limb or hand laterally away from the body, or spreading the fingers or toes, is abduction. Adduction brings the limb or hand toward or across the midline of the body, or brings the fingers or toes together. Circumduction is the movement of the limb, hand, or fingers in a circular pattern, using the sequential combination of flexion, adduction, extension, and abduction motions. Adduction/abduction and circumduction take place at the shoulder, hip, wrist, metacarpophalangeal, and metatarsophalangeal joints. (f) Turning of the head side to side or twisting of the body is rotation. Medial and lateral rotation of the upper limb at the shoulder or lower limb at the hip involves turning the anterior surface of the limb toward the midline of the body (medial or internal rotation) or away from the midline (lateral or external rotation).[/caption]

[caption id="attachment_1605" align="aligncenter" width="600"] Figure 2. Movements of the Body, Part 2. (g) Supination of the forearm turns the hand to the palm forward position in which the radius and ulna are parallel, while forearm pronation turns the hand to the palm backward position in which the radius crosses over the ulna to form an "X." (h) Dorsiflexion of the foot at the ankle joint moves the top of the foot toward the leg, while plantar flexion lifts the heel and points the toes. (i) Eversion of the foot moves the bottom (sole) of the foot away from the midline of the body, while foot inversion faces the sole toward the midline. (j) Protraction of the mandible pushes the chin forward, and retraction pulls the chin back. (k) Depression of the mandible opens the mouth, while elevation closes it. (l) Opposition of the thumb brings the tip of the thumb into contact with the tip of the fingers of the same hand and reposition brings the thumb back next to the index finger.[/caption]

Flexion and Extension

Flexion and extension are movements that take place within the sagittal plane and involve anterior or posterior movements of the body or limbs. For the vertebral column, flexion (anterior flexion) is an anterior (forward) bending of the neck or body, while extension involves a posterior-directed motion, such as straightening from a flexed position or bending backward. Lateral flexion is the bending of the neck or body toward the right or left side. These movements of the vertebral column involve both the symphysis joint formed by each intervertebral disc, as well as the plane type of synovial joint formed between the inferior articular processes of one vertebra and the superior articular processes of the next lower vertebra. In the limbs, flexion decreases the angle between the bones (bending of the joint), while extension increases the angle and straightens the joint. For the upper limb, all anterior-going motions are flexion and all posterior-going motions are extension. These include anterior-posterior movements of the arm at the shoulder, the forearm at the elbow, the hand at the wrist, and the fingers at the metacarpophalangeal and interphalangeal joints. For the thumb, extension moves the thumb away from the palm of the hand, within the same plane as the palm, while flexion brings the thumb back against the index finger or into the palm. These motions take place at the first carpometacarpal joint. In the lower limb, bringing the thigh forward and upward is flexion at the hip joint, while any posterior-going motion of the thigh is extension. Note that extension of the thigh beyond the anatomical (standing) position is greatly limited by the ligaments that support the hip joint. Knee flexion is the bending of the knee to bring the foot toward the posterior thigh, and extension is the straightening of the knee. Flexion and extension movements are seen at the hinge, condyloid, saddle, and ball-and-socket joints of the limbs (see Figure 1a-d). Hyperextension is the abnormal or excessive extension of a joint beyond its normal range of motion, thus resulting in injury. Similarly, hyperflexion is excessive flexion at a joint. Hyperextension injuries are common at hinge joints such as the knee or elbow. In cases of “whiplash” in which the head is suddenly moved backward and then forward, a patient may experience both hyperextension and hyperflexion of the cervical region.

Abduction and Adduction

Abduction and adduction motions occur within the coronal plane and involve medial-lateral motions of the limbs, fingers, toes, or thumb. Abduction moves the limb laterally away from the midline of the body, while adduction is the opposing movement that brings the limb toward the body or across the midline. For example, abduction is raising the arm at the shoulder joint, moving it laterally away from the body, while adduction brings the arm down to the side of the body. Similarly, abduction and adduction at the wrist moves the hand away from or toward the midline of the body. Spreading the fingers or toes apart is also abduction, while bringing the fingers or toes together is adduction. For the thumb, abduction is the anterior movement that brings the thumb to a 90° perpendicular position, pointing straight out from the palm. Adduction moves the thumb back to the anatomical position, next to the index finger. Abduction and adduction movements are seen at condyloid, saddle, and ball-and-socket joints (see Figure 1e).

Circumduction

Circumduction is the movement of a body region in a circular manner, in which one end of the body region being moved stays relatively stationary while the other end describes a circle. It involves the sequential combination of flexion, adduction, extension, and abduction at a joint. This type of motion is found at biaxial condyloid and saddle joints, and at multiaxial ball-and-sockets joints (see Figure 1e).

Rotation

Rotation can occur within the vertebral column, at a pivot joint, or at a ball-and-socket joint. Rotation of the neck or body is the twisting movement produced by the summation of the small rotational movements available between adjacent vertebrae. At a pivot joint, one bone rotates in relation to another bone. This is a uniaxial joint, and thus rotation is the only motion allowed at a pivot joint. For example, at the atlantoaxial joint, the first cervical (C1) vertebra (atlas) rotates around the dens, the upward projection from the second cervical (C2) vertebra (axis). This allows the head to rotate from side to side as when shaking the head “no.” The proximal radioulnar joint is a pivot joint formed by the head of the radius and its articulation with the ulna. This joint allows for the radius to rotate along its length during pronation and supination movements of the forearm.

Rotation can also occur at the ball-and-socket joints of the shoulder and hip. Here, the humerus and femur rotate around their long axis, which moves the anterior surface of the arm or thigh either toward or away from the midline of the body. Movement that brings the anterior surface of the limb toward the midline of the body is called medial (internal) rotation. Conversely, rotation of the limb so that the anterior surface moves away from the midline is lateral (external) rotation (see Figure 1f). Be sure to distinguish medial and lateral rotation, which can only occur at the multiaxial shoulder and hip joints, from circumduction, which can occur at either biaxial or multiaxial joints.

Supination and Pronation

Supination and pronation are movements of the forearm. In the anatomical position, the upper limb is held next to the body with the palm facing forward. This is the supinated position of the forearm. In this position, the radius and ulna are parallel to each other. When the palm of the hand faces backward, the forearm is in the pronated position, and the radius and ulna form an X-shape.

Supination and pronation are the movements of the forearm that go between these two positions. Pronation is the motion that moves the forearm from the supinated (anatomical) position to the pronated (palm backward) position. This motion is produced by rotation of the radius at the proximal radioulnar joint, accompanied by movement of the radius at the distal radioulnar joint. The proximal radioulnar joint is a pivot joint that allows for rotation of the head of the radius. Because of the slight curvature of the shaft of the radius, this rotation causes the distal end of the radius to cross over the distal ulna at the distal radioulnar joint. This crossing over brings the radius and ulna into an X-shape position. Supination is the opposite motion, in which rotation of the radius returns the bones to their parallel positions and moves the palm to the anterior facing (supinated) position. It helps to remember that supination is the motion you use when scooping up soup with a spoon (see Figure 2g).

Dorsiflexion and Plantar Flexion

Dorsiflexion and plantar flexion are movements at the ankle joint, which is a hinge joint. Lifting the front of the foot, so that the top of the foot moves toward the anterior leg is dorsiflexion, while lifting the heel of the foot from the ground or pointing the toes downward is plantar flexion. These are the only movements available at the ankle joint (see Figure 2h).

Inversion and Eversion

Inversion and eversion are complex movements that involve the multiple plane joints among the tarsal bones of the posterior foot (intertarsal joints) and thus are not motions that take place at the ankle joint. Inversion is the turning of the foot to angle the bottom of the foot toward the midline, while eversion turns the bottom of the foot away from the midline. The foot has a greater range of inversion than eversion motion. These are important motions that help to stabilize the foot when walking or running on an uneven surface and aid in the quick side-to-side changes in direction used during active sports such as basketball, racquetball, or soccer (see Figure 2i).

Protraction and Retraction

Protraction and retraction are anterior-posterior movements of the scapula or mandible. Protraction of the scapula occurs when the shoulder is moved forward, as when pushing against something or throwing a ball. Retraction is the opposite motion, with the scapula being pulled posteriorly and medially, toward the vertebral column. For the mandible, protraction occurs when the lower jaw is pushed forward, to stick out the chin, while retraction pulls the lower jaw backward. (See Figure 2j.)

Depression and Elevation

Depression and elevation are downward and upward movements of the scapula or mandible. The upward movement of the scapula and shoulder is elevation, while a downward movement is depression. These movements are used to shrug your shoulders. Similarly, elevation of the mandible is the upward movement of the lower jaw used to close the mouth or bite on something, and depression is the downward movement that produces opening of the mouth (see Figure 2k).

Excursion

Excursion is the side to side movement of the mandible. Lateral excursion moves the mandible away from the midline, toward either the right or left side. Medial excursion returns the mandible to its resting position at the midline.

Superior Rotation and Inferior Rotation

Superior and inferior rotation are movements of the scapula and are defined by the direction of movement of the glenoid cavity. These motions involve rotation of the scapula around a point inferior to the scapular spine and are produced by combinations of muscles acting on the scapula. During superior rotation, the glenoid cavity moves upward as the medial end of the scapular spine moves downward. This is a very important motion that contributes to upper limb abduction. Without superior rotation of the scapula, the greater tubercle of the humerus would hit the acromion of the scapula, thus preventing any abduction of the arm above shoulder height. Superior rotation of the scapula is thus required for full abduction of the upper limb. Superior rotation is also used without arm abduction when carrying a heavy load with your hand or on your shoulder. You can feel this rotation when you pick up a load, such as a heavy book bag and carry it on only one shoulder. To increase its weight-bearing support for the bag, the shoulder lifts as the scapula superiorly rotates. Inferior rotation occurs during limb adduction and involves the downward motion of the glenoid cavity with upward movement of the medial end of the scapular spine.

Opposition and Reposition

Opposition is the thumb movement that brings the tip of the thumb in contact with the tip of a finger. This movement is produced at the first carpometacarpal joint, which is a saddle joint formed between the trapezium carpal bone and the first metacarpal bone. Thumb opposition is produced by a combination of flexion and abduction of the thumb at this joint. Returning the thumb to its anatomical position next to the index finger is called reposition (see Figure 2l).

Movements of the Joints (Table 1)
Type of Joint	Movement	Example
Pivot	Uniaxial joint; allows rotational movement	Atlantoaxial joint (C1–C2 vertebrae articulation); proximal radioulnar joint
Hinge	Uniaxial joint; allows flexion/extension movements	Knee; elbow; ankle; interphalangeal joints of fingers and toes
Condyloid	Biaxial joint; allows flexion/extension, abduction/adduction, and circumduction movements	Metacarpophalangeal (knuckle) joints of fingers; radiocarpal joint of wrist; metatarsophalangeal joints for toes
Saddle	Biaxial joint; allows flexion/extension, abduction/adduction, and circumduction movements	First carpometacarpal joint of the thumb; sternoclavicular joint
Plane	Multiaxial joint; allows inversion and eversion of foot, or flexion, extension, and lateral flexion of the vertebral column	Intertarsal joints of foot; superior-inferior articular process articulations between vertebrae
Ball-and-socket	Multiaxial joint; allows flexion/extension, abduction/adduction, circumduction, and medial/lateral rotation movements	Shoulder and hip joints

9.6 Anatomy of Selected Synovial Joints

barkerj1 — Wed, 30 Aug 2017 18:38:06 +0000

Learning Objectives

By the end of this section, you will be able to

Specify the function of each of the following components of the knee joint:
- Joint capsule
- Synovial membrane
- Synovial cavity
- Synovial fluid
- Articular cartilage
- Ligaments
- Meniscus
- Bursa

Each synovial joint of the body is specialized to perform certain movements. The movements that are allowed are determined by the structural classification for each joint. For example, a multiaxial ball-and-socket joint has much more mobility than a uniaxial hinge joint. However, the ligaments and muscles that support a joint may place restrictions on the total range of motion available. Thus, the ball-and-socket joint of the shoulder has little in the way of ligament support, which gives the shoulder a very large range of motion. In contrast, movements at the hip joint are restricted by strong ligaments, which reduce its range of motion but confer stability during standing and weight bearing.

This section will examine the anatomy of selected synovial joints of the body. Anatomical names for most joints are derived from the names of the bones that articulate at that joint, although some joints, such as the elbow, hip, and knee joints are exceptions to this general naming scheme.

Knee Joint

The knee joint is the largest joint of the body (Figure 6). It actually consists of three articulations. The femoropatellar joint is found between the patella and the distal femur. The medial tibiofemoral joint and lateral tibiofemoral joint are located between the medial and lateral condyles of the femur and the medial and lateral condyles of the tibia. All of these articulations are enclosed within a single articular capsule. The knee functions as a hinge joint, allowing flexion and extension of the leg. This action is generated by both rolling and gliding motions of the femur on the tibia. In addition, some rotation of the leg is available when the knee is flexed, but not when extended. The knee is well constructed for weight bearing in its extended position, but is vulnerable to injuries associated with hyperextension, twisting, or blows to the medial or lateral side of the joint, particularly while weight bearing.

At the femoropatellar joint, the patella slides vertically within a groove on the distal femur. The patella is a sesamoid bone incorporated into the tendon of the quadriceps femoris muscle, the large muscle of the anterior thigh. The patella serves to protect the quadriceps tendon from friction against the distal femur. Continuing from the patella to the anterior tibia just below the knee is the patellar ligament. Acting via the patella and patellar ligament, the quadriceps femoris is a powerful muscle that acts to extend the leg at the knee. It also serves as a “dynamic ligament” to provide very important support and stabilization for the knee joint.

The medial and lateral tibiofemoral joints are the articulations between the rounded condyles of the femur and the relatively flat condyles of the tibia. During flexion and extension motions, the condyles of the femur both roll and glide over the surfaces of the tibia. The rolling action produces flexion or extension, while the gliding action serves to maintain the femoral condyles centered over the tibial condyles, thus ensuring maximal bony, weight-bearing support for the femur in all knee positions. As the knee comes into full extension, the femur undergoes a slight medial rotation in relation to tibia. The rotation results because the lateral condyle of the femur is slightly smaller than the medial condyle. Thus, the lateral condyle finishes its rolling motion first, followed by the medial condyle. The resulting small medial rotation of the femur serves to “lock” the knee into its fully extended and most stable position. Flexion of the knee is initiated by a slight lateral rotation of the femur on the tibia, which “unlocks” the knee. This lateral rotation motion is produced by the popliteus muscle of the posterior leg.

Located between the articulating surfaces of the femur and tibia are two articular discs, the medial meniscus and lateral meniscus (see Figure 6b). Each is a C-shaped fibrocartilage structure that is thin along its inside margin and thick along the outer margin. They are attached to their tibial condyles, but do not attach to the femur. While both menisci are free to move during knee motions, the medial meniscus shows less movement because it is anchored at its outer margin to the articular capsule and tibial collateral ligament. The menisci provide padding between the bones and help to fill the gap between the round femoral condyles and flattened tibial condyles. Some areas of each meniscus lack an arterial blood supply and thus these areas heal poorly if damaged.

The knee joint has multiple ligaments that provide support, particularly in the extended position (see Figure 6c). Outside of the articular capsule, located at the sides of the knee, are two extrinsic ligaments. The fibular collateral ligament (lateral collateral ligament) is on the lateral side and spans from the lateral epicondyle of the femur to the head of the fibula. The tibial collateral ligament (medial collateral ligament) of the medial knee runs from the medial epicondyle of the femur to the medial tibia. As it crosses the knee, the tibial collateral ligament is firmly attached on its deep side to the articular capsule and to the medial meniscus, an important factor when considering knee injuries. In the fully extended knee position, both collateral ligaments are taut (tight), thus serving to stabilize and support the extended knee and preventing side-to-side or rotational motions between the femur and tibia.

The articular capsule of the posterior knee is thickened by intrinsic ligaments that help to resist knee hyperextension. Inside the knee are two intracapsular ligaments, the anterior cruciate ligament and posterior cruciate ligament. These ligaments are anchored inferiorly to the tibia at the intercondylar eminence, the roughened area between the tibial condyles. The cruciate ligaments are named for whether they are attached anteriorly or posteriorly to this tibial region. Each ligament runs diagonally upward to attach to the inner aspect of a femoral condyle. The cruciate ligaments are named for the X-shape formed as they pass each other (cruciate means “cross”). The posterior cruciate ligament is the stronger ligament. It serves to support the knee when it is flexed and weight bearing, as when walking downhill. In this position, the posterior cruciate ligament prevents the femur from sliding anteriorly off the top of the tibia. The anterior cruciate ligament becomes tight when the knee is extended, and thus resists hyperextension.

[caption id="" align="aligncenter" width="620"] Figure 6. Knee Joint. (a) The knee joint is the largest joint of the body. (b)–(c) It is supported by the tibial and fibular collateral ligaments located on the sides of the knee outside of the articular capsule, and the anterior and posterior cruciate ligaments found inside the capsule. The medial and lateral menisci provide padding and support between the femoral condyles and tibial condyles.[/caption]

[caption id="" align="alignleft" width="120"] Watch this video to learn more about the flexion and extension of the knee, as the femur both rolls and glides on the tibia to maintain stable contact between the bones in all knee positions.[/caption]

[caption id="" align="alignright" width="120"] Watch this video to learn more about the anatomy of the knee joint, including bones, joints, muscles, nerves, and blood vessels.[/caption]

Introduction

barkerj1 — Wed, 30 Aug 2017 18:38:07 +0000

[caption id="" align="aligncenter" width="600"] Figure 1. Tennis Player. Athletes rely on toned skeletal muscles to supply the force required for movement. (credit: Emmanuel Huybrechts/flickr)[/caption] When most people think of muscles, they think of the muscles that are visible just under the skin, particularly of the limbs. These are skeletal muscles, so-named because most of them move the skeleton. But there are two other types of muscle in the body, with distinctly different jobs. Cardiac muscle, found in the heart, is concerned with pumping blood through the circulatory system. Smooth muscle is concerned with various involuntary movements, such as having one’s hair stand on end when cold or frightened, or moving food through the digestive system. This chapter will examine the structure and function of these three types of muscles.

10.1 Overview of Muscle Tissues

barkerj1 — Wed, 30 Aug 2017 18:38:07 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the different types of muscle

Muscle is one of the four primary tissue types of the body, and the body contains three types of muscle tissue: skeletal muscle, cardiac muscle, and smooth muscle (Figure 1). All three muscle tissues have some properties in common; they all exhibit a quality called excitability as their plasma membranes can change their electrical states (from polarized to depolarized) and send an electrical wave called an action potential along the entire length of the membrane. While the nervous system can influence the excitability of cardiac and smooth muscle to some degree, skeletal muscle completely depends on signaling from the nervous system to work properly. On the other hand, both cardiac muscle and smooth muscle can respond to other stimuli, such as hormones and local stimuli.

[caption id="" align="aligncenter" width="320"] Figure 1. The Three Types of Muscle Tissue. The body contains three types of muscle tissue: (a) skeletal muscle, (b) smooth muscle, and (c) cardiac muscle. From top, LM × 1600, LM × 1600, LM × 1600. (Micrographs provided by the Regents of University of Michigan Medical School © 2012)[/caption]

The muscles all begin the actual process of contracting (shortening) when a protein called actin is pulled by a protein called myosin. This occurs in striated muscle (skeletal and cardiac) after specific binding sites on the actin have been exposed in response to the interaction between calcium ions (Ca⁺⁺) and proteins (troponin and tropomyosin) that “shield” the actin-binding sites. Ca⁺⁺ also is required for the contraction of smooth muscle, although its role is different: here Ca⁺⁺ activates enzymes, which in turn activate myosin heads. All muscles require adenosine triphosphate (ATP) to continue the process of contracting, and they all relax when the Ca⁺⁺ is removed and the actin-binding sites are re-shielded.

A muscle can return to its original length when relaxed due to a quality of muscle tissue called elasticity. It can recoil back to its original length due to elastic fibers. Muscle tissue also has the quality of extensibility; it can stretch or extend. Contractility allows muscle tissue to pull on its attachment points and shorten with force.

Differences among the three muscle types include the microscopic organization of their contractile proteins—actin and myosin. The actin and myosin proteins are arranged very regularly in the cytoplasm of individual muscle cells (referred to as fibers) in both skeletal muscle and cardiac muscle, which creates a pattern, or stripes, called striations. The striations are visible with a light microscope under high magnification (see Figure 1). Skeletal muscle fibers are multinucleated structures that compose the skeletal muscle. Cardiac muscle fibers each have one to two nuclei and are physically and electrically connected to each other so that the entire heart contracts as one unit (called a syncytium).

Because the actin and myosin are not arranged in such regular fashion in smooth muscle, the cytoplasm of a smooth muscle fiber (which has only a single nucleus) has a uniform, nonstriated appearance (resulting in the name smooth muscle). However, the less organized appearance of smooth muscle should not be interpreted as less efficient. Smooth muscle in the walls of arteries is a critical component that regulates blood pressure necessary to push blood through the circulatory system; and smooth muscle in the skin, visceral organs, and internal passageways is essential for moving all materials through the body.

10.2 Skeletal Muscle

barkerj1 — Wed, 30 Aug 2017 18:38:12 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the levels of muscle organization: fasica, fascicles, muscle fibres
Describe a tendon
Describe the following structures of a muscle cell:
- Sarcolemma and sarcoplasm
- Nuclei and mitochondria
- Sarcoplasmic reticulum and transverse tubules
- Myofibrils, myofilaments, and sarcomeres
Describe the following structures of a sarcomere: Z line, I band, A band, H zone, M line
Describe the basic structure of the thick filaments and their primary protein component
Describe the following components of the thin filaments and their organization within a thin filament: actin, tropomyosin, troponin
Describe the anatomy of a neuromuscular junction
Describe the generation of a muscle action potential, including the roles of acetylcholine (ACh) and sodium (Na+) ions
Describe paralysis

The best-known feature of skeletal muscle is its ability to contract and cause movement. Skeletal muscles act not only to produce movement but also to stop movement, such as resisting gravity to maintain posture. Small, constant adjustments of the skeletal muscles are needed to hold a body upright or balanced in any position. Muscles also prevent excess movement of the bones and joints, maintaining skeletal stability and preventing skeletal structure damage or deformation. Joints can become misaligned or dislocated entirely by pulling on the associated bones; muscles work to keep joints stable. Skeletal muscles are located throughout the body at the openings of internal tracts to control the movement of various substances. These muscles allow functions, such as swallowing, urination, and defecation, to be under voluntary control. Skeletal muscles also protect internal organs (particularly abdominal and pelvic organs) by acting as an external barrier or shield to external trauma and by supporting the weight of the organs.

Skeletal muscles contribute to the maintenance of homeostasis in the body by generating heat. Muscle contraction requires energy, and when ATP is broken down, heat is produced. This heat is very noticeable during exercise, when sustained muscle movement causes body temperature to rise, and in cases of extreme cold, when shivering produces random skeletal muscle contractions to generate heat.

Each skeletal muscle is an organ that consists of various integrated tissues. These tissues include the skeletal muscle fibers, blood vessels, nerve fibers, and connective tissue. Each skeletal muscle has three layers of connective tissue (called “mysia”) that enclose it and provide structure to the muscle as a whole, and also compartmentalize the muscle fibers within the muscle (Figure 1). Each muscle is wrapped in a sheath of dense, irregular connective tissue called the epimysium, which allows a muscle to contract and move powerfully while maintaining its structural integrity. The epimysium also separates muscle from other tissues and organs in the area, allowing the muscle to move independently.

[caption id="" align="aligncenter" width="420"] Figure 1. The Three Connective Tissue Layers. Bundles of muscle fibers, called fascicles, are covered by the perimysium. Muscle fibers are covered by the endomysium.[/caption]

Inside each skeletal muscle, muscle fibers are organized into individual bundles, each called a fascicle, by a middle layer of connective tissue called the perimysium. This fascicular organization is common in muscles of the limbs; it allows the nervous system to trigger a specific movement of a muscle by activating a subset of muscle fibers within a bundle, or fascicle of the muscle. Inside each fascicle, each muscle fiber is encased in a thin connective tissue layer of collagen and reticular fibers called the endomysium. The endomysium contains the extracellular fluid and nutrients to support the muscle fiber. These nutrients are supplied via blood to the muscle tissue.

In skeletal muscles that work with tendons to pull on bones, the collagen in the three tissue layers (the mysia) intertwines with the collagen of a tendon. At the other end of the tendon, it fuses with the periosteum coating the bone. The tension created by contraction of the muscle fibers is then transferred though the mysia, to the tendon, and then to the periosteum to pull on the bone for movement of the skeleton. In other places, the mysia may fuse with a broad, tendon-like sheet called an aponeurosis, or to fascia, the connective tissue between skin and bones. The broad sheet of connective tissue in the lower back that the latissimus dorsi muscles (the “lats”) fuse into is an example of an aponeurosis.

Every skeletal muscle is also richly supplied by blood vessels for nourishment, oxygen delivery, and waste removal. In addition, every muscle fiber in a skeletal muscle is supplied by the axon branch of a somatic motor neuron, which signals the fiber to contract. Unlike cardiac and smooth muscle, the only way to functionally contract a skeletal muscle is through signaling from the nervous system.

Skeletal Muscle Fibers

Because skeletal muscle cells are long and cylindrical, they are commonly referred to as muscle fibers. Skeletal muscle fibers can be quite large for human cells, with diameters up to 100 μm and lengths up to 30 cm (11.8 in) in the Sartorius of the upper leg. During early development, embryonic myoblasts, each with its own nucleus, fuse with up to hundreds of other myoblasts to form the multinucleated skeletal muscle fibers. Multiple nuclei mean multiple copies of genes, permitting the production of the large amounts of proteins and enzymes needed for muscle contraction.

Some other terminology associated with muscle fibers is rooted in the Greek sarco, which means “flesh.” The plasma membrane of muscle fibers is called the sarcolemma, the cytoplasm is referred to as sarcoplasm, and the specialized smooth endoplasmic reticulum, which stores, releases, and retrieves calcium ions (Ca⁺⁺) is called the sarcoplasmic reticulum (SR) (Figure 2). As will soon be described, the functional unit of a skeletal muscle fiber is the sarcomere, a highly organized arrangement of the contractile myofilaments actin (thin filament) and myosin (thick filament), along with other support proteins.

[caption id="" align="aligncenter" width="420"] Figure 2. Muscle Fiber. A skeletal muscle fiber is surrounded by a plasma membrane called the sarcolemma, which contains sarcoplasm, the cytoplasm of muscle cells. A muscle fiber is composed of many fibrils, which give the cell its striated appearance.[/caption]

The Sarcomere

The striated appearance of skeletal muscle fibers is due to the arrangement of the myofilaments of actin and myosin in sequential order from one end of the muscle fiber to the other. Each packet of these microfilaments and their regulatory proteins, troponin and tropomyosin (along with other proteins) is called a sarcomere.

[caption id="" align="aligncenter" width="120"] Watch this video to learn more about macro- and microstructures of skeletal muscles.[/caption] [caption id="attachment_2969" align="aligncenter" width="150"] Watch this CrashCourse video to find out more about skeletal muscle structure.[/caption]

The sarcomere is the functional unit of the muscle fiber. The sarcomere itself is bundled within the myofibril that runs the entire length of the muscle fiber and attaches to the sarcolemma at its end. As myofibrils contract, the entire muscle cell contracts. Because myofibrils are only approximately 1.2 μm in diameter, hundreds to thousands (each with thousands of sarcomeres) can be found inside one muscle fiber. Each sarcomere is approximately 2 μm in length with a three-dimensional cylinder-like arrangement and is bordered by structures called Z-discs (also called Z-lines, because pictures are two-dimensional), to which the actin myofilaments are anchored (Figure 3). Because the actin and its troponin-tropomyosin complex (projecting from the Z-discs toward the center of the sarcomere) form strands that are thinner than the myosin, it is called the thin filament of the sarcomere. Likewise, because the myosin strands and their multiple heads (projecting from the center of the sarcomere, toward but not all to way to, the Z-discs) have more mass and are thicker, they are called the thick filament of the sarcomere.

[caption id="" align="aligncenter" width="390"] Figure 3. The Sarcomere. The sarcomere, the region from one Z-line to the next Z-line, is the functional unit of a skeletal muscle fiber.[/caption]

The Neuromuscular Junction

Another specialization of the skeletal muscle is the site where a motor neuron’s terminal meets the muscle fiber—called the neuromuscular junction (NMJ). This is where the muscle fiber first responds to signaling by the motor neuron. Every skeletal muscle fiber in every skeletal muscle is innervated by a motor neuron at the NMJ. Excitation signals from the neuron are the only way to functionally activate the fiber to contract.

[caption id="" align="aligncenter" width="120"] Watch this video to learn more about what happens at the NMJ.[/caption]

Excitation-Contraction Coupling

All living cells have membrane potentials, or electrical gradients across their membranes. The inside of the membrane is usually around -60 to -90 mV, relative to the outside. This is referred to as a cell’s membrane potential. Neurons and muscle cells can use their membrane potentials to generate electrical signals. They do this by controlling the movement of charged particles, called ions, across their membranes to create electrical currents. This is achieved by opening and closing specialized proteins in the membrane called ion channels. Although the currents generated by ions moving through these channel proteins are very small, they form the basis of both neural signaling and muscle contraction.

Both neurons and skeletal muscle cells are electrically excitable, meaning that they are able to generate action potentials. An action potential is a special type of electrical signal that can travel along a cell membrane as a wave. This allows a signal to be transmitted quickly and faithfully over long distances.

Although the term excitation-contraction coupling confuses or scares some students, it comes down to this: for a skeletal muscle fiber to contract, its membrane must first be “excited”—in other words, it must be stimulated to fire an action potential. The muscle fiber action potential, which sweeps along the sarcolemma as a wave, is “coupled” to the actual contraction through the release of calcium ions (Ca²⁺) from the SR. Once released, the Ca²⁺ interacts with the shielding proteins, forcing them to move aside so that the actin-binding sites are available for attachment by myosin heads. The myosin then pulls the actin filaments toward the center, shortening the muscle fiber.

In skeletal muscle, this sequence begins with signals from the somatic motor division of the nervous system. In other words, the “excitation” step in skeletal muscles is always triggered by signaling from the nervous system (Figure 4).

[caption id="" align="aligncenter" width="380"] Figure 4. Motor End-Plate and Innervation. At the NMJ, the axon terminal releases ACh. The motor end-plate is the location of the ACh-receptors in the muscle fiber sarcolemma. When ACh molecules are released, they diffuse across a minute space called the synaptic cleft and bind to the receptors.[/caption]

The motor neurons that tell the skeletal muscle fibers to contract originate in the spinal cord, with a smaller number located in the brainstem for activation of skeletal muscles of the face, head, and neck. These neurons have long processes, called axons, which are specialized to transmit action potentials long distances— in this case, all the way from the spinal cord to the muscle itself (which may be up to three feet away). The axons of multiple neurons bundle together to form nerves, like wires bundled together in a cable.

Signaling begins when a neuronal action potential travels along the axon of a motor neuron, and then along the individual branches to terminate at the NMJ. At the NMJ, the axon terminal releases a chemical messenger, or neurotransmitter, called acetylcholine (ACh). The ACh molecules diffuse across a minute space called the synaptic cleft and bind to ACh receptors located within the motor end-plate of the sarcolemma on the other side of the synapse. Once ACh binds, a channel in the ACh receptor opens and positively charged ions can pass through into the muscle fiber, causing it to depolarize, meaning that the membrane potential of the muscle fiber becomes less negative (closer to zero.)

As the membrane depolarizes, another set of ion channels called voltage-gated sodium channels are triggered to open. Sodium ions enter the muscle fiber, and an action potential rapidly spreads (or “fires”) along the entire membrane to initiate excitation-contraction coupling.

Things happen very quickly in the world of excitable membranes (just think about how quickly you can snap your fingers as soon as you decide to do it). Immediately following depolarization of the membrane, it repolarizes, re-establishing the negative membrane potential. Meanwhile, the ACh in the synaptic cleft is degraded by the enzyme acetylcholinesterase (AChE) so that the ACh cannot rebind to a receptor and reopen its channel, which would cause unwanted extended muscle excitation and contraction.

Propagation of an action potential along the sarcolemma is the excitation portion of excitation-contraction coupling. Recall that this excitation actually triggers the release of calcium ions (Ca²⁺) from its storage in the cell’s SR. For the action potential to reach the membrane of the SR, there are periodic invaginations in the sarcolemma, called T-tubules (“T” stands for “transverse”). You will recall that the diameter of a muscle fiber can be up to 100 μm, so these T-tubules ensure that the membrane can get close to the SR in the sarcoplasm. The arrangement of a T-tubule with the membranes of SR on either side is called a triad (Figure 5). The triad surrounds the cylindrical structure called a myofibril, which contains actin and myosin.

[caption id="" align="aligncenter" width="350"] Figure 5. The T-tubule. Narrow T-tubules permit the conduction of electrical impulses. The SR functions to regulate intracellular levels of calcium. Two terminal cisternae (where enlarged SR connects to the T-tubule) and one T-tubule comprise a triad—a “threesome” of membranes, with those of SR on two sides and the T-tubule sandwiched between them.[/caption]

The T-tubules carry the action potential into the interior of the cell, which triggers the opening of calcium channels in the membrane of the adjacent SR, causing Ca²⁺ to diffuse out of the SR and into the sarcoplasm. It is the arrival of Ca²⁺ in the sarcoplasm that initiates contraction of the muscle fiber by its contractile units, or sarcomeres.

10.3 Muscle Fiber Contraction and Relaxation

barkerj1 — Wed, 30 Aug 2017 18:38:15 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the physiology of muscle contraction, including the roles of the following components:
- Calcium (Ca²⁺) ions
- Troponin, tropomyosin, myosin, actin
- ATP
Describe the importance of the following in energy supply for muscles: cellular respiration, anaerobic cellular respiration, creatine phosphate, myoglobin
Describe the physiology of muscle relaxation
Describe paralysis

The sequence of events that result in the contraction of an individual muscle fiber begins with an electrical signal - an action potential - travelling down a motor neuron innervating the muscle fiber. This change in membrane potential causes calcium channels in the membrane of the neuron to open, allowing calcium ions (Ca²⁺) to diffuse into the neuron's cytosol. This influx of Ca²⁺ causes calcium-dependent vesicles in the neuron to fuse with its plasma membrane, releasing their contents - the neurotransmitter acetylcholine (ACh) - into the space between the neuron and the muscle fiber called the synaptic cleft.

When ACh reaches the muscle fiber's sarcolemma, it binds to closed ACh-gated ion channels there, that open as a result. In the area where these ion channels open, the sarcolemma of the muscle fiber will depolarize as positively charged sodium ions (Na⁺) enter, triggering an action potential that spreads to the rest of the sarcolemma. The whole sarcolemma will depolarize, including the T-tubules. Embedded in the wall of the T-tubules of skeletal muscle fibers are voltage-sensitive proteins that are connected to calcium channels in the membrane of the sarcoplasmic reticulum (SR). When the action potential travels along each T-tubule, the voltage-sensitive proteins there change shape, pulling on the calcium channels of the SR and opening them. This allows calcium ions (Ca²⁺) to be released from their storage in the SR, out to the cytosol of the muscle fiber. The Ca²⁺ then initiates contraction, which is sustained by ATP (Figure 1). As long as Ca²⁺ ions remain in the sarcoplasm to bind to troponin, which keeps the actin-binding sites “unshielded,” and as long as ATP is available to drive the cross-bridge cycling and the pulling of actin strands by myosin, the muscle fiber will continue to shorten to an anatomical limit.

[caption id="" align="aligncenter" width="400"] Figure 1. Contraction of a Muscle Fiber. A cross-bridge forms between actin and the myosin heads triggering contraction. As long as Ca++ ions remain in the sarcoplasm to bind to troponin, and as long as ATP is available, the muscle fiber will continue to shorten.[/caption]

Muscle contraction usually stops when signaling from the motor neuron ends, which repolarizes the sarcolemma and T-tubules, and closes the voltage-gated calcium channels in the SR. Ca⁺⁺ ions are then pumped back into the SR, which causes the tropomyosin to reshield (or re-cover) the binding sites on the actin strands. A muscle also can stop contracting when it runs out of ATP and becomes fatigued (Figure 2).

[caption id="" align="aligncenter" width="380"] Figure 2. Relaxation of a Muscle Fiber. Ca++ ions are pumped back into the SR, which causes the tropomyosin to reshield the binding sites on the actin strands. A muscle may also stop contracting when it runs out of ATP and becomes fatigued.[/caption]

[caption id="" align="aligncenter" width="120"] Watch this video to learn more about the role of calcium.[/caption]

The molecular events of muscle fiber shortening occur within the fiber’s sarcomeres (see Figure 3). The contraction of a striated muscle fiber occurs as the sarcomeres, linearly arranged within myofibrils, shorten as myosin heads pull on the actin filaments.

The region where thick and thin filaments overlap has a dense appearance, as there is little space between the filaments. This zone where thin and thick filaments overlap is very important to muscle contraction, as it is the site where filament movement starts. Thin filaments, anchored at their ends by the Z-discs, do not extend completely into the central region that only contains thick filaments, anchored at their bases at a spot called the M-line. A myofibril is composed of many sarcomeres running along its length; thus, myofibrils and muscle cells contract as the sarcomeres contract.

The Sliding Filament Model of Contraction

When signaled by a motor neuron, a skeletal muscle fiber contracts as the thin filaments are pulled and then slide past the thick filaments within the fiber’s sarcomeres. This process is known as the sliding filament model of muscle contraction (Figure 3). The sliding can only occur when myosin-binding sites on the actin filaments are exposed by a series of steps that begins with Ca⁺⁺ entry into the sarcoplasm.

[caption id="" align="aligncenter" width="450"] Figure 3. The Sliding Filament Model of Muscle Contraction. When a sarcomere contracts, the Z lines move closer together, and the I band becomes smaller. The A band stays the same width. At full contraction, the thin and thick filaments overlap.[/caption]

Tropomyosin is a protein that winds around the chains of the actin filament and covers the myosin-binding sites to prevent actin from binding to myosin. Tropomyosin binds to troponin to form a troponin-tropomyosin complex. The troponin-tropomyosin complex prevents the myosin “heads” from binding to the active sites on the actin microfilaments. Troponin also has a binding site for Ca⁺⁺ ions.

To initiate muscle contraction, tropomyosin has to expose the myosin-binding site on an actin filament to allow cross-bridge formation between the actin and myosin microfilaments. The first step in the process of contraction is for Ca⁺⁺ to bind to troponin so that tropomyosin can slide away from the binding sites on the actin strands. This allows the myosin heads to bind to these exposed binding sites and form cross-bridges. The thin filaments are then pulled by the myosin heads to slide past the thick filaments toward the center of the sarcomere. But each head can only pull a very short distance before it has reached its limit and must be “re-cocked” before it can pull again, a step that requires ATP.

ATP and Muscle Contraction

For thin filaments to continue to slide past thick filaments during muscle contraction, myosin heads must pull the actin at the binding sites, detach, re-cock, attach to more binding sites, pull, detach, re-cock, etc. This repeated movement is known as the cross-bridge cycle. This motion of the myosin heads is similar to the oars when an individual rows a boat: The paddle of the oars (the myosin heads) pull, are lifted from the water (detach), repositioned (re-cocked) and then immersed again to pull (Figure 4). Each cycle requires energy, and the action of the myosin heads in the sarcomeres repetitively pulling on the thin filaments also requires energy, which is provided by ATP.

[caption id="" align="aligncenter" width="450"] Figure 4. Skeletal Muscle Contraction. (a) The active site on actin is exposed as calcium binds to troponin. (b) The myosin head is attracted to actin, and myosin binds actin at its actin-binding site, forming the cross-bridge. (c) During the power stroke, the phosphate generated in the previous contraction cycle is released. This results in the myosin head pivoting toward the center of the sarcomere, after which the attached ADP and phosphate group are released. (d) A new molecule of ATP attaches to the myosin head, causing the cross-bridge to detach. (e) The myosin head hydrolyzes ATP to ADP and phosphate, which returns the myosin to the cocked position.[/caption]

Cross-bridge formation occurs when the myosin head attaches to the actin while adenosine diphosphate (ADP) and inorganic phosphate (P_i) are still bound to myosin (Figure 4a,b). P_i is then released, causing myosin to form a stronger attachment to the actin, after which the myosin head moves toward the M-line, pulling the actin along with it. As actin is pulled, the filaments move approximately 10 nm toward the M-line. This movement is called the power stroke, as movement of the thin filament occurs at this step (Figure 4c). In the absence of ATP, the myosin head will not detach from actin.

One part of the myosin head attaches to the binding site on the actin, but the head has another binding site for ATP. ATP binding causes the myosin head to detach from the actin (Figure 4d). After this occurs, ATP is converted to ADP and P_i by the intrinsic ATPase activity of myosin. The energy released during ATP hydrolysis changes the angle of the myosin head into a cocked position (Figure 4e). The myosin head is now in position for further movement.

When the myosin head is cocked, myosin is in a high-energy configuration. This energy is expended as the myosin head moves through the power stroke, and at the end of the power stroke, the myosin head is in a low-energy position. After the power stroke, ADP is released; however, the formed cross-bridge is still in place, and actin and myosin are bound together. As long as ATP is available, it readily attaches to myosin, the cross-bridge cycle can recur, and muscle contraction can continue.

Note that each thick filament of roughly 300 myosin molecules has multiple myosin heads, and many cross-bridges form and break continuously during muscle contraction. Multiply this by all of the sarcomeres in one myofibril, all the myofibrils in one muscle fiber, and all of the muscle fibers in one skeletal muscle, and you can understand why so much energy (ATP) is needed to keep skeletal muscles working. In fact, it is the loss of ATP that results in the rigor mortis observed soon after someone dies. With no further ATP production possible, there is no ATP available for myosin heads to detach from the actin-binding sites, so the cross-bridges stay in place, causing the rigidity in the skeletal muscles.

Sources of ATP

ATP supplies the energy for muscle contraction to take place. In addition to its direct role in the cross-bridge cycle, ATP also provides the energy for the active-transport Ca⁺⁺ pumps in the SR. Muscle contraction does not occur without sufficient amounts of ATP. The amount of ATP stored in muscle is very low, only sufficient to power a few seconds worth of contractions. As it is broken down, ATP must therefore be regenerated and replaced quickly to allow for sustained contraction. There are three mechanisms by which ATP can be regenerated: creatine phosphate metabolism, anaerobic glycolysis, fermentation and aerobic respiration.

Creatine phosphate is a molecule that can store energy in its phosphate bonds. In a resting muscle, excess ATP transfers its energy to creatine, producing ADP and creatine phosphate. This acts as an energy reserve that can be used to quickly create more ATP. When the muscle starts to contract and needs energy, creatine phosphate transfers its phosphate back to ADP to form ATP and creatine. This reaction is catalyzed by the enzyme creatine kinase and occurs very quickly; thus, creatine phosphate-derived ATP powers the first few seconds of muscle contraction. However, creatine phosphate can only provide approximately 15 seconds worth of energy, at which point another energy source has to be used (Figure 5).

[caption id="" align="aligncenter" width="430"] Figure 5. Muscle Metabolism. (a) Some ATP is stored in a resting muscle. As contraction starts, it is used up in seconds. More ATP is generated from creatine phosphate for about 15 seconds. (b) Each glucose molecule produces two ATP and two molecules of pyruvic acid, which can be used in aerobic respiration or converted to lactic acid. If oxygen is not available, pyruvic acid is converted to lactic acid, which may contribute to muscle fatigue. This occurs during strenuous exercise when high amounts of energy are needed but oxygen cannot be sufficiently delivered to muscle. (c) Aerobic respiration is the breakdown of glucose in the presence of oxygen (O2) to produce carbon dioxide, water, and ATP. Approximately 95 percent of the ATP required for resting or moderately active muscles is provided by aerobic respiration, which takes place in mitochondria.[/caption]

As the ATP produced by creatine phosphate is depleted, muscles turn to glycolysis as an ATP source. Glycolysis is an anaerobic (non-oxygen-dependent) process that breaks down glucose (sugar) to produce ATP; however, glycolysis cannot generate ATP as quickly as creatine phosphate. Thus, the switch to glycolysis results in a slower rate of ATP availability to the muscle. The sugar used in glycolysis can be provided by blood glucose or by metabolizing glycogen that is stored in the muscle. The breakdown of one glucose molecule produces two ATP and two molecules of pyruvic acid, which can be used in aerobic respiration or when oxygen levels are low, converted to lactic acid (Figure 5b).

If oxygen is available, pyruvic acid is used in aerobic respiration. However, if oxygen is not available, pyruvic acid is converted to lactic acid, which may contribute to muscle fatigue. This conversion allows the recycling of the enzyme NAD⁺ from NADH, which is needed for glycolysis to continue. This occurs during strenuous exercise when high amounts of energy are needed but oxygen cannot be sufficiently delivered to muscle. Glycolysis itself cannot be sustained for very long (approximately 1 minute of muscle activity), but it is useful in facilitating short bursts of high-intensity output. This is because glycolysis does not utilize glucose very efficiently, producing a net gain of two ATPs per molecule of glucose, and the end product of lactic acid, which may contribute to muscle fatigue as it accumulates.

Aerobic respiration is the breakdown of glucose or other nutrients in the presence of oxygen (O₂) to produce carbon dioxide, water, and ATP. Approximately 95 percent of the ATP required for resting or moderately active muscles is provided by aerobic respiration, which takes place in mitochondria. The inputs for aerobic respiration include glucose circulating in the bloodstream, pyruvic acid, and fatty acids. Aerobic respiration is much more efficient than anaerobic glycolysis, producing approximately 36 ATPs per molecule of glucose versus four from glycolysis. However, aerobic respiration cannot be sustained without a steady supply of O₂ to the skeletal muscle and is much slower (Figure 5c). To compensate, muscles store small amount of excess oxygen in proteins call myoglobin, allowing for more efficient muscle contractions and less fatigue. Aerobic training also increases the efficiency of the circulatory system so that O₂ can be supplied to the muscles for longer periods of time.

Muscle fatigue occurs when a muscle can no longer contract in response to signals from the nervous system. The exact causes of muscle fatigue are not fully known, although certain factors have been correlated with the decreased muscle contraction that occurs during fatigue. ATP is needed for normal muscle contraction, and as ATP reserves are reduced, muscle function may decline. This may be more of a factor in brief, intense muscle output rather than sustained, lower intensity efforts. Lactic acid buildup may lower intracellular pH, affecting enzyme and protein activity. Imbalances in Na⁺ and K⁺ levels as a result of membrane depolarization may disrupt Ca⁺⁺ flow out of the SR. Long periods of sustained exercise may damage the SR and the sarcolemma, resulting in impaired Ca⁺⁺ regulation.

Intense muscle activity results in an oxygen debt, which is the amount of oxygen needed to compensate for ATP produced without oxygen during muscle contraction. Oxygen is required to restore ATP and creatine phosphate levels, convert lactic acid to pyruvic acid, and, in the liver, to convert lactic acid into glucose or glycogen. Other systems used during exercise also require oxygen, and all of these combined processes result in the increased breathing rate that occurs after exercise. Until the oxygen debt has been met, oxygen intake is elevated, even after exercise has stopped.

Relaxation of a Skeletal Muscle

Relaxing skeletal muscle fibers, and ultimately, the skeletal muscle, begins with the motor neuron, which stops releasing its chemical signal, ACh, into the synapse at the NMJ. The muscle fiber will repolarize, which closes the gates in the SR where Ca⁺⁺ was being released. ATP-driven pumps will move Ca⁺⁺ out of the sarcoplasm back into the SR. This results in the “reshielding” of the actin-binding sites on the thin filaments. Without the ability to form cross-bridges between the thin and thick filaments, the muscle fiber loses its tension and relaxes.

Muscle Strength

The number of skeletal muscle fibers in a given muscle is genetically determined and does not change. Muscle strength is directly related to the amount of myofibrils and sarcomeres within each fiber. Factors, such as hormones and stress (and artificial anabolic steroids), acting on the muscle can increase the production of sarcomeres and myofibrils within the muscle fibers, a change called hypertrophy, which results in the increased mass and bulk in a skeletal muscle. Likewise, decreased use of a skeletal muscle results in atrophy, where the number of sarcomeres and myofibrils disappear (but not the number of muscle fibers). It is common for a limb in a cast to show atrophied muscles when the cast is removed, and certain diseases, such as polio, show atrophied muscles.

Disorders of the Muscular System

Duchenne muscular dystrophy (DMD) is a progressive weakening of the skeletal muscles. It is one of several diseases collectively referred to as “muscular dystrophy.” DMD is caused by a lack of the protein dystrophin, which helps the thin filaments of myofibrils bind to the sarcolemma. Without sufficient dystrophin, muscle contractions cause the sarcolemma to tear, causing an influx of Ca⁺⁺, leading to cellular damage and muscle fiber degradation. Over time, as muscle damage accumulates, muscle mass is lost, and greater functional impairments develop.

DMD is an inherited disorder caused by an abnormal X chromosome. It primarily affects males, and it is usually diagnosed in early childhood. DMD usually first appears as difficulty with balance and motion, and then progresses to an inability to walk. It continues progressing upward in the body from the lower extremities to the upper body, where it affects the muscles responsible for breathing and circulation. It ultimately causes death due to respiratory failure, and those afflicted do not usually live past their 20s.

Because DMD is caused by a mutation in the gene that codes for dystrophin, it was thought that introducing healthy myoblasts into patients might be an effective treatment. Myoblasts are the embryonic cells responsible for muscle development, and ideally, they would carry healthy genes that could produce the dystrophin needed for normal muscle contraction. This approach has been largely unsuccessful in humans. A recent approach has involved attempting to boost the muscle’s production of utrophin, a protein similar to dystrophin that may be able to assume the role of dystrophin and prevent cellular damage from occurring.

10.4 Nervous System Control of Muscle Tension

barkerj1 — Wed, 30 Aug 2017 18:38:15 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe muscle tone

To move an object, referred to as load, the sarcomeres in the muscle fibers of the skeletal muscle must shorten. The force generated by the contraction of the muscle (or shortening of the sarcomeres) is called muscle tension. However, muscle tension also is generated when the muscle is contracting against a load that does not move, resulting in two main types of skeletal muscle contractions: isotonic contractions and isometric contractions.

In isotonic contractions, where the tension in the muscle stays constant, a load is moved as the length of the muscle changes (shortens). There are two types of isotonic contractions: concentric and eccentric. A concentric contraction involves the muscle shortening to move a load. An example of this is the biceps brachii muscle contracting when a hand weight is brought upward with increasing muscle tension. As the biceps brachii contract, the angle of the elbow joint decreases as the forearm is brought toward the body. Here, the biceps brachii contracts as sarcomeres in its muscle fibers are shortening and cross-bridges form; the myosin heads pull the actin. An eccentric contraction occurs as the muscle tension diminishes and the muscle lengthens. In this case, the hand weight is lowered in a slow and controlled manner as the amount of cross-bridges being activated by nervous system stimulation decreases. In this case, as tension is released from the biceps brachii, the angle of the elbow joint increases. Eccentric contractions are also used for movement and balance of the body.

An isometric contraction occurs as the muscle produces tension without changing the angle of a skeletal joint. Isometric contractions involve sarcomere shortening and increasing muscle tension, but do not move a load, as the force produced cannot overcome the resistance provided by the load. For example, if one attempts to lift a hand weight that is too heavy, there will be sarcomere activation and shortening to a point, and ever-increasing muscle tension, but no change in the angle of the elbow joint. In everyday living, isometric contractions are active in maintaining posture and maintaining bone and joint stability. However, holding your head in an upright position occurs not because the muscles cannot move the head, but because the goal is to remain stationary and not produce movement. Most actions of the body are the result of a combination of isotonic and isometric contractions working together to produce a wide range of outcomes (Figure 1).

[caption id="" align="aligncenter" width="390"] Figure 1. Types of Muscle Contractions. During isotonic contractions, muscle length changes to move a load. During isometric contractions, muscle length does not change because the load exceeds the tension the muscle can generate.[/caption]

All of these muscle activities are under the exquisite control of the nervous system. Neural control regulates concentric, eccentric and isometric contractions, muscle fiber recruitment, and muscle tone. A crucial aspect of nervous system control of skeletal muscles is the role of motor units.

Motor Units

As you have learned, every skeletal muscle fiber must be innervated by the axon terminal of a motor neuron in order to contract. Each muscle fiber is innervated by only one motor neuron. The actual group of muscle fibers in a muscle innervated by a single motor neuron is called a motor unit. The size of a motor unit is variable depending on the nature of the muscle.

A small motor unit is an arrangement where a single motor neuron supplies a small number of muscle fibers in a muscle. Small motor units permit very fine motor control of the muscle. The best example in humans is the small motor units of the extraocular eye muscles that move the eyeballs. There are thousands of muscle fibers in each muscle, but every six or so fibers are supplied by a single motor neuron, as the axons branch to form synaptic connections at their individual NMJs. This allows for exquisite control of eye movements so that both eyes can quickly focus on the same object. Small motor units are also involved in the many fine movements of the fingers and thumb of the hand for grasping, texting, etc.

A large motor unit is an arrangement where a single motor neuron supplies a large number of muscle fibers in a muscle. Large motor units are concerned with simple, or “gross,” movements, such as powerfully extending the knee joint. The best example is the large motor units of the thigh muscles or back muscles, where a single motor neuron will supply thousands of muscle fibers in a muscle, as its axon splits into thousands of branches.

There is a wide range of motor units within many skeletal muscles, which gives the nervous system a wide range of control over the muscle. The small motor units in the muscle will have smaller, lower-threshold motor neurons that are more excitable, firing first to their skeletal muscle fibers, which also tend to be the smallest. Activation of these smaller motor units, results in a relatively small degree of contractile strength (tension) generated in the muscle. As more strength is needed, larger motor units, with bigger, higher-threshold motor neurons are enlisted to activate larger muscle fibers. This increasing activation of motor units produces an increase in muscle contraction known as recruitment. As more motor units are recruited, the muscle contraction grows progressively stronger. In some muscles, the largest motor units may generate a contractile force of 50 times more than the smallest motor units in the muscle. This allows a feather to be picked up using the biceps brachii arm muscle with minimal force, and a heavy weight to be lifted by the same muscle by recruiting the largest motor units.

When necessary, the maximal number of motor units in a muscle can be recruited simultaneously, producing the maximum force of contraction for that muscle, but this cannot last for very long because of the energy requirements to sustain the contraction. To prevent complete muscle fatigue, motor units are generally not all simultaneously active, but instead some motor units rest while others are active, which allows for longer muscle contractions. The nervous system uses recruitment as a mechanism to efficiently utilize a skeletal muscle.

The Length-Tension Range of a Sarcomere

When a skeletal muscle fiber contracts, myosin heads attach to actin to form cross-bridges followed by the thin filaments sliding over the thick filaments as the heads pull the actin, and this results in sarcomere shortening, creating the tension of the muscle contraction. The cross-bridges can only form where thin and thick filaments already overlap, so that the length of the sarcomere has a direct influence on the force generated when the sarcomere shortens. This is called the length-tension relationship.

The ideal length of a sarcomere to produce maximal tension occurs at 80 percent to 120 percent of its resting length, with 100 percent being the state where the medial edges of the thin filaments are just at the most-medial myosin heads of the thick filaments (Figure 2). This length maximizes the overlap of actin-binding sites and myosin heads. If a sarcomere is stretched past this ideal length (beyond 120 percent), thick and thin filaments do not overlap sufficiently, which results in less tension produced. If a sarcomere is shortened beyond 80 percent, the zone of overlap is reduced with the thin filaments jutting beyond the last of the myosin heads and shrinks the H zone, which is normally composed of myosin tails. Eventually, there is nowhere else for the thin filaments to go and the amount of tension is diminished. If the muscle is stretched to the point where thick and thin filaments do not overlap at all, no cross-bridges can be formed, and no tension is produced in that sarcomere. This amount of stretching does not usually occur, as accessory proteins and connective tissue oppose extreme stretching.

[caption id="" align="aligncenter" width="380"] Figure 2. The Ideal Length of a Sarcomere. Sarcomeres produce maximal tension when thick and thin filaments overlap between about 80 percent to 120 percent.[/caption]

Muscle Tone

Skeletal muscles are rarely completely relaxed, or flaccid. Even if a muscle is not producing movement, it is contracted a small amount to maintain its contractile proteins and produce muscle tone. The tension produced by muscle tone allows muscles to continually stabilize joints and maintain posture.

Muscle tone is accomplished by a complex interaction between the nervous system and skeletal muscles that results in the activation of a few motor units at a time, most likely in a cyclical manner. In this manner, muscles never fatigue completely, as some motor units can recover while others are active.

The absence of the low-level contractions that lead to muscle tone is referred to as hypotonia or atrophy, and can result from damage to parts of the central nervous system (CNS), such as the cerebellum, or from loss of innervations to a skeletal muscle, as in poliomyelitis. Hypotonic muscles have a flaccid appearance and display functional impairments, such as weak reflexes. Conversely, excessive muscle tone is referred to as hypertonia, accompanied by hyperreflexia (excessive reflex responses), often the result of damage to upper motor neurons in the CNS. Hypertonia can present with muscle rigidity (as seen in Parkinson’s disease) or spasticity, a phasic change in muscle tone, where a limb will “snap” back from passive stretching (as seen in some strokes).

10.6 Exercise and Muscle Performance

barkerj1 — Wed, 30 Aug 2017 18:38:16 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe muscular hypertrophy, muscular atrophy, and muscular dystrophy

Physical training alters the appearance of skeletal muscles and can produce changes in muscle performance. Conversely, a lack of use can result in decreased performance and muscle appearance. Although muscle cells can change in size, new cells are not formed when muscles grow. Instead, structural proteins are added to muscle fibers in a process called hypertrophy, so cell diameter increases. The reverse, when structural proteins are lost and muscle mass decreases, is called atrophy. Age-related muscle atrophy is called sarcopenia. Cellular components of muscles can also undergo changes in response to changes in muscle use.

Endurance Exercise

Slow fibers are predominantly used in endurance exercises that require little force but involve numerous repetitions. The aerobic metabolism used by slow-twitch fibers allows them to maintain contractions over long periods. Endurance training modifies these slow fibers to make them even more efficient by producing more mitochondria to enable more aerobic metabolism and more ATP production. Endurance exercise can also increase the amount of myoglobin in a cell, as increased aerobic respiration increases the need for oxygen. Myoglobin is found in the sarcoplasm and acts as an oxygen storage supply for the mitochondria.

The training can trigger the formation of more extensive capillary networks around the fiber, a process called angiogenesis, to supply oxygen and remove metabolic waste. To allow these capillary networks to supply the deep portions of the muscle, muscle mass does not greatly increase in order to maintain a smaller area for the diffusion of nutrients and gases. All of these cellular changes result in the ability to sustain low levels of muscle contractions for greater periods without fatiguing.

The proportion of SO muscle fibers in muscle determines the suitability of that muscle for endurance, and may benefit those participating in endurance activities. Postural muscles have a large number of SO fibers and relatively few FO and FG fibers, to keep the back straight (Figure 1). Endurance athletes, like marathon-runners also would benefit from a larger proportion of SO fibers, but it is unclear if the most-successful marathoners are those with naturally high numbers of SO fibers, or whether the most successful marathon runners develop high numbers of SO fibers with repetitive training. Endurance training can result in overuse injuries such as stress fractures and joint and tendon inflammation.

[caption id="" align="aligncenter" width="380"] Figure 1. Marathoners. Long-distance runners have a large number of SO fibers and relatively few FO and FG fibers. (credit: “Tseo2”/Wikimedia Commons)[/caption]

Resistance Exercise

Resistance exercises, as opposed to endurance exercise, require large amounts of FG fibers to produce short, powerful movements that are not repeated over long periods. The high rates of ATP hydrolysis and cross-bridge formation in FG fibers result in powerful muscle contractions. Muscles used for power have a higher ratio of FG to SO/FO fibers, and trained athletes possess even higher levels of FG fibers in their muscles. Resistance exercise affects muscles by increasing the formation of myofibrils, thereby increasing the thickness of muscle fibers. This added structure causes hypertrophy, or the enlargement of muscles, exemplified by the large skeletal muscles seen in body builders and other athletes (Figure 2). Because this muscular enlargement is achieved by the addition of structural proteins, athletes trying to build muscle mass often ingest large amounts of protein.

[caption id="" align="aligncenter" width="350"] Figure 2. Hypertrophy. Body builders have a large number of FG fibers and relatively few FO and SO fibers. (credit: Lin Mei/flickr)[/caption]

Except for the hypertrophy that follows an increase in the number of sarcomeres and myofibrils in a skeletal muscle, the cellular changes observed during endurance training do not usually occur with resistance training. There is usually no significant increase in mitochondria or capillary density. However, resistance training does increase the development of connective tissue, which adds to the overall mass of the muscle and helps to contain muscles as they produce increasingly powerful contractions. Tendons also become stronger to prevent tendon damage, as the force produced by muscles is transferred to tendons that attach the muscle to bone.

For effective strength training, the intensity of the exercise must continually be increased. For instance, continued weight lifting without increasing the weight of the load does not increase muscle size. To produce ever-greater results, the weights lifted must become increasingly heavier, making it more difficult for muscles to move the load. The muscle then adapts to this heavier load, and an even heavier load must be used if even greater muscle mass is desired.

If done improperly, resistance training can lead to overuse injuries of the muscle, tendon, or bone. These injuries can occur if the load is too heavy or if the muscles are not given sufficient time between workouts to recover or if joints are not aligned properly during the exercises. Cellular damage to muscle fibers that occurs after intense exercise includes damage to the sarcolemma and myofibrils. This muscle damage contributes to the feeling of soreness after strenuous exercise, but muscles gain mass as this damage is repaired, and additional structural proteins are added to replace the damaged ones. Overworking skeletal muscles can also lead to tendon damage and even skeletal damage if the load is too great for the muscles to bear.

Performance-Enhancing Substances

Some athletes attempt to boost their performance by using various agents that may enhance muscle performance. Anabolic steroids are one of the more widely known agents used to boost muscle mass and increase power output. Anabolic steroids are a form of testosterone, a male sex hormone that stimulates muscle formation, leading to increased muscle mass.

Endurance athletes may also try to boost the availability of oxygen to muscles to increase aerobic respiration by using substances such as erythropoietin (EPO), a hormone normally produced in the kidneys, which triggers the production of red blood cells. The extra oxygen carried by these blood cells can then be used by muscles for aerobic respiration. Human growth hormone (hGH) is another supplement, and although it can facilitate building muscle mass, its main role is to promote the healing of muscle and other tissues after strenuous exercise. Increased hGH may allow for faster recovery after muscle damage, reducing the rest required after exercise, and allowing for more sustained high-level performance.

Although performance-enhancing substances often do improve performance, most are banned by governing bodies in sports and are illegal for nonmedical purposes. Their use to enhance performance raises ethical issues of cheating because they give users an unfair advantage over nonusers. A greater concern, however, is that their use carries serious health risks. The side effects of these substances are often significant, nonreversible, and in some cases fatal. The physiological strain caused by these substances is often greater than what the body can handle, leading to effects that are unpredictable and dangerous. Anabolic steroid use has been linked to infertility, aggressive behavior, cardiovascular disease, and brain cancer.

Similarly, some athletes have used creatine to increase power output. Creatine phosphate provides quick bursts of ATP to muscles in the initial stages of contraction. Increasing the amount of creatine available to cells is thought to produce more ATP and therefore increase explosive power output, although its effectiveness as a supplement has been questioned.

Muscle Atrophy

Although atrophy due to disuse can often be reversed with exercise, muscle atrophy can also be the result of any of a number of genetic diseases, called muscular dystrophy, that result in increasing weakness of muscles and loss of muscle tissue over time. Although there are medications that can slow muscle degeneration and reduce damage to dying muscle cells, the atrophy due to muscular dystrophy is irreversible. Muscle atrophy with age, referred to as sarcopenia, is also irreversible. This is a primary reason why even highly trained athletes succumb to declining performance with age. This decline is noticeable in athletes whose sports require strength and powerful movements, such as sprinting, whereas the effects of age are less noticeable in endurance athletes such as marathon runners or long-distance cyclists. As muscles age, muscle fibers die, and they are replaced by connective tissue and adipose tissue (Figure 3). Because those tissues cannot contract and generate force as muscle can, muscles lose the ability to produce powerful contractions. The decline in muscle mass causes a loss of strength, including the strength required for posture and mobility. This may be caused by a reduction in FG fibers that hydrolyze ATP quickly to produce short, powerful contractions. Muscles in older people sometimes possess greater numbers of SO fibers, which are responsible for longer contractions and do not produce powerful movements. There may also be a reduction in the size of motor units, resulting in fewer fibers being stimulated and less muscle tension being produced.

[caption id="" align="aligncenter" width="325"] Figure 3. Atrophy. Muscle mass is reduced as muscles atrophy with disuse.[/caption]

Sarcopenia can be delayed to some extent by exercise, as training adds structural proteins and causes cellular changes that can offset the effects of atrophy. Increased exercise can produce greater numbers of cellular mitochondria, increase capillary density, and increase the mass and strength of connective tissue. The effects of age-related atrophy are especially pronounced in people who are sedentary, as the loss of muscle cells is displayed as functional impairments such as trouble with locomotion, balance, and posture. This can lead to a decrease in quality of life and medical problems, such as joint problems because the muscles that stabilize bones and joints are weakened. Problems with locomotion and balance can also cause various injuries due to falls.

Introduction

barkerj1 — Wed, 30 Aug 2017 18:38:17 +0000

[caption id="" align="aligncenter" width="500"] Figure 1. A Body in Motion. The muscular system allows us to move, flex and contort our bodies. Practicing yoga, as pictured here, is a good example of the voluntary use of the muscular system. (credit: Dmitry Yanchylenko)[/caption]

Think about the things that you do each day—talking, walking, sitting, standing, and running—all of these activities require movement of particular skeletal muscles. Skeletal muscles are even used during sleep. The diaphragm is a sheet of skeletal muscle that has to contract and relax for you to breathe day and night. If you recall from your study of the skeletal system and joints, body movement occurs around the joints in the body. The focus of this chapter is on skeletal muscle organization. The system to name skeletal muscles will be explained; in some cases, the muscle is named by its shape, and in other cases it is named by its location or attachments to the skeleton. If you understand the meaning of the name of the muscle, often it will help you remember its location and/or what it does. This chapter also will describe how skeletal muscles are arranged to accomplish movement, and how other muscles may assist, or be arranged on the skeleton to resist or carry out the opposite movement. The actions of the skeletal muscles will be covered in a regional manner, working from the head down to the toes.

11.1 Interactions of Skeletal Muscles, Their Fascicle Arrangement, and Their Lever Systems

barkerj1 — Wed, 30 Aug 2017 18:38:19 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe how muscles are attached to bones to produce movement
Explain how the location of the insertion and origin of a muscle determine the type of movement accomplished by contraction of that muscle
Describe the principle of muscular antagonism in movement, using the forearm as an example
Explain how synergists influence the type of movement accomplished by contraction of a muscle
Define the following terms: level, fulcrum, resistance, effort
Describe three kinds of levers and give an example of each type in the human body
Calculate the force that has to be exerted by the biceps brachii to maintain the forearm in equilibrium when the hand is holding a mass of 10 kilograms
Describe one mechanical disadvantage and two advantages of the insertion of the biceps brachii being near the elbow joint

To move the skeleton, the tension created by the contraction of the fibers in most skeletal muscles is transferred to the tendons. The tendons are strong bands of dense, regular connective tissue that connect muscles to bones. The bone connection is why this muscle tissue is called skeletal muscle.

Interactions of Skeletal Muscles in the Body

To pull on a bone, that is, to change the angle at its synovial joint, which essentially moves the skeleton, a skeletal muscle must also be attached to a fixed part of the skeleton. The moveable end of the muscle that attaches to the bone being pulled is called the muscle’s insertion, and the end of the muscle attached to a fixed (stabilized) bone is called the origin. During forearm flexion—bending the elbow—the brachioradialis assists the brachialis.

Although a number of muscles may be involved in an action, the principal muscle involved is called the prime mover, or agonist. To lift a cup, a muscle called the biceps brachii is actually the prime mover; however, because it can be assisted by the brachialis, the brachialis is called a synergist in this action (Figure 1). A synergist can also be a fixator that stabilizes the bone that is the attachment for the prime mover’s origin.

[caption id="" align="aligncenter" width="420"] Figure 1. Prime Movers and Synergists. The biceps brachii flex the lower arm. The brachoradialis, in the forearm, and brachialis, located deep to the biceps in the upper arm, are both synergists that aid in this motion.[/caption]

A muscle with the opposite action of the prime mover is called an antagonist. Antagonists play two important roles in muscle function: (1) they maintain body or limb position, such as holding the arm out or standing erect; and (2) they control rapid movement, as in shadow boxing without landing a punch or the ability to check the motion of a limb.

For example, to extend the knee, a group of four muscles called the quadriceps femoris in the anterior compartment of the thigh are activated (and would be called the agonists of knee extension). However, to flex the knee joint, an opposite or antagonistic set of muscles called the hamstrings is activated.

As you can see, these terms would also be reversed for the opposing action. If you consider the first action as the knee bending, the hamstrings would be called the agonists and the quadriceps femoris would then be called the antagonists. See Table 1 for a list of some agonists and antagonists.

Agonist and Antagonist Skeletal Muscle Pairs (Table 1)
Agonist	Antagonist	Movement
Biceps brachii: in the anterior compartment of the arm	Triceps brachii: in the posterior compartment of the arm	The biceps brachii flexes the forearm, whereas the triceps brachii extends it.
Hamstrings: group of three muscles in the posterior compartment of the thigh	Quadriceps femoris: group of four muscles in the anterior compartment of the thigh	The hamstrings flex the leg, whereas the quadriceps femoris extend it.
Flexor digitorum superficialis and flexor digitorum profundus: in the anterior compartment of the forearm	Extensor digitorum: in the posterior compartment of the forearm	The flexor digitorum superficialis and flexor digitorum profundus flex the fingers and the hand at the wrist, whereas the extensor digitorum extends the fingers and the hand at the wrist.

There are also skeletal muscles that do not pull against the skeleton for movements. For example, there are the muscles that produce facial expressions. The insertions and origins of facial muscles are in the skin, so that certain individual muscles contract to form a smile or frown, form sounds or words, and raise the eyebrows. There also are skeletal muscles in the tongue, and the external urinary and anal sphincters that allow for voluntary regulation of urination and defecation, respectively. In addition, the diaphragm contracts and relaxes to change the volume of the pleural cavities but it does not move the skeleton to do this.

The Lever System of Muscle and Bone Interactions

Skeletal muscles do not work by themselves. Muscles are arranged in pairs based on their functions. For muscles attached to the bones of the skeleton, the connection determines the force, speed, and range of movement. These characteristics depend on each other and can explain the general organization of the muscular and skeletal systems.

The skeleton and muscles act together to move the body. Have you ever used the back of a hammer to remove a nail from wood? The handle acts as a lever and the head of the hammer acts as a fulcrum, the fixed point that the force is applied to when you pull back or push down on the handle. The effort applied to this system is the pulling or pushing on the handle to remove the nail, which is the load, or “resistance” to the movement of the handle in the system. Our musculoskeletal system works in a similar manner, with bones being stiff levers and the articular endings of the bones—encased in synovial joints—acting as fulcrums. The load would be an object being lifted or any resistance to a movement (your head is a load when you are lifting it), and the effort, or applied force, comes from contracting skeletal muscle.

There are several types of lever systems in the body that are identified as either first-class, second-class, or third-class levers. When classifying a lever system in the human body, the "load" is located at the center of mass of the limb or structure being moved. The "effort" is applied by a muscle (or group of muscles), but its location is not the belly of the muscle being contracted; instead, it is located at the point where the muscle inserts on the structure being moved. First-class levers are the most simple types of lever, where the balance depends on the distance between the effort and the load from the fulcrum, and the size of the load. In the body the best example of this is the way your head is raised off your chest. As shown in Figure 3 the posterior neck muscles act as the effort, the facial skeleton is the load, and the atlanto-occipital joint behaves as the fulcrum. [caption id="" align="alignnone" width="648"] Figure 2. First class lever.[/caption] [caption id="" align="alignnone" width="615"] Figure 3. First class lever as seen in the body. (credit: sarahmckinnon/flickr.com, original image: celtibere/pixabay.com)[/caption] Second-class levers are levers where the load is applied between the effort and the fulcrum. The effort is closer to the load than the fulcrum, which allows a large load to be moved by a small amount of effort. However this means that the load will be moved at a slower pace, and can only be moved a short distance. Any time you stand up on your toes as shown in Figure 5, you are using a second class lever. The weight of your body acts as the load, your calf muscles are the effort, and the joints in the balls of your feet act as fulcrums. [embed]https://www.flickr.com/photos/144136128@N02/29327887125/[/embed] [caption id="" align="alignnone" width="682"] Figure 5. Second class lever. (credit: sarahmckinnon/flickr.com, original image: thenarratographer/flickr.com)[/caption] Third Class levers are the most common type of levers in your body. The effort is applied between the fulcrum and the load, which allows the load to be moved quickly over large distances. When you lift your hand by flexing your bicep you are using a third class lever. The Elbow joint acts as the fulcrum, the insertion of the biceps brachii becomes the effort, and the weight of your hand is the load being lifted (Figure 3). [caption id="" align="alignnone" width="647"] Figure 6. Third class Lever.[/caption] [caption id="" align="alignnone" width="621"] Figure 7. Third class lever. (credit: sarahmckinnon/flickr.com)[/caption]

11.2 Naming Skeletal Muscles

barkerj1 — Wed, 30 Aug 2017 18:38:21 +0000

Learning Objectives

By the end of this section, you will be able to:

Specify some of the criteria used in the naming of muscles

The Greeks and Romans conducted the first studies done on the human body in Western culture. The educated class of subsequent societies studied Latin and Greek, and therefore the early pioneers of anatomy continued to apply Latin and Greek terminology or roots when they named the skeletal muscles. The large number of muscles in the body and unfamiliar words can make learning the names of the muscles in the body seem daunting, but understanding the etymology can help. Etymology is the study of how the root of a particular word entered a language and how the use of the word evolved over time. Taking the time to learn the root of the words is crucial to understanding the vocabulary of anatomy and physiology. When you understand the names of muscles it will help you remember where the muscles are located and what they do (Figure 1, Figure 2, and Table 2). Pronunciation of words and terms will take a bit of time to master, but after you have some basic information; the correct names and pronunciations will become easier.

[caption id="" align="aligncenter" width="380"] Figure 1. Overview of the Muscular System. On the anterior and posterior views of the muscular system above, superficial muscles (those at the surface) are shown on the right side of the body while deep muscles (those underneath the superficial muscles) are shown on the left half of the body. For the legs, superficial muscles are shown in the anterior view while the posterior view shows both superficial and deep muscles.[/caption]

[caption id="" align="aligncenter" width="520"] Figure 2. Understanding a Muscle Name from the Latin[/caption]

Mnemonic Device for Latin Roots (Table 2)
Example	Latin or Greek Translation	Mnemonic Device
ad	to; toward	ADvance toward your goal
ab	away from	n/a
sub	under	SUBmarines move under water.
ductor	something that moves	A conDUCTOR makes a train move.
anti	against	If you are antisocial, you are against engaging in social activities.
epi	on top of	n/a
apo	to the side of	n/a
longissimus	longest	“Longissimus” is longer than the word “long.”
longus	long	long
brevis	short	brief
maximus	large	max
medius	medium	“Medius” and “medium” both begin with “med.”
minimus	tiny; little	mini
rectus	straight	To RECTify a situation is to straighten it out.
multi	many	If something is MULTIcolored, it has many colors.
uni	one	A UNIcorn has one horn.
bi/di	two	If a ring is DIcast, it is made of two metals.
tri	three	TRIple the amount of money is three times as much.
quad	four	QUADruplets are four children born at one birth.
externus	outside	EXternal
internus	inside	INternal

Anatomists name the skeletal muscles according to a number of criteria, each of which describes the muscle in some way. These include naming the muscle after its shape, the direction of its muscle fibers, its size compared to other muscles in the area, its location in the body or the location of its attachments to the skeleton, how many origins it has, or its action. Often, a muscle's name will refer to several of these characteristics.

The shapes of some muscles are very distinctive and the names, such as orbicularis for "orbit" or deltoid for the Greek letter delta (which looks like a triangle), reflect their shape. The direction of the muscle fibers and fascicles of a muscle can be used to name muscles by describing their orientation relative to the longitudinal axis of the body or of a limb, such as the rectus (straight) abdominis, or the oblique (at an angle) muscles of the abdomen, or the rectus femoris. For the buttocks, the size of the muscles influences the names: gluteus maximus (largest), gluteus medius (medium), and the gluteus minimus (smallest). Names are also given to muscles that indicate length—brevis (short), or longus (long). Some muscle names are used indicate the number of muscles in a group. One example of this is the quadriceps, a group of four muscles located on the anterior (front) thigh. The skeletal muscle’s anatomical location or its relationship to a particular bone often determines its name. For example, the frontalis muscle is located on top of the frontal bone of the skull, and the rectus femoris is located along the femur. Some muscles are named after their position relative to the midline: lateralis appears in the names of muscles located away from the midline, and medialis for muscles closer to the midline.

The location of a muscle’s attachment can also appear in its name. When the name of a muscle is based on the attachments, the origin is always named first. For instance, the sternocleidomastoid muscle of the neck has a dual origin on the sternum ("sterno") and clavicle ("cleido"), and inserts on the mastoid process of the temporal bone. Other muscle names can provide information as to how many origins a particular muscle has, such as the biceps brachii. The prefix bi indicates that the muscle has two origins, and tri indicates three origins.

The last feature by which to name a muscle is its action. When muscles are named for the movement they produce, one can find action words in their name. Some examples are flexor (decreases the angle at the joint), extensor (increases the angle at the joint), abductor (moves the bone away from the midline), or adductor (moves the bone toward the midline).

11.3 Axial Muscles of the Head, Neck, and Back

barkerj1 — Wed, 30 Aug 2017 18:38:24 +0000

Learning Objectives

By the end of this section, you will be able to:

The skeletal muscles are divided into axial (muscles of the trunk and head) and appendicular (muscles of the arms and legs) categories. This system reflects the bones of the skeleton system, which are also arranged in this manner. The axial muscles are grouped based on location, function, or both. Some of the axial muscles may seem to blur the boundaries because they cross over to the appendicular skeleton. The first grouping of the axial muscles you will review includes the muscles of the head and neck, then you will review the muscles of the vertebral column, and finally you will review the oblique and rectus muscles.

Muscles That Move the Head

The head, attached to the top of the vertebral column, is balanced, moved, and rotated by the neck muscles (Table 5). When these muscles act unilaterally, the head rotates. When they contract bilaterally, the head flexes or extends. The major muscle that laterally flexes and rotates the head is the sternocleidomastoid. In addition, both muscles working together are the flexors of the head. Place your fingers on both sides of the neck and turn your head to the left and to the right. You will feel the movement originate there. This muscle divides the neck into anterior and posterior triangles when viewed from the side (Figure 8).

[caption id="" align="aligncenter" width="655"] Figure 8. Posterior and Lateral Views of the Neck. The superficial and deep muscles of the neck are responsible for moving the head, cervical vertebrae, and scapulas.[/caption]

Muscles That Move the Head (Table 5)
Movement	Target	Target motion direction	Prime mover	Origin	Insertion
Rotates and tilts head to the side; tilts head forward	Skull; vertebrae	Individually: rotates head to opposite side; bilaterally: flexion	Sternocleidomastoid	Sternum; clavicle	Temporal bone (mastoid process); occipital bone
Rotates and tilts head backward	Skull; vertebrae	Individually: laterally flexes and rotates head to same side; bilaterally: extension	Semispinalis capitis	Transverse and articular processes of cervical and thoracic vertebra	Occipital bone
Rotates and tilts head to the side; tilts head backward	Skull; vertebrae	Individually: laterally flexes and rotates head to same side; bilaterally: extension	Splenius capitis	Spinous processes of cervical and thoracic vertebra	Temporal bone (mastoid process); occipital bone
Rotates and tilts head to the side; tilts head backward	Skull; vertebrae	Individually: laterally flexes and rotates head to same side; bilaterally: extension	Longissimus capitis	Transverse and articular processes of cervical and thoracic vertebra	Temporal bone (mastoid process)

Muscles of the Posterior Neck and the Back

The posterior muscles of the neck are primarily concerned with head movements, like extension. The back muscles stabilize and move the vertebral column, and are grouped according to the lengths and direction of the fascicles.

The splenius muscles originate at the midline and run laterally and superiorly to their insertions. From the sides and the back of the neck, the splenius capitis inserts onto the head region, and the splenius cervicis extends onto the cervical region. These muscles can extend the head, laterally flex it, and rotate it (Figure 9).

[caption id="" align="aligncenter" width="520"] Figure 9. Muscles of the Neck and Back. The large, complex muscles of the neck and back move the head, shoulders, and vertebral column.[/caption]

The erector spinae group forms the majority of the muscle mass of the back and it is the primary extensor of the vertebral column. It controls flexion, lateral flexion, and rotation of the vertebral column, and maintains the lumbar curve. The erector spinae comprises the iliocostalis (laterally placed) group, the longissimus (intermediately placed) group, and the spinalis (medially placed) group.

The iliocostalis group includes the iliocostalis cervicis, associated with the cervical region; the iliocostalis thoracis, associated with the thoracic region; and the iliocostalis lumborum, associated with the lumbar region. The three muscles of the longissimus group are the longissimus capitis, associated with the head region; the longissimus cervicis, associated with the cervical region; and the longissimus thoracis, associated with the thoracic region. The third group, the spinalis group, comprises the spinalis capitis (head region), the spinalis cervicis (cervical region), and the spinalis thoracis (thoracic region).

The transversospinales muscles run from the transverse processes to the spinous processes of the vertebrae. Similar to the erector spinae muscles, the semispinalis muscles in this group are named for the areas of the body with which they are associated. The semispinalis muscles include the semispinalis capitis, the semispinalis cervicis, and the semispinalis thoracis. The multifidus muscle of the lumbar region helps extend and laterally flex the vertebral column.

Important in the stabilization of the vertebral column is the segmental muscle group, which includes the interspinales and intertransversarii muscles. These muscles bring together the spinous and transverse processes of each consecutive vertebra. Finally, the scalene muscles work together to flex, laterally flex, and rotate the head. They also contribute to deep inhalation. The scalene muscles include the anterior scalene muscle (anterior to the middle scalene), the middle scalene muscle (the longest, intermediate between the anterior and posterior scalenes), and the posterior scalene muscle (the smallest, posterior to the middle scalene).

11.4 Axial Muscles of the Abdominal Wall, and Thorax

barkerj1 — Wed, 30 Aug 2017 18:38:26 +0000

Learning Objectives

By the end of this section, you will be able to:

It is a complex job to balance the body on two feet and walk upright. The muscles of the vertebral column, thorax, and abdominal wall extend, flex, and stabilize different parts of the body’s trunk. The deep muscles of the core of the body help maintain posture as well as carry out other functions. The brain sends out electrical impulses to these various muscle groups to control posture by alternate contraction and relaxation. This is necessary so that no single muscle group becomes fatigued too quickly. If any one group fails to function, body posture will be compromised.

Muscles of the Abdomen

There are four pairs of abdominal muscles that cover the anterior and lateral abdominal region and meet at the anterior midline. These muscles of the anterolateral abdominal wall can be divided into four groups: the external obliques, the internal obliques, the transversus abdominis, and the rectus abdominis (Figure 1 and Table 6).

[caption id="" align="aligncenter" width="520"] Figure 1. Muscles of the Abdomen. (a) The anterior abdominal muscles include the medially located rectus abdominis, which is covered by a sheet of connective tissue called the rectus sheath. On the flanks of the body, medial to the rectus abdominis, the abdominal wall is composed of three layers. The external oblique muscles form the superficial layer, while the internal oblique muscles form the middle layer, and the transverses abdominus forms the deepest layer. (b) The muscles of the lower back move the lumbar spine but also assist in femur movements.[/caption]

Muscles of the Abdomen (Table 6)
Movement	Target	Target motion direction	Prime mover	Origin	Insertion
Twisting at waist; also bending to the side	Vertebral column	Supination; lateral flexion	External obliques; internal obliques	Ribs 5–12; ilium	Ribs 7–10; linea alba; ilium
Squeezing abdomen during forceful exhalations, defecation, urination, and childbirth	Abdominal cavity	Compression	Transversus abdominus	Ilium; ribs 5–10	Sternum; linea alba; pubis
Sitting up	Vertebral column	Flexion	Rectus abdominis	Pubis	Sternum; ribs 5 and 7
Bending to the side	Vertebral column	Lateral flexion	Quadratus lumborum	Ilium; ribs 5–10	Rib 12; vertebrae L1–L4

There are three flat skeletal muscles in the antero-lateral wall of the abdomen. The external oblique, closest to the surface, extend inferiorly and medially, in the direction of sliding one’s four fingers into pants pockets. Perpendicular to it is the intermediate internal oblique, extending superiorly and medially, the direction the thumbs usually go when the other fingers are in the pants pocket. The deep muscle, the transversus abdominis, is arranged transversely around the abdomen, similar to the front of a belt on a pair of pants. This arrangement of three bands of muscles in different orientations allows various movements and rotations of the trunk. The three layers of muscle also help to protect the internal abdominal organs in an area where there is no bone.

The linea alba is a white, fibrous band that is made of the bilateral rectus sheaths that join at the anterior midline of the body. These enclose the rectus abdominis muscles (a pair of long, linear muscles, commonly called the “sit-up” muscles) that originate at the pubic crest and symphysis, and extend the length of the body’s trunk. Each muscle is segmented by three transverse bands of collagen fibers called the tendinous intersections. This results in the look of “six-pack abs,” as each segment hypertrophies on individuals at the gym who do many sit-ups.

The posterior abdominal wall is formed by the lumbar vertebrae, parts of the ilia of the hip bones, psoas major and iliacus muscles, and quadratus lumborum muscle. This part of the core plays a key role in stabilizing the rest of the body and maintaining posture.

Muscles of the Thorax

The muscles of the chest serve to facilitate breathing by changing the size of the thoracic cavity (Table 7). When you inhale, your chest rises because the cavity expands. Alternately, when you exhale, your chest falls because the thoracic cavity decreases in size.

Muscles of the Thorax (Table 7)
Movement	Target	Target motion direction	Prime mover	Origin	Insertion
Inhalation; exhalation	Thoracic cavity	Compression; expansion	Diaphragm	Sternum; ribs 6–12; lumbar vertebrae	Central tendon
Inhalation;exhalation	Ribs	Elevation (expands thoracic cavity)	External intercostals	Rib superior to each intercostal muscle	Rib inferior to each intercostal muscle
Forced exhalation	Ribs	Movement along superior/inferior axis to bring ribs closer together	Internal intercostals	Rib inferior to each intercostal muscle	Rib superior to each intercostal muscle

The Diaphragm

The change in volume of the thoracic cavity during breathing is due to the alternate contraction and relaxation of the diaphragm (Figure 2). It separates the thoracic and abdominal cavities, and is dome-shaped at rest. The superior surface of the diaphragm is convex, creating the elevated floor of the thoracic cavity. The inferior surface is concave, creating the curved roof of the abdominal cavity.

[caption id="" align="aligncenter" width="450"] Figure 2. Muscles of the Diaphragm. The diaphragm separates the thoracic and abdominal cavities.[/caption]

Defecating, urination, and even childbirth involve cooperation between the diaphragm and abdominal muscles (this cooperation is referred to as the “Valsalva maneuver”). You hold your breath by a steady contraction of the diaphragm; this stabilizes the volume and pressure of the peritoneal cavity. When the abdominal muscles contract, the pressure cannot push the diaphragm up, so it increases pressure on the intestinal tract (defecation), urinary tract (urination), or reproductive tract (childbirth).

The inferior surface of the pericardial sac and the inferior surfaces of the pleural membranes (parietal pleura) fuse onto the central tendon of the diaphragm. To the sides of the tendon are the skeletal muscle portions of the diaphragm, which insert into the tendon while having a number of origins including the xiphoid process of the sternum anteriorly, the inferior six ribs and their cartilages laterally, and the lumbar vertebrae and 12th ribs posteriorly.

The diaphragm also includes three openings for the passage of structures between the thorax and the abdomen. The inferior vena cava passes through the caval opening, and the esophagus and attached nerves pass through the esophageal hiatus. The aorta, thoracic duct, and azygous vein pass through the aortic hiatus of the posterior diaphragm.

The Intercostal Muscles

There are three sets of muscles, called intercostal muscles, which span each of the intercostal spaces. The principal role of the intercostal muscles is to assist in breathing by changing the dimensions of the rib cage (Figure 3).

[caption id="" align="aligncenter" width="620"] Figure 3. Intercostal Muscles. The external intercostals are located laterally on the sides of the body. The internal intercostals are located medially near the sternum. The innermost intercostals are located deep to both the internal and external intercostals.[/caption]

The 11 pairs of superficial external intercostal muscles aid in inspiration of air during breathing because when they contract, they raise the rib cage, which expands it. The 11 pairs of internal intercostal muscles, just under the externals, are used for expiration because they draw the ribs together to constrict the rib cage. The innermost intercostal muscles are the deepest, and they act as synergists for the action of the internal intercostals.

11.5 Muscles of the Pectoral Girdle and Upper Limbs

barkerj1 — Wed, 30 Aug 2017 18:38:34 +0000

Learning Objectives

By the end of this section, you will be able to:

Muscles of the shoulder and upper limb can be divided into four groups: muscles that stabilize and position the pectoral girdle, muscles that move the arm, muscles that move the forearm, and muscles that move the wrists, hands, and fingers. The pectoral girdle, or shoulder girdle, consists of the lateral ends of the clavicle and scapula, along with the proximal end of the humerus, and the muscles covering these three bones to stabilize the shoulder joint. The girdle creates a base from which the head of the humerus, in its ball-and-socket joint with the glenoid fossa of the scapula, can move the arm in multiple directions.

Muscles That Position the Pectoral Girdle

Muscles that position the pectoral girdle are located either on the anterior thorax or on the posterior thorax (Figure 1 and Table 8). The anterior muscles include the subclavius, pectoralis minor, and serratus anterior. The posterior muscles include the trapezius, rhomboid major, and rhomboid minor. When the rhomboids are contracted, your scapula moves medially, which can pull the shoulder and upper limb posteriorly.

[caption id="" align="aligncenter" width="540"] Figure 1. Muscles That Position the Pectoral Girdle. The muscles that stabilize the pectoral girdle make it a steady base on which other muscles can move the arm. Note that the pectoralis major and deltoid, which move the humerus, are cut here to show the deeper positioning muscles.[/caption]

Muscles that Position the Pectoral Girdle (Table 8)
Position in the thorax	Movement	Target	Target motion direction	Prime mover	Origin	Insertion
Anterior thorax	Stabilizes clavicle during movement by depressing it	Clavicle	Depression	Subclavius	First rib	Inferior surface of clavicle
Anterior thorax	Rotates shoulder anteriorly (throwing motion); assists with inhalation	Scapula; ribs	Scapula: depresses; ribs: elevates	Pectoralis minor	Anterior surfaces of certain ribs (2–4 or 3–5)	Coracoid process of scapula
Anterior thorax	Moves arm from side of body to front of body; assists with inhalation	Scapula; ribs	Scapula: protracts; ribs: elevates	Serratus anterior	Muscle slips from certain ribs (1–8 or 1–9)	Anterior surface of vertebral border of scapula
Posterior thorax	Elevates shoulders (shrugging); pulls shoulder blades together; tilts head backwards	Scapula; cervical spine	Scapula: rotests inferiorly, retracts, elevates, and depresses; spine: extends	Trapezius	Skull; vertebral column	Acromion and spine of scapula; clavicle
Posterior thorax	Stabilizes scapula during pectoral girdle movement	Scapula	Retracts; rotates inferiorly	Rhomboid major	Thoracic vertebrae (T2–T5)	Medial border of scapula
Posterior thorax	Stabilizes scapula during pectoral girdle movement	Scapula	Retracts; rotates inferiorly	Rhomboid minor	Cervical and thoracic vertebrae (C7 and T1)	Medial border of scapula

Muscles That Move the Humerus

Similar to the muscles that position the pectoral girdle, muscles that cross the shoulder joint and move the humerus bone of the arm include both axial and scapular muscles (Figure 2 and Figure 3). The two axial muscles are the pectoralis major and the latissimus dorsi. The pectoralis major is thick and fan-shaped, covering much of the superior portion of the anterior thorax. The broad, triangular latissimus dorsi is located on the inferior part of the back, where it inserts into a thick connective tissue shealth called an aponeurosis.

[caption id="" align="aligncenter" width="520"] Figure 2. Muscles That Move the Humerus. (a, c) The muscles that move the humerus anteriorly are generally located on the anterior side of the body and originate from the sternum (e.g., pectoralis major) or the anterior side of the scapula (e.g., subscapularis). (b) The muscles that move the humerus superiorly generally originate from the superior surfaces of the scapula and/or the clavicle (e.g., deltoids). The muscles that move the humerus inferiorly generally originate from middle or lower back (e.g., latissiumus dorsi). (d) The muscles that move the humerus posteriorly are generally located on the posterior side of the body and insert into the scapula (e.g., infraspinatus).[/caption]

[caption id="" align="aligncenter" width="520"] Figure 3. Muscles That Move the Humerus[/caption] The rest of the shoulder muscles originate on the scapula. The anatomical and ligamental structure of the shoulder joint and the arrangements of the muscles covering it, allows the arm to carry out different types of movements. The deltoid, the thick muscle that creates the rounded lines of the shoulder is the major abductor of the arm, but it also facilitates flexing and medial rotation, as well as extension and lateral rotation. The subscapularis originates on the anterior scapula and medially rotates the arm. Named for their locations, the supraspinatus (superior to the spine of the scapula) and the infraspinatus (inferior to the spine of the scapula) abduct the arm, and laterally rotate the arm, respectively. The thick and flat teres major is inferior to the teres minor and extends the arm, and assists in adduction and medial rotation of it. The long teres minor laterally rotates and extends the arm. Finally, the coracobrachialis flexes and adducts the arm.

The tendons of the deep subscapularis, supraspinatus, infraspinatus, and teres minor connect the scapula to the humerus, forming the rotator cuff (musculotendinous cuff), the circle of tendons around the shoulder joint. When baseball pitchers undergo shoulder surgery it is usually on the rotator cuff, which becomes pinched and inflamed, and may tear away from the bone due to the repetitive motion of bring the arm overhead to throw a fast pitch.

Muscles That Move the Forearm

The forearm, made of the radius and ulna bones, has four main types of action at the hinge of the elbow joint: flexion, extension, pronation, and supination. The forearm flexors include the biceps brachii, brachialis, and brachioradialis. The extensors are the triceps brachii and anconeus. The pronators are the pronator teres and the pronator quadratus, and the supinator is the only one that turns the forearm anteriorly. When the forearm faces anteriorly, it is supinated. When the forearm faces posteriorly, it is pronated.

The biceps brachii, brachialis, and brachioradialis flex the forearm. The two-headed biceps brachii crosses the shoulder and elbow joints to flex the forearm, also taking part in supinating the forearm at the radioulnar joints and flexing the arm at the shoulder joint. Deep to the biceps brachii, the brachialis provides additional power in flexing the forearm. Finally, the brachioradialis can flex the forearm quickly or help lift a load slowly. These muscles and their associated blood vessels and nerves form the anterior compartment of the arm (anterior flexor compartment of the arm) (Figure 4 and Figure 5).

[caption id="" align="aligncenter" width="630"] Figure 4. Muscles That Move the Forearm. The muscles originating in the upper arm flex, extend, pronate, and supinate the forearm. The muscles originating in the forearm move the wrists, hands, and fingers.[/caption]

[caption id="" align="aligncenter" width="520"] Figure 5. Muscles That Move the Forearm[/caption]

11.6 Appendicular Muscles of the Pelvic Girdle and Lower Limbs

barkerj1 — Wed, 30 Aug 2017 18:38:41 +0000

Learning Objectives

By the end of this section, you will be able to:

The appendicular muscles of the lower body position and stabilize the pelvic girdle, which serves as a foundation for the lower limbs. Comparatively, there is much more movement at the pectoral girdle than at the pelvic girdle. There is very little movement of the pelvic girdle because of its connection with the sacrum at the base of the axial skeleton. The pelvic girdle is less range of motion because it was designed to stabilize and support the body.

Muscles of the Thigh

What would happen if the pelvic girdle, which attaches the lower limbs to the torso, were capable of the same range of motion as the pectoral girdle? For one thing, walking would expend more energy if the heads of the femurs were not secured in the acetabula of the pelvis. The body’s center of gravity is in the area of the pelvis. If the center of gravity were not to remain fixed, standing up would be difficult as well. Therefore, what the leg muscles lack in range of motion and versatility, they make up for in size and power, facilitating the body’s stabilization, posture, and movement.

Gluteal Region Muscles That Move the Femur

Most muscles that insert on the femur (the thigh bone) and move it, originate on the pelvic girdle. The psoas major and iliacus make up the iliopsoas group. Some of the largest and most powerful muscles in the body are the gluteal muscles or gluteal group. The gluteus maximus is the largest; deep to the gluteus maximus is the gluteus medius, and deep to the gluteus medius is the gluteus minimus, the smallest of the trio (Figure 1 and Figure 2).

[caption id="" align="aligncenter" width="450"] Figure 1. Hip and Thigh Muscles. The large and powerful muscles of the hip that move the femur generally originate on the pelvic girdle and insert into the femur. The muscles that move the lower leg typically originate on the femur and insert into the bones of the knee joint. The anterior muscles of the femur extend the lower leg but also aid in flexing the thigh. The posterior muscles of the femur flex the lower leg but also aid in extending the thigh. A combination of gluteal and thigh muscles also adduct, abduct, and rotate the thigh and lower leg.[/caption]

[caption id="" align="aligncenter" width="550"] Figure 2. Gluteal Region Muscles That Move the Femur[/caption]

The tensor fascia latae is a thick, squarish muscle in the superior aspect of the lateral thigh. It acts as a synergist of the gluteus medius and iliopsoas in flexing and abducting the thigh. It also helps stabilize the lateral aspect of the knee by pulling on the iliotibial tract (band), making it taut. Deep to the gluteus maximus, the piriformis, obturator internus, obturator externus, superior gemellus, inferior gemellus, and quadratus femoris laterally rotate the femur at the hip.

The adductor longus, adductor brevis, and adductor magnus can both medially and laterally rotate the thigh depending on the placement of the foot. The adductor longus flexes the thigh, whereas the adductor magnus extends it. The pectineus adducts and flexes the femur at the hip as well. The pectineus is located in the femoral triangle, which is formed at the junction between the hip and the leg and also includes the femoral nerve, the femoral artery, the femoral vein, and the deep inguinal lymph nodes.

Thigh Muscles That Move the Femur, Tibia, and Fibula

Deep fascia in the thigh separates it into medial, anterior, and posterior compartments (see Figure 1 and Figure 3). The muscles in the medial compartment of the thigh are responsible for adducting the femur at the hip. Along with the adductor longus, adductor brevis, adductor magnus, and pectineus, the strap-like gracilis adducts the thigh in addition to flexing the leg at the knee.

[caption id="" align="aligncenter" width="520"] Figure 3. Thigh Muscles That Move the Femur, Tibia, and Fibula[/caption]

The muscles of the anterior compartment of the thigh flex the thigh and extend the leg. This compartment contains the quadriceps femoris group, which actually comprises four muscles that extend and stabilize the knee. The rectus femoris is on the anterior aspect of the thigh, the vastus lateralis is on the lateral aspect of the thigh, the vastus medialis is on the medial aspect of the thigh, and the vastus intermedius is between the vastus lateralis and vastus medialis and deep to the rectus femoris. The tendon common to all four is the quadriceps tendon (patellar tendon), which inserts into the patella and continues below it as the patellar ligament. The patellar ligament attaches to the tibial tuberosity. In addition to the quadriceps femoris, the sartorius is a band-like muscle that extends from the anterior superior iliac spine to the medial side of the proximal tibia. This versatile muscle flexes the leg at the knee and flexes, abducts, and laterally rotates the leg at the hip. This muscle allows us to sit cross-legged.

The posterior compartment of the thigh includes muscles that flex the leg and extend the thigh. The three long muscles on the back of the knee are the hamstring group, which flexes the knee. These are the biceps femoris, semitendinosus, and semimembranosus. The tendons of these muscles form the popliteal fossa, the diamond-shaped space at the back of the knee.

Muscles That Move the Feet and Toes

Similar to the thigh muscles, the muscles of the leg are divided by deep fascia into compartments, although the leg has three: anterior, lateral, and posterior (Figure 4 and Figure 5).

[caption id="" align="aligncenter" width="530"] Figure 4. Muscles of the Lower Leg The muscles of the anterior compartment of the lower leg are generally responsible for dorsiflexion, and the muscles of the posterior compartment of the lower leg are generally responsible for plantar flexion. The lateral and medial muscles in both compartments invert, evert, and rotate the foot.[/caption]

[caption id="" align="aligncenter" width="550"] Figure 5. Muscles That Move the Feet and Toes[/caption]

The muscles in the anterior compartment of the leg: the tibialis anterior, a long and thick muscle on the lateral surface of the tibia, the extensor hallucis longus, deep under it, and the extensor digitorum longus, lateral to it, all contribute to raising the front of the foot when they contract. The fibularis tertius, a small muscle that originates on the anterior surface of the fibula, is associated with the extensor digitorum longus and sometimes fused to it, but is not present in all people. Thick bands of connective tissue called the superior extensor retinaculum (transverse ligament of the ankle) and the inferior extensor retinaculum, hold the tendons of these muscles in place during dorsiflexion.

The lateral compartment of the leg includes two muscles: the fibularis longus (peroneus longus) and the fibularis brevis (peroneus brevis). The superficial muscles in the posterior compartment of the leg all insert onto the calcaneal tendon (Achilles tendon), a strong tendon that inserts into the calcaneal bone of the ankle. The muscles in this compartment are large and strong and keep humans upright. The most superficial and visible muscle of the calf is the gastrocnemius. Deep to the gastrocnemius is the wide, flat soleus. The plantaris runs obliquely between the two; some people may have two of these muscles, whereas no plantaris is observed in about seven percent of other cadaver dissections. The plantaris tendon is a desirable substitute for the fascia lata in hernia repair, tendon transplants, and repair of ligaments. There are four deep muscles in the posterior compartment of the leg as well: the popliteus, flexor digitorum longus, flexor hallucis longus, and tibialis posterior.

Introduction

barkerj1 — Wed, 30 Aug 2017 18:38:42 +0000

[caption id="" align="aligncenter" width="550"] Blood Cells A single drop of blood contains millions of red blood cells, white blood cells, and platelets. One of each type is shown here, isolated from a scanning electron micrograph.[/caption] Single-celled organisms do not need blood. They obtain nutrients directly from and excrete wastes directly into their environment. The human organism cannot do that. Our large, complex bodies need blood to deliver nutrients to and remove wastes from our trillions of cells. The heart pumps blood throughout the body in a network of blood vessels. Together, these three components—blood, heart, and vessels—makes up the cardiovascular system. This chapter focuses on the medium of transport: blood.

18.1 An Overview of Blood

barkerj1 — Wed, 30 Aug 2017 18:38:44 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the functions of blood
Describe the general nature of blood
Specify the three main components of blood, and describe the importance of each
Specify the two components of blood that give blood its viscosity, and describe the importance of each to the blood
Describe the procedure, what information is provided by, and the normal range for the following tests: hemoglobin (Hb), hematocrit (Hct), differential count

Recall that blood is a connective tissue. Like all connective tissues, it is made up of cellular elements and an extracellular matrix. The cellular elements—referred to as the formed elements—include red blood cells (RBCs), white blood cells (WBCs), and cell fragments called platelets. The extracellular matrix, called plasma, makes blood unique among connective tissues because it is fluid. This fluid, which is mostly water, perpetually suspends the formed elements and enables them to circulate throughout the body within the cardiovascular system.

Functions of Blood

The primary function of blood is to deliver oxygen and nutrients to and remove wastes from body cells, but that is only the beginning of the story. The specific functions of blood also include defense, distribution of heat, and maintenance of homeostasis.

Transportation

Nutrients from the foods you eat are absorbed in the digestive tract. Most of these travel in the bloodstream directly to the liver, where they are processed and released back into the bloodstream for delivery to body cells. Oxygen from the air you breathe diffuses into the blood, which moves from the lungs to the heart, which then pumps it out to the rest of the body. Moreover, endocrine glands scattered throughout the body release their products, called hormones, into the bloodstream, which carries them to distant target cells. Blood also picks up cellular wastes and byproducts, and transports them to various organs for removal. For instance, blood moves carbon dioxide to the lungs for exhalation from the body, and various waste products are transported to the kidneys and liver for excretion from the body in the form of urine or bile.

Defense

Many types of WBCs protect the body from external threats, such as disease-causing bacteria that have entered the bloodstream in a wound. Other WBCs seek out and destroy internal threats, such as cells with mutated DNA that could multiply to become cancerous, or body cells infected with viruses.

When damage to the vessels results in bleeding, blood platelets and certain proteins dissolved in the plasma, the fluid portion of the blood, interact to block the ruptured areas of the blood vessels involved. This protects the body from further blood loss.

Maintenance of Homeostasis

Recall that body temperature is regulated via a classic negative-feedback loop. If you were exercising on a warm day, your rising core body temperature would trigger several homeostatic mechanisms, including increased transport of blood from your core to your body periphery, which is typically cooler. As blood passes through the vessels of the skin, heat would be dissipated to the environment, and the blood returning to your body core would be cooler. In contrast, on a cold day, blood is diverted away from the skin to maintain a warmer body core. In extreme cases, this may result in frostbite.

Blood also helps to maintain the chemical balance of the body. Proteins and other compounds in blood act as buffers, which thereby help to regulate the pH of body tissues. Blood also helps to regulate the water content of body cells.

Composition of Blood

You have probably had blood drawn from a superficial vein in your arm, which was then sent to a lab for analysis. Some of the most common blood tests—for instance, those measuring lipid or glucose levels in plasma—determine which substances are present within blood and in what quantities. Other blood tests check for the composition of the blood itself, including the quantities and types of formed elements.

One such test, called a hematocrit, measures the percentage of RBCs, clinically known as erythrocytes, in a blood sample. It is performed by spinning the blood sample in a specialized centrifuge, a process that causes the heavier elements suspended within the blood sample to separate from the lightweight, liquid plasma (Figure 1). Because the heaviest elements in blood are the erythrocytes, these settle at the very bottom of the hematocrit tube. Located above the erythrocytes is a pale, thin layer composed of the remaining formed elements of blood. These are the WBCs, clinically known as leukocytes, and the platelets, cell fragments also called thrombocytes. This layer is referred to as the buffy coat because of its color; it normally constitutes less than 1 percent of a blood sample. Above the buffy coat is the blood plasma, normally a pale, straw-colored fluid, which constitutes the remainder of the sample.

The volume of erythrocytes after centrifugation is also commonly referred to as packed cell volume (PCV). In normal blood, about 45 percent of a sample is erythrocytes. The hematocrit of any one sample can vary significantly, however, about 36–50 percent, according to gender and other factors. Normal hematocrit values for females range from 37 to 47, with a mean value of 41; for males, hematocrit ranges from 42 to 52, with a mean of 47. The percentage of other formed elements, the WBCs and platelets, is extremely small so it is not normally considered with the hematocrit. So the mean plasma percentage is the percent of blood that is not erythrocytes: for females, it is approximately 59 (or 100 minus 41), and for males, it is approximately 53 (or 100 minus 47).

[caption id="" align="aligncenter" width="380"] Figure 1. Composition of Blood. The cellular elements of blood include a vast number of erythrocytes and comparatively fewer leukocytes and platelets. Plasma is the fluid in which the formed elements are suspended. A sample of blood spun in a centrifuge reveals that plasma is the lightest component. It floats at the top of the tube separated from the heaviest elements, the erythrocytes, by a buffy coat of leukocytes and platelets. Hematocrit is the percentage of the total sample that is comprised of erythrocytes. Depressed and elevated hematocrit levels are shown for comparison.[/caption]

Characteristics of Blood

When you think about blood, the first characteristic that probably comes to mind is its color. Blood that has just taken up oxygen in the lungs is bright red, and blood that has released oxygen in the tissues is a more dusky red. This is because hemoglobin is a pigment that changes color, depending upon the degree of oxygen saturation.

Blood is viscous and somewhat sticky to the touch. It has a viscosity approximately five times greater than water. Viscosity is a measure of a fluid’s thickness or resistance to flow, and is influenced by the presence of the plasma proteins and formed elements within the blood. The viscosity of blood has a dramatic impact on blood pressure and flow. Consider the difference in flow between water and honey. The more viscous honey would demonstrate a greater resistance to flow than the less viscous water. The same principle applies to blood.

The normal temperature of blood is slightly higher than normal body temperature—about 38 °C (or 100.4 °F), compared to 37 °C (or 98.6 °F) for an internal body temperature reading, although daily variations of 0.5 °C are normal. Although the surface of blood vessels is relatively smooth, as blood flows through them, it experiences some friction and resistance, especially as vessels age and lose their elasticity, thereby producing heat. This accounts for its slightly higher temperature.

The pH of blood averages about 7.4; however, it can range from 7.35 to 7.45 in a healthy person. Blood is therefore somewhat more basic (alkaline) on a chemical scale than pure water, which has a pH of 7.0. Blood contains numerous buffers that actually help to regulate pH.

Blood constitutes approximately 8 percent of adult body weight. Adult males typically average about 5 to 6 liters of blood. Females average 4–5 liters.

Blood Plasma

Like other fluids in the body, plasma is composed primarily of water: In fact, it is about 92 percent water. Dissolved or suspended within this water is a mixture of substances, most of which are proteins. There are literally hundreds of substances dissolved or suspended in the plasma, although many of them are found only in very small quantities.

[caption id="" align="aligncenter" width="120"] Visit this site for a list of normal levels established for many of the substances found in a sample of blood.[/caption]

Plasma Proteins

About 7 percent of the volume of plasma—nearly all that is not water—is made of proteins. These include several plasma proteins (proteins that are unique to the plasma), plus a much smaller number of regulatory proteins, including enzymes and some hormones. The major components of plasma are summarized in Figure 2.

The three major groups of plasma proteins are as follows:

Albumin is the most abundant of the plasma proteins. Manufactured by the liver, albumin molecules serve as binding proteins—transport vehicles for fatty acids and steroid hormones. Recall that lipids are hydrophobic; however, their binding to albumin enables their transport in the watery plasma. Albumin is also the most significant contributor to the osmotic pressure of blood; that is, its presence holds water inside the blood vessels and draws water from the tissues, across blood vessel walls, and into the bloodstream. This in turn helps to maintain both blood volume and blood pressure. Albumin normally accounts for approximately 54 percent of the total plasma protein content, in clinical levels of 3.5–5.0 g/dL blood.
The second most common plasma proteins are the globulins. A heterogeneous group, there are three main subgroups known as alpha, beta, and gamma globulins. The alpha and beta globulins transport iron, lipids, and the fat-soluble vitamins A, D, E, and K to the cells; like albumin, they also contribute to osmotic pressure. The gamma globulins are proteins involved in immunity and are better known as an antibodies or immunoglobulins. Although other plasma proteins are produced by the liver, immunoglobulins are produced by specialized leukocytes known as plasma cells. (Seek additional content for more information about immunoglobulins.) Globulins make up approximately 38 percent of the total plasma protein volume, in clinical levels of 1.0–1.5 g/dL blood.
The least abundant plasma protein is fibrinogen. Like albumin and the alpha and beta globulins, fibrinogen is produced by the liver. It is essential for blood clotting, a process described later in this chapter. Fibrinogen accounts for about 7 percent of the total plasma protein volume, in clinical levels of 0.2–0.45 g/dL blood.

Other Plasma Solutes

In addition to proteins, plasma contains a wide variety of other substances. These include various electrolytes, such as sodium, potassium, and calcium ions; dissolved gases, such as oxygen, carbon dioxide, and nitrogen; various organic nutrients, such as vitamins, lipids, glucose, and amino acids; and metabolic wastes. All of these nonprotein solutes combined contribute approximately 1 percent to the total volume of plasma.

[caption id="" align="aligncenter" width="600"] Figure 2. Major Blood Components[/caption]

[caption id="attachment_2971" align="aligncenter" width="150"] Check out this CrashCourse video to learn more about the components of blood![/caption]

18.2 Production of the Formed Elements

barkerj1 — Wed, 30 Aug 2017 18:38:45 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the major factors that stimulate the body to produce more erythrocytes
Specify the origins of leukocytes

The lifespan of the formed elements is very brief. Although one type of leukocyte called memory cells can survive for years, most erythrocytes, leukocytes, and platelets normally live only a few hours to a few weeks. Thus, the body must form new blood cells and platelets quickly and continuously. When you donate a unit of blood during a blood drive (approximately 475 mL, or about 1 pint), your body typically replaces the donated plasma within 24 hours, but it takes about 4 to 6 weeks to replace the blood cells. This restricts the frequency with which donors can contribute their blood. The process by which this replacement occurs is called hemopoiesis, or hematopoiesis (from the Greek root haima- = “blood”; -poiesis = “production”).

Sites of Hemopoiesis

Prior to birth, hemopoiesis occurs in a number of tissues, beginning with the yolk sac of the developing embryo, and continuing in the fetal liver, spleen, lymphatic tissue, and eventually the red bone marrow. Following birth, most hemopoiesis occurs in the red marrow, a connective tissue within the spaces of spongy (cancellous) bone tissue. In children, hemopoiesis can occur in the medullary cavity of long bones; in adults, the process is largely restricted to the cranial and pelvic bones, the vertebrae, the sternum, and the proximal epiphyses of the femur and humerus.

Throughout adulthood, the liver and spleen maintain their ability to generate the formed elements. This process is referred to as extramedullary hemopoiesis (meaning hemopoiesis outside the medullary cavity of adult bones). When a disease such as bone cancer destroys the bone marrow, causing hemopoiesis to fail, extramedullary hemopoiesis may be initiated.

Differentiation of Formed Elements from Stem Cells

All formed elements arise from stem cells of the red bone marrow. Recall that stem cells undergo mitosis plus cytokinesis (cellular division) to give rise to new daughter cells: One of these remains a stem cell and the other differentiates into one of any number of diverse cell types. Stem cells may be viewed as occupying a hierarchal system, with some loss of the ability to diversify at each step. The totipotent stem cell is the zygote, or fertilized egg. The totipotent (toti- = “all”) stem cell gives rise to all cells of the human body. The next level is the pluripotent stem cell, which gives rise to multiple types of cells of the body and some of the supporting fetal membranes. Beneath this level, the mesenchymal cell is a stem cell that develops only into types of connective tissue, including fibrous connective tissue, bone, cartilage, and blood, but not epithelium, muscle, and nervous tissue. One step lower on the hierarchy of stem cells is the hemopoietic stem cell, or hemocytoblast. All of the formed elements of blood originate from this specific type of cell.

Hemopoiesis begins when the hemopoietic stem cell is exposed to appropriate chemical stimuli collectively called hemopoietic growth factors, which prompt it to divide and differentiate. One daughter cell remains a hemopoietic stem cell, allowing hemopoiesis to continue. The other daughter cell becomes either of two types of more specialized stem cells (Figure 1):

Lymphoid stem cells give rise to a class of leukocytes known as lymphocytes, which include the various T cells, B cells, and natural killer (NK) cells, all of which function in immunity. However, hemopoiesis of lymphocytes progresses somewhat differently from the process for the other formed elements. In brief, lymphoid stem cells quickly migrate from the bone marrow to lymphatic tissues, including the lymph nodes, spleen, and thymus, where their production and differentiation continues. B cells are so named since they mature in the bone marrow, while T cells mature in the thymus.
Myeloid stem cells give rise to all the other formed elements, including the erythrocytes; megakaryocytes that produce platelets; and a myeloblast lineage that gives rise to monocytes and three forms of granular leukocytes: neutrophils, eosinophils, and basophils.

[caption id="" align="aligncenter" width="600"] Figure 1. Hematopoietic System of Bone Marrow. Hemopoiesis is the proliferation and differentiation of the formed elements of blood.[/caption]

Lymphoid and myeloid stem cells do not immediately divide and differentiate into mature formed elements. As you can see in the figure above, there are several intermediate stages of precursor cells (literally, forerunner cells), many of which can be recognized by their names, which have the suffix -blast. For instance, megakaryoblasts are the precursors of megakaryocytes, and proerythroblasts become reticulocytes, which eject their nucleus and most other organelles before maturing into erythrocytes.

Hemopoietic Growth Factors

Development from stem cells to precursor cells to mature cells is again initiated by hemopoietic growth factors. These include the following:

Erythropoietin (EPO) is a glycoprotein hormone secreted by the interstitial fibroblast cells of the kidneys in response to low oxygen levels. It prompts the production of erythrocytes. Some athletes use synthetic EPO as a performance-enhancing drug (called blood doping) to increase RBC counts and subsequently increase oxygen delivery to tissues throughout the body. EPO is a banned substance in most organized sports, but it is also used medically in the treatment of certain anemia, specifically those triggered by certain types of cancer, and other disorders in which increased erythrocyte counts and oxygen levels are desirable.
Thrombopoietin, another glycoprotein hormone, is produced by the liver and kidneys. It triggers the development of megakaryocytes into platelets.
Cytokines are glycoproteins secreted by a wide variety of cells, including red bone marrow, leukocytes, macrophages, fibroblasts, and endothelial cells. They act locally as autocrine or paracrine factors, stimulating the proliferation of progenitor cells and helping to stimulate both nonspecific and specific resistance to disease. There are two major subtypes of cytokines known as colony-stimulating factors and interleukins.
- Colony-stimulating factors (CSFs) are glycoproteins that act locally, as autocrine or paracrine factors. Some trigger the differentiation of myeloblasts into granular leukocytes, namely, neutrophils, eosinophils, and basophils. These are referred to as granulocyte CSFs. A different CSF induces the production of monocytes, called monocyte CSFs. Both granulocytes and monocytes are stimulated by GM-CSF; granulocytes, monocytes, platelets, and erythrocytes are stimulated by multi-CSF. Synthetic forms of these hormones are often administered to patients with various forms of cancer who are receiving chemotherapy to revive their WBC counts.
- Interleukins are another class of cytokine signaling molecules important in hemopoiesis. They were initially thought to be secreted uniquely by leukocytes and to communicate only with other leukocytes, and were named accordingly, but are now known to be produced by a variety of cells including bone marrow and endothelium. Researchers now suspect that interleukins may play other roles in body functioning, including differentiation and maturation of cells, producing immunity and inflammation. To date, more than a dozen interleukins have been identified, with others likely to follow. They are generally numbered IL-1, IL-2, IL-3, etc.

18.3 Erythrocytes

barkerj1 — Wed, 30 Aug 2017 18:38:51 +0000

Learning Objectives

By the end of this section, you will be able to:

Specify the types of leukocytes and their relative quantities in normal blood

The erythrocyte, commonly known as a red blood cell (or RBC), is by far the most common formed element: A single drop of blood contains millions of erythrocytes and just thousands of leukocytes. Specifically, males have about 5.4 million erythrocytes per microliter (µL) of blood, and females have approximately 4.8 million per µL. In fact, erythrocytes are estimated to make up about 25 percent of the total cells in the body. As you can imagine, they are quite small cells, with a mean diameter of only about 7–8 micrometers (µm) (Figure 1). The primary functions of erythrocytes are to pick up inhaled oxygen from the lungs and transport it to the body’s tissues, and to pick up some (about 24 percent) carbon dioxide waste at the tissues and transport it to the lungs for exhalation. Erythrocytes remain within the vascular network. Although leukocytes typically leave the blood vessels to perform their defensive functions, movement of erythrocytes from the blood vessels is abnormal.

[caption id="" align="aligncenter" width="600"] Figure 1. Summary of Formed Elements in Blood[/caption]

Shape and Structure of Erythrocytes

As an erythrocyte matures in the red bone marrow, it extrudes its nucleus and most of its other organelles. During the first day or two that it is in the circulation, an immature erythrocyte, known as a reticulocyte, will still typically contain remnants of organelles. Reticulocytes should comprise approximately 1–2 percent of the erythrocyte count and provide a rough estimate of the rate of RBC production, with abnormally low or high rates indicating deviations in the production of these cells. These remnants, primarily of networks (reticulum) of ribosomes, are quickly shed, however, and mature, circulating erythrocytes have few internal cellular structural components. Lacking mitochondria, for example, they rely on anaerobic respiration. This means that they do not utilize any of the oxygen they are transporting, so they can deliver it all to the tissues. They also lack endoplasmic reticula and do not synthesize proteins. Erythrocytes do, however, contain some structural proteins that help the blood cells maintain their unique structure and enable them to change their shape to squeeze through capillaries. This includes the protein spectrin, a cytoskeletal protein element.

Erythrocytes are biconcave disks; that is, they are plump at their periphery and very thin in the center (Figure 2). Since they lack most organelles, there is more interior space for the presence of the hemoglobin molecules that, as you will see shortly, transport gases. The biconcave shape also provides a greater surface area across which gas exchange can occur, relative to its volume; a sphere of a similar diameter would have a lower surface area-to-volume ratio. In the capillaries, the oxygen carried by the erythrocytes can diffuse into the plasma and then through the capillary walls to reach the cells, whereas some of the carbon dioxide produced by the cells as a waste product diffuses into the capillaries to be picked up by the erythrocytes. Capillary beds are extremely narrow, slowing the passage of the erythrocytes and providing an extended opportunity for gas exchange to occur. However, the space within capillaries can be so minute that, despite their own small size, erythrocytes may have to fold in on themselves if they are to make their way through. Fortunately, their structural proteins like spectrin are flexible, allowing them to bend over themselves to a surprising degree, then spring back again when they enter a wider vessel. In wider vessels, erythrocytes may stack up much like a roll of coins, forming a rouleaux, from the French word for “roll.”

[caption id="" align="aligncenter" width="300"] Figure 2. Shape of Red Blood Cells. Erythrocytes are biconcave discs with very shallow centers. This shape optimizes the ratio of surface area to volume, facilitating gas exchange. It also enables them to fold up as they move through narrow blood vessels.[/caption]

Hemoglobin

Hemoglobin is a large molecule made up of proteins and iron. It consists of four folded chains of a protein called globin, designated alpha 1 and 2, and beta 1 and 2 (Figure 3a). Each of these globin molecules is bound to a red pigment molecule called heme, which contains an ion of iron (Fe²⁺) (Figure 3b).

[caption id="" align="aligncenter" width="500"] Figure 3. Hemoglobin. (a) A molecule of hemoglobin contains four globin proteins, each of which is bound to one molecule of the iron-containing pigment heme. (b) A single erythrocyte can contain 300 million hemoglobin molecules, and thus more than 1 billion oxygen molecules.[/caption]

Each iron ion in the heme can bind to one oxygen molecule; therefore, each hemoglobin molecule can transport four oxygen molecules. An individual erythrocyte may contain about 300 million hemoglobin molecules, and therefore can bind to and transport up to 1.2 billion oxygen molecules (see Figure 3b).

In the lungs, hemoglobin picks up oxygen, which binds to the iron ions, forming oxyhemoglobin. The bright red, oxygenated hemoglobin travels to the body tissues, where it releases some of the oxygen molecules, becoming darker red deoxyhemoglobin, sometimes referred to as reduced hemoglobin. Oxygen release depends on the need for oxygen in the surrounding tissues, so hemoglobin rarely if ever leaves all of its oxygen behind. In the capillaries, carbon dioxide enters the bloodstream. About 76 percent dissolves in the plasma, some of it remaining as dissolved CO₂, and the remainder forming bicarbonate ion. About 23–24 percent of it binds to the amino acids in hemoglobin, forming a molecule known as carbaminohemoglobin. From the capillaries, the hemoglobin carries carbon dioxide back to the lungs, where it releases it for exchange of oxygen.

Changes in the levels of erythrocytes can have significant effects on the body’s ability to effectively deliver oxygen to the tissues. Ineffective hematopoiesis results in insufficient numbers of erythrocytes and results in one of several forms of anemia. An overproduction of erythrocytes produces a condition called polycythemia. The primary drawback with polycythemia is not a failure to directly deliver enough oxygen to the tissues, but rather the increased viscosity of the blood, which makes it more difficult for the heart to circulate the blood.

In patients with insufficient hemoglobin, the tissues may not receive sufficient oxygen, resulting in another form of anemia. In determining oxygenation of tissues, the value of greatest interest in healthcare is the percent saturation; that is, the percentage of hemoglobin sites occupied by oxygen in a patient’s blood. Clinically this value is commonly referred to simply as “percent sat.”

Percent saturation is normally monitored using a device known as a pulse oximeter, which is applied to a thin part of the body, typically the tip of the patient’s finger. The device works by sending two different wavelengths of light (one red, the other infrared) through the finger and measuring the light with a photodetector as it exits. Hemoglobin absorbs light differentially depending upon its saturation with oxygen. The machine calibrates the amount of light received by the photodetector against the amount absorbed by the partially oxygenated hemoglobin and presents the data as percent saturation. Normal pulse oximeter readings range from 95–100 percent. Lower percentages reflect hypoxemia, or low blood oxygen. The term hypoxia is more generic and simply refers to low oxygen levels. Oxygen levels are also directly monitored from free oxygen in the plasma typically following an arterial stick. When this method is applied, the amount of oxygen present is expressed in terms of partial pressure of oxygen or simply pO₂ and is typically recorded in units of millimeters of mercury, mm Hg.

The kidneys filter about 180 liters (~380 pints) of blood in an average adult each day, or about 20 percent of the total resting volume, and thus serve as ideal sites for receptors that determine oxygen saturation. In response to hypoxemia, less oxygen will exit the vessels supplying the kidney, resulting in hypoxia (low oxygen concentration) in the tissue fluid of the kidney where oxygen concentration is actually monitored. Interstitial fibroblasts within the kidney secrete EPO, thereby increasing erythrocyte production and restoring oxygen levels. In a classic negative-feedback loop, as oxygen saturation rises, EPO secretion falls, and vice versa, thereby maintaining homeostasis. Populations dwelling at high elevations, with inherently lower levels of oxygen in the atmosphere, naturally maintain a hematocrit higher than people living at sea level. Consequently, people traveling to high elevations may experience symptoms of hypoxemia, such as fatigue, headache, and shortness of breath, for a few days after their arrival. In response to the hypoxemia, the kidneys secrete EPO to step up the production of erythrocytes until homeostasis is achieved once again. To avoid the symptoms of hypoxemia, or altitude sickness, mountain climbers typically rest for several days to a week or more at a series of camps situated at increasing elevations to allow EPO levels and, consequently, erythrocyte counts to rise. When climbing the tallest peaks, such as Mt. Everest and K2 in the Himalayas, many mountain climbers rely upon bottled oxygen as they near the summit.

Lifecycle of Erythrocytes

Production of erythrocytes in the marrow occurs at the staggering rate of more than 2 million cells per second. For this production to occur, a number of raw materials must be present in adequate amounts. These include the same nutrients that are essential to the production and maintenance of any cell, such as glucose, lipids, and amino acids. However, erythrocyte production also requires several trace elements:

Iron. We have said that each heme group in a hemoglobin molecule contains an ion of the trace mineral iron. On average, less than 20 percent of the iron we consume is absorbed. Heme iron, from animal foods such as meat, poultry, and fish, is absorbed more efficiently than non-heme iron from plant foods. Upon absorption, iron becomes part of the body’s total iron pool. The bone marrow, liver, and spleen can store iron in the protein compounds ferritin and hemosiderin. Ferroportin transports the iron across the intestinal cell plasma membranes and from its storage sites into tissue fluid where it enters the blood. When EPO stimulates the production of erythrocytes, iron is released from storage, bound to transferrin, and carried to the red marrow where it attaches to erythrocyte precursors.
Copper. A trace mineral, copper is a component of two plasma proteins, hephaestin and ceruloplasmin. Without these, hemoglobin could not be adequately produced. Located in intestinal villi, hephaestin enables iron to be absorbed by intestinal cells. Ceruloplasmin transports copper. Both enable the oxidation of iron from Fe²⁺ to Fe³⁺, a form in which it can be bound to its transport protein, transferrin, for transport to body cells. In a state of copper deficiency, the transport of iron for heme synthesis decreases, and iron can accumulate in tissues, where it can eventually lead to organ damage.
Zinc. The trace mineral zinc functions as a co-enzyme that facilitates the synthesis of the heme portion of hemoglobin.
B vitamins. The B vitamins folate and vitamin B₁₂ function as co-enzymes that facilitate DNA synthesis. Thus, both are critical for the synthesis of new cells, including erythrocytes.

Erythrocytes live up to 120 days in the circulation, after which the worn-out cells are removed by a type of myeloid phagocytic cell called a macrophage, located primarily within the bone marrow, liver, and spleen. The components of the degraded erythrocytes’ hemoglobin are further processed as follows:

Globin, the protein portion of hemoglobin, is broken down into amino acids, which can be sent back to the bone marrow to be used in the production of new erythrocytes. Hemoglobin that is not phagocytized is broken down in the circulation, releasing alpha and beta chains that are removed from circulation by the kidneys.
The iron contained in the heme portion of hemoglobin may be stored in the liver or spleen, primarily in the form of ferritin or hemosiderin, or carried through the bloodstream by transferrin to the red bone marrow for recycling into new erythrocytes.
The non-iron portion of heme is degraded into the waste product biliverdin, a green pigment, and then into another waste product, bilirubin, a yellow pigment. Bilirubin binds to albumin and travels in the blood to the liver, which uses it in the manufacture of bile, a compound released into the intestines to help emulsify dietary fats. In the large intestine, bacteria breaks the bilirubin apart from the bile and converts it to urobilinogen and then into stercobilin. It is then eliminated from the body in the feces. Broad-spectrum antibiotics typically eliminate these bacteria as well and may alter the color of feces. The kidneys also remove any circulating bilirubin and other related metabolic byproducts such as urobilins and secrete them into the urine.

The breakdown pigments formed from the destruction of hemoglobin can be seen in a variety of situations. At the site of an injury, biliverdin from damaged erythrocytes produces some of the dramatic colors associated with bruising. With a failing liver, bilirubin cannot be removed effectively from circulation and causes the body to assume a yellowish tinge associated with jaundice. Stercobilins within the feces produce the typical brown color associated with this waste. And the yellow of urine is associated with the urobilins.

The erythrocyte lifecycle is summarized in Figure 4.

[caption id="" align="aligncenter" width="600"] Figure 4. Erythrocyte Lifecycle. Erythrocytes are produced in the bone marrow and sent into the circulation. At the end of their lifecycle, they are destroyed by macrophages, and their components are recycled.[/caption]

Disorders of Erythrocytes

The size, shape, and number of erythrocytes, and the number of hemoglobin molecules can have a major impact on a person’s health. When the number of erythrocytes or hemoglobin is deficient, the general condition is called anemia. There are more than 400 types of anemia and more than 3.5 million Americans suffer from this condition. Anemia can be broken down into three major groups: those caused by blood loss, those caused by faulty or decreased erythrocyte production, and those caused by excessive destruction of erythrocytes . Clinicians often use two groupings in diagnosis: The kinetic approach focuses on evaluating the production, destruction, and removal of erythrocytes , whereas the morphological approach examines the erythrocytes themselves, paying particular emphasis to their size. A common test is the mean corpuscle volume (MCV), which measures size. Normal-sized cells are referred to as normocytic, smaller-than-normal cells are referred to as microcytic, and larger-than-normal cells are referred to as macrocytic. Reticulocyte counts are also important and may reveal inadequate production of erythrocytes . Finally, the hemoglobin content of the blood can be measured by lysing the erythrocytes to release the hemoglobin molecules into solution. Hemoglobin is red in colour, so the shade and intensity of the fluid sample containing the freed hemoglobin molecules can be compared to standard prepared solutions of known hemoglobin concentrations to determine the actual quantity of hemoglobin present in the blood sample.

The effects of the various anemias are widespread, because reduced numbers of erythrocytes or hemoglobin will result in lower levels of oxygen being delivered to body tissues. Since oxygen is required for tissue functioning, anemia produces fatigue, lethargy, and an increased risk for infection. An oxygen deficit in the brain impairs the ability to think clearly, and may prompt headaches and irritability. Lack of oxygen leaves the patient short of breath, even as the heart and lungs work harder in response to the deficit.

Blood loss anemias are fairly straightforward. In addition to bleeding from wounds or other lesions, these forms of anemia may be due to ulcers, hemorrhoids, inflammation of the stomach (gastritis), and some cancers of the gastrointestinal tract. The excessive use of aspirin or other nonsteroidal anti-inflammatory drugs such as ibuprofen can trigger ulceration and gastritis. Excessive menstruation and loss of blood during childbirth are also potential causes.

Anemias caused by faulty or decreased erythrocyte production include sickle cell anemia, iron deficiency anemia, vitamin deficiency anemia, and diseases of the bone marrow and stem cells.

A characteristic change in the shape of erythrocytes is seen in sickle cell disease (also referred to as sickle cell anemia). A genetic disorder, it is caused by production of an abnormal type of hemoglobin, called hemoglobin S, which delivers less oxygen to tissues and causes erythrocytes to assume a sickle (or crescent) shape, especially at low oxygen concentrations (Figure 5). These abnormally shaped cells can then become lodged in narrow capillaries because they are unable to fold in on themselves to squeeze through, blocking blood flow to tissues and causing a variety of serious problems from painful joints to delayed growth and even blindness and cerebrovascular accidents (strokes). Sickle cell anemia is a genetic condition particularly found in individuals of African descent.

[caption id="" align="aligncenter" width="300"] Figure 5. Sickle Cells. Sickle cell anemia is caused by a mutation in one of the hemoglobin genes. Erythrocytes produce an abnormal type of hemoglobin, which causes the cell to take on a sickle or crescent shape. (credit: Janice Haney Carr)[/caption]

Iron deficiency anemia is the most common type and results when the amount of available iron is insufficient to allow production of sufficient heme. This condition can occur in individuals with a deficiency of iron in the diet and is especially common in teens and children as well as in vegans and vegetarians. Additionally, iron deficiency anemia may be caused by either an inability to absorb and transport iron or slow, chronic bleeding.
Vitamin-deficient anemias generally involve insufficient vitamin B12 and folate.
- Megaloblastic anemia involves a deficiency of vitamin B12 and/or folate, and often involves diets deficient in these essential nutrients. Lack of meat or a viable alternate source, and overcooking or eating insufficient amounts of vegetables may lead to a lack of folate.
- Pernicious anemia is caused by poor absorption of vitamin B12 and is often seen in patients with Crohn’s disease (a severe intestinal disorder often treated by surgery), surgical removal of the intestines or stomach (common in some weight loss surgeries), intestinal parasites, and AIDS.
- Pregnancies, some medications, excessive alcohol consumption, and some diseases such as celiac disease are also associated with vitamin deficiencies. It is essential to provide sufficient folic acid during the early stages of pregnancy to reduce the risk of neurological defects, including spina bifida, a failure of the neural tube to close.
Assorted disease processes can also interfere with the production and formation of RBCs and hemoglobin. If myeloid stem cells are defective or replaced by cancer cells, there will be insufficient quantities of erythrocytes produced.
- Aplastic anemia is the condition in which there are deficient numbers of RBC stem cells. Aplastic anemia is often inherited, or it may be triggered by radiation, medication, chemotherapy, or infection.
- Thalassemia is an inherited condition typically occurring in individuals from the Middle East, the Mediterranean, African, and Southeast Asia, in which maturation of the erythrocytes does not proceed normally. The most severe form is called Cooley’s anemia.
- Lead exposure from industrial sources or even dust from paint chips of iron-containing paints or pottery that has not been properly glazed may also lead to destruction of the red marrow.
Various disease processes also can lead to anemias. These include chronic kidney diseases often associated with a decreased production of EPO, hypothyroidism, some forms of cancer, lupus, and rheumatoid arthritis.

In contrast to anemia, an elevated erythrocyte count is called polycythemia and is detected in a patient’s elevated hematocrit. It can occur transiently in a person who is dehydrated; when water intake is inadequate or water losses are excessive, the plasma volume falls. As a result, the hematocrit rises. For reasons mentioned earlier, a mild form of polycythemia is chronic but normal in people living at high altitudes. Some elite athletes train at high elevations specifically to induce this phenomenon. Finally, a type of bone marrow disease called polycythemia vera (from the Greek vera = “true”) causes an excessive production of immature erythrocytes. Polycythemia vera can dangerously elevate the viscosity of blood, raising blood pressure and making it more difficult for the heart to pump blood throughout the body. It is a relatively rare disease that occurs more often in men than women, and is more likely to be present in elderly patients those over 60 years of age.

18.4 Leukocytes and Platelets

barkerj1 — Wed, 30 Aug 2017 18:38:55 +0000

Learning Objectives

By the end of this section, you will be able to:

Specify the types of leukocytes, their origins and relative quantities in normal blood
Describe the origins of T cells and B cells
Describe the major factors that stimulate the body to produce more leukocytes
Describe the procedure, what information is provided by, and the normal range for a differential count
Specify the origin, characteristics, and function of platelets

The leukocyte, commonly known as a white blood cell (or WBC), is a major component of the body’s defenses against disease. Leukocytes protect the body against invading microorganisms and body cells with mutated DNA, and they clean up debris. Platelets are essential for the repair of blood vessels when damage to them has occurred; they also provide growth factors for healing and repair.

Characteristics of Leukocytes

Although leukocytes and erythrocytes both originate from hematopoietic stem cells in the bone marrow, they are very different from each other in many significant ways. For instance, leukocytes are far less numerous than erythrocytes: Typically there are only 5000 to 10,000 per µL. They are also larger than erythrocytes and are the only formed elements that are complete cells, possessing a nucleus and organelles. And although there is just one type of erythrocyte, there are many types of leukocytes. Most of these types have a much shorter lifespan than that of erythrocytes, some as short as a few hours or even a few minutes in the case of acute infection.

One of the most distinctive characteristics of leukocytes is their movement. Whereas erythrocytes spend their days circulating within the blood vessels, leukocytes routinely leave the bloodstream to perform their defensive functions in the body’s tissues. For leukocytes, the vascular network is simply a highway they travel and soon exit to reach their true destination. When they arrive, they are often given distinct names, such as macrophage or microglia, depending on their function. As shown in Figure 1, they leave the capillaries—the smallest blood vessels—or other small vessels through a process known as emigration (from the Latin for “removal”) or diapedesis (dia- = “through”; -pedan = “to leap”) in which they squeeze through adjacent cells in a blood vessel wall.

Once they have exited the capillaries, some leukocytes will take up fixed positions in lymphatic tissue, bone marrow, the spleen, the thymus, or other organs. Others will move about through the tissue spaces very much like amoebas, continuously extending their plasma membranes, sometimes wandering freely, and sometimes moving toward the direction in which they are drawn by chemical signals. This attracting of leukocytes occurs because of positive chemotaxis (literally “movement in response to chemicals”), a phenomenon in which injured or infected cells and nearby leukocytes emit the equivalent of a chemical “911” call, attracting more leukocytes to the site. In clinical medicine, the differential counts of the types and percentages of leukocytes present are often key indicators in making a diagnosis and selecting a treatment.

[caption id="" align="aligncenter" width="600"] Figure 1. Emigration. Leukocytes exit the blood vessel and then move through the connective tissue of the dermis toward the site of a wound. Some leukocytes, such as the eosinophil and neutrophil, are characterized as granular leukocytes. They release chemicals from their granules that destroy pathogens; they are also capable of phagocytosis. The monocyte, an agranular leukocyte, differentiates into a macrophage that then phagocytizes the pathogens.[/caption]

Classification of Leukocytes

When scientists first began to observe stained blood slides, it quickly became evident that leukocytes could be divided into two groups, according to whether their cytoplasm contained highly visible granules:

Granular leukocytes contain abundant granules within the cytoplasm. They include neutrophils, eosinophils, and basophils (you can view their lineage from myeloid stem cells in Chapter 18.2 Production of Formed Elements).
While granules are not totally lacking in agranular leukocytes, they are far fewer and less obvious. Agranular leukocytes include monocytes, which mature into macrophages that are phagocytic, and lymphocytes, which arise from the lymphoid stem cell line.

Granular Leukocytes

We will consider the granular leukocytes in order from most common to least common. All of these are produced in the red bone marrow and have a short lifespan of hours to days. They typically have a lobed nucleus and are classified according to which type of stain best highlights their granules (Figure 2).

[caption id="" align="aligncenter" width="380"] Figure 2. Granular Leukocytes. A neutrophil has small granules that stain light lilac and a nucleus with two to five lobes. An eosinophil’s granules are slightly larger and stain reddish-orange, and its nucleus has two to three lobes. A basophil has large granules that stain dark blue to purple and a two-lobed nucleus.[/caption]

The most common of all the leukocytes, neutrophils will normally comprise 50–70 percent of total leukocyte count. They are 10–12 µm in diameter, significantly larger than erythrocytes. They are called neutrophils because their granules show up most clearly with stains that are chemically neutral (neither acidic nor basic). The granules are numerous but quite fine and normally appear light lilac. The nucleus has a distinct lobed appearance and may have two to five lobes, the number increasing with the age of the cell. Older neutrophils have increasing numbers of lobes and are often referred to as polymorphonuclear (a nucleus with many forms), or simply “polys.” Younger and immature neutrophils begin to develop lobes and are known as “bands.”

Neutrophils are rapid responders to the site of infection and are efficient phagocytes with a preference for bacteria. Their granules include lysozyme, an enzyme capable of lysing, or breaking down, bacterial cell walls; oxidants such as hydrogen peroxide; and defensins, proteins that bind to and puncture bacterial and fungal plasma membranes, so that the cell contents leak out. Abnormally high counts of neutrophils indicate infection and/or inflammation, particularly triggered by bacteria, but are also found in burn patients and others experiencing unusual stress. A burn injury increases the proliferation of neutrophils in order to fight off infection that can result from the destruction of the barrier of the skin. Low counts may be caused by drug toxicity and other disorders, and may increase an individual’s susceptibility to infection.

Eosinophils typically represent 2–4 percent of total leukocyte count. They are also 10–12 µm in diameter. The granules of eosinophils stain best with an acidic stain known as eosin. The nucleus of the eosinophil will typically have two to three lobes and, if stained properly, the granules will have a distinct red to orange color.

The granules of eosinophils include antihistamine molecules, which counteract the activities of histamines, inflammatory chemicals produced by basophils and mast cells. Some eosinophil granules contain molecules toxic to parasitic worms, which can enter the body through the integument, or when an individual consumes raw or undercooked fish or meat. Eosinophils are also capable of phagocytosis and are particularly effective when antibodies bind to the target and form an antigen-antibody complex. High counts of eosinophils are typical of patients experiencing allergies, parasitic worm infestations, and some autoimmune diseases. Low counts may be due to drug toxicity and stress.

Basophils are the least common leukocytes, typically comprising less than one percent of the total leukocyte count. They are slightly smaller than neutrophils and eosinophils at 8–10 µm in diameter. The granules of basophils stain best with basic (alkaline) stains. Basophils contain large granules that pick up a dark blue stain and are so common they may make it difficult to see the two-lobed nucleus.

In general, basophils intensify the inflammatory response. They share this trait with mast cells. In the past, mast cells were considered to be basophils that left the circulation. However, this appears not to be the case, as the two cell types develop from different lineages.

The granules of basophils release histamines, which contribute to inflammation, and heparin, which opposes blood clotting. High counts of basophils are associated with allergies, parasitic infections, and hypothyroidism. Low counts are associated with pregnancy, stress, and hyperthyroidism.

Agranular Leukocytes

Agranular leukocytes contain smaller, less-visible granules in their cytoplasm than do granular leukocytes. The nucleus is simple in shape, sometimes with an indentation but without distinct lobes. There are two major types of agranulocytes: lymphocytes and monocytes.

Lymphocytes are the only formed element of blood that arises from lymphoid stem cells. Although they form initially in the bone marrow, much of their subsequent development and reproduction occurs in the lymphatic tissues. Lymphocytes are the second most common type of leukocyte, accounting for about 20–30 percent of all leukocytes, and are essential for the immune response. The size range of lymphocytes is quite extensive, with some authorities recognizing two size classes and others three. Typically, the large cells are 10–14 µm and have a smaller nucleus-to-cytoplasm ratio and more granules. The smaller cells are typically 6–9 µm with a larger volume of nucleus to cytoplasm, creating a “halo” effect. A few cells may fall outside these ranges, at 14–17 µm. This finding has led to the three size range classification.

The three major groups of lymphocytes include natural killer cells, B cells, and T cells. Natural killer (NK) cells are capable of recognizing cells that do not express “self” proteins on their plasma membrane or that contain foreign or abnormal markers. These “nonself” cells include cancer cells, cells infected with a virus, and other cells with atypical surface proteins. Thus, they provide generalized, nonspecific immunity. The larger lymphocytes are typically NK cells.

B cells and T cells, also called B lymphocytes and T lymphocytes, play prominent roles in defending the body against specific pathogens (disease-causing microorganisms) and are involved in specific immunity. One form of B cells (plasma cells) produces the antibodies or immunoglobulins that bind to specific foreign or abnormal components of plasma membranes. This is also referred to as humoral (body fluid) immunity. T cells provide cellular-level immunity by physically attacking foreign or diseased cells. A memory cell is a variety of both B and T cells that forms after exposure to a pathogen and mounts rapid responses upon subsequent exposures. Unlike other leukocytes, memory cells live for many years. B cells undergo a maturation process in the bone marrow, whereas T cells undergo maturation in the thymus. This site of the maturation process gives rise to the name B and T cells. The functions of lymphocytes are complex and will be covered in detail in the chapter covering the lymphatic system and immunity. Smaller lymphocytes are either B or T cells, although they cannot be differentiated in a normal blood smear.

Abnormally high lymphocyte counts are characteristic of viral infections as well as some types of cancer. Abnormally low lymphocyte counts are characteristic of prolonged (chronic) illness or immunosuppression, including that caused by HIV infection and drug therapies that often involve steroids.

Monocytes originate from myeloid stem cells. They normally represent 2–8 percent of the total leukocyte count. They are typically easily recognized by their large size of 12–20 µm and indented or horseshoe-shaped nuclei. Macrophages are monocytes that have left the circulation and phagocytize debris, foreign pathogens, worn-out erythrocytes, and many other dead, worn out, or damaged cells. Macrophages also release antimicrobial defensins and chemotactic chemicals that attract other leukocytes to the site of an infection. Some macrophages occupy fixed locations, whereas others wander through the tissue fluid.

Abnormally high counts of monocytes are associated with viral or fungal infections, tuberculosis, and some forms of leukemia and other chronic diseases. Abnormally low counts are typically caused by suppression of the bone marrow.

Lifecycle of Leukocytes

Most leukocytes have a relatively short lifespan, typically measured in hours or days. Production of all leukocytes begins in the bone marrow under the influence of CSFs and interleukins. Secondary production and maturation of lymphocytes occurs in specific regions of lymphatic tissue known as germinal centers. Lymphocytes are fully capable of mitosis and may produce clones of cells with identical properties. This capacity enables an individual to maintain immunity throughout life to many threats that have been encountered in the past.

Disorders of Leukocytes

Leukopenia is a condition in which too few leukocytes are produced. If this condition is pronounced, the individual may be unable to ward off disease. Excessive leukocyte proliferation is known as leukocytosis. Although leukocyte counts are high, the cells themselves are often nonfunctional, leaving the individual at increased risk for disease.

Leukemia is a cancer involving an abundance of leukocytes. It may involve only one specific type of leukocyte from either the myeloid line (myelocytic leukemia) or the lymphoid line (lymphocytic leukemia). In chronic leukemia, mature leukocytes accumulate and fail to die. In acute leukemia, there is an overproduction of young, immature leukocytes. In both conditions the cells do not function properly.

Lymphoma is a form of cancer in which masses of malignant T and/or B lymphocytes collect in lymph nodes, the spleen, the liver, and other tissues. As in leukemia, the malignant leukocytes do not function properly, and the patient is vulnerable to infection. Some forms of lymphoma tend to progress slowly and respond well to treatment. Others tend to progress quickly and require aggressive treatment, without which they are rapidly fatal.

Irregular lymphocyte production can be detected by the creation of a blood smear, where blood is collected and literally smeared onto a glass microscope slide in a very thin layer - ideally, no more than a single cell deep - fixed to the slide and stained. Stains that colour nuclei can be used to pick out leukocytes from the background of enucleate erythrocytes, and the different types of leukocytes identified and counted. Depending on how the blood smear was produced, these counts may be expressed as a fraction or percentage of total leukocytes, or as a concentration per unit volume of blood.

Platelets

You may occasionally see platelets referred to as thrombocytes, but because this name suggests they are a type of cell, it is not accurate. A platelet is not a cell but rather a fragment of the cytoplasm of a cell called a megakaryocyte that is surrounded by a plasma membrane. Megakaryocytes are descended from myeloid stem cells (see Chapter 18.2 Production of the Formed Elements) and are large, typically 50–100 µm in diameter, and contain an enlarged, lobed nucleus. As noted earlier, thrombopoietin, a glycoprotein secreted by the kidneys and liver, stimulates the proliferation of megakaryoblasts, which mature into megakaryocytes. These remain within bone marrow tissue (Figure 3) and ultimately form platelet-precursor extensions that extend through the walls of bone marrow capillaries to release into the circulation thousands of cytoplasmic fragments, each enclosed by a bit of plasma membrane. These enclosed fragments are platelets. Each megakarocyte releases 2000–3000 platelets during its lifespan. Following platelet release, megakaryocyte remnants, which are little more than a cell nucleus, are consumed by macrophages.

Platelets are relatively small, 2–4 µm in diameter, but numerous, with typically 150,000–160,000 per µL of blood. After entering the circulation, approximately one-third migrate to the spleen for storage for later release in response to any rupture in a blood vessel. They then become activated to perform their primary function, which is to limit blood loss. Platelets remain only about 10 days, then are phagocytized by macrophages.

Platelets are critical to hemostasis, the stoppage of blood flow following damage to a vessel. They also secrete a variety of growth factors essential for growth and repair of tissue, particularly connective tissue. Infusions of concentrated platelets are now being used in some therapies to stimulate healing.

Disorders of Platelets

Thrombocytosis is a condition in which there are too many platelets. This may trigger formation of unwanted blood clots (thrombosis), a potentially fatal disorder. If there is an insufficient number of platelets, called thrombocytopenia, blood may not clot properly, and excessive bleeding may result.

[caption id="" align="aligncenter" width="200"] Figure 3. Platelets. Platelets are derived from cells called megakaryocytes.[/caption]

[caption id="" align="aligncenter" width="120"] View University of Michigan Webscopes at http://virtualslides.med.umich.edu/Histology/Cardiovascular%20System/081-2_HISTO_40X.svs/view.apml?cwidth=860&cheight=733&chost=virtualslides.med.umich.edu&listview=1&title=&csis=1 and explore the blood slides in greater detail.[/caption]

18.5 Hemostasis

barkerj1 — Wed, 30 Aug 2017 18:38:57 +0000

Learning Objectives

By the end of this section, you will be able to:

Define hemostasis
Describe the three mechanisms involved in achieving hemostasis: vascular spasm, platelet plug formation, blood clotting
Describe how the process of blood clotting is regulated by describing:
- The prevention of blood clotting when it is not required
- The rapid initiation and progression of blood clotting when damage occurs
- The localization of blood clotting to the damaged region
- The dissolution of clots (fibrinolysis)
Describe how each of the following affects blood clotting: vitamin K, anticoagulant drugs, thrombolytic agents
Describe the following disorders of hemostasis: thrombus, embolus, hemophilia

Platelets are key players in hemostasis, the process by which the body seals a ruptured blood vessel and prevents further loss of blood. Although rupture of larger vessels usually requires medical intervention, hemostasis is quite effective in dealing with small, simple wounds. There are three steps to the process: vascular spasm, the formation of a platelet plug, and coagulation (blood clotting). Failure of any of these steps will result in hemorrhage—excessive bleeding.

Vascular Spasm

When a vessel is severed or punctured, or when the wall of a vessel is damaged, vascular spasm occurs. In vascular spasm, the smooth muscle in the walls of the vessel contracts dramatically. This smooth muscle has both circular layers; larger vessels also have longitudinal layers. The circular layers tend to constrict the flow of blood, whereas the longitudinal layers, when present, draw the vessel back into the surrounding tissue, often making it more difficult for a surgeon to locate, clamp, and tie off a severed vessel. The vascular spasm response is believed to be triggered by several chemicals called endothelins that are released by vessel-lining cells and by pain receptors in response to vessel injury. This phenomenon typically lasts for up to 30 minutes, although it can last for hours.

Formation of the Platelet Plug

In the second step, platelets, which normally float free in the plasma, encounter the area of vessel rupture with the exposed underlying connective tissue and collagenous fibers. The platelets begin to clump together, become spiked and sticky, and bind to the exposed collagen and endothelial lining. This process is assisted by a glycoprotein in the blood plasma called von Willebrand factor, which helps stabilize the growing platelet plug. As platelets collect, they simultaneously release chemicals from their granules into the plasma that further contribute to hemostasis. Among the substances released by the platelets are:

adenosine diphosphate (ADP), which helps additional platelets to adhere to the injury site, reinforcing and expanding the platelet plug
serotonin, which maintains vasoconstriction
prostaglandins and phospholipids, which also maintain vasoconstriction and help to activate further clotting chemicals, as discussed next

A platelet plug can temporarily seal a small opening in a blood vessel. Plug formation, in essence, buys the body time while more sophisticated and durable repairs are being made. In a similar manner, even modern naval warships still carry an assortment of wooden plugs to temporarily repair small breaches in their hulls until permanent repairs can be made.

Coagulation

Those more sophisticated and more durable repairs are collectively called coagulation, the formation of a blood clot. The process is sometimes characterized as a cascade, because one event prompts the next as in a multi-level waterfall. The result is the production of a gelatinous but robust clot made up of a mesh of fibrin—an insoluble filamentous protein derived from fibrinogen, the plasma protein introduced earlier—in which platelets and blood cells are trapped. Figure 1 summarizes the three steps of hemostasis.

[caption id="" align="aligncenter" width="600"] Figure 1. Hemostasis. (a) An injury to a blood vessel initiates the process of hemostasis. Blood clotting involves three steps. First, vascular spasm constricts the flow of blood. Next, a platelet plug forms to temporarily seal small openings in the vessel. Coagulation then enables the repair of the vessel wall once the leakage of blood has stopped. (b) The synthesis of fibrin in blood clots involves either an intrinsic pathway or an extrinsic pathway, both of which lead to a common pathway. (credit a: Kevin MacKenzie)[/caption]

Clotting Factors Involved in Coagulation

In the coagulation cascade, chemicals called clotting factors (or coagulation factors) prompt reactions that activate still more coagulation factors. The process is complex, but is initiated along two basic pathways:

The extrinsic pathway, which normally is triggered by trauma.
The intrinsic pathway, which begins in the bloodstream and is triggered by internal damage to the wall of the vessel.

Both of these merge into a third pathway, referred to as the common pathway (see Figure 1b). All three pathways are dependent upon the 12 known clotting factors, including Ca²⁺ and vitamin K (Table 1). Clotting factors are secreted primarily by the liver and the platelets. The liver requires the fat-soluble vitamin K to produce many of them. Vitamin K (along with biotin and folate) is somewhat unusual among vitamins in that it is not only consumed in the diet but is also synthesized by bacteria residing in the large intestine. The calcium ion, considered factor IV, is derived from the diet and from the breakdown of bone. Some recent evidence indicates that activation of various clotting factors occurs on specific receptor sites on the surfaces of platelets.

The 12 clotting factors are numbered I through XIII according to the order of their discovery. Factor VI was once believed to be a distinct clotting factor, but is now thought to be identical to factor V. Rather than renumber the other factors, factor VI was allowed to remain as a placeholder and also a reminder that knowledge changes over time.

Extrinsic Pathway

The quicker responding and more direct extrinsic pathway (also known as the tissue factor pathway) begins when damage occurs to the surrounding tissues, such as in a traumatic injury. Upon contact with blood plasma, the damaged extravascular cells, which are extrinsic to the bloodstream, release factor III (thromboplastin). Sequentially, Ca²⁺ then factor VII (proconvertin), which is activated by factor III, are added, forming an enzyme complex. This enzyme complex leads to activation of factor X (Stuart–Prower factor), which activates the common pathway discussed below. The events in the extrinsic pathway are completed in a matter of seconds.

Intrinsic Pathway

The intrinsic pathway (also known as the contact activation pathway) is longer and more complex. In this case, the factors involved are intrinsic to (present within) the bloodstream. The pathway can be prompted by damage to the tissues, resulting from internal factors such as arterial disease; however, it is most often initiated when factor XII (Hageman factor) comes into contact with foreign materials, such as when a blood sample is put into a glass test tube. Within the body, factor XII is typically activated when it encounters negatively charged molecules, such as inorganic polymers and phosphate produced earlier in the series of intrinsic pathway reactions. Factor XII sets off a series of reactions that in turn activates factor XI (antihemolytic factor C or plasma thromboplastin antecedent) then factor IX (antihemolytic factor B or plasma thromboplasmin). In the meantime, chemicals released by the platelets increase the rate of these activation reactions. Finally, factor VIII (antihemolytic factor A) from the platelets and endothelial cells combines with factor IX (antihemolytic factor B or plasma thromboplasmin) to form an enzyme complex that activates factor X (Stuart–Prower factor or thrombokinase), leading to the common pathway. The events in the intrinsic pathway are completed in a few minutes.

Common Pathway

Both the intrinsic and extrinsic pathways lead to the common pathway, in which fibrin is produced to seal off the vessel. Once factor X has been activated by either the intrinsic or extrinsic pathway, the enzyme prothrombinase converts factor II, the inactive enzyme prothrombin, into the active enzyme thrombin. (Note that if the enzyme thrombin were not normally in an inactive form, clots would form spontaneously, a condition not consistent with life.) Then, thrombin converts factor I, the insoluble fibrinogen, into the soluble fibrin protein strands. Factor XIII then stabilizes the fibrin clot.

*Vitamin K required.
Clotting Factors (Table 1
Factor number	Name	Type of molecule	Source	Pathway(s)
I	Fibrinogen	Plasma protein	Liver	Common; converted into fibrin
II	Prothrombin	Plasma protein	Liver*	Common; converted into thrombin
III	Tissue thromboplastin or tissue factor	Lipoprotein mixture	Damaged cells and platelets	Extrinsic
IV	Calcium ions	Inorganic ions in plasma	Diet, platelets, bone matrix	Entire process
V	Proaccelerin	Plasma protein	Liver, platelets	Extrinsic and intrinsic
VI	Not used	Not used	Not used	Not used
VII	Proconvertin	Plasma protein	Liver *	Extrinsic
VIII	Antihemolytic factor A	Plasma protein factor	Platelets and endothelial cells	Intrinsic; deficiency results in hemophilia A
IX	Antihemolytic factor B (plasma thromboplastin component)	Plasma protein	Liver*	Intrinsic; deficiency results in hemophilia B
X	Stuart–Prower factor (thrombokinase)	Protein	Liver*	Extrinsic and intrinsic
XI	Antihemolytic factor C (plasma thromboplastin antecedent)	Plasma protein	Liver	Intrinsic; deficiency results in hemophilia C
XII	Hageman factor	Plasma protein	Liver	Intrinsic; initiates clotting in vitro also activates plasmin
XIII	Fibrin-stabilizing factor	Plasma protein	Liver, platelets	Stabilizes fibrin; slows fibrinolysis

Fibrinolysis

The stabilized clot is acted upon by contractile proteins within the platelets. As these proteins contract, they pull on the fibrin threads, bringing the edges of the clot more tightly together, somewhat as we do when tightening loose shoelaces (see Figure 1a). This process also wrings out of the clot a small amount of fluid called serum, which is blood plasma without its clotting factors.

To restore normal blood flow as the vessel heals, the clot must eventually be removed. Fibrinolysis is the gradual degradation of the clot. Again, there is a fairly complicated series of reactions that involves factor XII and protein-catabolizing enzymes. During this process, the inactive protein plasminogen is converted into the active plasmin, which gradually breaks down the fibrin of the clot. Additionally, bradykinin, a vasodilator, is released, reversing the effects of the serotonin and prostaglandins from the platelets. This allows the smooth muscle in the walls of the vessels to relax and helps to restore the circulation.

Plasma Anticoagulants

An anticoagulant is any substance that opposes coagulation. Several circulating plasma anticoagulants play a role in limiting the coagulation process to the region of injury and restoring a normal, clot-free condition of blood. For instance, a cluster of proteins collectively referred to as the protein C system inactivates clotting factors involved in the intrinsic pathway. TFPI (tissue factor pathway inhibitor) inhibits the conversion of the inactive factor VII to the active form in the extrinsic pathway. Antithrombin inactivates factor X and opposes the conversion of prothrombin (factor II) to thrombin in the common pathway. And as noted earlier, basophils release heparin, a short-acting anticoagulant that also opposes prothrombin. Heparin is also found on the surfaces of cells lining the blood vessels. A pharmaceutical form of heparin is often administered therapeutically, for example, in surgical patients at risk for blood clots.

[caption id="" align="aligncenter" width="120"] View these animations to explore the intrinsic, extrinsic, and common pathways that are involved the process of coagulation.[/caption]

Disorders of Clotting

Either an insufficient or an excessive production of platelets can lead to severe disease or death. As discussed earlier, an insufficient number of platelets, called thrombocytopenia, typically results in the inability of blood to form clots. This can lead to excessive bleeding, even from minor wounds.

Another reason for failure of the blood to clot is the inadequate production of functional amounts of one or more clotting factors. This is the case in the genetic disorder hemophilia, which is actually a group of related disorders, the most common of which is hemophilia A, accounting for approximately 80 percent of cases. This disorder results in the inability to synthesize sufficient quantities of factor VIII. Hemophilia B is the second most common form, accounting for approximately 20 percent of cases. In this case, there is a deficiency of factor IX. Both of these defects are linked to the X chromosome and are typically passed from a healthy (carrier) mother to her male offspring, since males are XY. Females would need to inherit a defective gene from each parent to manifest the disease, since they are XX. Patients with hemophilia bleed from even minor internal and external wounds, and leak blood into joint spaces after exercise and into urine and stool. Hemophilia C is a rare condition that is triggered by an autosomal (not sex) chromosome that renders factor XI nonfunctional. It is not a true recessive condition, since even individuals with a single copy of the mutant gene show a tendency to bleed. Regular infusions of clotting factors isolated from healthy donors can help prevent bleeding in hemophiliac patients. At some point, genetic therapy will become a viable option.

In contrast to the disorders characterized by coagulation failure is thrombocytosis, also mentioned earlier, a condition characterized by excessive numbers of platelets that increases the risk for excessive clot formation, a condition known as thrombosis. A thrombus (plural = thrombi) is an aggregation of platelets, erythrocytes, and even WBCs typically trapped within a mass of fibrin strands. While the formation of a clot is normal following the hemostatic mechanism just described, thrombi can form within an intact or only slightly damaged blood vessel. In a large vessel, a thrombus will adhere to the vessel wall and decrease the flow of blood, and is referred to as a mural thrombus. In a small vessel, it may actually totally block the flow of blood and is termed an occlusive thrombus. Thrombi are most commonly caused by vessel damage to the endothelial lining, which activates the clotting mechanism. These may include venous stasis, when blood in the veins, particularly in the legs, remains stationary for long periods. This is one of the dangers of long airplane flights in crowded conditions and may lead to deep vein thrombosis or atherosclerosis, an accumulation of debris in arteries. Thrombophilia, also called hypercoagulation, is a condition in which there is a tendency to form thrombosis. This may be familial (genetic) or acquired. Acquired forms include the autoimmune disease lupus, immune reactions to heparin, polycythemia vera, thrombocytosis, sickle cell disease, pregnancy, and even obesity. A thrombus can seriously impede blood flow to or from a region and will cause a local increase in blood pressure. If flow is to be maintained, the heart will need to generate a greater pressure to overcome the resistance.

When a portion of a thrombus breaks free from the vessel wall and enters the circulation, it is referred to as an embolus. An embolus that is carried through the bloodstream can be large enough to block a vessel critical to a major organ. When it becomes trapped, an embolus is called an embolism. In the heart, brain, or lungs, an embolism may accordingly cause a heart attack, a stroke, or a pulmonary embolism. These are medical emergencies.

Among the many known biochemical activities of aspirin is its role as an anticoagulant. Aspirin (acetylsalicylic acid) is very effective at inhibiting the aggregation of platelets. It is routinely administered during a heart attack or stroke to reduce the adverse effects. Physicians sometimes recommend that patients at risk for cardiovascular disease take a low dose of aspirin on a daily basis as a preventive measure. However, aspirin can also lead to serious side effects, including increasing the risk of ulcers. A patient is well advised to consult a physician before beginning any aspirin regimen.

A class of drugs collectively known as thrombolytic agents can help speed up the degradation of an abnormal clot. If a thrombolytic agent is administered to a patient within 3 hours following a thrombotic stroke, the patient’s prognosis improves significantly. However, some strokes are not caused by thrombi, but by hemorrhage. Thus, the cause must be determined before treatment begins. Tissue plasminogen activator is an enzyme that catalyzes the conversion of plasminogen to plasmin, the primary enzyme that breaks down clots. It is released naturally by endothelial cells but is also used in clinical medicine. New research is progressing using compounds isolated from the venom of some species of snakes, particularly vipers and cobras, which may eventually have therapeutic value as thrombolytic agents.

18.6 Blood Typing

barkerj1 — Wed, 30 Aug 2017 18:39:00 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the basis of the ABO blood groups
Explain the significance of the ABO blood groups to transfusions
Describe the Rh factor
Explain the significance of the Rh factor in blood transfusions
Explain the significance of the Rh factor in maternal-fetal blood type incompatability.

Blood transfusions in humans were risky procedures until the discovery of the major human blood groups by Karl Landsteiner, an Austrian biologist and physician, in 1900. Until that point, physicians did not understand that death sometimes followed blood transfusions, when the type of donor blood infused into the patient was incompatible with the patient’s own blood. Blood groups are determined by the presence or absence of specific marker molecules on the plasma membranes of erythrocytes. With their discovery, it became possible for the first time to match patient-donor blood types and prevent transfusion reactions and deaths.

Antigens, Antibodies, and Transfusion Reactions

Antigens are substances that the body does not recognize as belonging to the “self” and that therefore trigger a defensive response from the leukocytes of the immune system. (Seek more content for additional information on immunity.) Here, we will focus on the role of immunity in blood transfusion reactions. With RBCs in particular, you may see the antigens referred to as isoantigens or agglutinogens (surface antigens) and the antibodies referred to as isoantibodies or agglutinins. In this chapter, we will use the more common terms antigens and antibodies.

Antigens are generally large proteins, but may include other classes of organic molecules, including carbohydrates, lipids, and nucleic acids. Following an infusion of incompatible blood, erythrocytes with foreign antigens appear in the bloodstream and trigger an immune response. Proteins called antibodies (immunoglobulins), which are produced by certain B lymphocytes called plasma cells, attach to the antigens on the plasma membranes of the infused erythrocytes and cause them to adhere to one another.

Because the arms of the Y-shaped antibodies attach randomly to more than one nonself erythrocyte surface, they form clumps of erythrocytes. This process is called agglutination.
The clumps of erythrocytes block small blood vessels throughout the body, depriving tissues of oxygen and nutrients.
As the erythrocyte clumps are degraded, in a process called hemolysis, their hemoglobin is released into the bloodstream. This hemoglobin travels to the kidneys, which are responsible for filtration of the blood. However, the load of hemoglobin released can easily overwhelm the kidney’s capacity to clear it, and the patient can quickly develop kidney failure.

More than 50 antigens have been identified on erythrocyte membranes, but the most significant in terms of their potential harm to patients are classified in two groups: the ABO blood group and the Rh blood group.

The ABO Blood Group

Although the ABO blood group name consists of three letters, ABO blood typing designates the presence or absence of just two antigens, A and B. Both are glycoproteins. People whose erythrocytes have A antigens on their erythrocyte membrane surfaces are designated blood type A, and those whose erythrocytes have B antigens are blood type B. People can also have both A and B antigens on their erythrocytes, in which case they are blood type AB. People with neither A nor B antigens are designated blood type O. ABO blood types are genetically determined.

Normally the body must be exposed to a foreign antigen before an antibody can be produced. This is not the case for the ABO blood group. Individuals with type A blood—without any prior exposure to incompatible blood—have preformed antibodies to the B antigen circulating in their blood plasma. These antibodies, referred to as anti-B antibodies, will cause agglutination and hemolysis if they ever encounter erythrocytes with B antigens. Similarly, an individual with type B blood has pre-formed anti-A antibodies. Individuals with type AB blood, which has both antigens, do not have preformed antibodies to either of these. People with type O blood lack antigens A and B on their erythrocytes, but both anti-A and anti-B antibodies circulate in their blood plasma.

Rh Blood Groups

The Rh blood group is classified according to the presence or absence of a second erythrocyte antigen identified as Rh. (It was first discovered in a type of primate known as a rhesus macaque, which is often used in research, because its blood is similar to that of humans.) Although dozens of Rh antigens have been identified, only one, designated D, is clinically important. Those who have the Rh D antigen present on their erythrocytes—about 85 percent of Americans—are described as Rh positive (Rh⁺) and those who lack it are Rh negative (Rh⁻). Note that the Rh group is distinct from the ABO group, so any individual, no matter their ABO blood type, may have or lack this Rh antigen. When identifying a patient’s blood type, the Rh group is designated by adding the word positive or negative to the ABO type. For example, A positive (A⁺) means ABO group A blood with the Rh antigen present, and AB negative (AB⁻) means ABO group AB blood without the Rh antigen.

Table 2 summarizes the distribution of the ABO and Rh blood types within the United States.

Summary of ABO and Rh Blood Types within the United States (Table 2)
Blood Type	African-Americans	Asian-Americans	Caucasian-Americans	Latino/Latina-Americans
A⁺	24	27	33	29
A⁻	2	0.5	7	2
B⁺	18	25	9	9
B⁻	1	0.4	2	1
AB⁺	4	7	3	2
AB⁻	0.3	0.1	1	0.2
O⁺	47	39	37	53
O⁻	4	1	8	4

In contrast to the ABO group antibodies, which are preformed, antibodies to the Rh antigen are produced only in Rh⁻ individuals after exposure to the antigen. This process, called sensitization, occurs following a transfusion with Rh-incompatible blood or, more commonly, with the birth of an Rh⁺ baby to an Rh⁻ mother. Problems are rare in a first pregnancy, since the baby’s Rh⁺ cells rarely cross the placenta (the organ of gas and nutrient exchange between the baby and the mother). However, during or immediately after birth, the Rh⁻ mother can be exposed to the baby’s Rh⁺ cells (Figure 1). Research has shown that this occurs in about 13−14 percent of such pregnancies. After exposure, the mother’s immune system begins to generate anti-Rh antibodies. If the mother should then conceive another Rh⁺ baby, the Rh antibodies she has produced can cross the placenta into the fetal bloodstream and destroy the fetal RBCs. This condition, known as hemolytic disease of the newborn (HDN) or erythroblastosis fetalis, may cause anemia in mild cases, but the agglutination and hemolysis can be so severe that without treatment the fetus may die in the womb or shortly after birth.

[caption id="" align="aligncenter" width="600"] Figure 1. Erythroblastosis Fetalis. The first exposure of an Rh− mother to Rh+ erythrocytes during pregnancy induces sensitization. Anti-Rh antibodies begin to circulate in the mother’s bloodstream. A second exposure occurs with a subsequent pregnancy with an Rh+ fetus in the uterus. Maternal anti-Rh antibodies may cross the placenta and enter the fetal bloodstream, causing agglutination and hemolysis of fetal erythrocytes.[/caption]

A drug known as RhoGAM, short for Rh immune globulin, can temporarily prevent the development of Rh antibodies in the Rh⁻ mother, thereby averting this potentially serious disease for the fetus. RhoGAM antibodies destroy any fetal Rh⁺ erythrocytes that may cross the placental barrier. RhoGAM is normally administered to Rh⁻ mothers during weeks 26−28 of pregnancy and within 72 hours following birth. It has proven remarkably effective in decreasing the incidence of HDN. Earlier we noted that the incidence of HDN in an Rh⁺ subsequent pregnancy to an Rh⁻ mother is about 13–14 percent without preventive treatment. Since the introduction of RhoGAM in 1968, the incidence has dropped to about 0.1 percent in the United States.

Determining ABO Blood Types

Clinicians are able to determine a patient’s blood type quickly and easily using commercially prepared antibodies. An unknown blood sample is allocated into separate wells. Into one well a small amount of anti-A antibody is added, and to another a small amount of anti-B antibody. If the antigen is present, the antibodies will cause visible agglutination of the cells (Figure 2). The blood should also be tested for Rh antibodies.

[caption id="" align="aligncenter" width="430"] Figure 2. Cross Matching Blood Types. This sample of a commercially produced “bedside” card enables quick typing of both a recipient’s and donor’s blood before transfusion. The card contains three reaction sites or wells. One is coated with an anti-A antibody, one with an anti-B antibody, and one with an anti-D antibody (tests for the presence of Rh factor D). Mixing a drop of blood and saline into each well enables the blood to interact with a preparation of type-specific antibodies, also called anti-seras. Agglutination of RBCs in a given site indicates a positive identification of the blood antigens, in this case A and Rh antigens for blood type A+. For the purpose of transfusion, the donor’s and recipient’s blood types must match.[/caption]

ABO Transfusion Protocols

To avoid transfusion reactions, it is best to transfuse only matching blood types; that is, a type B⁺ recipient should ideally receive blood only from a type B⁺ donor and so on. That said, in emergency situations, when acute hemorrhage threatens the patient’s life, there may not be time for cross matching to identify blood type. In these cases, blood from a universal donor—an individual with type O⁻ blood—may be transfused. Recall that type O erythrocytes do not display A or B antigens. Thus, anti-A or anti-B antibodies that might be circulating in the patient’s blood plasma will not encounter any erythrocyte surface antigens on the donated blood and therefore will not be provoked into a response. One problem with this designation of universal donor is if the O⁻ individual had prior exposure to Rh antigen, Rh antibodies may be present in the donated blood. Also, introducing type O blood into an individual with type A, B, or AB blood will nevertheless introduce antibodies against both A and B antigens, as these are always circulating in the type O blood plasma. This may cause problems for the recipient, but because the volume of blood transfused is much lower than the volume of the patient’s own blood, the adverse effects of the relatively few infused plasma antibodies are typically limited. Rh factor also plays a role. If Rh⁻ individuals receiving blood have had prior exposure to Rh antigen, antibodies for this antigen may be present in the blood and trigger agglutination to some degree. Although it is always preferable to cross match a patient’s blood before transfusing, in a true life-threatening emergency situation, this is not always possible, and these procedures may be implemented.

A patient with blood type AB⁺ is known as the universal recipient. This patient can theoretically receive any type of blood, because the patient’s own blood—having both A and B antigens on the erythrocyte surface—does not produce anti-A or anti-B antibodies. In addition, an Rh⁺ patient can receive both Rh⁺ and Rh⁻ blood. However, keep in mind that the donor’s blood will contain circulating antibodies, again with possible negative implications. Figure 3 summarizes the blood types and compatibilities.

At the scene of multiple-vehicle accidents, military engagements, and natural or human-caused disasters, many victims may suffer simultaneously from acute hemorrhage, yet type O blood may not be immediately available. In these circumstances, medics may at least try to replace some of the volume of blood that has been lost. This is done by intravenous administration of a saline solution that provides fluids and electrolytes in proportions equivalent to those of normal blood plasma. Research is ongoing to develop a safe and effective artificial blood that would carry out the oxygen-carrying function of blood without the RBCs, enabling transfusions in the field without concern for incompatibility. These blood substitutes normally contain hemoglobin- as well as perfluorocarbon-based oxygen carriers.

[caption id="" align="aligncenter" width="420"] Figure 3. ABO Blood Group. This chart summarizes the characteristics of the blood types in the ABO blood group. See the text for more on the concept of a universal donor or recipient.[/caption]

Introduction

barkerj1 — Wed, 30 Aug 2017 18:39:01 +0000

[caption id="" align="aligncenter" width="500"] Human Heart This artist’s conception of the human heart suggests a powerful engine—not inappropriate for a muscular pump that keeps the body continually supplied with blood. (credit: Patrick J. Lynch)[/caption] In this chapter, you will explore the remarkable pump that propels the blood into the vessels. There is no single better word to describe the function of the heart other than “pump,” since its contraction develops the pressure that ejects blood into the major vessels: the aorta and pulmonary trunk. From these vessels, the blood is distributed to the remainder of the body. Although the connotation of the term “pump” suggests a mechanical device made of steel and plastic, the anatomical structure is a living, sophisticated muscle. As you read this chapter, try to keep these twin concepts in mind: pump and muscle. Although the term “heart” is an English word, cardiac (heart-related) terminology can be traced back to the Latin term, “kardia.” Cardiology is the study of the heart, and cardiologists are the physicians who deal primarily with the heart.

19.1 Heart Anatomy

barkerj1 — Wed, 30 Aug 2017 18:39:14 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the location, size, and anatomy of the human heart
Describe the functions of the atria and ventricles of the heart
Define and describe the location of the pericardium, epicardium, myocardium, and endocardium
Describe the double circulation and blood flow through the heart. Explain the role of the four valves in controlling the direction of blood flow

The vital importance of the heart is obvious. If one assumes an average rate of contraction of 75 contractions per minute, a human heart would contract approximately 108,000 times in one day, more than 39 million times in one year, and nearly 3 billion times during a 75-year lifespan. Each of the major pumping chambers of the heart ejects approximately 70 mL blood per contraction in a resting adult. This would be equal to 5.25 liters of fluid per minute and approximately 14,000 liters per day. Over one year, that would equal 10,000,000 liters or 2.6 million gallons of blood sent through roughly 60,000 miles of vessels. In order to understand how that happens, it is necessary to understand the anatomy and physiology of the heart.

Location of the Heart

The human heart is located within the thoracic cavity, medially between the lungs in the space known as the mediastinum. Figure 1 shows the position of the heart within the thoracic cavity. Within the mediastinum, the heart is separated from the other mediastinal structures by a tough membrane known as the pericardium, or pericardial sac, and sits in its own space called the pericardial cavity. The dorsal surface of the heart lies near the bodies of the vertebrae, and its anterior surface sits deep to the sternum and costal cartilages. The great veins, the superior and inferior venae cavae, and the great arteries, the aorta and pulmonary trunk, are attached to the superior surface of the heart, called the base. The base of the heart is located at the level of the third costal cartilage, as seen in Figure 1. The inferior tip of the heart, the apex, lies just to the left of the sternum between the junction of the fourth and fifth ribs near their articulation with the costal cartilages. The right side of the heart is deflected anteriorly, and the left side is deflected posteriorly. It is important to remember the position and orientation of the heart when placing a stethoscope on the chest of a patient and listening for heart sounds, and also when looking at images taken from a midsagittal perspective. The slight deviation of the apex to the left is reflected in a depression in the medial surface of the inferior lobe of the left lung, called the cardiac notch.

[caption id="" align="aligncenter" width="500"] Figure 1. Position of the Heart in the Thorax. The heart is located within the thoracic cavity, medially between the lungs in the mediastinum. It is about the size of a fist, is broad at the top, and tapers toward the base.[/caption]

Shape and Size of the Heart

The shape of the heart is similar to a pinecone, rather broad at the superior surface and tapering to the apex (see Figure 1). A typical heart is approximately the size of your fist: 12 cm (5 in) in length, 8 cm (3.5 in) wide, and 6 cm (2.5 in) in thickness. Given the size difference between most members of the sexes, the weight of a female heart is approximately 250–300 grams (9 to 11 ounces), and the weight of a male heart is approximately 300–350 grams (11 to 12 ounces). The heart of a well-trained athlete, especially one specializing in aerobic sports, can be considerably larger than this. Cardiac muscle responds to exercise in a manner similar to that of skeletal muscle. That is, exercise results in the addition of protein myofilaments that increase the size of the individual cells without increasing their numbers, a concept called hypertrophy. Hearts of athletes can pump blood more effectively at lower rates than those of nonathletes. Enlarged hearts are not always a result of exercise; they can result from pathologies, such as hypertrophic cardiomyopathy. The cause of an abnormally enlarged heart muscle is unknown, but the condition is often undiagnosed and can cause sudden death in apparently otherwise healthy young people.

Chambers and Circulation through the Heart

The human heart consists of four chambers: The left side and the right side each have one atrium and one ventricle. Each of the upper chambers, the right atrium (plural = atria) and the left atrium, acts as a receiving chamber and contracts to push blood into the lower chambers, the right ventricle and the left ventricle. The ventricles serve as the primary pumping chambers of the heart, propelling blood to the lungs or to the rest of the body.

There are two distinct but linked circuits in the human circulation called the pulmonary and systemic circuits. Although both circuits transport blood and everything it carries, we can initially view the circuits from the point of view of gases. The pulmonary circuit transports blood to and from the lungs, where it picks up oxygen and delivers carbon dioxide for exhalation. The systemic circuit transports oxygenated blood to virtually all of the tissues of the body and returns relatively deoxygenated blood and carbon dioxide to the heart to be sent back to the pulmonary circulation.

The right ventricle pumps deoxygenated blood into the pulmonary trunk, which leads toward the lungs and bifurcates into the left and right pulmonary arteries. These vessels in turn branch many times before reaching the pulmonary capillaries, where gas exchange occurs: Carbon dioxide exits the blood and oxygen enters. The pulmonary trunk arteries and their branches are the only arteries in the post-natal body that carry relatively deoxygenated blood. Highly oxygenated blood returning from the pulmonary capillaries in the lungs passes through a series of vessels that join together to form the pulmonary veins—the only post-natal veins in the body that carry highly oxygenated blood. The pulmonary veins conduct blood into the left atrium, which pumps the blood into the left ventricle, which in turn pumps oxygenated blood into the aorta and on to the many branches of the systemic circuit. Eventually, these vessels will lead to the systemic capillaries, where exchange with the tissue fluid and cells of the body occurs. In this case, oxygen and nutrients exit the systemic capillaries to be used by the cells in their metabolic processes, and carbon dioxide and waste products will enter the blood.

The blood exiting the systemic capillaries is lower in oxygen concentration than when it entered. The capillaries will ultimately unite to form venules, joining to form ever-larger veins, eventually flowing into the two major systemic veins, the superior vena cava and the inferior vena cava, which return blood to the right atrium. The blood in the superior and inferior venae cavae flows into the right atrium, which pumps blood into the right ventricle. This process of blood circulation continues as long as the individual remains alive. Understanding the flow of blood through the pulmonary and systemic circuits is critical to all health professions (Figure 3).

[caption id="" align="aligncenter" width="520"] Figure 3. Dual System of the Human Blood Circulation. Blood flows from the right atrium to the right ventricle, where it is pumped into the pulmonary circuit. The blood in the pulmonary artery branches is low in oxygen but relatively high in carbon dioxide. Gas exchange occurs in the pulmonary capillaries (oxygen into the blood, carbon dioxide out), and blood high in oxygen and low in carbon dioxide is returned to the left atrium. From here, blood enters the left ventricle, which pumps it into the systemic circuit. Following exchange in the systemic capillaries (oxygen and nutrients out of the capillaries and carbon dioxide and wastes in), blood returns to the right atrium and the cycle is repeated.[/caption]

Membranes, Surface Features, and Layers

Our exploration of more in-depth heart structures begins by examining the membrane that surrounds the heart, the prominent surface features of the heart, and the layers that form the wall of the heart. Each of these components plays its own unique role in terms of function.

Membranes

The membrane that directly surrounds the heart and defines the pericardial cavity is called the pericardium or pericardial sac. It also surrounds the “roots” of the major vessels, or the areas of closest proximity to the heart. The pericardium, which literally translates as “around the heart,” consists of two distinct sublayers: the sturdy outer fibrous pericardium and the inner serous pericardium. The fibrous pericardium is made of tough, dense connective tissue that protects the heart and maintains its position in the thorax. The more delicate serous pericardium consists of two layers: the parietal pericardium, which is fused to the fibrous pericardium, and an inner visceral pericardium, or epicardium, which is fused to the heart and is part of the heart wall. The pericardial cavity, filled with lubricating serous fluid, lies between the epicardium and the pericardium.

In most organs within the body, visceral serous membranes such as the epicardium are microscopic. However, in the case of the heart, it is not a microscopic layer but rather a macroscopic layer, consisting of a simple squamous epithelium called a mesothelium, reinforced with loose, irregular, or areolar connective tissue that attaches to the pericardium. This mesothelium secretes the lubricating serous fluid that fills the pericardial cavity and reduces friction as the heart contracts. Figure 4 illustrates the pericardial membrane and the layers of the heart.

[caption id="" align="aligncenter" width="480"] Figure 4. Pericardial Membranes and Layers of the Heart Wall. The pericardial membrane that surrounds the heart consists of three layers and the pericardial cavity. The heart wall also consists of three layers. The pericardial membrane and the heart wall share the epicardium.[/caption]

Surface Features of the Heart

Inside the pericardium, the surface features of the heart are visible, including the four chambers. There is a superficial leaf-like extension of the atria near the superior surface of the heart, one on each side, called an auricle—a name that means “ear like”—because its shape resembles the external ear of a human (Figure 5). Auricles are relatively thin-walled structures that can fill with blood and empty into the atria or upper chambers of the heart. You may also hear them referred to as atrial appendages. Also prominent is a series of fat-filled grooves, each of which is known as a sulcus (plural = sulci), along the superior surfaces of the heart. Major coronary blood vessels are located in these sulci. The deep coronary sulcus is located between the atria and ventricles. Located between the left and right ventricles are two additional sulci that are not as deep as the coronary sulcus. The anterior interventricular sulcus is visible on the anterior surface of the heart, whereas the posterior interventricular sulcus is visible on the posterior surface of the heart. Figure 5 illustrates anterior and posterior views of the surface of the heart.

[caption id="" align="aligncenter" width="530"] Figure 5. External Anatomy of the Heart. Inside the pericardium, the surface features of the heart are visible.[/caption]

Layers

The wall of the heart is composed of three layers of unequal thickness. From superficial to deep, these are the epicardium, the myocardium, and the endocardium (see Figure 4). The outermost layer of the wall of the heart is also the innermost layer of the pericardium, the epicardium, or the visceral pericardium discussed earlier.

The middle and thickest layer is the myocardium, made largely of cardiac muscle cells. It is built upon a framework of collagenous fibers, plus the blood vessels that supply the myocardium and the nerve fibers that help regulate the heart. It is the contraction of the myocardium that pumps blood through the heart and into the major arteries. The muscle pattern is elegant and complex, as the muscle cells swirl and spiral around the chambers of the heart. They form a figure 8 pattern around the atria and around the bases of the great vessels. Deeper ventricular muscles also form a figure 8 around the two ventricles and proceed toward the apex. More superficial layers of ventricular muscle wrap around both ventricles. This complex swirling pattern allows the heart to pump blood more effectively than a simple linear pattern would. Figure 6 illustrates the arrangement of muscle cells.

[caption id="" align="aligncenter" width="280"] Figure 6. Heart Musculature. The swirling pattern of cardiac muscle tissue contributes significantly to the heart’s ability to pump blood effectively.[/caption]

Although the ventricles on the right and left sides pump the same amount of blood per contraction, the muscle of the left ventricle is much thicker and better developed than that of the right ventricle. In order to overcome the high resistance required to pump blood into the long systemic circuit, the left ventricle must generate a great amount of pressure. The right ventricle does not need to generate as much pressure, since the pulmonary circuit is shorter and provides less resistance. Figure 7 illustrates the differences in muscular thickness needed for each of the ventricles.

[caption id="" align="aligncenter" width="480"] Figure 7. Differences in Ventricular Muscle Thickness. The myocardium in the left ventricle is significantly thicker than that of the right ventricle. Both ventricles pump the same amount of blood, but the left ventricle must generate a much greater pressure to overcome greater resistance in the systemic circuit. The ventricles are shown in both relaxed and contracting states. Note the differences in the relative size of the lumens, the region inside each ventricle where the blood is contained.[/caption]

The innermost layer of the heart wall, the endocardium, is joined to the myocardium with a thin layer of connective tissue. The endocardium lines the chambers where the blood circulates and covers the heart valves. It is made of simple squamous epithelium called endothelium, which is continuous with the endothelial lining of the blood vessels (see Figure 4).

Once regarded as a simple lining layer, recent evidence indicates that the endothelium of the endocardium and the coronary capillaries may play active roles in regulating the contraction of the muscle within the myocardium. The endothelium may also regulate the growth patterns of the cardiac muscle cells throughout life, and the endothelins it secretes create an environment in the surrounding tissue fluids that regulates ionic concentrations and states of contractility. Endothelins are potent vasoconstrictors and, in a normal individual, establish a homeostatic balance with other vasoconstrictors and vasodilators.

Internal Structure of the Heart

Recall that the heart’s contraction cycle follows a dual pattern of circulation—the pulmonary and systemic circuits—because of the pairs of chambers that pump blood into the circulation. In order to develop a more precise understanding of cardiac function, it is first necessary to explore the internal anatomical structures in more detail.

Septa of the Heart

The word septum is derived from the Latin for “something that encloses;” in this case, a septum (plural = septa) refers to a wall or partition that divides the heart into chambers. The septa are physical extensions of the myocardium lined with endocardium. Located between the two atria is the interatrial septum. Normally in an adult heart, the interatrial septum bears an oval-shaped depression known as the fossa ovalis, a remnant of an opening in the fetal heart known as the foramen ovale. The foramen ovale allowed blood in the fetal heart to pass directly from the right atrium to the left atrium, allowing some blood to bypass the pulmonary circuit. Within seconds after birth, a flap of tissue known as the septum primum that previously acted as a valve closes the foramen ovale and establishes the typical cardiac circulation pattern.

Between the two ventricles is a second septum known as the interventricular septum. Unlike the interatrial septum, the interventricular septum is normally intact after its formation during fetal development. It is substantially thicker than the interatrial septum, since the ventricles generate far greater pressure when they contract.

The septum between the atria and ventricles is known as the atrioventricular septum. It is marked by the presence of four openings that allow blood to move from the atria into the ventricles and from the ventricles into the pulmonary trunk and aorta. Located in each of these openings between the atria and ventricles is a valve, a specialized structure that ensures one-way flow of blood. The valves between the atria and ventricles are known generically as atrioventricular valves. The valves at the openings that lead to the pulmonary trunk and aorta are known generically as semilunar valves. The interventricular septum is visible in Figure 8. In this figure, the atrioventricular septum has been removed to better show the bicupid and tricuspid valves; the interatrial septum is not visible, since its location is covered by the aorta and pulmonary trunk. Since these openings and valves structurally weaken the atrioventricular septum, the remaining tissue is heavily reinforced with dense connective tissue called the cardiac skeleton, or skeleton of the heart. It includes four rings that surround the openings between the atria and ventricles, and the openings to the pulmonary trunk and aorta, and serve as the point of attachment for the heart valves. The cardiac skeleton also provides an important boundary in the heart electrical conduction system.

[caption id="" align="aligncenter" width="480"] Figure 8. Internal Structures of the Heart. This anterior view of the heart shows the four chambers, the major vessels and their early branches, as well as the valves. The presence of the pulmonary trunk and aorta covers the interatrial septum, and the atrioventricular septum is cut away to show the atrioventricular valves.[/caption]

Right Atrium

The right atrium serves as the receiving chamber for blood returning to the heart from the systemic circulation. The two major systemic veins, the superior and inferior venae cavae, and the large coronary vein called the coronary sinus that drains the heart myocardium empty into the right atrium. The superior vena cava drains blood from regions superior to the diaphragm: the head, neck, upper limbs, and the thoracic region. It empties into the superior and posterior portions of the right atrium. The inferior vena cava drains blood from areas inferior to the diaphragm: the lower limbs and abdominopelvic region of the body. It, too, empties into the posterior portion of the atria, but inferior to the opening of the superior vena cava. Immediately superior and slightly medial to the opening of the inferior vena cava on the posterior surface of the atrium is the opening of the coronary sinus. This thin-walled vessel drains most of the coronary veins that return systemic blood from the heart. The majority of the internal heart structures discussed in this and subsequent sections are illustrated in Figure 8.

While the bulk of the internal surface of the right atrium is smooth, the depression of the fossa ovalis is medial, and the anterior surface demonstrates prominent ridges of muscle called the pectinate muscles. The right auricle also has pectinate muscles. The left atrium does not have pectinate muscles except in the auricle.

The atria receive venous blood on a nearly continuous basis, preventing venous flow from stopping while the ventricles are contracting. While most ventricular filling occurs while the atria are relaxed, they do demonstrate a contractile phase and actively pump blood into the ventricles just prior to ventricular contraction. The opening between the atrium and ventricle is guarded by the tricuspid valve.

Right Ventricle

The right ventricle receives blood from the right atrium through the tricuspid valve. Each flap of the valve is attached to strong strands of connective tissue, the chordae tendineae, literally “tendinous cords,” or sometimes more poetically referred to as “heart strings.” There are several chordae tendineae associated with each of the flaps. They are composed of approximately 80 percent collagenous fibers with the remainder consisting of elastic fibers and endothelium. They connect each of the flaps to a papillary muscle that extends from the inferior ventricular surface. There are three papillary muscles in the right ventricle, called the anterior, posterior, and septal muscles, which correspond to the three sections of the valves.

When the myocardium of the ventricle contracts, pressure within the ventricular chamber rises. Blood, like any fluid, flows from higher pressure to lower pressure areas, in this case, toward the pulmonary trunk and the atrium. To prevent any potential backflow, the papillary muscles also contract, generating tension on the chordae tendineae. This prevents the flaps of the valves from being forced into the atria and regurgitation of the blood back into the atria during ventricular contraction. Figure 10 shows papillary muscles and chordae tendineae attached to the tricuspid valve.

[caption id="" align="aligncenter" width="400"] Figure 10. Chordae Tendineae and Papillary Muscles. In this frontal section, you can see papillary muscles attached to the tricuspid valve on the right as well as the mitral valve on the left via chordae tendineae. (credit: modification of work by “PV KS”/flickr.com)[/caption]

The walls of the ventricle are lined with trabeculae carneae, ridges of cardiac muscle covered by endocardium. In addition to these muscular ridges, a band of cardiac muscle, also covered by endocardium, known as the moderator band (see Figure 8) reinforces the thin walls of the right ventricle and plays a crucial role in cardiac conduction. It arises from the inferior portion of the interventricular septum and crosses the interior space of the right ventricle to connect with the inferior papillary muscle.

When the right ventricle contracts, it ejects blood into the pulmonary trunk, which branches into the left and right pulmonary arteries that carry it to each lung. The superior surface of the right ventricle begins to taper as it approaches the pulmonary trunk. At the base of the pulmonary trunk is the pulmonary semilunar valve that prevents backflow from the pulmonary trunk.

Left Atrium

After exchange of gases in the pulmonary capillaries, blood returns to the left atrium high in oxygen via one of the four pulmonary veins. While the left atrium does not contain pectinate muscles, it does have an auricle that includes these pectinate ridges. Blood flows nearly continuously from the pulmonary veins back into the atrium, which acts as the receiving chamber, and from here through an opening into the left ventricle. Most blood flows passively into the heart while both the atria and ventricles are relaxed, but toward the end of the ventricular relaxation period, the left atrium will contract, pumping blood into the ventricle. This atrial contraction accounts for approximately 20 percent of ventricular filling. The opening between the left atrium and ventricle is guarded by the mitral valve.

Left Ventricle

Recall that, although both sides of the heart will pump the same amount of blood, the muscular layer is much thicker in the left ventricle compared to the right (see Figure 7). Like the right ventricle, the left also has trabeculae carneae, but there is no moderator band. The mitral valve is connected to papillary muscles via chordae tendineae. There are two papillary muscles on the left—the anterior and posterior—as opposed to three on the right.

The left ventricle is the major pumping chamber for the systemic circuit; it ejects blood into the aorta through the aortic semilunar valve.

Heart Valve Structure and Function

A transverse section through the heart slightly above the level of the atrioventricular septum reveals all four heart valves along the same plane (Figure 11). The valves ensure unidirectional blood flow through the heart. Between the right atrium and the right ventricle is the right atrioventricular valve, or tricuspid valve. It typically consists of three flaps, or leaflets, made of endocardium reinforced with additional connective tissue. The flaps are connected by chordae tendineae to the papillary muscles, which control the opening and closing of the valves.

[caption id="" align="aligncenter" width="420"] Figure 11. Heart Valves. With the atria and major vessels removed, all four valves are clearly visible, although it is difficult to distinguish the three separate cusps of the tricuspid valve.[/caption]

Emerging from the right ventricle at the base of the pulmonary trunk is the pulmonary semilunar valve, or the pulmonary valve; it is also known as the pulmonic valve or the right semilunar valve. The pulmonary valve is comprised of three small flaps of endothelium reinforced with connective tissue. When the ventricle relaxes, the pressure differential causes blood to flow back into the ventricle from the pulmonary trunk. This flow of blood fills the pocket-like flaps of the pulmonary valve, causing the valve to close and producing an audible sound. Unlike the atrioventricular valves, there are no papillary muscles or chordae tendineae associated with the pulmonary valve.

Located at the opening between the left atrium and left ventricle is the mitral valve, also called the bicuspid valve or the left atrioventricular valve. Structurally, this valve consists of two cusps, known as the anterior medial cusp and the posterior medial cusp, compared to the three cusps of the tricuspid valve. In a clinical setting, the valve is referred to as the mitral valve, rather than the bicuspid valve. The two cusps of the mitral valve are attached by chordae tendineae to two papillary muscles that project from the wall of the ventricle.

At the base of the aorta is the aortic semilunar valve, or the aortic valve, which prevents backflow from the aorta. It normally is composed of three flaps. When the ventricle relaxes and blood attempts to flow back into the ventricle from the aorta, blood will fill the cusps of the valve, causing it to close and producing an audible sound.

In Figure 12a, the two atrioventricular valves are open and the two semilunar valves are closed. This occurs when both atria and ventricles are relaxed and when the atria contract to pump blood into the ventricles. Figure 12b shows a frontal view. Although only the left side of the heart is illustrated, the process is virtually identical on the right.

[caption id="" align="aligncenter" width="480"] Figure 12. Blood Flow from the Left Atrium to the Left Ventricle. (a) A transverse section through the heart illustrates the four heart valves. The two atrioventricular valves are open; the two semilunar valves are closed. The atria and vessels have been removed. (b) A frontal section through the heart illustrates blood flow through the mitral valve. When the mitral valve is open, it allows blood to move from the left atrium to the left ventricle. The aortic semilunar valve is closed to prevent backflow of blood from the aorta to the left ventricle.[/caption]

Figure 13a shows the atrioventricular valves closed while the two semilunar valves are open. This occurs when the ventricles contract to eject blood into the pulmonary trunk and aorta. Closure of the two atrioventricular valves prevents blood from being forced back into the atria. This stage can be seen from a frontal view in Figure 13b.

[caption id="" align="aligncenter" width="480"] Figure 13. Blood Flow from the Left Ventricle into the Great Vessels. (a) A transverse section through the heart illustrates the four heart valves during ventricular contraction. The two atrioventricular valves are closed, but the two semilunar valves are open. The atria and vessels have been removed. (b) A frontal view shows the closed mitral (bicuspid) valve that prevents backflow of blood into the left atrium. The aortic semilunar valve is open to allow blood to be ejected into the aorta.[/caption]

When the ventricles begin to contract, pressure within the ventricles rises and blood flows toward the area of lowest pressure, which is initially in the atria. This backflow causes the cusps of the tricuspid and mitral (bicuspid) valves to close. These valves are tied down to the papillary muscles by chordae tendineae. During the relaxation phase of the cardiac cycle, the papillary muscles are also relaxed and the tension on the chordae tendineae is slight (see Figure 12b). However, as the myocardium of the ventricle contracts, so do the papillary muscles. This creates tension on the chordae tendineae (see Figure 13b), helping to hold the cusps of the atrioventricular valves in place and preventing them from being blown back into the atria.

The aortic and pulmonary semilunar valves lack the chordae tendineae and papillary muscles associated with the atrioventricular valves. Instead, they consist of pocket-like folds of endocardium reinforced with additional connective tissue. When the ventricles relax and the change in pressure forces the blood toward the ventricles, the blood presses against these cusps and seals the openings.

Coronary Circulation

You will recall that the heart is a remarkable pump composed largely of cardiac muscle cells that are incredibly active throughout life. Like all other cells, a cardiomyocyte requires a reliable supply of oxygen and nutrients, and a way to remove wastes, so it needs a dedicated, complex, and extensive coronary circulation. And because of the critical and nearly ceaseless activity of the heart throughout life, this need for a blood supply is even greater than for a typical cell. However, coronary circulation is not continuous; rather, it cycles, reaching a peak when the heart muscle is relaxed and nearly ceasing while it is contracting.

Coronary Arteries

Coronary arteries supply blood to the myocardium and other components of the heart. The first portion of the aorta after it arises from the left ventricle gives rise to the coronary arteries. There are three dilations in the wall of the aorta just superior to the aortic semilunar valve. Two of these, the left posterior aortic sinus and anterior aortic sinus, give rise to the left and right coronary arteries, respectively. The third sinus, the right posterior aortic sinus, typically does not give rise to a vessel. Coronary vessel branches that remain on the surface of the artery and follow the sulci are called epicardial coronary arteries.

The left coronary artery distributes blood to the left side of the heart, the left atrium and ventricle, and the interventricular septum. The circumflex artery arises from the left coronary artery and follows the coronary sulcus to the left. Eventually, it will fuse with the small branches of the right coronary artery. The larger anterior interventricular artery, also known as the left anterior descending artery (LAD), is the second major branch arising from the left coronary artery. It follows the anterior interventricular sulcus around the pulmonary trunk. Along the way it gives rise to numerous smaller branches that interconnect with the branches of the posterior interventricular artery, forming anastomoses. An anastomosis is an area where vessels unite to form interconnections that normally allow blood to circulate to a region even if there may be partial blockage in another branch. The anastomoses in the heart are very small. Therefore, this ability is somewhat restricted in the heart so a coronary artery blockage often results in death of the cells (myocardial infarction) supplied by the particular vessel.

The right coronary artery proceeds along the coronary sulcus and distributes blood to the right atrium, portions of both ventricles, and the heart conduction system. Normally, one or more marginal arteries arise from the right coronary artery inferior to the right atrium. The marginal arteries supply blood to the superficial portions of the right ventricle. On the posterior surface of the heart, the right coronary artery gives rise to the posterior interventricular artery, also known as the posterior descending artery. It runs along the posterior portion of the interventricular sulcus toward the apex of the heart, giving rise to branches that supply the interventricular septum and portions of both ventricles. Figure 14 presents views of the coronary circulation from both the anterior and posterior views.

[caption id="" align="aligncenter" width="550"] Figure 14. Coronary Circulation. The anterior view of the heart shows the prominent coronary surface vessels. The posterior view of the heart shows the prominent coronary surface vessels.[/caption]

Coronary Veins

Coronary veins drain the heart and generally parallel the large surface arteries (see Figure 14). The great cardiac vein can be seen initially on the surface of the heart following the interventricular sulcus, but it eventually flows along the coronary sulcus into the coronary sinus on the posterior surface. The great cardiac vein initially parallels the anterior interventricular artery and drains the areas supplied by this vessel. It receives several major branches, including the posterior cardiac vein, the middle cardiac vein, and the small cardiac vein. The posterior cardiac vein parallels and drains the areas supplied by the marginal artery branch of the circumflex artery. The middle cardiac vein parallels and drains the areas supplied by the posterior interventricular artery. The small cardiac vein parallels the right coronary artery and drains the blood from the posterior surfaces of the right atrium and ventricle. The coronary sinus is a large, thin-walled vein on the posterior surface of the heart lying within the atrioventricular sulcus and emptying directly into the right atrium. The anterior cardiac veins parallel the small cardiac arteries and drain the anterior surface of the right ventricle. Unlike these other cardiac veins, it bypasses the coronary sinus and drains directly into the right atrium.

[caption id="attachment_2973" align="aligncenter" width="150"] Watch this CrashCourse video for an overview of the heart.[/caption]

19.2 Cardiac Muscle and Electrical Activity

barkerj1 — Wed, 30 Aug 2017 18:39:24 +0000

Learning Objectives

By the end of this section, you will be able to:

Specify the four components of the conduction system of the heart
Describe the normal conduction of an electrical impulse through the heart
Describe the major components of the human electrocardiogram (ECG) and relate these to the electrical and mechanical events of the heart

Recall that cardiac muscle shares a few characteristics with both skeletal muscle and smooth muscle, but it has some unique properties of its own. Not the least of these exceptional properties is its ability to initiate an electrical potential at a fixed rate that spreads rapidly from cell to cell to trigger the contractile mechanism. This property is known as autorhythmicity. Neither smooth nor skeletal muscle can do this. Even though cardiac muscle has autorhythmicity, heart rate is modulated by the endocrine and nervous systems.

There are two major types of cardiac muscle cells: myocardial contractile cells and myocardial conducting cells. The myocardial contractile cells constitute the bulk (99 percent) of the cells in the atria and ventricles. Contractile cells conduct impulses and are responsible for contractions that pump blood through the body. The myocardial conducting cells (1 percent of the cells) form the conduction system of the heart. Except for Purkinje cells, they are generally much smaller than the contractile cells and have few of the myofibrils or filaments needed for contraction. Their function is similar in many respects to neurons, although they are specialized muscle cells. Myocardial conduction cells initiate and propagate the action potential (the electrical impulse) that travels throughout the heart and triggers the contractions that propel the blood.

Structure of Cardiac Muscle

Compared to the giant cylinders of skeletal muscle, cardiac muscle cells, or cardiomyocytes, are considerably shorter with much smaller diameters. Cardiac muscle also demonstrates striations, the alternating pattern of dark A bands and light I bands attributed to the precise arrangement of the myofilaments and fibrils that are organized in sarcomeres along the length of the cell (Figure 1a). These contractile elements are virtually identical to skeletal muscle. T (transverse) tubules penetrate from the surface plasma membrane, the sarcolemma, to the interior of the cell, allowing the electrical impulse to reach the interior. The T tubules are only found at the Z discs, whereas in skeletal muscle, they are found at the junction of the A and I bands. Therefore, there are one-half as many T tubules in cardiac muscle as in skeletal muscle. In addition, the sarcoplasmic reticulum stores few calcium ions, so most of the calcium ions must come from outside the cells. The result is a slower onset of contraction. Mitochondria are plentiful, providing energy for the contractions of the heart. Typically, cardiomyocytes have a single, central nucleus, but two or more nuclei may be found in some cells.

Cardiac muscle cells branch freely. A junction between two adjoining cells is marked by a critical structure called an intercalated disc, which helps support the synchronized contraction of the muscle (Figure 1b). The sarcolemmas from adjacent cells bind together at the intercalated discs. They consist of desmosomes, specialized linking proteoglycans, tight junctions, and large numbers of gap junctions that allow the passage of ions between the cells and help to synchronize the contraction (Figure 1c). Intercellular connective tissue also helps to bind the cells together. The importance of strongly binding these cells together is necessitated by the forces exerted by contraction.

[caption id="" align="aligncenter" width="520"] Figure 1. Cardiac Muscle. (a) Cardiac muscle cells have myofibrils composed of myofilaments arranged in sarcomeres, T tubules to transmit the impulse from the sarcolemma to the interior of the cell, numerous mitochondria for energy, and intercalated discs that are found at the junction of different cardiac muscle cells. (b) A photomicrograph of cardiac muscle cells shows the nuclei and intercalated discs. (c) An intercalated disc connects cardiac muscle cells and consists of desmosomes and gap junctions. LM × 1600. (Micrograph provided by the Regents of the University of Michigan Medical School © 2012)[/caption]

Cardiac muscle undergoes aerobic respiration patterns, primarily metabolizing lipids and carbohydrates. Myoglobin, lipids, and glycogen are all stored within the cytoplasm. Cardiac muscle cells undergo twitch-type contractions with long refractory periods followed by brief relaxation periods. The relaxation is essential so the heart can fill with blood for the next cycle. The refractory period is very long to prevent the possibility of tetany, a condition in which muscle remains involuntarily contracted. In the heart, tetany is not compatible with life, since it would prevent the heart from pumping blood.

Repair and Replacement

Damaged cardiac muscle cells have extremely limited abilities to repair themselves or to replace dead cells via mitosis. Recent evidence indicates that at least some stem cells remain within the heart that continue to divide and at least potentially replace these dead cells. However, newly formed or repaired cells are rarely as functional as the original cells, and cardiac function is reduced. In the event of a heart attack or MI, dead cells are often replaced by patches of scar tissue. Autopsies performed on individuals who had successfully received heart transplants show some proliferation of original cells. If researchers can unlock the mechanism that generates new cells and restore full mitotic capabilities to heart muscle, the prognosis for heart attack survivors will be greatly enhanced. To date, myocardial cells produced within the patient (in situ) by cardiac stem cells seem to be nonfunctional, although those grown in Petri dishes (in vitro) do beat. Perhaps soon this mystery will be solved, and new advances in treatment will be commonplace.

Conduction System of the Heart

If embryonic heart cells are separated into a Petri dish and kept alive, each is capable of generating its own electrical impulse followed by contraction. When two independently beating embryonic cardiac muscle cells are placed together, the cell with the higher inherent rate sets the pace, and the impulse spreads from the faster to the slower cell to trigger a contraction. As more cells are joined together, the fastest cell continues to assume control of the rate. A fully developed adult heart maintains the capability of generating its own electrical impulse, triggered by the fastest cells, as part of the cardiac conduction system. The components of the cardiac conduction system include the sinoatrial node, the atrioventricular node, the atrioventricular bundle, the atrioventricular bundle branches, and the Purkinje cells (Figure 2).

[caption id="" align="aligncenter" width="500"] Figure 2. Conduction System of the Heart. Specialized conducting components of the heart include the sinoatrial node, the internodal pathways, the atrioventricular node, the atrioventricular bundle, the right and left bundle branches, and the Purkinje fibers.[/caption]

Sinoatrial (SA) Node

Normal cardiac rhythm is established by the sinoatrial (SA) node, a specialized clump of myocardial conducting cells located in the superior and posterior walls of the right atrium in close proximity to the orifice of the superior vena cava. The SA node has the highest inherent rate of depolarization and is known as the pacemaker of the heart. It initiates the sinus rhythm, or normal electrical pattern followed by contraction of the heart.

This impulse spreads from its initiation in the SA node throughout the atria through specialized internodal pathways, to the atrial myocardial contractile cells and the atrioventricular node. The internodal pathways consist of three bands (anterior, middle, and posterior) that lead directly from the SA node to the next node in the conduction system, the atrioventricular node (see Figure 2). The impulse takes approximately 50 ms (milliseconds) to travel between these two nodes. The relative importance of this pathway has been debated since the impulse would reach the atrioventricular node simply following the cell-by-cell pathway through the contractile cells of the myocardium in the atria. In addition, there is a specialized pathway called Bachmann’s bundle or the interatrial band that conducts the impulse directly from the right atrium to the left atrium. Regardless of the pathway, as the impulse reaches the atrioventricular septum, the connective tissue of the cardiac skeleton prevents the impulse from spreading into the myocardial cells in the ventricles except at the atrioventricular node. Figure 3 illustrates the initiation of the impulse in the SA node that then spreads the impulse throughout the atria to the atrioventricular node.

[caption id="" align="aligncenter" width="400"] Figure 3. Cardiac Conduction. (1) The sinoatrial (SA) node and the remainder of the conduction system are at rest. (2) The SA node initiates the action potential, which sweeps across the atria. (3) After reaching the atrioventricular node, there is a delay of approximately 100 ms that allows the atria to complete pumping blood before the impulse is transmitted to the atrioventricular bundle. (4) Following the delay, the impulse travels through the atrioventricular bundle and bundle branches to the Purkinje fibers, and also reaches the right papillary muscle via the moderator band. (5) The impulse spreads to the contractile fibers of the ventricle. (6) Ventricular contraction begins.[/caption]

The electrical event, the wave of depolarization, is the trigger for muscular contraction. The wave of depolarization begins in the right atrium, and the impulse spreads across the superior portions of both atria and then down through the contractile cells. The contractile cells then begin contraction from the superior to the inferior portions of the atria, efficiently pumping blood into the ventricles.

Atrioventricular (AV) Node

The atrioventricular (AV) node is a second clump of specialized myocardial conductive cells, located in the inferior portion of the right atrium within the atrioventricular septum. The septum prevents the impulse from spreading directly to the ventricles without passing through the AV node. There is a critical pause before the AV node depolarizes and transmits the impulse to the atrioventricular bundle (see Figure 3, step 3). This delay in transmission is partially attributable to the small diameter of the cells of the node, which slow the impulse. Also, conduction between nodal cells is less efficient than between conducting cells. These factors mean that it takes the impulse approximately 100 ms to pass through the node. This pause is critical to heart function, as it allows the atrial cardiomyocytes to complete their contraction that pumps blood into the ventricles before the impulse is transmitted to the cells of the ventricle itself. With extreme stimulation by the SA node, the AV node can transmit impulses maximally at 220 per minute. This establishes the typical maximum heart rate in a healthy young individual. Damaged hearts or those stimulated by drugs can contract at higher rates, but at these rates, the heart can no longer effectively pump blood.

Atrioventricular Bundle (Bundle of His), Bundle Branches, and Purkinje Fibers

Arising from the AV node, the atrioventricular bundle, or bundle of His, proceeds through the interventricular septum before dividing into two atrioventricular bundle branches, commonly called the left and right bundle branches. The left bundle branch has two fascicles. The left bundle branch supplies the left ventricle, and the right bundle branch the right ventricle. Since the left ventricle is much larger than the right, the left bundle branch is also considerably larger than the right. Portions of the right bundle branch are found in the moderator band and supply the right papillary muscles. Because of this connection, each papillary muscle receives the impulse at approximately the same time, so they begin to contract simultaneously just prior to the remainder of the myocardial contractile cells of the ventricles. This is believed to allow tension to develop on the chordae tendineae prior to right ventricular contraction. There is no corresponding moderator band on the left. Both bundle branches descend and reach the apex of the heart where they connect with the Purkinje fibers (see Figure 3, step 4). This passage takes approximately 25 ms.

The Purkinje fibers are additional myocardial conductive fibers that spread the impulse to the myocardial contractile cells in the ventricles. They extend throughout the myocardium from the apex of the heart toward the atrioventricular septum and the base of the heart. The Purkinje fibers have a fast inherent conduction rate, and the electrical impulse reaches all of the ventricular muscle cells in about 75 ms (see Figure 3, step 5). Since the electrical stimulus begins at the apex, the contraction also begins at the apex and travels toward the base of the heart, similar to squeezing a tube of toothpaste from the bottom. This allows the blood to be pumped out of the ventricles and into the aorta and pulmonary trunk. The total time elapsed from the initiation of the impulse in the SA node until depolarization of the ventricles is approximately 225 ms.

Membrane Potentials and Ion Movement in Cardiac Conductive Cells

Action potentials are considerably different between cardiac conductive cells and cardiac contractive cells. While Na⁺ and K⁺ play essential roles, Ca²⁺ is also critical for both types of cells. Unlike skeletal muscles and neurons, cardiac conductive cells do not have a stable resting potential. Conductive cells contain a series of sodium ion channels that allow a normal and slow influx of sodium ions that causes the membrane potential to rise slowly from an initial value of −60 mV up to about –40 mV. The resulting movement of sodium ions creates spontaneous depolarization (or prepotential depolarization). At this point, calcium ion channels open and Ca²⁺enters the cell, further depolarizing it at a more rapid rate until it reaches a value of approximately +5 mV. At this point, the calcium ion channels close and K⁺ channels open, allowing outflux of K⁺ and resulting in repolarization. When the membrane potential reaches approximately −60 mV, the K⁺channels close and Na⁺ channels open, and the prepotential phase begins again. This phenomenon explains the autorhythmicity properties of cardiac muscle (Figure 4).

[caption id="" align="aligncenter" width="430"] Figure 4. Action Potential at the SA Node. The prepotential is due to a slow influx of sodium ions until the threshold is reached followed by a rapid depolarization and repolarization. The prepotential accounts for the membrane reaching threshold and initiates the spontaneous depolarization and contraction of the cell. Note the lack of a resting potential.[/caption]

Membrane Potentials and Ion Movement in Cardiac Contractile Cells

There is a distinctly different electrical pattern involving the contractile cells. In this case, there is a rapid depolarization, followed by a plateau phase and then repolarization. This phenomenon accounts for the long refractory periods required for the cardiac muscle cells to pump blood effectively before they are capable of firing for a second time. These cardiac myocytes normally do not initiate their own electrical potential, although they are capable of doing so, but rather wait for an impulse to reach them.

Contractile cells demonstrate a much more stable resting phase than conductive cells at approximately −80 mV for cells in the atria and −90 mV for cells in the ventricles. Despite this initial difference, the other components of their action potentials are virtually identical. In both cases, when stimulated by an action potential, voltage-gated channels rapidly open, beginning the positive-feedback mechanism of depolarization. This rapid influx of positively charged ions raises the membrane potential to approximately +30 mV, at which point the sodium channels close. The rapid depolarization period typically lasts 3–5 ms. Depolarization is followed by the plateau phase, in which membrane potential declines relatively slowly. This is due in large part to the opening of the slow Ca²⁺ channels, allowing Ca²⁺ to enter the cell while few K⁺ channels are open, allowing K⁺ to exit the cell. The relatively long plateau phase lasts approximately 175 ms. Once the membrane potential reaches approximately zero, the Ca²⁺channels close and K⁺channels open, allowing K⁺to exit the cell. The repolarization lasts approximately 75 ms. At this point, membrane potential drops until it reaches resting levels once more and the cycle repeats. The entire event lasts between 250 and 300 ms (Figure 5).

The absolute refractory period for cardiac contractile muscle lasts approximately 200 ms, and the relative refractory period lasts approximately 50 ms, for a total of 250 ms. This extended period is critical, since the heart muscle must contract to pump blood effectively and the contraction must follow the electrical events. Without extended refractory periods, premature contractions would occur in the heart and would not be compatible with life.

[caption id="" align="aligncenter" width="480"] Figure 5. Action Potential in Cardiac Contractile Cells. (a) Note the long plateau phase due to the influx of calcium ions. The extended refractory period allows the cell to fully contract before another electrical event can occur. (b) The action potential for heart muscle is compared to that of skeletal muscle.[/caption]

Calcium Ions

Calcium ions play two critical roles in the physiology of cardiac muscle. Their influx through slow calcium channels accounts for the prolonged plateau phase and absolute refractory period that enable cardiac muscle to function properly. Calcium ions also combine with the regulatory protein troponin in the troponin-tropomyosin complex; this complex removes the inhibition that prevents the heads of the myosin molecules from forming cross bridges with the active sites on actin that provide the power stroke of contraction. This mechanism is virtually identical to that of skeletal muscle. Approximately 20 percent of the calcium required for contraction is supplied by the influx of Ca²⁺ during the plateau phase. The remaining Ca²⁺ for contraction is released from storage in the sarcoplasmic reticulum.

Comparative Rates of Conduction System Firing

The pattern of prepotential or spontaneous depolarization, followed by rapid depolarization and repolarization just described, are seen in the SA node and a few other conductive cells in the heart. Since the SA node is the pacemaker, it reaches threshold faster than any other component of the conduction system. It will initiate the impulses spreading to the other conducting cells. The SA node, without nervous or endocrine control, would initiate a heart impulse approximately 80–100 times per minute. Although each component of the conduction system is capable of generating its own impulse, the rate progressively slows as you proceed from the SA node to the Purkinje fibers. Without the SA node, the AV node would generate a heart rate of 40–60 beats per minute. If the AV node were blocked, the atrioventricular bundle would fire at a rate of approximately 30–40 impulses per minute. The bundle branches would have an inherent rate of 20–30 impulses per minute, and the Purkinje fibers would fire at 15–20 impulses per minute. While a few exceptionally trained aerobic athletes demonstrate resting heart rates in the range of 30–40 beats per minute (the lowest recorded figure is 28 beats per minute for Miguel Indurain, a cyclist), for most individuals, rates lower than 50 beats per minute would indicate a condition called bradycardia. Depending upon the specific individual, as rates fall much below this level, the heart would be unable to maintain adequate flow of blood to vital tissues, initially resulting in decreasing loss of function across the systems, unconsciousness, and ultimately death.

Electrocardiogram

By careful placement of surface electrodes on the body, it is possible to record the complex, compound electrical signal of the heart. This tracing of the electrical signal is the electrocardiogram (ECG), also commonly abbreviated EKG (K coming kardiology, from the German term for cardiology). Careful analysis of the ECG reveals a detailed picture of both normal and abnormal heart function, and is an indispensable clinical diagnostic tool. The standard electrocardiograph (the instrument that generates an ECG) uses 3, 5, or 12 leads. The greater the number of leads an electrocardiograph uses, the more information the ECG provides. The term “lead” may be used to refer to the cable from the electrode to the electrical recorder, but it typically describes the voltage difference between two of the electrodes. The 12-lead electrocardiograph uses 10 electrodes placed in standard locations on the patient’s skin (Figure 6). In continuous ambulatory electrocardiographs, the patient wears a small, portable, battery-operated device known as a Holter monitor, or simply a Holter, that continuously monitors heart electrical activity, typically for a period of 24 hours during the patient’s normal routine.

[caption id="" align="aligncenter" width="350"] Figure 6. Standard Placement of ECG Leads. In a 12-lead ECG, six electrodes are placed on the chest, and four electrodes are placed on the limbs.[/caption]

A normal ECG tracing is presented in Figure 7. Each component, segment, and interval is labeled and corresponds to important electrical events, demonstrating the relationship between these events and contraction in the heart.

There are five prominent points on the ECG: the P wave, the QRS complex, and the T wave. The small P wave represents the depolarization of the atria. The atria begin contracting approximately 25 ms after the start of the P wave. The large QRS complex represents the depolarization of the ventricles, which requires a much stronger electrical signal because of the larger size of the ventricular cardiac muscle. The ventricles begin to contract as the QRS reaches the peak of the R wave. Lastly, the T wave represents the repolarization of the ventricles. The repolarization of the atria occurs during the QRS complex, which masks it on an ECG.

The major segments and intervals of an ECG tracing are indicated in Figure 7. Segments are defined as the regions between two waves. Intervals include one segment plus one or more waves. For example, the PR segment begins at the end of the P wave and ends at the beginning of the QRS complex. The PR interval starts at the beginning of the P wave and ends with the beginning of the QRS complex. The PR interval is more clinically relevant, as it measures the duration from the beginning of atrial depolarization (the P wave) to the initiation of the QRS complex. Since the Q wave may be difficult to view in some tracings, the measurement is often extended to the R that is more easily visible. Should there be a delay in passage of the impulse from the SA node to the AV node, it would be visible in the PR interval. Figure 8 correlates events of heart contraction to the corresponding segments and intervals of an ECG.

[caption id="" align="aligncenter" width="120"] Visit this site for a more detailed analysis of ECGs.[/caption]

[caption id="" align="aligncenter" width="430"] Figure 7. Electrocardiogram. A normal tracing shows the P wave, QRS complex, and T wave. Also indicated are the PR, QT, QRS, and ST intervals, plus the P-R and S-T segments.[/caption]

[caption id="" align="aligncenter" width="480"] Figure 8. ECG Tracing Correlated to the Cardiac Cycle. This diagram correlates an ECG tracing with the electrical and mechanical events of a heart contraction. Each segment of an ECG tracing corresponds to one event in the cardiac cycle.[/caption]

Occassionally, an area of the heart other than the SA node will initiate an impulse that will be followed by a premature contraction. Such an area, which may actually be a component of the conduction system or some other contractile cells, is known as an ectopic focus or ectopic pacemaker. An ectopic focus may be stimulated by localized ischemia; exposure to certain drugs, including caffeine, digitalis, or acetylcholine; elevated stimulation by both sympathetic or parasympathetic divisions of the autonomic nervous system; or a number of disease or pathological conditions. Occasional occurances are generally transitory and nonlife threatening, but if the condition becomes chronic, it may lead to either an arrhythmia, a deviation from the normal pattern of impulse conduction and contraction, or to fibrillation, an uncoordinated beating of the heart.

While interpretation of an ECG is possible and extremely valuable after some training, a full understanding of the complexities and intricacies generally requires several years of experience. In general, the size of the electrical variations, the duration of the events, and detailed vector analysis provide the most comprehensive picture of cardiac function. For example, an amplified P wave may indicate enlargement of the atria, an enlarged Q wave may indicate a MI, and an enlarged suppressed or inverted Q wave often indicates enlarged ventricles. T waves often appear flatter when insufficient oxygen is being delivered to the myocardium. An elevation of the ST segment above baseline is often seen in patients with an acute MI, and may appear depressed below the baseline when hypoxia is occurring.

As useful as analyzing these electrical recordings may be, there are limitations. For example, not all areas suffering a MI may be obvious on the ECG. Additionally, it will not reveal the effectiveness of the pumping, which requires further testing, such as an ultrasound test called an echocardiogram or nuclear medicine imaging. It is also possible for there to be pulseless electrical activity, which will show up on an ECG tracing, although there is no corresponding pumping action. Common abnormalities that may be detected by the ECGs are shown in Figure 9.

[caption id="" align="aligncenter" width="520"] Figure 9. Common ECG Abnormalities. (a) In a second-degree or partial block, one-half of the P waves are not followed by the QRS complex and T waves while the other half are. (b) In atrial fibrillation, the electrical pattern is abnormal prior to the QRS complex, and the frequency between the QRS complexes has increased. (c) In ventricular tachycardia, the shape of the QRS complex is abnormal. (d) In ventricular fibrillation, there is no normal electrical activity. (e) In a third-degree block, there is no correlation between atrial activity (the P wave) and ventricular activity (the QRS complex).[/caption]

[caption id="attachment_1737" align="aligncenter" width="150"] Visit this site for a more complete library of abnormal ECGs.[/caption]

19.3 Cardiac Cycle

barkerj1 — Wed, 30 Aug 2017 18:39:27 +0000

Learning Objectives

By the end of this section, you will be able to:

Explain the events which constitute and complete the heart beat (i.e., one cardiac cycle)

The period of time that begins with contraction of the atria and ends with ventricular relaxation is known as the cardiac cycle (Figure 1). The period of contraction that the heart undergoes while it pumps blood into circulation is called systole. The period of relaxation that occurs as the chambers fill with blood is called diastole. Both the atria and ventricles undergo systole and diastole, and it is essential that these components be carefully regulated and coordinated to ensure blood is pumped efficiently to the body.

[caption id="" align="aligncenter" width="420"] Figure 1. Overview of the Cardiac Cycle. The cardiac cycle begins with atrial systole and progresses to ventricular systole, atrial diastole, and ventricular diastole, when the cycle begins again. Correlations to the ECG are highlighted.[/caption]

Pressures and Flow

Fluids, whether gases or liquids, are materials that flow according to pressure gradients—that is, they move from regions that are higher in pressure to regions that are lower in pressure. Accordingly, when the heart chambers are relaxed (diastole), blood will flow into the atria from the veins, which are higher in pressure. As blood flows into the atria, the pressure will rise, so the blood will initially move passively from the atria into the ventricles. When the action potential triggers the muscles in the atria to contract (atrial systole), the pressure within the atria rises further, pumping blood into the ventricles. During ventricular systole, pressure rises in the ventricles, pumping blood into the pulmonary trunk from the right ventricle and into the aorta from the left ventricle. Again, as you consider this flow and relate it to the conduction pathway, the elegance of the system should become apparent.

Phases of the Cardiac Cycle

At the beginning of the cardiac cycle, both the atria and ventricles are relaxed (diastole). Blood is flowing into the right atrium from the superior and inferior venae cavae and the coronary sinus. Blood flows into the left atrium from the four pulmonary veins. The two atrioventricular valves, the tricuspid and mitral valves, are both open, so blood flows unimpeded from the atria and into the ventricles. Approximately 70–80 percent of ventricular filling occurs by this method. The two semilunar valves, the pulmonary and aortic valves, are closed, preventing backflow of blood into the right and left ventricles from the pulmonary trunk on the right and the aorta on the left.

Atrial Systole and Diastole

Contraction of the atria follows depolarization, represented by the P wave of the ECG. As the atrial muscles contract from the superior portion of the atria toward the atrioventricular septum, pressure rises within the atria and blood is pumped into the ventricles through the open atrioventricular (tricuspid, and mitral or bicuspid) valves. At the start of atrial systole, the ventricles are normally filled with approximately 70–80 percent of their capacity due to inflow during diastole. Atrial contraction, also referred to as the “atrial kick,” contributes the remaining 20–30 percent of filling (see Figure 1). Atrial systole lasts approximately 100 ms and ends prior to ventricular systole, as the atrial muscle returns to diastole.

Ventricular Systole

Ventricular systole (see Figure 1) follows the depolarization of the ventricles and is represented by the QRS complex in the ECG. It may be conveniently divided into two phases, lasting a total of 270 ms. At the end of atrial systole and just prior to atrial contraction, the ventricles contain approximately 130 mL blood in a resting adult in a standing position. This volume is known as the end diastolic volume (EDV) or preload.

Initially, as the muscles in the ventricle contract, the pressure of the blood within the chamber rises, but it is not yet high enough to open the semilunar (pulmonary and aortic) valves and be ejected from the heart. However, blood pressure quickly rises above that of the atria that are now relaxed and in diastole. This increase in pressure causes blood to flow back toward the atria, closing the tricuspid and mitral valves. Since blood is not being ejected from the ventricles at this early stage, the volume of blood within the chamber remains constant. Consequently, this initial phase of ventricular systole is known as isovolumic contraction, also called isovolumetric contraction (see Figure 1).

In the second phase of ventricular systole, the ventricular ejection phase, the contraction of the ventricular muscle has raised the pressure within the ventricle to the point that it is greater than the pressures in the pulmonary trunk and the aorta. Blood is pumped from the heart, pushing open the pulmonary and aortic semilunar valves. Pressure generated by the left ventricle will be appreciably greater than the pressure generated by the right ventricle, since the existing pressure in the aorta will be so much higher. Nevertheless, both ventricles pump the same amount of blood. This quantity is referred to as stroke volume. Stroke volume will normally be in the range of 70–80 mL. Since ventricular systole began with an EDV of approximately 130 mL of blood, this means that there is still 50–60 mL of blood remaining in the ventricle following contraction. This volume of blood is known as the end systolic volume (ESV).

Ventricular Diastole

Ventricular relaxation, or diastole, follows repolarization of the ventricles and is represented by the T wave of the ECG. It too is divided into two distinct phases and lasts approximately 430 ms.

During the early phase of ventricular diastole, as the ventricular muscle relaxes, pressure on the remaining blood within the ventricle begins to fall. When pressure within the ventricles drops below pressure in both the pulmonary trunk and aorta, blood flows back toward the heart, producing the dicrotic notch (small dip) seen in blood pressure tracings. The semilunar valves close to prevent backflow into the heart. Since the atrioventricular valves remain closed at this point, there is no change in the volume of blood in the ventricle, so the early phase of ventricular diastole is called the isovolumic ventricular relaxation phase, also called isovolumetric ventricular relaxation phase (see Figure 1).

In the second phase of ventricular diastole, called late ventricular diastole, as the ventricular muscle relaxes, pressure on the blood within the ventricles drops even further. Eventually, it drops below the pressure in the atria. When this occurs, blood flows from the atria into the ventricles, pushing open the tricuspid and mitral valves. As pressure drops within the ventricles, blood flows from the major veins into the relaxed atria and from there into the ventricles. Both chambers are in diastole, the atrioventricular valves are open, and the semilunar valves remain closed (see Figure 1). The cardiac cycle is complete.

Figure 2 illustrates the relationship between the cardiac cycle and the ECG.

[caption id="" align="aligncenter" width="480"] Figure 2. Relationship between the Cardiac Cycle and ECG. Initially, both the atria and ventricles are relaxed (diastole). The P wave represents depolarization of the atria and is followed by atrial contraction (systole). Atrial systole extends until the QRS complex, at which point, the atria relax. The QRS complex represents depolarization of the ventricles and is followed by ventricular contraction. The T wave represents the repolarization of the ventricles and marks the beginning of ventricular relaxation.[/caption]

Heart Sounds

One of the simplest, yet effective, diagnostic techniques applied to assess the state of a patient’s heart is auscultation using a stethoscope.

In a normal, healthy heart, there are only two audible heart sounds: S₁ and S₂. S₁ is the sound created by the closing of the atrioventricular valves during ventricular contraction and is normally described as a “lub,” or first heart sound. The second heart sound, S₂, is the sound of the closing of the semilunar valves during ventricular diastole and is described as a “dub” (Figure 3). In both cases, as the valves close, the openings within the atrioventricular septum guarded by the valves will become reduced, and blood flow through the opening will become more turbulent until the valves are fully closed. There is a third heart sound, S₃, but it is rarely heard in healthy individuals. It may be the sound of blood flowing into the atria, or blood sloshing back and forth in the ventricle, or even tensing of the chordae tendineae. S₃ may be heard in youth, some athletes, and pregnant women. If the sound is heard later in life, it may indicate congestive heart failure, warranting further tests. Some cardiologists refer to the collective S₁, S₂, and S₃ sounds as the “Kentucky gallop,” because they mimic those produced by a galloping horse. The fourth heart sound, S₄, results from the contraction of the atria pushing blood into a stiff or hypertrophic ventricle, indicating failure of the left ventricle. S₄ occurs prior to S₁ and the collective sounds S₄, S₁, and S₂ are referred to by some cardiologists as the “Tennessee gallop,” because of their similarity to the sound produced by a galloping horse with a different gait. A few individuals may have both S₃and S₄, and this combined sound is referred to as S₇.

[caption id="" align="aligncenter" width="480"] Figure 3. Heart Sounds and the Cardiac Cycle. In this illustration, the x-axis reflects time with a recording of the heart sounds. The y-axis represents pressure.[/caption]

The term murmur is used to describe an unusual sound coming from the heart that is caused by the turbulent flow of blood. Murmurs are graded on a scale of 1 to 6, with 1 being the most common, the most difficult sound to detect, and the least serious. The most severe is a 6. Phonocardiograms or auscultograms can be used to record both normal and abnormal sounds using specialized electronic stethoscopes.

During auscultation, it is common practice for the clinician to ask the patient to breathe deeply. This procedure not only allows for listening to airflow, but it may also amplify heart murmurs. Inhalation increases blood flow into the right side of the heart and may increase the amplitude of right-sided heart murmurs. Expiration partially restricts blood flow into the left side of the heart and may amplify left-sided heart murmurs. Figure 4 indicates proper placement of the bell of the stethoscope to facilitate auscultation.

[caption id="" align="aligncenter" width="480"] Figure 4. Stethoscope Placement for Auscultation. Proper placement of the bell of the stethoscope facilitates auscultation. At each of the four locations on the chest, a different valve can be heard.[/caption]

19.4 Cardiac Physiology

barkerj1 — Wed, 30 Aug 2017 18:39:31 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the major mechanisms that control heart rate

The autorhythmicity inherent in cardiac cells keeps the heart beating at a regular pace; however, the heart is regulated by and responds to outside influences as well. Neural and endocrine controls are vital to the regulation of cardiac function. In addition, the heart is sensitive to several environmental factors, including electrolytes.

Resting Cardiac Output

Cardiac output (CO) is a measurement of the amount of blood pumped by each ventricle in one minute. To calculate this value, multiply stroke volume (SV), the amount of blood pumped by each ventricle, by heart rate (HR), in contractions per minute (or beats per minute, bpm). It can be represented mathematically by the following equation:

CO = HR × SV

SV is normally measured using an echocardiogram to record EDV and ESV, and calculating the difference: SV = EDV – ESV. SV can also be measured using a specialized catheter, but this is an invasive procedure and far more dangerous to the patient. A mean SV for a resting 70-kg (150-lb) individual would be approximately 70 mL. There are several important variables, including size of the heart, physical and mental condition of the individual, sex, contractility, duration of contraction, preload or EDV, and afterload or resistance. Normal range for SV would be 55–100 mL. An average resting HR would be approximately 75 bpm but could range from 60–100 in some individuals.

Using these numbers, the mean CO is 5.25 L/min, with a range of 4.0–8.0 L/min. Remember, however, that these numbers refer to CO from each ventricle separately, not the total for the heart. Factors influencing CO are summarized in Figure 1.

[caption id="" align="aligncenter" width="450"] Figure 1. Major Factors Influencing Cardiac Output. Cardiac output is influenced by heart rate and stroke volume, both of which are also variable.[/caption]

SVs are also used to calculate ejection fraction, which is the portion of the blood that is pumped or ejected from the heart with each contraction. To calculate ejection fraction, SV is divided by EDV. Despite the name, the ejection fraction is normally expressed as a percentage. Ejection fractions range from approximately 55–70 percent, with a mean of 58 percent.

Exercise and Maximum Cardiac Output

In healthy young individuals, HR may increase to 150 bpm during exercise. SV can also increase from 70 to approximately 130 mL due to increased strength of contraction. This would increase CO to approximately 19.5 L/min, 4–5 times the resting rate. Top cardiovascular athletes can achieve even higher levels. At their peak performance, they may increase resting CO by 7–8 times.

Since the heart is a muscle, exercising it increases its efficiency. The difference between maximum and resting CO is known as the cardiac reserve. It measures the residual capacity of the heart to pump blood.

Heart Rates

HRs vary considerably, not only with exercise and fitness levels, but also with age. Newborn resting HRs may be 120 bpm. HR gradually decreases until young adulthood and then gradually increases again with age.

Maximum HRs are normally in the range of 200–220 bpm, although there are some extreme cases in which they may reach higher levels. As one ages, the ability to generate maximum rates decreases. This may be estimated by taking the maximal value of 220 bpm and subtracting the individual’s age. So a 40-year-old individual would be expected to hit a maximum rate of approximately 180, and a 60-year-old person would achieve a HR of 160.

Disorders of the…

Heart: Abnormal Heart Rates For an adult, normal resting HR will be in the range of 60–100 bpm. Bradycardia is the condition in which resting rate drops below 60 bpm, and tachycardia is the condition in which the resting rate is above 100 bpm. Trained athletes typically have very low HRs. If the patient is not exhibiting other symptoms, such as weakness, fatigue, dizziness, fainting, chest discomfort, palpitations, or respiratory distress, bradycardia is not considered clinically significant. However, if any of these symptoms are present, they may indicate that the heart is not providing sufficient oxygenated blood to the tissues. The term relative bradycardia may be used with a patient who has a HR in the normal range but is still suffering from these symptoms. Most patients remain asymptomatic as long as the HR remains above 50 bpm.

Bradycardia may be caused by either inherent factors or causes external to the heart. While the condition may be inherited, typically it is acquired in older individuals. Inherent causes include abnormalities in either the SA or AV node. If the condition is serious, a pacemaker may be required. Other causes include ischemia to the heart muscle or diseases of the heart vessels or valves. External causes include metabolic disorders, pathologies of the endocrine system often involving the thyroid, electrolyte imbalances, neurological disorders including inappropriate autonomic responses, autoimmune pathologies, over-prescription of beta blocker drugs that reduce HR, recreational drug use, or even prolonged bed rest. Treatment relies upon establishing the underlying cause of the disorder and may necessitate supplemental oxygen.

Tachycardia is not normal in a resting patient but may be detected in pregnant women or individuals experiencing extreme stress. In the latter case, it would likely be triggered by stimulation from the limbic system or disorders of the autonomic nervous system. In some cases, tachycardia may involve only the atria. Some individuals may remain asymptomatic, but when present, symptoms may include dizziness, shortness of breath, lightheadedness, rapid pulse, heart palpations, chest pain, or fainting (syncope). While tachycardia is defined as a HR above 100 bpm, there is considerable variation among people. Further, the normal resting HRs of children are often above 100 bpm, but this is not considered to be tachycardia Many causes of tachycardia may be benign, but the condition may also be correlated with fever, anemia, hypoxia, hyperthyroidism, hypersecretion of catecholamines, some cardiomyopathies, some disorders of the valves, and acute exposure to radiation. Elevated rates in an exercising or resting patient are normal and expected. Resting rate should always be taken after recovery from exercise. Treatment depends upon the underlying cause but may include medications, implantable cardioverter defibrillators, ablation, or surgery.

Correlation Between Heart Rates and Cardiac Output

Initially, physiological conditions that cause HR to increase also trigger an increase in SV. During exercise, the rate of blood returning to the heart increases. However as the HR rises, there is less time spent in diastole and consequently less time for the ventricles to fill with blood. Even though there is less filling time, SV will initially remain high. However, as HR continues to increase, SV gradually decreases due to decreased filling time. CO will initially stabilize as the increasing HR compensates for the decreasing SV, but at very high rates, CO will eventually decrease as increasing rates are no longer able to compensate for the decreasing SV. Consider this phenomenon in a healthy young individual. Initially, as HR increases from resting to approximately 120 bpm, CO will rise. As HR increases from 120 to 160 bpm, CO remains stable, since the increase in rate is offset by decreasing ventricular filling time and, consequently, SV. As HR continues to rise above 160 bpm, CO actually decreases as SV falls faster than HR increases. So although aerobic exercises are critical to maintain the health of the heart, individuals are cautioned to monitor their HR to ensure they stay within the target heart rate range of between 120 and 160 bpm, so CO is maintained. The target HR is loosely defined as the range in which both the heart and lungs receive the maximum benefit from the aerobic workout and is dependent upon age.

Cardiovascular Centers

Nervous control over HR is centralized within the two paired cardiovascular centers of the medulla oblongata (Figure 2). The cardioaccelerator regions stimulate activity via sympathetic stimulation of the cardioaccelerator nerves, and the cardioinhibitory centers decrease heart activity via parasympathetic stimulation as one component of the vagus nerve, cranial nerve X. During rest, both centers provide slight stimulation to the heart, contributing to autonomic tone. This is a similar concept to tone in skeletal muscles. Normally, vagal stimulation predominates as, left unregulated, the SA node would initiate a sinus rhythm of approximately 100 bpm.

Both sympathetic and parasympathetic stimulations flow through a paired complex network of nerve fibers known as the cardiac plexus near the base of the heart. The cardioaccelerator center also sends additional fibers, forming the cardiac nerves via sympathetic ganglia (the cervical ganglia plus superior thoracic ganglia T1–T4) to both the SA and AV nodes, plus additional fibers to the atria and ventricles. The ventricles are more richly innervated by sympathetic fibers than parasympathetic fibers. Sympathetic stimulation causes the release of the neurotransmitter norepinephrine (NE) at the neuromuscular junction of the cardiac nerves. NE shortens the repolarization period, thus speeding the rate of depolarization and contraction, which results in an increase in HR. It opens chemical- or ligand-gated sodium and calcium ion channels, allowing an influx of positively charged ions.

NE binds to the beta-1 receptor. Some cardiac medications (for example, beta blockers) work by blocking these receptors, thereby slowing HR and are one possible treatment for hypertension. Overprescription of these drugs may lead to bradycardia and even stoppage of the heart.

[caption id="" align="aligncenter" width="280"] Figure 2. Autonomic Innervation of the Heart. Cardioaccelerator and cardioinhibitory areas are components of the paired cardiac centers located in the medulla oblongata of the brain. They innervate the heart via sympathetic cardiac nerves that increase cardiac activity and vagus (parasympathetic) nerves that slow cardiac activity.[/caption]

Parasympathetic stimulation originates from the cardioinhibitory region with impulses traveling via the vagus nerve (cranial nerve X). The vagus nerve sends branches to both the SA and AV nodes, and to portions of both the atria and ventricles. Parasympathetic stimulation releases the neurotransmitter acetylcholine (ACh) at the neuromuscular junction. ACh slows HR by opening chemical- or ligand-gated potassium ion channels to slow the rate of spontaneous depolarization, which extends repolarization and increases the time before the next spontaneous depolarization occurs. Without any nervous stimulation, the SA node would establish a sinus rhythm of approximately 100 bpm. Since resting rates are considerably less than this, it becomes evident that parasympathetic stimulation normally slows HR. This is similar to an individual driving a car with one foot on the brake pedal. To speed up, one need merely remove one’s foot from the break and let the engine increase speed. In the case of the heart, decreasing parasympathetic stimulation decreases the release of ACh, which allows HR to increase up to approximately 100 bpm. Any increases beyond this rate would require sympathetic stimulation. Figure 3 illustrates the effects of parasympathetic and sympathetic stimulation on the normal sinus rhythm.

[caption id="" align="aligncenter" width="350"] Figure 3. Effects of Parasympathetic and Sympathetic Stimulation on Normal Sinus Rhythm. The wave of depolarization in a normal sinus rhythm shows a stable resting HR. Following parasympathetic stimulation, HR slows. Following sympathetic stimulation, HR increases.[/caption]

Input to the Cardiovascular Center

The cardiovascular center receives input from a series of visceral receptors with impulses traveling through visceral sensory fibers within the vagus and sympathetic nerves via the cardiac plexus. Among these receptors are various proprioreceptors, baroreceptors, and chemoreceptors, plus stimuli from the limbic system. Collectively, these inputs normally enable the cardiovascular centers to regulate heart function precisely, a process known as cardiac reflexes. Increased physical activity results in increased rates of firing by various proprioreceptors located in muscles, joint capsules, and tendons. Any such increase in physical activity would logically warrant increased blood flow. The cardiac centers monitor these increased rates of firing, and suppress parasympathetic stimulation and increase sympathetic stimulation as needed in order to increase blood flow.

Similarly, baroreceptors are stretch receptors located in the aortic sinus, carotid bodies, the venae cavae, and other locations, including pulmonary vessels and the right side of the heart itself. Rates of firing from the baroreceptors represent blood pressure, level of physical activity, and the relative distribution of blood. The cardiac centers monitor baroreceptor firing to maintain cardiac homeostasis, a mechanism called the baroreceptor reflex. With increased pressure and stretch, the rate of baroreceptor firing increases, and the cardiac centers decrease sympathetic stimulation and increase parasympathetic stimulation. As pressure and stretch decrease, the rate of baroreceptor firing decreases, and the cardiac centers increase sympathetic stimulation and decrease parasympathetic stimulation.

There is a similar reflex, called the atrial reflex or Bainbridge reflex, associated with varying rates of blood flow to the atria. Increased venous return stretches the walls of the atria where specialized baroreceptors are located. However, as the atrial baroreceptors increase their rate of firing and as they stretch due to the increased blood pressure, the cardiac center responds by increasing sympathetic stimulation and inhibiting parasympathetic stimulation to increase HR. The opposite is also true.

Increased metabolic byproducts associated with increased activity, such as carbon dioxide, hydrogen ions, and lactic acid, plus falling oxygen levels, are detected by a suite of chemoreceptors innervated by the glossopharyngeal and vagus nerves. These chemoreceptors provide feedback to the cardiovascular centers about the need for increased or decreased blood flow, based on the relative levels of these substances.

The limbic system can also significantly impact HR related to emotional state. During periods of stress, it is not unusual to identify higher than normal HRs, often accompanied by a surge in the stress hormone cortisol. Individuals experiencing extreme anxiety may manifest panic attacks with symptoms that resemble those of heart attacks. These events are typically transient and treatable. Meditation techniques have been developed to ease anxiety and have been shown to lower HR effectively. Doing simple deep and slow breathing exercises with one’s eyes closed can also significantly reduce this anxiety and HR.

Disorders of the…

Heart: Broken Heart Syndrome

Extreme stress from such life events as the death of a loved one, an emotional break up, loss of income, or foreclosure of a home may lead to a condition commonly referred to as broken heart syndrome. This condition may also be called Takotsubo cardiomyopathy, transient apical ballooning syndrome, apical ballooning cardiomyopathy, stress-induced cardiomyopathy, Gebrochenes-Herz syndrome, and stress cardiomyopathy. The recognized effects on the heart include congestive heart failure due to a profound weakening of the myocardium not related to lack of oxygen. This may lead to acute heart failure, lethal arrhythmias, or even the rupture of a ventricle. The exact etiology is not known, but several factors have been suggested, including transient vasospasm, dysfunction of the cardiac capillaries, or thickening of the myocardium—particularly in the left ventricle—that may lead to the critical circulation of blood to this region. While many patients survive the initial acute event with treatment to restore normal function, there is a strong correlation with death. Careful statistical analysis by the Cass Business School, a prestigious institution located in London, published in 2008, revealed that within one year of the death of a loved one, women are more than twice as likely to die and males are six times as likely to die as would otherwise be expected.

Other Factors Influencing Heart Rate

Using a combination of autorhythmicity and innervation, the cardiovascular center is able to provide relatively precise control over HR. However, there are a number of other factors that have an impact on HR as well, including epinephrine, NE, and thyroid hormones; levels of various ions including calcium, potassium, and sodium; body temperature; hypoxia; and pH balance (Table 1 and Table 2). After reading this section, the importance of maintaining homeostasis should become even more apparent.

Major Factors Increasing Heart Rate and Force of Contraction (Table 1)
Factor	Effect
Cardioaccelerator nerves	Release of norepinephrine
Proprioreceptors	Increased rates of firing during exercise
Chemoreceptors	Decreased levels of O₂; increased levels of H⁺, CO₂, and lactic acid
Baroreceptors	Decreased rates of firing, indicating falling blood volume/pressure
Limbic system	Anticipation of physical exercise or strong emotions
Catecholamines	Increased epinephrine and norepinephrine
Thyroid hormones	Increased T₃and T₄
Calcium	Increased Ca²⁺
Potassium	Decreased K⁺
Sodium	Decreased Na⁺
Body temperature	Increased body temperature
Nicotine and caffeine	Stimulants, increasing heart rate

Factors Decreasing Heart Rate and Force of Contraction (Table 2)
Factor	Effect
Cardioinhibitor nerves (vagus)	Release of acetylcholine
Proprioreceptors	Decreased rates of firing following exercise
Chemoreceptors	Increased levels of O₂; decreased levels of H⁺ and CO₂
Baroreceptors	Increased rates of firing, indicating higher blood volume/pressure
Limbic system	Anticipation of relaxation
Catecholamines	Decreased epinephrine and norepinephrine
Thyroid hormones	Decreased T₃and T₄
Calcium	Decreased Ca²⁺
Potassium	Increased K⁺
Sodium	Increased Na⁺
Body temperature	Decrease in body temperature

Epinephrine and Norepinephrine

The catecholamines, epinephrine and NE, secreted by the adrenal medulla form one component of the extended fight-or-flight mechanism. The other component is sympathetic stimulation. Epinephrine and NE have similar effects: binding to the beta-1 receptors, and opening sodium and calcium ion chemical- or ligand-gated channels. The rate of depolarization is increased by this additional influx of positively charged ions, so the threshold is reached more quickly and the period of repolarization is shortened. However, massive releases of these hormones coupled with sympathetic stimulation may actually lead to arrhythmias. There is no parasympathetic stimulation to the adrenal medulla.

Thyroid Hormones

In general, increased levels of thyroid hormone, or thyroxin, increase cardiac rate and contractility. The impact of thyroid hormone is typically of a much longer duration than that of the catecholamines. The physiologically active form of thyroid hormone, T₃ or triiodothyronine, has been shown to directly enter cardiomyocytes and alter activity at the level of the genome. It also impacts the beta adrenergic response similar to epinephrine and NE described above. Excessive levels of thyroxin may trigger tachycardia.

Calcium

Calcium ion levels have great impacts upon both HR and contractility; as the levels of calcium ions increase, so do HR and contractility. High levels of calcium ions (hypercalcemia) may be implicated in a short QT interval and a widened T wave in the ECG. The QT interval represents the time from the start of depolarization to repolarization of the ventricles, and includes the period of ventricular systole. Extremely high levels of calcium may induce cardiac arrest. Drugs known as calcium channel blockers slow HR by binding to these channels and blocking or slowing the inward movement of calcium ions.

Caffeine and Nicotine

Caffeine and nicotine are not found naturally within the body. Both of these nonregulated drugs have an excitatory effect on membranes of neurons in general and have a stimulatory effect on the cardiac centers specifically, causing an increase in HR. Caffeine works by increasing the rates of depolarization at the SA node, whereas nicotine stimulates the activity of the sympathetic neurons that deliver impulses to the heart.

Although it is the world’s most widely consumed psychoactive drug, caffeine is legal and not regulated. While precise quantities have not been established, “normal” consumption is not considered harmful to most people, although it may cause disruptions to sleep and acts as a diuretic. Its consumption by pregnant women is cautioned against, although no evidence of negative effects has been confirmed. Tolerance and even physical and mental addiction to the drug result in individuals who routinely consume the substance.

Nicotine, too, is a stimulant and produces addiction. While legal and nonregulated, concerns about nicotine’s safety and documented links to respiratory and cardiac disease have resulted in warning labels on cigarette packages.

Factors Decreasing Heart Rate

HR can be slowed when a person experiences altered sodium and potassium levels, hypoxia, acidosis, alkalosis, and hypothermia (see Table 1). The relationship between electrolytes and HR is complex, but maintaining electrolyte balance is critical to the normal wave of depolarization. Of the two ions, potassium has the greater clinical significance. Initially, both hyponatremia (low sodium levels) and hypernatremia (high sodium levels) may lead to tachycardia. Severely high hypernatremia may lead to fibrillation, which may cause CO to cease. Severe hyponatremia leads to both bradycardia and other arrhythmias. Hypokalemia (low potassium levels) also leads to arrhythmias, whereas hyperkalemia (high potassium levels) causes the heart to become weak and flaccid, and ultimately to fail.

Heart muscle relies exclusively on aerobic metabolism for energy. Hypoxia (an insufficient supply of oxygen) leads to decreasing HRs, since metabolic reactions fueling heart contraction are restricted.

Acidosis is a condition in which excess hydrogen ions are present, and the patient’s blood expresses a low pH value. Alkalosis is a condition in which there are too few hydrogen ions, and the patient’s blood has an elevated pH. Normal blood pH falls in the range of 7.35–7.45, so a number lower than this range represents acidosis and a higher number represents alkalosis. Recall that enzymes are the regulators or catalysts of virtually all biochemical reactions; they are sensitive to pH and will change shape slightly with values outside their normal range. These variations in pH and accompanying slight physical changes to the active site on the enzyme decrease the rate of formation of the enzyme-substrate complex, subsequently decreasing the rate of many enzymatic reactions, which can have complex effects on HR. Severe changes in pH will lead to denaturation of the enzyme.

The last variable is body temperature. Elevated body temperature is called hyperthermia, and suppressed body temperature is called hypothermia. Slight hyperthermia results in increasing HR and strength of contraction. Hypothermia slows the rate and strength of heart contractions. This distinct slowing of the heart is one component of the larger diving reflex that diverts blood to essential organs while submerged. If sufficiently chilled, the heart will stop beating, a technique that may be employed during open heart surgery. In this case, the patient’s blood is normally diverted to an artificial heart-lung machine to maintain the body’s blood supply and gas exchange until the surgery is complete, and sinus rhythm can be restored. Excessive hyperthermia and hypothermia will both result in death, as enzymes drive the body systems to cease normal function, beginning with the central nervous system.

Stroke Volume

Many of the same factors that regulate HR also impact cardiac function by altering SV. While a number of variables are involved, SV is ultimately dependent upon the difference between EDV and ESV. The three primary factors to consider are preload, or the stretch on the ventricles prior to contraction; the contractility, or the force or strength of the contraction itself; and afterload, the force the ventricles must generate to pump blood against the resistance in the vessels. These factors are summarized in Table 1 and Table 2.

Preload

Preload is another way of expressing EDV. Therefore, the greater the EDV is, the greater the preload is. One of the primary factors to consider is filling time, or the duration of ventricular diastole during which filling occurs. The more rapidly the heart contracts, the shorter the filling time becomes, and the lower the EDV and preload are. This effect can be partially overcome by increasing the second variable, contractility, and raising SV, but over time, the heart is unable to compensate for decreased filling time, and preload also decreases.

With increasing ventricular filling, both EDV or preload increase, and the cardiac muscle itself is stretched to a greater degree. At rest, there is little stretch of the ventricular muscle, and the sarcomeres remain short. With increased ventricular filling, the ventricular muscle is increasingly stretched and the sarcomere length increases. As the sarcomeres reach their optimal lengths, they will contract more powerfully, because more of the myosin heads can bind to the actin on the thin filaments, forming cross bridges and increasing the strength of contraction and SV. If this process were to continue and the sarcomeres stretched beyond their optimal lengths, the force of contraction would decrease. However, due to the physical constraints of the location of the heart, this excessive stretch is not a concern.

The relationship between ventricular stretch and contraction has been stated in the well-known Frank-Starling mechanism or simply Starling’s Law of the Heart. This principle states that, within physiological limits, the force of heart contraction is directly proportional to the initial length of the muscle fiber. This means that the greater the stretch of the ventricular muscle (within limits), the more powerful the contraction is, which in turn increases SV. Therefore, by increasing preload, you increase the second variable, contractility.

Otto Frank (1865–1944) was a German physiologist; among his many published works are detailed studies of this important heart relationship. Ernest Starling (1866–1927) was an important English physiologist who also studied the heart. Although they worked largely independently, their combined efforts and similar conclusions have been recognized in the name “Frank-Starling mechanism.”

Any sympathetic stimulation to the venous system will increase venous return to the heart, which contributes to ventricular filling, and EDV and preload. While much of the ventricular filling occurs while both atria and ventricles are in diastole, the contraction of the atria, the atrial kick, plays a crucial role by providing the last 20–30 percent of ventricular filling.

Contractility

It is virtually impossible to consider preload or ESV without including an early mention of the concept of contractility. Indeed, the two parameters are intimately linked. Contractility refers to the force of the contraction of the heart muscle, which controls SV, and is the primary parameter for impacting ESV. The more forceful the contraction is, the greater the SV and smaller the ESV are. Less forceful contractions result in smaller SVs and larger ESVs. Factors that increase contractility are described as positive inotropic factors, and those that decrease contractility are described as negative inotropic factors (ino- = “fiber;” -tropic = “turning toward”).

Not surprisingly, sympathetic stimulation is a positive inotrope, whereas parasympathetic stimulation is a negative inotrope. Sympathetic stimulation triggers the release of NE at the neuromuscular junction from the cardiac nerves and also stimulates the adrenal cortex to secrete epinephrine and NE. In addition to their stimulatory effects on HR, they also bind to both alpha and beta receptors on the cardiac muscle cell membrane to increase metabolic rate and the force of contraction. This combination of actions has the net effect of increasing SV and leaving a smaller residual ESV in the ventricles. In comparison, parasympathetic stimulation releases ACh at the neuromuscular junction from the vagus nerve. The membrane hyperpolarizes and inhibits contraction to decrease the strength of contraction and SV, and to raise ESV. Since parasympathetic fibers are more widespread in the atria than in the ventricles, the primary site of action is in the upper chambers. Parasympathetic stimulation in the atria decreases the atrial kick and reduces EDV, which decreases ventricular stretch and preload, thereby further limiting the force of ventricular contraction. Stronger parasympathetic stimulation also directly decreases the force of contraction of the ventricles.

Several synthetic drugs, including dopamine and isoproterenol, have been developed that mimic the effects of epinephrine and NE by stimulating the influx of calcium ions from the extracellular fluid. Higher concentrations of intracellular calcium ions increase the strength of contraction. Excess calcium (hypercalcemia) also acts as a positive inotropic agent. The drug digitalis lowers HR and increases the strength of the contraction, acting as a positive inotropic agent by blocking the sequestering of calcium ions into the sarcoplasmic reticulum. This leads to higher intracellular calcium levels and greater strength of contraction. In addition to the catecholamines from the adrenal medulla, other hormones also demonstrate positive inotropic effects. These include thyroid hormones and glucagon from the pancreas.

Negative inotropic agents include hypoxia, acidosis, hyperkalemia, and a variety of synthetic drugs. These include numerous beta blockers and calcium channel blockers. Early beta blocker drugs include propranolol and pronethalol, and are credited with revolutionizing treatment of cardiac patients experiencing angina pectoris. There is also a large class of dihydropyridine, phenylalkylamine, and benzothiazepine calcium channel blockers that may be administered decreasing the strength of contraction and SV.

Afterload

Afterload refers to the tension that the ventricles must develop to pump blood effectively against the resistance in the vascular system. Any condition that increases resistance requires a greater afterload to force open the semilunar valves and pump the blood. Damage to the valves, such as stenosis, which makes them harder to open will also increase afterload. Any decrease in resistance decreases the afterload. Figure 4 summarizes the major factors influencing SV, Figure 5 summarizes the major factors influencing CO, and Table 3 and Table 4 summarize cardiac responses to increased and decreased blood flow and pressure in order to restore homeostasis.

[caption id="" align="aligncenter" width="550"] Figure 4. Major Factors Influencing Stroke Volume. Multiple factors impact preload, afterload, and contractility, and are the major considerations influencing SV.[/caption]

[caption id="" align="aligncenter" width="550"] Figure 5. Summary of Major Factors Influencing Cardiac Output. The primary factors influencing HR include autonomic innervation plus endocrine control. Not shown are environmental factors, such as electrolytes, metabolic products, and temperature. The primary factors controlling SV include preload, contractility, and afterload. Other factors such as electrolytes may be classified as either positive or negative inotropic agents.[/caption]

Cardiac Response to Decreasing Blood Flow and Pressure Due to Decreasing Cardiac Output (Table 3)
	Baroreceptors (aorta, carotid arteries, venae cavae, and atria)	Chemoreceptors (both central nervous system and in proximity to baroreceptors)
Sensitive to	Decreasing stretch	Decreasing O₂ and increasing CO₂, H⁺, and lactic acid
Target	Parasympathetic stimulation suppressed	Sympathetic stimulation increased
Response of heart	Increasing heart rate and increasing stroke volume	Increasing heart rate and increasing stroke volume
Overall effect	Increasing blood flow and pressure due to increasing cardiac output; hemostasis restored	Increasing blood flow and pressure due to increasing cardiac output; hemostasis restored

Cardiac Response to Increasing Blood Flow and Pressure Due to Increasing Cardiac Output (Table 4)
	Baroreceptors (aorta, carotid arteries, venae cavae, and atria)	Chemoreceptors (both central nervous system and in proximity to baroreceptors)
Sensitive to	Increasing stretch	Increasing O₂ and decreasing CO₂, H⁺, and lactic acid
Target	Parasympathetic stimulation increased	Sympathetic stimulation suppressed
Response of heart	Decreasing heart rate and decreasing stroke volume	Decreasing heart rate and decreasing stroke volume
Overall effect	Decreasing blood flow and pressure due to decreasing cardiac output; hemostasis restored	Decreasing blood flow and pressure due to decreasing cardiac output; hemostasis restored

Introduction

barkerj1 — Wed, 30 Aug 2017 18:39:32 +0000

[caption id="" align="aligncenter" width="500"] Figure 1. Blood Vessels. While most blood vessels are located deep from the surface and are not visible, the superficial veins of the upper limb provide an indication of the extent, prominence, and importance of these structures to the body. (credit: Colin Davis)[/caption] In this chapter, you will learn about the vascular part of the cardiovascular system, that is, the vessels that transport blood throughout the body and provide the physical site where gases, nutrients, and other substances are exchanged with body cells. When vessel functioning is reduced, blood-borne substances do not circulate effectively throughout the body. As a result, tissue injury occurs, metabolism is impaired, and the functions of every bodily system are threatened.

20.1 Structure and Function of Blood Vessels

barkerj1 — Wed, 30 Aug 2017 18:39:38 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the relationships between the blood, arteries, veins, capillaries, atria, and ventricles of the cardiovascular system
Describe the functions of arteries, veins, and capillaries
Compare the structure and function of arteries, veins, and capillaries

Blood is carried through the body via blood vessels. An artery is a blood vessel that carries blood away from the heart, where it branches into ever-smaller vessels. Eventually, the smallest arteries, vessels called arterioles, further branch into tiny capillaries, where nutrients and wastes are exchanged, and then combine with other vessels that exit capillaries to form venules, small blood vessels that carry blood to a vein, a larger blood vessel that returns blood to the heart.

Arteries and veins transport blood in two distinct circuits: the systemic circuit and the pulmonary circuit (Figure 1). Systemic arteries provide blood rich in oxygen to the body’s tissues. The blood returned to the heart through systemic veins has less oxygen, since much of the oxygen carried by the arteries has been delivered to the cells. In contrast, in the pulmonary circuit, arteries carry blood low in oxygen exclusively to the lungs for gas exchange. Pulmonary veins then return freshly oxygenated blood from the lungs to the heart to be pumped back out into systemic circulation. Although arteries and veins differ structurally and functionally, they share certain features.

[caption id="" align="aligncenter" width="520"] Figure 1. Cardiovascular Circulation. The pulmonary circuit moves blood from the right side of the heart to the lungs and back to the heart. The systemic circuit moves blood from the left side of the heart to the head and body and returns it to the right side of the heart to repeat the cycle. The arrows indicate the direction of blood flow, and the colors show the relative levels of oxygen concentration.[/caption]

Shared Structures

Different types of blood vessels vary slightly in their structures, but they share the same general features. Arteries and arterioles have thicker walls than veins and venules because they are closer to the heart and receive blood that is surging at a far greater pressure (Figure 2). Each type of vessel has a lumen—a hollow passageway through which blood flows. Arteries have smaller lumens than veins, a characteristic that helps to maintain the pressure of blood moving through the system. Together, their thicker walls and smaller diameters give arterial lumens a more rounded appearance in cross section than the lumens of veins.

[caption id="" align="aligncenter" width="425"] Figure 2. Structure of Blood Vessels. (a) Arteries and (b) veins share the same general features, but the walls of arteries are much thicker because of the higher pressure of the blood that flows through them. (c) A micrograph shows the relative differences in thickness. LM × 160. (Micrograph provided by the Regents of the University of Michigan Medical School © 2012)[/caption]

By the time blood has passed through capillaries and entered venules, the pressure initially exerted upon it by heart contractions has diminished. In other words, in comparison to arteries, venules and veins withstand a much lower pressure from the blood that flows through them. Their walls are considerably thinner and their lumens are correspondingly larger in diameter, allowing more blood to flow with less vessel resistance. In addition, many veins of the body, particularly those of the limbs, contain valves that assist the unidirectional flow of blood toward the heart. This is critical because blood flow becomes sluggish in the extremities, as a result of the lower pressure and the effects of gravity.

The walls of arteries and veins are largely composed of living cells and their products (including collagenous and elastic fibers); the cells require nourishment and produce waste. Since blood passes through the larger vessels relatively quickly, there is limited opportunity for blood in the lumen of the vessel to provide nourishment to or remove waste from the vessel’s cells. Further, the walls of the larger vessels are too thick for nutrients to diffuse through to all of the cells. Larger arteries and veins contain small blood vessels within their walls known as the vasa vasorum—literally “vessels of the vessel”—to provide them with this critical exchange. Since the pressure within arteries is relatively high, the vasa vasorum must function in the outer layers of the vessel (see Figure 2) or the pressure exerted by the blood passing through the vessel would collapse it, preventing any exchange from occurring. The lower pressure within veins allows the vasa vasorum to be located closer to the lumen. The restriction of the vasa vasorum to the outer layers of arteries is thought to be one reason that arterial diseases are more common than venous diseases, since its location makes it more difficult to nourish the cells of the arteries and remove waste products. There are also minute nerves within the walls of both types of vessels that control the contraction and dilation of smooth muscle. These minute nerves are known as the nervi vasorum.

Both arteries and veins have the same three distinct tissue layers, called tunics (from the Latin term tunica), for the garments first worn by ancient Romans; the term tunic is also used for some modern garments. From the most interior layer to the outer, these tunics are the tunica intima, the tunica media, and the tunica externa (see Figure 2). Table 1 compares and contrasts the tunics of the arteries and veins.

Comparison of Tunics in Arteries and Veins (Table 1)
	Arteries	Veins
General appearance	Thick walls with small lumens Generally appear rounded	Thin walls with large lumens Generally appear flattened
Tunica intima	Endothelium usually appears wavy due to constriction of smooth muscle Internal elastic membrane present in larger vessels	Endothelium appears smooth Internal elastic membrane absent
Tunica media	Normally the thickest layer in arteries Smooth muscle cells and elastic fibers predominate (the proportions of these vary with distance from the heart) External elastic membrane present in larger vessels	Normally thinner than the tunica externa Smooth muscle cells and collagenous fibers predominate Nervi vasorum and vasa vasorum present External elastic membrane absent
Tunica externa	Normally thinner than the tunica media in all but the largest arteries Collagenous and elastic fibers Nervi vasorum and vasa vasorum present	Normally the thickest layer in veins Collagenous and smooth fibers predominate Some smooth muscle fibers Nervi vasorum and vasa vasorum present

Tunica Intima

The tunica intima (also called the tunica interna) is composed of epithelial and connective tissue layers. Lining the tunica intima is the specialized simple squamous epithelium called the endothelium, which is continuous throughout the entire vascular system, including the lining of the chambers of the heart. Damage to this endothelial lining and exposure of blood to the collagenous fibers beneath is one of the primary causes of clot formation. Until recently, the endothelium was viewed simply as the boundary between the blood in the lumen and the walls of the vessels. Recent studies, however, have shown that it is physiologically critical to such activities as helping to regulate capillary exchange and altering blood flow. The endothelium releases local chemicals called endothelins that can constrict the smooth muscle within the walls of the vessel to increase blood pressure. Uncompensated overproduction of endothelins may contribute to hypertension (high blood pressure) and cardiovascular disease.

Next to the endothelium is the basement membrane, or basal lamina, that effectively binds the endothelium to the connective tissue. The basement membrane provides strength while maintaining flexibility, and it is permeable, allowing materials to pass through it. The thin outer layer of the tunica intima contains a small amount of areolar connective tissue that consists primarily of elastic fibers to provide the vessel with additional flexibility; it also contains some collagenous fibers to provide additional strength.

In larger arteries, there is also a thick, distinct layer of elastic fibers known as the internal elastic membrane (also called the internal elastic lamina) at the boundary with the tunica media. Like the other components of the tunica intima, the internal elastic membrane provides structure while allowing the vessel to stretch. It is permeated with small openings that allow exchange of materials between the tunics. The internal elastic membrane is not apparent in veins. In addition, many veins, particularly in the lower limbs, contain valves formed by sections of thickened endothelium that are reinforced with connective tissue, extending into the lumen.

Under the microscope, the lumen and the entire tunica intima of a vein will appear smooth, whereas those of an artery will normally appear wavy because of the partial constriction of the smooth muscle in the tunica media, the next layer of blood vessel walls.

Tunica Media

The tunica media is the substantial middle layer of the vessel wall (see Figure 2). It is generally the thickest layer in arteries, and it is much thicker in arteries than it is in veins. The tunica media consists of layers of smooth muscle supported by connective tissue that is primarily made up of elastic fibers, most of which are arranged in circular sheets. Toward the outer portion of the tunic, there are also layers of longitudinal muscle. Contraction and relaxation of the circular muscles decrease and increase the diameter of the vessel lumen, respectively. Specifically in arteries, vasoconstriction decreases blood flow as the smooth muscle in the walls of the tunica media contracts, making the lumen narrower and increasing blood pressure. Similarly, vasodilation increases blood flow as the smooth muscle relaxes, allowing the lumen to widen and blood pressure to drop. Both vasoconstriction and vasodilation are regulated in part by small vascular nerves, known as nervi vasorum, or “nerves of the vessel,” that run within the walls of blood vessels. These are generally all sympathetic fibers, although some trigger vasodilation and others induce vasoconstriction, depending upon the nature of the neurotransmitter and receptors located on the target cell. Parasympathetic stimulation does trigger vasodilation as well as erection during sexual arousal in the external genitalia of both sexes. Nervous control over vessels tends to be more generalized than the specific targeting of individual blood vessels. Local controls, discussed later, account for this phenomenon. (Seek additional content for more information on these dynamic aspects of the autonomic nervous system.) Hormones and local chemicals also control blood vessels. Together, these neural and chemical mechanisms reduce or increase blood flow in response to changing body conditions, from exercise to hydration. Regulation of both blood flow and blood pressure is discussed in detail later in this chapter.

The smooth muscle layers of the tunica media are supported by a framework of collagenous fibers that also binds the tunica media to the inner and outer tunics. Along with the collagenous fibers are large numbers of elastic fibers that appear as wavy lines in prepared slides. Separating the tunica media from the outer tunica externa in larger arteries is the external elastic membrane (also called the external elastic lamina), which also appears wavy in slides. This structure is not usually seen in smaller arteries, nor is it seen in veins.

Tunica Externa

The outer tunic, the tunica externa (also called the tunica adventitia), is a substantial sheath of connective tissue composed primarily of collagenous fibers. Some bands of elastic fibers are found here as well. The tunica externa in veins also contains groups of smooth muscle fibers. This is normally the thickest tunic in veins and may be thicker than the tunica media in some larger arteries. The outer layers of the tunica externa are not distinct but rather blend with the surrounding connective tissue outside the vessel, helping to hold the vessel in relative position. If you are able to palpate some of the superficial veins on your upper limbs and try to move them, you will find that the tunica externa prevents this. If the tunica externa did not hold the vessel in place, any movement would likely result in disruption of blood flow.

Arteries

An artery is a blood vessel that conducts blood away from the heart. All arteries have relatively thick walls that can withstand the high pressure of blood ejected from the heart. However, those close to the heart have the thickest walls, containing a high percentage of elastic fibers in all three of their tunics. This type of artery is known as an elastic artery (Figure 3). Vessels larger than 10 mm in diameter are typically elastic. Their abundant elastic fibers allow them to expand, as blood pumped from the ventricles passes through them, and then to recoil after the surge has passed. If artery walls were rigid and unable to expand and recoil, their resistance to blood flow would greatly increase and blood pressure would rise to even higher levels, which would in turn require the heart to pump harder to increase the volume of blood expelled by each pump (the stroke volume) and maintain adequate pressure and flow. Artery walls would have to become even thicker in response to this increased pressure. The elastic recoil of the vascular wall helps to maintain the pressure gradient that drives the blood through the arterial system. An elastic artery is also known as a conducting artery, because the large diameter of the lumen enables it to accept a large volume of blood from the heart and conduct it to smaller branches.

[caption id="" align="aligncenter" width="550"] Figure 3. Types of Arteries and Arterioles. Comparison of the walls of an elastic artery, a muscular artery, and an arteriole is shown. In terms of scale, the diameter of an arteriole is measured in micrometers compared to millimeters for elastic and muscular arteries.[/caption]

Farther from the heart, where the surge of blood has dampened, the percentage of elastic fibers in an artery’s tunica intima decreases and the amount of smooth muscle in its tunica media increases. The artery at this point is described as a muscular artery. The diameter of muscular arteries typically ranges from 0.1 mm to 10 mm. Their thick tunica media allows muscular arteries to play a leading role in vasoconstriction. In contrast, their decreased quantity of elastic fibers limits their ability to expand. Fortunately, because the blood pressure has eased by the time it reaches these more distant vessels, elasticity has become less important.

Notice that although the distinctions between elastic and muscular arteries are important, there is no “line of demarcation” where an elastic artery suddenly becomes muscular. Rather, there is a gradual transition as the vascular tree repeatedly branches. In turn, muscular arteries branch to distribute blood to the vast network of arterioles. For this reason, a muscular artery is also known as a distributing artery.

Arterioles

An arteriole is a very small artery that leads to a capillary. Arterioles have the same three tunics as the larger vessels, but the thickness of each is greatly diminished. The critical endothelial lining of the tunica intima is intact. The tunica media is restricted to one or two smooth muscle cell layers in thickness. The tunica externa remains but is very thin (see Figure 3).

With a lumen averaging 30 micrometers or less in diameter, arterioles are critical in slowing down—or resisting—blood flow and, thus, causing a substantial drop in blood pressure. Because of this, you may see them referred to as resistance vessels. The muscle fibers in arterioles are normally slightly contracted, causing arterioles to maintain a consistent muscle tone—in this case referred to as vascular tone—in a similar manner to the muscular tone of skeletal muscle. In reality, all blood vessels exhibit vascular tone due to the partial contraction of smooth muscle. The importance of the arterioles is that they will be the primary site of both resistance and regulation of blood pressure. The precise diameter of the lumen of an arteriole at any given moment is determined by neural and chemical controls, and vasoconstriction and vasodilation in the arterioles are the primary mechanisms for distribution of blood flow.

Capillaries

A capillary is a microscopic channel that supplies blood to the tissues themselves, a process called perfusion. Exchange of gases and other substances occurs in the capillaries between the blood and the surrounding cells and their tissue fluid (interstitial fluid). The diameter of a capillary lumen ranges from 5–10 micrometers; the smallest are just barely wide enough for an erythrocyte to squeeze through. Flow through capillaries is often described as microcirculation.

The wall of a capillary consists of the endothelial layer surrounded by a basement membrane with occasional smooth muscle fibers. There is some variation in wall structure: In a large capillary, several endothelial cells bordering each other may line the lumen; in a small capillary, there may be only a single cell layer that wraps around to contact itself.

For capillaries to function, their walls must be leaky, allowing substances to pass through. There are three major types of capillaries, which differ according to their degree of “leakiness:” continuous, fenestrated, and sinusoid capillaries (Figure 4).

Continuous Capillaries

The most common type of capillary, the continuous capillary, is found in almost all vascularized tissues. Continuous capillaries are characterized by a complete endothelial lining with tight junctions between endothelial cells. Although a tight junction is usually impermeable and only allows for the passage of water and ions, they are often incomplete in capillaries, leaving intercellular clefts that allow for exchange of water and other very small molecules between the blood plasma and the interstitial fluid. Substances that can pass between cells include metabolic products, such as glucose, water, and small hydrophobic molecules like gases and hormones, as well as various leukocytes. Continuous capillaries not associated with the brain are rich in transport vesicles, contributing to either endocytosis or exocytosis. Those in the brain are part of the blood-brain barrier. Here, there are tight junctions and no intercellular clefts, plus a thick basement membrane and astrocyte extensions called end feet; these structures combine to prevent the movement of nearly all substances.

[caption id="" align="aligncenter" width="500"] Figure 4. Types of Capillaries. The three major types of capillaries: continuous, fenestrated, and sinusoid.[/caption]

Fenestrated Capillaries

A fenestrated capillary is one that has pores (or fenestrations) in addition to tight junctions in the endothelial lining. These make the capillary permeable to larger molecules. The number of fenestrations and their degree of permeability vary, however, according to their location. Fenestrated capillaries are common in the small intestine, which is the primary site of nutrient absorption, as well as in the kidneys, which filter the blood. They are also found in the choroid plexus of the brain and many endocrine structures, including the hypothalamus, pituitary, pineal, and thyroid glands.

Sinusoid Capillaries

A sinusoid capillary (or sinusoid) is the least common type of capillary. Sinusoid capillaries are flattened, and they have extensive intercellular gaps and incomplete basement membranes, in addition to intercellular clefts and fenestrations. This gives them an appearance not unlike Swiss cheese. These very large openings allow for the passage of the largest molecules, including plasma proteins and even cells. Blood flow through sinusoids is very slow, allowing more time for exchange of gases, nutrients, and wastes. Sinusoids are found in the liver and spleen, bone marrow, lymph nodes (where they carry lymph, not blood), and many endocrine glands including the pituitary and adrenal glands. Without these specialized capillaries, these organs would not be able to provide their myriad of functions. For example, when bone marrow forms new blood cells, the cells must enter the blood supply and can only do so through the large openings of a sinusoid capillary; they cannot pass through the small openings of continuous or fenestrated capillaries. The liver also requires extensive specialized sinusoid capillaries in order to process the materials brought to it by the hepatic portal vein from both the digestive tract and spleen, and to release plasma proteins into circulation.

Metarterioles and Capillary Beds

A metarteriole is a type of vessel that has structural characteristics of both an arteriole and a capillary. Slightly larger than the typical capillary, the smooth muscle of the tunica media of the metarteriole is not continuous but forms rings of smooth muscle (sphincters) prior to the entrance to the capillaries. Each metarteriole arises from a terminal arteriole and branches to supply blood to a capillary bed that may consist of 10–100 capillaries.

The precapillary sphincters, circular smooth muscle cells that surround the capillary at its origin with the metarteriole, tightly regulate the flow of blood from a metarteriole to the capillaries it supplies. Their function is critical: If all of the capillary beds in the body were to open simultaneously, they would collectively hold every drop of blood in the body and there would be none in the arteries, arterioles, venules, veins, or the heart itself. Normally, the precapillary sphincters are closed. When the surrounding tissues need oxygen and have excess waste products, the precapillary sphincters open, allowing blood to flow through and exchange to occur before closing once more (Figure 5). If all of the precapillary sphincters in a capillary bed are closed, blood will flow from the metarteriole directly into a thoroughfare channel and then into the venous circulation, bypassing the capillary bed entirely. This creates what is known as a vascular shunt. In addition, an arteriovenous anastomosis may bypass the capillary bed and lead directly to the venous system. Although you might expect blood flow through a capillary bed to be smooth, in reality, it moves with an irregular, pulsating flow. This pattern is called vasomotion and is regulated by chemical signals that are triggered in response to changes in internal conditions, such as oxygen, carbon dioxide, hydrogen ion, and lactic acid levels. For example, during strenuous exercise when oxygen levels decrease and carbon dioxide, hydrogen ion, and lactic acid levels all increase, the capillary beds in skeletal muscle are open, as they would be in the digestive system when nutrients are present in the digestive tract. During sleep or rest periods, vessels in both areas are largely closed; they open only occasionally to allow oxygen and nutrient supplies to travel to the tissues to maintain basic life processes.

[caption id="" align="aligncenter" width="480"] Figure 5. Capillary Bed. In a capillary bed, arterioles give rise to metarterioles. Precapillary sphincters located at the junction of a metarteriole with a capillary regulate blood flow. A thoroughfare channel connects the metarteriole to a venule. An arteriovenous anastomosis, which directly connects the arteriole with the venule, is shown at the bottom.[/caption]

Venules

A venule is an extremely small vein, generally 8–100 micrometers in diameter. Postcapillary venules join multiple capillaries exiting from a capillary bed. Multiple venules join to form veins. The walls of venules consist of endothelium, a thin middle layer with a few muscle cells and elastic fibers, plus an outer layer of connective tissue fibers that constitute a very thin tunica externa (Figure 6). Venules as well as capillaries are the primary sites of emigration or diapedesis, in which the white blood cells adhere to the endothelial lining of the vessels and then squeeze through adjacent cells to enter the tissue fluid.

Veins

A vein is a blood vessel that conducts blood toward the heart. Compared to arteries, veins are thin-walled vessels with large and irregular lumens (see Figure 6). Because they are low-pressure vessels, larger veins are commonly equipped with valves that promote the unidirectional flow of blood toward the heart and prevent backflow toward the capillaries caused by the inherent low blood pressure in veins as well as the pull of gravity. Table 2 compares the features of arteries and veins.

[caption id="" align="aligncenter" width="390"] Figure 6. Comparison of Veins and Venules. Many veins have valves to prevent back flow of blood, whereas venules do not. In terms of scale, the diameter of a venule is measured in micrometers compared to millimeters for veins.[/caption]

Comparison of Arteries and Veins (Table 2)
	Arteries	Veins
Direction of blood flow	Conducts blood away from the heart	Conducts blood toward the heart
General appearance	Rounded	Irregular, often collapsed
Pressure	High	Low
Wall thickness	Thick	Thin
Relative oxygen concentration	Higher in systemic arteries Lower in pulmonary arteries	Lower in systemic veins Higher in pulmonary veins
Valves	Not present	Present most commonly in limbs and in veins inferior to the heart

Veins as Blood Reservoirs

In addition to their primary function of returning blood to the heart, veins may be considered blood reservoirs, since systemic veins contain approximately 64 percent of the blood volume at any given time (Figure 8). Their ability to hold this much blood is due to their high capacitance, that is, their capacity to distend (expand) readily to store a high volume of blood, even at a low pressure. The large lumens and relatively thin walls of veins make them far more distensible than arteries; thus, they are said to be capacitance vessels.

[caption id="" align="aligncenter" width="450"] Figure 8. Distribution of Blood Flow[/caption]

When blood flow needs to be redistributed to other portions of the body, the vasomotor center located in the medulla oblongata sends sympathetic stimulation to the smooth muscles in the walls of the veins, causing constriction—or in this case, venoconstriction. Less dramatic than the vasoconstriction seen in smaller arteries and arterioles, venoconstriction may be likened to a “stiffening” of the vessel wall. This increases pressure on the blood within the veins, speeding its return to the heart. As you will note in Figure 8, approximately 21 percent of the venous blood is located in venous networks within the liver, bone marrow, and integument. This volume of blood is referred to as venous reserve. Through venoconstriction, this “reserve” volume of blood can get back to the heart more quickly for redistribution to other parts of the circulation.

20.2 Blood Flow, Blood Pressure, and Resistance

barkerj1 — Wed, 30 Aug 2017 18:39:42 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe what is felt when a pulse is located, and specify four points where an arterial pulse may be felt
Describe what is meant by "blood pressure"
Specify the average blood pressure of a young adult
Specify five factors which affect blood pressure
Specify the major mechanisms that control blood pressure

Blood flow refers to the movement of blood through a vessel, tissue, or organ, and is usually expressed in terms of volume of blood per unit of time. It is initiated by the contraction of the ventricles of the heart. Ventricular contraction ejects blood into the major arteries, resulting in flow from regions of higher pressure to regions of lower pressure, as blood encounters smaller arteries and arterioles, then capillaries, then the venules and veins of the venous system. This section discusses a number of critical variables that contribute to blood flow throughout the body. It also discusses the factors that impede or slow blood flow, a phenomenon known as resistance.

As noted earlier, hydrostatic pressure is the force exerted by a fluid due to gravitational pull, usually against the wall of the container in which it is located. One form of hydrostatic pressure is blood pressure, the force exerted by blood upon the walls of the blood vessels or the chambers of the heart. Blood pressure may be measured in capillaries and veins, as well as the vessels of the pulmonary circulation; however, the term blood pressure without any specific descriptors typically refers to systemic arterial blood pressure—that is, the pressure of blood flowing in the arteries of the systemic circulation. In clinical practice, this pressure is measured in mm Hg and is usually obtained using the brachial artery of the arm.

Components of Arterial Blood Pressure

Arterial blood pressure in the larger vessels consists of several distinct components (Figure 1): systolic and diastolic pressures, pulse pressure, and mean arterial pressure.

Systolic and Diastolic Pressures

When systemic arterial blood pressure is measured, it is recorded as a ratio of two numbers (e.g., 120/80 is a normal adult blood pressure), expressed as systolic pressure over diastolic pressure. The systolic pressure is the higher value (typically around 120 mm Hg) and reflects the arterial pressure resulting from the ejection of blood during ventricular contraction, or systole. The diastolic pressure is the lower value (usually about 80 mm Hg) and represents the arterial pressure of blood during ventricular relaxation, or diastole.

[caption id="" align="aligncenter" width="500"] Figure 1. Systemic Blood Pressure. The graph shows the components of blood pressure throughout the blood vessels, including systolic, diastolic, mean arterial, and pulse pressures.[/caption]

Pulse Pressure

As shown in Figure 1, the difference between the systolic pressure and the diastolic pressure is the pulse pressure. For example, an individual with a systolic pressure of 120 mm Hg and a diastolic pressure of 80 mm Hg would have a pulse pressure of 40 mmHg.

Generally, a pulse pressure should be at least 25 percent of the systolic pressure. A pulse pressure below this level is described as low or narrow. This may occur, for example, in patients with a low stroke volume, which may be seen in congestive heart failure, stenosis of the aortic valve, or significant blood loss following trauma. In contrast, a high or wide pulse pressure is common in healthy people following strenuous exercise, when their resting pulse pressure of 30–40 mm Hg may increase temporarily to 100 mm Hg as stroke volume increases. A persistently high pulse pressure at or above 100 mm Hg may indicate excessive resistance in the arteries and can be caused by a variety of disorders. Chronic high resting pulse pressures can degrade the heart, brain, and kidneys, and warrant medical treatment.

Mean Arterial Pressure

Mean arterial pressure (MAP) represents the “average” pressure of blood in the arteries, that is, the average force driving blood into vessels that serve the tissues. Mean is a statistical concept and is calculated by taking the sum of the values divided by the number of values. Although complicated to measure directly and complicated to calculate, MAP can be approximated by adding the diastolic pressure to one-third of the pulse pressure or systolic pressure minus the diastolic pressure:

MAP = diastolic BP + ((systolic-diastolic BP) / 3)

In Figure 1, this value is approximately 80 + (120 − 80) / 3, or 93.33. Normally, the MAP falls within the range of 70–110 mm Hg. If the value falls below 60 mm Hg for an extended time, blood pressure will not be high enough to ensure circulation to and through the tissues, which results in ischemia, or insufficient blood flow. A condition called hypoxia, inadequate oxygenation of tissues, commonly accompanies ischemia. The term hypoxemia refers to low levels of oxygen in systemic arterial blood. Neurons are especially sensitive to hypoxia and may die or be damaged if blood flow and oxygen supplies are not quickly restored.

Pulse

After blood is ejected from the heart, elastic fibers in the arteries help maintain a high-pressure gradient as they expand to accommodate the blood, then recoil. This expansion and recoiling effect, known as the pulse, can be palpated manually or measured electronically. Although the effect diminishes over distance from the heart, elements of the systolic and diastolic components of the pulse are still evident down to the level of the arterioles.

Because pulse indicates heart rate, it is measured clinically to provide clues to a patient’s state of health. It is recorded as beats per minute. Both the rate and the strength of the pulse are important clinically. A high or irregular pulse rate can be caused by physical activity or other temporary factors, but it may also indicate a heart condition. The pulse strength indicates the strength of ventricular contraction and cardiac output. If the pulse is strong, then systolic pressure is high. If it is weak, systolic pressure has fallen, and medical intervention may be warranted.

Pulse can be palpated manually by placing the tips of the fingers across an artery that runs close to the body surface and pressing lightly. While this procedure is normally performed using the radial artery in the wrist or the common carotid artery in the neck, any superficial artery that can be palpated may be used (Figure 2). Common sites to find a pulse include temporal and facial arteries in the head, brachial arteries in the upper arm, femoral arteries in the thigh, popliteal arteries behind the knees, posterior tibial arteries near the medial tarsal regions, and dorsalis pedis arteries in the feet. A variety of commercial electronic devices are also available to measure pulse.

[caption id="" align="aligncenter" width="320"] Figure 2. Pulse Sites. The pulse is most readily measured at the radial artery, but can be measured at any of the pulse points shown.[/caption]

Measurement of Blood Pressure

Blood pressure is one of the critical parameters measured on virtually every patient in every healthcare setting. The technique used today was developed more than 100 years ago by a pioneering Russian physician, Dr. Nikolai Korotkoff. Turbulent blood flow through the vessels can be heard as a soft ticking while measuring blood pressure; these sounds are known as Korotkoff sounds. The technique of measuring blood pressure requires the use of a sphygmomanometer (a blood pressure cuff attached to a measuring device) and a stethoscope. The technique is as follows:

The clinician wraps an inflatable cuff tightly around the patient’s arm at about the level of the heart.
The clinician squeezes a rubber pump to inject air into the cuff, raising pressure around the artery and temporarily cutting off blood flow into the patient’s arm.
The clinician places the stethoscope on the patient’s antecubital region and, while gradually allowing air within the cuff to escape, listens for the Korotkoff sounds.

Although there are five recognized Korotkoff sounds, only two are normally recorded. Initially, no sounds are heard since there is no blood flow through the vessels, but as air pressure drops, the cuff relaxes, and blood flow returns to the arm. As shown in Figure 3, the first sound heard through the stethoscope—the first Korotkoff sound—indicates systolic pressure. As more air is released from the cuff, blood is able to flow freely through the brachial artery and all sounds disappear. The point at which the last sound is heard is recorded as the patient’s diastolic pressure.

[caption id="" align="aligncenter" width="450"] Figure 3. Blood Pressure Measurement. When pressure in a sphygmomanometer cuff is released, a clinician can hear the Korotkoff sounds. In this graph, a blood pressure tracing is aligned to a measurement of systolic and diastolic pressures.[/caption]

The majority of hospitals and clinics have automated equipment for measuring blood pressure that work on the same principles. An even more recent innovation is a small instrument that wraps around a patient’s wrist. The patient then holds the wrist over the heart while the device measures blood flow and records pressure.

Variables Affecting Blood Flow and Blood Pressure

Five variables influence blood flow and blood pressure:

Cardiac output
Compliance
Volume of the blood
Viscosity of the blood
Blood vessel length and diameter

Recall that blood moves from higher pressure to lower pressure. It is pumped from the heart into the arteries at high pressure. If you increase pressure in the arteries (afterload), and cardiac function does not compensate, blood flow will actually decrease. In the venous system, the opposite relationship is true. Increased pressure in the veins does not decrease flow as it does in arteries, but actually increases flow. Since pressure in the veins is normally relatively low, for blood to flow back into the heart, the pressure in the atria during atrial diastole must be even lower. It normally approaches zero, except when the atria contract (see Figure 1).

Cardiac Output

Cardiac output is the measurement of blood flow from the heart through the ventricles, and is usually measured in liters per minute. Any factor that causes cardiac output to increase, by elevating heart rate or stroke volume or both, will elevate blood pressure and promote blood flow. These factors include sympathetic stimulation, the catecholamines epinephrine and norepinephrine, thyroid hormones, and increased calcium ion levels. Conversely, any factor that decreases cardiac output, by decreasing heart rate or stroke volume or both, will decrease arterial pressure and blood flow. These factors include parasympathetic stimulation, elevated or decreased potassium ion levels, decreased calcium levels, anoxia, and acidosis.

Compliance

Compliance is the ability of any compartment to expand to accommodate increased content. A metal pipe, for example, is not compliant, whereas a balloon is. The greater the compliance of an artery, the more effectively it is able to expand to accommodate surges in blood flow without increased resistance or blood pressure. Veins are more compliant than arteries and can expand to hold more blood. When vascular disease causes stiffening of arteries, compliance is reduced and resistance to blood flow is increased. The result is more turbulence, higher pressure within the vessel, and reduced blood flow. This increases the work of the heart.

A Mathematical Approach to Factors Affecting Blood Flow

Jean Louis Marie Poiseuille was a French physician and physiologist who devised a mathematical equation describing blood flow and its relationship to known parameters. The same equation also applies to engineering studies of the flow of fluids. Although understanding the math behind the relationships among the factors affecting blood flow is not necessary to understand blood flow, it can help solidify an understanding of their relationships. Please note that even if the equation looks intimidating, breaking it down into its components and following the relationships will make these relationships clearer, even if you are weak in math. Focus on the three critical variables: radius (r), vessel length (λ), and viscosity (η).

Poiseuille’s equation:

Blood flow = π ΔP r48ηλ

π is the Greek letter pi, used to represent the mathematical constant that is the ratio of a circle’s circumference to its diameter. It may commonly be represented as 3.14, although the actual number extends to infinity.
ΔP represents the difference in pressure.
r⁴is the radius (one-half of the diameter) of the vessel to the fourth power.
η is the Greek letter eta and represents the viscosity of the blood.
λ is the Greek letter lambda and represents the length of a blood vessel.

One of several things this equation allows us to do is calculate the resistance in the vascular system. Normally this value is extremely difficult to measure, but it can be calculated from this known relationship:

Blood flow = ΔP/Resistance

If we rearrange this slightly,

Resistance = ΔP/Blood flow

Then by substituting Pouseille’s equation for blood flow:

Resistance =8ηλ/πr⁴

By examining this equation, you can see that there are only three variables: viscosity, vessel length, and radius, since 8 and π are both constants. The important thing to remember is this: Two of these variables, viscosity and vessel length, will change slowly in the body. Only one of these factors, the radius, can be changed rapidly by vasoconstriction and vasodilation, thus dramatically impacting resistance and flow. Further, small changes in the radius will greatly affect flow, since it is raised to the fourth power in the equation.

We have briefly considered how cardiac output and blood volume impact blood flow and pressure; the next step is to see how the other variables (contraction, vessel length, and viscosity) articulate with Pouseille’s equation and what they can teach us about the impact on blood flow.

Blood Volume

The relationship between blood volume, blood pressure, and blood flow is intuitively obvious. Water may merely trickle along a creek bed in a dry season, but rush quickly and under great pressure after a heavy rain. Similarly, as blood volume decreases, pressure and flow decrease. As blood volume increases, pressure and flow increase.

Under normal circumstances, blood volume varies little. Low blood volume, called hypovolemia, may be caused by bleeding, dehydration, vomiting, severe burns, or some medications used to treat hypertension. It is important to recognize that other regulatory mechanisms in the body are so effective at maintaining blood pressure that an individual may be asymptomatic until 10–20 percent of the blood volume has been lost. Treatment typically includes intravenous fluid replacement.

Hypervolemia, excessive fluid volume, may be caused by retention of water and sodium, as seen in patients with heart failure, liver cirrhosis, some forms of kidney disease, hyperaldosteronism, and some glucocorticoid steroid treatments. Restoring homeostasis in these patients depends upon reversing the condition that triggered the hypervolemia.

Blood Viscosity

Viscosity is the thickness of fluids that affects their ability to flow. Clean water, for example, is less viscous than mud. The viscosity of blood is directly proportional to resistance and inversely proportional to flow; therefore, any condition that causes viscosity to increase will also increase resistance and decrease flow. For example, imagine sipping milk, then a milkshake, through the same size straw. You experience more resistance and therefore less flow from the milkshake. Conversely, any condition that causes viscosity to decrease (such as when the milkshake melts) will decrease resistance and increase flow.

Normally the viscosity of blood does not change over short periods of time. The two primary determinants of blood viscosity are the formed elements and plasma proteins. Since the vast majority of formed elements are erythrocytes, any condition affecting erythropoiesis, such as polycythemia or anemia, can alter viscosity. Since most plasma proteins are produced by the liver, any condition affecting liver function can also change the viscosity slightly and therefore decrease blood flow. Liver abnormalities include hepatitis, cirrhosis, alcohol damage, and drug toxicities. While leukocytes and platelets are normally a small component of the formed elements, there are some rare conditions in which severe overproduction can impact viscosity as well.

Vessel Length and Diameter

The length of a vessel is directly proportional to its resistance: the longer the vessel, the greater the resistance and the lower the flow. As with blood volume, this makes intuitive sense, since the increased surface area of the vessel will impede the flow of blood. Likewise, if the vessel is shortened, the resistance will decrease and flow will increase.

The length of our blood vessels increases throughout childhood as we grow, of course, but is unchanging in adults under normal physiological circumstances. Further, the distribution of vessels is not the same in all tissues. Adipose tissue does not have an extensive vascular supply. One pound of adipose tissue contains approximately 200 miles of vessels, whereas skeletal muscle contains more than twice that. Overall, vessels decrease in length only during loss of mass or amputation. An individual weighing 150 pounds has approximately 60,000 miles of vessels in the body. Gaining about 10 pounds adds from 2000 to 4000 miles of vessels, depending upon the nature of the gained tissue. One of the great benefits of weight reduction is the reduced stress to the heart, which does not have to overcome the resistance of as many miles of vessels.

In contrast to length, the diameter of blood vessels changes throughout the body, according to the type of vessel, as we discussed earlier. The diameter of any given vessel may also change frequently throughout the day in response to neural and chemical signals that trigger vasodilation and vasoconstriction. The vascular tone of the vessel is the contractile state of the smooth muscle and the primary determinant of diameter, and thus of resistance and flow. The effect of vessel diameter on resistance is inverse: Given the same volume of blood, an increased diameter means there is less blood contacting the vessel wall, thus lower friction and lower resistance, subsequently increasing flow. A decreased diameter means more of the blood contacts the vessel wall, and resistance increases, subsequently decreasing flow.

The influence of lumen diameter on resistance is dramatic: A slight increase or decrease in diameter causes a huge decrease or increase in resistance. This is because resistance is inversely proportional to the radius of the blood vessel (one-half of the vessel’s diameter) raised to the fourth power (R = 1/r⁴). This means, for example, that if an artery or arteriole constricts to one-half of its original radius, the resistance to flow will increase 16 times. And if an artery or arteriole dilates to twice its initial radius, then resistance in the vessel will decrease to 1/16 of its original value and flow will increase 16 times.

The Roles of Vessel Diameter and Total Area in Blood Flow and Blood Pressure

Recall that we classified arterioles as resistance vessels, because given their small lumen, they dramatically slow the flow of blood from arteries. In fact, arterioles are the site of greatest resistance in the entire vascular network. This may seem surprising, given that capillaries have a smaller size. How can this phenomenon be explained?

Figure 4 compares vessel diameter, total cross-sectional area, average blood pressure, and blood velocity through the systemic vessels. Notice in parts (a) and (b) that the total cross-sectional area of the body’s capillary beds is far greater than any other type of vessel. Although the diameter of an individual capillary is significantly smaller than the diameter of an arteriole, there are vastly more capillaries in the body than there are other types of blood vessels. Part (c) shows that blood pressure drops unevenly as blood travels from arteries to arterioles, capillaries, venules, and veins, and encounters greater resistance. However, the site of the most precipitous drop, and the site of greatest resistance, is the arterioles. This explains why vasodilation and vasoconstriction of arterioles play more significant roles in regulating blood pressure than do the vasodilation and vasoconstriction of other vessels.

Part (d) shows that the velocity (speed) of blood flow decreases dramatically as the blood moves from arteries to arterioles to capillaries. This slow flow rate allows more time for exchange processes to occur. As blood flows through the veins, the rate of velocity increases, as blood is returned to the heart.

[caption id="" align="aligncenter" width="520"] Figure 4. Relationships among Vessels in the Systemic Circuit. The relationships among blood vessels that can be compared include (a) vessel diameter, (b) total cross-sectional area, (c) average blood pressure, and (d) velocity of blood flow.[/caption]

Venous System

The pumping action of the heart propels the blood into the arteries, from an area of higher pressure toward an area of lower pressure. If blood is to flow from the veins back into the heart, the pressure in the veins must be greater than the pressure in the atria of the heart. Two factors help maintain this pressure gradient between the veins and the heart. First, the pressure in the atria during diastole is very low, often approaching zero when the atria are relaxed (atrial diastole). Second, two physiologic “pumps” increase pressure in the venous system. The use of the term “pump” implies a physical device that speeds flow. These physiological pumps are less obvious.

Skeletal Muscle Pump

In many body regions, the pressure within the veins can be increased by the contraction of the surrounding skeletal muscle. This mechanism, known as the skeletal muscle pump (Figure 6), helps the lower-pressure veins counteract the force of gravity, increasing pressure to move blood back to the heart. As leg muscles contract, for example during walking or running, they exert pressure on nearby veins with their numerous one-way valves. This increased pressure causes blood to flow upward, opening valves superior to the contracting muscles so blood flows through. Simultaneously, valves inferior to the contracting muscles close; thus, blood should not seep back downward toward the feet. Military recruits are trained to flex their legs slightly while standing at attention for prolonged periods. Failure to do so may allow blood to pool in the lower limbs rather than returning to the heart. Consequently, the brain will not receive enough oxygenated blood, and the individual may lose consciousness.

[caption id="" align="aligncenter" width="380"] Figure 6. Skeletal Muscle Pump. The contraction of skeletal muscles surrounding a vein compresses the blood and increases the pressure in that area. This action forces blood closer to the heart where venous pressure is lower. Note the importance of the one-way valves to assure that blood flows only in the proper direction.[/caption]

Respiratory Pump

The respiratory pump aids blood flow through the veins of the thorax and abdomen. During inhalation, the volume of the thorax increases, largely through the contraction of the diaphragm, which moves downward and compresses the abdominal cavity. The elevation of the chest caused by the contraction of the external intercostal muscles also contributes to the increased volume of the thorax. The volume increase causes air pressure within the thorax to decrease, allowing us to inhale. Additionally, as air pressure within the thorax drops, blood pressure in the thoracic veins also decreases, falling below the pressure in the abdominal veins. This causes blood to flow along its pressure gradient from veins outside the thorax, where pressure is higher, into the thoracic region, where pressure is now lower. This in turn promotes the return of blood from the thoracic veins to the atria. During exhalation, when air pressure increases within the thoracic cavity, pressure in the thoracic veins increases, speeding blood flow into the heart while valves in the veins prevent blood from flowing backward from the thoracic and abdominal veins.

Pressure Relationships in the Venous System

Although vessel diameter increases from the smaller venules to the larger veins and eventually to the venae cavae (singular = vena cava), the total cross-sectional area actually decreases (see Figure 6a and b). The individual veins are larger in diameter than the venules, but their total number is much lower, so their total cross-sectional area is also lower.

Also notice that, as blood moves from venules to veins, the average blood pressure drops (see Figure 6c), but the blood velocity actually increases (see Figure 6). This pressure gradient drives blood back toward the heart. Again, the presence of one-way valves and the skeletal muscle and respiratory pumps contribute to this increased flow. Since approximately 64 percent of the total blood volume resides in systemic veins, any action that increases the flow of blood through the veins will increase venous return to the heart. Maintaining vascular tone within the veins prevents the veins from merely distending, dampening the flow of blood, and as you will see, vasoconstriction actually enhances the flow.

The Role of Venoconstriction in Resistance, Blood Pressure, and Flow

As previously discussed, vasoconstriction of an artery or arteriole decreases the radius, increasing resistance and pressure, but decreasing flow. Venoconstriction, on the other hand, has a very different outcome. The walls of veins are thin but irregular; thus, when the smooth muscle in those walls constricts, the lumen becomes more rounded. The more rounded the lumen, the less surface area the blood encounters, and the less resistance the vessel offers. Vasoconstriction increases pressure within a vein as it does in an artery, but in veins, the increased pressure increases flow. Recall that the pressure in the atria, into which the venous blood will flow, is very low, approaching zero for at least part of the relaxation phase of the cardiac cycle. Thus, venoconstriction increases the return of blood to the heart. Another way of stating this is that venoconstriction increases the preload or stretch of the cardiac muscle and increases contraction.

20.3 Capillary Exchange

barkerj1 — Wed, 30 Aug 2017 18:39:43 +0000

Learning Objectives

By the end of this section, you will be able to:

The primary purpose of the cardiovascular system is to circulate gases, nutrients, wastes, and other substances to and from the cells of the body. Small molecules, such as gases, lipids, and lipid-soluble molecules, can diffuse directly through the membranes of the endothelial cells of the capillary wall. Glucose, amino acids, and ions—including sodium, potassium, calcium, and chloride—use transporters to move through specific channels in the membrane by facilitated diffusion. Glucose, ions, and larger molecules may also leave the blood through intercellular clefts. Larger molecules can pass through the pores of fenestrated capillaries, and even large plasma proteins can pass through the great gaps in the sinusoids. Some large proteins in blood plasma can move into and out of the endothelial cells packaged within vesicles by endocytosis and exocytosis. Water moves by osmosis.

Bulk Flow

The mass movement of fluids into and out of capillary beds requires a transport mechanism far more efficient than mere diffusion. This movement, often referred to as bulk flow, involves two pressure-driven mechanisms: Volumes of fluid move from an area of higher pressure in a capillary bed to an area of lower pressure in the tissues via filtration. In contrast, the movement of fluid from an area of higher pressure in the tissues into an area of lower pressure in the capillaries is reabsorption. Two types of pressure interact to drive each of these movements: hydrostatic pressure and osmotic pressure.

Hydrostatic Pressure

The primary force driving fluid transport between the capillaries and tissues is hydrostatic pressure, which can be defined as the pressure of any fluid enclosed in a space. Blood hydrostatic pressure is the force exerted by the blood confined within blood vessels or heart chambers. Even more specifically, the pressure exerted by blood against the wall of a capillary is called capillary hydrostatic pressure (CHP), and is the same as capillary blood pressure. CHP is the force that drives fluid out of capillaries and into the tissues.

As fluid exits a capillary and moves into tissues, the hydrostatic pressure in the interstitial fluid correspondingly rises. This opposing hydrostatic pressure is called the interstitial fluid hydrostatic pressure (IFHP). Generally, the CHP originating from the arterial pathways is considerably higher than the IFHP, because lymphatic vessels are continually absorbing excess fluid from the tissues. Thus, fluid generally moves out of the capillary and into the interstitial fluid. This process is called filtration.

Osmotic Pressure

The net pressure that drives reabsorption—the movement of fluid from the interstitial fluid back into the capillaries—is called osmotic pressure (sometimes referred to as oncotic pressure). Whereas hydrostatic pressure forces fluid out of the capillary, osmotic pressure draws fluid back in. Osmotic pressure is determined by osmotic concentration gradients, that is, the difference in the solute-to-water concentrations in the blood and tissue fluid. A region higher in solute concentration (and lower in water concentration) draws water across a semipermeable membrane from a region higher in water concentration (and lower in solute concentration).

As we discuss osmotic pressure in blood and tissue fluid, it is important to recognize that the formed elements of blood do not contribute to osmotic concentration gradients. Rather, it is the plasma proteins that play the key role. Solutes also move across the capillary wall according to their concentration gradient, but overall, the concentrations should be similar and not have a significant impact on osmosis. Because of their large size and chemical structure, plasma proteins are not truly solutes, that is, they do not dissolve but are dispersed or suspended in their fluid medium, forming a colloid rather than a solution.

The pressure created by the concentration of colloidal proteins in the blood is called the blood colloidal osmotic pressure (BCOP). Its effect on capillary exchange accounts for the reabsorption of water. The plasma proteins suspended in blood cannot move across the semipermeable capillary cell membrane, and so they remain in the plasma. As a result, blood has a higher colloidal concentration and lower water concentration than tissue fluid. It therefore attracts water. We can also say that the BCOP is higher than the interstitial fluid colloidal osmotic pressure (IFCOP), which is always very low because interstitial fluid contains few proteins. Thus, water is drawn from the tissue fluid back into the capillary, carrying dissolved molecules with it. This difference in colloidal osmotic pressure accounts for reabsorption.

Interaction of Hydrostatic and Osmotic Pressures

The normal unit used to express pressures within the cardiovascular system is millimeters of mercury (mm Hg). When blood leaving an arteriole first enters a capillary bed, the CHP is quite high—about 35 mm Hg. Gradually, this initial CHP declines as the blood moves through the capillary so that by the time the blood has reached the venous end, the CHP has dropped to approximately 18 mm Hg. In comparison, the plasma proteins remain suspended in the blood, so the BCOP remains fairly constant at about 25 mm Hg throughout the length of the capillary and considerably below the osmotic pressure in the interstitial fluid.

The net filtration pressure (NFP) represents the interaction of the hydrostatic and osmotic pressures, driving fluid out of the capillary. It is equal to the difference between the CHP and the BCOP. Since filtration is, by definition, the movement of fluid out of the capillary, when reabsorption is occurring, the NFP is a negative number.

NFP changes at different points in a capillary bed (Figure 1). Close to the arterial end of the capillary, it is approximately 10 mm Hg, because the CHP of 35 mm Hg minus the BCOP of 25 mm Hg equals 10 mm Hg. Recall that the hydrostatic and osmotic pressures of the interstitial fluid are essentially negligible. Thus, the NFP of 10 mm Hg drives a net movement of fluid out of the capillary at the arterial end. At approximately the middle of the capillary, the CHP is about the same as the BCOP of 25 mm Hg, so the NFP drops to zero. At this point, there is no net change of volume: Fluid moves out of the capillary at the same rate as it moves into the capillary. Near the venous end of the capillary, the CHP has dwindled to about 18 mm Hg due to loss of fluid. Because the BCOP remains steady at 25 mm Hg, water is drawn into the capillary, that is, reabsorption occurs. Another way of expressing this is to say that at the venous end of the capillary, there is an NFP of −7 mm Hg.

[caption id="" align="aligncenter" width="520"] Figure 1. Capillary Exchange. Net filtration occurs near the arterial end of the capillary since capillary hydrostatic pressure (CHP) is greater than blood colloidal osmotic pressure (BCOP). There is no net movement of fluid near the midpoint since CHP = BCOP. Net reabsorption occurs near the venous end since BCOP is greater than CHP.[/caption]

20.4 Homeostatic Regulation of the Vascular System

barkerj1 — Wed, 30 Aug 2017 18:39:49 +0000

Learning Objectives

By the end of this section, you will be able to:

Specify five factors which affect blood pressure
Specify the major mechanisms that control blood pressure

In order to maintain homeostasis in the cardiovascular system and provide adequate blood to the tissues, blood flow must be redirected continually to the tissues as they become more active. In a very real sense, the cardiovascular system engages in resource allocation, because there is not enough blood flow to distribute blood equally to all tissues simultaneously. For example, when an individual is exercising, more blood will be directed to skeletal muscles, the heart, and the lungs. Following a meal, more blood is directed to the digestive system. Only the brain receives a more or less constant supply of blood whether you are active, resting, thinking, or engaged in any other activity.

Table 3 provides the distribution of systemic blood at rest and during exercise. Although most of the data appears logical, the values for the distribution of blood to the integument may seem surprising. During exercise, the body distributes more blood to the body surface where it can dissipate the excess heat generated by increased activity into the environment.

Systemic Blood Flow During Rest, Mild Exercise, and Maximal Exercise in a Healthy Young Individual (Table 3)
Organ	Resting (mL/min)	Mild exercise (mL/min)	Maximal exercise (mL/min)
Skeletal muscle	1200	4500	12,500
Heart	250	350	750
Brain	750	750	750
Integument	500	1500	1900
Kidney	1100	900	600
Gastrointestinal	1400	1100	600
Others (i.e., liver, spleen)	600	400	400
Total	5800	9500	17,500

Three homeostatic mechanisms ensure adequate blood flow, blood pressure, distribution, and ultimately perfusion: neural, endocrine, and autoregulatory mechanisms. They are summarized in Figure 1.

[caption id="" align="aligncenter" width="580"] Figure 1. Summary of Factors Maintaining Vascular Homeostasis. Adequate blood flow, blood pressure, distribution, and perfusion involve autoregulatory, neural, and endocrine mechanisms.[/caption]

Neural Regulation

The nervous system plays a critical role in the regulation of vascular homeostasis. The primary regulatory sites include the cardiovascular centers in the brain that control both cardiac and vascular functions. In addition, more generalized neural responses from the limbic system and the autonomic nervous system are factors.

The Cardiovascular Centers in the Brain

Neurological regulation of blood pressure and flow depends on the cardiovascular centers located in the medulla oblongata. This cluster of neurons responds to changes in blood pressure as well as blood concentrations of oxygen, carbon dioxide, and hydrogen ions. The cardiovascular center contains three distinct paired components:

The cardioaccelerator centers stimulate cardiac function by regulating heart rate and stroke volume via sympathetic stimulation from the cardiac accelerator nerve.
The cardioinhibitor centers slow cardiac function by decreasing heart rate and stroke volume via parasympathetic stimulation from the vagus nerve.
The vasomotor centers control vessel tone or contraction of the smooth muscle in the tunica media. Changes in diameter affect peripheral resistance, pressure, and flow, which affect cardiac output. The majority of these neurons act via the release of the neurotransmitter norepinephrine from sympathetic neurons.

Although each center functions independently, they are not anatomically distinct.

There is also a small population of neurons that control vasodilation in the vessels of the brain and skeletal muscles by relaxing the smooth muscle fibers in the vessel tunics. Many of these are cholinergic neurons, that is, they release acetylcholine, which in turn stimulates the vessels’ endothelial cells to release nitric oxide (NO), which causes vasodilation. Others release norepinephrine that binds to β₂ receptors. A few neurons release NO directly as a neurotransmitter.

Recall that mild stimulation of the skeletal muscles maintains muscle tone. A similar phenomenon occurs with vascular tone in vessels. As noted earlier, arterioles are normally partially constricted: With maximal stimulation, their radius may be reduced to one-half of the resting state. Full dilation of most arterioles requires that this sympathetic stimulation be suppressed. When it is, an arteriole can expand by as much as 150 percent. Such a significant increase can dramatically affect resistance, pressure, and flow.

Baroreceptor Reflexes

Baroreceptors are specialized stretch receptors located within thin areas of blood vessels and heart chambers that respond to the degree of stretch caused by the presence of blood. They send impulses to the cardiovascular center to regulate blood pressure. Vascular baroreceptors are found primarily in sinuses (small cavities) within the aorta and carotid arteries: The aortic sinuses are found in the walls of the ascending aorta just superior to the aortic valve, whereas the carotid sinuses are in the base of the internal carotid arteries. There are also low-pressure baroreceptors located in the walls of the venae cavae and right atrium. When blood pressure increases, the baroreceptors are stretched more tightly and initiate action potentials at a higher rate. At lower blood pressures, the degree of stretch is lower and the rate of firing is slower. When the cardiovascular center in the medulla oblongata receives this input, it triggers a reflex that maintains homeostasis (Figure 2):

When blood pressure rises too high, the baroreceptors fire at a higher rate and trigger parasympathetic stimulation of the heart. As a result, cardiac output falls. Sympathetic stimulation of the peripheral arterioles will also decrease, resulting in vasodilation. Combined, these activities cause blood pressure to fall.
When blood pressure drops too low, the rate of baroreceptor firing decreases. This will trigger an increase in sympathetic stimulation of the heart, causing cardiac output to increase. It will also trigger sympathetic stimulation of the peripheral vessels, resulting in vasoconstriction. Combined, these activities cause blood pressure to rise.

[caption id="" align="aligncenter" width="530"] Figure 2. Baroreceptor Reflexes for Maintaining Vascular Homeostasis. Increased blood pressure results in increased rates of baroreceptor firing, whereas decreased blood pressure results in slower rates of fire, both initiating the homeostatic mechanism to restore blood pressure.[/caption]

The baroreceptors in the venae cavae and right atrium monitor blood pressure as the blood returns to the heart from the systemic circulation. Normally, blood flow into the aorta is the same as blood flow back into the right atrium. If blood is returning to the right atrium more rapidly than it is being ejected from the left ventricle, the atrial receptors will stimulate the cardiovascular centers to increase sympathetic firing and increase cardiac output until homeostasis is achieved. The opposite is also true. This mechanism is referred to as the atrial reflex.

Chemoreceptor Reflexes

In addition to the baroreceptors are chemoreceptors that monitor levels of oxygen, carbon dioxide, and hydrogen ions (pH), and thereby contribute to vascular homeostasis. Chemoreceptors monitoring the blood are located in close proximity to the baroreceptors in the aortic and carotid sinuses. They signal the cardiovascular center as well as the respiratory centers in the medulla oblongata.

Since tissues consume oxygen and produce carbon dioxide and acids as waste products, when the body is more active, oxygen levels fall and carbon dioxide levels rise as cells undergo cellular respiration to meet the energy needs of activities. This causes more hydrogen ions to be produced, causing the blood pH to drop. When the body is resting, oxygen levels are higher, carbon dioxide levels are lower, more hydrogen is bound, and pH rises. (Seek additional content for more detail about pH.)

The chemoreceptors respond to increasing carbon dioxide and hydrogen ion levels (falling pH) by stimulating the cardioaccelerator and vasomotor centers, increasing cardiac output and constricting peripheral vessels. The cardioinhibitor centers are suppressed. With falling carbon dioxide and hydrogen ion levels (increasing pH), the cardioinhibitor centers are stimulated, and the cardioaccelerator and vasomotor centers are suppressed, decreasing cardiac output and causing peripheral vasodilation. In order to maintain adequate supplies of oxygen to the cells and remove waste products such as carbon dioxide, it is essential that the respiratory system respond to changing metabolic demands. In turn, the cardiovascular system will transport these gases to the lungs for exchange, again in accordance with metabolic demands. This interrelationship of cardiovascular and respiratory control cannot be overemphasized.

Other neural mechanisms can also have a significant impact on cardiovascular function. These include the limbic system that links physiological responses to psychological stimuli, as well as generalized sympathetic and parasympathetic stimulation.

Endocrine Regulation

Endocrine control over the cardiovascular system involves the catecholamines, epinephrine and norepinephrine, as well as several hormones that interact with the kidneys in the regulation of blood volume.

Epinephrine and Norepinephrine

The catecholamines epinephrine and norepinephrine are released by the adrenal medulla, and enhance and extend the body’s sympathetic or “fight-or-flight” response (see Figure 1). They increase heart rate and force of contraction, while temporarily constricting blood vessels to organs not essential for flight-or-fight responses and redirecting blood flow to the liver, muscles, and heart.

Antidiuretic Hormone

Antidiuretic hormone (ADH), also known as vasopressin, is secreted by the cells in the hypothalamus and transported via the hypothalamic-hypophyseal tracts to the posterior pituitary where it is stored until released upon nervous stimulation. The primary trigger prompting the hypothalamus to release ADH is increasing osmolarity of tissue fluid, usually in response to significant loss of blood volume. ADH signals its target cells in the kidneys to reabsorb more water, thus preventing the loss of additional fluid in the urine. This will increase overall fluid levels and help restore blood volume and pressure. In addition, ADH constricts peripheral vessels.

Renin-Angiotensin-Aldosterone Mechanism

The renin-angiotensin-aldosterone mechanism has a major effect upon the cardiovascular system (Figure 3). Renin is an enzyme, although because of its importance in the renin-angiotensin-aldosterone pathway, some sources identify it as a hormone. Specialized cells in the kidneys found in the juxtaglomerular apparatus respond to decreased blood flow by secreting renin into the blood. Renin converts the plasma protein angiotensinogen, which is produced by the liver, into its active form—angiotensin I. Angiotensin I circulates in the blood and is then converted into angiotensin II in the lungs. This reaction is catalyzed by the enzyme angiotensin-converting enzyme (ACE).

Angiotensin II is a powerful vasoconstrictor, greatly increasing blood pressure. It also stimulates the release of ADH and aldosterone, a hormone produced by the adrenal cortex. Aldosterone increases the reabsorption of sodium into the blood by the kidneys. Since water follows sodium, this increases the reabsorption of water. This in turn increases blood volume, raising blood pressure. Angiotensin II also stimulates the thirst center in the hypothalamus, so an individual will likely consume more fluids, again increasing blood volume and pressure.

[caption id="" align="aligncenter" width="560"] Figure 3. Hormones Involved in Renal Control of Blood Pressure. In the renin-angiotensin-aldosterone mechanism, increasing angiotensin II will stimulate the production of antidiuretic hormone and aldosterone. In addition to renin, the kidneys produce erythropoietin, which stimulates the production of red blood cells, further increasing blood volume.[/caption]

Erythropoietin

Erythropoietin (EPO) is released by the kidneys when blood flow and/or oxygen levels decrease. EPO stimulates the production of erythrocytes within the bone marrow. Erythrocytes are the major formed element of the blood and may contribute 40 percent or more to blood volume, a significant factor of viscosity, resistance, pressure, and flow. In addition, EPO is a vasoconstrictor. Overproduction of EPO or excessive intake of synthetic EPO, often to enhance athletic performance, will increase viscosity, resistance, and pressure, and decrease flow in addition to its contribution as a vasoconstrictor.

Atrial Natriuretic Hormone

Secreted by cells in the atria of the heart, atrial natriuretic hormone (ANH) (also known as atrial natriuretic peptide) is secreted when blood volume is high enough to cause extreme stretching of the cardiac cells. Cells in the ventricle produce a hormone with similar effects, called B-type natriuretic hormone. Natriuretic hormones are antagonists to angiotensin II. They promote loss of sodium and water from the kidneys, and suppress renin, aldosterone, and ADH production and release. All of these actions promote loss of fluid from the body, so blood volume and blood pressure drop.

Autoregulation of Perfusion

As the name would suggest, autoregulation mechanisms require neither specialized nervous stimulation nor endocrine control. Rather, these are local, self-regulatory mechanisms that allow each region of tissue to adjust its blood flow—and thus its perfusion. These local mechanisms include chemical signals and myogenic controls.

Chemical Signals Involved in Autoregulation

Chemical signals work at the level of the precapillary sphincters to trigger either constriction or relaxation. As you know, opening a precapillary sphincter allows blood to flow into that particular capillary, whereas constricting a precapillary sphincter temporarily shuts off blood flow to that region. The factors involved in regulating the precapillary sphincters include the following:

Opening of the sphincter is triggered in response to decreased oxygen concentrations; increased carbon dioxide concentrations; increasing levels of lactic acid or other byproducts of cellular metabolism; increasing concentrations of potassium ions or hydrogen ions (falling pH); inflammatory chemicals such as histamines; and increased body temperature. These conditions in turn stimulate the release of NO, a powerful vasodilator, from endothelial cells (see Figure 1).
Contraction of the precapillary sphincter is triggered by the opposite levels of the regulators, which prompt the release of endothelins, powerful vasoconstricting peptides secreted by endothelial cells. Platelet secretions and certain prostaglandins may also trigger constriction.

Again, these factors alter tissue perfusion via their effects on the precapillary sphincter mechanism, which regulates blood flow to capillaries. Since the amount of blood is limited, not all capillaries can fill at once, so blood flow is allocated based upon the needs and metabolic state of the tissues as reflected in these parameters. Bear in mind, however, that dilation and constriction of the arterioles feeding the capillary beds is the primary control mechanism.

The Myogenic Response

The myogenic response is a reaction to the stretching of the smooth muscle in the walls of arterioles as changes in blood flow occur through the vessel. This may be viewed as a largely protective function against dramatic fluctuations in blood pressure and blood flow to maintain homeostasis. If perfusion of an organ is too low (ischemia), the tissue will experience low levels of oxygen (hypoxia). In contrast, excessive perfusion could damage the organ’s smaller and more fragile vessels. The myogenic response is a localized process that serves to stabilize blood flow in the capillary network that follows that arteriole.

When blood flow is low, the vessel’s smooth muscle will be only minimally stretched. In response, it relaxes, allowing the vessel to dilate and thereby increase the movement of blood into the tissue. When blood flow is too high, the smooth muscle will contract in response to the increased stretch, prompting vasoconstriction that reduces blood flow.

Figure 4 summarizes the effects of nervous, endocrine, and local controls on arterioles.

[caption id="" align="aligncenter" width="520"] Figure 4. Summary of Mechanisms Regulating Arteriole Smooth Muscle and Veins.[/caption]

Effect of Exercise on Vascular Homeostasis

The heart is a muscle and, like any muscle, it responds dramatically to exercise. For a healthy young adult, cardiac output (heart rate × stroke volume) increases in the nonathlete from approximately 5.0 liters (5.25 quarts) per minute to a maximum of about 20 liters (21 quarts) per minute. Accompanying this will be an increase in blood pressure from about 120/80 to 185/75. However, well-trained aerobic athletes can increase these values substantially. For these individuals, cardiac output soars from approximately 5.3 liters (5.57 quarts) per minute resting to more than 30 liters (31.5 quarts) per minute during maximal exercise. Along with this increase in cardiac output, blood pressure increases from 120/80 at rest to 200/90 at maximum values. In addition to improved cardiac function, exercise increases the size and mass of the heart. The average weight of the heart for the nonathlete is about 300 g, whereas in an athlete it will increase to 500 g. This increase in size generally makes the heart stronger and more efficient at pumping blood, increasing both stroke volume and cardiac output.

Tissue perfusion also increases as the body transitions from a resting state to light exercise and eventually to heavy exercise (see Figure 4). These changes result in selective vasodilation in the skeletal muscles, heart, lungs, liver, and integument. Simultaneously, vasoconstriction occurs in the vessels leading to the kidneys and most of the digestive and reproductive organs. The flow of blood to the brain remains largely unchanged whether at rest or exercising, since the vessels in the brain largely do not respond to regulatory stimuli, in most cases, because they lack the appropriate receptors.

As vasodilation occurs in selected vessels, resistance drops and more blood rushes into the organs they supply. This blood eventually returns to the venous system. Venous return is further enhanced by both the skeletal muscle and respiratory pumps. As blood returns to the heart more quickly, preload rises and the Frank-Starling principle tells us that contraction of the cardiac muscle in the atria and ventricles will be more forceful. Eventually, even the best-trained athletes will fatigue and must undergo a period of rest following exercise. Cardiac output and distribution of blood then return to normal.

Regular exercise promotes cardiovascular health in a variety of ways. Because an athlete’s heart is larger than a nonathlete’s, stroke volume increases, so the athletic heart can deliver the same amount of blood as the nonathletic heart but with a lower heart rate. This increased efficiency allows the athlete to exercise for longer periods of time before muscles fatigue and places less stress on the heart. Exercise also lowers overall cholesterol levels by removing from the circulation a complex form of cholesterol, triglycerides, and proteins known as low-density lipoproteins (LDLs), which are widely associated with increased risk of cardiovascular disease. Although there is no way to remove deposits of plaque from the walls of arteries other than specialized surgery, exercise does promote the health of vessels by decreasing the rate of plaque formation and reducing blood pressure, so the heart does not have to generate as much force to overcome resistance.

Generally as little as 30 minutes of noncontinuous exercise over the course of each day has beneficial effects and has been shown to lower the rate of heart attack by nearly 50 percent. While it is always advisable to follow a healthy diet, stop smoking, and lose weight, studies have clearly shown that fit, overweight people may actually be healthier overall than sedentary slender people. Thus, the benefits of moderate exercise are undeniable.

Clinical Considerations in Vascular Homeostasis

Any disorder that affects blood volume, vascular tone, or any other aspect of vascular functioning is likely to affect vascular homeostasis as well. That includes hypertension, hemorrhage, and shock.

Hypertension and Hypotension

Chronically elevated blood pressure is known clinically as hypertension. It is defined as chronic and persistent blood pressure measurements of 140/90 mm Hg or above. Pressures between 120/80 and 140/90 mm Hg are defined as prehypertension. About 68 million Americans currently suffer from hypertension. Unfortunately, hypertension is typically a silent disorder; therefore, hypertensive patients may fail to recognize the seriousness of their condition and fail to follow their treatment plan. The result is often a heart attack or stroke. Hypertension may also lead to an aneurism (ballooning of a blood vessel caused by a weakening of the wall), peripheral arterial disease (obstruction of vessels in peripheral regions of the body), chronic kidney disease, or heart failure. [caption id="" align="aligncenter" width="120"] Listen to this CDC podcast to learn about hypertension, often described as a “silent killer.”[/caption]

Hemorrhage

Minor blood loss is managed by hemostasis and repair. Hemorrhage is a loss of blood that cannot be controlled by hemostatic mechanisms. Initially, the body responds to hemorrhage by initiating mechanisms aimed at increasing blood pressure and maintaining blood flow. Ultimately, however, blood volume will need to be restored, either through physiological processes or through medical intervention.

In response to blood loss, stimuli from the baroreceptors trigger the cardiovascular centers to stimulate sympathetic responses to increase cardiac output and vasoconstriction. This typically prompts the heart rate to increase to about 180–200 contractions per minute, restoring cardiac output to normal levels. Vasoconstriction of the arterioles increases vascular resistance, whereas constriction of the veins increases venous return to the heart. Both of these steps will help increase blood pressure. Sympathetic stimulation also triggers the release of epinephrine and norepinephrine, which enhance both cardiac output and vasoconstriction. If blood loss were less than 20 percent of total blood volume, these responses together would usually return blood pressure to normal and redirect the remaining blood to the tissues.

Additional endocrine involvement is necessary, however, to restore the lost blood volume. The angiotensin-renin-aldosterone mechanism stimulates the thirst center in the hypothalamus, which increases fluid consumption to help restore the lost blood. More importantly, it increases renal reabsorption of sodium and water, reducing water loss in urine output. The kidneys also increase the production of EPO, stimulating the formation of erythrocytes that not only deliver oxygen to the tissues but also increase overall blood volume. Figure 5 summarizes the responses to loss of blood volume.

[caption id="" align="aligncenter" width="490"] Figure 5. Homeostatic Responses to Loss of Blood Volume[/caption]

20.5 Circulatory Pathways

barkerj1 — Wed, 30 Aug 2017 18:40:20 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the main arteries leaving the heart
Describe the main arteries serving the trunk, appendages, and heart
Describe the main veins entering the heart
Describe the main veins draining the trunk, appendages, and heart

Virtually every cell, tissue, organ, and system in the body is impacted by the circulatory system. This includes the generalized and more specialized functions of transport of materials, capillary exchange, maintaining health by transporting white blood cells and various immunoglobulins (antibodies), hemostasis, regulation of body temperature, and helping to maintain acid-base balance. In addition to these shared functions, many systems enjoy a unique relationship with the circulatory system. Figure 1 summarizes these relationships.

[caption id="" align="aligncenter" width="520"] Figure 1. Interaction of the Circulatory System with Other Body Systems[/caption]

As you learn about the vessels of the systemic and pulmonary circuits, notice that many arteries and veins share the same names, parallel one another throughout the body, and are very similar on the right and left sides of the body. These pairs of vessels will be traced through only one side of the body. Where differences occur in branching patterns or when vessels are singular, this will be indicated. For example, you will find a pair of femoral arteries and a pair of femoral veins, with one vessel on each side of the body. In contrast, some vessels closer to the midline of the body, such as the aorta, are unique. Moreover, some superficial veins, such as the great saphenous vein in the femoral region, have no arterial counterpart. Another phenomenon that can make the study of vessels challenging is that names of vessels can change with location. Like a street that changes name as it passes through an intersection, an artery or vein can change names as it passes an anatomical landmark. For example, the left subclavian artery becomes the axillary artery as it passes through the body wall and into the axillary region, and then becomes the brachial artery as it flows from the axillary region into the upper arm (or brachium). You will also find examples of anastomoses where two blood vessels that previously branched reconnect. Anastomoses are especially common in veins, where they help maintain blood flow even when one vessel is blocked or narrowed, although there are some important ones in the arteries supplying the brain.

As you read about circular pathways, notice that there is an occasional, very large artery referred to as a trunk, a term indicating that the vessel gives rise to several smaller arteries. For example, the celiac trunk gives rise to the left gastric, common hepatic, and splenic arteries.

As you study this section, imagine you are on a “Voyage of Discovery” similar to Lewis and Clark’s expedition in 1804–1806, which followed rivers and streams through unfamiliar territory, seeking a water route from the Atlantic to the Pacific Ocean. You might envision being inside a miniature boat, exploring the various branches of the circulatory system. This simple approach has proven effective for many students in mastering these major circulatory patterns. Another approach that works well for many students is to create simple line drawings similar to the ones provided, labeling each of the major vessels. It is beyond the scope of this text to name every vessel in the body. However, we will attempt to discuss the major pathways for blood and acquaint you with the major named arteries and veins in the body. Also, please keep in mind that individual variations in circulation patterns are not uncommon.

[caption id="attachment_2976" align="aligncenter" width="150"] Watch this CrashCourse video to learn more about the blood vessels.[/caption]

Pulmonary Circulation

Recall that blood returning from the systemic circuit enters the right atrium (Figure 2) via the superior and inferior venae cavae and the coronary sinus, which drains the blood supply of the heart muscle. These vessels will be described more fully later in this section. This blood is relatively low in oxygen and relatively high in carbon dioxide, since much of the oxygen has been extracted for use by the tissues and the waste gas carbon dioxide was picked up to be transported to the lungs for elimination. From the right atrium, blood moves into the right ventricle, which pumps it to the lungs for gas exchange. This system of vessels is referred to as the pulmonary circuit.

The single vessel exiting the right ventricle is the pulmonary trunk. At the base of the pulmonary trunk is the pulmonary semilunar valve, which prevents backflow of blood into the right ventricle during ventricular diastole. As the pulmonary trunk reaches the superior surface of the heart, it curves posteriorly and rapidly bifurcates (divides) into two branches, a left and a right pulmonary artery. To prevent confusion between these vessels, it is important to refer to the vessel exiting the heart as the pulmonary trunk, rather than also calling it a pulmonary artery. The pulmonary arteries in turn branch many times within the lung, forming a series of smaller arteries and arterioles that eventually lead to the pulmonary capillaries. The pulmonary capillaries surround lung structures known as alveoli that are the sites of oxygen and carbon dioxide exchange.

Once gas exchange is completed, oxygenated blood flows from the pulmonary capillaries into a series of pulmonary venules that eventually lead to a series of larger pulmonary veins. Four pulmonary veins, two on the left and two on the right, return blood to the left atrium. At this point, the pulmonary circuit is complete. Table 4 defines the major arteries and veins of the pulmonary circuit discussed in the text.

[caption id="" align="aligncenter" width="420"] Figure 2. Pulmonary Circuit. Blood exiting from the right ventricle flows into the pulmonary trunk, which bifurcates into the two pulmonary arteries. These vessels branch to supply blood to the pulmonary capillaries, where gas exchange occurs within the lung alveoli. Blood returns via the pulmonary veins to the left atrium.[/caption]

Pulmonary Arteries and Veins (Table 4)
Vessel	Description
Pulmonary trunk	Single large vessel exiting the right ventricle that divides to form the right and left pulmonary arteries
Pulmonary arteries	Left and right vessels that form from the pulmonary trunk and lead to smaller arterioles and eventually to the pulmonary capillaries
Pulmonary veins	Two sets of paired vessels—one pair on each side—that are formed from the small venules, leading away from the pulmonary capillaries to flow into the left atrium

Overview of Systemic Arteries

Blood relatively high in oxygen concentration is returned from the pulmonary circuit to the left atrium via the four pulmonary veins. From the left atrium, blood moves into the left ventricle, which pumps blood into the aorta. The aorta and its branches—the systemic arteries—send blood to virtually every organ of the body (Figure 3).

[caption id="" align="aligncenter" width="400"] Figure 3. Systemic Arteries. The major systemic arteries shown here deliver oxygenated blood throughout the body.[/caption]

The Aorta

The aorta is the largest artery in the body (Figure 4). It arises from the left ventricle and eventually descends to the abdominal region, where it bifurcates at the level of the fourth lumbar vertebra into the two common iliac arteries. The aorta consists of the ascending aorta, the aortic arch, and the descending aorta, which passes through the diaphragm and a landmark that divides into the superior thoracic and inferior abdominal components. Arteries originating from the aorta ultimately distribute blood to virtually all tissues of the body. At the base of the aorta is the aortic semilunar valve that prevents backflow of blood into the left ventricle while the heart is relaxing. After exiting the heart, the ascending aorta moves in a superior direction for approximately 5 cm and ends at the sternal angle. Following this ascent, it reverses direction, forming a graceful arc to the left, called the aortic arch. The aortic arch descends toward the inferior portions of the body and ends at the level of the intervertebral disk between the fourth and fifth thoracic vertebrae. Beyond this point, the descending aorta continues close to the bodies of the vertebrae and passes through an opening in the diaphragm known as the aortic hiatus. Superior to the diaphragm, the aorta is called the thoracic aorta, and inferior to the diaphragm, it is called the abdominal aorta. The abdominal aorta terminates when it bifurcates into the two common iliac arteries at the level of the fourth lumbar vertebra. See Figure 4 for an illustration of the ascending aorta, the aortic arch, and the initial segment of the descending aorta plus major branches; Table 5 summarizes the structures of the aorta.

[caption id="" align="aligncenter" width="380"] Figure 4. Aorta. The aorta has distinct regions, including the ascending aorta, aortic arch, and the descending aorta, which includes the thoracic and abdominal regions.[/caption]

Components of the Aorta (Table 5)
Vessel	Description
Aorta	Largest artery in the body, originating from the left ventricle and descending to the abdominal region, where it bifurcates into the common iliac arteries at the level of the fourth lumbar vertebra; arteries originating from the aorta distribute blood to virtually all tissues of the body
Ascending aorta	Initial portion of the aorta, rising superiorly from the left ventricle for a distance of approximately 5 cm
Aortic arch	Graceful arc to the left that connects the ascending aorta to the descending aorta; ends at the intervertebral disk between the fourth and fifth thoracic vertebrae
Descending aorta	Portion of the aorta that continues inferiorly past the end of the aortic arch; subdivided into the thoracic aorta and the abdominal aorta
Thoracic aorta	Portion of the descending aorta superior to the aortic hiatus
Abdominal aorta	Portion of the aorta inferior to the aortic hiatus and superior to the common iliac arteries

Coronary Circulation

The first vessels that branch from the ascending aorta are the paired coronary arteries (see Figure 4), which arise from two of the three sinuses in the ascending aorta just superior to the aortic semilunar valve. These sinuses contain the aortic baroreceptors and chemoreceptors critical to maintain cardiac function. The left coronary artery arises from the left posterior aortic sinus. The right coronary artery arises from the anterior aortic sinus. Normally, the right posterior aortic sinus does not give rise to a vessel.

The coronary arteries encircle the heart, forming a ring-like structure that divides into the next level of branches that supplies blood to the heart tissues. (Seek additional content for more detail on cardiac circulation.)

Aortic Arch Branches

There are three major branches of the aortic arch: the brachiocephalic artery, the left common carotid artery, and the left subclavian (literally “under the clavicle”) artery. As you would expect based upon proximity to the heart, each of these vessels is classified as an elastic artery.

The brachiocephalic artery is located only on the right side of the body; there is no corresponding artery on the left. The brachiocephalic artery branches into the right subclavian artery and the right common carotid artery. The left subclavian and left common carotid arteries arise independently from the aortic arch but otherwise follow a similar pattern and distribution to the corresponding arteries on the right side (see Figure 2).

Each subclavian artery supplies blood to the arms, chest, shoulders, back, and central nervous system. It then gives rise to three major branches: the internal thoracic artery, the vertebral artery, and the thyrocervical artery. The internal thoracic artery, or mammary artery, supplies blood to the thymus, the pericardium of the heart, and the anterior chest wall. The vertebral artery passes through the vertebral foramen in the cervical vertebrae and then through the foramen magnum into the cranial cavity to supply blood to the brain and spinal cord. The paired vertebral arteries join together to form the large basilar artery at the base of the medulla oblongata. This is an example of an anastomosis. The subclavian artery also gives rise to the thyrocervical artery that provides blood to the thyroid, the cervical region of the neck, and the upper back and shoulder.

The common carotid artery divides into internal and external carotid arteries. The right common carotid artery arises from the brachiocephalic artery and the left common carotid artery arises directly from the aortic arch. The external carotid artery supplies blood to numerous structures within the face, lower jaw, neck, esophagus, and larynx. These branches include the lingual, facial, occipital, maxillary, and superficial temporal arteries. The internal carotid artery initially forms an expansion known as the carotid sinus, containing the carotid baroreceptors and chemoreceptors. Like their counterparts in the aortic sinuses, the information provided by these receptors is critical to maintaining cardiovascular homeostasis (see Figure 2).

The internal carotid arteries along with the vertebral arteries are the two primary suppliers of blood to the human brain. Given the central role and vital importance of the brain to life, it is critical that blood supply to this organ remains uninterrupted. Recall that blood flow to the brain is remarkably constant, with approximately 20 percent of blood flow directed to this organ at any given time. When blood flow is interrupted, even for just a few seconds, a transient ischemic attack (TIA), or mini-stroke, may occur, resulting in loss of consciousness or temporary loss of neurological function. In some cases, the damage may be permanent. Loss of blood flow for longer periods, typically between 3 and 4 minutes, will likely produce irreversible brain damage or a stroke, also called a cerebrovascular accident (CVA). The locations of the arteries in the brain not only provide blood flow to the brain tissue but also prevent interruption in the flow of blood. Both the carotid and vertebral arteries branch once they enter the cranial cavity, and some of these branches form a structure known as the arterial circle (or circle of Willis), an anastomosis that is remarkably like a traffic circle that sends off branches (in this case, arterial branches to the brain). As a rule, branches to the anterior portion of the cerebrum are normally fed by the internal carotid arteries; the remainder of the brain receives blood flow from branches associated with the vertebral arteries.

The internal carotid artery continues through the carotid canal of the temporal bone and enters the base of the brain through the carotid foramen where it gives rise to several branches (Figure 5 and Figure 6). One of these branches is the anterior cerebral artery that supplies blood to the frontal lobe of the cerebrum. Another branch, the middle cerebral artery, supplies blood to the temporal and parietal lobes, which are the most common sites of CVAs. The ophthalmic artery, the third major branch, provides blood to the eyes.

The right and left anterior cerebral arteries join together to form an anastomosis called the anterior communicating artery. The initial segments of the anterior cerebral arteries and the anterior communicating artery form the anterior portion of the arterial circle. The posterior portion of the arterial circle is formed by a left and a right posterior communicating artery that branches from the posterior cerebral artery, which arises from the basilar artery. It provides blood to the posterior portion of the cerebrum and brain stem. The basilar artery is an anastomosis that begins at the junction of the two vertebral arteries and sends branches to the cerebellum and brain stem. It flows into the posterior cerebral arteries. Table 6 summarizes the aortic arch branches, including the major branches supplying the brain.

[caption id="" align="aligncenter" width="420"] Figure 5. Arteries Supplying the Head and Neck. The common carotid artery gives rise to the external and internal carotid arteries. The external carotid artery remains superficial and gives rise to many arteries of the head. The internal carotid artery first forms the carotid sinus and then reaches the brain via the carotid canal and carotid foramen, emerging into the cranium via the foramen lacerum. The vertebral artery branches from the subclavian artery and passes through the transverse foramen in the cervical vertebrae, entering the base of the skull at the vertebral foramen. The subclavian artery continues toward the arm as the axillary artery.[/caption]

[caption id="" align="aligncenter" width="450"] Figure 6. Arteries Serving the Brain. This inferior view shows the network of arteries serving the brain. The structure is referred to as the arterial circle or circle of Willis.[/caption]

Aortic Arch Branches and Brain Circulation (Table 6)
Vessel	Description
Brachiocephalic artery	Single vessel located on the right side of the body; the first vessel branching from the aortic arch; gives rise to the right subclavian artery and the right common carotid artery; supplies blood to the head, neck, upper limb, and wall of the thoracic region
Subclavian artery	The right subclavian artery arises from the brachiocephalic artery while the left subclavian artery arises from the aortic arch; gives rise to the internal thoracic, vertebral, and thyrocervical arteries; supplies blood to the arms, chest, shoulders, back, and central nervous system
Internal thoracic artery	Also called the mammary artery; arises from the subclavian artery; supplies blood to the thymus, pericardium of the heart, and anterior chest wall
Vertebral artery	Arises from the subclavian artery and passes through the vertebral foramen through the foramen magnum to the brain; joins with the internal carotid artery to form the arterial circle; supplies blood to the brain and spinal cord
Thyrocervical artery	Arises from the subclavian artery; supplies blood to the thyroid, the cervical region, the upper back, and shoulder
Common carotid artery	The right common carotid artery arises from the brachiocephalic artery and the left common carotid artery arises from the aortic arch; each gives rise to the external and internal carotid arteries; supplies the respective sides of the head and neck
External carotid artery	Arises from the common carotid artery; supplies blood to numerous structures within the face, lower jaw, neck, esophagus, and larynx
Internal carotid artery	Arises from the common carotid artery and begins with the carotid sinus; goes through the carotid canal of the temporal bone to the base of the brain; combines with the branches of the vertebral artery, forming the arterial circle; supplies blood to the brain
Arterial circle or circle of Willis	An anastomosis located at the base of the brain that ensures continual blood supply; formed from the branches of the internal carotid and vertebral arteries; supplies blood to the brain
Anterior cerebral artery	Arises from the internal carotid artery; supplies blood to the frontal lobe of the cerebrum
Middle cerebral artery	Another branch of the internal carotid artery; supplies blood to the temporal and parietal lobes of the cerebrum
Ophthalmic artery	Branch of the internal carotid artery; supplies blood to the eyes
Anterior communicating artery	An anastomosis of the right and left internal carotid arteries; supplies blood to the brain
Posterior communicating artery	Branches of the posterior cerebral artery that form part of the posterior portion of the arterial circle; supplies blood to the brain
Posterior cerebral artery	Branch of the basilar artery that forms a portion of the posterior segment of the arterial circle of Willis; supplies blood to the posterior portion of the cerebrum and brain stem
Basilar artery	Formed from the fusion of the two vertebral arteries; sends branches to the cerebellum, brain stem, and the posterior cerebral arteries; the main blood supply to the brain stem

Thoracic Aorta and Major Branches

The thoracic aorta begins at the level of vertebra T5 and continues through to the diaphragm at the level of T12, initially traveling within the mediastinum to the left of the vertebral column. As it passes through the thoracic region, the thoracic aorta gives rise to several branches, which are collectively referred to as visceral branches and parietal branches (Figure 7). Those branches that supply blood primarily to visceral organs are known as the visceral branches and include the bronchial arteries, pericardial arteries, esophageal arteries, and the mediastinal arteries, each named after the tissues it supplies. Each bronchial artery (typically two on the left and one on the right) supplies systemic blood to the lungs and visceral pleura, in addition to the blood pumped to the lungs for oxygenation via the pulmonary circuit. The bronchial arteries follow the same path as the respiratory branches, beginning with the bronchi and ending with the bronchioles. There is considerable, but not total, intermingling of the systemic and pulmonary blood at anastomoses in the smaller branches of the lungs. This may sound incongruous—that is, the mixing of systemic arterial blood high in oxygen with the pulmonary arterial blood lower in oxygen—but the systemic vessels also deliver nutrients to the lung tissue just as they do elsewhere in the body. The mixed blood drains into typical pulmonary veins, whereas the bronchial artery branches remain separate and drain into bronchial veins described later. Each pericardial artery supplies blood to the pericardium, the esophageal artery provides blood to the esophagus, and the mediastinal artery provides blood to the mediastinum. The remaining thoracic aorta branches are collectively referred to as parietal branches or somatic branches, and include the intercostal and superior phrenic arteries. Each intercostal artery provides blood to the muscles of the thoracic cavity and vertebral column. The superior phrenic artery provides blood to the superior surface of the diaphragm. Table 7 lists the arteries of the thoracic region.

[caption id="" align="aligncenter" width="480"] Figure 7. Arteries of the Thoracic and Abdominal Regions. The thoracic aorta gives rise to the arteries of the visceral and parietal branches.[/caption]

Arteries of the Thoracic Region (Table 7)
Vessel	Description
Visceral branches	A group of arterial branches of the thoracic aorta; supplies blood to the viscera (i.e., organs) of the thorax
Bronchial artery	Systemic branch from the aorta that provides oxygenated blood to the lungs; this blood supply is in addition to the pulmonary circuit that brings blood for oxygenation
Pericardial artery	Branch of the thoracic aorta; supplies blood to the pericardium
Esophageal artery	Branch of the thoracic aorta; supplies blood to the esophagus
Mediastinal artery	Branch of the thoracic aorta; supplies blood to the mediastinum
Parietal branches	Also called somatic branches, a group of arterial branches of the thoracic aorta; include those that supply blood to the thoracic wall, vertebral column, and the superior surface of the diaphragm
Intercostal artery	Branch of the thoracic aorta; supplies blood to the muscles of the thoracic cavity and vertebral column
Superior phrenic artery	Branch of the thoracic aorta; supplies blood to the superior surface of the diaphragm

Abdominal Aorta and Major Branches

After crossing through the diaphragm at the aortic hiatus, the thoracic aorta is called the abdominal aorta (see Figure 7). This vessel remains to the left of the vertebral column and is embedded in adipose tissue behind the peritoneal cavity. It formally ends at approximately the level of vertebra L4, where it bifurcates to form the common iliac arteries. Before this division, the abdominal aorta gives rise to several important branches. A single celiac trunk (artery) emerges and divides into the left gastric artery to supply blood to the stomach and esophagus, the splenic artery to supply blood to the spleen, and the common hepatic artery, which in turn gives rise to the hepatic artery proper to supply blood to the liver, the right gastric artery to supply blood to the stomach, the cystic artery to supply blood to the gall bladder, and several branches, one to supply blood to the duodenum and another to supply blood to the pancreas. Two additional single vessels arise from the abdominal aorta. These are the superior and inferior mesenteric arteries. The superior mesenteric artery arises approximately 2.5 cm after the celiac trunk and branches into several major vessels that supply blood to the small intestine (duodenum, jejunum, and ileum), the pancreas, and a majority of the large intestine. The inferior mesenteric artery supplies blood to the distal segment of the large intestine, including the rectum. It arises approximately 5 cm superior to the common iliac arteries.

In addition to these single branches, the abdominal aorta gives rise to several significant paired arteries along the way. These include the inferior phrenic arteries, the adrenal arteries, the renal arteries, the gonadal arteries, and the lumbar arteries. Each inferior phrenic artery is a counterpart of a superior phrenic artery and supplies blood to the inferior surface of the diaphragm. The adrenal artery supplies blood to the adrenal (suprarenal) glands and arises near the superior mesenteric artery. Each renal artery branches approximately 2.5 cm inferior to the superior mesenteric arteries and supplies a kidney. The right renal artery is longer than the left since the aorta lies to the left of the vertebral column and the vessel must travel a greater distance to reach its target. Renal arteries branch repeatedly to supply blood to the kidneys. Each gonadal artery supplies blood to the gonads, or reproductive organs, and is also described as either an ovarian artery or a testicular artery (internal spermatic), depending upon the sex of the individual. An ovarian artery supplies blood to an ovary, uterine (Fallopian) tube, and the uterus, and is located within the suspensory ligament of the uterus. It is considerably shorter than a testicular artery, which ultimately travels outside the body cavity to the testes, forming one component of the spermatic cord. The gonadal arteries arise inferior to the renal arteries and are generally retroperitoneal. The ovarian artery continues to the uterus where it forms an anastomosis with the uterine artery that supplies blood to the uterus. Both the uterine arteries and vaginal arteries, which distribute blood to the vagina, are branches of the internal iliac artery. The four paired lumbar arteries are the counterparts of the intercostal arteries and supply blood to the lumbar region, the abdominal wall, and the spinal cord. In some instances, a fifth pair of lumbar arteries emerges from the median sacral artery.

The aorta divides at approximately the level of vertebra L4 into a left and a right common iliac artery but continues as a small vessel, the median sacral artery, into the sacrum. The common iliac arteries provide blood to the pelvic region and ultimately to the lower limbs. They split into external and internal iliac arteries approximately at the level of the lumbar-sacral articulation. Each internal iliac artery sends branches to the urinary bladder, the walls of the pelvis, the external genitalia, and the medial portion of the femoral region. In females, they also provide blood to the uterus and vagina. The much larger external iliac artery supplies blood to each of the lower limbs. Figure 8 shows the distribution of the major branches of the aorta into the thoracic and abdominal regions. Figure 9 shows the distribution of the major branches of the common iliac arteries. Table 8 summarizes the major branches of the abdominal aorta.

[caption id="" align="aligncenter" width="480"] Figure 8. Major Branches of the Aorta. The flow chart summarizes the distribution of the major branches of the aorta into the thoracic and abdominal regions.[/caption]

Major Branches of the Iliac Arteries

The flow chart summarizes the distribution of the major branches of the common iliac arteries into the pelvis and lower limbs. The left side follows a similar pattern to the right.

[caption id="" align="aligncenter" width="480"] Figure 9. Major Branches of the Iliac Arteries. The flow chart summarizes the distribution of the major branches of the common iliac arteries into the pelvis and lower limbs. The left side follows a similar pattern to the right.[/caption]

Vessels of the Abdominal Aorta
Vessel	Description
Celiac trunk	Also called the celiac artery; a major branch of the abdominal aorta; gives rise to the left gastric artery, the splenic artery, and the common hepatic artery that forms the hepatic artery to the liver, the right gastric artery to the stomach, and the cystic artery to the gall bladder
Left gastric artery	Branch of the celiac trunk; supplies blood to the stomach
Splenic artery	Branch of the celiac trunk; supplies blood to the spleen
Common hepatic artery	Branch of the celiac trunk that forms the hepatic artery, the right gastric artery, and the cystic artery
Hepatic artery proper	Branch of the common hepatic artery; supplies systemic blood to the liver
Right gastric artery	Branch of the common hepatic artery; supplies blood to the stomach
Cystic artery	Branch of the common hepatic artery; supplies blood to the gall bladder
Superior mesenteric artery	Branch of the abdominal aorta; supplies blood to the small intestine (duodenum, jejunum, and ileum), the pancreas, and a majority of the large intestine
Inferior mesenteric artery	Branch of the abdominal aorta; supplies blood to the distal segment of the large intestine and rectum
Inferior phrenic arteries	Branches of the abdominal aorta; supply blood to the inferior surface of the diaphragm
Adrenal artery	Branch of the abdominal aorta; supplies blood to the adrenal (suprarenal) glands
Renal artery	Branch of the abdominal aorta; supplies each kidney
Gonadal artery	Branch of the abdominal aorta; supplies blood to the gonads or reproductive organs; also described as ovarian arteries or testicular arteries, depending upon the sex of the individual
Ovarian artery	Branch of the abdominal aorta; supplies blood to ovary, uterine (Fallopian) tube, and uterus
Testicular artery	Branch of the abdominal aorta; ultimately travels outside the body cavity to the testes and forms one component of the spermatic cord
Lumbar arteries	Branches of the abdominal aorta; supply blood to the lumbar region, the abdominal wall, and spinal cord
Common iliac artery	Branch of the aorta that leads to the internal and external iliac arteries
Median sacral artery	Continuation of the aorta into the sacrum
Internal iliac artery	Branch from the common iliac arteries; supplies blood to the urinary bladder, walls of the pelvis, external genitalia, and the medial portion of the femoral region; in females, also provides blood to the uterus and vagina
External iliac artery	Branch of the common iliac artery that leaves the body cavity and becomes a femoral artery; supplies blood to the lower limbs

Arteries Serving the Upper Limbs

As the subclavian artery exits the thorax into the axillary region, it is renamed the axillary artery. Although it does branch and supply blood to the region near the head of the humerus (via the humeral circumflex arteries), the majority of the vessel continues into the upper arm, or brachium, and becomes the brachial artery (Figure 10). The brachial artery supplies blood to much of the brachial region and divides at the elbow into several smaller branches, including the deep brachial arteries, which provide blood to the posterior surface of the arm, and the ulnar collateral arteries, which supply blood to the region of the elbow. As the brachial artery approaches the coronoid fossa, it bifurcates into the radial and ulnar arteries, which continue into the forearm, or antebrachium. The radial artery and ulnar artery parallel their namesake bones, giving off smaller branches until they reach the wrist, or carpal region. At this level, they fuse to form the superficial and deep palmar arches that supply blood to the hand, as well as the digital arteries that supply blood to the digits. Figure 11 shows the distribution of systemic arteries from the heart into the upper limb. Table 9 summarizes the arteries serving the upper limbs.

[caption id="" align="aligncenter" width="280"] Figure 10. Major Arteries Serving the Thorax and Upper Limb. The arteries that supply blood to the arms and hands are extensions of the subclavian arteries.[/caption]

[caption id="" align="aligncenter" width="520"] Figure 11. Major Arteries of the Upper Limb. The flow chart summarizes the distribution of the major arteries from the heart into the upper limb.[/caption]

Arteries Serving the Upper Limbs (Table 9)
Vessel	Description
Axillary artery	Continuation of the subclavian artery as it penetrates the body wall and enters the axillary region; supplies blood to the region near the head of the humerus (humeral circumflex arteries); the majority of the vessel continues into the brachium and becomes the brachial artery
Brachial artery	Continuation of the axillary artery in the brachium; supplies blood to much of the brachial region; gives off several smaller branches that provide blood to the posterior surface of the arm in the region of the elbow; bifurcates into the radial and ulnar arteries at the coronoid fossa
Radial artery	Formed at the bifurcation of the brachial artery; parallels the radius; gives off smaller branches until it reaches the carpal region where it fuses with the ulnar artery to form the superficial and deep palmar arches; supplies blood to the lower arm and carpal region
Ulnar artery	Formed at the bifurcation of the brachial artery; parallels the ulna; gives off smaller branches until it reaches the carpal region where it fuses with the radial artery to form the superficial and deep palmar arches; supplies blood to the lower arm and carpal region
Palmar arches (superficial and deep)	Formed from anastomosis of the radial and ulnar arteries; supply blood to the hand and digital arteries
Digital arteries	Formed from the superficial and deep palmar arches; supply blood to the digits

Arteries Serving the Lower Limbs

The external iliac artery exits the body cavity and enters the femoral region of the lower leg (Figure 12). As it passes through the body wall, it is renamed the femoral artery. It gives off several smaller branches as well as the lateral deep femoral artery that in turn gives rise to a lateral circumflex artery. These arteries supply blood to the deep muscles of the thigh as well as ventral and lateral regions of the integument. The femoral artery also gives rise to the genicular artery, which provides blood to the region of the knee. As the femoral artery passes posterior to the knee near the popliteal fossa, it is called the popliteal artery. The popliteal artery branches into the anterior and posterior tibial arteries.

The anterior tibial artery is located between the tibia and fibula, and supplies blood to the muscles and integument of the anterior tibial region. Upon reaching the tarsal region, it becomes the dorsalis pedis artery, which branches repeatedly and provides blood to the tarsal and dorsal regions of the foot. The posterior tibial artery provides blood to the muscles and integument on the posterior surface of the tibial region. The fibular or peroneal artery branches from the posterior tibial artery. It bifurcates and becomes the medial plantar artery and lateral plantar artery, providing blood to the plantar surfaces. There is an anastomosis with the dorsalis pedis artery, and the medial and lateral plantar arteries form two arches called the dorsal arch (also called the arcuate arch) and the plantar arch, which provide blood to the remainder of the foot and toes. Figure 13 shows the distribution of the major systemic arteries in the lower limb. Table 10 summarizes the major systemic arteries discussed in the text.

[caption id="" align="aligncenter" width="500"] Figure 12. Major Arteries Serving the Lower Limb. Major arteries serving the lower limb are shown in anterior and posterior views.[/caption]

[caption id="" align="aligncenter" width="520"] Figure 13. Systemic Arteries of the Lower Limb. The flow chart summarizes the distribution of the systemic arteries from the external iliac artery into the lower limb.[/caption]

Arteries Serving the Lower Limbs (Table 10)
Vessel	Description
Femoral artery	Continuation of the external iliac artery after it passes through the body cavity; divides into several smaller branches, the lateral deep femoral artery, and the genicular artery; becomes the popliteal artery as it passes posterior to the knee
Deep femoral artery	Branch of the femoral artery; gives rise to the lateral circumflex arteries
Lateral circumflex artery	Branch of the deep femoral artery; supplies blood to the deep muscles of the thigh and the ventral and lateral regions of the integument
Genicular artery	Branch of the femoral artery; supplies blood to the region of the knee
Popliteal artery	Continuation of the femoral artery posterior to the knee; branches into the anterior and posterior tibial arteries
Anterior tibial artery	Branches from the popliteal artery; supplies blood to the anterior tibial region; becomes the dorsalis pedis artery
Dorsalis pedis artery	Forms from the anterior tibial artery; branches repeatedly to supply blood to the tarsal and dorsal regions of the foot
Posterior tibial artery	Branches from the popliteal artery and gives rise to the fibular or peroneal artery; supplies blood to the posterior tibial region
Medial plantar artery	Arises from the bifurcation of the posterior tibial arteries; supplies blood to the medial plantar surfaces of the foot
Lateral plantar artery	Arises from the bifurcation of the posterior tibial arteries; supplies blood to the lateral plantar surfaces of the foot
Dorsal or arcuate arch	Formed from the anastomosis of the dorsalis pedis artery and the medial and plantar arteries; branches supply the distal portions of the foot and digits
Plantar arch	Formed from the anastomosis of the dorsalis pedis artery and the medial and plantar arteries; branches supply the distal portions of the foot and digits

Overview of Systemic Veins

Systemic veins return blood to the right atrium. Since the blood has already passed through the systemic capillaries, it will be relatively low in oxygen concentration. In many cases, there will be veins draining organs and regions of the body with the same name as the arteries that supplied these regions and the two often parallel one another. This is often described as a “complementary” pattern. However, there is a great deal more variability in the venous circulation than normally occurs in the arteries. For the sake of brevity and clarity, this text will discuss only the most commonly encountered patterns. However, keep this variation in mind when you move from the classroom to clinical practice.

In both the neck and limb regions, there are often both superficial and deeper levels of veins. The deeper veins generally correspond to the complementary arteries. The superficial veins do not normally have direct arterial counterparts, but in addition to returning blood, they also make contributions to the maintenance of body temperature. When the ambient temperature is warm, more blood is diverted to the superficial veins where heat can be more easily dissipated to the environment. In colder weather, there is more constriction of the superficial veins and blood is diverted deeper where the body can retain more of the heat.

The “Voyage of Discovery” analogy and stick drawings mentioned earlier remain valid techniques for the study of systemic veins, but veins present a more difficult challenge because there are numerous anastomoses and multiple branches. It is like following a river with many tributaries and channels, several of which interconnect. Tracing blood flow through arteries follows the current in the direction of blood flow, so that we move from the heart through the large arteries and into the smaller arteries to the capillaries. From the capillaries, we move into the smallest veins and follow the direction of blood flow into larger veins and back to the heart. Figure 14 outlines the path of the major systemic veins.

[caption id="" align="aligncenter" width="460"] Figure 14. Major Systemic Veins of the Body. The major systemic veins of the body are shown here in an anterior view.[/caption]

The right atrium receives all of the systemic venous return. Most of the blood flows into either the superior vena cava or inferior vena cava. If you draw an imaginary line at the level of the diaphragm, systemic venous circulation from above that line will generally flow into the superior vena cava; this includes blood from the head, neck, chest, shoulders, and upper limbs. The exception to this is that most venous blood flow from the coronary veins flows directly into the coronary sinus and from there directly into the right atrium. Beneath the diaphragm, systemic venous flow enters the inferior vena cava, that is, blood from the abdominal and pelvic regions and the lower limbs.

The Superior Vena Cava

The superior vena cava drains most of the body superior to the diaphragm (Figure 15). On both the left and right sides, the subclavian vein forms when the axillary vein passes through the body wall from the axillary region. It fuses with the external and internal jugular veins from the head and neck to form the brachiocephalic vein. Each vertebral vein also flows into the brachiocephalic vein close to this fusion. These veins arise from the base of the brain and the cervical region of the spinal cord, and flow largely through the intervertebral foramina in the cervical vertebrae. They are the counterparts of the vertebral arteries. Each internal thoracic vein, also known as an internal mammary vein, drains the anterior surface of the chest wall and flows into the brachiocephalic vein.

The remainder of the blood supply from the thorax drains into the azygos vein. Each intercostal vein drains muscles of the thoracic wall, each esophageal vein delivers blood from the inferior portions of the esophagus, each bronchial vein drains the systemic circulation from the lungs, and several smaller veins drain the mediastinal region. Bronchial veins carry approximately 13 percent of the blood that flows into the bronchial arteries; the remainder intermingles with the pulmonary circulation and returns to the heart via the pulmonary veins. These veins flow into the azygos vein, and with the smaller hemiazygos vein (hemi- = “half”) on the left of the vertebral column, drain blood from the thoracic region. The hemiazygos vein does not drain directly into the superior vena cava but enters the brachiocephalic vein via the superior intercostal vein.

The azygos vein passes through the diaphragm from the thoracic cavity on the right side of the vertebral column and begins in the lumbar region of the thoracic cavity. It flows into the superior vena cava at approximately the level of T2, making a significant contribution to the flow of blood. It combines with the two large left and right brachiocephalic veins to form the superior vena cava.

Table 11 summarizes the veins of the thoracic region that flow into the superior vena cava.

[caption id="" align="aligncenter" width="480"] Figure 15. Veins of the Thoracic and Abdominal Regions. Veins of the thoracic and abdominal regions drain blood from the area above the diaphragm, returning it to the right atrium via the superior vena cava.[/caption]

Veins of the Thoracic Region (Table 11)
Vessel	Description
Superior vena cava	Large systemic vein; drains blood from most areas superior to the diaphragm; empties into the right atrium
Subclavian vein	Located deep in the thoracic cavity; formed by the axillary vein as it enters the thoracic cavity from the axillary region; drains the axillary and smaller local veins near the scapular region and leads to the brachiocephalic vein
Brachiocephalic veins	Pair of veins that form from a fusion of the external and internal jugular veins and the subclavian vein; subclavian, external and internal jugulars, vertebral, and internal thoracic veins flow into it; drain the upper thoracic region and lead to the superior vena cava
Vertebral vein	Arises from the base of the brain and the cervical region of the spinal cord; passes through the intervertebral foramina in the cervical vertebrae; drains smaller veins from the cranium, spinal cord, and vertebrae, and leads to the brachiocephalic vein; counterpart of the vertebral artery
Internal thoracic veins	Also called internal mammary veins; drain the anterior surface of the chest wall and lead to the brachiocephalic vein
Intercostal vein	Drains the muscles of the thoracic wall and leads to the azygos vein
Esophageal vein	Drains the inferior portions of the esophagus and leads to the azygos vein
Bronchial vein	Drains the systemic circulation from the lungs and leads to the azygos vein
Azygos vein	Originates in the lumbar region and passes through the diaphragm into the thoracic cavity on the right side of the vertebral column; drains blood from the intercostal veins, esophageal veins, bronchial veins, and other veins draining the mediastinal region, and leads to the superior vena cava
Hemiazygos vein	Smaller vein complementary to the azygos vein; drains the esophageal veins from the esophagus and the left intercostal veins, and leads to the brachiocephalic vein via the superior intercostal vein

Veins of the Head and Neck

Blood from the brain and the superficial facial vein flow into each internal jugular vein (Figure 16). Blood from the more superficial portions of the head, scalp, and cranial regions, including the temporal vein and maxillary vein, flow into each external jugular vein. Although the external and internal jugular veins are separate vessels, there are anastomoses between them close to the thoracic region. Blood from the external jugular vein empties into the subclavian vein. Table 12 summarizes the major veins of the head and neck.

Major Veins of the Head and Neck (Table 12)
Vessel	Description
Internal jugular vein	Parallel to the common carotid artery, which is more or less its counterpart, and passes through the jugular foramen and canal; primarily drains blood from the brain, receives the superficial facial vein, and empties into the subclavian vein
Temporal vein	Drains blood from the temporal region and flows into the external jugular vein
Maxillary vein	Drains blood from the maxillary region and flows into the external jugular vein
External jugular vein	Drains blood from the more superficial portions of the head, scalp, and cranial regions, and leads to the subclavian vein

Venous Drainage of the Brain

Circulation to the brain is both critical and complex (see Table 16). Many smaller veins of the brain stem and the superficial veins of the cerebrum lead to larger vessels referred to as intracranial sinuses. These include the superior and inferior sagittal sinuses, straight sinus, cavernous sinuses, left and right sinuses, the petrosal sinuses, and the occipital sinuses. Ultimately, sinuses will lead back to either the inferior jugular vein or vertebral vein.

Most of the veins on the superior surface of the cerebrum flow into the largest of the sinuses, the superior sagittal sinus. It is located midsagittally between the meningeal and periosteal layers of the dura mater within the falx cerebri and, at first glance in images or models, can be mistaken for the subarachnoid space. Most reabsorption of cerebrospinal fluid occurs via the chorionic villi (arachnoid granulations) into the superior sagittal sinus. Blood from most of the smaller vessels originating from the inferior cerebral veins flows into the great cerebral vein and into the straight sinus. Other cerebral veins and those from the eye socket flow into the cavernous sinus, which flows into the petrosal sinus and then into the internal jugular vein. The occipital sinus, sagittal sinus, and straight sinuses all flow into the left and right transverse sinuses near the lambdoid suture. The transverse sinuses in turn flow into the sigmoid sinuses that pass through the jugular foramen and into the internal jugular vein. The internal jugular vein flows parallel to the common carotid artery and is more or less its counterpart. It empties into the brachiocephalic vein. The veins draining the cervical vertebrae and the posterior surface of the skull, including some blood from the occipital sinus, flow into the vertebral veins. These parallel the vertebral arteries and travel through the transverse foramina of the cervical vertebrae. The vertebral veins also flow into the brachiocephalic veins. Table 13 summarizes the major veins of the brain.

[caption id="" align="aligncenter" width="460"] Figure 16. Veins of the Head and Neck. This left lateral view shows the veins of the head and neck, including the intercranial sinuses.[/caption]

Major Veins of the Brain (Table 13)
Vessel	Description
Superior sagittal sinus	Enlarged vein located midsagittally between the meningeal and periosteal layers of the dura mater within the falx cerebri; receives most of the blood drained from the superior surface of the cerebrum and leads to the inferior jugular vein and the vertebral vein
Great cerebral vein	Receives most of the smaller vessels from the inferior cerebral veins and leads to the straight sinus
Straight sinus	Enlarged vein that drains blood from the brain; receives most of the blood from the great cerebral vein and leads to the left or right transverse sinus
Cavernous sinus	Enlarged vein that receives blood from most of the other cerebral veins and the eye socket, and leads to the petrosal sinus
Petrosal sinus	Enlarged vein that receives blood from the cavernous sinus and leads into the internal jugular veins
Occipital sinus	Enlarged vein that drains the occipital region near the falx cerebelli and leads to the left and right transverse sinuses, and also the vertebral veins
Transverse sinuses	Pair of enlarged veins near the lambdoid suture that drains the occipital, sagittal, and straight sinuses, and leads to the sigmoid sinuses
Sigmoid sinuses	Enlarged vein that receives blood from the transverse sinuses and leads through the jugular foramen to the internal jugular vein

Veins Draining the Upper Limbs

The digital veins in the fingers come together in the hand to form the palmar venous arches (Figure 17). From here, the veins come together to form the radial vein, the ulnar vein, and the median antebrachial vein. The radial vein and the ulnar vein parallel the bones of the forearm and join together at the antebrachium to form the brachial vein, a deep vein that flows into the axillary vein in the brachium.

The median antebrachial vein parallels the ulnar vein, is more medial in location, and joins the basilic vein in the forearm. As the basilic vein reaches the antecubital region, it gives off a branch called the median cubital vein that crosses at an angle to join the cephalic vein. The median cubital vein is the most common site for drawing venous blood in humans. The basilic vein continues through the arm medially and superficially to the axillary vein.

The cephalic vein begins in the antebrachium and drains blood from the superficial surface of the arm into the axillary vein. It is extremely superficial and easily seen along the surface of the biceps brachii muscle in individuals with good muscle tone and in those without excessive subcutaneous adipose tissue in the arms.

The subscapular vein drains blood from the subscapular region and joins the cephalic vein to form the axillary vein. As it passes through the body wall and enters the thorax, the axillary vein becomes the subclavian vein.

Many of the larger veins of the thoracic and abdominal region and upper limb are further represented in the flow chart in Figure 18. Table 14 summarizes the veins of the upper limbs.

[caption id="" align="aligncenter" width="385"] Figure 17. Veins of the Upper Limb. This anterior view shows the veins that drain the upper limb.[/caption]

[caption id="" align="aligncenter" width="530"] Figure 18. Veins Flowing into the Superior Vena Cava. The flow chart summarizes the distribution of the veins flowing into the superior vena cava.[/caption]

Veins of the Upper Limbs (Table 14)
Vessel	Description
Digital veins	Drain the digits and lead to the palmar arches of the hand and dorsal venous arch of the foot
Palmar venous arches	Drain the hand and digits, and lead to the radial vein, ulnar veins, and the median antebrachial vein
Radial vein	Vein that parallels the radius and radial artery; arises from the palmar venous arches and leads to the brachial vein
Ulnar vein	Vein that parallels the ulna and ulnar artery; arises from the palmar venous arches and leads to the brachial vein
Brachial vein	Deeper vein of the arm that forms from the radial and ulnar veins in the lower arm; leads to the axillary vein
Median antebrachial vein	Vein that parallels the ulnar vein but is more medial in location; intertwines with the palmar venous arches; leads to the basilic vein
Basilic vein	Superficial vein of the arm that arises from the median antebrachial vein, intersects with the median cubital vein, parallels the ulnar vein, and continues into the upper arm; along with the brachial vein, it leads to the axillary vein
Median cubital vein	Superficial vessel located in the antecubital region that links the cephalic vein to the basilic vein in the form of a v; a frequent site from which to draw blood
Cephalic vein	Superficial vessel in the upper arm; leads to the axillary vein
Subscapular vein	Drains blood from the subscapular region and leads to the axillary vein
Axillary vein	The major vein in the axillary region; drains the upper limb and becomes the subclavian vein

The Inferior Vena Cava

Other than the small amount of blood drained by the azygos and hemiazygos veins, most of the blood inferior to the diaphragm drains into the inferior vena cava before it is returned to the heart (see Figure 15). Lying just beneath the parietal peritoneum in the abdominal cavity, the inferior vena cava parallels the abdominal aorta, where it can receive blood from abdominal veins. The lumbar portions of the abdominal wall and spinal cord are drained by a series of lumbar veins, usually four on each side. The ascending lumbar veins drain into either the azygos vein on the right or the hemiazygos vein on the left, and return to the superior vena cava. The remaining lumbar veins drain directly into the inferior vena cava.

Blood supply from the kidneys flows into each renal vein, normally the largest veins entering the inferior vena cava. A number of other, smaller veins empty into the left renal vein. Each adrenal vein drains the adrenal or suprarenal glands located immediately superior to the kidneys. The right adrenal vein enters the inferior vena cava directly, whereas the left adrenal vein enters the left renal vein.

From the male reproductive organs, each testicular vein flows from the scrotum, forming a portion of the spermatic cord. Each ovarian vein drains an ovary in females. Each of these veins is generically called a gonadal vein. The right gonadal vein empties directly into the inferior vena cava, and the left gonadal vein empties into the left renal vein.

Each side of the diaphragm drains into a phrenic vein; the right phrenic vein empties directly into the inferior vena cava, whereas the left phrenic vein empties into the left renal vein. Blood supply from the liver drains into each hepatic vein and directly into the inferior vena cava. Since the inferior vena cava lies primarily to the right of the vertebral column and aorta, the left renal vein is longer, as are the left phrenic, adrenal, and gonadal veins. The longer length of the left renal vein makes the left kidney the primary target of surgeons removing this organ for donation. Figure 19 provides a flow chart of the veins flowing into the inferior vena cava. Table 15 summarizes the major veins of the abdominal region.

[caption id="" align="aligncenter" width="540"] Figure 19. Venous Flow into Inferior Vena Cava. The flow chart summarizes veins that deliver blood to the inferior vena cava.[/caption]

Major Veins of the Abdominal Region (Table 15)
Vessel	Description
Inferior vena cava	Large systemic vein that drains blood from areas largely inferior to the diaphragm; empties into the right atrium
Lumbar veins	Series of veins that drain the lumbar portion of the abdominal wall and spinal cord; the ascending lumbar veins drain into the azygos vein on the right or the hemiazygos vein on the left; the remaining lumbar veins drain directly into the inferior vena cava
Renal vein	Largest vein entering the inferior vena cava; drains the kidneys and flows into the inferior vena cava
Adrenal vein	Drains the adrenal or suprarenal; the right adrenal vein enters the inferior vena cava directly and the left adrenal vein enters the left renal vein
Testicular vein	Drains the testes and forms part of the spermatic cord; the right testicular vein empties directly into the inferior vena cava and the left testicular vein empties into the left renal vein
Ovarian vein	Drains the ovary; the right ovarian vein empties directly into the inferior vena cava and the left ovarian vein empties into the left renal vein
Gonadal vein	Generic term for a vein draining a reproductive organ; may be either an ovarian vein or a testicular vein, depending on the sex of the individual
Phrenic vein	Drains the diaphragm; the right phrenic vein flows into the inferior vena cava and the left phrenic vein empties into the left renal vein
Hepatic vein	Drains systemic blood from the liver and flows into the inferior vena cava

Veins Draining the Lower Limbs

The superior surface of the foot drains into the digital veins, and the inferior surface drains into the plantar veins, which flow into a complex series of anastomoses in the feet and ankles, including the dorsal venous arch and the plantar venous arch (Figure 20). From the dorsal venous arch, blood supply drains into the anterior and posterior tibial veins. The anterior tibial vein drains the area near the tibialis anterior muscle and combines with the posterior tibial vein and the fibular vein to form the popliteal vein. The posterior tibial vein drains the posterior surface of the tibia and joins the popliteal vein. The fibular vein drains the muscles and integument in proximity to the fibula and also joins the popliteal vein. The small saphenous vein located on the lateral surface of the leg drains blood from the superficial regions of the lower leg and foot, and flows into to the popliteal vein. As the popliteal vein passes behind the knee in the popliteal region, it becomes the femoral vein. It is palpable in patients without excessive adipose tissue.

Close to the body wall, the great saphenous vein, the deep femoral vein, and the femoral circumflex vein drain into the femoral vein. The great saphenous vein is a prominent surface vessel located on the medial surface of the leg and thigh that collects blood from the superficial portions of these areas. The deep femoral vein, as the name suggests, drains blood from the deeper portions of the thigh. The femoral circumflex vein forms a loop around the femur just inferior to the trochanters and drains blood from the areas in proximity to the head and neck of the femur.

As the femoral vein penetrates the body wall from the femoral portion of the upper limb, it becomes the external iliac vein, a large vein that drains blood from the leg to the common iliac vein. The pelvic organs and integument drain into the internal iliac vein, which forms from several smaller veins in the region, including the umbilical veins that run on either side of the bladder. The external and internal iliac veins combine near the inferior portion of the sacroiliac joint to form the common iliac vein. In addition to blood supply from the external and internal iliac veins, the middle sacral vein drains the sacral region into the common iliac vein. Similar to the common iliac arteries, the common iliac veins come together at the level of L5 to form the inferior vena cava.

Figure 21 is a flow chart of veins flowing into the lower limb. Table 16 summarizes the major veins of the lower limbs.

[caption id="" align="aligncenter" width="480"] Figure 20. Major Veins Serving the Lower Limbs Anterior and posterior views show the major veins that drain the lower limb into the inferior vena cava.[/caption]

[caption id="" align="aligncenter" width="480"] Figure 21. Major Veins of the Lower Limb. The flow chart summarizes venous flow from the lower limb.[/caption]

Veins of the Lower Limbs (Table 16)
Vessel	Description
Plantar veins	Drain the foot and flow into the plantar venous arch
Dorsal venous arch	Drains blood from digital veins and vessels on the superior surface of the foot
Plantar venous arch	Formed from the plantar veins; flows into the anterior and posterior tibial veins through anastomoses
Anterior tibial vein	Formed from the dorsal venous arch; drains the area near the tibialis anterior muscle and flows into the popliteal vein
Posterior tibial vein	Formed from the dorsal venous arch; drains the area near the posterior surface of the tibia and flows into the popliteal vein
Fibular vein	Drains the muscles and integument near the fibula and flows into the popliteal vein
Small saphenous vein	Located on the lateral surface of the leg; drains blood from the superficial regions of the lower leg and foot, and flows into the popliteal vein
Popliteal vein	Drains the region behind the knee and forms from the fusion of the fibular, anterior, and posterior tibial veins; flows into the femoral vein
Great saphenous vein	Prominent surface vessel located on the medial surface of the leg and thigh; drains the superficial portions of these areas and flows into the femoral vein
Deep femoral vein	Drains blood from the deeper portions of the thigh and flows into the femoral vein
Femoral circumflex vein	Forms a loop around the femur just inferior to the trochanters; drains blood from the areas around the head and neck of the femur; flows into the femoral vein
Femoral vein	Drains the upper leg; receives blood from the great saphenous vein, the deep femoral vein, and the femoral circumflex vein; becomes the external iliac vein when it crosses the body wall
External iliac vein	Formed when the femoral vein passes into the body cavity; drains the legs and flows into the common iliac vein
Internal iliac vein	Drains the pelvic organs and integument; formed from several smaller veins in the region; flows into the common iliac vein
Middle sacral vein	Drains the sacral region and flows into the left common iliac vein
Common iliac vein	Flows into the inferior vena cava at the level of L5; the left common iliac vein drains the sacral region; formed from the union of the external and internal iliac veins near the inferior portion of the sacroiliac joint

Hepatic Portal System

The liver is a complex biochemical processing plant. It packages nutrients absorbed by the digestive system; produces plasma proteins, clotting factors, and bile; and disposes of worn-out cell components and waste products. Instead of entering the circulation directly, absorbed nutrients and certain wastes (for example, materials produced by the spleen) travel to the liver for processing. They do so via the hepatic portal system (Figure 22). Portal systems begin and end in capillaries. In this case, the initial capillaries from the stomach, small intestine, large intestine, and spleen lead to the hepatic portal vein and end in specialized capillaries within the liver, the hepatic sinusoids. You saw the only other portal system with the hypothalamic-hypophyseal portal vessel in the endocrine chapter.

The hepatic portal system consists of the hepatic portal vein and the veins that drain into it. The hepatic portal vein itself is relatively short, beginning at the level of L2 with the confluence of the superior mesenteric and splenic veins. It also receives branches from the inferior mesenteric vein, plus the splenic veins and all their tributaries. The superior mesenteric vein receives blood from the small intestine, two-thirds of the large intestine, and the stomach. The inferior mesenteric vein drains the distal third of the large intestine, including the descending colon, the sigmoid colon, and the rectum. The splenic vein is formed from branches from the spleen, pancreas, and portions of the stomach, and the inferior mesenteric vein. After its formation, the hepatic portal vein also receives branches from the gastric veins of the stomach and cystic veins from the gall bladder. The hepatic portal vein delivers materials from these digestive and circulatory organs directly to the liver for processing.

Because of the hepatic portal system, the liver receives its blood supply from two different sources: from normal systemic circulation via the hepatic artery and from the hepatic portal vein. The liver processes the blood from the portal system to remove certain wastes and excess nutrients, which are stored for later use. This processed blood, as well as the systemic blood that came from the hepatic artery, exits the liver via the right, left, and middle hepatic veins, and flows into the inferior vena cava. Overall systemic blood composition remains relatively stable, since the liver is able to metabolize the absorbed digestive components.

[caption id="" align="aligncenter" width="480"] Figure 22. Hepatic Portal System. The liver receives blood from the normal systemic circulation via the hepatic artery. It also receives and processes blood from other organs, delivered via the veins of the hepatic portal system. All blood exits the liver via the hepatic vein, which delivers the blood to the inferior vena cava. (Different colors are used to help distinguish among the different vessels in the system.)[/caption]

Introduction

barkerj1 — Wed, 30 Aug 2017 18:40:21 +0000

[caption id="" align="aligncenter" width="600"] Figure 1. The Worldwide AIDS Epidemic. (a) As of 2008, more than 15 percent of adults were infected with HIV in certain African countries. This grim picture had changed little by 2012. (b) In this scanning electron micrograph, HIV virions (green particles) are budding off the surface of a macrophage (pink structure). (credit b: C. Goldsmith)[/caption] In June 1981, the Centers for Disease Control and Prevention (CDC), in Atlanta, Georgia, published a report of an unusual cluster of five patients in Los Angeles, California. All five were diagnosed with a rare pneumonia caused by a fungus called Pneumocystis jirovecii (formerly known as Pneumocystis carinii).

Why was this unusual? Although commonly found in the lungs of healthy individuals, this fungus is an opportunistic pathogen that causes disease in individuals with suppressed or underdeveloped immune systems. The very young, whose immune systems have yet to mature, and the elderly, whose immune systems have declined with age, are particularly susceptible. The five patients from LA, though, were between 29 and 36 years of age and should have been in the prime of their lives, immunologically speaking. What could be going on?

A few days later, a cluster of eight cases was reported in New York City, also involving young patients, this time exhibiting a rare form of skin cancer known as Kaposi’s sarcoma. This cancer of the cells that line the blood and lymphatic vessels was previously observed as a relatively innocuous disease of the elderly. The disease that doctors saw in 1981 was frighteningly more severe, with multiple, fast-growing lesions that spread to all parts of the body, including the trunk and face. Could the immune systems of these young patients have been compromised in some way? Indeed, when they were tested, they exhibited extremely low numbers of a specific type of white blood cell in their bloodstreams, indicating that they had somehow lost a major part of the immune system. Acquired immune deficiency syndrome, or AIDS, turned out to be a new disease caused by the previously unknown human immunodeficiency virus (HIV). Although nearly 100 percent fatal in those with active HIV infections in the early years, the development of anti-HIV drugs has transformed HIV infection into a chronic, manageable disease and not the certain death sentence it once was. One positive outcome resulting from the emergence of HIV disease was that the public’s attention became focused as never before on the importance of having a functional and healthy immune system.

21.1 Anatomy of the Lymphatic and Immune Systems

barkerj1 — Wed, 30 Aug 2017 18:40:28 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the major functions of the lymphatic system
Describe the relationships between the following components of the lymphatic system and explain their functions: vessels, nodes, tissues and organs, lymph
Distinguish between the cardiovascular system and the lymphatic system
Specify the types of leukocytes and their origins

The immune system is the complex collection of cells and organs that destroys or neutralizes pathogens that would otherwise cause disease or death. The lymphatic system, for most people, is associated with the immune system to such a degree that the two systems are virtually indistinguishable. The lymphatic system is the system of vessels, cells, and organs that carries excess fluids to the bloodstream and filters pathogens from the blood. The swelling of lymph nodes during an infection and the transport of lymphocytes via the lymphatic vessels are but two examples of the many connections between these critical organ systems.

Functions of the Lymphatic System

A major function of the lymphatic system is to drain body fluids and return them to the bloodstream. Blood pressure causes leakage of fluid from the capillaries, resulting in the accumulation of fluid in the interstitial space—that is, spaces between individual cells in the tissues. In humans, 20 liters of plasma is released into the interstitial space of the tissues each day due to capillary filtration. Once this filtrate is out of the bloodstream and in the tissue spaces, it is referred to as interstitial fluid. Of this, 17 liters is reabsorbed directly by the blood vessels. But what happens to the remaining three liters? This is where the lymphatic system comes into play. It drains the excess fluid and empties it back into the bloodstream via a series of vessels, trunks, and ducts. Lymph is the term used to describe interstitial fluid once it has entered the lymphatic system. When the lymphatic system is damaged in some way, such as by being blocked by cancer cells or destroyed by injury, protein-rich interstitial fluid accumulates (sometimes “backs up” from the lymph vessels) in the tissue spaces. This inappropriate accumulation of fluid referred to as lymphedema may lead to serious medical consequences.

As the vertebrate immune system evolved, the network of lymphatic vessels became convenient avenues for transporting the cells of the immune system. Additionally, the transport of dietary lipids and fat-soluble vitamins absorbed in the gut uses this system.

Cells of the immune system not only use lymphatic vessels to make their way from interstitial spaces back into the circulation, but they also use lymph nodes as major staging areas for the development of critical immune responses. A lymph node is one of the small, bean-shaped organs located throughout the lymphatic system.

[caption id="" align="aligncenter" width="120"] Visit this website for an overview of the lymphatic system.[/caption]

Structure of the Lymphatic System

The lymphatic vessels begin as open-ended capillaries, which feed into larger and larger lymphatic vessels, and eventually empty into the bloodstream by a series of ducts. Along the way, the lymph travels through the lymph nodes, which are commonly found near the groin, armpits, neck, chest, and abdomen. Humans have about 500–600 lymph nodes throughout the body (Figure 1).

[caption id="" align="aligncenter" width="480"] Figure 1. Anatomy of the Lymphatic System. Lymphatic vessels in the arms and legs convey lymph to the larger lymphatic vessels in the torso.[/caption]

A major distinction between the lymphatic and cardiovascular systems in humans is that lymph is not actively pumped by the heart, but is forced through the vessels by the movements of the body, the contraction of skeletal muscles during body movements, and breathing. One-way valves (semi-lunar valves) in lymphatic vessels keep the lymph moving toward the heart. Lymph flows from the lymphatic capillaries, through lymphatic vessels, and then is dumped into the circulatory system via the lymphatic ducts located at the junction of the jugular and subclavian veins in the neck.

Lymphatic Capillaries

Lymphatic capillaries, also called the terminal lymphatics, are vessels where interstitial fluid enters the lymphatic system to become lymph fluid. Located in almost every tissue in the body, these vessels are interlaced among the arterioles and venules of the circulatory system in the soft connective tissues of the body (Figure 2). Exceptions are the central nervous system, bone marrow, bones, teeth, and the cornea of the eye, which do not contain lymph vessels.

[caption id="" align="aligncenter" width="500"] Figure 2. Lymphatic Capillaries. Lymphatic capillaries are interlaced with the arterioles and venules of the cardiovascular system. Collagen fibers anchor a lymphatic capillary in the tissue (inset). Interstitial fluid slips through spaces between the overlapping endothelial cells that compose the lymphatic capillary.[/caption]

Lymphatic capillaries are formed by a one cell-thick layer of endothelial cells and represent the open end of the system, allowing interstitial fluid to flow into them via overlapping cells (see Figure 2). When interstitial pressure is low, the endothelial flaps close to prevent “backflow.” As interstitial pressure increases, the spaces between the cells open up, allowing the fluid to enter. Entry of fluid into lymphatic capillaries is also enabled by the collagen filaments that anchor the capillaries to surrounding structures. As interstitial pressure increases, the filaments pull on the endothelial cell flaps, opening up them even further to allow easy entry of fluid.

In the small intestine, lymphatic capillaries called lacteals are critical for the transport of dietary lipids and lipid-soluble vitamins to the bloodstream. In the small intestine, dietary triglycerides combine with other lipids and proteins, and enter the lacteals to form a milky fluid called chyle. The chyle then travels through the lymphatic system, eventually entering the liver and then the bloodstream.

Larger Lymphatic Vessels, Trunks, and Ducts

The lymphatic capillaries empty into larger lymphatic vessels, which are similar to veins in terms of their three-tunic structure and the presence of valves. These one-way valves are located fairly close to one another, and each one causes a bulge in the lymphatic vessel, giving the vessels a beaded appearance (see Figure 2).

The superficial and deep lymphatics eventually merge to form larger lymphatic vessels known as lymphatic trunks. On the right side of the body, the right sides of the head, thorax, and right upper limb drain lymph fluid into the right subclavian vein via the right lymphatic duct (Figure 3). On the left side of the body, the remaining portions of the body drain into the larger thoracic duct, which drains into the left subclavian vein. The thoracic duct itself begins just beneath the diaphragm in the cisterna chyli, a sac-like chamber that receives lymph from the lower abdomen, pelvis, and lower limbs by way of the left and right lumbar trunks and the intestinal trunk.

[caption id="" align="aligncenter" width="480"] Figure 3. Major Trunks and Ducts of the Lymphatic System. The thoracic duct drains a much larger portion of the body than does the right lymphatic duct.[/caption]

The overall drainage system of the body is asymmetrical (see Figure 3). The right lymphatic duct receives lymph from only the upper right side of the body. The lymph from the rest of the body enters the bloodstream through the thoracic duct via all the remaining lymphatic trunks. In general, lymphatic vessels of the subcutaneous tissues of the skin, that is, the superficial lymphatics, follow the same routes as veins, whereas the deep lymphatic vessels of the viscera generally follow the paths of arteries.

The Organization of Immune Function

The immune system is a collection of barriers, cells, and soluble proteins that interact and communicate with each other in extraordinarily complex ways. The modern model of immune function is organized into three phases based on the timing of their effects. The three temporal phases consist of the following:

Barrier defenses such as the skin and mucous membranes, which act instantaneously to prevent pathogenic invasion into the body tissues
The rapid but nonspecific innate immune response, which consists of a variety of specialized cells and soluble factors
The slower but more specific and effective adaptive immune response, which involves many cell types and soluble factors, but is primarily controlled by white blood cells (leukocytes) known as lymphocytes, which help control immune responses

The cells of the blood, including all those involved in the immune response, arise in the bone marrow via various differentiation pathways from hematopoietic stem cells (Figure 4). In contrast with embryonic stem cells, hematopoietic stem cells are present throughout adulthood and allow for the continuous differentiation of blood cells to replace those lost to age or function. These cells can be divided into three classes based on function:

Phagocytic cells, which ingest pathogens to destroy them
Lymphocytes, which specifically coordinate the activities of adaptive immunity
Cells containing cytoplasmic granules, which help mediate immune responses against parasites and intracellular pathogens such as viruses

[caption id="" align="aligncenter" width="600"] Figure 4. Hematopoietic System of the Bone Marrow. All the cells of the immune response as well as of the blood arise by differentiation from hematopoietic stem cells. Platelets are cell fragments involved in the clotting of blood.[/caption]

Lymphocytes: B Cells, T Cells, Plasma Cells, and Natural Killer Cells

As stated above, lymphocytes are the primary cells of adaptive immune responses (Table 1). The two basic types of lymphocytes, B cells and T cells, are identical morphologically with a large central nucleus surrounded by a thin layer of cytoplasm. They are distinguished from each other by their surface protein markers as well as by the molecules they secrete. While B cells mature in red bone marrow and T cells mature in the thymus, they both initially develop from bone marrow. T cells migrate from bone marrow to the thymus gland where they further mature. B cells and T cells are found in many parts of the body, circulating in the bloodstream and lymph, and residing in secondary lymphoid organs, including the spleen and lymph nodes, which will be described later in this section. The human body contains approximately 10¹² lymphocytes.

B Cells

B cells are immune cells that function primarily by producing antibodies. An antibody is any of the group of proteins that binds specifically to pathogen-associated molecules known as antigens. An antigen is a chemical structure on the surface of a pathogen that binds to T or B lymphocyte antigen receptors. Once activated by binding to antigen, B cells differentiate into cells that secrete a soluble form of their surface antibodies. These activated B cells are known as plasma cells.

T Cells

The T cell, on the other hand, does not secrete antibody but performs a variety of functions in the adaptive immune response. Different T cell types have the ability to either secrete soluble factors that communicate with other cells of the adaptive immune response or destroy cells infected with intracellular pathogens. The roles of T and B lymphocytes in the adaptive immune response will be discussed further in this chapter.

Plasma Cells

Another type of lymphocyte of importance is the plasma cell. A plasma cell is a B cell that has differentiated in response to antigen binding, and has thereby gained the ability to secrete soluble antibodies. These cells differ in morphology from standard B and T cells in that they contain a large amount of cytoplasm packed with the protein-synthesizing machinery known as rough endoplasmic reticulum.

Natural Killer Cells

A fourth important lymphocyte is the natural killer cell, a participant in the innate immune response. A natural killer cell (NK) is a circulating blood cell that contains cytotoxic (cell-killing) granules in its extensive cytoplasm. It shares this mechanism with the cytotoxic T cells of the adaptive immune response. NK cells are among the body’s first lines of defense against viruses and certain types of cancer.

Lymphocytes
Type of lymphocyte	Primary function
B lymphocyte	Generates diverse antibodies
T lymphocyte	Secretes chemical messengers
Plasma cell	Secretes antibodies
NK cell	Destroys virally infected cells

[caption id="" align="aligncenter" width="120"] Visit this website to learn about the many different cell types in the immune system and their very specialized jobs.[/caption]

Primary Lymphoid Organs and Lymphocyte Development

Understanding the differentiation and development of B and T cells is critical to the understanding of the adaptive immune response. It is through this process that the body (ideally) learns to destroy only pathogens and leaves the body’s own cells relatively intact. The primary lymphoid organs are the bone marrow and thymus gland. The lymphoid organs are where lymphocytes mature, proliferate, and are selected, which enables them to attack pathogens without harming the cells of the body.

Bone Marrow

In the embryo, blood cells are made in the yolk sac. As development proceeds, this function is taken over by the spleen, lymph nodes, and liver. Later, the bone marrow takes over most hematopoietic functions, although the final stages of the differentiation of some cells may take place in other organs. The red bone marrow is a loose collection of cells where hematopoiesis occurs, and the yellow bone marrow is a site of energy storage, which consists largely of fat cells (Figure 5). The B cell undergoes nearly all of its development in the red bone marrow, whereas the immature T cell, called a thymocyte, leaves the bone marrow and matures largely in the thymus gland.

[caption id="" align="aligncenter" width="300"] Figure 5. Bone Marrow. Red bone marrow fills the head of the femur, and a spot of yellow bone marrow is visible in the center. The white reference bar is 1 cm.[/caption]

Thymus

The thymus gland is a bilobed organ found in the space between the sternum and the aorta of the heart (Figure 6). Connective tissue holds the lobes closely together but also separates them and forms a capsule.

[caption id="" align="aligncenter" width="480"] Figure 6. Location, Structure, and Histology of the Thymus. The thymus lies above the heart. The trabeculae and lobules, including the darkly staining cortex and the lighter staining medulla of each lobule, are clearly visible in the light micrograph of the thymus of a newborn. LM × 100. (Micrograph provided by the Regents of the University of Michigan Medical School © 2012)[/caption]

The connective tissue capsule further divides the thymus into lobules via extensions called trabeculae. The outer region of the organ is known as the cortex and contains large numbers of thymocytes with some epithelial cells, macrophages, and dendritic cells (two types of phagocytic cells that are derived from monocytes). The cortex is densely packed so it stains more intensely than the rest of the thymus (see Figure 6). The medulla, where thymocytes migrate before leaving the thymus, contains a less dense collection of thymocytes, epithelial cells, and dendritic cells.

Secondary Lymphoid Organs and their Roles in Active Immune Responses

Lymphocytes develop and mature in the primary lymphoid organs, but they mount immune responses from the secondary lymphoid organs. A naïve lymphocyte is one that has left the primary organ and entered a secondary lymphoid organ. Naïve lymphocytes are fully functional immunologically, but have yet to encounter an antigen to respond to. In addition to circulating in the blood and lymph, lymphocytes concentrate in secondary lymphoid organs, which include the lymph nodes, spleen, and lymphoid nodules. All of these tissues have many features in common, including the following:

The presence of lymphoid follicles, the sites of the formation of lymphocytes, with specific B cell-rich and T cell-rich areas
An internal structure of reticular fibers with associated fixed macrophages
Germinal centers, which are the sites of rapidly dividing B lymphocytes and plasma cells, with the exception of the spleen
Specialized post-capillary vessels known as high endothelial venules; the cells lining these venules are thicker and more columnar than normal endothelial cells, which allow cells from the blood to directly enter these tissues

Lymph Nodes

Lymph nodes function to remove debris and pathogens from the lymph, and are thus sometimes referred to as the “filters of the lymph” (Figure 7). Any bacteria that infect the interstitial fluid are taken up by the lymphatic capillaries and transported to a regional lymph node. Dendritic cells and macrophages within this organ internalize and kill many of the pathogens that pass through, thereby removing them from the body. The lymph node is also the site of adaptive immune responses mediated by T cells, B cells, and accessory cells of the adaptive immune system. Like the thymus, the bean-shaped lymph nodes are surrounded by a tough capsule of connective tissue and are separated into compartments by trabeculae, the extensions of the capsule. In addition to the structure provided by the capsule and trabeculae, the structural support of the lymph node is provided by a series of reticular fibers laid down by fibroblasts.

[caption id="" align="aligncenter" width="500"] Figure 7. Structure and Histology of a Lymph Node. Lymph nodes are masses of lymphatic tissue located along the larger lymph vessels. The micrograph of the lymph nodes shows a germinal center, which consists of rapidly dividing B cells surrounded by a layer of T cells and other accessory cells. LM × 128. (Micrograph provided by the Regents of the University of Michigan Medical School © 2012)[/caption]

The major routes into the lymph node are via afferent lymphatic vessels (see [link]). Cells and lymph fluid that leave the lymph node may do so by another set of vessels known as the efferent lymphatic vessels. Lymph enters the lymph node via the subcapsular sinus, which is occupied by dendritic cells, macrophages, and reticular fibers. Within the cortex of the lymph node are lymphoid follicles, which consist of germinal centers of rapidly dividing B cells surrounded by a layer of T cells and other accessory cells. As the lymph continues to flow through the node, it enters the medulla, which consists of medullary cords of B cells and plasma cells, and the medullary sinuses where the lymph collects before leaving the node via the efferent lymphatic vessels.

Spleen

In addition to the lymph nodes, the spleen is a major secondary lymphoid organ (Figure 8). It is about 12 cm (5 in) long and is attached to the lateral border of the stomach via the gastrosplenic ligament. The spleen is a fragile organ without a strong capsule, and is dark red due to its extensive vascularization. The spleen is sometimes called the “filter of the blood” because of its extensive vascularization and the presence of macrophages and dendritic cells that remove microbes and other materials from the blood, including dying red blood cells. The spleen also functions as the location of immune responses to blood-borne pathogens.

[caption id="" align="aligncenter" width="500"] Figure 8. Spleen. (a) The spleen is attached to the stomach. (b) A micrograph of spleen tissue shows the germinal center. The marginal zone is the region between the red pulp and white pulp, which sequesters particulate antigens from the circulation and presents these antigens to lymphocytes in the white pulp. EM × 660. (Micrograph provided by the Regents of the University of Michigan Medical School © 2012)[/caption]

The spleen is also divided by trabeculae of connective tissue, and within each splenic nodule is an area of red pulp, consisting of mostly red blood cells, and white pulp, which resembles the lymphoid follicles of the lymph nodes. Upon entering the spleen, the splenic artery splits into several arterioles (surrounded by white pulp) and eventually into sinusoids. Blood from the capillaries subsequently collects in the venous sinuses and leaves via the splenic vein. The red pulp consists of reticular fibers with fixed macrophages attached, free macrophages, and all of the other cells typical of the blood, including some lymphocytes. The white pulp surrounds a central arteriole and consists of germinal centers of dividing B cells surrounded by T cells and accessory cells, including macrophages and dendritic cells. Thus, the red pulp primarily functions as a filtration system of the blood, using cells of the relatively nonspecific immune response, and white pulp is where adaptive T and B cell responses are mounted.

Lymphoid Nodules

The other lymphoid tissues, the lymphoid nodules, have a simpler architecture than the spleen and lymph nodes in that they consist of a dense cluster of lymphocytes without a surrounding fibrous capsule. These nodules are located in the respiratory and digestive tracts, areas routinely exposed to environmental pathogens.

Tonsils are lymphoid nodules located along the inner surface of the pharynx and are important in developing immunity to oral pathogens (Figure 9). The tonsil located at the back of the throat, the pharyngeal tonsil, is sometimes referred to as the adenoid when swollen. Such swelling is an indication of an active immune response to infection. Histologically, tonsils do not contain a complete capsule, and the epithelial layer invaginates deeply into the interior of the tonsil to form tonsillar crypts. These structures, which accumulate all sorts of materials taken into the body through eating and breathing, actually “encourage” pathogens to penetrate deep into the tonsillar tissues where they are acted upon by numerous lymphoid follicles and eliminated. This seems to be the major function of tonsils—to help children’s bodies recognize, destroy, and develop immunity to common environmental pathogens so that they will be protected in their later lives. Tonsils are often removed in those children who have recurring throat infections, especially those involving the palatine tonsils on either side of the throat, whose swelling may interfere with their breathing and/or swallowing.

[caption id="" align="aligncenter" width="480"] Figure 9. Locations and Histology of the Tonsils. (a) The pharyngeal tonsil is located on the roof of the posterior superior wall of the nasopharynx. The palatine tonsils lay on each side of the pharynx. (b) A micrograph shows the palatine tonsil tissue. LM × 40. (Micrograph provided by the Regents of the University of Michigan Medical School © 2012)[/caption]

Mucosa-associated lymphoid tissue (MALT) consists of an aggregate of lymphoid follicles directly associated with the mucous membrane epithelia. MALT makes up dome-shaped structures found underlying the mucosa of the gastrointestinal tract, breast tissue, lungs, and eyes. Peyer’s patches, a type of MALT in the small intestine, are especially important for immune responses against ingested substances (Figure 10). Peyer’s patches contain specialized endothelial cells called M (or microfold) cells that sample material from the intestinal lumen and transport it to nearby follicles so that adaptive immune responses to potential pathogens can be mounted.

[caption id="" align="aligncenter" width="480"] Figure 10. Mucosa-associated Lymphoid Tissue (MALT) Nodule. LM × 40. (Micrograph provided by the Regents of the University of Michigan Medical School © 2012)[/caption]

Bronchus-associated lymphoid tissue (BALT) consists of lymphoid follicular structures with an overlying epithelial layer found along the bifurcations of the bronchi, and between bronchi and arteries. They also have the typically less-organized structure of other lymphoid nodules. These tissues, in addition to the tonsils, are effective against inhaled pathogens.

[caption id="attachment_2978" align="aligncenter" width="150"] Watch this CrashCourse video to learn more about the lymphatic system.[/caption]

21.2 Barrier Defenses and the Innate Immune Response

barkerj1 — Wed, 30 Aug 2017 18:40:30 +0000

Learning Objectives

By the end of this section, you will be able to:

Explain nonspecific (innate) resistance to disease
Specify the general components of nonspecific (innate) resistance

The immune system can be divided into two overlapping mechanisms to destroy pathogens: the innate immune response, which is relatively rapid but nonspecific and thus not always effective, and the adaptive immune response, which is slower in its development during an initial infection with a pathogen, but is highly specific and effective at attacking a wide variety of pathogens (Figure 1).

[caption id="" align="aligncenter" width="550"] Figure 1. Cooperation between Innate and Adaptive Immune Responses. The innate immune system enhances adaptive immune responses so they can be more effective[/caption]

Any discussion of the innate immune response usually begins with the physical barriers that prevent pathogens from entering the body, destroy them after they enter, or flush them out before they can establish themselves in the hospitable environment of the body’s soft tissues. Barrier defenses are part of the body’s most basic defense mechanisms. The barrier defenses are not a response to infections, but they are continuously working to protect against a broad range of pathogens.

The different modes of barrier defenses are associated with the external surfaces of the body, where pathogens may try to enter (Table 2). The primary barrier to the entrance of microorganisms into the body is the skin. Not only is the skin covered with a layer of dead, keratinized epithelium that is too dry for bacteria in which to grow, but as these cells are continuously sloughed off from the skin, they carry bacteria and other pathogens with them. Additionally, sweat and other skin secretions may lower pH, contain toxic lipids, contain antimicrobial peptides such as dermcidin, and physically wash microbes away.

Barrier Defenses (Table 2)
Site	Specific defense	Protective aspect
Skin	Epidermal surface	Keratinized cells of surface, Langerhans cells
Skin (sweat/secretions)	Sweat glands, sebaceous glands	Low pH, dermcidin, washing action
Oral cavity	Salivary glands	Lysozyme
Stomach	Gastrointestinal tract	Low pH
Mucosal surfaces	Mucosal epithelium	Nonkeratinized epithelial cells
Normal flora (nonpathogenic bacteria)	Mucosal tissues	Prevent pathogens from growing on mucosal surfaces

Another barrier is the saliva in the mouth, which is rich in lysozyme—an enzyme that destroys bacteria by digesting their cell walls. The acidic environment of the stomach, which is fatal to many pathogens, is also a barrier. Additionally, the mucus layer of the gastrointestinal tract, respiratory tract, reproductive tract, eyes, ears, and nose traps both microbes and debris, and facilitates their removal. In the case of the upper respiratory tract, ciliated epithelial cells move potentially contaminated mucus upwards to the mouth, where it is then swallowed into the digestive tract, ending up in the harsh acidic environment of the stomach. Considering how often you breathe compared to how often you eat or perform other activities that expose you to pathogens, it is not surprising that multiple barrier mechanisms have evolved to work in concert to protect this vital area.

Cells of the Innate Immune Response

A phagocyte is a cell that is able to surround and engulf a particle or cell, a process called phagocytosis. The phagocytes of the immune system engulf other particles or cells, either to clean an area of debris, old cells, or to kill pathogenic organisms such as bacteria. The phagocytes are the body’s fast acting, first line of immunological defense against organisms that have breached barrier defenses and have entered the vulnerable tissues of the body.

Phagocytes: Macrophages and Neutrophils

Many of the cells of the immune system have a phagocytic ability, at least at some point during their life cycles. Phagocytosis is an important and effective mechanism of destroying pathogens during innate immune responses. The phagocyte takes the organism inside itself as a phagosome, which subsequently fuses with a lysosome and its digestive enzymes, effectively killing many pathogens. On the other hand, some bacteria including Mycobacteria tuberculosis, the cause of tuberculosis, may be resistant to these enzymes and are therefore much more difficult to clear from the body. Macrophages, neutrophils, and dendritic cells are the major phagocytes of the immune system.

A macrophage is an irregularly shaped phagocyte that is amoeboid in nature and is the most versatile of the phagocytes in the body. Macrophages move through tissues and squeeze through capillary walls using pseudopodia. They not only participate in innate immune responses but have also evolved to cooperate with lymphocytes as part of the adaptive immune response. Macrophages exist in many tissues of the body, either freely roaming through connective tissues or fixed to reticular fibers within specific tissues such as lymph nodes. When pathogens breach the body’s barrier defenses, macrophages are the first line of defense (Table 3). They are called different names, depending on the tissue: Kupffer cells in the liver, histiocytes in connective tissue, and alveolar macrophages in the lungs.

A neutrophil is a phagocytic cell that is attracted via chemotaxis from the bloodstream to infected tissues. These spherical cells are granulocytes. A granulocyte contains cytoplasmic granules, which in turn contain a variety of vasoactive mediators such as histamine. In contrast, macrophages are agranulocytes. An agranulocyte has few or no cytoplasmic granules. Whereas macrophages act like sentries, always on guard against infection, neutrophils can be thought of as military reinforcements that are called into a battle to hasten the destruction of the enemy. Although, usually thought of as the primary pathogen-killing cell of the inflammatory process of the innate immune response, new research has suggested that neutrophils play a role in the adaptive immune response as well, just as macrophages do.

A monocyte is a circulating precursor cell that differentiates into either a macrophage or dendritic cell, which can be rapidly attracted to areas of infection by signal molecules of inflammation.

Phagocytic Cells of the Innate Immune System (Table 3)
Cell	Cell type	Primary location	Function in the innate immune response
Macrophage	Agranulocyte	Body cavities/organs	Phagocytosis
Neutrophil	Granulocyte	Blood	Phagocytosis
Monocyte	Agranulocyte	Blood	Precursor of macrophage/dendritic cell

Natural Killer Cells

NK cells are a type of lymphocyte that have the ability to induce apoptosis, that is, programmed cell death, in cells infected with intracellular pathogens such as obligate intracellular bacteria and viruses. NK cells recognize these cells by mechanisms that are still not well understood, but that presumably involve their surface receptors. NK cells can induce apoptosis, in which a cascade of events inside the cell causes its own death by either of two mechanisms:

1) NK cells are able to respond to chemical signals and express the fas ligand. The fas ligand is a surface molecule that binds to the fas molecule on the surface of the infected cell, sending it apoptotic signals, thus killing the cell and the pathogen within it; or

2) The granules of the NK cells release perforins and granzymes. A perforin is a protein that forms pores in the membranes of infected cells. A granzyme is a protein-digesting enzyme that enters the cell via the perforin pores and triggers apoptosis intracellularly.

Both mechanisms are especially effective against virally infected cells. If apoptosis is induced before the virus has the ability to synthesize and assemble all its components, no infectious virus will be released from the cell, thus preventing further infection.

Recognition of Pathogens

Cells of the innate immune response, the phagocytic cells, and the cytotoxic NK cells recognize patterns of pathogen-specific molecules, such as bacterial cell wall components or bacterial flagellar proteins, using pattern recognition receptors. A pattern recognition receptor (PRR) is a membrane-bound receptor that recognizes characteristic features of a pathogen and molecules released by stressed or damaged cells.

These receptors, which are thought to have evolved prior to the adaptive immune response, are present on the cell surface whether they are needed or not. Their variety, however, is limited by two factors. First, the fact that each receptor type must be encoded by a specific gene requires the cell to allocate most or all of its DNA to make receptors able to recognize all pathogens. Secondly, the variety of receptors is limited by the finite surface area of the cell membrane. Thus, the innate immune system must “get by” using only a limited number of receptors that are active against as wide a variety of pathogens as possible. This strategy is in stark contrast to the approach used by the adaptive immune system, which uses large numbers of different receptors, each highly specific to a particular pathogen.

Should the cells of the innate immune system come into contact with a species of pathogen they recognize, the cell will bind to the pathogen and initiate phagocytosis (or cellular apoptosis in the case of an intracellular pathogen) in an effort to destroy the offending microbe. Receptors vary somewhat according to cell type, but they usually include receptors for bacterial components and for complement, discussed below.

Soluble Mediators of the Innate Immune Response

The previous discussions have alluded to chemical signals that can induce cells to change various physiological characteristics, such as the expression of a particular receptor. These soluble factors are secreted during innate or early induced responses, and later during adaptive immune responses.

Cytokines and Chemokines

A cytokine is signaling molecule that allows cells to communicate with each other over short distances. Cytokines are secreted into the intercellular space, and the action of the cytokine induces the receiving cell to change its physiology. A chemokine is a soluble chemical mediator similar to cytokines except that its function is to attract cells (chemotaxis) from longer distances.

Early induced Proteins

Early induced proteins are those that are not constitutively present in the body, but are made as they are needed early during the innate immune response. Interferons are an example of early induced proteins. Cells infected with viruses secrete interferons that travel to adjacent cells and induce them to make antiviral proteins. Thus, even though the initial cell is sacrificed, the surrounding cells are protected. Other early induced proteins specific for bacterial cell wall components are mannose-binding protein and C-reactive protein, made in the liver, which bind specifically to polysaccharide components of the bacterial cell wall. Phagocytes such as macrophages have receptors for these proteins, and they are thus able to recognize them as they are bound to the bacteria. This brings the phagocyte and bacterium into close proximity and enhances the phagocytosis of the bacterium by the process known as opsonization. Opsonization is the tagging of a pathogen for phagocytosis by the binding of an antibody or an antimicrobial protein.

Complement System

The complement system is a series of proteins constitutively found in the blood plasma. As such, these proteins are not considered part of the early induced immune response, even though they share features with some of the antibacterial proteins of this class. Made in the liver, they have a variety of functions in the innate immune response, using what is known as the “alternate pathway” of complement activation. Additionally, complement functions in the adaptive immune response as well, in what is called the classical pathway. The complement system consists of several proteins that enzymatically alter and fragment later proteins in a series, which is why it is termed cascade. Once activated, the series of reactions is irreversible, and releases fragments that have the following actions:

Bind to the cell membrane of the pathogen that activates it, labeling it for phagocytosis (opsonization)
Diffuse away from the pathogen and act as chemotactic agents to attract phagocytic cells to the site of inflammation
Form damaging pores in the plasma membrane of the pathogen

Figure 2 shows the classical pathway, which requires antibodies of the adaptive immune response. The alternate pathway does not require an antibody to become activated.

[caption id="" align="aligncenter" width="500"] Figure 2. Complement Cascade and Function. The classical pathway, used during adaptive immune responses, occurs when C1 reacts with antibodies that have bound an antigen.[/caption]

The splitting of the C3 protein is the common step to both pathways. In the alternate pathway, C3 is activated spontaneously and, after reacting with the molecules factor P, factor B, and factor D, splits apart. The larger fragment, C3b, binds to the surface of the pathogen and C3a, the smaller fragment, diffuses outward from the site of activation and attracts phagocytes to the site of infection. Surface-bound C3b then activates the rest of the cascade, with the last five proteins, C5–C9, forming the membrane-attack complex (MAC). The MAC can kill certain pathogens by disrupting their osmotic balance. The MAC is especially effective against a broad range of bacteria. The classical pathway is similar, except the early stages of activation require the presence of antibody bound to antigen, and thus is dependent on the adaptive immune response. The earlier fragments of the cascade also have important functions. Phagocytic cells such as macrophages and neutrophils are attracted to an infection site by chemotactic attraction to smaller complement fragments. Additionally, once they arrive, their receptors for surface-bound C3b opsonize the pathogen for phagocytosis and destruction.

Inflammatory Response

The hallmark of the innate immune response is inflammation. Inflammation is something everyone has experienced. Stub a toe, cut a finger, or do any activity that causes tissue damage and inflammation will result, with its four characteristics: heat, redness, pain, and swelling (“loss of function” is sometimes mentioned as a fifth characteristic). It is important to note that inflammation does not have to be initiated by an infection, but can also be caused by tissue injuries. The release of damaged cellular contents into the site of injury is enough to stimulate the response, even in the absence of breaks in physical barriers that would allow pathogens to enter (by hitting your thumb with a hammer, for example). The inflammatory reaction brings in phagocytic cells to the damaged area to clear cellular debris and to set the stage for wound repair (Figure 3).

[caption id="" align="aligncenter" width="350"] Figure 3. Inflammatory Response.[/caption]

This reaction also brings in the cells of the innate immune system, allowing them to get rid of the sources of a possible infection. Inflammation is part of a very basic form of immune response. The process not only brings fluid and cells into the site to destroy the pathogen and remove it and debris from the site, but also helps to isolate the site, limiting the spread of the pathogen. Acute inflammation is a short-term inflammatory response to an insult to the body. If the cause of the inflammation is not resolved, however, it can lead to chronic inflammation, which is associated with major tissue destruction and fibrosis. Chronic inflammation is ongoing inflammation. It can be caused by foreign bodies, persistent pathogens, and autoimmune diseases such as rheumatoid arthritis.

There are four important parts to the inflammatory response:

Tissue Injury. The released contents of injured cells stimulate the release of mast cell granules and their potent inflammatory mediators such as histamine, leukotrienes, and prostaglandins. Histamine increases the diameter of local blood vessels (vasodilation), causing an increase in blood flow. Histamine also increases the permeability of local capillaries, causing plasma to leak out and form interstitial fluid. This causes the swelling associated with inflammation.Additionally, injured cells, phagocytes, and basophils are sources of inflammatory mediators, including prostaglandins and leukotrienes. Leukotrienes attract neutrophils from the blood by chemotaxis and increase vascular permeability. Prostaglandins cause vasodilation by relaxing vascular smooth muscle and are a major cause of the pain associated with inflammation. Nonsteroidal anti-inflammatory drugs such as aspirin and ibuprofen relieve pain by inhibiting prostaglandin production.
Vasodilation. Many inflammatory mediators such as histamine are vasodilators that increase the diameters of local capillaries. This causes increased blood flow and is responsible for the heat and redness of inflamed tissue. It allows greater access of the blood to the site of inflammation.
Increased Vascular Permeability. At the same time, inflammatory mediators increase the permeability of the local vasculature, causing leakage of fluid into the interstitial space, resulting in the swelling, or edema, associated with inflammation.
Recruitment of Phagocytes. Leukotrienes are particularly good at attracting neutrophils from the blood to the site of infection by chemotaxis. Following an early neutrophil infiltrate stimulated by macrophage cytokines, more macrophages are recruited to clean up the debris left over at the site. When local infections are severe, neutrophils are attracted to the sites of infections in large numbers, and as they phagocytose the pathogens and subsequently die, their accumulated cellular remains are visible as pus at the infection site.

Overall, inflammation is valuable for many reasons. Not only are the pathogens killed and debris removed, but the increase in vascular permeability encourages the entry of clotting factors, the first step towards wound repair. Inflammation also facilitates the transport of antigen to lymph nodes by dendritic cells for the development of the adaptive immune response.

Fever

The mechanisms of inflammation described so far are primarily local. Another inflammatory response that is systemic in nature is that of fever. Fever is defined as an increase in the set-point of the body’s thermostat, with the result that homeostatic mechanisms raise the temperature of the body above the normal of about 37ºC.

There are several metabolic pathways by which fever is produced. One of the major mechanisms begins with the engulfing of an infectious organism by a phagocyte. This will stimulate the phagocyte to produce cytokines that interact with specific cells located in the brain, causing the production of a particular prostaglandin (PGE2). (Structural components or toxins of infectious organisms can also directly interact with these specific brain cells, with the same result.) When this prostaglandin is released into the bloodstream, it causes cells in the hypothalamus that are responsible for maintenance of body temperature to increase the normal temperature set-point. Signals from the hypothalamus to the body then cause shivering, peripheral vasoconstriction, and an increase in metabolism, which in turn cause a rise in body temperature. Homeostatic mechanisms then maintain body temperature at this new higher value. The increase in temperature has several effects that are beneficial to the body’s defense. These include increasing the activity of the immune system (e.g., enhancing the efficiency of white blood cells). Fever also results in an increase in the production of the iron-binding protein transferin which reduces the availability of iron in the blood, which in turn can reduce the rate of growth of microbes. The beneficial effects of such an increase in body temperature disappear, however, should the value go over 41ºC, as human proteins begin denaturing. [caption id="attachment_2980" align="aligncenter" width="150"] Watch this CrashCourse video to learn more about the immune system.[/caption]

21.3 The Adaptive Immune Response: T lymphocytes and Their Functional Types

barkerj1 — Wed, 30 Aug 2017 18:40:33 +0000

Learning Objectives

By the end of this section, you will be able to:

Explain specific (adaptive) resistance to disease (immunity)
Describe the origins of T cells
Describe the role of T cells in cellular immunity

Innate immune responses (and early induced responses) are in many cases ineffective at completely controlling pathogen growth. However, they slow pathogen growth and allow time for the adaptive immune response to strengthen and either control or eliminate the pathogen. The innate immune system also sends signals to the cells of the adaptive immune system, guiding them in how to attack the pathogen. Thus, these are the two important arms of the immune response.

The Benefits of the Adaptive Immune Response

The specificity of the adaptive immune response—its ability to specifically recognize and make a response against a wide variety of pathogens—is its great strength. Antigens, the small chemical groups often associated with pathogens, are recognized by receptors on the surface of B and T lymphocytes. The adaptive immune response to these antigens is so versatile that it can respond to nearly any pathogen. This increase in specificity comes because the adaptive immune response has a unique way to develop as many as 10¹¹, or 100 trillion, different receptors to recognize nearly every conceivable pathogen. How could so many different types of antibodies be encoded? And what about the many specificities of T cells? There is not nearly enough DNA in a cell to have a separate gene for each specificity. The mechanism was finally worked out in the 1970s and 1980s using the new tools of molecular genetics

Primary Disease and Immunological Memory

The immune system’s first exposure to a pathogen is called a primary adaptive response. Symptoms of a first infection, called primary disease, are always relatively severe because it takes time for an initial adaptive immune response to a pathogen to become effective.

Upon re-exposure to the same pathogen, a secondary adaptive immune response is generated, which is stronger and faster that the primary response. The secondary adaptive response often eliminates a pathogen before it can cause significant tissue damage or any symptoms. Without symptoms, there is no disease, and the individual is not even aware of the infection. This secondary response is the basis of immunological memory, which protects us from getting diseases repeatedly from the same pathogen. By this mechanism, an individual’s exposure to pathogens early in life spares the person from these diseases later in life.

Self Recognition

A third important feature of the adaptive immune response is its ability to distinguish between self-antigens, those that are normally present in the body, and foreign antigens, those that might be on a potential pathogen. As T and B cells mature, there are mechanisms in place that prevent them from recognizing self-antigen, preventing a damaging immune response against the body. These mechanisms are not 100 percent effective, however, and their breakdown leads to autoimmune diseases, which will be discussed later in this chapter.

T Cell-Mediated Immune Responses

The primary cells that control the adaptive immune response are the lymphocytes, the T and B cells. T cells are particularly important, as they not only control a multitude of immune responses directly, but also control B cell immune responses in many cases as well. Thus, many of the decisions about how to attack a pathogen are made at the T cell level, and knowledge of their functional types is crucial to understanding the functioning and regulation of adaptive immune responses as a whole.

T lymphocytes recognize antigens based on a two-chain protein receptor. The most common and important of these are the alpha-beta T cell receptors (Figure 1).

[caption id="" align="aligncenter" width="300"] Figure 1. Alpha-beta T Cell Receptor. Notice the constant and variable regions of each chain, anchored by the transmembrane region.[/caption]

There are two chains in the T cell receptor, and each chain consists of two domains. The variable region domain is furthest away from the T cell membrane and is so named because its amino acid sequence varies between receptors. In contrast, the constant region domain has less variation. The differences in the amino acid sequences of the variable domains are the molecular basis of the diversity of antigens the receptor can recognize. Thus, the antigen-binding site of the receptor consists of the terminal ends of both receptor chains, and the amino acid sequences of those two areas combine to determine its antigenic specificity. Each T cell produces only one type of receptor and thus is specific for a single particular antigen.

Antigens

Antigens on pathogens are usually large and complex, and consist of many antigenic determinants. An antigenic determinant (epitope) is one of the small regions within an antigen to which a receptor can bind, and antigenic determinants are limited by the size of the receptor itself. They usually consist of six or fewer amino acid residues in a protein, or one or two sugar moieties in a carbohydrate antigen. Antigenic determinants on a carbohydrate antigen are usually less diverse than on a protein antigen. Carbohydrate antigens are found on bacterial cell walls and on red blood cells (the ABO blood group antigens). Protein antigens are complex because of the variety of three-dimensional shapes that proteins can assume, and are especially important for the immune responses to viruses and worm parasites. It is the interaction of the shape of the antigen and the complementary shape of the amino acids of the antigen-binding site that accounts for the chemical basis of specificity (Figure 2).

[caption id="" align="aligncenter" width="480"] Figure 2. Antigenic Determinants. A typical protein antigen has multiple antigenic determinants, shown by the ability of T cells with three different specificities to bind to different parts of the same antigen.[/caption]

Antigen Processing and Presentation

Although Figure 2 shows T cell receptors interacting with antigenic determinants directly, the mechanism that T cells use to recognize antigens is, in reality, much more complex. T cells do not recognize free-floating or cell-bound antigens as they appear on the surface of the pathogen. They only recognize antigen on the surface of specialized cells called antigen-presenting cells. Antigens are internalized by these cells. Antigen processing is a mechanism that enzymatically cleaves the antigen into smaller pieces. The antigen fragments are then brought to the cell’s surface and associated with a specialized type of antigen-presenting protein known as a major histocompatibility complex (MHC) molecule. The MHC is the cluster of genes that encode these antigen-presenting molecules. The association of the antigen fragments with an MHC molecule on the surface of a cell is known as antigen presentation and results in the recognition of antigen by a T cell. This association of antigen and MHC occurs inside the cell, and it is the complex of the two that is brought to the surface. The peptide-binding cleft is a small indentation at the end of the MHC molecule that is furthest away from the cell membrane; it is here that the processed fragment of antigen sits. MHC molecules are capable of presenting a variety of antigens, depending on the amino acid sequence, in their peptide-binding clefts. It is the combination of the MHC molecule and the fragment of the original peptide or carbohydrate that is actually physically recognized by the T cell receptor (Figure 3).

[caption id="" align="aligncenter" width="560"] Figure 3. Antigen Processing and Presentation.[/caption]

Two distinct types of MHC molecules, MHC class I and MHC class II, play roles in antigen presentation. Although produced from different genes, they both have similar functions. They bring processed antigen to the surface of the cell via a transport vesicle and present the antigen to the T cell and its receptor. Antigens from different classes of pathogens, however, use different MHC classes and take different routes through the cell to get to the surface for presentation. The basic mechanism, though, is the same. Antigens are processed by digestion, are brought into the endomembrane system of the cell, and then are expressed on the surface of the antigen-presenting cell for antigen recognition by a T cell. Intracellular antigens are typical of viruses, which replicate inside the cell, and certain other intracellular parasites and bacteria. These antigens are processed in the cytosol by an enzyme complex known as the proteasome and are then brought into the endoplasmic reticulum by the transporter associated with antigen processing (TAP) system, where they interact with class I MHC molecules and are eventually transported to the cell surface by a transport vesicle.

Extracellular antigens, characteristic of many bacteria, parasites, and fungi that do not replicate inside the cell’s cytoplasm, are brought into the endomembrane system of the cell by receptor-mediated endocytosis. The resulting vesicle fuses with vesicles from the Golgi complex, which contain pre-formed MHC class II molecules. After fusion of these two vesicles and the association of antigen and MHC, the new vesicle makes its way to the cell surface.

Professional Antigen-presenting Cells

Many cell types express class I molecules for the presentation of intracellular antigens. These MHC molecules may then stimulate a cytotoxic T cell immune response, eventually destroying the cell and the pathogen within. This is especially important when it comes to the most common class of intracellular pathogens, the virus. Viruses infect nearly every tissue of the body, so all these tissues must necessarily be able to express class I MHC or no T cell response can be made.

On the other hand, class II MHC molecules are expressed only on the cells of the immune system, specifically cells that affect other arms of the immune response. Thus, these cells are called “professional” antigen-presenting cells to distinguish them from those that bear class I MHC. The three types of professional antigen presenters are macrophages, dendritic cells, and B cells (Table 4).

Macrophages stimulate T cells to release cytokines that enhance phagocytosis. Dendritic cells also kill pathogens by phagocytosis (see Figure 3), but their major function is to bring antigens to regional draining lymph nodes. The lymph nodes are the locations in which most T cell responses against pathogens of the interstitial tissues are mounted. Macrophages are found in the skin and in the lining of mucosal surfaces, such as the nasopharynx, stomach, lungs, and intestines. B cells may also present antigens to T cells, which are necessary for certain types of antibody responses, to be covered later in this chapter.

Classes of Antigen-presenting Cells (Table 4)
MHC	Cell type	Phagocytic?	Function
Class I	Many	No	Stimulates cytotoxic T cell immune response
Class II	Macrophage	Yes	Stimulates phagocytosis and presentation at primary infection site
Class II	Dendritic	Yes, in tissues	Brings antigens to regional lymph nodes
Class II	B cell	Yes, internalizes surface Ig and antigen	Stimulates antibody secretion by B cells

T Cell Development and Differentiation

The process of eliminating T cells that might attack the cells of one’s own body is referred to as T cell tolerance. While thymocytes are in the cortex of the thymus, they are referred to as “double negatives,” meaning that they do not bear the CD4 or CD8 molecules that you can use to follow their pathways of differentiation (Figure 4). In the cortex of the thymus, they are exposed to cortical epithelial cells. In a process known as positive selection, double-negative thymocytes bind to the MHC molecules they observe on the thymic epithelia, and the MHC molecules of “self” are selected. This mechanism kills many thymocytes during T cell differentiation. In fact, only two percent of the thymocytes that enter the thymus leave it as mature, functional T cells.

[caption id="" align="aligncenter" width="500"] Figure 4. Differentiation of T Cells within the Thymus. Thymocytes enter the thymus and go through a series of developmental stages that ensures both function and tolerance before they leave and become functional components of the adaptive immune response.[/caption]

Later, the cells become double positives that express both CD4 and CD8 markers and move from the cortex to the junction between the cortex and medulla. It is here that negative selection takes place. In negative selection, self-antigens are brought into the thymus from other parts of the body by professional antigen-presenting cells. The T cells that bind to these self-antigens are selected for negatively and are killed by apoptosis. In summary, the only T cells left are those that can bind to MHC molecules of the body with foreign antigens presented on their binding clefts, preventing an attack on one’s own body tissues, at least under normal circumstances. Tolerance can be broken, however, by the development of an autoimmune response, to be discussed later in this chapter.

The cells that leave the thymus become single positives, expressing either CD4 or CD8, but not both (see Figure 4). The CD4⁺ T cells will bind to class II MHC and the CD8⁺ cells will bind to class I MHC. The discussion that follows explains the functions of these molecules and how they can be used to differentiate between the different T cell functional types.

Mechanisms of T Cell-mediated Immune Responses

Mature T cells become activated by recognizing processed foreign antigen in association with a self-MHC molecule and begin dividing rapidly by mitosis. This proliferation of T cells is called clonal expansion and is necessary to make the immune response strong enough to effectively control a pathogen. How does the body select only those T cells that are needed against a specific pathogen? Again, the specificity of a T cell is based on the amino acid sequence and the three-dimensional shape of the antigen-binding site formed by the variable regions of the two chains of the T cell receptor (Figure 5). Clonal selection is the process of antigen binding only to those T cells that have receptors specific to that antigen. Each T cell that is activated has a specific receptor “hard-wired” into its DNA, and all of its progeny will have identical DNA and T cell receptors, forming clones of the original T cell.

[caption id="" align="aligncenter" width="450"] Figure 5. Clonal Selection and Expansion of T Lymphocytes. Stem cells differentiate into T cells with specific receptors, called clones. The clones with receptors specific for antigens on the pathogen are selected for and expanded.[/caption]

Clonal Selection and Expansion

The clonal selection theory was proposed by Frank Burnet in the 1950s. However, the term clonal selection is not a complete description of the theory, as clonal expansion goes hand in glove with the selection process. The main tenet of the theory is that a typical individual has a multitude (10¹¹) of different types of T cell clones based on their receptors. In this use, a clone is a group of lymphocytes that share the same antigen receptor. Each clone is necessarily present in the body in low numbers. Otherwise, the body would not have room for lymphocytes with so many specificities.

Only those clones of lymphocytes whose receptors are activated by the antigen are stimulated to proliferate. Keep in mind that most antigens have multiple antigenic determinants, so a T cell response to a typical antigen involves a polyclonal response. A polyclonal response is the stimulation of multiple T cell clones. Once activated, the selected clones increase in number and make many copies of each cell type, each clone with its unique receptor. By the time this process is complete, the body will have large numbers of specific lymphocytes available to fight the infection (see Figure 5).

The Cellular Basis of Immunological Memory

As already discussed, one of the major features of an adaptive immune response is the development of immunological memory.

During a primary adaptive immune response, both memory T cells and effector T cells are generated. Memory T cells are long-lived and can even persist for a lifetime. Memory cells are primed to act rapidly. Thus, any subsequent exposure to the pathogen will elicit a very rapid T cell response. This rapid, secondary adaptive response generates large numbers of effector T cells so fast that the pathogen is often overwhelmed before it can cause any symptoms of disease. This is what is meant by immunity to a disease. The same pattern of primary and secondary immune responses occurs in B cells and the antibody response, as will be discussed later in the chapter.

T Cell Types and their Functions

In the discussion of T cell development, you saw that mature T cells express either the CD4 marker or the CD8 marker, but not both. These markers are cell adhesion molecules that keep the T cell in close contact with the antigen-presenting cell by directly binding to the MHC molecule (to a different part of the molecule than does the antigen). Thus, T cells and antigen-presenting cells are held together in two ways: by CD4 or CD8 attaching to MHC and by the T cell receptor binding to antigen (Figure 6).

[caption id="" align="aligncenter" width="380"] Figure 6. Pathogen Presentation. (a) CD4 is associated with helper and regulatory T cells. An extracellular pathogen is processed and presented in the binding cleft of a class II MHC molecule, and this interaction is strengthened by the CD4 molecule. (b) CD8 is associated with cytotoxic T cells. An intracellular pathogen is presented by a class I MHC molecule, and CD8 interacts with it.[/caption]

Although the correlation is not 100 percent, CD4-bearing T cells are associated with helper functions and CD8-bearing T cells are associated with cytotoxicity. These functional distinctions based on CD4 and CD8 markers are useful in defining the function of each type.

Helper T Cells and their Cytokines

Helper T cells (Th), bearing the CD4 molecule, function by secreting cytokines that act to enhance other immune responses. There are two classes of Th cells, and they act on different components of the immune response. These cells are not distinguished by their surface molecules but by the characteristic set of cytokines they secrete (Table 5).

Th1 cells are a type of helper T cell that secretes cytokines that regulate the immunological activity and development of a variety of cells, including macrophages and other types of T cells.

Th2 cells, on the other hand, are cytokine-secreting cells that act on B cells to drive their differentiation into plasma cells that make antibody. In fact, T cell help is required for antibody responses to most protein antigens, and these are called T cell-dependent antigens.

Cytotoxic T cells

Cytotoxic T cells (Tc) are T cells that kill target cells by inducing apoptosis using the same mechanism as NK cells. They either express Fas ligand, which binds to the fas molecule on the target cell, or act by using perforins and granzymes contained in their cytoplasmic granules. As was discussed earlier with NK cells, killing a virally infected cell before the virus can complete its replication cycle results in the production of no infectious particles. As more Tc cells are developed during an immune response, they overwhelm the ability of the virus to cause disease. In addition, each Tc cell can kill more than one target cell, making them especially effective. Tc cells are so important in the antiviral immune response that some speculate that this was the main reason the adaptive immune response evolved in the first place.

Regulatory T Cells

Regulatory T cells (Treg), or suppressor T cells, are the most recently discovered of the types listed here, so less is understood about them. In addition to CD4, they bear the molecules CD25 and FOXP3. Exactly how they function is still under investigation, but it is known that they suppress other T cell immune responses. This is an important feature of the immune response, because if clonal expansion during immune responses were allowed to continue uncontrolled, these responses could lead to autoimmune diseases and other medical issues.

Not only do T cells directly destroy pathogens, but they regulate nearly all other types of the adaptive immune response as well, as evidenced by the functions of the T cell types, their surface markers, the cells they work on, and the types of pathogens they work against (see Table 5).

Functions of T Cell Types and Their Cytokines (Table 5)
T cell	Main target	Function	Pathogen	Surface marker	MHC	Cytokines or mediators
Tc	Infected cells	Cytotoxicity	Intracellular	CD8	Class I	Perforins, granzymes, and fas ligand
Th1	Macrophage	Helper inducer	Extracellular	CD4	Class II	Interferon-γ and TGF-β
Th2	B cell	Helper inducer	Extracellular	CD4	Class II	IL-4, IL-6, IL-10, and others
Treg	Th cell	Suppressor	None	CD4, CD25	?	TGF-β and IL-10

21.4 The Adaptive Immune Response: B-lymphocytes and Antibodies

barkerj1 — Wed, 30 Aug 2017 18:40:36 +0000

Learning Objectives

By the end of this section, you will be able to:

Distinguish between T-cell mediated (cellular) immunity and B-cell mediated (humoral) immunity
Describe the origins of B cells
Describe the role of B cells in humoral immunity
Specify the ways in which antibodies destroy or inactivate a foreign substance in the body
Discuss the relationship between antibodies and immunization and specify four ways of conferring immunity

Antibodies were the first component of the adaptive immune response to be characterized by scientists working on the immune system. It was already known that individuals who survived a bacterial infection were immune to re-infection with the same pathogen. Early microbiologists took serum from an immune patient and mixed it with a fresh culture of the same type of bacteria, then observed the bacteria under a microscope. The bacteria became clumped in a process called agglutination. When a different bacterial species was used, the agglutination did not happen. Thus, there was something in the serum of immune individuals that could specifically bind to and agglutinate bacteria.

Scientists now know the cause of the agglutination is an antibody molecule, also called an immunoglobulin. What is an antibody? An antibody protein is essentially a secreted form of a B cell receptor. (In fact, surface immunoglobulin is another name for the B cell receptor.) Not surprisingly, the same genes encode both the secreted antibodies and the surface immunoglobulins. One minor difference in the way these proteins are synthesized distinguishes a naïve B cell with antibody on its surface from an antibody-secreting plasma cell with no antibodies on its surface. The antibodies of the plasma cell have the exact same antigen-binding site and specificity as their B cell precursors.

There are five different classes of antibody found in humans: IgM, IgD, IgG, IgA, and IgE. Each of these has specific functions in the immune response, so by learning about them, researchers can learn about the great variety of antibody functions critical to many adaptive immune responses.

B cells do not recognize antigen in the complex fashion of T cells. B cells can recognize native, unprocessed antigen and do not require the participation of MHC molecules and antigen-presenting cells.

B Cell Differentiation and Activation

B cells differentiate in the bone marrow. During the process of maturation, up to 100 trillion different clones of B cells are generated, which is similar to the diversity of antigen receptors seen in T cells.

B cell differentiation and the development of tolerance are not quite as well understood as it is in T cells. Central tolerance is the destruction or inactivation of B cells that recognize self-antigens in the bone marrow, and its role is critical and well established. In the process of clonal deletion, immature B cells that bind strongly to self-antigens expressed on tissues are signaled to commit suicide by apoptosis, removing them from the population. In the process of clonal anergy, however, B cells exposed to soluble antigen in the bone marrow are not physically deleted, but become unable to function.

Another mechanism called peripheral tolerance is a direct result of T cell tolerance. In peripheral tolerance, functional, mature B cells leave the bone marrow but have yet to be exposed to self-antigen. Most protein antigens require signals from helper T cells (Th2) to proceed to make antibody. When a B cell binds to a self-antigen but receives no signals from a nearby Th2 cell to produce antibody, the cell is signaled to undergo apoptosis and is destroyed. This is yet another example of the control that T cells have over the adaptive immune response.

After B cells are activated by their binding to antigen, they differentiate into plasma cells. Plasma cells often leave the secondary lymphoid organs, where the response is generated, and migrate back to the bone marrow, where the whole differentiation process started. After secreting antibodies for a specific period, they die, as most of their energy is devoted to making antibodies and not to maintaining themselves. Thus, plasma cells are said to be terminally differentiated.

The final B cell of interest is the memory B cell, which results from the clonal expansion of an activated B cell. Memory B cells function in a way similar to memory T cells. They lead to a stronger and faster secondary response when compared to the primary response, as illustrated below.

Antibody Structure

Antibodies are glycoproteins consisting of two types of polypeptide chains with attached carbohydrates. The heavy chain and the light chain are the two polypeptides that form the antibody. The main differences between the classes of antibodies are in the differences between their heavy chains, but as you shall see, the light chains have an important role, forming part of the antigen-binding site on the antibody molecules.

Four-chain Models of Antibody Structures

All antibody molecules have two identical heavy chains and two identical light chains. (Some antibodies contain multiple units of this four-chain structure.) The Fc region of the antibody is formed by the two heavy chains coming together, usually linked by disulfide bonds (Figure 1). The Fc portion of the antibody is important in that many effector cells of the immune system have Fc receptors. Cells having these receptors can then bind to antibody-coated pathogens, greatly increasing the specificity of the effector cells. At the other end of the molecule are two identical antigen-binding sites.

[caption id="attachment_1771" align="aligncenter" width="550"] Figure 1. Antibody and IgG2 Structures. The typical four chain structure of a generic antibody (a) and the corresponding three-dimensional structure of the antibody IgG2 (b). (credit b: modification of work by Tim Vickers)[/caption]

Five Classes of Antibodies and their Functions

In general, antibodies have two basic functions. They can act as the B cell antigen receptor or they can be secreted, circulate, and bind to a pathogen, often labeling it for identification by other forms of the immune response. Of the five antibody classes, notice that only two can function as the antigen receptor for naïve B cells: IgM and IgD (Figure 2). Mature B cells that leave the bone marrow express both IgM and IgD, but both antibodies have the same antigen specificity. Only IgM is secreted, however, and no other nonreceptor function for IgD has been discovered.

[caption id="" align="aligncenter" width="480"] Figure 2. Five Classes of Antibodies.[/caption]

IgM consists of five four-chain structures (20 total chains with 10 identical antigen-binding sites) and is thus the largest of the antibody molecules. IgM is usually the first antibody made during a primary response. Its 10 antigen-binding sites and large shape allow it to bind well to many bacterial surfaces. It is excellent at binding complement proteins and activating the complement cascade, consistent with its role in promoting chemotaxis, opsonization, and cell lysis. Thus, it is a very effective antibody against bacteria at early stages of a primary antibody response. As the primary response proceeds, the antibody produced in a B cell can change to IgG, IgA, or IgE by the process known as class switching. Class switching is the change of one antibody class to another. While the class of antibody changes, the specificity and the antigen-binding sites do not. Thus, the antibodies made are still specific to the pathogen that stimulated the initial IgM response.

IgG is a major antibody of late primary responses and the main antibody of secondary responses in the blood. This is because class switching occurs during primary responses. IgG is a monomeric antibody that clears pathogens from the blood and can activate complement proteins (although not as well as IgM), taking advantage of its antibacterial activities. Furthermore, this class of antibody is the one that crosses the placenta to protect the developing fetus from disease exits the blood to the interstitial fluid to fight extracellular pathogens.

IgA exists in two forms, a four-chain monomer in the blood and an eight-chain structure, or dimer, in exocrine gland secretions of the mucous membranes, including mucus, saliva, and tears. Thus, dimeric IgA is the only antibody to leave the interior of the body to protect body surfaces. IgA is also of importance to newborns, because this antibody is present in mother’s breast milk (colostrum), which serves to protect the infant from disease.

IgE is usually associated with allergies and anaphylaxis. It is present in the lowest concentration in the blood, because its Fc region binds strongly to an IgE-specific Fc receptor on the surfaces of mast cells. IgE makes mast cell degranulation very specific, such that if a person is allergic to peanuts, there will be peanut-specific IgE bound to his or her mast cells. In this person, eating peanuts will cause the mast cells to degranulate, sometimes causing severe allergic reactions, including anaphylaxis, a severe, systemic allergic response that can cause death.

Effects of Antibody-Antigen Binding

Antibodies that bind to antigens can lead to a number of different outcomes, depending on the nature of the antigen and the structure of the antibody. In a process called neutralization, antibodies bind to antigens on the surface of some viruses, or to toxins secreted by bacteria, in a way that prevents them from negatively affecting body cells. The antibodies neutralize the pathogen or toxin by physically covering up the dangerous parts so it cannot damage body cells. Antibodies have at least two antigen-binding sites (Figure 1 and Figure 2), they can bind to antigen on the surface of two or more cells or to multiple molecules of a soluble antigen or toxin, clumping whole cells together in a process known as agglutination, or causing antigen molecules to clump together and precipitate out of solution. Neutralization, agglutination, and precipitation or antigens all enhance the likelihood that phagocytotic cells will engulf the antigen (or antigen-bearing cell).

An antibody bound to an antigen molecule on the surface of a pathogen generally has its Fc region exposed. As noted above, the Fc region can then be bound by cells with Fc receptors and enhance the phagocytosis of the pathogen. The Fc region can also fix and activate the complement system, which in turn can lead to an enhancement of phagocytosis, a local inflammatory response, and lysis of the pathogen. Clonal Selection of B Cells

Clonal selection and expansion work much the same way in B cells as in T cells. Only B cells with appropriate antigen specificity are selected for and expanded (Figure 3). Eventually, the plasma cells secrete antibodies with antigenic specificity identical to those that were on the surfaces of the selected B cells. Notice in the figure that both plasma cells and memory B cells are generated simultaneously.

[caption id="" align="aligncenter" width="480"] Figure 3. Clonal Selection of B Cells. During a primary B cell immune response, both antibody-secreting plasma cells and memory B cells are produced. These memory cells lead to the differentiation of more plasma cells and memory B cells during secondary responses.[/caption]

Primary versus Secondary B Cell Responses

Primary and secondary responses as they relate to T cells were discussed earlier. This section will look at these responses with B cells and antibody production. Because antibodies are easily obtained from blood samples, they are easy to follow and graph (Figure 4). As you will see from the figure, the primary response to an antigen (representing a pathogen) is delayed by several days. This is the time it takes for the B cell clones to expand and differentiate into plasma cells. The level of antibody produced is low, but it is sufficient for immune protection. The second time a person encounters the same antigen, there is no time delay, and the amount of antibody made is much higher. Thus, the secondary antibody response overwhelms the pathogens quickly and, in most situations, no symptoms are felt. When a different antigen is used, another primary response is made with its low antibody levels and time delay.

[caption id="" align="aligncenter" width="380"] Figure 4. Primary and Secondary Antibody Responses. Antigen A is given once to generate a primary response and later to generate a secondary response. When a different antigen is given for the first time, a new primary response is made.[/caption]

Active versus Passive Immunity

Immunity to pathogens, and the ability to control pathogen growth so that damage to the tissues of the body is limited, can be acquired by (1) the active development of an immune response in the infected individual or (2) the passive transfer of immune components from an immune individual to a nonimmune one. Both active and passive immunity have examples in the natural world and as part of medicine.

Active immunity is the resistance to pathogens acquired during an adaptive immune response within an individual (Table 6). Naturally acquired active immunity, the response to a pathogen, is the focus of this chapter. Artificially acquired active immunity involves the use of vaccines. A vaccine is a killed or weakened pathogen or its components that, when administered to a healthy individual, leads to the development of immunological memory (a weakened primary immune response) without causing much in the way of symptoms. Killed vaccines or inactivated vaccines consist of pathogens that have been killed and so are no longer viable, but still retain antigens that can be recognized and used to mount an immune response. Live attenuated vaccines are generally used when the pathogen involved does not trigger an immune response when introduced in a killed or inactivated state. The virus that causes measles, for example, when introduced in an inactivated form does not confer lasting immunity to measles. However, this same virus can be left viable but modified to render it incapable of producing the symptoms of measles, while still triggering an appropriate immune response. The pathogens contained in a live attenuated vaccine remain viable, but have been rendered harmless or less virulent. This type of vaccine is generally Toxoid vaccines include a toxin molecule that has been modified to be harmless but still elicits an immune response against the toxin. The tetanus vaccine for example contains a modified version of the toxin tetanospasmin that is normally released by the bacterium Clostridium tetani. This vaccine triggers the production of anti-tetanospasmin antibodies that confer immunity to the live bacterium's harmful effects. Thus, with the use of vaccines, one can avoid the damage from disease that results from the first exposure to the pathogen, yet reap the benefits of protection from immunological memory. The advent of vaccines was one of the major medical advances of the twentieth century and led to the eradication of smallpox and the control of many infectious diseases, including polio, measles, and whooping cough.

Active versus Passive Immunity (Table 6)
	Natural	Artificial
Active	Adaptive immune response	Vaccine response
Passive	Trans-placental antibodies/breastfeeding	Immune globulin injections

Passive immunity arises from the transfer of antibodies to an individual without requiring them to mount their own active immune response. Naturally acquired passive immunity is seen during fetal development. IgG is transferred from the maternal circulation to the fetus via the placenta, protecting the fetus from infection and protecting the newborn for the first few months of its life. As already stated, a newborn benefits from the IgA antibodies it obtains from milk during breastfeeding. The fetus and newborn thus benefit from the immunological memory of the mother to the pathogens to which she has been exposed. In medicine, artificially acquired passive immunity usually involves injections of immunoglobulins, taken from animals previously exposed to a specific pathogen. This treatment is a fast-acting method of temporarily protecting an individual who was possibly exposed to a pathogen. The downside to both types of passive immunity is the lack of the development of immunological memory. Once the antibodies are transferred, they are effective for only a limited time before they degrade.

T cell-dependent versus T cell-independent Antigens

As discussed previously, Th2 cells secrete cytokines that drive the production of antibodies in a B cell, responding to complex antigens such as those made by proteins. On the other hand, some antigens are T cell independent. A T cell-independent antigen usually is in the form of repeated carbohydrate moieties found on the cell walls of bacteria. Each antibody on the B cell surface has two binding sites, and the repeated nature of T cell-independent antigen leads to crosslinking of the surface antibodies on the B cell. The crosslinking is enough to activate it in the absence of T cell cytokines.

A T cell-dependent antigen, on the other hand, usually is not repeated to the same degree on the pathogen and thus does not crosslink surface antibody with the same efficiency. To elicit a response to such antigens, the B and T cells must come close together (Figure 5). The B cell must receive two signals to become activated. Its surface immunoglobulin must recognize native antigen. Some of this antigen is internalized, processed, and presented to the Th2 cells on a class II MHC molecule. The T cell then binds using its antigen receptor and is activated to secrete cytokines that diffuse to the B cell, finally activating it completely. Thus, the B cell receives signals from both its surface antibody and the T cell via its cytokines, and acts as a professional antigen-presenting cell in the process.

[caption id="" align="aligncenter" width="480"] Figure 5. T and B Cell Binding. To elicit a response to a T cell-dependent antigen, the B and T cells must come close together. To become fully activated, the B cell must receive two signals from the native antigen and the T cell’s cytokines.[/caption] [caption id="attachment_2982" align="aligncenter" width="150"] Watch this CrashCourse video for an overview of the adaptive immune response.[/caption]

21.5 The Immune Response against Pathogens

barkerj1 — Wed, 30 Aug 2017 18:40:36 +0000

Learning Objectives

By the end of this section, you will be able to:

Now that you understand the development of mature, naïve B cells and T cells, and some of their major functions, how do all of these various cells, proteins, and cytokines come together to actually resolve an infection? Ideally, the immune response will rid the body of a pathogen entirely. The adaptive immune response, with its rapid clonal expansion, is well suited to this purpose. Think of a primary infection as a race between the pathogen and the immune system. The pathogen bypasses barrier defenses and starts multiplying in the host’s body. During the first 4 to 5 days, the innate immune response will partially control, but not stop, pathogen growth. As the adaptive immune response gears up, however, it will begin to clear the pathogen from the body, while at the same time becoming stronger and stronger. When following antibody responses in patients with a particular disease such as a virus, this clearance is referred to as seroconversion (sero- = “serum”). Seroconversion is the reciprocal relationship between virus levels in the blood and antibody levels. As the antibody levels rise, the virus levels decline, and this is a sign that the immune response is being at least partially effective (partially, because in many diseases, seroconversion does not necessarily mean a patient is getting well).

An excellent example of this is seroconversion during HIV disease (Figure 1). Notice that antibodies are made early in this disease, and the increase in anti-HIV antibodies correlates with a decrease in detectable virus in the blood. Although these antibodies are an important marker for diagnosing the disease, they are not sufficient to completely clear the virus. Several years later, the vast majority of these individuals, if untreated, will lose their entire adaptive immune response, including the ability to make antibodies, during the final stages of AIDS.

[caption id="" align="aligncenter" width="480"] Figure 1. HIV Disease Progression. Seroconversion, the rise of anti-HIV antibody levels and the concomitant decline in measurable virus levels, happens during the first several months of HIV disease. Unfortunately, this antibody response is ineffective at controlling the disease, as seen by the progression of the disease towards AIDS, in which all adaptive immune responses are compromised.[/caption]

The Mucosal Immune Response

Mucosal tissues are major barriers to the entry of pathogens into the body. The IgA (and sometimes IgM) antibodies in mucus and other secretions can bind to the pathogen, and in the cases of many viruses and bacteria, neutralize them. Neutralization is the process of coating a pathogen with antibodies, making it physically impossible for the pathogen to bind to receptors. Neutralization, which occurs in the blood, lymph, and other body fluids and secretions, protects the body constantly. Neutralizing antibodies are the basis for the disease protection offered by vaccines. Vaccinations for diseases that commonly enter the body via mucous membranes, such as influenza, are usually formulated to enhance IgA production.

Immune responses in some mucosal tissues such as the Peyer’s patches (see Chapter 21.1 Figure 10) in the small intestine take up particulate antigens by specialized cells known as microfold or M cells (Figure 2). These cells allow the body to sample potential pathogens from the intestinal lumen. Dendritic cells then take the antigen to the regional lymph nodes, where an immune response is mounted.

[caption id="" align="aligncenter" width="480"] Figure 2. IgA Immunity. The nasal-associated lymphoid tissue and Peyer’s patches of the small intestine generate IgA immunity. Both use M cells to transport antigen inside the body so that immune responses can be mounted.[/caption]

Defenses against Bacteria and Fungi

The body fights bacterial pathogens with a wide variety of immunological mechanisms, essentially trying to find one that is effective. Bacteria such as Mycobacterium leprae, the cause of leprosy, are resistant to lysosomal enzymes and can persist in macrophage organelles or escape into the cytosol. In such situations, infected macrophages receiving cytokine signals from Th1 cells turn on special metabolic pathways. Macrophage oxidative metabolism is hostile to intracellular bacteria, often relying on the production of nitric oxide to kill the bacteria inside the macrophage.

Fungal infections, such as those from Aspergillus, Candida, and Pneumocystis, are largely opportunistic infections that take advantage of suppressed immune responses. Most of the same immune mechanisms effective against bacteria have similar effects on fungi, both of which have characteristic cell wall structures that protect their cells.

Defenses against Parasites

Worm parasites such as helminths are seen as the primary reason why the mucosal immune response, IgE-mediated allergy and asthma, and eosinophils evolved. These parasites were at one time very common in human society. When infecting a human, often via contaminated food, some worms take up residence in the gastrointestinal tract. Eosinophils are attracted to the site by T cell cytokines, which release their granule contents upon their arrival. Mast cell degranulation also occurs, and the fluid leakage caused by the increase in local vascular permeability is thought to have a flushing action on the parasite, expelling its larvae from the body. Furthermore, if IgE labels the parasite, the eosinophils can bind to it by its Fc receptor.

Defenses against Viruses

The primary mechanisms against viruses are NK cells, interferons, and cytotoxic T cells. Antibodies are effective against viruses mostly during protection, where an immune individual can neutralize them based on a previous exposure. Antibodies have no effect on viruses or other intracellular pathogens once they enter the cell, since antibodies are not able to penetrate the plasma membrane of the cell. Many cells respond to viral infections by downregulating their expression of MHC class I molecules. This is to the advantage of the virus, because without class I expression, cytotoxic T cells have no activity. NK cells, however, can recognize virally infected class I-negative cells and destroy them. Thus, NK and cytotoxic T cells have complementary activities against virally infected cells.

Interferons have activity in slowing viral replication and are used in the treatment of certain viral diseases, such as hepatitis B and C, but their ability to eliminate the virus completely is limited. The cytotoxic T cell response, though, is key, as it eventually overwhelms the virus and kills infected cells before the virus can complete its replicative cycle. Clonal expansion and the ability of cytotoxic T cells to kill more than one target cell make these cells especially effective against viruses. In fact, without cytotoxic T cells, it is likely that humans would all die at some point from a viral infection (if no vaccine were available).

Evasion of the Immune System by Pathogens

It is important to keep in mind that although the immune system has evolved to be able to control many pathogens, pathogens themselves have evolved ways to evade the immune response. An example already mentioned is in Mycobactrium tuberculosis, which has evolved a complex cell wall that is resistant to the digestive enzymes of the macrophages that ingest them, and thus persists in the host, causing the chronic disease tuberculosis. This section briefly summarizes other ways in which pathogens can “outwit” immune responses. But keep in mind, although it seems as if pathogens have a will of their own, they do not. All of these evasive “strategies” arose strictly by evolution, driven by selection.

Bacteria sometimes evade immune responses because they exist in multiple strains, such as different groups of Staphylococcus aureus. S. aureus is commonly found in minor skin infections, such as boils, and some healthy people harbor it in their nose. One small group of strains of this bacterium, however, called methicillin-resistant Staphylococcus aureus, has become resistant to multiple antibiotics and is essentially untreatable. Different bacterial strains differ in the antigens on their surfaces. The immune response against one strain (antigen) does not affect the other; thus, the species survives.

Another method of immune evasion is mutation. Because viruses’ surface molecules mutate continuously, viruses like influenza change enough each year that the flu vaccine for one year may not protect against the flu common to the next. New vaccine formulations must be derived for each flu season.

Genetic recombination—the combining of gene segments from two different pathogens—is an efficient form of immune evasion. For example, the influenza virus contains gene segments that can recombine when two different viruses infect the same cell. Recombination between human and pig influenza viruses led to the 2010 H1N1 swine flu outbreak.

Pathogens can produce immunosuppressive molecules that impair immune function, and there are several different types. Viruses are especially good at evading the immune response in this way, and many types of viruses have been shown to suppress the host immune response in ways much more subtle than the wholesale destruction caused by HIV.

21.6 Diseases Associated with Depressed or Overactive Immune Responses

barkerj1 — Wed, 30 Aug 2017 18:40:40 +0000

Learning Objectives

By the end of this section, you will be able to:

Explain the immunological basis of autoimmune disease
Provide some examples of autoimmune diseases
Describe the immunological basis of Acquired Immune Deficiency Syndrome

This section is about how the immune system goes wrong. When it goes haywire, and becomes too weak or too strong, it leads to a state of disease. The factors that maintain immunological homeostasis are complex and incompletely understood.

Immunodeficiencies

As you have seen, the immune system is quite complex. It has many pathways using many cell types and signals. Because it is so complex, there are many ways for it to go wrong. Inherited immunodeficiencies arise from gene mutations that affect specific components of the immune response. There are also acquired immunodeficiencies with potentially devastating effects on the immune system, such as HIV.

Inherited Immunodeficiencies

A list of all inherited immunodeficiencies is well beyond the scope of this book. The list is almost as long as the list of cells, proteins, and signaling molecules of the immune system itself. Some deficiencies, such as those for complement, cause only a higher susceptibility to some Gram-negative bacteria. Others are more severe in their consequences. Certainly, the most serious of the inherited immunodeficiencies is severe combined immunodeficiency disease (SCID). This disease is complex because it is caused by many different genetic defects. What groups them together is the fact that both the B cell and T cell arms of the adaptive immune response are affected.

Children with this disease usually die of opportunistic infections within their first year of life unless they receive a bone marrow transplant. Such a procedure had not yet been perfected for David Vetter, the “boy in the bubble,” who was treated for SCID by having to live almost his entire life in a sterile plastic cocoon for the 12 years before his death from infection in 1984. One of the features that make bone marrow transplants work as well as they do is the proliferative capability of hematopoietic stem cells of the bone marrow. Only a small amount of bone marrow from a healthy donor is given intravenously to the recipient. It finds its own way to the bone where it populates it, eventually reconstituting the patient’s immune system, which is usually destroyed beforehand by treatment with radiation or chemotherapeutic drugs.

New treatments for SCID using gene therapy, inserting nondefective genes into cells taken from the patient and giving them back, have the advantage of not needing the tissue match required for standard transplants. Although not a standard treatment, this approach holds promise, especially for those in whom standard bone marrow transplantation has failed.

Human Immunodeficiency Virus/AIDS

Although many viruses cause suppression of the immune system, only one wipes it out completely, and that is the previously mentioned HIV. It is worth discussing the biology of this virus, which can lead to the well-known AIDS, so that its full effects on the immune system can be understood. The virus is transmitted through semen, vaginal fluids, and blood, and can be caught by risky sexual behaviors and the sharing of needles by intravenous drug users. There are sometimes, but not always, flu-like symptoms in the first 1 to 2 weeks after infection. This is later followed by seroconversion. The anti-HIV antibodies formed during seroconversion are the basis for most initial HIV screening done in the United States. Because seroconversion takes different lengths of time in different individuals, multiple AIDS tests are given months apart to confirm or eliminate the possibility of infection.

After seroconversion, the amount of virus circulating in the blood drops and stays at a low level for several years. During this time, the levels of CD4⁺cells, especially helper T cells, decline steadily, until at some point, the immune response is so weak that opportunistic disease and eventually death result. CD4 is the receptor that HIV uses to get inside T cells and reproduce. Given that CD4⁺ helper T cells play an important role in other in T cell immune responses and antibody responses, it should be no surprise that both types of immune responses are eventually seriously compromised.

Treatment for the disease consists of drugs that target virally encoded proteins that are necessary for viral replication but are absent from normal human cells. By targeting the virus itself and sparing the cells, this approach has been successful in significantly prolonging the lives of HIV-positive individuals. On the other hand, an HIV vaccine has been 30 years in development and is still years away. Because the virus mutates rapidly to evade the immune system, scientists have been looking for parts of the virus that do not change and thus would be good targets for a vaccine candidate.

Hypersensitivities

The word “hypersensitivity” simply means sensitive beyond normal levels of activation. Allergies and inflammatory responses to nonpathogenic environmental substances have been observed since the dawn of history. Hypersensitivity is a medical term describing symptoms that are now known to be caused by unrelated mechanisms of immunity. Still, it is useful for this discussion to use the four types of hypersensitivities as a guide to understand these mechanisms (Figure 1).

[caption id="" align="aligncenter" width="525"] Figure 1. Immune Hypersensitivity. Components of the immune system cause four types of hypersensitivity. Notice that types I–III are B cell mediated, whereas type IV hypersensitivity is exclusively a T cell phenomenon.[/caption]

Immediate (Type I) Hypersensitivity

Antigens that cause allergic responses are often referred to as allergens. The specificity of the immediate hypersensitivity response is predicated on the binding of allergen-specific IgE to the mast cell surface. The process of producing allergen-specific IgE is called sensitization, and is a necessary prerequisite for the symptoms of immediate hypersensitivity to occur. Allergies and allergic asthma are mediated by mast cell degranulation that is caused by the crosslinking of the antigen-specific IgE molecules on the mast cell surface. The mediators released have various vasoactive effects already discussed, but the major symptoms of inhaled allergens are the nasal edema and runny nose caused by the increased vascular permeability and increased blood flow of nasal blood vessels. As these mediators are released with mast cell degranulation, type I hypersensitivity reactions are usually rapid and occur within just a few minutes, hence the term immediate hypersensitivity.

Most allergens are in themselves nonpathogenic and therefore innocuous. Some individuals develop mild allergies, which are usually treated with antihistamines. Others develop severe allergies that may cause anaphylactic shock, which can potentially be fatal within 20 to 30 minutes if untreated. This drop in blood pressure (shock) with accompanying contractions of bronchial smooth muscle is caused by systemic mast cell degranulation when an allergen is eaten (for example, shellfish and peanuts), injected (by a bee sting or being administered penicillin), or inhaled (asthma). Because epinephrine raises blood pressure and relaxes bronchial smooth muscle, it is routinely used to counteract the effects of anaphylaxis and can be lifesaving. Patients with known severe allergies are encouraged to keep automatic epinephrine injectors with them at all times, especially when away from easy access to hospitals.

Allergists use skin testing to identify allergens in type I hypersensitivity. In skin testing, allergen extracts are injected into the epidermis, and a positive result of a soft, pale swelling at the site surrounded by a red zone (called the wheal and flare response), caused by the release of histamine and the granule mediators, usually occurs within 30 minutes. The soft center is due to fluid leaking from the blood vessels and the redness is caused by the increased blood flow to the area that results from the dilation of local blood vessels at the site.

Type II and Type III Hypersensitivities

Type II hypersensitivity, which involves IgG-mediated lysis of cells by complement proteins, occurs during mismatched blood transfusions and blood compatibility diseases such as erythroblastosis fetalis (see section on transplantation). Type III hypersensitivity occurs with diseases such as systemic lupus erythematosus, where soluble antigens, mostly DNA and other material from the nucleus, and antibodies accumulate in the blood to the point that the antigen and antibody precipitate along blood vessel linings. These immune complexes often lodge in the kidneys, joints, and other organs where they can activate complement proteins and cause inflammation.

Delayed (Type IV) Hypersensitivity

Delayed hypersensitivity, or type IV hypersensitivity, is basically a standard cellular immune response. In delayed hypersensitivity, the first exposure to an antigen is called sensitization, such that on re-exposure, a secondary cellular response results, secreting cytokines that recruit macrophages and other phagocytes to the site. These sensitized T cells, of the Th1 class, will also activate cytotoxic T cells. The time it takes for this reaction to occur accounts for the 24- to 72-hour delay in development.

The classical test for delayed hypersensitivity is the tuberculin test for tuberculosis, where bacterial proteins from M. tuberculosis are injected into the skin. A couple of days later, a positive test is indicated by a raised red area that is hard to the touch, called an induration, which is a consequence of the cellular infiltrate, an accumulation of activated macrophages. A positive tuberculin test means that the patient has been exposed to the bacteria and exhibits a cellular immune response to it.

Another type of delayed hypersensitivity is contact sensitivity, where substances such as the metal nickel cause a red and swollen area upon contact with the skin. The individual must have been previously sensitized to the metal. A much more severe case of contact sensitivity is poison ivy, but many of the harshest symptoms of the reaction are associated with the toxicity of its oils and are not T cell mediated.

Autoimmune Responses

The worst cases of the immune system over-reacting are autoimmune diseases. Somehow, tolerance breaks down and the immune systems in individuals with these diseases begin to attack their own bodies, causing significant damage. The trigger for these diseases is, more often than not, unknown, and the treatments are usually based on resolving the symptoms using immunosuppressive and anti-inflammatory drugs such as steroids. These diseases can be localized and crippling, as in rheumatoid arthritis, or diffuse in the body with multiple symptoms that differ in different individuals, as is the case with systemic lupus erythematosus (Figure 2).

[caption id="" align="aligncenter" width="500"] Figure 2. Autoimmune Disorders: Rheumatoid Arthritis and Lupus. (a) Extensive damage to the right hand of a rheumatoid arthritis sufferer is shown in the x-ray. (b) The diagram shows a variety of possible symptoms of systemic lupus erythematosus.[/caption]

Environmental triggers seem to play large roles in autoimmune responses. One explanation for the breakdown of tolerance is that, after certain bacterial infections, an immune response to a component of the bacterium cross-reacts with a self-antigen. This mechanism is seen in rheumatic fever, a result of infection with Streptococcus bacteria, which causes strep throat. The antibodies to this pathogen’s M protein cross-react with an antigenic component of heart myosin, a major contractile protein of the heart that is critical to its normal function. The antibody binds to these molecules and activates complement proteins, causing damage to the heart, especially to the heart valves. On the other hand, some theories propose that having multiple common infectious diseases actually prevents autoimmune responses. The fact that autoimmune diseases are rare in countries that have a high incidence of infectious diseases supports this idea, another example of the hygiene hypothesis discussed earlier in this chapter.

There are genetic factors in autoimmune diseases as well. Some diseases are associated with the MHC genes that an individual expresses. The reason for this association is likely because if one’s MHC molecules are not able to present a certain self-antigen, then that particular autoimmune disease cannot occur. Overall, there are more than 80 different autoimmune diseases, which are a significant health problem in the elderly. Table 7 lists several of the most common autoimmune diseases, the antigens that are targeted, and the segment of the adaptive immune response that causes the damage.

Autoimmune Diseases (Table 7)
Disease	Autoantigen	Symptoms
Celiac disease	Tissue transglutaminase	Damage to small intestine
Diabetes mellitus type I	Beta cells of pancreas	Low insulin production; inability to regulate serum glucose
Graves’ disease	Thyroid-stimulating hormone receptor (antibody blocks receptor)	Hyperthyroidism
Hashimoto’s thyroiditis	Thyroid-stimulating hormone receptor (antibody mimics hormone and stimulates receptor)	Hypothyroidism
Lupus erythematosus	Nuclear DNA and proteins	Damage of many body systems
Myasthenia gravis	Acetylcholine receptor in neuromuscular junctions	Debilitating muscle weakness
Rheumatoid arthritis	Joint capsule antigens	Chronic inflammation of joints

21.7 Transplantation and Cancer Immunology

barkerj1 — Wed, 30 Aug 2017 18:40:41 +0000

Learning Objectives

By the end of this section, you will be able to:

Explain the significance of the Rh factor in maternal-fetal blood type incompatability.

The immune responses to transplanted organs and to cancer cells are both important medical issues. With the use of tissue typing and anti-rejection drugs, transplantation of organs and the control of the anti-transplant immune response have made huge strides in the past 50 years. Today, these procedures are commonplace. Tissue typing is the determination of MHC molecules in the tissue to be transplanted to better match the donor to the recipient. The immune response to cancer, on the other hand, has been more difficult to understand and control. Although it is clear that the immune system can recognize some cancers and control them, others seem to be resistant to immune mechanisms.

The Rh Factor

Red blood cells can be typed based on their surface antigens. ABO blood type, in which individuals are type A, B, AB, or O according to their genetics, is one example. A separate antigen system seen on red blood cells is the Rh antigen. When someone is “A positive” for example, the positive refers to the presence of the Rh antigen, whereas someone who is “A negative” would lack this molecule.

An interesting consequence of Rh factor expression is seen in erythroblastosis fetalis, a hemolytic disease of the newborn (Figure 1). This disease occurs when mothers negative for Rh antigen have multiple Rh-positive children. During the birth of a first Rh-positive child, the mother makes a primary anti-Rh antibody response to the fetal blood cells that enter the maternal bloodstream. If the mother has a second Rh-positive child, IgG antibodies against Rh-positive blood mounted during this secondary response cross the placenta and attack the fetal blood, causing anemia. This is a consequence of the fact that the fetus is not genetically identical to the mother, and thus the mother is capable of mounting an immune response against it. This disease is treated with antibodies specific for Rh factor. These are given to the mother during the subsequent births, destroying any fetal blood that might enter her system and preventing the immune response.

[caption id="" align="aligncenter" width="500"] Figure 1. Erythroblastosis Fetalis. Erythroblastosis fetalis (hemolytic disease of the newborn) is the result of an immune response in an Rh-negative mother who has multiple children with an Rh-positive father. During the first birth, fetal blood enters the mother’s circulatory system, and anti-Rh antibodies are made. During the gestation of the second child, these antibodies cross the placenta and attack the blood of the fetus. The treatment for this disease is to give the mother anti-Rh antibodies (RhoGAM) during the first pregnancy to destroy Rh-positive fetal red blood cells from entering her system and causing the anti-Rh antibody response in the first place.[/caption]

Tissue Transplantation

Tissue transplantation is more complicated than blood transfusions because of two characteristics of MHC molecules. These molecules are the major cause of transplant rejection (hence the name “histocompatibility”). MHC polygeny refers to the multiple MHC proteins on cells, and MHC polymorphism refers to the multiple alleles for each individual MHC locus. Thus, there are many alleles in the human population that can be expressed (Table 8 and Table 9). When a donor organ expresses MHC molecules that are different from the recipient, the latter will often mount a cytotoxic T cell response to the organ and reject it. Histologically, if a biopsy of a transplanted organ exhibits massive infiltration of T lymphocytes within the first weeks after transplant, it is a sign that the transplant is likely to fail. The response is a classical, and very specific, primary T cell immune response. As far as medicine is concerned, the immune response in this scenario does the patient no good at all and causes significant harm.

Partial Table of Alleles of the Human MHC (Class I) (Table 8)
Gene	# of alleles	# of possible MHC I protein components
A	2132	1527
B	2798	2110
C	1672	1200
E	11	3
F	22	4
G	50	16

Partial Table of Alleles of the Human MHC (Class II) (Table 9)
Gene	# of alleles	# of possible MHC II protein components
DRA	7	2
DRB	1297	958
DQA1	49	31
DQB1	179	128
DPA1	36	18
DPB1	158	136
DMA	7	4
DMB	13	7
DOA	12	3
DOB	13	5

Immunosuppressive drugs such as cyclosporine A have made transplants more successful, but matching the MHC molecules is still key. In humans, there are six MHC molecules that show the most polymorphisms, three class I molecules (A, B, and C) and three class II molecules called DP, DQ, and DR. A successful transplant usually requires a match between at least 3–4 of these molecules, with more matches associated with greater success. Family members, since they share a similar genetic background, are much more likely to share MHC molecules than unrelated individuals do. In fact, due to the extensive polymorphisms in these MHC molecules, unrelated donors are found only through a worldwide database. The system is not foolproof however, as there are not enough individuals in the system to provide the organs necessary to treat all patients needing them.

One disease of transplantation occurs with bone marrow transplants, which are used to treat various diseases, including SCID and leukemia. Because the bone marrow cells being transplanted contain lymphocytes capable of mounting an immune response, and because the recipient’s immune response has been destroyed before receiving the transplant, the donor cells may attack the recipient tissues, causing graft-versus-host disease. Symptoms of this disease, which usually include a rash and damage to the liver and mucosa, are variable, and attempts have been made to moderate the disease by first removing mature T cells from the donor bone marrow before transplanting it.

Immune Responses Against Cancer

It is clear that with some cancers, for example Kaposi’s sarcoma, a healthy immune system does a good job at controlling them (Figure 2). This disease, which is caused by the human herpesvirus, is almost never observed in individuals with strong immune systems, such as the young and immunocompetent. Other examples of cancers caused by viruses include liver cancer caused by the hepatitis B virus and cervical cancer caused by the human papilloma virus. As these last two viruses have vaccines available for them, getting vaccinated can help prevent these two types of cancer by stimulating the immune response.

[caption id="" align="aligncenter" width="380"] Figure 2. Karposi’s Sarcoma Lesions. (credit: National Cancer Institute)[/caption]

On the other hand, as cancer cells are often able to divide and mutate rapidly, they may escape the immune response, just as certain pathogens such as HIV do. There are three stages in the immune response to many cancers: elimination, equilibrium, and escape. Elimination occurs when the immune response first develops toward tumor-specific antigens specific to the cancer and actively kills most cancer cells, followed by a period of controlled equilibrium during which the remaining cancer cells are held in check. Unfortunately, many cancers mutate, so they no longer express any specific antigens for the immune system to respond to, and a subpopulation of cancer cells escapes the immune response, continuing the disease process.

This fact has led to extensive research in trying to develop ways to enhance the early immune response to completely eliminate the early cancer and thus prevent a later escape. One method that has shown some success is the use of cancer vaccines, which differ from viral and bacterial vaccines in that they are directed against the cells of one’s own body. Treated cancer cells are injected into cancer patients to enhance their anti-cancer immune response and thereby prolong survival. The immune system has the capability to detect these cancer cells and proliferate faster than the cancer cells do, overwhelming the cancer in a similar way as they do for viruses. Cancer vaccines have been developed for malignant melanoma, a highly fatal skin cancer, and renal (kidney) cell carcinoma. These vaccines are still in the development stages, but some positive and encouraging results have been obtained clinically.

It is tempting to focus on the complexity of the immune system and the problems it causes as a negative. The upside to immunity, however, is so much greater: The benefit of staying alive far outweighs the negatives caused when the system does sometimes go awry. Working on “autopilot,” the immune system helps to maintain your health and kill pathogens. The only time you really miss the immune response is when it is not being effective and illness results, or, as in the extreme case of HIV disease, the immune system is gone completely.

Introduction

barkerj1 — Wed, 30 Aug 2017 18:40:42 +0000

[caption id="" align="aligncenter" width="400"] Figure 1. Mountain Climbers. The thin air at high elevations can strain the human respiratory system. (credit: “bortescristian”/flickr.com)[/caption] Hold your breath. Really! See how long you can hold your breath as you continue reading…How long can you do it? Chances are you are feeling uncomfortable already. A typical human cannot survive without breathing for more than 3 minutes, and even if you wanted to hold your breath longer, your autonomic nervous system would take control. This is because every cell in the body needs to run the oxidative stages of cellular respiration, the process by which energy is produced in the form of adenosine triphosphate (ATP). For oxidative phosphorylation to occur, oxygen is used as a reactant and carbon dioxide is released as a waste product. You may be surprised to learn that although oxygen is a critical need for cells, it is actually the accumulation of carbon dioxide that primarily drives your need to breathe. Carbon dioxide is exhaled and oxygen is inhaled through the respiratory system, which includes muscles to move air into and out of the lungs, passageways through which air moves, and microscopic gas exchange surfaces covered by capillaries. The circulatory system transports gases from the lungs to tissues throughout the body and vice versa. A variety of diseases can affect the respiratory system, such as asthma, emphysema, chronic obstruction pulmonary disorder (COPD), and lung cancer. All of these conditions affect the gas exchange process and result in labored breathing and other difficulties.

22.1 Organs and Structures of the Respiratory System

barkerj1 — Wed, 30 Aug 2017 18:40:52 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the location and function(s) of each of the following components of the human respiratory system:
- External nares, nasal cavity, internal nares
- Oral cavity, pharynx
- Epiglottis, glottis, larynx, trachea
- Bronchi, bronchiole, alveoli

The major organs of the respiratory system function primarily to provide oxygen to body tissues for cellular respiration, remove the waste product carbon dioxide, and help to maintain acid-base balance. Portions of the respiratory system are also used for non-vital functions, such as sensing odors, speech production, and for straining, such as during childbirth or coughing (Figure 1).

[caption id="" align="aligncenter" width="420"] Figure 1. Major Respiratory Structures. The major respiratory structures span the nasal cavity to the diaphragm.[/caption]

Functionally, the respiratory system can be divided into a conducting zone and a respiratory zone. The conducting zone of the respiratory system includes the organs and structures not directly involved in gas exchange. The gas exchange occurs in the respiratory zone.

Conducting Zone

The major functions of the conducting zone are to provide a route for incoming and outgoing air, remove debris and pathogens from the incoming air, and warm and humidify the incoming air. Several structures within the conducting zone perform other functions as well. The epithelium of the nasal passages, for example, is essential to sensing odors, and the bronchial epithelium that lines the lungs can metabolize some airborne carcinogens.

The Nose and its Adjacent Structures

The major entrance and exit for the respiratory system is through the nose. When discussing the nose, it is helpful to divide it into two major sections: the external nose, and the nasal cavity or internal nose.

The external nose consists of the surface and skeletal structures that result in the outward appearance of the nose and contribute to its numerous functions (Figure 2). The root is the region of the nose located between the eyebrows. The bridge is the part of the nose that connects the root to the rest of the nose. The dorsum nasi is the length of the nose. The apex is the tip of the nose. On either side of the apex, the nostrils are formed by the alae (singular = ala). An ala is a cartilaginous structure that forms the lateral side of each naris (plural = nares), or nostril opening. The philtrum is the concave surface that connects the apex of the nose to the upper lip.

[caption id="" align="aligncenter" width="450"] Figure 2. Nose. This illustration shows features of the external nose (top) and skeletal features of the nose (bottom).[/caption]

Underneath the thin skin of the nose are its skeletal features (see Figure 2, lower illustration). While the root and bridge of the nose consist of bone, the protruding portion of the nose is composed of cartilage. As a result, when looking at a skull, the nose is missing. The nasal bone is one of a pair of bones that lies under the root and bridge of the nose. The nasal bone articulates superiorly with the frontal bone and laterally with the maxillary bones. Septal cartilage is flexible hyaline cartilage connected to the nasal bone, forming the dorsum nasi. The alar cartilage consists of the apex of the nose; it surrounds the naris.

The nares open into the nasal cavity, which is separated into left and right sections by the nasal septum (Figure 3). The nasal septum is formed anteriorly by a portion of the septal cartilage (the flexible portion you can touch with your fingers) and posteriorly by the perpendicular plate of the ethmoid bone (a cranial bone located just posterior to the nasal bones) and the thin vomer bones (whose name refers to its plough shape). Each lateral wall of the nasal cavity has three bony projections, called the superior, middle, and inferior nasal conchae. The inferior conchae are separate bones, whereas the superior and middle conchae are portions of the ethmoid bone. Conchae serve to increase the surface area of the nasal cavity and to disrupt the flow of air as it enters the nose, causing air to bounce along the epithelium, where it is cleaned and warmed. The conchae and meatuses also conserve water and prevent dehydration of the nasal epithelium by trapping water during exhalation. The floor of the nasal cavity is composed of the palate. The hard palate at the anterior region of the nasal cavity is composed of bone. The soft palate at the posterior portion of the nasal cavity consists of muscle tissue. Air exits the nasal cavities via the internal nares and moves into the pharynx.

[caption id="" align="aligncenter" width="450"] Figure 3. Upper Airway[/caption]

Several bones that help form the walls of the nasal cavity have air-containing spaces called the paranasal sinuses, which serve to warm and humidify incoming air. Sinuses are lined with a mucosa. Each paranasal sinus is named for its associated bone: frontal sinus, maxillary sinus, sphenoidal sinus, and ethmoidal sinus. The sinuses produce mucus and lighten the weight of the skull.

The nares and anterior portion of the nasal cavities are lined with mucous membranes, containing sebaceous glands and hair follicles that serve to prevent the passage of large debris, such as dirt, through the nasal cavity. An olfactory epithelium used to detect odors is found deeper in the nasal cavity.

The conchae, meatuses, and paranasal sinuses are lined by respiratory epithelium composed of pseudostratified ciliated columnar epithelium (Figure 4). The epithelium contains goblet cells, one of the specialized, columnar epithelial cells that produce mucus to trap debris. The cilia of the respiratory epithelium help remove the mucus and debris from the nasal cavity with a constant beating motion, sweeping materials towards the throat to be swallowed. Interestingly, cold air slows the movement of the cilia, resulting in accumulation of mucus that may in turn lead to a runny nose during cold weather. This moist epithelium functions to warm and humidify incoming air. Capillaries located just beneath the nasal epithelium warm the air by convection. Serous and mucus-producing cells also secrete the lysozyme enzyme and proteins called defensins, which have antibacterial properties. Immune cells that patrol the connective tissue deep to the respiratory epithelium provide additional protection.

[caption id="" align="aligncenter" width="500"] Figure 4. Pseudostratified Ciliated Columnar Epithelium. Respiratory epithelium is pseudostratified ciliated columnar epithelium. Seromucous glands provide lubricating mucus. LM × 680. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption]

Pharynx

The pharynx is a tube formed by skeletal muscle and lined by mucous membrane that is continuous with that of the nasal cavities (see Figure 3). The pharynx is divided into three major regions: the nasopharynx, the oropharynx, and the laryngopharynx (Figure 5).

[caption id="" align="aligncenter" width="475"] Figure 5. Divisions of the Pharynx. The pharynx is divided into three regions: the nasopharynx, the oropharynx, and the laryngopharynx.[/caption]

The nasopharynx is flanked by the conchae of the nasal cavity, and it serves only as an airway. At the top of the nasopharynx are the pharyngeal tonsils. A pharyngeal tonsil, also called an adenoid, is an aggregate of lymphoid reticular tissue similar to a lymph node that lies at the superior portion of the nasopharynx. The function of the pharyngeal tonsil is not well understood, but it contains a rich supply of lymphocytes and is covered with ciliated epithelium that traps and destroys invading pathogens that enter during inhalation. The pharyngeal tonsils are large in children, but interestingly, tend to regress with age and may even disappear. The uvula is a small bulbous, teardrop-shaped structure located at the apex of the soft palate. Both the uvula and soft palate move like a pendulum during swallowing, swinging upward to close off the nasopharynx to prevent ingested materials from entering the nasal cavity. In addition, auditory (Eustachian) tubes that connect to each middle ear cavity open into the nasopharynx. This connection is why colds often lead to ear infections.

The oropharynx is a passageway for both air and food. The oropharynx is bordered superiorly by the nasopharynx and anteriorly by the oral cavity. The fauces is the opening at the connection between the oral cavity and the oropharynx. As the nasopharynx becomes the oropharynx, the epithelium changes from pseudostratified ciliated columnar epithelium to stratified squamous epithelium. The oropharynx contains two distinct sets of tonsils, the palatine and lingual tonsils. A palatine tonsil is one of a pair of structures located laterally in the oropharynx in the area of the fauces. The lingual tonsil is located at the base of the tongue. Similar to the pharyngeal tonsil, the palatine and lingual tonsils are composed of lymphoid tissue, and trap and destroy pathogens entering the body through the oral or nasal cavities.

The laryngopharynx is inferior to the oropharynx and posterior to the larynx. It continues the route for ingested material and air until its inferior end, where the digestive and respiratory systems diverge. The stratified squamous epithelium of the oropharynx is continuous with the laryngopharynx. Anteriorly, the laryngopharynx opens into the larynx, whereas posteriorly, it enters the esophagus.

Larynx

The larynx is a cartilaginous structure inferior to the laryngopharynx that connects the pharynx to the trachea and helps regulate the volume of air that enters and leaves the lungs (Figure 6). The structure of the larynx is formed by several pieces of cartilage. Three large cartilage pieces—the thyroid cartilage (anterior), epiglottis (superior), and cricoid cartilage (inferior)—form the major structure of the larynx. The thyroid cartilage is the largest piece of cartilage that makes up the larynx. The thyroid cartilage consists of the laryngeal prominence, or “Adam’s apple,” which tends to be more prominent in males. The thick cricoid cartilage forms a ring, with a wide posterior region and a thinner anterior region. Three smaller, paired cartilages—the arytenoids, corniculates, and cuneiforms—attach to the epiglottis and the vocal cords and muscle that help move the vocal cords to produce speech.

[caption id="" align="aligncenter" width="450"] Figure 6. Larynx. The larynx extends from the laryngopharynx and the hyoid bone to the trachea.[/caption]

The epiglottis, attached to the thyroid cartilage, is a very flexible piece of elastic cartilage that covers the opening of the trachea (see Figure 3). When in the “closed” position, the unattached end of the epiglottis rests on the glottis. The glottis is composed of the vestibular folds, the true vocal cords, and the space between these folds (Figure 7). A vestibular fold, or false vocal cord, is one of a pair of folded sections of mucous membrane. A true vocal cord is one of the white, membranous folds attached by muscle to the thyroid and arytenoid cartilages of the larynx on their outer edges. The inner edges of the true vocal cords are free, allowing oscillation to produce sound. The size of the membranous folds of the true vocal cords differs between individuals, producing voices with different pitch ranges. Folds in males tend to be larger than those in females, which create a deeper voice. The act of swallowing causes the pharynx and larynx to lift upward, allowing the pharynx to expand and the epiglottis of the larynx to swing downward, closing the opening to the trachea. These movements produce a larger area for food to pass through, while preventing food and beverages from entering the trachea.

[caption id="" align="aligncenter" width="450"] Figure 7. Vocal Cords. The true vocal cords and vestibular folds of the larynx are viewed inferiorly from the laryngopharynx.[/caption]

Continuous with the laryngopharynx, the superior portion of the larynx is lined with stratified squamous epithelium, transitioning into pseudostratified ciliated columnar epithelium that contains goblet cells. Similar to the nasal cavity and nasopharynx, this specialized epithelium produces mucus to trap debris and pathogens as they enter the trachea. The cilia beat the mucus upward towards the laryngopharynx, where it can be swallowed down the esophagus.

Trachea

The trachea (windpipe) extends from the larynx toward the lungs (Figure 8a). The trachea is formed by 16 to 20 stacked, C-shaped pieces of hyaline cartilage that are connected by dense connective tissue. The trachealis muscle and elastic connective tissue together form the fibroelastic membrane, a flexible membrane that closes the posterior surface of the trachea, connecting the C-shaped cartilages. The fibroelastic membrane allows the trachea to stretch and expand slightly during inhalation and exhalation, whereas the rings of cartilage provide structural support and prevent the trachea from collapsing. In addition, the trachealis muscle can be contracted to force air through the trachea during exhalation. The trachea is lined with pseudostratified ciliated columnar epithelium, which is continuous with the larynx. The esophagus borders the trachea posteriorly.

[caption id="" align="aligncenter" width="560"] Figure 8. Trachea. (a) The tracheal tube is formed by stacked, C-shaped pieces of hyaline cartilage. (b) The layer visible in this cross-section of tracheal wall tissue between the hyaline cartilage and the lumen of the trachea is the mucosa, which is composed of pseudostratified ciliated columnar epithelium that contains goblet cells. LM × 1220. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption]

Bronchial Tree

The trachea branches into the right and left primary bronchi at the carina. These bronchi are also lined by pseudostratified ciliated columnar epithelium containing mucus-producing goblet cells (Figure 8b). The carina is a raised structure that contains specialized nervous tissue that induces violent coughing if a foreign body, such as food, is present. Rings of cartilage, similar to those of the trachea, support the structure of the bronchi and prevent their collapse. The primary bronchi enter the lungs at the hilum, a concave region where blood vessels, lymphatic vessels, and nerves also enter the lungs. The bronchi continue to branch into bronchial a tree. A bronchial tree (or respiratory tree) is the collective term used for these multiple-branched bronchi. The main function of the bronchi, like other conducting zone structures, is to provide a passageway for air to move into and out of each lung. In addition, the mucous membrane traps debris and pathogens.

A bronchiole branches from the tertiary bronchi. Bronchioles, which are about 1 mm in diameter, further branch until they become the tiny terminal bronchioles, which lead to the structures of gas exchange. There are more than 1000 terminal bronchioles in each lung. The muscular walls of the bronchioles do not contain cartilage like those of the bronchi. This muscular wall can change the size of the tubing to increase or decrease airflow through the tube.

Respiratory Zone

In contrast to the conducting zone, the respiratory zone includes structures that are directly involved in gas exchange. The respiratory zone begins where the terminal bronchioles join a respiratory bronchiole, the smallest type of bronchiole (Figure 9), which then leads to an alveolar duct, opening into a cluster of alveoli.

[caption id="" align="aligncenter" width="525"] Figure 9. Respiratory Zone. Bronchioles lead to alveolar sacs in the respiratory zone, where gas exchange occurs.[/caption]

Alveoli

An alveolar duct is a tube composed of smooth muscle and connective tissue, which opens into a cluster of alveoli. An alveolus is one of the many small, grape-like sacs that are attached to the alveolar ducts.

An alveolar sac is a cluster of many individual alveoli that are responsible for gas exchange. An alveolus is approximately 200 μm in diameter with elastic walls that allow the alveolus to stretch during air intake, which greatly increases the surface area available for gas exchange. Alveoli are connected to their neighbors by alveolar pores, which help maintain equal air pressure throughout the alveoli and lung (Figure 10).

[caption id="" align="aligncenter" width="560"] Figure 10. Structures of the Respiratory Zone. (a) The alveolus is responsible for gas exchange. (b) A micrograph shows the alveolar structures within lung tissue. LM × 178. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption] The alveolar wall consists of three major cell types: type I alveolar cells, type II alveolar cells, and alveolar macrophages. A type I alveolar cell is a squamous epithelial cell of the alveoli, which constitute up to 97 percent of the alveolar surface area. These cells are about 25 nm thick and are highly permeable to gases. A type II alveolar cell is interspersed among the type I cells and secretes pulmonary surfactant, a substance composed of phospholipids and proteins that reduces the surface tension of the alveoli. Roaming around the alveolar wall is the alveolar macrophage, a phagocytic cell of the immune system that removes debris and pathogens that have reached the alveoli.

The simple squamous epithelium formed by type I alveolar cells is attached to a thin, elastic basement membrane. This epithelium is extremely thin and borders the endothelial membrane of capillaries. Taken together, the alveoli and capillary membranes form a respiratory membrane that is approximately 0.5 mm thick. The respiratory membrane allows gases to cross by simple diffusion, allowing oxygen to be picked up by the blood for transport and CO₂to be released into the air of the alveoli.

[caption id="attachment_2984" align="aligncenter" width="150"] Watch this CrashCourse video for an overview of the respiratory system![/caption]

22.2 The Lungs

barkerj1 — Wed, 30 Aug 2017 18:40:54 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the location and function(s) of the visceral pleura, parietal pleura, and pleural cavity

A major organ of the respiratory system, each lung houses structures of both the conducting and respiratory zones. The main function of the lungs is to perform the exchange of oxygen and carbon dioxide with air from the atmosphere. To this end, the lungs exchange respiratory gases across a very large epithelial surface area—about 70 square meters—that is highly permeable to gases.

Gross Anatomy of the Lungs

The lungs are pyramid-shaped, paired organs that are connected to the trachea by the right and left bronchi; on the inferior surface, the lungs are bordered by the diaphragm. The diaphragm is the flat, dome-shaped muscle located at the base of the lungs and thoracic cavity. The lungs are enclosed by the pleurae, which are attached to the mediastinum. The right lung is shorter and wider than the left lung, and the left lung occupies a smaller volume than the right. The cardiac notch is an indentation on the surface of the left lung, and it allows space for the heart (Figure 1). The apex of the lung is the superior region, whereas the base is the opposite region near the diaphragm. The costal surface of the lung borders the ribs. The mediastinal surface faces the midline.

[caption id="" align="aligncenter" width="430"] Figure 1. Gross Anatomy of the Lungs.[/caption]

Each lung is composed of smaller units called lobes. Fissures separate these lobes from each other. The right lung consists of three lobes: the superior, middle, and inferior lobes. The left lung consists of two lobes: the superior and inferior lobes. A bronchopulmonary segment is a division of a lobe, and each lobe houses multiple bronchopulmonary segments. Each segment receives air from its own tertiary bronchus and is supplied with blood by its own artery. Some diseases of the lungs typically affect one or more bronchopulmonary segments, and in some cases, the diseased segments can be surgically removed with little influence on neighboring segments. A pulmonary lobule is a subdivision formed as the bronchi branch into bronchioles. Each lobule receives its own large bronchiole that has multiple branches. An interlobular septum is a wall, composed of connective tissue, which separates lobules from one another.

Blood Supply and Nervous Innervation of the Lungs

The blood supply of the lungs plays an important role in gas exchange and serves as a transport system for gases throughout the body. In addition, innervation by the both the parasympathetic and sympathetic nervous systems provides an important level of control through dilation and constriction of the airway.

Blood Supply

The major function of the lungs is to perform gas exchange, which requires blood from the pulmonary circulation. This blood supply contains deoxygenated blood and travels to the lungs where erythrocytes, also known as red blood cells, pick up oxygen to be transported to tissues throughout the body. The pulmonary artery is an artery that arises from the pulmonary trunk and carries deoxygenated, arterial blood to the alveoli. The pulmonary artery branches multiple times as it follows the bronchi, and each branch becomes progressively smaller in diameter. One arteriole and an accompanying venule supply and drain one pulmonary lobule. As they near the alveoli, the pulmonary arteries become the pulmonary capillary network. The pulmonary capillary network consists of tiny vessels with very thin walls that lack smooth muscle fibers. The capillaries branch and follow the bronchioles and structure of the alveoli. It is at this point that the capillary wall meets the alveolar wall, creating the respiratory membrane. Once the blood is oxygenated, it drains from the alveoli by way of multiple pulmonary veins, which exit the lungs through the hilum.

Nervous Innervation

Dilation and constriction of the airway are achieved through nervous control by the parasympathetic and sympathetic nervous systems. The parasympathetic system causes bronchoconstriction, whereas the sympathetic nervous system stimulates bronchodilation. Reflexes such as coughing, and the ability of the lungs to regulate oxygen and carbon dioxide levels, also result from this autonomic nervous system control. Sensory nerve fibers arise from the vagus nerve, and from the second to fifth thoracic ganglia. The pulmonary plexus is a region on the lung root formed by the entrance of the nerves at the hilum. The nerves then follow the bronchi in the lungs and branch to innervate muscle fibers, glands, and blood vessels.

Pleura of the Lungs

Each lung is enclosed within a cavity that is surrounded by the pleura. The pleura (plural = pleurae) is a serous membrane that surrounds the lung. The right and left pleurae, which enclose the right and left lungs, respectively, are separated by the mediastinum. The pleurae consist of two layers. The visceral pleura is the layer that is superficial to the lungs, and extends into and lines the lung fissures (Figure 2). In contrast, the parietal pleura is the outer layer that connects to the thoracic wall, the mediastinum, and the diaphragm. The visceral and parietal pleurae connect to each other at the hilum. The pleural cavity is the space between the visceral and parietal layers.

[caption id="" align="aligncenter" width="440"] Figure 2. Parietal and Visceral Pleurae of the Lungs.[/caption]

The pleurae perform two major functions: They produce pleural fluid and create cavities that separate the major organs. Pleural fluid is secreted by mesothelial cells from both pleural layers and acts to lubricate their surfaces. This lubrication reduces friction between the two layers to prevent trauma during breathing, and creates surface tension that helps maintain the position of the lungs against the thoracic wall. This adhesive characteristic of the pleural fluid causes the lungs to enlarge when the thoracic wall expands during ventilation, allowing the lungs to fill with air. The pleurae also create a division between major organs that prevents interference due to the movement of the organs, while preventing the spread of infection.

22.3 The Process of Breathing

barkerj1 — Wed, 30 Aug 2017 18:41:00 +0000

Learning Objectives

By the end of this section, you will be able to:

Explain the mechanism of ventilation (inspiration and expiration)
Describe the role of each structure involved in ventilation
Interpret a spirogram
Understand the usefulness of a spirogram
Describe the terms related to a spirogram and ventilation
Describe the nervous control of breathing
Describe how carbon dioxide, oxygen, and hydrogen ions control the rate of breathing

Pulmonary ventilation is the act of breathing, which can be described as the movement of air into and out of the lungs. The major mechanisms that drive pulmonary ventilation are atmospheric pressure (P_atm); the air pressure within the alveoli, called alveolar pressure (P_alv); and the pressure within the pleural cavity, called intrapleural pressure (P_ip).

Mechanisms of Breathing

The alveolar and intrapleural pressures are dependent on certain physical features of the lung. However, the ability to breathe—to have air enter the lungs during inspiration and air leave the lungs during expiration—is dependent on the air pressure of the atmosphere and the air pressure within the lungs.

Pressure Relationships

Inspiration (or inhalation) and expiration (or exhalation) are dependent on the differences in pressure between the atmosphere and the lungs. In a gas, pressure is a force created by the movement of gas molecules that are confined. For example, a certain number of gas molecules in a two-liter container has more room than the same number of gas molecules in a one-liter container (Figure 1). In this case, the force exerted by the movement of the gas molecules against the walls of the two-liter container is lower than the force exerted by the gas molecules in the one-liter container. Therefore, the pressure is lower in the two-liter container and higher in the one-liter container. At a constant temperature, changing the volume occupied by the gas changes the pressure, as does changing the number of gas molecules. Boyle’s law describes the relationship between volume and pressure in a gas at a constant temperature. Boyle discovered that the pressure of a gas is inversely proportional to its volume: If volume increases, pressure decreases. Likewise, if volume decreases, pressure increases. Pressure and volume are inversely related (P = k/V). Therefore, the pressure in the one-liter container (one-half the volume of the two-liter container) would be twice the pressure in the two-liter container. Boyle’s law is expressed by the following formula:

P₁V₁= P₂V₂

In this formula, P₁ represents the initial pressure and V₁ represents the initial volume, whereas the final pressure and volume are represented by P₂ and V_2,respectively. If the two- and one-liter containers were connected by a tube and the volume of one of the containers were changed, then the gases would move from higher pressure (lower volume) to lower pressure (higher volume).

[caption id="" align="aligncenter" width="420"] Figure 1. Boyle's Law. In a gas, pressure increases as volume decreases.[/caption]

Pulmonary ventilation is dependent on three types of pressure: atmospheric, intra-alveolar, and interpleural. Atmospheric pressure is the amount of force that is exerted by gases in the air surrounding any given surface, such as the body. Atmospheric pressure can be expressed in terms of the unit atmosphere, abbreviated atm, or in millimeters of mercury (mm Hg). One atm is equal to 760 mm Hg, which is the atmospheric pressure at sea level. Typically, for respiration, other pressure values are discussed in relation to atmospheric pressure. Therefore, negative pressure is pressure lower than the atmospheric pressure, whereas positive pressure is pressure that it is greater than the atmospheric pressure. A pressure that is equal to the atmospheric pressure is expressed as zero.

Intra-alveolar pressure is the pressure of the air within the alveoli, which changes during the different phases of breathing (Figure 2). Because the alveoli are connected to the atmosphere via the tubing of the airways (similar to the two- and one-liter containers in the example above), the interpulmonary pressure of the alveoli always equalizes with the atmospheric pressure.

[caption id="" align="aligncenter" width="455"] Figure 2. Intrapulmonary and Intrapleural Pressure Relationships. Alveolar pressure changes during the different phases of the cycle. It equalizes at 760 mm Hg but does not remain at 760 mm Hg.[/caption]

Intrapleural pressure is the pressure of the air within the pleural cavity, between the visceral and parietal pleurae. Similar to intra-alveolar pressure, intrapleural pressure also changes during the different phases of breathing. However, due to certain characteristics of the lungs, the intrapleural pressure is always lower than, or negative to, the intra-alveolar pressure (and therefore also to atmospheric pressure). Although it fluctuates during inspiration and expiration, intrapleural pressure remains approximately –4 mm Hg throughout the breathing cycle.

Competing forces within the thorax cause the formation of the negative intrapleural pressure. One of these forces relates to the elasticity of the lungs themselves—elastic tissue pulls the lungs inward, away from the thoracic wall. Surface tension of alveolar fluid, which is mostly water, also creates an inward pull of the lung tissue. This inward tension from the lungs is countered by opposing forces from the pleural fluid and thoracic wall. Surface tension within the pleural cavity pulls the lungs outward. Too much or too little pleural fluid would hinder the creation of the negative intrapleural pressure; therefore, the level must be closely monitored by the mesothelial cells and drained by the lymphatic system. Since the parietal pleura is attached to the thoracic wall, the natural elasticity of the chest wall opposes the inward pull of the lungs. Ultimately, the outward pull is slightly greater than the inward pull, creating the –4 mm Hg intrapleural pressure relative to the intra-alveolar pressure. Transpulmonary pressure is the difference between the intrapleural and intra-alveolar pressures, and it determines the size of the lungs. A higher transpulmonary pressure corresponds to a larger lung.

Physical Factors Affecting Ventilation

In addition to the differences in pressures, breathing is also dependent upon the contraction and relaxation of muscle fibers of both the diaphragm and thorax. The lungs themselves are passive during breathing, meaning they are not involved in creating the movement that helps inspiration and expiration. This is because of the adhesive nature of the pleural fluid, which allows the lungs to be pulled outward when the thoracic wall moves during inspiration. The recoil of the thoracic wall during expiration causes compression of the lungs. Contraction and relaxation of the diaphragm and intercostals muscles (found between the ribs) cause most of the pressure changes that result in inspiration and expiration. These muscle movements and subsequent pressure changes cause air to either rush in or be forced out of the lungs.

Other characteristics of the lungs influence the effort that must be expended to ventilate. Resistance is a force that slows motion, in this case, the flow of gases. The size of the airway is the primary factor affecting resistance. A small tubular diameter forces air through a smaller space, causing more collisions of air molecules with the walls of the airways. The following formula helps to describe the relationship between airway resistance and pressure changes:

F = ∆P / R

As noted earlier, there is surface tension within the alveoli caused by water present in the lining of the alveoli. This surface tension tends to inhibit expansion of the alveoli. However, pulmonary surfactant secreted by type II alveolar cells mixes with that water and helps reduce this surface tension. Without pulmonary surfactant, the alveoli would collapse during expiration.

Thoracic wall compliance is the ability of the thoracic wall to stretch while under pressure. This can also affect the effort expended in the process of breathing. In order for inspiration to occur, the thoracic cavity must expand. The expansion of the thoracic cavity directly influences the capacity of the lungs to expand. If the tissues of the thoracic wall are not very compliant, it will be difficult to expand the thorax to increase the size of the lungs.

Pulmonary Ventilation

The difference in pressures drives pulmonary ventilation because air flows down a pressure gradient, that is, air flows from an area of higher pressure to an area of lower pressure. Air flows into the lungs largely due to a difference in pressure; atmospheric pressure is greater than intra-alveolar pressure, and intra-alveolar pressure is greater than intrapleural pressure. Air flows out of the lungs during expiration based on the same principle; pressure within the lungs becomes greater than the atmospheric pressure.

Pulmonary ventilation comprises two major steps: inspiration and expiration. Inspiration is the process that causes air to enter the lungs, and expiration is the process that causes air to leave the lungs (Figure 3). A respiratory cycle is one sequence of inspiration and expiration. In general, two muscle groups are used during normal inspiration: the diaphragm and the external intercostal muscles. Additional muscles can be used if a bigger breath is required. When the diaphragm contracts, it moves inferiorly toward the abdominal cavity, creating a larger thoracic cavity and more space for the lungs. Contraction of the external intercostal muscles moves the ribs upward and outward, causing the rib cage to expand, which increases the volume of the thoracic cavity. Due to the adhesive force of the pleural fluid, the expansion of the thoracic cavity forces the lungs to stretch and expand as well. This increase in volume leads to a decrease in intra-alveolar pressure, creating a pressure lower than atmospheric pressure. As a result, a pressure gradient is created that drives air into the lungs.

[caption id="" align="aligncenter" width="450"] Figure 3. Inspiration and Expiration. Inspiration and expiration occur due to the expansion and contraction of the thoracic cavity, respectively.[/caption]

The process of normal expiration is passive, meaning that energy is not required to push air out of the lungs. Instead, the elasticity of the lung tissue causes the lung to recoil, as the diaphragm and intercostal muscles relax following inspiration. In turn, the thoracic cavity and lungs decrease in volume, causing an increase in interpulmonary pressure. The interpulmonary pressure rises above atmospheric pressure, creating a pressure gradient that causes air to leave the lungs.

There are different types, or modes, of breathing that require a slightly different process to allow inspiration and expiration. Quiet breathing, also known as eupnea, is a mode of breathing that occurs at rest and does not require the cognitive thought of the individual. During quiet breathing, the diaphragm and external intercostals must contract.

A deep breath, called diaphragmatic breathing, requires the diaphragm to contract. As the diaphragm relaxes, air passively leaves the lungs. A shallow breath, called costal breathing, requires contraction of the intercostal muscles. As the intercostal muscles relax, air passively leaves the lungs.

In contrast, forced breathing, also known as hyperpnea, is a mode of breathing that can occur during exercise or actions that require the active manipulation of breathing, such as singing. During forced breathing, inspiration and expiration both occur due to muscle contractions. In addition to the contraction of the diaphragm and intercostal muscles, other accessory muscles must also contract. During forced inspiration, muscles of the neck, including the scalenes, contract and lift the thoracic wall, increasing lung volume. During forced expiration, accessory muscles of the abdomen, including the obliques, contract, forcing abdominal organs upward against the diaphragm. This helps to push the diaphragm further into the thorax, pushing more air out. In addition, accessory muscles (primarily the internal intercostals) help to compress the rib cage, which also reduces the volume of the thoracic cavity.

Respiratory Volumes and Capacities

Respiratory volume is the term used for various volumes of air moved by or associated with the lungs at a given point in the respiratory cycle. There are four major types of respiratory volumes: tidal, residual, inspiratory reserve, and expiratory reserve (Figure 4). Tidal volume (TV) is the amount of air that normally enters the lungs during quiet breathing, which is about 500 milliliters. Expiratory reserve volume (ERV) is the amount of air you can forcefully exhale past a normal tidal expiration, up to 1200 milliliters for men. Inspiratory reserve volume (IRV) is produced by a deep inhalation, past a tidal inspiration. This is the extra volume that can be brought into the lungs during a forced inspiration. Residual volume (RV) is the air left in the lungs if you exhale as much air as possible. The residual volume makes breathing easier by preventing the alveoli from collapsing. Respiratory volume is dependent on a variety of factors, and measuring the different types of respiratory volumes by using a spirometer to generate a spirogram can provide important clues about a person’s respiratory health (Figure 5).

[caption id="" align="aligncenter" width="455"] Figure 4. Respiratory Volumes and Capacities. These two graphs show (a) respiratory volumes and (b) the combination of volumes that results in respiratory capacity.[/caption]

[caption id="" align="aligncenter" width="500"] Figure 5. Pulmonary Function Testing.[/caption]

Respiratory capacity is the combination of two or more selected volumes, which further describes the amount of air in the lungs during a given time. For example, total lung capacity (TLC) is the sum of all of the lung volumes (TV, ERV, IRV, and RV), which represents the total amount of air a person can hold in the lungs after a forceful inhalation. TLC is about 6000 mL air for men, and about 4200 mL for women. Vital capacity (VC) is the amount of air a person can move into or out of his or her lungs, and is the sum of all of the volumes except residual volume (TV, ERV, and IRV), which is between 4000 and 5000 milliliters. Inspiratory capacity (IC) is the maximum amount of air that can be inhaled past a normal tidal expiration, is the sum of the tidal volume and inspiratory reserve volume. On the other hand, the functional residual capacity (FRC) is the amount of air that remains in the lung after a normal tidal expiration; it is the sum of expiratory reserve volume and residual volume (see Figure 4).

In addition to the air that creates respiratory volumes, the respiratory system also contains anatomical dead space, which is air that is present in the airway that never reaches the alveoli and therefore never participates in gas exchange. Alveolar dead space involves air found within alveoli that are unable to function, such as those affected by disease or abnormal blood flow. Total dead space is the anatomical dead space and alveolar dead space together, and represents all of the air in the respiratory system that is not being used in the gas exchange process.

Respiratory Rate and Control of Ventilation

Breathing usually occurs without thought, although at times you can consciously control it, such as when you swim under water, sing a song, or blow bubbles. The respiratory rate is the total number of breaths, or respiratory cycles, that occur each minute. Respiratory rate can be an important indicator of disease, as the rate may increase or decrease during an illness or in a disease condition. The respiratory rate is controlled by the respiratory center located within the medulla oblongata in the brain, which responds primarily to changes in carbon dioxide, oxygen, and pH levels in the blood.

The normal respiratory rate of a child decreases from birth to adolescence. A child under 1 year of age has a normal respiratory rate between 30 and 60 breaths per minute, but by the time a child is about 10 years old, the normal rate is closer to 18 to 30. By adolescence, the normal respiratory rate is similar to that of adults, 12 to 18 breaths per minute.

Ventilation Control Centers

The control of ventilation is a complex interplay of multiple regions in the brain that signal the muscles used in pulmonary ventilation to contract (Table 1). The result is typically a rhythmic, consistent ventilation rate that provides the body with sufficient amounts of oxygen, while adequately removing carbon dioxide.

Summary of Ventilation Regulation (Table 1)
System component	Function
Medullary respiratory renter	Sets the basic rhythm of breathing
Ventral respiratory group (VRG)	Generates the breathing rhythm and integrates data coming into the medulla
Dorsal respiratory group (DRG)	Integrates input from the stretch receptors and the chemoreceptors in the periphery
Pontine respiratory group (PRG)	Influences and modifies the medulla oblongata’s functions
Aortic body	Monitors blood PCO₂, PO₂, and pH
Carotid body	Monitors blood PCO₂, PO₂, and pH
Hypothalamus	Monitors emotional state and body temperature
Cortical areas of the brain	Control voluntary breathing
Proprioceptors	Send impulses regarding joint and muscle movements
Pulmonary stretch receptors	Detect lung inflation
Pulmonary irritant receptors	Detect foreign material in the lungs

Neurons that innervate the muscles of the respiratory system are responsible for controlling and regulating pulmonary ventilation. The major brain centers involved in pulmonary ventilation are the medulla oblongata and the pontine respiratory group (Figure 6).

[caption id="" align="aligncenter" width="465"] Figure 6. Respiratory Centers of the Brain.[/caption]

The medulla oblongata contains the dorsal respiratory group (DRG) and the ventral respiratory group (VRG). The DRG is involved in maintaining a constant breathing rhythm by stimulating the diaphragm and intercostal muscles to contract, resulting in inspiration. When activity in the DRG ceases, it no longer stimulates the diaphragm and intercostals to contract, allowing them to relax, resulting in expiration. The VRG is involved in forced breathing, as the neurons in the VRG stimulate the accessory muscles involved in forced breathing to contract, resulting in forced inspiration. The VRG also stimulates the accessory muscles involved in forced expiration to contract.

The second respiratory center of the brain is located within the pons, called the pontine respiratory group, and consists of the apneustic and pneumotaxic centers. The apneustic center is a double cluster of neuronal cell bodies that stimulate neurons in the DRG, controlling the depth of inspiration, particularly for deep breathing. The pneumotaxic center is a network of neurons that inhibits the activity of neurons in the DRG, allowing relaxation after inspiration, and thus controlling the overall rate.

Factors That Affect the Rate and Depth of Respiration

The respiratory rate and the depth of inspiration are regulated by the medulla oblongata and pons; however, these regions of the brain do so in response to systemic stimuli. It is a dose-response, positive-feedback relationship in which the greater the stimulus, the greater the response. Thus, increasing stimuli results in forced breathing. Multiple systemic factors are involved in stimulating the brain to produce pulmonary ventilation.

The major factor that stimulates the medulla oblongata and pons to produce respiration is surprisingly not oxygen concentration, but rather the concentration of carbon dioxide in the blood. As you recall, carbon dioxide is a waste product of cellular respiration and can be toxic. Concentrations of chemicals are sensed by chemoreceptors. A central chemoreceptor is one of the specialized receptors that are located in the brain and brainstem, whereas a peripheral chemoreceptor is one of the specialized receptors located in the carotid arteries and aortic arch. Concentration changes in certain substances, such as carbon dioxide or hydrogen ions, stimulate these receptors, which in turn signal the respiration centers of the brain. In the case of carbon dioxide, as the concentration of CO₂ in the blood increases, it readily diffuses across the blood-brain barrier, where it collects in the extracellular fluid. As will be explained in more detail later, increased carbon dioxide levels lead to increased levels of hydrogen ions, decreasing pH. The increase in hydrogen ions in the brain triggers the central chemoreceptors to stimulate the respiratory centers to initiate contraction of the diaphragm and intercostal muscles. As a result, the rate and depth of respiration increase, allowing more carbon dioxide to be expelled, which brings more air into and out of the lungs promoting a reduction in the blood levels of carbon dioxide, and therefore hydrogen ions, in the blood. In contrast, low levels of carbon dioxide in the blood cause low levels of hydrogen ions in the brain, leading to a decrease in the rate and depth of pulmonary ventilation, producing shallow, slow breathing.

Another factor involved in influencing the respiratory activity of the brain is systemic arterial concentrations of hydrogen ions. Increasing carbon dioxide levels can lead to increased H⁺ levels, as mentioned above, as well as other metabolic activities, such as lactic acid accumulation after strenuous exercise. Peripheral chemoreceptors of the aortic arch and carotid arteries sense arterial levels of hydrogen ions. When peripheral chemoreceptors sense decreasing, or more acidic, pH levels, they stimulate an increase in ventilation to remove carbon dioxide from the blood at a quicker rate. Removal of carbon dioxide from the blood helps to reduce hydrogen ions, thus increasing systemic pH.

Blood levels of oxygen are also important in influencing respiratory rate. The peripheral chemoreceptors are responsible for sensing large changes in blood oxygen levels. If blood oxygen levels become quite low—about 60 mm Hg or less—then peripheral chemoreceptors stimulate an increase in respiratory activity. The chemoreceptors are only able to sense dissolved oxygen molecules, not the oxygen that is bound to hemoglobin. As you recall, the majority of oxygen is bound by hemoglobin; when dissolved levels of oxygen drop, hemoglobin releases oxygen. Therefore, a large drop in oxygen levels is required to stimulate the chemoreceptors of the aortic arch and carotid arteries.

The hypothalamus and other brain regions associated with the limbic system also play roles in influencing the regulation of breathing by interacting with the respiratory centers. The hypothalamus and other regions associated with the limbic system are involved in regulating respiration in response to emotions, pain, and temperature. For example, an increase in body temperature causes an increase in respiratory rate. Feeling excited or the fight-or-flight response will also result in an increase in respiratory rate. Watch this CrashCourse video to earn more about the breathing process.

22.4 Gas Exchange

barkerj1 — Wed, 30 Aug 2017 18:41:01 +0000

Learning Objectives

By the end of this section, you will be able to:

Specify the major difference between oxygenated and deoxygenated blood
Explain the basic principle governing the reciprocal exchange of gases between the alveoli and the blood
Explain the basic principle governing the reciprocal exchange of gases between the blood and individual cells

The purpose of the respiratory system is to perform gas exchange. Pulmonary ventilation provides air to the alveoli for this gas exchange process. At the respiratory membrane, where the alveolar and capillary walls meet, gases move across the membranes, with oxygen entering the bloodstream and carbon dioxide exiting. It is through this mechanism that blood is oxygenated and carbon dioxide, the waste product of cellular respiration, is removed from the body.

Gas Exchange

In order to understand the mechanisms of gas exchange in the lung, it is important to understand the underlying principles of gases and their behavior. In addition to Boyle’s law, several other gas laws help to describe the behavior of gases.

Gas Laws and Air Composition

Gas molecules exert force on the surfaces with which they are in contact; this force is called pressure. In natural systems, gases are normally present as a mixture of different types of molecules. For example, the atmosphere consists of oxygen, nitrogen, carbon dioxide, and other gaseous molecules, and this gaseous mixture exerts a certain pressure referred to as atmospheric pressure (Table 2). Partial pressure (P_x) is the pressure of a single type of gas in a mixture of gases. For example, in the atmosphere, oxygen exerts a partial pressure, and nitrogen exerts another partial pressure, independent of the partial pressure of oxygen (Figure 1). Total pressure is the sum of all the partial pressures of a gaseous mixture. Dalton’s law describes the behavior of nonreactive gases in a gaseous mixture and states that a specific gas type in a mixture exerts its own pressure; thus, the total pressure exerted by a mixture of gases is the sum of the partial pressures of the gases in the mixture.

Partial Pressures of Atmospheric Gases (Table 2)
Gas	Percent of total composition	Partial pressure (mm Hg)
Nitrogen (N₂)	78.6	597.4
Oxygen (O₂)	20.9	158.8
Water (H₂O)	0.04	3.0
Carbon dioxide (CO₂)	0.004	0.3
Others	0.0006	0.5
Total composition/total atmospheric pressure	100%	760.0

[caption id="" align="aligncenter" width="420"] Figure 1. Partial and Total Pressures of a Gas. Partial pressure is the force exerted by a gas. The sum of the partial pressures of all the gases in a mixture equals the total pressure.[/caption]

Partial pressure is extremely important in predicting the movement of gases. Recall that gases tend to equalize their pressure in two regions that are connected. A gas will move from an area where its partial pressure is higher to an area where its partial pressure is lower. In addition, the greater the partial pressure difference between the two areas, the more rapid is the movement of gases.

Solubility of Gases in Liquids

Henry’s law describes the behavior of gases when they come into contact with a liquid, such as blood. Henry’s law states that the concentration of gas in a liquid is directly proportional to the solubility and partial pressure of that gas. The greater the partial pressure of the gas, the greater the number of gas molecules that will dissolve in the liquid. The concentration of the gas in a liquid is also dependent on the solubility of the gas in the liquid. For example, although nitrogen is present in the atmosphere, very little nitrogen dissolves into the blood, because the solubility of nitrogen in blood is very low. The exception to this occurs in scuba divers; the composition of the compressed air that divers breathe causes nitrogen to have a higher partial pressure than normal, causing it to dissolve in the blood in greater amounts than normal. Too much nitrogen in the bloodstream results in a serious condition that can be fatal if not corrected. Gas molecules establish an equilibrium between those molecules dissolved in liquid and those in air.

The composition of air in the atmosphere and in the alveoli differs. In both cases, the relative concentration of gases is nitrogen > oxygen > water vapor > carbon dioxide. The amount of water vapor present in alveolar air is greater than that in atmospheric air (Table 3). Recall that the respiratory system works to humidify incoming air, thereby causing the air present in the alveoli to have a greater amount of water vapor than atmospheric air. In addition, alveolar air contains a greater amount of carbon dioxide and less oxygen than atmospheric air. This is no surprise, as gas exchange removes oxygen from and adds carbon dioxide to alveolar air. Both deep and forced breathing cause the alveolar air composition to be changed more rapidly than during quiet breathing. As a result, the partial pressures of oxygen and carbon dioxide change, affecting the diffusion process that moves these materials across the membrane. This will cause oxygen to enter and carbon dioxide to leave the blood more quickly.

Composition and Partial Pressures of Alveolar Air (Table 3)
Gas	Percent of total composition	Partial pressure (mm Hg)
Nitrogen (N₂)	74.9	569
Oxygen (O₂)	13.7	104
Water (H₂O)	6.2	40
Carbon dioxide (CO₂)	5.2	47
Total composition/total alveolar pressure	100%	760.0

Ventilation and Perfusion

Two important aspects of gas exchange in the lung are ventilation and perfusion. Ventilation is the movement of air into and out of the lungs, and perfusion is the flow of blood in the pulmonary capillaries. For gas exchange to be efficient, the volumes involved in ventilation and perfusion should be compatible. However, factors such as regional gravity effects on blood, blocked alveolar ducts, or disease can cause ventilation and perfusion to be imbalanced.

The partial pressure of oxygen in alveolar air is about 104 mm Hg, whereas the partial pressure of the oxygenated pulmonary venous blood is about 100 mm Hg. When ventilation is sufficient, oxygen enters the alveoli at a high rate, and the partial pressure of oxygen in the alveoli remains high. In contrast, when ventilation is insufficient, the partial pressure of oxygen in the alveoli drops. Without the large difference in partial pressure between the alveoli and the blood, oxygen does not diffuse efficiently across the respiratory membrane. The body has mechanisms that counteract this problem. In cases when ventilation is not sufficient for an alveolus, the body redirects blood flow to alveoli that are receiving sufficient ventilation. This is achieved by constricting the pulmonary arterioles that serves the dysfunctional alveolus, which redirects blood to other alveoli that have sufficient ventilation. At the same time, the pulmonary arterioles that serve alveoli receiving sufficient ventilation vasodilate, which brings in greater blood flow. Factors such as carbon dioxide, oxygen, and pH levels can all serve as stimuli for adjusting blood flow in the capillary networks associated with the alveoli.

Ventilation is regulated by the diameter of the airways, whereas perfusion is regulated by the diameter of the blood vessels. The diameter of the bronchioles is sensitive to the partial pressure of carbon dioxide in the alveoli. A greater partial pressure of carbon dioxide in the alveoli causes the bronchioles to increase their diameter as will a decreased level of oxygen in the blood supply, allowing carbon dioxide to be exhaled from the body at a greater rate. As mentioned above, a greater partial pressure of oxygen in the alveoli causes the pulmonary arterioles to dilate, increasing blood flow.

Gas Exchange

Gas exchange occurs at two sites in the body: in the lungs, where oxygen is picked up and carbon dioxide is released at the respiratory membrane, and at the tissues, where oxygen is released and carbon dioxide is picked up. External respiration is the exchange of gases with the external environment, and occurs in the alveoli of the lungs. Internal respiration is the exchange of gases with the internal environment, and occurs in the tissues. The actual exchange of gases occurs due to simple diffusion. Energy is not required to move oxygen or carbon dioxide across membranes. Instead, these gases follow pressure gradients that allow them to diffuse. The anatomy of the lung maximizes the diffusion of gases: The respiratory membrane is highly permeable to gases; the respiratory and blood capillary membranes are very thin; and there is a large surface area throughout the lungs.

External Respiration

The pulmonary artery carries deoxygenated blood into the lungs from the heart, where it branches and eventually becomes the capillary network composed of pulmonary capillaries. These pulmonary capillaries create the respiratory membrane with the alveoli (Figure 2). As the blood is pumped through this capillary network, gas exchange occurs. Although a small amount of the oxygen is able to dissolve directly into plasma from the alveoli, most of the oxygen is picked up by erythrocytes (red blood cells) and binds to a protein called hemoglobin, a process described later in this chapter. Oxygenated hemoglobin is red, causing the overall appearance of bright red oxygenated blood, which returns to the heart through the pulmonary veins. Carbon dioxide is released in the opposite direction of oxygen, from the blood to the alveoli. Some of the carbon dioxide is returned on hemoglobin, but can also be dissolved in plasma or is present as a converted form, also explained in greater detail later in this chapter.

External respiration occurs as a function of partial pressure differences in oxygen and carbon dioxide between the alveoli and the blood in the pulmonary capillaries.

[caption id="" align="aligncenter" width="425"] Figure 3. External Respiration. In external respiration, oxygen diffuses across the respiratory membrane from the alveolus to the capillary, whereas carbon dioxide diffuses out of the capillary into the alveolus.[/caption]

Although the solubility of oxygen in blood is not high, there is a drastic difference in the partial pressure of oxygen in the alveoli versus in the blood of the pulmonary capillaries. This difference is about 64 mm Hg: The partial pressure of oxygen in the alveoli is about 104 mm Hg, whereas its partial pressure in the blood of the capillary is about 40 mm Hg. This large difference in partial pressure creates a very strong pressure gradient that causes oxygen to rapidly cross the respiratory membrane from the alveoli into the blood.

The partial pressure of carbon dioxide is also different between the alveolar air and the blood of the capillary. However, the partial pressure difference is less than that of oxygen, about 5 mm Hg. The partial pressure of carbon dioxide in the blood of the capillary is about 45 mm Hg, whereas its partial pressure in the alveoli is about 40 mm Hg. However, the solubility of carbon dioxide is much greater than that of oxygen—by a factor of about 20—in both blood and alveolar fluids. As a result, the relative concentrations of oxygen and carbon dioxide that diffuse across the respiratory membrane are similar.

Internal Respiration

Internal respiration is gas exchange that occurs at the level of body tissues (Figure 3). Similar to external respiration, internal respiration also occurs as simple diffusion due to a partial pressure gradient. However, the partial pressure gradients are opposite of those present at the respiratory membrane. The partial pressure of oxygen in tissues is low, about 40 mm Hg, because oxygen is continuously used for cellular respiration. In contrast, the partial pressure of oxygen in the blood is about 100 mm Hg. This creates a pressure gradient that causes oxygen to dissociate from hemoglobin, diffuse out of the blood, cross the interstitial space, and enter the tissue. Hemoglobin that has little oxygen bound to it loses much of its brightness, so that blood returning to the heart is more burgundy in color.

Considering that cellular respiration continuously produces carbon dioxide, the partial pressure of carbon dioxide is lower in the blood than it is in the tissue, causing carbon dioxide to diffuse out of the tissue, cross the interstitial fluid, and enter the blood. It is then carried back to the lungs either bound to hemoglobin, dissolved in plasma, or in a converted form. By the time blood returns to the heart, the partial pressure of oxygen has returned to about 40 mm Hg, and the partial pressure of carbon dioxide has returned to about 45 mm Hg. The blood is then pumped back to the lungs to be oxygenated once again during external respiration.

[caption id="" align="aligncenter" width="425"] Figure 3. Internal Respiration. Oxygen diffuses out of the capillary and into cells, whereas carbon dioxide diffuses out of cells and into the capillary.[/caption]

22.5 Transport of Gases

barkerj1 — Wed, 30 Aug 2017 18:41:06 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the mechanisms by which oxygen and carbon dioxide are transported in the blood

The other major activity in the lungs is the process of respiration, the process of gas exchange. The function of respiration is to provide oxygen for use by body cells during cellular respiration and to eliminate carbon dioxide, a waste product of cellular respiration, from the body. In order for the exchange of oxygen and carbon dioxide to occur, both gases must be transported between the external and internal respiration sites. Although carbon dioxide is more soluble than oxygen in blood, both gases require a specialized transport system for the majority of the gas molecules to be moved between the lungs and other tissues.

Oxygen Transport in the Blood

Even though oxygen is transported via the blood, you may recall that oxygen is not very soluble in liquids. A small amount of oxygen does dissolve in the blood and is transported in the bloodstream, but it is only about 1.5% of the total amount. The majority of oxygen molecules are carried from the lungs to the body’s tissues by a specialized transport system, which relies on the erythrocyte—the red blood cell. Erythrocytes contain a metalloprotein, hemoglobin, which serves to bind oxygen molecules to the erythrocyte (Figure 1). Heme is the portion of hemoglobin that contains iron, and it is heme that binds oxygen. One hemoglobin molecule contains iron-containing Heme molecules, and because of this, each hemoglobin molecule is capable of carrying up to four molecules of oxygen. As oxygen diffuses across the respiratory membrane from the alveolus to the capillary, it also diffuses into the red blood cell and is bound by hemoglobin. The following reversible chemical reaction describes the production of the final product, oxyhemoglobin (Hb–O₂), which is formed when oxygen binds to hemoglobin. Oxyhemoglobin is a bright red-colored molecule that contributes to the bright red color of oxygenated blood.

Hb + O₂ ↔ Hb − O₂

In this formula, Hb represents reduced hemoglobin, that is, hemoglobin that does not have oxygen bound to it. There are multiple factors involved in how readily heme binds to and dissociates from oxygen, which will be discussed in the subsequent sections.

[caption id="" align="aligncenter" width="300"] Figure 1. Erythrocyte and Hemoglobin. Hemoglobin consists of four subunits, each of which contains one molecule of iron.[/caption]

Function of Hemoglobin

Hemoglobin is composed of subunits, a protein structure that is referred to as a quaternary structure. Each of the four subunits that make up hemoglobin is arranged in a ring-like fashion, with an iron atom covalently bound to the heme in the center of each subunit. Binding of the first oxygen molecule causes a conformational change in hemoglobin that allows the second molecule of oxygen to bind more readily. As each molecule of oxygen is bound, it further facilitates the binding of the next molecule, until all four heme sites are occupied by oxygen. The opposite occurs as well: After the first oxygen molecule dissociates and is “dropped off” at the tissues, the next oxygen molecule dissociates more readily. When all four heme sites are occupied, the hemoglobin is said to be saturated. When one to three heme sites are occupied, the hemoglobin is said to be partially saturated. Therefore, when considering the blood as a whole, the percent of the available heme units that are bound to oxygen at a given time is called hemoglobin saturation. Hemoglobin saturation of 100 percent means that every heme unit in all of the erythrocytes of the body is bound to oxygen. In a healthy individual with normal hemoglobin levels, hemoglobin saturation generally ranges from 95 percent to 99 percent.

Oxygen Dissociation from Hemoglobin

Partial pressure is an important aspect of the binding of oxygen to and disassociation from heme. An oxygen–hemoglobin dissociation curve is a graph that describes the relationship of partial pressure to the binding of oxygen to heme and its subsequent dissociation from heme (Figure 2). Remember that gases travel from an area of higher partial pressure to an area of lower partial pressure. In addition, the affinity of an oxygen molecule for heme increases as more oxygen molecules are bound. Therefore, in the oxygen–hemoglobin saturation curve, as the partial pressure of oxygen increases, a proportionately greater number of oxygen molecules are bound by heme. Not surprisingly, the oxygen–hemoglobin saturation/dissociation curve also shows that the lower the partial pressure of oxygen, the fewer oxygen molecules are bound to heme. As a result, the partial pressure of oxygen plays a major role in determining the degree of binding of oxygen to heme at the site of the respiratory membrane, as well as the degree of dissociation of oxygen from heme at the site of body tissues.

[caption id="" align="aligncenter" width="400"] Figure 2. Oxygen-Hemoglobin Dissociation and Effects of pH and Temperature. These three graphs show (a) the relationship between the partial pressure of oxygen and hemoglobin saturation, (b) the effect of pH on the oxygen–hemoglobin dissociation curve, and (c) the effect of temperature on the oxygen–hemoglobin dissociation curve.[/caption]

The mechanisms behind the oxygen–hemoglobin saturation/dissociation curve also serve as automatic control mechanisms that regulate how much oxygen is delivered to different tissues throughout the body. This is important because some tissues have a higher metabolic rate than others. Highly active tissues, such as muscle, rapidly use oxygen to produce ATP, lowering the partial pressure of oxygen in the tissue to about 20 mm Hg. The partial pressure of oxygen inside capillaries is about 100 mm Hg, so the difference between the two becomes quite high, about 80 mm Hg. As a result, a greater number of oxygen molecules dissociate from hemoglobin and enter the tissues. The reverse is true of tissues, such as adipose (body fat), which have lower metabolic rates. Because less oxygen is used by these cells, the partial pressure of oxygen within such tissues remains relatively high, resulting in fewer oxygen molecules dissociating from hemoglobin and entering the tissue interstitial fluid. Although venous blood is said to be deoxygenated, some oxygen is still bound to hemoglobin in its red blood cells. This provides an oxygen reserve that can be used when tissues suddenly demand more oxygen.

Factors other than partial pressure also affect the oxygen–hemoglobin saturation/dissociation curve. For example, a higher temperature promotes hemoglobin and oxygen to dissociate faster, whereas a lower temperature inhibits dissociation (see Figure 2, middle). However, the human body tightly regulates temperature, so this factor may not affect gas exchange throughout the body. The exception to this is in highly active tissues, which may release a larger amount of energy than is given off as heat. As a result, oxygen readily dissociates from hemoglobin, which is a mechanism that helps to provide active tissues with more oxygen.

Certain hormones, such as androgens, epinephrine, thyroid hormones, and growth hormone, can affect the oxygen–hemoglobin saturation/disassociation curve by stimulating the production of a compound called 2,3-bisphosphoglycerate (BPG) by erythrocytes. BPG is a byproduct of glycolysis. Because erythrocytes do not contain mitochondria, glycolysis is the sole method by which these cells produce ATP. BPG promotes the disassociation of oxygen from hemoglobin. Therefore, the greater the concentration of BPG, the more readily oxygen dissociates from hemoglobin, despite its partial pressure.

The pH of the blood is another factor that influences the oxygen–hemoglobin saturation/dissociation curve (see Figure 2). The Bohr effect is a phenomenon that arises from the relationship between pH and oxygen’s affinity for hemoglobin: A lower, more acidic pH promotes oxygen dissociation from hemoglobin. In contrast, a higher, or more basic, pH inhibits oxygen dissociation from hemoglobin. The greater the amount of carbon dioxide in the blood, the more molecules that must be converted, which in turn generates hydrogen ions and thus lowers blood pH. Furthermore, blood pH may become more acidic when certain byproducts of cell metabolism, such as lactic acid, carbonic acid, and carbon dioxide, are released into the bloodstream.

Hemoglobin of the Fetus

The fetus has its own circulation with its own erythrocytes; however, it is dependent on the mother for oxygen. Blood is supplied to the fetus by way of the umbilical cord, which is connected to the placenta and separated from maternal blood by the chorion. The mechanism of gas exchange at the chorion is similar to gas exchange at the respiratory membrane. However, the partial pressure of oxygen is lower in the maternal blood in the placenta, at about 35 to 50 mm Hg, than it is in maternal arterial blood. The difference in partial pressures between maternal and fetal blood is not large, as the partial pressure of oxygen in fetal blood at the placenta is about 20 mm Hg. Therefore, there is not as much diffusion of oxygen into the fetal blood supply. The fetus’ hemoglobin overcomes this problem by having a greater affinity for oxygen than maternal hemoglobin (Figure 3). Both fetal and adult hemoglobin have four subunits, but two of the subunits of fetal hemoglobin have a different structure that causes fetal hemoglobin to have a greater affinity for oxygen than does adult hemoglobin.

[caption id="" align="aligncenter" width="430"] Figure 3. Oxygen-Hemoglobin Dissociation Curves in Fetus and Adult. Fetal hemoglobin has a greater affinity for oxygen than does adult hemoglobin.[/caption]

Carbon Dioxide Transport in the Blood

Carbon dioxide is transported by three major mechanisms. The first mechanism of carbon dioxide transport is by blood plasma, as some carbon dioxide molecules dissolve in the blood. The second mechanism is transport in the form of bicarbonate (HCO₃^–), which also dissolves in plasma. The third mechanism of carbon dioxide transport is similar to the transport of oxygen by erythrocytes (Figure 4).

[caption id="" align="aligncenter" width="435"] Carbon Dioxide Transport Carbon dioxide is transported by three different methods: (a) in erythrocytes; (b) after forming carbonic acid (H₂CO₃ ), which is dissolved in plasma; (c) and in plasma.[/caption]

Dissolved Carbon Dioxide

Although carbon dioxide is not considered to be highly soluble in blood, a small fraction—about 7 to 10 percent—of the carbon dioxide that diffuses into the blood from the tissues dissolves in plasma. The dissolved carbon dioxide then travels in the bloodstream and when the blood reaches the pulmonary capillaries, the dissolved carbon dioxide diffuses across the respiratory membrane into the alveoli, where it is then exhaled during pulmonary ventilation.

Bicarbonate Buffer

A large fraction—about 70 percent—of the carbon dioxide molecules that diffuse into the blood is transported to the lungs as bicarbonate. Most bicarbonate is produced in erythrocytes after carbon dioxide diffuses into the capillaries, and subsequently into red blood cells. Carbonic anhydrase (CA) causes carbon dioxide and water to form carbonic acid (H₂CO₃), which dissociates into two ions: bicarbonate (HCO₃^–) and hydrogen (H⁺). The following formula depicts this reaction:

CO₂ + H₂O CA ↔ H₂CO₃↔H⁺ + HCO₃₋

Bicarbonate tends to build up in the erythrocytes, so that there is a greater concentration of bicarbonate in the erythrocytes than in the surrounding blood plasma. As a result, some of the bicarbonate will leave the erythrocytes and move down its concentration gradient into the plasma in exchange for chloride (Cl^–) ions. This phenomenon is referred to as the chloride shift and occurs because by exchanging one negative ion for another negative ion, neither the electrical charge of the erythrocytes nor that of the blood is altered.

At the pulmonary capillaries, the chemical reaction that produced bicarbonate (shown above) is reversed, and carbon dioxide and water are the products. Much of the bicarbonate in the plasma re-enters the erythrocytes in exchange for chloride ions. Hydrogen ions and bicarbonate ions join to form carbonic acid, which is converted into carbon dioxide and water by carbonic anhydrase. Carbon dioxide diffuses out of the erythrocytes and into the plasma, where it can further diffuse across the respiratory membrane into the alveoli to be exhaled during pulmonary ventilation.

Carbaminohemoglobin

About 20 percent of carbon dioxide is bound by hemoglobin and is transported to the lungs. Carbon dioxide does not bind to iron as oxygen does; instead, carbon dioxide binds amino acid moieties on the globin portions of hemoglobin to form carbaminohemoglobin, which forms when hemoglobin and carbon dioxide bind. When hemoglobin is not transporting oxygen, it tends to have a bluish-purple tone to it, creating the darker maroon color typical of deoxygenated blood. The following formula depicts this reversible reaction:

CO₂ + Hb ↔ HbCO₂

Similar to the transport of oxygen by heme, the binding and dissociation of carbon dioxide to and from hemoglobin is dependent on the partial pressure of carbon dioxide. Because carbon dioxide is released from the lungs, blood that leaves the lungs and reaches body tissues has a lower partial pressure of carbon dioxide than is found in the tissues. As a result, carbon dioxide leaves the tissues because of its higher partial pressure, enters the blood, and then moves into red blood cells, binding to hemoglobin. In contrast, in the pulmonary capillaries, the partial pressure of carbon dioxide is high compared to within the alveoli. As a result, carbon dioxide dissociates readily from hemoglobin and diffuses across the respiratory membrane into the air.

In addition to the partial pressure of carbon dioxide, the oxygen saturation of hemoglobin and the partial pressure of oxygen in the blood also influence the affinity of hemoglobin for carbon dioxide. The Haldane effect is a phenomenon that arises from the relationship between the partial pressure of oxygen and the affinity of hemoglobin for carbon dioxide. Hemoglobin that is saturated with oxygen does not readily bind carbon dioxide. However, when oxygen is not bound to heme and the partial pressure of oxygen is low, hemoglobin readily binds to carbon dioxide. [caption id="attachment_2986" align="aligncenter" width="150"] Watch this CrashCourse video for an overview of how oxygen is exchanged![/caption]

22.6 Modifications in Respiratory Functions

barkerj1 — Wed, 30 Aug 2017 18:41:07 +0000

Learning Objectives

By the end of this section, you will be able to:

Define hypoxia
Identify some causes of hypoxia, giving examples for each
Specify some physiological consequences of hypoxia
Define hyperventilation
Identify some causes of hyperventilation
Explain the physiological effects of hyperventilation

At rest, the respiratory system performs its functions at a constant, rhythmic pace, as regulated by the respiratory centers of the brain. At this pace, ventilation provides sufficient oxygen to all the tissues of the body. However, there are times that the respiratory system must alter the pace of its functions in order to accommodate the oxygen demands of the body.

Hyperpnea

Hyperpnea is an increased depth and rate of ventilation to meet an increase in oxygen demand as might be seen in exercise or disease, particularly diseases that target the respiratory or digestive tracts. This does not significantly alter blood oxygen or carbon dioxide levels, but merely increases the depth and rate of ventilation to meet the demand of the cells. In contrast, hyperventilation is an increased ventilation rate that is independent of the cellular oxygen needs and leads to abnormally low blood carbon dioxide levels and high (alkaline) blood pH.

Interestingly, exercise does not cause hyperpnea as one might think. Muscles that perform work during exercise do increase their demand for oxygen, stimulating an increase in ventilation. However, hyperpnea during exercise appears to occur before a drop in oxygen levels within the muscles can occur. Therefore, hyperpnea must be driven by other mechanisms, either instead of or in addition to a drop in oxygen levels. The exact mechanisms behind exercise hyperpnea are not well understood, and some hypotheses are somewhat controversial. However, in addition to low oxygen, high carbon dioxide, and low pH levels, there appears to be a complex interplay of factors related to the nervous system and the respiratory centers of the brain.

First, a conscious decision to partake in exercise, or another form of physical exertion, results in a psychological stimulus that may trigger the respiratory centers of the brain to increase ventilation. In addition, the respiratory centers of the brain may be stimulated through the activation of motor neurons that innervate muscle groups that are involved in the physical activity. Finally, physical exertion stimulates proprioceptors, which are receptors located within the muscles, joints, and tendons, which sense movement and stretching; proprioceptors thus create a stimulus that may also trigger the respiratory centers of the brain. These neural factors are consistent with the sudden increase in ventilation that is observed immediately as exercise begins. Because the respiratory centers are stimulated by psychological, motor neuron, and proprioceptor inputs throughout exercise, the fact that there is also a sudden decrease in ventilation immediately after the exercise ends when these neural stimuli cease, further supports the idea that they are involved in triggering the changes of ventilation.

In contrast to hyperpnea, hyperventilation is independent of physiological oxygen demands. Instead, it may be caused by abnormal functioning of the lungs as a result of conditions such as asthma or early emphysema). It may also be caused by increased metabolism as a result of such conditions as hyperthyroidism, infection, or fever. Although it has no effect on oxygen levels in the blood, hyperventilation significantly reduces the amount of carbon dioxide in the blood. This reduction in CO₂ levels in turn leads to reduced carbonic acid levels in the blood, which results in alkalosis (blood plasma pH higher than normal). Decreased blood CO₂ also decreases blood pressure, as the signals coming from peripheral CO₂ receptors (normally stimulated by CO₂) decrease in frequency and cause the vasomotor centre in the medulla oblongata to reduce constriction of the smooth muscle fibres in the walls of blood vessels and allow vasodilation. Finally, low CO₂ and the associated high pH interfere with the ability of hemoglobin to release oxygen molecules to body tissues, including the brain, which can cause dizziness or unconsciousness.

High Altitude Effects

An increase in altitude results in a decrease in atmospheric pressure. Although the proportion of oxygen relative to gases in the atmosphere remains at 21 percent, its partial pressure decreases (Table 4). As a result, it is more difficult for a body to achieve the same level of oxygen saturation at high altitude than at low altitude, due to lower atmospheric pressure. In fact, hemoglobin saturation is lower at high altitudes compared to hemoglobin saturation at sea level. For example, hemoglobin saturation is about 67 percent at 19,000 feet above sea level, whereas it reaches about 98 percent at sea level.

Partial Pressure of Oxygen at Different Altitudes (Table 4)
Example location	Altitude (feet above sea level)	Atmospheric pressure (mm Hg)	Partial pressure of oxygen (mm Hg)
New York City, New York	0	760	159
Boulder, Colorado	5000	632	133
Aspen, Colorado	8000	565	118
Pike’s Peak, Colorado	14,000	447	94
Denali (Mt. McKinley), Alaska	20,000	350	73
Mt. Everest, Tibet	29,000	260	54

As you recall, partial pressure is extremely important in determining how much gas can cross the respiratory membrane and enter the blood of the pulmonary capillaries. A lower partial pressure of oxygen means that there is a smaller difference in partial pressures between the alveoli and the blood, so less oxygen crosses the respiratory membrane. As a result, fewer oxygen molecules are bound by hemoglobin. Despite this, the tissues of the body still receive a sufficient amount of oxygen during rest at high altitudes. This is due to two major mechanisms. First, the number of oxygen molecules that enter the tissue from the blood is nearly equal between sea level and high altitudes. At sea level, hemoglobin saturation is higher, but only a quarter of the oxygen molecules are actually released into the tissue. At high altitudes, a greater proportion of molecules of oxygen are released into the tissues. Secondly, at high altitudes, a greater amount of BPG is produced by erythrocytes, which enhances the dissociation of oxygen from hemoglobin. Physical exertion, such as skiing or hiking, can lead to altitude sickness due to the low amount of oxygen reserves in the blood at high altitudes. At sea level, there is a large amount of oxygen reserve in venous blood (even though venous blood is thought of as “deoxygenated”) from which the muscles can draw during physical exertion. Because the oxygen saturation is much lower at higher altitudes, this venous reserve is small, resulting in pathological symptoms of low blood oxygen levels. You may have heard that it is important to drink more water when traveling at higher altitudes than you are accustomed to. This is because your body will increase micturition (urination) at high altitudes to counteract the effects of lower oxygen levels. By removing fluids, blood plasma levels drop but not the total number of erythrocytes. In this way, the overall concentration of erythrocytes in the blood increases, which helps tissues obtain the oxygen they need.

Acute mountain sickness (AMS), or altitude sickness, is a condition that results from acute exposure to high altitudes due to a low partial pressure of oxygen at high altitudes. AMS typically can occur at 2400 meters (8000 feet) above sea level. AMS is a result of low blood oxygen levels, as the body has acute difficulty adjusting to the low partial pressure of oxygen. In serious cases, AMS can cause pulmonary or cerebral edema. Symptoms of AMS include nausea, vomiting, fatigue, lightheadedness, drowsiness, feeling disoriented, increased pulse, and nosebleeds. The only treatment for AMS is descending to a lower altitude; however, pharmacologic treatments and supplemental oxygen can improve symptoms. AMS can be prevented by slowly ascending to the desired altitude, allowing the body to acclimate, as well as maintaining proper hydration.

Acclimatization

Especially in situations where the ascent occurs too quickly, traveling to areas of high altitude can cause AMS. Acclimatization is the process of adjustment that the respiratory system makes due to chronic exposure to a high altitude. Over a period of time, the body adjusts to accommodate the lower partial pressure of oxygen. The low partial pressure of oxygen at high altitudes results in a lower oxygen saturation level of hemoglobin in the blood. In turn, the tissue levels of oxygen are also lower. As a result, the kidneys are stimulated to produce the hormone erythropoietin (EPO), which stimulates the production of erythrocytes, resulting in a greater number of circulating erythrocytes in an individual at a high altitude over a long period. With more red blood cells, there is more hemoglobin to help transport the available oxygen. Even though there is low saturation of each hemoglobin molecule, there will be more hemoglobin present, and therefore more oxygen in the blood. Over time, this allows the person to partake in physical exertion without developing AMS.

Hypoxia

The effects of high altitude discussed above are in part the result of hypoxia, a reduction in the amount of oxygen reaching body tissues. Hypoxia may be caused by a deficiency in atmospheric oxygen, whether due to high altitude or being in an enclosed space with limited airflow (e.g. a crowded room with poor ventilation).

Hypoxia may also be caused by physiological problems with the respiratory or cardiovascular system. In the case of the respiratory system, any interference in the process of breathing (e.g. abnormal muscle contractions) or obstruction in the air passages (e.g. excessive mucus) will cause hypoxia by ventilatory deficiency. Alternatively, hypoxia may be caused by a pulmonary diffusion defect in which the diffusion of oxygen gas across the respiratory membrane is impaired. Fluid in the pulmonary alveoli, for example, increases the distance across which oxygen must diffuse through liquid, effectively increasing the thickness of the respiratory membrane and therefore slowing the rate at which oxygen can move into the blood. In the cardiovascular system, hypoxia may be caused by a hemoglobin deficiency or a circulatory deficiency. A hemoglobin deficiency may be the result of anemia, where there is a shortage of functional red blood cells. It may also be the result of conditions such as carbon monoxide poisoning, where carbon monoxide displaces oxygen bound to hemoglobin molecules, rendering the hemoglobin incapable of carrying oxygen and thus effectively nonfunctional. Circulatory deficiencies may be the result of obstruction of a blood vessel (e.g. as a result of atherosclerosis), of low blood pressure (hypotension), or of structural problems that make the cardiovascular system less efficient than it should normally be (e.g. if the ductus arteriosus or foramen ovale fail to close after birth). Finally, hypoxia may result from edema, where excessive fluid accumulates around cells, for example as a result of inflammation, renal failure, or congestive heart failure. This fluid buildup may occur in the lung tissue or alveoli (pulmonary edema), where it slows the diffusion of oxygen across respiratory membranes, or in other tissues where it can slow the diffusion of oxygen to body cells. Hypoxia can result in cyanosis, where the skin and mucous membranes take on a bluish (or purplish) discoloration. It can also result in tachycardia, or increased heart rate, and dizziness as a result of insufficient oxygen reaching the brain.

24.6 Energy and Heat Balance

barkerj1 — Wed, 30 Aug 2017 18:41:07 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the role of the skin in monitoring body temperature as an example of a negative feedback system

The body tightly regulates the body temperature through a process called thermoregulation, in which the body can maintain its temperature within certain boundaries, even when the surrounding temperature is very different. The core temperature of the body remains steady at around 36.5–37.5 °C (or 97.7–99.5 °F). In the process of ATP production by cells throughout the body, approximately 60 percent of the energy produced is in the form of heat used to maintain body temperature. Thermoregulation is an example of negative feedback.

The hypothalamus in the brain is the master switch that works as a thermostat to regulate the body’s core temperature (Figure 1). If the temperature is too high, the hypothalamus can initiate several processes to lower it. These include increasing the circulation of the blood to the surface of the body to allow for the dissipation of heat through the skin and initiation of sweating to allow evaporation of water on the skin to cool its surface. Conversely, if the temperature falls below the set core temperature, the hypothalamus can initiate shivering to generate heat. The body uses more energy and generates more heat. In addition, thyroid hormone will stimulate more energy use and heat production by cells throughout the body. An environment is said to be thermoneutral when the body does not expend or release energy to maintain its core temperature. For a naked human, this is an ambient air temperature of around 84 °F. If the temperature is higher, for example, when wearing clothes, the body compensates with cooling mechanisms. The body loses heat through the mechanisms of heat exchange.

[caption id="attachment_1826" align="aligncenter" width="500"] Figure 1. Hypothalamus Controls Thermoregulation. The hypothalamus controls thermoregulation.[/caption]

Mechanisms of Heat Exchange

When the environment is not thermoneutral, the body uses four mechanisms of heat exchange to maintain homeostasis: conduction, convection, radiation, and evaporation. Each of these mechanisms relies on the property of heat to flow from a higher concentration to a lower concentration; therefore, each of the mechanisms of heat exchange varies in rate according to the temperature and conditions of the environment.

Conduction is the transfer of heat by two objects that are in direct contact with one another. It occurs when the skin comes in contact with a cold or warm object. For example, when holding a glass of ice water, the heat from your skin will warm the glass and in turn melt the ice. Alternatively, on a cold day, you might warm up by wrapping your cold hands around a hot mug of coffee. Only about 3 percent of the body’s heat is lost through conduction.

Convection is the transfer of heat to the air surrounding the skin. The warmed air rises away from the body and is replaced by cooler air that is subsequently heated. Convection can also occur in water. When the water temperature is lower than the body’s temperature, the body loses heat by warming the water closest to the skin, which moves away to be replaced by cooler water. The convection currents created by the temperature changes continue to draw heat away from the body more quickly than the body can replace it, resulting in hyperthermia. About 15 percent of the body’s heat is lost through convection.

Radiation is the transfer of heat via infrared waves. This occurs between any two objects when their temperatures differ. A radiator can warm a room via radiant heat. On a sunny day, the radiation from the sun warms the skin. The same principle works from the body to the environment. About 60 percent of the heat lost by the body is lost through radiation.

Evaporation is the transfer of heat by the evaporation of water. Because it takes a great deal of energy for a water molecule to change from a liquid to a gas, evaporating water (in the form of sweat) takes with it a great deal of energy from the skin. However, the rate at which evaporation occurs depends on relative humidity—more sweat evaporates in lower humidity environments. Sweating is the primary means of cooling the body during exercise, whereas at rest, about 20 percent of the heat lost by the body occurs through evaporation.

Introduction

barkerj1 — Tue, 04 Apr 2017 22:16:37 +0000

Welcome to the Douglas College Anatomy & Physiology open textbook! This textbook is a project under development by our Biology faculty to ultimately provide students with all the factual information they need to succeed in the BIOL 1103 and BIOL 1109 courses at Douglas College in BC, Canada. Readers should be aware that the information herein is subject to change at any time as corrections, additions, or other important modifications are made. Only the most recent version will be considered to be complete and correct. The most recent version is accessible online at https://pressbooks.bccampus.ca/dcbiol11031109/, and the most recent version of the companion textbook (developed for Douglas College's BIOL 1203 and BIOL 1209 courses) is also accessible online at https://pressbooks.bccampus.ca/dcbiol12031209/. The material herein is drawn largely from the OpenStax Anatomy & Physiology textbook, also freely and perpetually available online at http://cnx.org/content/col11496/latest/. Chapter and section numbers have been left as they were in the version of the OpenStax A&P textbook from which they are drawn; some sections have been removed, and others have had some material added, to correspond with the curriculum used at Douglas College.

Authors

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Cover

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About

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Buy

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Access Denied

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Book Information

barkerj1 — Tue, 04 Apr 2017 22:16:37 +0000

Preface

barkerj1 — Tue, 05 Sep 2017 16:33:19 +0000

Human Anatomy and Physiology I is designed for the first of two introductory human anatomy and physiology course offered at Douglas College. The textbook follows the scope and sequence of our own Human Anatomy and Physiology courses, and its coverage and organization were informed by the instructors who teach the course here at Douglas College.

About Douglas College

Douglas College is located in the province of British Columbia, Canada, hosting local, domestic, and international students. This textbook was adapted directly from the Human Anatomy & Physiology textbook originally created by OpenStax College to suit the needs of our own students and instructors, and will continue to be adapted and updated as those needs are recognized and change over time.

About Anatomy and Physiology I

Anatomy and Physiology I is designed for the first of two introductory human anatomy and physiology course offered at Douglas College. The text focuses on directly addressing the Course Objectives defined for BIOL 1103 and BIOL 1109 at Douglas College, covering the most important concepts and aiming to minimize distracting students with more minor details.

The development choices for this textbook were made with the guidance of hundreds of faculty who are deeply involved in teaching this course. These choices led to innovations in art, terminology, career orientation, practical applications, and multimedia-based learning, all with a goal of increasing relevance to students. We strove to make the discipline meaningful and memorable to students, so that they can draw from it a working knowledge that will enrich their future studies.

Cost

This textbook and its companion textbook Human Anatomy & Physiology II are available for free online, and in low-cost print editions from the Douglas College Bookstore.

Coverage and Scope

The units of our Human Anatomy and Physiology textbooks adhere to the scope and sequence followed by our courses at Douglas College.

Unit 1: Levels of Organization

Chapters 1–4 provide students with a basic understanding of human anatomy and physiology, including its language, the levels of organization, and the basics of chemistry and cell biology. These chapters provide a foundation for the further study of the body. They also focus particularly on how the body’s regions, important chemicals, and cells maintain homeostasis.

Chapter 1 An Introduction to the Human Body Chapter 2 The Chemical Level of Organization Chapter 3 The Cellular Level of Organization Chapter 4 The Tissue Level of Organization

Unit 2: Support and Movement

In Chapters 5–11, students explore the skin, the largest organ of the body, and examine the body’s skeletal and muscular systems, following a traditional sequence of topics. This unit is the first to walk students through specific systems of the body, and as it does so, it maintains a focus on homeostasis as well as those diseases and conditions that can disrupt it.

Chapter 5 The Integumentary System Chapter 6 Bone and Skeletal Tissue Chapter 7 The Axial Skeleton Chapter 8 The Appendicular Skeleton Chapter 9 Joints Chapter 10 Muscle Tissue Chapter 11 The Muscular System

Unit 3: Regulation, Integration, and Control

Chapters 12–17 help students answer questions about nervous and endocrine system control and regulation. In a break with the traditional sequence of topics, the special senses are integrated into the chapter on the somatic nervous system. The chapter on the neurological examination offers students a unique approach to understanding nervous system function using five simple but powerful diagnostic tests.

Chapter 12 Introduction to the Nervous System Chapter 13 The Anatomy of the Nervous System Chapter 14 The Somatic Nervous System Chapter 15 The Autonomic Nervous System Chapter 16 The Neurological Exam Chapter 17 The Endocrine System

Unit 4: Fluids and Transport

In Chapters 18–21, students examine the principal means of transport for materials needed to support the human body, regulate its internal environment, and provide protection. Chapter 18 Blood Chapter 19 The Cardiovascular System: The Heart Chapter 20 The Cardiovascular System: Blood Vessels and Circulation Chapter 21 The Lymphatic System and Immunity

Unit 5: Energy, Maintenance, and Environmental Exchange

In Chapters 22–26, students discover the interaction between body systems and the outside environment for the exchange of materials, the capture of energy, the release of waste, and the overall maintenance of the internal systems that regulate the exchange. The explanations and illustrations are particularly focused on how structure relates to function.

Chapter 22 The Respiratory System Chapter 23 The Digestive System Chapter 24 Nutrition and Metabolism Chapter 25 The Urinary System Chapter 26 Fluid, Electrolyte, and Acid–Base Balance

Unit 6: Human Development and the Continuity of Life

The closing chapters examine the male and female reproductive systems, describe the process of human development and the different stages of pregnancy, and end with a review of the mechanisms of inheritance.

Chapter 27 The Reproductive System Chapter 28 Development and Genetic Inheritance

Pedagogical Foundation and Features

Anatomy and Physiology is designed to promote scientific literacy. Throughout the text, you will find features that engage the students by taking selected topics a step further.

Homeostatic Imbalances discusses the effects and results of imbalances in the body.
Disorders showcases a disorder that is relevant to the body system at hand. This feature may focus on a specific disorder, or a set of related disorders.
Diseases showcases a disease that is relevant to the body system at hand.
Aging explores the effect aging has on a body’s system and specific disorders that manifest over time.
Career Connections presents information on the various careers often pursued by allied health students, such as medical technician, medical examiner, and neurophysiologist. Students are introduced to the educational requirements for and day-to-day responsibilities in these careers.
Everyday Connections tie anatomical and physiological concepts to emerging issues and discuss these in terms of everyday life. Topics include “Anabolic Steroids” and “The Effect of Second-Hand Tobacco Smoke.”
Interactive Links direct students to online exercises, simulations, animations, and videos to add a fuller context to core content and help improve understanding of the material. Many features include links to the University of Michigan’s interactive WebScopes, which allow students to zoom in on micrographs in the collection. These resources were vetted by reviewers and other subject matter experts to ensure that they are effective and accurate. We strongly urge students to explore these links, whether viewing a video or inputting data into a simulation, to gain the fullest experience and to learn how to search for information independently.

Dynamic, Learner-Centered Art

Our unique approach to visuals is designed to emphasize only the components most important in any given illustration. The art style is particularly aimed at focusing student learning through a powerful blend of traditional depictions and instructional innovations.

Much of the art in this book consists of black line illustrations. The strongest line is used to highlight the most important structures, and shading is used to show dimension and shape. Color is used sparingly to highlight and clarify the primary anatomical or functional point of the illustration. This technique is intended to draw students’ attention to the critical learning point in the illustration, without distraction from excessive gradients, shadows, and highlights. Full color is used when the structure or process requires it (for example, muscle diagrams and cardiovascular system illustrations).

[caption id="" align="aligncenter" width="300"] The Pharynx. By highlighting the most important portions of the illustration, the artwork helps students focus on the most important points, without overwhelming them.[/caption]

Micrographs

Micrograph magnifications have been calculated based on the objective provided with the image. If a micrograph was recorded at 40×, and the image was magnified an additional 2×, the final magnification of the micrograph is indicated as 80×.

Please note that, when viewing the textbook electronically, the micrograph magnification provided in the text does not take into account the size and magnification of the screen on your electronic device. There may be some variation.

[caption id="" align="aligncenter" width="500"] Sebaceous Glands. These glands secrete oils that lubricate and protect the skin. LM × 400. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption]

About Our Team

Senior Contributing Authors

Jennifer M. Barker	Douglas College

Contributing Authors

Sarah McKinnon	Douglas College
Lois Schwarz	Douglas College

Special Thanks

The authors wish to thank all those who provided vital resources without which production of this textbook would not have been possible. First, we wish to thank OpenStax College in general and more specifically all the contributors to the Anatomy & Physiology textbook from which the majority of this textbook was derived. We also wish to thank BCcampus for financial and technical support throughout the adaptation of this textbook. Finally, we wish to thank the Douglas College Research and Scholarly Fund Adjudication Committee and the Douglas College Vice President's Academic Council for providing internal funding to allow the production and continued development of this work.

1103 Chapter 1. An Introduction to the Human Body

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1103 Chapter 2. The Chemical Level of Organization

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1103 Chapter 3. The Cellular Level of Organization

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1103 Chapter 4. The Tissue Level of Organization

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1103 Chapter 5. The Integumentary System

barkerj1 — Wed, 30 Aug 2017 18:37:13 +0000

1103 Chapter 6. Bone Tissue and the Skeletal System

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1103 Chapter 7. Axial Skeleton

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26.1 Body Fluids and Fluid Compartments

barkerj1 — Wed, 30 Aug 2017 18:41:10 +0000

Learning Objectives

By the end of this section, you will be able to:

Specify the percentage of body weight that is composed of water
Estimate the amount of body water you contain in litres
Describe the distribution of body water

The chemical reactions of life take place in aqueous solutions. The dissolved substances in a solution are called solutes. In the human body, solutes vary in different parts of the body, but may include proteins—including those that transport lipids, carbohydrates, and, very importantly, electrolytes. Often in medicine, a mineral dissociated from a salt that carries an electrical charge (an ion) is called and electrolyte. For instance, sodium ions (Na⁺) and chloride ions (Cl^-) are often referred to as electrolytes.

In the body, water moves through semi-permeable membranes of cells and from one compartment of the body to another by a process called osmosis. Osmosis is basically the diffusion of water from regions of higher concentration to regions of lower concentration, along an osmotic gradient across a semi-permeable membrane. As a result, water will move into and out of cells and tissues, depending on the relative concentrations of the water and solutes found there. An appropriate balance of solutes inside and outside of cells must be maintained to ensure normal function.

Body Water Content

Human beings are mostly water, ranging from about 75 percent of body mass in infants to about 50–60 percent in adult men and women, to as low as 45 percent in old age. The percent of body water changes with development, because the proportions of the body given over to each organ and to muscles, fat, bone, and other tissues change from infancy to adulthood (Figure 1). Your brain and kidneys have the highest proportions of water, which composes 80–85 percent of their masses. In contrast, teeth have the lowest proportion of water, at 8–10 percent.

[caption id="" align="aligncenter" width="450"] Figure 1. Water Content of the Body’s Organs and Tissues. Water content varies in different body organs and tissues, from as little as 8 percent in the teeth to as much as 85 percent in the brain.[/caption]

Fluid Compartments

Body fluids can be discussed in terms of their specific fluid compartment, a location that is largely separate from another compartment by some form of a physical barrier. The intracellular fluid (ICF) compartment is the system that includes all fluid enclosed in cells by their plasma membranes. Extracellular fluid (ECF) surrounds all cells in the body. Extracellular fluid has two primary constituents: the fluid component of the blood (called plasma) and the interstitial fluid (IF) that surrounds all cells not in the blood (Figure 2).

[caption id="" align="aligncenter" width="380"] Figure 2. Fluid Compartments in the Human Body. The intracellular fluid (ICF) is the fluid within cells. The interstitial fluid (IF) is part of the extracellular fluid (ECF) between the cells. Blood plasma is the second part of the ECF. Materials travel between cells and the plasma in capillaries through the IF.[/caption]

Intracellular Fluid

The ICF lies within cells and is the principal component of the cytosol/cytoplasm. The ICF makes up about 60 percent of the total water in the human body, and in an average-size adult male, the ICF accounts for about 25 liters (seven gallons) of fluid (Figure 3). This fluid volume tends to be very stable, because the amount of water in living cells is closely regulated. If the amount of water inside a cell falls to a value that is too low, the cytosol becomes too concentrated with solutes to carry on normal cellular activities; if too much water enters a cell, the cell may burst and be destroyed.

[caption id="" align="aligncenter" width="380"] Figure 3. A Pie Graph Showing the Proportion of Total Body Fluid in Each of the Body’s Fluid Compartments. Most of the water in the body is intracellular fluid. The second largest volume is the interstitial fluid, which surrounds cells that are not blood cells.[/caption]

Extracellular Fluid

The ECF accounts for the other one-third of the body’s water content. Approximately 20 percent of the ECF is found in plasma. Plasma travels through the body in blood vessels and transports a range of materials, including blood cells, proteins (including clotting factors and antibodies), electrolytes, nutrients, gases, and wastes. Gases, nutrients, and waste materials travel between capillaries and cells through the IF. Cells are separated from the IF by a selectively permeable cell membrane that helps regulate the passage of materials between the IF and the interior of the cell.

The body has other water-based ECF. These include the cerebrospinal fluid that bathes the brain and spinal cord, lymph, the synovial fluid in joints, the pleural fluid in the pleural cavities, the pericardial fluid in the cardiac sac, the peritoneal fluid in the peritoneal cavity, and the aqueous humor of the eye. Because these fluids are outside of cells, these fluids are also considered components of the ECF compartment.

Composition of Body Fluids

The compositions of the two components of the ECF—plasma and IF—are more similar to each other than either is to the ICF (Figure 4). Blood plasma has high concentrations of sodium, chloride, bicarbonate, and protein. The IF has high concentrations of sodium, chloride, and bicarbonate, but a relatively lower concentration of protein. In contrast, the ICF has elevated amounts of potassium, phosphate, magnesium, and protein. Overall, the ICF contains high concentrations of potassium and phosphate (HPO42−HPO42−), whereas both plasma and the ECF contain high concentrations of sodium and chloride.

[caption id="" align="aligncenter" width="380"] Figure 4. The Concentrations of Different Elements in Key Bodily Fluids. The graph shows the composition of the ICF, IF, and plasma. The compositions of plasma and IF are similar to one another but are quite different from the composition of the ICF.[/caption]

Most body fluids are neutral in charge. Thus, cations, or positively charged ions, and anions, or negatively charged ions, are balanced in fluids. As seen in the previous graph, sodium (Na⁺) ions and chloride (Cl^-) ions are concentrated in the ECF of the body, whereas potassium (K⁺) ions are concentrated inside cells. Although sodium and potassium can “leak” through “pores” into and out of cells, respectively, the high levels of potassium and low levels of sodium in the ICF are maintained by sodium-potassium pumps in the cell membranes. These pumps use the energy supplied by ATP to pump sodium out of the cell and potassium into the cell (Figure 5).

[caption id="" align="aligncenter" width="520"] Figure 5. The Sodium-Potassium Pump. The sodium-potassium pump is powered by ATP to transfer sodium out of the cytoplasm and into the ECF. The pump also transfers potassium out of the ECF and into the cytoplasm. (credit: modification of work by Mariana Ruiz Villarreal)[/caption]

Fluid Movement between Compartments

Hydrostatic pressure, the force exerted by a fluid against a wall, causes movement of fluid between compartments. The hydrostatic pressure of blood is the pressure exerted by blood against the walls of the blood vessels by the pumping action of the heart. In capillaries, hydrostatic pressure (also known as capillary blood pressure) is higher than the opposing “colloid osmotic pressure” in blood—a “constant” pressure primarily produced by circulating albumin—at the arteriolar end of the capillary (Figure 6). This pressure forces plasma and nutrients out of the capillaries and into surrounding tissues. Fluid and the cellular wastes in the tissues enter the capillaries at the venule end, where the hydrostatic pressure is less than the osmotic pressure in the vessel. Filtration pressure squeezes fluid from the plasma in the blood to the IF surrounding the tissue cells. The surplus fluid in the interstitial space that is not returned directly back to the capillaries is drained from tissues by the lymphatic system, and then re-enters the vascular system at the subclavian veins.

[caption id="" align="aligncenter" width="480"] Figure 6. Capillary Exchange. Net filtration occurs near the arterial end of the capillary since capillary hydrostatic pressure (CHP) is greater than blood colloidal osmotic pressure (BCOP). There is no net movement of fluid near the midpoint of the capillary since CHP = BCOP. Net reabsorption occurs near the venous end of the capillary since BCOP is greater than CHP.[/caption]

Hydrostatic pressure is especially important in governing the movement of water in the nephrons of the kidneys to ensure proper filtering of the blood to form urine. As hydrostatic pressure in the kidneys increases, the amount of water leaving the capillaries also increases, and more urine filtrate is formed. If hydrostatic pressure in the kidneys drops too low, as can happen in dehydration, the functions of the kidneys will be impaired, and less nitrogenous wastes will be removed from the bloodstream. Extreme dehydration can result in kidney failure.

Fluid also moves between compartments along an osmotic gradient. Recall that an osmotic gradient is produced by the difference in concentration of all solutes on either side of a semi-permeable membrane. The magnitude of the osmotic gradient is proportional to the difference in the concentration of solutes on one side of the cell membrane to that on the other side. Water will move by osmosis from the side where its concentration is high (and the concentration of solute is low) to the side of the membrane where its concentration is low (and the concentration of solute is high). In the body, water moves by osmosis from plasma to the IF (and the reverse) and from the IF to the ICF (and the reverse). In the body, water moves constantly into and out of fluid compartments as conditions change in different parts of the body.

For example, if you are sweating, you will lose water through your skin. Sweating depletes your tissues of water and increases the solute concentration in those tissues. As this happens, water diffuses from your blood into sweat glands and surrounding skin tissues that have become dehydrated because of the osmotic gradient. Additionally, as water leaves the blood, it is replaced by the water in other tissues throughout your body that are not dehydrated. If this continues, dehydration spreads throughout the body. When a dehydrated person drinks water and rehydrates, the water is redistributed by the same gradient, but in the opposite direction, replenishing water in all of the tissues.

Solute Movement between Compartments

The movement of some solutes between compartments is active, which consumes energy and is an active transport process, whereas the movement of other solutes is passive, which does not require energy. Active transport allows cells to move a specific substance against its concentration gradient through a membrane protein, requiring energy in the form of ATP. For example, the sodium-potassium pump employs active transport to pump sodium out of cells and potassium into cells, with both substances moving against their concentration gradients.

Passive transport of a molecule or ion depends on its ability to pass through the membrane, as well as the existence of a concentration gradient that allows the molecules to diffuse from an area of higher concentration to an area of lower concentration. Some molecules, like gases, lipids, and water itself (which also utilizes water channels in the membrane called aquaporins), slip fairly easily through the cell membrane; others, including polar molecules like glucose, amino acids, and ions do not. Some of these molecules enter and leave cells using facilitated transport, whereby the molecules move down a concentration gradient through specific protein channels in the membrane. This process does not require energy. For example, glucose is transferred into cells by glucose transporters that use facilitated transport (Figure 7).

[caption id="" align="aligncenter" width="480"] Figure 7. Facilitated Diffusion. Glucose molecules use facilitated diffusion to move down a concentration gradient through the carrier protein channels in the membrane. (credit: modification of work by Mariana Ruiz Villarreal)[/caption]

Disorders of the…

Fluid Balance: Edema Edema is the accumulation of excess water in the tissues. It is most common in the soft tissues of the extremities. The physiological causes of edema include water leakage from blood capillaries. Edema is almost always caused by an underlying medical condition, by the use of certain therapeutic drugs, by pregnancy, by localized injury, or by an allergic reaction. In the limbs, the symptoms of edema include swelling of the subcutaneous tissues, an increase in the normal size of the limb, and stretched, tight skin. One quick way to check for subcutaneous edema localized in a limb is to press a finger into the suspected area. Edema is likely if the depression persists for several seconds after the finger is removed (which is called “pitting”).

Pulmonary edema is excess fluid in the air sacs of the lungs, a common symptom of heart and/or kidney failure. People with pulmonary edema likely will experience difficulty breathing, and they may experience chest pain. Pulmonary edema can be life threatening, because it compromises gas exchange in the lungs, and anyone having symptoms should immediately seek medical care.

In pulmonary edema resulting from heart failure, excessive leakage of water occurs because fluids get “backed up” in the pulmonary capillaries of the lungs, when the left ventricle of the heart is unable to pump sufficient blood into the systemic circulation. Because the left side of the heart is unable to pump out its normal volume of blood, the blood in the pulmonary circulation gets “backed up,” starting with the left atrium, then into the pulmonary veins, and then into pulmonary capillaries. The resulting increased hydrostatic pressure within pulmonary capillaries, as blood is still coming in from the pulmonary arteries, causes fluid to be pushed out of them and into lung tissues.

Other causes of edema include damage to blood vessels and/or lymphatic vessels, or a decrease in osmotic pressure in chronic and severe liver disease, where the liver is unable to manufacture plasma proteins (Figure 8). A decrease in the normal levels of plasma proteins results in a decrease of colloid osmotic pressure (which counterbalances the hydrostatic pressure) in the capillaries. This process causes loss of water from the blood to the surrounding tissues, resulting in edema.

[caption id="" align="aligncenter" width="350"] Figure 8. Edema. An allergic reaction can cause capillaries in the hand to leak excess fluid that accumulates in the tissues. (credit: Jane Whitney)[/caption]

Mild, transient edema of the feet and legs may be caused by sitting or standing in the same position for long periods of time, as in the work of a toll collector or a supermarket cashier. This is because deep veins in the lower limbs rely on skeletal muscle contractions to push on the veins and thus “pump” blood back to the heart. Otherwise, the venous blood pools in the lower limbs and can leak into surrounding tissues.

Medications that can result in edema include vasodilators, calcium channel blockers used to treat hypertension, non-steroidal anti-inflammatory drugs, estrogen therapies, and some diabetes medications. Underlying medical conditions that can contribute to edema include congestive heart failure, kidney damage and kidney disease, disorders that affect the veins of the legs, and cirrhosis and other liver disorders.

Therapy for edema usually focuses on elimination of the cause. Activities that can reduce the effects of the condition include appropriate exercises to keep the blood and lymph flowing through the affected areas. Other therapies include elevation of the affected part to assist drainage, massage and compression of the areas to move the fluid out of the tissues, and decreased salt intake to decrease sodium and water retention.

Muscle Anatomy Review

barkerj1 — Wed, 30 Aug 2017 18:41:12 +0000

All images by Henry Gray (1918), Anatomy of the Human Body, Bartleby.com http://www.bartleby.com/107/indexillus.html

10.7 Cardiac Muscle Tissue

barkerj1 — Sat, 21 Apr 2018 20:31:30 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the microscopic anatomy of cardiac muscle cells by outlining the structure and function of:
- Intercalated discs
- Sarcomeres
- T-tubules and the sarcoplasmic reticulum
Describe the mechanism of contraction in cardiac muscle, including the triggers for calcium release, the roles of calcium during contraction, and the source of energy for cardiac muscle cells
Describe the functional significance of self-excitatory cardiac muscle cells

Cardiac muscle tissue is only found in the heart. Highly coordinated contractions of cardiac muscle pump blood into the vessels of the circulatory system. Similar to skeletal muscle, cardiac muscle is striated and organized into sarcomeres, possessing the same banding organization as skeletal muscle (Figure 1). However, cardiac muscle fibers are shorter than skeletal muscle fibers and usually contain only one nucleus, which is located in the central region of the cell. Cardiac muscle fibers also possess many mitochondria and myoglobin, as ATP is produced primarily through aerobic metabolism. Cardiac muscle fibers cells also are extensively branched and are connected to one another at their ends by intercalated discs. An intercalated disc allows the cardiac muscle cells to contract in a wave-like pattern so that the heart can work as a pump.

[caption id="" align="aligncenter" width="380"] Figure 1. Cardiac Muscle Tissue. Cardiac muscle tissue is only found in the heart. LM × 1600. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption]

Intercalated discs are part of the sarcolemma and contain two structures important in cardiac muscle contraction: gap junctions and desmosomes. A gap junction forms channels between adjacent cardiac muscle fibers that allow the depolarizing current produced by cations to flow from one cardiac muscle cell to the next. This joining is called electric coupling, and in cardiac muscle it allows the quick transmission of action potentials and the coordinated contraction of the entire heart. This network of electrically connected cardiac muscle cells creates a functional unit of contraction called a syncytium. The remainder of the intercalated disc is composed of desmosomes. A desmosome is a cell structure that anchors the ends of cardiac muscle fibers together so the cells do not pull apart during the stress of individual fibers contracting (Figure 2).

[caption id="" align="aligncenter" width="480"] Figure 2. Cardiac Muscle. Intercalated discs are part of the cardiac muscle sarcolemma and they contain gap junctions and desmosomes.[/caption]

Contractions of the heart (heartbeats) are controlled by specialized cardiac muscle cells called pacemaker cells that directly control heart rate. Although cardiac muscle cannot be consciously controlled, the pacemaker cells respond to signals from the autonomic nervous system (ANS) to speed up or slow down the heart rate. The pacemaker cells can also respond to various hormones that modulate heart rate to control blood pressure.

The wave of contraction that allows the heart to work as a unit, called a functional syncytium, begins with the pacemaker cells. This group of cells is self-excitable and able to depolarize to threshold and fire action potentials on their own, a feature called autorhythmicity; they do this at set intervals which determine heart rate. Because they are connected with gap junctions to surrounding muscle fibers and the specialized fibers of the heart’s conduction system, the pacemaker cells are able to transfer the depolarization to the other cardiac muscle fibers in a manner that allows the heart to contract in a coordinated manner.

Unlike skeletal muscle, extracellular Ca²⁺ is required to initiate release from the sarcoplasmic reticulum (SR). The SR in cardiac muscle fibers is simpler than that of skeletal muscle fibers, lacking terminal cisterns, and there is no direct physical link between proteins in the T-tubule and proteins in the SR membrane, so depolarization of the T-tubule membrane cannot directly cause Ca²⁺ release from the SR. Instead, cardiac muscle cells have voltage-gated calcium channels in the sarcolemma and along the T-tubules that open when the membrane is depolarized, allowing Ca²⁺ to enter the cardiac muscle fiber from the extracellular fluid. This calcium then causes the opening of calcium-gated calcium channels in the SR membrane that release additional Ca²⁺ into the sarcoplasm. This mechanism allows cardiac muscle to have a relatively long-lasting depolarization "plateau" in its fibers. This sustained depolarization (and Ca²⁺ entry) provides for a longer contraction than is produced by an action potential in skeletal muscle.

10.8 Smooth Muscle

barkerj1 — Sat, 21 Apr 2018 20:32:03 +0000

Learning Objectives

By the end of this section, you will be able to:

Describe the microscopic anatomy of a smooth muscle cell, including the functions of:
- Caveolae
- Sarcoplasmic reticulum
- Myofilaments
- Intermediate filaments
- Dense bodies
Outline the mechanism of contraction and relaxation in smooth muscle. Include:
- The roles of calcium and calmodulin
- The roles of myofilaments, dense bodies, gap junctions and calcium pumps
- The source of energy for contraction
Describe the neural, hormonal and chemical factors that regulate contraction of smooth muscle
Define peristalsis and describe the organization of smooth muscles required for peristalsis

Smooth muscle (so named because the cells do not have striations) is present in the walls of hollow organs like the urinary bladder, uterus, stomach, intestines, and in the walls of passageways, such as the arteries and veins of the circulatory system, and the tracts of the respiratory, urinary, and reproductive systems (Figure 1ab). Smooth muscle is also present in the eyes, where it functions to change the size of the iris and alter the shape of the lens; and in the skin where it causes hair to stand erect in response to cold temperature or fear.

[caption id="" align="aligncenter" width="550"] Figure 1. Smooth Muscle Tissue. Smooth muscle tissue is found around organs in the digestive, respiratory, reproductive tracts and the iris of the eye. LM × 1600. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)[/caption]

[caption id="" align="aligncenter" width="120"] View the University of Michigan WebScope at http://virtualslides.med.umich.edu/Histology/Digestive%20System/Intestines/169_HISTO_40X.svs/view.apml to explore the tissue sample in greater detail.[/caption]

Smooth muscle fibers are spindle-shaped (wide in the middle and tapered at both ends, somewhat like a football) and have a single nucleus; they range from about 30 to 200 μm (thousands of times shorter than skeletal muscle fibers), and they produce their own connective tissue, endomysium. Although they do not have striations and sarcomeres, smooth muscle fibers do have actin and myosin contractile proteins, and thick and thin filaments. These thin filaments are anchored by dense bodies. A dense body is analogous to the Z-discs of skeletal and cardiac muscle fibers and is fastened to the sarcolemma. Calcium ions are supplied by the sarcoplasmic retibulum (SR) in the fibers and by sequestration from the extracellular fluid through membrane indentations called calveolae.

Because smooth muscle cells do not contain troponin, cross-bridge formation is not regulated by the troponin-tropomyosin complex but instead by the regulatory protein calmodulin. In a smooth muscle fiber, external Ca²⁺ ions passing through opened calcium channels in the sarcolemma, and additional Ca²⁺ released from SR, bind to calmodulin. The Ca²⁺-calmodulin complex then activates an enzyme called myosin (light chain) kinase, which, in turn, activates the myosin heads by phosphorylating them (converting ATP to ADP and P_i, with the P_i attaching to the head). The heads can then attach to actin-binding sites and pull on the thin filaments. The thin filaments also are anchored to the dense bodies; the structures invested in the inner membrane of the sarcolemma (at adherens junctions) that also have cord-like intermediate filaments attached to them. When the thin filaments slide past the thick filaments, they pull on the dense bodies, structures tethered to the sarcolemma, which then pull on the intermediate filaments networks throughout the sarcoplasm. This arrangement causes the entire muscle fiber to contract in a manner whereby the ends are pulled toward the center, causing the midsection to bulge in a corkscrew motion (Figure 2).

[caption id="" align="aligncenter" width="550"] Figure 2. Muscle Contraction. The dense bodies and intermediate filaments are networked through the sarcoplasm, which cause the muscle fiber to contract.[/caption]

Although smooth muscle contraction relies on the presence of Ca²⁺ ions, smooth muscle fibers have a much smaller diameter than skeletal muscle cells. T-tubules are not required to reach the interior of the cell and therefore not necessary to transmit an action potential deep into the fiber. Smooth muscle fibers have a limited calcium-storing SR but have calcium channels in the sarcolemma (similar to cardiac muscle fibers) that open during the action potential along the sarcolemma. The influx of extracellular Ca²⁺ ions, which diffuse into the sarcoplasm to reach the calmodulin, accounts for most of the Ca²⁺ that triggers contraction of a smooth muscle cell.

Muscle contraction continues until ATP-dependent calcium pumps actively transport Ca²⁺ ions back into the SR and out of the cell. However, a low concentration of calcium remains in the sarcoplasm to maintain muscle tone. This remaining calcium keeps the muscle slightly contracted, which is important in certain tracts and around blood vessels.

Because most smooth muscles must function for long periods without rest, their power output is relatively low, but contractions can continue without using large amounts of energy. Some smooth muscle can also maintain contractions even as Ca²⁺ is removed and myosin kinase is inactivated/dephosphorylated. This can happen as a subset of cross-bridges between myosin heads and actin, called latch-bridges, keep the thick and thin filaments linked together for a prolonged period, and without the need for ATP. This allows for the maintaining of muscle “tone” in smooth muscle that lines arterioles and other visceral organs with very little energy expenditure.

Smooth muscle is not under voluntary control; thus, it is called involuntary muscle. The triggers for smooth muscle contraction include hormones, neural stimulation by the autonomic nervous system (ANS), and local factors. In certain locations, such as the walls of visceral organs, stretching the muscle can trigger its contraction (the stretch-relaxation response).

Axons of neurons in the ANS do not form highly organized neuromuscular junctions (as seen between motor neurons and skeletal muscle fibers) with smooth muscle. Instead, there is a series of neurotransmitter-filled bulges called varicosities as an axon courses through smooth muscle, loosely forming motor units (Figure 3). A varicosity releases neurotransmitters into the synaptic cleft. Also, visceral muscle in the walls of the hollow organs (except the heart) contains pacesetter cells. A pacesetter cell can spontaneously trigger action potentials and contractions in the muscle.

Different autonomic nerves release various neurotransmitters onto smooth muscle. For example some nerves release acetylcholine that causes contraction of smooth muscle around some respiratory ducts and thus constriction of these airways. Other nerves release norepinephrine that causes relaxation of smooth muscle and thus widening of the airways. The same neurotransmitter can even cause opposite effects depending partly on the tissue where it acts. Although norepinephrine causes relaxation of smooth muscle and thus widening of some airways, it also causes contraction of smooth muscle and thus constriction of most blood vessels.

[caption id="" align="aligncenter" width="550"] Figure 3. Motor Units. A series of axon-like swelling, called varicosities or “boutons,” from autonomic neurons form motor units through the smooth muscle.[/caption] Some chemicals can stimulate smooth muscle contraction without an action potential because they cause movement of calcium into the cell. They include histamine, high levels of CO₂, low pH, and low levels of O₂. Several hormones also affect the activity of smooth muscle, either by encouraging contraction or relaxation. For example in the digestive system, cholecystokinin induces relaxation of the smooth muscle around the hepatopancreatic sphincter causing it to open. Conversely, gastrin stimulates contraction of smooth muscle in the stomach to enhance the churning activity of the stomach. Within the reproductive system, oxytocin stimulates uterine smooth muscle contraction to facilitate childbirth.

Smooth muscle is organized in two ways: as single-unit smooth muscle, which is much more common; and as multiunit smooth muscle. The two types have different locations in the body and have different characteristics. Single-unit muscle has its muscle fibers joined by gap junctions so that the muscle contracts as a single unit. This type of smooth muscle is found in the walls of all visceral organs except the heart (which has cardiac muscle in its walls), and so it is commonly called visceral muscle. Because the muscle fibers are not constrained by the organization and stretchability limits of sarcomeres, visceral smooth muscle has a stress-relaxation response. This means that as the muscle of a hollow organ is stretched when it fills, the mechanical stress of the stretching will trigger contraction, but this is immediately followed by relaxation so that the organ does not empty its contents prematurely. This is important for hollow organs, such as the stomach or urinary bladder, which continuously expand as they fill. The smooth muscle around these organs also can maintain a muscle tone when the organ empties and shrinks, a feature that prevents “flabbiness” in the empty organ.

Visceral smooth muscle arranged in layers around a hollow organ generally produces slow, steady contractions known as peristalsis that allow substances, such as food in the digestive tract, to move through the body. One layer of smooth muscle is parallel to the longitudinal axis of the lumen and the other layer is wrapped around the lumen in a circular fashion. A third layer of longitudinal muscle (ureters) or obliquely arranged muscle (stomach) is present in some organs. This action and arrangement of smooth muscle layers, causes mixing and/or unidirectional propulsion of materials through the lumen. Movement of substances through lumens by peristalsis occurs in some organs (uterus, urinary bladder, esophagus, stomach, small and large intestines) and ducts (ureters, uterine tubes, vas deferens, bile ducts).

Multiunit smooth muscle cells rarely possess gap junctions, and thus are not electrically coupled. As a result, contraction does not spread from one cell to the next, but is instead confined to the cell that was originally stimulated. Stimuli for multiunit smooth muscles come from autonomic nerves or hormones but not from stretching. This type of tissue is found around large blood vessels, in the respiratory airways, and in the eyes.

Hyperplasia in Smooth Muscle

Similar to skeletal and cardiac muscle cells, smooth muscle can undergo hypertrophy to increase in size. Unlike other muscle, smooth muscle can also divide to produce more cells, a process called hyperplasia. This can most evidently be observed in the uterus at puberty, which responds to increased estrogen levels by producing more uterine smooth muscle fibers, and greatly increases the size of the myometrium.

Section Summary

Smooth muscle is found throughout the body around various organs and tracts. Smooth muscle cells have a single nucleus, and are spindle-shaped. Smooth muscle cells can undergo hyperplasia, mitotically dividing to produce new cells. The smooth cells are nonstriated, but their sarcoplasm is filled with actin and myosin, along with dense bodies in the sarcolemma to anchor the thin filaments and a network of intermediate filaments involved in pulling the sarcolemma toward the fiber’s middle, shortening it in the process. Ca²⁺ ions trigger contraction when they are released from SR and enter through opened voltage-gated calcium channels. Smooth muscle contraction is initiated when the Ca²⁺ binds to intracellular calmodulin, which then activates an enzyme called myosin kinase that phosphorylates myosin heads so they can form the cross-bridges with actin and then pull on the thin filaments. Smooth muscle can be stimulated by pacesetter cells, by the autonomic nervous system, by hormones, spontaneously, or by stretching. The fibers in some smooth muscle have latch-bridges, cross-bridges that cycle slowly without the need for ATP; these muscles can maintain low-level contractions for long periods. Single-unit smooth muscle tissue contains gap junctions to synchronize membrane depolarization and contractions so that the muscle contracts as a single unit. Single-unit smooth muscle in the walls of the viscera, called visceral muscle, has a stress-relaxation response that permits muscle to stretch, contract, and relax as the organ expands. Multiunit smooth muscle cells do not possess gap junctions, and contraction does not spread from one cell to the next.

1103 Chapter 8. The Appendicular Skeleton

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1103 Chapter 9. Joints

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1103 Chapter 10. Muscle Tissue

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1103 Chapter 11. The Muscular System

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1103 Chapter 18. The Cardiovascular System: Blood

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1103 Chapter 19. The Cardiovascular System: The Heart

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1103 Chapter 20. The Cardiovascular System: Blood Vessels and Circulation

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1103 Chapter 21. The Lymphatic and Immune System

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1103 Chapter 22. The Respiratory System

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1103 Chapter 24. Metabolism and Nutrition

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1103 Chapter 26. Fluid, Electrolyte, and Acid-Base Balance

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1103 Review

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