{"id":30,"date":"2023-05-23T17:43:02","date_gmt":"2023-05-23T21:43:02","guid":{"rendered":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/?post_type=chapter&p=30"},"modified":"2026-01-03T16:16:56","modified_gmt":"2026-01-03T21:16:56","slug":"hematopoiesis-formation-and-roles-of-rbcs-wbcs-and-platelets","status":"web-only","type":"chapter","link":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/chapter\/hematopoiesis-formation-and-roles-of-rbcs-wbcs-and-platelets\/","title":{"raw":"Hematopoiesis - Formation and Roles of RBCs, WBCs and platelets","rendered":"Hematopoiesis – Formation and Roles of RBCs, WBCs and platelets"},"content":{"raw":"Blood Development, Blood Cells, and Blood Components<\/strong>\r\n\r\nEmbryonic Blood<\/strong>\r\n\r\nThe development of blood during embryogenesis goes through many changes.\u00a0 The first blood cells<\/strong> are produced at day 7 of embryonic life.\u00a0 The blood cell lineage expands its development in the yolk sac<\/strong> within the first two weeks of gestation.\u00a0 As the embryo grows, blood stem cells migrate to the liver<\/strong> and spleen<\/strong> beginning at week 7.\u00a0 As a fetus, blood cell formation begins to occur in the newly formed bone marrow of the developing skeleton (~week 20).\u00a0 Blood stem cells remain in the bone marrow<\/strong> through deveopment and adulthood and continue their production from this location.\u00a0 The formation of blood cells is termed hematopoiesis.<\/strong>\u00a0 The pluripotent stem cells that continually divide to give rise to all of the blood cell types (red blood cells, RBCs and white blood cells, WBCs) are termed hematocytoblasts.<\/strong>\r\n\r\nBlood Cell Lineage<\/strong>\r\n\r\nDaughter cells of hematocytoblasts differentiate into various lineages.\u00a0 The majority of daughter cells become erthryocytes<\/strong> (RBCs).\u00a0 Some daughter cells become megakaryocytes<\/strong> and some daughter cells become leukocytes<\/strong> (WBCs).\r\n\r\nRed Blood Cell Lineage:<\/strong>\r\n\r\nThe part of hematopoiesis that results in the production of red blood cells (erythrocytes) is termed erythropoiesis.\u00a0 Daughter cells of hematocytoblasts that become erythroblasts will mature into erythrocytes after going through several stages, of maturation as they grow and become more packed full of hemoglobin.<\/strong>\u00a0 When erythroblasts grow and differentiate into the normoblast stage, they lose their nucleus and become reticulocytes and after another 2-3 days enter the bloodstream.\u00a0 Two days later, they become mature erythrocytes whose main function is the transportation of oxygen and carbon dioxide.\u00a0 Lifespan of erythrocytes is approximately 120 days after which they are recycled by macrophages in the liver, bone marrow, and spleen.\u00a0 The proportion of RBCs in the blood that are reticulocytes is called the \"retic count\" and is normally 1-2%.\u00a0 If the retic count is low (e.g. 0.5%) it indicated erytrhopoiesis levels are low.\r\n\r\nTo maintain RBC homeostasis, approximately 3 million RBCs are recycle and produced per second.\u00a0 Erythroipoiesis is stimulated by the hormone, erythropoietin (EPO) which is secreted by the kidneys (and some cells in the liver) in response to low blood-oxygen levels.\u00a0 EPO is also secreted in reponse to growth hormone, thyroxine and testosterone.\u00a0 If RBC or hemoglobin levels are too low, there will be a lower level of oxygen delivery, potentially resulting in weakness, fatigue, and confusion. RBC production requires B vitamins, folic acid (folate), amino acids, and iron.\u00a0 Nutritional deficiencies in protein, vitamin B12<\/sub> or folate can cause reduced production in other blood cell lineages as well (i.e. WBCs and platelets).\u00a0 Reduced WBC production is termed leukopenia.<\/strong>\u00a0 Reduced platelet production is termed thrombocytopenia.<\/strong>\r\n\r\n \r\n\r\nMegakaryocytes and Platelets (Thrombocytes):<\/strong>\r\n\r\nWithin the bone marrow, hematocytoblasts, blood stem cells, divide to produce many types of daughter cells, some of which are large cells called megakaryocytes that fragment into approximately 1000 anuclear platelets (thrombocytes).\u00a0 Even though platelets lack a nucleus they contain 300 different chemicals involved in blood clotting<\/strong> (hemostasis) and are able to see out areas of cellular or vascular damage to provide assistance.\u00a0 Platelets play a vital role in innate (non-specific defense, and are essentail in forming clots to prevent excessive bleeding from damaged blood vessels.\r\n\r\n \r\n\r\nWhite Blood Cell Lineage:\u00a0\u00a0<\/strong>\r\n\r\nIn addition to producing RBCs and platelets, hematocytoblast blood stem cells in the bone marrow also produce daughter cells that will become WBCs.\u00a0 There are 2 broad categories of WBCs, the granulocytes and agranulocytes.\u00a0 As the name suggests, the granulocytes, which have large granules that are easily viewable under the microscope.\u00a0 The agranulocytes have smaller granules.\r\n\r\nWhite Blood Cells - Granulocytes\u00a0<\/strong>\r\n\r\nGranulocytes provide innate (non-specific) defense. \u00a0There are four types of granulocytes: neutrophils, eosinophils, basophils<\/strong> and mast cells.<\/strong>\u00a0 All of the granulocytes are also termed polymorphonuclear leukocytes (PMNs) as they each have a nucleus that is segmented or irregularly shaped. This characteristic is useful in identifying these cells under the microscope, as is their staining characteristics.\u00a0 Neutrophils stain a neutral pink colour with H&E dye.\u00a0 Eosinophils stain a red colour with an acidic eosin dye. Basophils and mast cells stain blue colours with basic dye.<\/b>\r\n\r\nNeutrophils and eosinophils are phagocytes<\/strong> and are able to protect against pathogens.\r\n\r\nMature neutrophils<\/strong> arise from immature band cells and live approximately 2-5 days.\u00a0 Neutrophils are distinguishable under the microscope, as they contain a 2-5 lobed nucleus.\u00a0 Neutrophils are the most plentiful WBC, making up 50-70% of circulating WBCs, and contain extensive lysosomes.\u00a0 Neutrophils use amoeboid movement (as do all WBCs) and are amongst the first cells to arrive at sites of cellular damage.\u00a0 Neutrophils play important roles in engulfing bacteria and cellular debris. The granules of neutrophils contain lactoferrin and proteases (proteolytic enzymes) for killing pathogens and the secretory vesicles contain cytokines and cytotoxic compounds such as ROSs which are used to destroy pathogens.\u00a0 Once activated, neutrophils live 24-48 hours.\u00a0 When neutrophils are active, their rate of production increases and there is an increase in number of neutrophils in the blood, which is revealed in a blood cell count.\u00a0 An increased number of neutrophils per mL of blood is called neutrophilia.<\/strong>\u00a0 Bacterial infections often cause neutrophilia and are also associated with a shift to the left which refers to an increased number of band cells (immature neutrophils) in the blood.\u00a0 At times, very severe bacterial or viral infections can lead to lower numbers of neutrophils, as the rate of mitosis of neutrophils is outpaced by their ability to defend against the infection.\u00a0 Low numbers of neutrophils per mL of blood is termed neutropenia.<\/strong>\u00a0 Nutritional deficiencies, some congenital defects, autoimmune diseases (Systemic Lupus Erythematosus) and cancers can also cause neutropenia.\r\n\r\nEosinophils<\/strong> stain pink with eosin dye, and appear at the site of infection or cellular damage 2-3 hours after neutrophils.\u00a0 Not only are eosinophils able to phagocytose debris and pathogens, they are also able to exocytose toxins destroying pathogens that are too large to phagocytose (e.g. helminths or parasitic worms).\u00a0 Eosinophils circulate the bloodstream, patrol tissues, and account for 2-3% of WBCs.\u00a0 The granules of eosinophils are filled with toxins (e.g. major basic protein).\u00a0 A large number of eosinophils will be produced in response to helminth (parasitic worm) infections.\u00a0 Eosinophilia<\/strong> (high number of eosinophils per mL blood) will also occur in cases of allergies and autoimmune diseases\r\n\r\nMast Cells<\/strong> are located in tissues throughout the body and most prevalent in sites that are most at risk for infection: the dermis of the skin, the mucosa of the lungs and the mucosa of the gastrointestinal (GI) tract.\u00a0 Basophils<\/strong> are very similar to mast cells as both contain granules filled with heparin and histamine.\u00a0 However, while mast cells are fixed patrolling certain tissue beds, basophils circulate the bloodstream.\u00a0 Both mast cells and basophils fulfill similar roles.\u00a0 In response to cellular injury, basophils and mast cells are activated, migrate to the affected area, and degranulate releasing pro-inflammatory cytokines (e.g. histamine, bradykinins, prostaglandins, and leukotrienes).\u00a0 Heparin<\/strong> is an anti-coagulant that is thought to decrease the number of microthrombi formed at sites of injury.\r\n\r\n \r\n\r\n \r\n\r\nWhite Blood Cells - Agranulocytes (White Blood Cells with smaller granules)<\/strong>\r\n\r\nThere are 2 major types of agranulocytes: monocytes and lymphocytes.\u00a0The monocytes mature to become macrophages and dendritic cells.\u00a0 There are 3 main types of lymphocytes: Natural Killer cells, T cells (T lymphocytes) and B cells (B lymphocytes).\r\n\r\nBlood Composition - Plasma and Formed Elements<\/strong>\r\n\r\nBlood is considered a fluid connective tissue and contains a liquid extracellular matrix called plasma.<\/strong> The formed elements<\/strong> within blood is the cellular portion and contain RBCs, WBCs, and platelets.\r\n\r\nIf one were to sit a test tube of blood in a tray, it would settle out by weight, with the ligher plasma on the top, the buffy coat<\/strong> containing leukocytes and platelets forming a small white layer, and then a dark red bottom layer consisting of the heavier iron-rich erythrocytes.\u00a0 By volume, blood is approximately 55% plasma, <1% leukocytes and platelets, and depending on biological sex, 41%-45% erythrocytes.\r\n\r\nPlasma<\/strong> is a yellowish fluid and contains water, electrolytes (Na+<\/sup>, K+<\/sup>, Ca2+<\/sup>, Mg2+<\/sup>, Cl-<\/sup>, HCO3<\/sub>-<\/sup>, HPO4<\/sub>-<\/sup>, SO4<\/sub>2-<\/sup>), dissolved gases, amino acids, fatty acids, glycerides, cholesterol, glucose, hormones, organic wastes (urea, uric acid, creatinine, bilirubin) and proteins which include antibodies, complement proteins, enzymes, and transport proteins such as albumin and lipoproteins. It is likely not surprising that interstitial fluid (the fluid between tissue cells) is very similar in composition to plasma as an equilibrium does exist particularly for small water soluble ions and molecules.\u00a0 In comparison with plasma, intersitial fluid contains similar concentrations of water, electrolytes, dissolved gases, amino acids and hormones.\u00a0 However plasma contains a lot of dissolved proteins, whereas interstitial fluid does not.\r\n\r\nPlasma Proteins:<\/strong>\r\n
    \r\n \t
  1. Albumin:<\/strong> 60% of plasma protein: The most abundant protein in the plasma, albumin is involved in transporting lipid soluble substances (i.e. fatty acids and steroid hormones) in the blood, and is produced in the liver. Albumin is responsible for the majority of the blood colloid osmotic force.<\/li>\r\n \t
  2. Globulins:<\/strong> 35% of plasma protein: Globulins includes antibodies (Immunoglobulins) produced by B cells (B lymphocytes) and transport globulins that are produced in the liver that transport vitamins, lipids, metal ions, and hormones (e.g. lipoproteins).<\/li>\r\n \t
  3. Antibodies:<\/strong> Antibodies are specialized proteins involved in immunity that are produced in lymph tissue by B cells.<\/li>\r\n \t
  4. C-reactive proteins (CRP):<\/strong> are small proteins produced by liver cells (hepatocytes) and circulate the blood binding to the surface of dead cells and bacteria in order to activate the complement system.\u00a0 The amount of damage often correlates with the number of CRP per mL of blood as CRP is produced in response to cytokines released by macrophages.<\/li>\r\n \t
  5. Complement proteins:\u00a0<\/strong> are produced by hepatocytes and circulate the blood as part of the immune system, capable of: a) acting as opsonins, b) creating membrane attack complexes on bacterial surfaces, and c) stimulating mast cell activity during infection.<\/li>\r\n \t
  6. Fibrinogen<\/strong> and Prothrombin:<\/strong> 4% of plasma protein: Fibrinogen and prothrombin are produced in the liver and are involved in blood clotting. Require vitamin K during synthesis.<\/li>\r\n \t
  7. Lipoproteins:<\/strong> Produced in the liver and involved in transporting triglycerides and cholesterol in the blood.<\/li>\r\n \t
  8. Hormones<\/strong> and enzymes:<\/strong> which perform specialized functions<\/li>\r\n<\/ol>\r\n*Note: Hormones<\/strong> are important signalling molecules that regulate complex biological processes, growth, development, maturation, and behavioiur.\u00a0 Hormones are classified into 5 main categories: lipids<\/strong> (e.g. prostaglandins, thromboxanes), steroids<\/strong> (estrogen and testosterone), amino acids<\/strong> (e.g. epinephrine), peptides<\/strong> (e.g. insulin), and gases<\/strong> (e.g. nitric oxide, NO)\r\n\r\nSerum<\/strong> is the fluid plasma component of blood, with all of the clotting factors, platelets, and cells removed.\u00a0 \u00a0 Serum is used in blood typing<\/strong> as well as several diagnostic tests.<\/strong>\u00a0 Serum is obtained by allowing blood to clot and then centrifuing to separate the blood by weight.\u00a0 The top liquid portion (that has not coagulated) is serum.\u00a0 Serum contains water, electrolytes and soluble proteins (e.g. antibodies),\u00a0 Diagnostic tests have been developed for some cancers, autoimmune reactions, and other diseases that analyze the presence or level of various serum biomarkers<\/strong> (e.g. C-reactive protein, CRP; specific antibodies; prostate specific antigen, PSA).\r\n\r\nHematocrit:<\/strong>\r\n\r\nHematocrit<\/strong> is defined as the percentage of blood that is formed elements.\u00a0 Biological males typically have a higher hematocrit than biological females due to testosterone stimulating EPO and red blood cell production.\u00a0 Hematocrit for biological males is approximately 46% and is 42% for biological females.\u00a0 To some extent a greater concentration of erythrocytes in biological males might be expected, as testosterone also stimulates a larger amount of skeletal muscle to form during puberty, which as a metabolically active tissue type requires sufficient levels of oxygen and nutrients to maintain and support.\u00a0<\/span>\r\n\r\nBlood Disorders - Examples:<\/strong>\r\n\r\nAnemia<\/strong> is defined as condition in which there is a reduced oxygen-carrying capacity,.\u00a0 Anemia can result from various causes, such as a low number of red blood cells or sickle-shaped cells (e.g. Sickle Cell Anemia).\u00a0 The word anemia originates from an- meaning without, and -emia referring to blood. Risk factors include: blood loss, systemic lupus erythematosus, autoimmune diseases that affect intestinal absorption of food (e.g. Crohn diseae, ulcerative colitis), blood cancers (e.g. lymphoma), chemotherapy and long term infections (e.g. HIV, osteomyelitis, hepatitis).\r\n\r\nIron-deficiency Anemia:<\/strong> most commone in biological femals, as females have lower iron reserves than biological males.\u00a0 Other contributing factors can include vegetarian diet, poor diet, menstruation, and frequent blood donors.\u00a0 A low retic count, indicating low levels of erythropoiesis may occur.\u00a0 Prevention involves healthy diet that includes iron-rich foods such as: eggs, meat, leafy green vegetables,\r\n\r\nSickle Cell Anemia:<\/strong> is due to an autosomal recessive disorder in which both inherited genes for hemoglobin's\u00a0 Hb beta-chain on chromosome 11 are mutated.\u00a0 This results in misfolding of hemoglobin and the rigid sickle-shape of RBCs.\u00a0 The RBCs have a shortened life expectancy and reduced flexibility.\u00a0 Sickled RBCs cause blockages and downstream hypoxia throughout the body.\u00a0 Blood transfusions and the donation of bone marrow stem cells is used to treat this disease.\r\n\r\nAlpha and Beta Thalassemia:<\/strong> are autosomal recessive diseases in which hemoglobin gene mutations have occured in either the alpha or beta chain respectively.\u00a0 Signs and symptoms range from mild to severe based on the types of mutations present.\r\n\r\nPernicious Anemia:<\/strong> is a rare auto-immune disease in which auto-antibodies binding to and inhibiting the action of Intrinsic Factor. Intrinsic Factor is produced by intestinal cells and is required for the absorbtion of dietary vitamin B12<\/sub>.\u00a0 A low retic count, indicating low levels of erythropoiesis may occur.\u00a0 Without treatment vitamin B12<\/sub> deficiency leads to anemia.\r\n\r\nHemorrhagic Anemia:<\/strong> as the name suggests is due to excessive blood loss.\r\n\r\n \r\n\r\nPolycythemia<\/strong> is defined as a condition in which there is excessive red blood cell production.\u00a0 The word polycythemia originates from poly- meaning many, cyte referring to cell, and -emia referring to blood.\u00a0 This condition can be dangerous as it thickens blood, increases the risk of blood clots, and also puts a strain on the heart to pump harder.\u00a0 Unfortunately many elite at<\/span>hletes\u00a0 have been found to have blood dope by injecting themselves with erythropoietin (EPO) to artificially increase red blood cell count for improved oxygen delivery and athletic performance.\r\n\r\nOn the other, moving to a higher altitude, with lower atmospheric oxygen levels, can naturally increase levels of EPO.\u00a0 In this case a higher hematocrit level may also be present.\r\n\r\nErythrocyte Sedimentation Rate (ESR):<\/strong> is a diagnostic blood test, that involves calculating the rate at which erythrocytes settle to the bottom of a tube of blood.\u00a0 RBCs are the heaviest component of blood and will settle to the bottom of the tube, however their rate of settling is affected by: the number of RBCs per mL of blood as well as the number of plasma proteins present.\u00a0 For example, an adult male (XY) typically has a higher hematocrit compared to an age-matched female (XX).\u00a0 Having more RBCs per mL results in slower settling as the erythrocytes are negatively charged and repel each other which slows down sedimentation.\u00a0 On average the ESR of young adult males is 12mm\/hr and the average ESR of age-matched females is 18mm\/hr.\u00a0 During injury or infection the number of plasma proteins (e.g. CRP, prothrombin, plasminogen, fibrinogen, complement proteins) per mL increases.\u00a0 These proteins allow the RBCs to stick closer together and fall faster.\u00a0 Therefore a ESR is often proportional to the amount of damage or inflammation that is present in the body.\u00a0 Serious infections, autoimmune disease, and chronic ailments can result in ESRs that are 100mm\/hr or more.\r\n\r\n \r\n\r\nSummary<\/strong>\r\n
      \r\n \t
    • Describe plasma components & define vocabulary words:<\/strong>\r\n
        \r\n \t
      • Plasma<\/strong> - liquid matrix containing water, electrolytes, and plasma proteins<\/li>\r\n \t
      • Plasma proteins<\/strong> - antibodies, complement proteins, clotting factors, albumen and transporter proteins<\/li>\r\n \t
      • Platelets\/Thrombocytes<\/strong> - a nuclear cell fragments formed from large megakaryocytes;\u00a0 involved in clotting (hemostasis)<\/li>\r\n \t
      • Leukocytes<\/strong> - WBCs<\/li>\r\n \t
      • Lymphocytes:<\/strong> type of WBC involved in antibody production (B lymphocytes), targeted immune response (T lymphocytes), and surveillance (NK lymphocytes)<\/li>\r\n \t
      • Neutrophils:<\/strong> The most abundant phagocyte in the blood; contain extensive lysosomes<\/li>\r\n \t
      • Eosinophils:<\/strong> Destroy parasitic worms & immune complexes<\/li>\r\n \t
      • Basophils<\/strong> & Mast cells<\/strong>: Release histamine, heparin, prostaglandins, and leukotrienes in process known as degranulation<\/li>\r\n \t
      • Erythrocytes<\/strong> - RBCs; transport oxygen & carbon dioxide<\/li>\r\n \t
      • Hematocrit<\/strong> -\u00a0 % by volume of blood that is \u00a0 formed elements<\/li>\r\n \t
      • Anemia:<\/strong> reduced oxygen-carrying capacity of blood due to low levels of functional RBCs or hemoglobin.<\/span><\/li>\r\n \t
      • Polycythemia;<\/strong> greater than normal # of RBCs<\/li>\r\n \t
      • EPO, erythropoietin<\/strong>: hormone that stimulates production of RBCs<\/li>\r\n<\/ul>\r\n<\/li>\r\n<\/ul>","rendered":"

        Blood Development, Blood Cells, and Blood Components<\/strong><\/p>\n

        Embryonic Blood<\/strong><\/p>\n

        The development of blood during embryogenesis goes through many changes.\u00a0 The first blood cells<\/strong> are produced at day 7 of embryonic life.\u00a0 The blood cell lineage expands its development in the yolk sac<\/strong> within the first two weeks of gestation.\u00a0 As the embryo grows, blood stem cells migrate to the liver<\/strong> and spleen<\/strong> beginning at week 7.\u00a0 As a fetus, blood cell formation begins to occur in the newly formed bone marrow of the developing skeleton (~week 20).\u00a0 Blood stem cells remain in the bone marrow<\/strong> through deveopment and adulthood and continue their production from this location.\u00a0 The formation of blood cells is termed hematopoiesis.<\/strong>\u00a0 The pluripotent stem cells that continually divide to give rise to all of the blood cell types (red blood cells, RBCs and white blood cells, WBCs) are termed hematocytoblasts.<\/strong><\/p>\n

        Blood Cell Lineage<\/strong><\/p>\n

        Daughter cells of hematocytoblasts differentiate into various lineages.\u00a0 The majority of daughter cells become erthryocytes<\/strong> (RBCs).\u00a0 Some daughter cells become megakaryocytes<\/strong> and some daughter cells become leukocytes<\/strong> (WBCs).<\/p>\n

        Red Blood Cell Lineage:<\/strong><\/p>\n

        The part of hematopoiesis that results in the production of red blood cells (erythrocytes) is termed erythropoiesis.\u00a0 Daughter cells of hematocytoblasts that become erythroblasts will mature into erythrocytes after going through several stages, of maturation as they grow and become more packed full of hemoglobin.<\/strong>\u00a0 When erythroblasts grow and differentiate into the normoblast stage, they lose their nucleus and become reticulocytes and after another 2-3 days enter the bloodstream.\u00a0 Two days later, they become mature erythrocytes whose main function is the transportation of oxygen and carbon dioxide.\u00a0 Lifespan of erythrocytes is approximately 120 days after which they are recycled by macrophages in the liver, bone marrow, and spleen.\u00a0 The proportion of RBCs in the blood that are reticulocytes is called the “retic count” and is normally 1-2%.\u00a0 If the retic count is low (e.g. 0.5%) it indicated erytrhopoiesis levels are low.<\/p>\n

        To maintain RBC homeostasis, approximately 3 million RBCs are recycle and produced per second.\u00a0 Erythroipoiesis is stimulated by the hormone, erythropoietin (EPO) which is secreted by the kidneys (and some cells in the liver) in response to low blood-oxygen levels.\u00a0 EPO is also secreted in reponse to growth hormone, thyroxine and testosterone.\u00a0 If RBC or hemoglobin levels are too low, there will be a lower level of oxygen delivery, potentially resulting in weakness, fatigue, and confusion. RBC production requires B vitamins, folic acid (folate), amino acids, and iron.\u00a0 Nutritional deficiencies in protein, vitamin B12<\/sub> or folate can cause reduced production in other blood cell lineages as well (i.e. WBCs and platelets).\u00a0 Reduced WBC production is termed leukopenia.<\/strong>\u00a0 Reduced platelet production is termed thrombocytopenia.<\/strong><\/p>\n

         <\/p>\n

        Megakaryocytes and Platelets (Thrombocytes):<\/strong><\/p>\n

        Within the bone marrow, hematocytoblasts, blood stem cells, divide to produce many types of daughter cells, some of which are large cells called megakaryocytes that fragment into approximately 1000 anuclear platelets (thrombocytes).\u00a0 Even though platelets lack a nucleus they contain 300 different chemicals involved in blood clotting<\/strong> (hemostasis) and are able to see out areas of cellular or vascular damage to provide assistance.\u00a0 Platelets play a vital role in innate (non-specific defense, and are essentail in forming clots to prevent excessive bleeding from damaged blood vessels.<\/p>\n

         <\/p>\n

        White Blood Cell Lineage:\u00a0\u00a0<\/strong><\/p>\n

        In addition to producing RBCs and platelets, hematocytoblast blood stem cells in the bone marrow also produce daughter cells that will become WBCs.\u00a0 There are 2 broad categories of WBCs, the granulocytes and agranulocytes.\u00a0 As the name suggests, the granulocytes, which have large granules that are easily viewable under the microscope.\u00a0 The agranulocytes have smaller granules.<\/p>\n

        White Blood Cells – Granulocytes\u00a0<\/strong><\/p>\n

        Granulocytes provide innate (non-specific) defense. \u00a0There are four types of granulocytes: neutrophils, eosinophils, basophils<\/strong> and mast cells.<\/strong>\u00a0 All of the granulocytes are also termed polymorphonuclear leukocytes (PMNs) as they each have a nucleus that is segmented or irregularly shaped. This characteristic is useful in identifying these cells under the microscope, as is their staining characteristics.\u00a0 Neutrophils stain a neutral pink colour with H&E dye.\u00a0 Eosinophils stain a red colour with an acidic eosin dye. Basophils and mast cells stain blue colours with basic dye.<\/b><\/p>\n

        Neutrophils and eosinophils are phagocytes<\/strong> and are able to protect against pathogens.<\/p>\n

        Mature neutrophils<\/strong> arise from immature band cells and live approximately 2-5 days.\u00a0 Neutrophils are distinguishable under the microscope, as they contain a 2-5 lobed nucleus.\u00a0 Neutrophils are the most plentiful WBC, making up 50-70% of circulating WBCs, and contain extensive lysosomes.\u00a0 Neutrophils use amoeboid movement (as do all WBCs) and are amongst the first cells to arrive at sites of cellular damage.\u00a0 Neutrophils play important roles in engulfing bacteria and cellular debris. The granules of neutrophils contain lactoferrin and proteases (proteolytic enzymes) for killing pathogens and the secretory vesicles contain cytokines and cytotoxic compounds such as ROSs which are used to destroy pathogens.\u00a0 Once activated, neutrophils live 24-48 hours.\u00a0 When neutrophils are active, their rate of production increases and there is an increase in number of neutrophils in the blood, which is revealed in a blood cell count.\u00a0 An increased number of neutrophils per mL of blood is called neutrophilia.<\/strong>\u00a0 Bacterial infections often cause neutrophilia and are also associated with a shift to the left which refers to an increased number of band cells (immature neutrophils) in the blood.\u00a0 At times, very severe bacterial or viral infections can lead to lower numbers of neutrophils, as the rate of mitosis of neutrophils is outpaced by their ability to defend against the infection.\u00a0 Low numbers of neutrophils per mL of blood is termed neutropenia.<\/strong>\u00a0 Nutritional deficiencies, some congenital defects, autoimmune diseases (Systemic Lupus Erythematosus) and cancers can also cause neutropenia.<\/p>\n

        Eosinophils<\/strong> stain pink with eosin dye, and appear at the site of infection or cellular damage 2-3 hours after neutrophils.\u00a0 Not only are eosinophils able to phagocytose debris and pathogens, they are also able to exocytose toxins destroying pathogens that are too large to phagocytose (e.g. helminths or parasitic worms).\u00a0 Eosinophils circulate the bloodstream, patrol tissues, and account for 2-3% of WBCs.\u00a0 The granules of eosinophils are filled with toxins (e.g. major basic protein).\u00a0 A large number of eosinophils will be produced in response to helminth (parasitic worm) infections.\u00a0 Eosinophilia<\/strong> (high number of eosinophils per mL blood) will also occur in cases of allergies and autoimmune diseases<\/p>\n

        Mast Cells<\/strong> are located in tissues throughout the body and most prevalent in sites that are most at risk for infection: the dermis of the skin, the mucosa of the lungs and the mucosa of the gastrointestinal (GI) tract.\u00a0 Basophils<\/strong> are very similar to mast cells as both contain granules filled with heparin and histamine.\u00a0 However, while mast cells are fixed patrolling certain tissue beds, basophils circulate the bloodstream.\u00a0 Both mast cells and basophils fulfill similar roles.\u00a0 In response to cellular injury, basophils and mast cells are activated, migrate to the affected area, and degranulate releasing pro-inflammatory cytokines (e.g. histamine, bradykinins, prostaglandins, and leukotrienes).\u00a0 Heparin<\/strong> is an anti-coagulant that is thought to decrease the number of microthrombi formed at sites of injury.<\/p>\n

         <\/p>\n

         <\/p>\n

        White Blood Cells – Agranulocytes (White Blood Cells with smaller granules)<\/strong><\/p>\n

        There are 2 major types of agranulocytes: monocytes and lymphocytes.\u00a0The monocytes mature to become macrophages and dendritic cells.\u00a0 There are 3 main types of lymphocytes: Natural Killer cells, T cells (T lymphocytes) and B cells (B lymphocytes).<\/p>\n

        Blood Composition – Plasma and Formed Elements<\/strong><\/p>\n

        Blood is considered a fluid connective tissue and contains a liquid extracellular matrix called plasma.<\/strong> The formed elements<\/strong> within blood is the cellular portion and contain RBCs, WBCs, and platelets.<\/p>\n

        If one were to sit a test tube of blood in a tray, it would settle out by weight, with the ligher plasma on the top, the buffy coat<\/strong> containing leukocytes and platelets forming a small white layer, and then a dark red bottom layer consisting of the heavier iron-rich erythrocytes.\u00a0 By volume, blood is approximately 55% plasma, <1% leukocytes and platelets, and depending on biological sex, 41%-45% erythrocytes.<\/p>\n

        Plasma<\/strong> is a yellowish fluid and contains water, electrolytes (Na+<\/sup>, K+<\/sup>, Ca2+<\/sup>, Mg2+<\/sup>, Cl–<\/sup>, HCO3<\/sub>–<\/sup>, HPO4<\/sub>–<\/sup>, SO4<\/sub>2-<\/sup>), dissolved gases, amino acids, fatty acids, glycerides, cholesterol, glucose, hormones, organic wastes (urea, uric acid, creatinine, bilirubin) and proteins which include antibodies, complement proteins, enzymes, and transport proteins such as albumin and lipoproteins. It is likely not surprising that interstitial fluid (the fluid between tissue cells) is very similar in composition to plasma as an equilibrium does exist particularly for small water soluble ions and molecules.\u00a0 In comparison with plasma, intersitial fluid contains similar concentrations of water, electrolytes, dissolved gases, amino acids and hormones.\u00a0 However plasma contains a lot of dissolved proteins, whereas interstitial fluid does not.<\/p>\n

        Plasma Proteins:<\/strong><\/p>\n

          \n
        1. Albumin:<\/strong> 60% of plasma protein: The most abundant protein in the plasma, albumin is involved in transporting lipid soluble substances (i.e. fatty acids and steroid hormones) in the blood, and is produced in the liver. Albumin is responsible for the majority of the blood colloid osmotic force.<\/li>\n
        2. Globulins:<\/strong> 35% of plasma protein: Globulins includes antibodies (Immunoglobulins) produced by B cells (B lymphocytes) and transport globulins that are produced in the liver that transport vitamins, lipids, metal ions, and hormones (e.g. lipoproteins).<\/li>\n
        3. Antibodies:<\/strong> Antibodies are specialized proteins involved in immunity that are produced in lymph tissue by B cells.<\/li>\n
        4. C-reactive proteins (CRP):<\/strong> are small proteins produced by liver cells (hepatocytes) and circulate the blood binding to the surface of dead cells and bacteria in order to activate the complement system.\u00a0 The amount of damage often correlates with the number of CRP per mL of blood as CRP is produced in response to cytokines released by macrophages.<\/li>\n
        5. Complement proteins:\u00a0<\/strong> are produced by hepatocytes and circulate the blood as part of the immune system, capable of: a) acting as opsonins, b) creating membrane attack complexes on bacterial surfaces, and c) stimulating mast cell activity during infection.<\/li>\n
        6. Fibrinogen<\/strong> and Prothrombin:<\/strong> 4% of plasma protein: Fibrinogen and prothrombin are produced in the liver and are involved in blood clotting. Require vitamin K during synthesis.<\/li>\n
        7. Lipoproteins:<\/strong> Produced in the liver and involved in transporting triglycerides and cholesterol in the blood.<\/li>\n
        8. Hormones<\/strong> and enzymes:<\/strong> which perform specialized functions<\/li>\n<\/ol>\n

          *Note: Hormones<\/strong> are important signalling molecules that regulate complex biological processes, growth, development, maturation, and behavioiur.\u00a0 Hormones are classified into 5 main categories: lipids<\/strong> (e.g. prostaglandins, thromboxanes), steroids<\/strong> (estrogen and testosterone), amino acids<\/strong> (e.g. epinephrine), peptides<\/strong> (e.g. insulin), and gases<\/strong> (e.g. nitric oxide, NO)<\/p>\n

          Serum<\/strong> is the fluid plasma component of blood, with all of the clotting factors, platelets, and cells removed.\u00a0 \u00a0 Serum is used in blood typing<\/strong> as well as several diagnostic tests.<\/strong>\u00a0 Serum is obtained by allowing blood to clot and then centrifuing to separate the blood by weight.\u00a0 The top liquid portion (that has not coagulated) is serum.\u00a0 Serum contains water, electrolytes and soluble proteins (e.g. antibodies),\u00a0 Diagnostic tests have been developed for some cancers, autoimmune reactions, and other diseases that analyze the presence or level of various serum biomarkers<\/strong> (e.g. C-reactive protein, CRP; specific antibodies; prostate specific antigen, PSA).<\/p>\n

          Hematocrit:<\/strong><\/p>\n

          Hematocrit<\/strong> is defined as the percentage of blood that is formed elements.\u00a0 Biological males typically have a higher hematocrit than biological females due to testosterone stimulating EPO and red blood cell production.\u00a0 Hematocrit for biological males is approximately 46% and is 42% for biological females.\u00a0 To some extent a greater concentration of erythrocytes in biological males might be expected, as testosterone also stimulates a larger amount of skeletal muscle to form during puberty, which as a metabolically active tissue type requires sufficient levels of oxygen and nutrients to maintain and support.\u00a0<\/span><\/p>\n

          Blood Disorders – Examples:<\/strong><\/p>\n

          Anemia<\/strong> is defined as condition in which there is a reduced oxygen-carrying capacity,.\u00a0 Anemia can result from various causes, such as a low number of red blood cells or sickle-shaped cells (e.g. Sickle Cell Anemia).\u00a0 The word anemia originates from an- meaning without, and -emia referring to blood. Risk factors include: blood loss, systemic lupus erythematosus, autoimmune diseases that affect intestinal absorption of food (e.g. Crohn diseae, ulcerative colitis), blood cancers (e.g. lymphoma), chemotherapy and long term infections (e.g. HIV, osteomyelitis, hepatitis).<\/p>\n

          Iron-deficiency Anemia:<\/strong> most commone in biological femals, as females have lower iron reserves than biological males.\u00a0 Other contributing factors can include vegetarian diet, poor diet, menstruation, and frequent blood donors.\u00a0 A low retic count, indicating low levels of erythropoiesis may occur.\u00a0 Prevention involves healthy diet that includes iron-rich foods such as: eggs, meat, leafy green vegetables,<\/p>\n

          Sickle Cell Anemia:<\/strong> is due to an autosomal recessive disorder in which both inherited genes for hemoglobin’s\u00a0 Hb beta-chain on chromosome 11 are mutated.\u00a0 This results in misfolding of hemoglobin and the rigid sickle-shape of RBCs.\u00a0 The RBCs have a shortened life expectancy and reduced flexibility.\u00a0 Sickled RBCs cause blockages and downstream hypoxia throughout the body.\u00a0 Blood transfusions and the donation of bone marrow stem cells is used to treat this disease.<\/p>\n

          Alpha and Beta Thalassemia:<\/strong> are autosomal recessive diseases in which hemoglobin gene mutations have occured in either the alpha or beta chain respectively.\u00a0 Signs and symptoms range from mild to severe based on the types of mutations present.<\/p>\n

          Pernicious Anemia:<\/strong> is a rare auto-immune disease in which auto-antibodies binding to and inhibiting the action of Intrinsic Factor. Intrinsic Factor is produced by intestinal cells and is required for the absorbtion of dietary vitamin B12<\/sub>.\u00a0 A low retic count, indicating low levels of erythropoiesis may occur.\u00a0 Without treatment vitamin B12<\/sub> deficiency leads to anemia.<\/p>\n

          Hemorrhagic Anemia:<\/strong> as the name suggests is due to excessive blood loss.<\/p>\n

           <\/p>\n

          Polycythemia<\/strong> is defined as a condition in which there is excessive red blood cell production.\u00a0 The word polycythemia originates from poly- meaning many, cyte referring to cell, and -emia referring to blood.\u00a0 This condition can be dangerous as it thickens blood, increases the risk of blood clots, and also puts a strain on the heart to pump harder.\u00a0 Unfortunately many elite at<\/span>hletes\u00a0 have been found to have blood dope by injecting themselves with erythropoietin (EPO) to artificially increase red blood cell count for improved oxygen delivery and athletic performance.<\/p>\n

          On the other, moving to a higher altitude, with lower atmospheric oxygen levels, can naturally increase levels of EPO.\u00a0 In this case a higher hematocrit level may also be present.<\/p>\n

          Erythrocyte Sedimentation Rate (ESR):<\/strong> is a diagnostic blood test, that involves calculating the rate at which erythrocytes settle to the bottom of a tube of blood.\u00a0 RBCs are the heaviest component of blood and will settle to the bottom of the tube, however their rate of settling is affected by: the number of RBCs per mL of blood as well as the number of plasma proteins present.\u00a0 For example, an adult male (XY) typically has a higher hematocrit compared to an age-matched female (XX).\u00a0 Having more RBCs per mL results in slower settling as the erythrocytes are negatively charged and repel each other which slows down sedimentation.\u00a0 On average the ESR of young adult males is 12mm\/hr and the average ESR of age-matched females is 18mm\/hr.\u00a0 During injury or infection the number of plasma proteins (e.g. CRP, prothrombin, plasminogen, fibrinogen, complement proteins) per mL increases.\u00a0 These proteins allow the RBCs to stick closer together and fall faster.\u00a0 Therefore a ESR is often proportional to the amount of damage or inflammation that is present in the body.\u00a0 Serious infections, autoimmune disease, and chronic ailments can result in ESRs that are 100mm\/hr or more.<\/p>\n

           <\/p>\n

          Summary<\/strong><\/p>\n

            \n
          • Describe plasma components & define vocabulary words:<\/strong>\n
              \n
            • Plasma<\/strong> – liquid matrix containing water, electrolytes, and plasma proteins<\/li>\n
            • Plasma proteins<\/strong> – antibodies, complement proteins, clotting factors, albumen and transporter proteins<\/li>\n
            • Platelets\/Thrombocytes<\/strong> – a nuclear cell fragments formed from large megakaryocytes;\u00a0 involved in clotting (hemostasis)<\/li>\n
            • Leukocytes<\/strong> – WBCs<\/li>\n
            • Lymphocytes:<\/strong> type of WBC involved in antibody production (B lymphocytes), targeted immune response (T lymphocytes), and surveillance (NK lymphocytes)<\/li>\n
            • Neutrophils:<\/strong> The most abundant phagocyte in the blood; contain extensive lysosomes<\/li>\n
            • Eosinophils:<\/strong> Destroy parasitic worms & immune complexes<\/li>\n
            • Basophils<\/strong> & Mast cells<\/strong>: Release histamine, heparin, prostaglandins, and leukotrienes in process known as degranulation<\/li>\n
            • Erythrocytes<\/strong> – RBCs; transport oxygen & carbon dioxide<\/li>\n
            • Hematocrit<\/strong> –\u00a0 % by volume of blood that is \u00a0 formed elements<\/li>\n
            • Anemia:<\/strong> reduced oxygen-carrying capacity of blood due to low levels of functional RBCs or hemoglobin.<\/span><\/li>\n
            • Polycythemia;<\/strong> greater than normal # of RBCs<\/li>\n
            • EPO, erythropoietin<\/strong>: hormone that stimulates production of RBCs<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n","protected":false},"author":1370,"menu_order":4,"template":"","meta":{"pb_show_title":"on","pb_short_title":"","pb_subtitle":"Pictures coming soon!","pb_authors":["zoe-soon"],"pb_section_license":"cc-by-nc-sa"},"chapter-type":[],"contributor":[60],"license":[57],"class_list":["post-30","chapter","type-chapter","status-web-only","hentry","contributor-zoe-soon","license-cc-by-nc-sa"],"part":25,"_links":{"self":[{"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/pressbooks\/v2\/chapters\/30","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/wp\/v2\/users\/1370"}],"version-history":[{"count":25,"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/pressbooks\/v2\/chapters\/30\/revisions"}],"predecessor-version":[{"id":1019,"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/pressbooks\/v2\/chapters\/30\/revisions\/1019"}],"part":[{"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/pressbooks\/v2\/parts\/25"}],"metadata":[{"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/pressbooks\/v2\/chapters\/30\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/wp\/v2\/media?parent=30"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/pressbooks\/v2\/chapter-type?post=30"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/wp\/v2\/contributor?post=30"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/pressbooks.bccampus.ca\/pathophysiology\/wp-json\/wp\/v2\/license?post=30"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}