25 The Inflammatory Response, Fever, Healing, Cell Proliferation, Tissue Regeneration and Repair – Learning Objectives

Learning Outcomes:

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

Describe common cellular adaptations and understand why each occurs, including:

1. Use of pathophysiology terminology
2. Listing of  common causes of cellular damage and types of cellular necrosis.
3. Familiarization with the steps of inflammation and its role in cell injury and healing
4. Exemplars include: Cuts, Pap smears, Fire Burn Injury, Electrical Burn, Frost bite, Mercury poisoning, Alzheimer’s, Radiation poisoning, Liquefaction of Brain, Liquefaction of infection, Pancreas/Breast trauma; Myocardial & Kidney Infarction, Tuberculosis, Hypercalcemia, Diabetes circulation

Specific Learning Objectives Study Guide:

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

Describe Normal Defenses of the Body:

• Innate (non-specific) Defenses:
  • Mechanical/Physical – skin, hair, mucus, sebum, urination, cilia, cell shedding
  • Biochemical – sweat, tears & saliva (lysozymes), bile, stomach pH, cerumen, mucus, vaginal secretions, prostatic and testicular secretions,
  • Normal Flora
  • Phagocytes: (WBCs such as monocytes, fixed and free macrophages, microglia, neutrophils, eosinophils, dendritic cells) capable of diapedesis/emigration/transmigration.
  • Complement System (Classical Pathway with antibody, Lectin Pathway, and Alternative Pathway) – involving 30+ complement plasma protein cascade of activation – resulting in opsonization, MAC (Membrane Attack Complexes), stimulation of mast cells & basophils
  • Cytokine family:  Glycoproteins produced by WBCs, fibroblasts, endothelial cells, stromal (connect tissue) cells
    • Interferons: (chemical messages that stimulate defense)
      • Alpha Interferons – produced by virally infected host cells to attract & stimulate NK cells and stimulate AVP production in neighbouring cells.
      • Beta Interferons – produced by fibroblasts to slow inflammation, and promote healing
      • Gamma Interferons – produced by T  & NK cells to stimulate macrophage activity
    • Chemokines: induce chemotaxis
    • Lymphokines: produced by T lymphocytes to: 1) attract macrophages & 2) stimulate B lymphocytes to produce antibodies
    • Interleukins: produced by helper T cells to:
      1. activate macrophages and stimulate fever (act as endogenous pyrogens)
      2. stimulate T & B cell differentiation
      3. Stimulate hemopoietic cells to proliferate → producing more WBCs
    • Natural Killer cells (NK Lymphocytes) – type of WBC (White Blood Cell/Leukocyte)
  • Inflammatory Response
  • Fever – speeds up WBC activity and repairs, inhibits pathogen activity

• Describe plasma components & define vocabulary words:
  • Plasma – liquid matrix containing water, electrolytes, and plasma proteins
  • Plasma proteins – antibodies, complement proteins, clotting factors, albumen and transporter proteins
  • Platelets/Thrombocytes – a nuclear cell fragments formed from large megakaryocytes;  involved in clotting (hemostasis)
  • Leukocytes – WBCs
  • Lymphocytes: type of WBC involved in antibody production (B lymphocytes), targeted immune response (T lymphocytes), and surveillance (NK lymphocytes)
  • Neutrophils: The most abundant phagocyte in the blood; contain extensive lysosomes
  • Eosinophils: Destroy parasitic worms & immune complexes
  • Basophils & Mast cells: Release histamine, heparin, prostaglandins, and leukotrienes in process known as degranulation
  • Erythrocytes – RBCs; transport oxygen & carbon dioxide
  • Hematocrit –  % by volume of blood that is   formed elements
  • Anemia: reduced oxygen-carrying capacity of blood due to low levels of functional RBCs or hemoglobin.
  • Polycythemia; greater than normal # of RBCs
  • EPO, erythropoietin: hormone that stimulates production of RBCs

• Describe 3 stages of hemostasis:  vascular spasm (role of endothelin and tunica media), platelet plug formation (extrinsic and intrinsic pathways, roles of Factor X, thrombin, clotting factors, and Ca++) and coagulation (role of fibrin)

• Describe stages of healing: fibrinolysis (role of tPA, and plasmin) and regeneration (role of PDGF)

• Describe components of the Lymphatic System:
  • Lymph Vessels
  • Lymph Nodes
  • Lymphocytes (Helper T, Cytotoxic T, Memory T, Suppressor/Regulator T, B, Memory B, plasma cells), Cell-mediated and Humoral Immunity
  • Macrophages, Dendritic Cells
  • Primary and Secondary Response, Vaccination
  • Antibody Roles – Neutralization, Agglutination, Precipitation, Opsonization
  • Cytotoxic T cell activity – perforin, lymphotoxin, apoptosis

• • Explain cause of Inflammation – innate (non-specific) response to tissue injury; caused by: tissue damage from cuts, sprains, chemicals, ischemia, heat, cold, infections, or foreign objects
    • Stimulated by vasoactive chemicals released by mast cells: histamine, prostaglandin, leukotrienes – all induce: vasodilation, increased capillary permeability, bronchoconstriction, mucous production (stim. gland secretion), and chemotaxis of WBCs
  • Explain 5 signs of Inflammation:
    • Redness & warmth: due to ↑ blood flow (hyperemia) to damaged area
    • Swelling (edema): protein & fluid into interstitial space
    • Pain: increased pressure of fluid on nerves; release of chemical mediators – i.e., bradykinins, histamine (itch), prostaglandins
    • Loss of function: may develop if cells lack nutrients; edema may interfere with movement

Explain 2 phases of inflammation:

• 1. Vascular:  vasodilation & increased cap perm → exudate (fluid); stagnation of flow & clotting of blood occurs which aids in localizing the spread of infectious microorganisms.
  • • Histamine, Leukotrienes, Bradykinin, Prostaglandins: induces vasodilation, increased capillary permeability
    • Histamine: additionally induces itch
    • Prostaglandins: additionally induce pain, fever
    • Bradykinogen (plasma protein): additionally induce pain when in active bradykinin form
    • Histamine receptors found on nerve endings and on blood vessel walls
• 2. Cellular: – emigration (diapedesis) of WBCs;  Production of more WBCS (e.g. neutrophils, shift to the left)