Pathology Lecture: Chemical Mediators (PDF)

Pathology lecture (6) CHEMICAL MEDIATORS OF ACUTE INFLAMMATION  Pathology Chemical substances released during acute inflammation & control inflammatory process (responsible for initiation and promotion of vascular phenomenon).  Derived from the inflammatory cells &...

Pathology lecture (6) CHEMICAL MEDIATORS OF ACUTE INFLAMMATION  Pathology Chemical substances released during acute inflammation & control inflammatory process (responsible for initiation and promotion of vascular phenomenon).  Derived from the inflammatory cells &  Derived from plasma proteins (synthesized endothelial cells. in liver). a. Amines: Histamine & Serotonin. a. Peptides: fibrin & fibrin degradation b. Arachidonic acid metabolites: products. Prostaglandins and Leukotriens. b. Kinins: bradykinin. c. Cytokines: Interleukin-1 (IL-1), Interferon c. Clotting System: converts fibrinogen into (INF) & Tumor necrosis factor (TNF). fibrin. d. Lysosomal Enzymes: Released from d. Fibrinolytic system: converts fibrin into neutrophils and macrophages. fibrin degradation product. e. Oxygen-derived Free Radicals: hydrogen e. Complement system: series of plasma peroxide (H2O2) or superoxide (O¯). proteins (named C1 to C9) and produce some active products e.g. C3a & C5a. Pathology  histamine, Prostaglandin & Bradykinin.  histamine, Bradykinin, C3a, C5a & Oxygen Free radicals.  C3a, C5a & leukotriens.  C3b, lysosomal enzymes and Oxygen free radicals.  IL-1 & TNF.  bradykinin & Prostaglandin. complements as chemical mediators These are plasma proteins numbered C1 to C9. Their role in inflammation include: a. C3a and C5a: increase vascular permeability and chemotaxis and leukocyte activation. b. C3b: opsonization during phagocytosis. c. C5b to C9: kills some bacteria.  Pathology 1) Redness due to V.D. 1) Necrotic damaged tissues. 2) Hotness due to V.D. and increased blood 2) Arterioles, venules & capillaries are flow. dilated and filled with blood. 3) Swelling due to presence of inflammatory 3) Fluid exudate: exudate.  Observed by separation of tissues and 4) Pain and Tenderness due to: pale staining of its fibers + fibrin”.  Pressure of exudate on the sensory 4) Cellular exudate: nerves.  Mainly neutrophils (in first 24-48h) and  Release of Bradykinin & Prostaglandins macrophages (after 48h)”. in inflammatory area. 5) Loss of function due to pain & tissue damage. Pathology Pathology  Due to release IL-1 & TNF which may originate either: a. exogenous (released from bacteria) or b. Endogenous (released from inflammatory cells).  They affect the heat regulating center in the brain thus disturbing the optimum temperature of bacterial living (but also harm the body tissue).  This means increase leukocytic count due to stimulationof the bone marrow by IL-1 & TNF.  Due to toxins and increased catabolism. Pathology If the body resistance overcomes the irritant. Inflammation may show:  The tissue returns completely to normal  Regeneration if mild tissue damage structure and function. occurred.  Fibrosis & the normal structure and  This occurs when: function are not restored. 1. No tissue damage occurred.  It occurs with: 2. Mild irritant. 1. Severe tissue 3. The injured tissue is capable of 2. Severe regeneration. 3. Tissues that do not regenerate If the irritant overcomes the body defense → spread of infection by:- by fluid exudate that passes to the surrounding tissues. if the organisms are still living inside the phagocytic cells. bacteremia, toxemia, septicemia and pyaemia. lymphangitis and lymphadenitis. The defense mechanism weakens the irritant but is not completely eliminated “the causative agent is not removed because the body is unable to get rid of it completely”. Thus the acute inflammation pass into chronic inflammation. Pathology