Inflammation by Ahmad


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chronic inflammation composed by ahmad, deptt of pharmacy university of peshawar 2010

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Inflammation by Ahmad

  1. 1. Composed by: Ahmad wali 3rd prof (M)
  2. 2. Definition: Inflammation is a protective response intended to remove injurious stimuli as well as the necrotic cells and tissues resulting from original insert. OR Repair process that causes the replacement of damaged tissues by regeneration of parenchyma cells or by filling of any residual defect by firous scar tissues.
  3. 3. ADVANTAGES:  It causes destruction of microbes.  Causes detoxification of toxins.  Clears infections.  Helps in healing process.  Causes repair of damaged tissues.
  4. 4. DISADVANTAGES: Inflammatory responses are sometimes harmful as they cause:  Life threatening anaphylactic reactions to insects bites, drugs and other chronic diseases like Rheumatoid arthritis, Atherosclerosis etc.  Inflammation of peritoneum leads to firous bands that causes obstruction of intestines.  Pericardial inflammation causes the formation of dense pericardium that impairs cardiac functions.
  5. 5. PLAYERS OF INFLAMMATION: The inflammatory responses have many players. They include: 1) CIRCULATING CELLS: I. Bone marrow derived polymorph nuclear leukocytes e.g., Basophils, Esinophils and Neutrophils. II. Lymphocytes III. Monocytes IV. Platelets. 2) CIRCULATING PROTEINS: I. Clotting factors II. Kininogens III. Complement proteins
  6. 6. 3) VASCULAR WALL CELLS: I. Connective tissue cells II. Smooth muscle cells III. Epithelial cells 4) EXTRA CELLULAR MATRIX: I. Fibrous structural proteins e.g., Elastin & Fibrinogen II. Gel-forming proteoglycans III. Adhesive glycoprotein e.g., Fibronectin, that are cell- ECM and ECM-ECM connectors.
  7. 7. Inflammatory stimulus Chemical mediators Inflammatory response until injurious stimulus is removed When the inflammatory stimulus is removed these mediators are then dissipated, catabolized or removed. TYPES OF INFLAMMATION:  Acute inflammation And  Chronic inflammation
  8. 8. Chronic inflammation is the inflammation with prolonged duration usually from weeks to months and sometimes to years in which active inflammation, tissue injury and healing process proceed simultaneously. DISTINGUISHING FEATURES:  Infiltration of mono-nuclear cells like lymphocytes, macrophages and plasma cells.  Destruction of tissue by inflammatory cells.  Proliferation of new vessels leading to repair (angiogenesis & fibrosis).
  9. 9. ORIGIN AND PROCESS: Chronic inflammation arises from acute inflammation. This transition takes place if the acute responses cannot be resolved either because of the persistence e.g., of injurious stimuli or by interference of the normal healing process e.g., peptic ulcer. Some types of injuries engender responses with chronic inflammation initially e.g., viral infections. SETTINGS LEADING TO CHRONIC INFLAMMATION: I. Viral infections II. Persistent microbial infections III. Prolonged exposure to potentially toxic materials IV. Autoimmune diseases
  10. 10. It is joined by lymphocytes and plasma cells, however mast cells and eosinophils are as well involved in chronic allergic diseases Blood monocytes Tissue macrophage (RES)migrate into tissue within 48 hours after injury and differentiate Kupffer cell (liver) Microglia (CNS) Histiocytes (spleen) Alveolar macs (lung) Lymphocyte Plasma cell
  11. 11. CHRONIC INFLAMMATORY CELLS & MEDIATORS: 1) MACROPHAGES: Macrophages are white blood cells within tissues, produced by the division of monocytes. A majority of macrophages are stationed at strategic points where microbial invasion or accumulation of dust is likely to occur. Each type of macrophage, determined by its location, has a specific name:  In liver Kupffer cells  Spleen and lymph nodes Sinus histocytes  Nervous system Microglial cells  Lungs Alveolar macrophages
  12. 12. During chronic inflammation macrophages serve to eliminate injurious agents and initiate repair- however, they are as well responsible for much of the tissue injury that occurs IFN-g Activated T cell or NK cell Tissue macrophage Activated macrophage Non Immune activation: Endotoxins, fibronectin, chemical mediators Tissue injury Toxic oxygen metabolites Metallo-proteases Coagulation factors AA metabolites and NO Fibrosis (Scaring) Growth factors involved in fibroblast proliferation (PDGF,TGFb,FGF) Angiogenesis factors (FGF,VEGF) Collagen deposition (IL-13 and TGFb)
  13. 13. FUNCTIONS OF MACROPHAGES: They help to:  Filter the particulate matter  Kill microbes  Alert immune system of the body.  Their life is 1-2 days. ACTIVATION OF MACROPHAGES: Activation of macrophages means:  Increase in size  Increase in lysosomal content  Increase in metabolism  Increase in microbial killing activity
  14. 14. ACTIVATION SIGNALS: Different signals required to activate macrophages are:  Cytokines produced by T-lymphocytes  Bacterial endotoxins  Different mediators produced during acute inflammation  Extra cellular matrix proteins e.g., Fibrinogen When macrophages become activated they produce different type of biologically active substances that either cause ; Cell injury OR Fibrosis.
  15. 15. Cell injury causing substances:  Acid and neutral proteases  Complement proteins C1 to C5  Coagulating factors V & VШ  Amino acids metabolites  Cytokines  Tumor necrosis factor Fibrosis causing substances:  Growth factors  Fibrogenic cytokines  Angiogenesis factors  Regeneration and remodeling factors
  16. 16. 2) LYMPHOCYTES: Both T- & B-lymphocytes are involved in chronic inflammation. Their migration is brought about by specific adhesion molecules and cytokines. The T- lymphocytes work in reciprocal with B-lymphocytes in chronic inflammation. The already activated macrophages release TNF & IL1 and activate the inactive lymphocytes which then produce different antibodies that cause destruction of antigens at the inflammatory site. 3) ESINOPHILS: They are usually found in parasitic infections and IgE mediated allergic reactions. Their migration is brought about by adhesion molecules produced by leukocytes and epithelial cells. Esinophils specific granules contain Major Basic Proteins which is highly cationic &toxic for parasites.
  17. 17. 4) MAST CELLS: Mast cells are tissue cells which are like basophils in shape. They are present in bone marrow and around blood vessels and do not enter the blood. They are specifically armed with IgE antibodies against certain antigens. When these antigens are encountered, they release histamines and amino acid metabolites. They cause initial vascular changes in acute inflammation and also cause anaphylactic reactions.
  18. 18. TYPES OF CHRONIC INFLAMMATION: 1) AGRANULOMATOUS: Granuloma is not formed, Inflammation is characterized by all features of chronic inflammation. Examples:  Chronic viral infections e.g., Hepatitis  Chronic autoimmune diseases e.g., Rheumatoid arthritis and Ulcerative colitis  Chronic chemical intoxication e.g., Chronic alcoholic liver disease  Allergic reactions e.g., Bronchial asthma
  19. 19. 2) GRANULOMATOUS INFLAMMATION: Characterized by aggregates of activated macrophages that assume a squamous cell like epithelloid appearance. GRANULOMA is defined as aggregates of macrophages formed due persistant response of T-lymphocytes to particular antigens. This has a granular cheesy appearance called as caseous necrosis. Examples are: Bacterial: Tuberculosis , Leprosy, Syphilis gumma etc.
  20. 20. Parasitic: Schistosomiasis Fungal: Histoplasma capsulatum, Blastomycosis. Inorganic metals / Dust: Silicosis Foreign bodies: Suture, Vascular graft. Unknown: Sarcodiosis.
  21. 21. Best Regards