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  1. 1. Inflammation and Repair
  2. 2. Chronic & Granulomatous Inflammation
  3. 3. OBJECTIVES AND KEY PRINCIPLES TO BE TAUGHT: Upon completion of these 2 lectures , the student should: • Define chronic inflammation • Describe the characteristic features of chronic inflammation. • Describe the mechanism of chronic inflammation. • Enumerate the cells of chronic inflammation. • Enumerate the biologically active products secreted by activated macrophage • Define granulomatous inflammation
  4. 4. Chronic inflammation • Definition : • Inflammation of prolonged duration in which active inflammation, tissue injury and the healing proceed simultaneously • It is slow evolving (weeks to months) resulting into fibrosis • It occurs in two major patterns : • 1-chronic non specific • 2-specific granulomatous inflammation
  5. 5. Causes of chronic inflammation • Persistent infections – Organisms usually of low toxicity that invoke delayed hypersensitivity reaction – Mycobacterium tuberculosis and Treponema pallidum causes granulomatous reaction • Prolonged exposure to potentially toxic agents – Exogenous agents include silica which causes silicosis – Endogenous causes include atherosclerosis caused by toxic plasma lipid components • Autoimmunity – Auto-antigens provoke self-perpetuating immune responses that cause chronic inflammatory diseases like Rheumatoid Arthritis, Multiple Sclerosis. – Responses against common environmental substances cause chronic allergic diseases, such as bronchial asthma
  6. 6. MORPHOLOGIC FEATURES OF CHRONIC INFLAMMATION • Infiltration with mononuclear cells include – Macrophages – Lymphocytes – Plasma cells – and Eosinophils may be present also • Tissue destruction and distortion – induced largely by inflammatory cells. • Healing (fibrosis) – by connective tissue replacement of damaged tissue, accomplished by proliferation of small blood vessels (angiogenesis) and, in particular, fibrosis (granulation tissue)
  7. 7. MONONUCLEAR CELL INFILTRATION Macrophages  the dominant cellular player in chronic inflammation  The mononuclear phagocyte system (sometimes called reticuloendothelial system) consists of closely related cells of bone marrow origin, including blood monocytes and tissue macrophages MORPHOLOGIC FEATURES OF CHRONIC INFLAMMATION
  8. 8. mononuclear phagocyte system –monocytes begin to emigrate into extravascular tissues quite early in acute inflammation and within 48 hours they may constitute the predominant cell type
  9. 9.  Macrophages may be activated by a variety of stimuli, including  cytokines (e.g., IFN-γ) secreted by sensitized T lymphocytes and by NK cells  bacterial endotoxins  other chemical mediators  Activation results in  increased cell size  increased levels of lysosomal enzymes  more active metabolism  greater ability to phagocytos and kill ingested microbes.  Activated macrophages secrete a wide variety of biologically active products that, if unchecked, result in the tissue injury and fibrosis MONONUCLEAR CELL INFILTRATION Macrophages
  10. 10. . Products of macrophages 1.Acid and neutral proteases 2.Chemotactic factors 3.Reactive oxygen metabolites 4.Complement components 5. Coagulation factors 6.Growth promoting factors for fibroblasts, blood vessels and myeloid progenitor cells 7.Cytokines : IL-1, TNF 8.Other biologic active agents ( PAF, interferon, AA metabolites) to eliminate injurious agents such as microbes  to initiate the process of repair  It is responsible for much of the tissue injury in chronic inflammation Function?!!..
  11. 11. The roles of activated macrophages in chronic inflammation. Acute & Chronic inflam. persist
  12. 12. • In chronic inflammation, macrophage accumulation persists, this is mediated by different mechanisms: 1. Recruitment of monocytes from the circulation, which results from the expression of adhesion molecules and chemotactic factors 2. Local proliferation of macrophages after their emigration from the bloodstream 3. Immobilization of macrophages within the site of inflammation Macrophages
  13. 13. • Lymphocytes – Both T & B Lymphocytes migrates into inflammation site OTHER CELLS IN CHRONIC INFLAMMATION
  14. 14. Activated lymphocytes and macrophages influence each other and also release inflammatory mediators that affect other cells. –Lymphocytes and macrophages interact in a bidirectional way, and these reactions play an important role in chronic inflammation
  15. 15. •Eosinophils are abundant in immune reactions mediated by IgE and in parasitic infections • respond to chemotactic agents derived largely from mast cells • Granules contain major basic protein: toxic to parasites and lead to lysis of mammalian epithelial cells
  16. 16. Morphological Features of Chronic Inflammation II - Tissue destruction Occur due to: • Inflammatory cells. • Persistent infecting material.
  17. 17. Morphological Features of Chronic Inflammation III - Removal of damaged tissue, (healing): • Occur by proliferation of small blood vessels, (angiogenesis). • Proliferation of fibroblast, (fibrosis-repair).
  18. 18. Chronic Inflammation (Rheumatoid arthritis)
  19. 19. 2nd Yr Pathology 2010 Chronic inflammation: tissue effects Knee joint in rheumatoid arthritis
  20. 20. Chronic Bronchitis
  21. 21. Chronic Inflammation (Chronic Bronchitis)
  22. 22. Chronic Inflammation (Lung)
  23. 23. Granulomatous Inflammation
  24. 24. Granulomatous Inflammation • Diffinition: A distinctive pattern of chronic inflammation characterised by; Aggregations of macrophages having an enlarged, squamous cell-like appearance (called epithelioid macrophages) • Granuloma = Nodular collection of epithelioid macrophages surrounded by a rim of lymphocytes
  25. 25. Granulomatous inflammation Granulomas are millimeter size nodules of chronic inflammatory cells that can be isolated or confluent. Granuloma formation is the result of dealing with indigestible substances or pathogens and walls them off The essential component are modified macrophages named epithelioid cell (because of shape). Epithelioid cells can form multinucleated giant cells. Epithelioid cells are surrounded by a collar of lymphocytes and occasionally plasma cells. Fibrous connective tissue often surrounds granulomas (remodeling of tissue) Areas within the granuloma can undergo necrosis (prototype: caseous necrosis in tuberculosis). calcification or liquefaction and formation of a cavern if drained.
  26. 26. Granulomatous Inflammation Causes • Bacteria – Tuberculosis – Leprosy – Actinomycosis – Cat scratch disease • Parasites – Schistosomiasis – Leishmaniasis
  27. 27. Granulomatous Inflammation • Fungi – Histoplasmosis – Blastomycosis • Metal/Dust – Berylliosis – Silicosis
  28. 28. Granulomatous Inflammation • Foreign body – Splinter – Suture – Graft material • Sarcoidosis
  29. 29. Disease Cause Tissue Reaction Tuberculosis Mycobacterium tuberculosis Noncaseating tubercle Caseating tubercles Leprosy Mycobacterium leprae Acid-fast bacilli in macrophages; noncaseating granulomas Syphilis Treponema pallidum Gumma: wall of histiocytes; plasma cell Cat-scratch disease Gram-negative bacillus Rounded or stellate granuloma Sarcoidosis Unknown etiology Noncaseating granulomas Crohn disease Immune reaction against intestinal bacterial dense chronic inflammatory infiltrate with noncaseating granulomas Examples of Diseases with Granulomatous Inflammations
  30. 30. TB Pathogenesis • Bacterial entry • T Lymphocytes. • Macrophages. • Epithelioid cells. • Proliferation. • Central Necrosis &calcification. • Giant cell formation. • Fibrosis.
  31. 31. Granuloma Caseous Necrosis Epithelioid Macrophage Langhans Giant Cell Lymphocytic Rim
  32. 32. Continuous assessment • In the site of chronic inflammation, which of the following component is LEAST likely to be seen? • A) Macrophages • B) Neutrophils • C) Plasma cells • D) Lymphocytes
  33. 33. Continuous assessment • Which is a good example of granulomatous inflammation ? • A) Abscess. • B) Tuberculosis . • C) Ulcer. • D) fistula .