Inflammation Lect


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Inflammation Lect

  2. 2. <ul><li>EDUCATION IS HANGING AROUND UNTIL YOU’VE CAUGHT ON </li></ul><ul><li>Charles Darwin </li></ul>
  3. 3. INFLAMMATION <ul><li>is the reaction of a tissue and its microcirculation to a pathogenic insult or it is a reaction which is characterized by the generation of inflammatory mediators and amount of fluid and leucocytes from the blood into extra vascular tissue </li></ul>
  4. 4. FOUR CARDINAL SIGNS OF INFLAMMATION <ul><li>Rubor (redness) </li></ul><ul><li>Color (heat) </li></ul><ul><li>Tumor (swelling) </li></ul><ul><li>Dolar (pain) </li></ul><ul><li>Aulus Celsus </li></ul><ul><li>Roman Encyclopedist </li></ul>
  5. 5. INFLAMMATION PROCEEDS AS FOLLOWS <ul><li>INITIATION of the inflammatory response, in which localization and clearance of foreign substances and onset of stimuli take place </li></ul>
  6. 6. <ul><li>AMPLIFICATION of the inflammatory response, in which both soluble mediators and cellular inflammatory system are activated, follows recognition of injury </li></ul>
  7. 7. <ul><li>TERMINATION of the inflammatory response, after generation of inflammatory agents and elimination of the foreign agent, is accomplished by specific inhibitors of the mediators </li></ul>
  8. 8.                                                       : CELLS OF INFLAMMATION
  9. 14. ACUTE INFLAMMATION <ul><li>is a stereotyped response to recent or ongoing injury. Although the process is complex, the principal features are dilatation and leaking of vessels, and involvement of circulating neutrophils </li></ul>
  10. 15. <ul><li>The hallmarks of acute inflammation are </li></ul><ul><li>(1) vasodilatation and increased vascular permeability; </li></ul><ul><li>(2) entry of neutrophils into the tissues. </li></ul>
  11. 16. <ul><li>Sequence of Acute Inflammation </li></ul><ul><li>Vascular changes transient </li></ul><ul><li>vasoconstriction of arterioles </li></ul><ul><li>vasodilation </li></ul><ul><li>of arterioles leading to increased blood flow </li></ul><ul><li>increased </li></ul><ul><li>permeability, loss of fluid, concentration of red cells, </li></ul><ul><li>increased blood viscosity, and slowing of circulation (stasis) </li></ul>
  12. 17. <ul><li>Hyperemia is a generic term for extra blood in an organ due to dilation of the arterioles </li></ul>
  13. 18. <ul><li>Edema </li></ul><ul><li>Increased vascular permeability hallmark </li></ul><ul><li>of acute inflammation </li></ul><ul><li>Loss of protein reduced intravascular osmotic pressure, increased extravascular osmotic pressure </li></ul><ul><li>Increased hydrostatic pressure from vasodilation </li></ul><ul><li>Increased extravascular fluid – edema </li></ul>
  14. 19. <ul><li>Leaky Endothelium </li></ul><ul><li>Gaps between endothelial cells </li></ul><ul><li>Direct endothelial cell injury </li></ul><ul><li>Chemical mediators histamine, bradykinin, leukotriences, complement, </li></ul>
  15. 20. <ul><li>Cellular Changes </li></ul><ul><li>Neutrophils </li></ul><ul><li>Margination </li></ul><ul><li>Rolling </li></ul><ul><li>Adherence/pavementing </li></ul><ul><li>Transmigration (diapedesis) </li></ul><ul><li>Migration toward chemotactic stimulus </li></ul>
  16. 21. <ul><li>Emigration (&quot;diapedesis&quot;) of neutrophils from the vessels into the tissues occurs when the cells squeeze through the widened endothelial cell gaps, then get through the basement membrane by digesting it with enzymes </li></ul>
  17. 22. <ul><li>Adhesion and transmigration </li></ul><ul><li>Binding of adhesion molecules on WBC and endothelial cell modulated by chemical mediators </li></ul><ul><li>Endothelial adhesion receptors: selectins (E,P,L), immunoglobulin family molecules (ICAM1, VCAM1), WBC receptors, integrins (CD11/18, VLA04), mucin like glycoproteins </li></ul><ul><li>Migration of PMN across endothelium (transmigration) CD31 </li></ul>
  18. 23. <ul><li>Chemotaxis </li></ul><ul><li>WBCs move toward site of injury under influence of chemoattractants </li></ul><ul><li>exogenous: bacterial products </li></ul><ul><li>endogenous: complement components (C5a), products of lipoxygenase pathway (LTB4), cytokines (e.g., IL8) </li></ul>
  19. 24. <ul><li>Phagocytosis by PMN, Macrophages </li></ul><ul><li>Recognition and attachment </li></ul><ul><li>opsonins (Fc fragments, C3b, C3bi) </li></ul><ul><li>receptors (IgG Fc, CR13) </li></ul><ul><li>· Engulfment </li></ul><ul><li>· Killing or degradation (e.g. H202) </li></ul><ul><li>· Release of WBC products (lysosomal enzymes, 02 metabolites, AA metabolites) </li></ul>
  20. 30. Acute inflammation - Acute pneumonia - lung. Almost every alveolar space is filled with cellular infiltrate. There is hardly any air space left in the lung
  21. 31. Acute inflammation - Acute pneumonia - lung. An abundance of eosinophilic material (neutrophils) with fine strands are present in the alveolar space.
  22. 32. Inflammatory infiltrate, fluid with fibrin into the alveolar spaces
  23. 33. Acute fibrinous pericarditis
  24. 34. the yellowish fluid in this opened pericardial cavity is a purulent exudate.
  25. 35. Multifocal, suppurative, hepatitis
  26. 36. Acute, suppurative, pneumonia
  27. 37. Infective endocarditis (bovine)
  28. 38. Chemical Mediators of Inflammation
  29. 39. <ul><li>Vasoactive amines (preformed) </li></ul><ul><li>histamine </li></ul><ul><li>mast cells, basophils, platelets </li></ul><ul><li>dilation of arterioles, increased Permeability of venules </li></ul><ul><li>Serotonin (5hydroxytryptamine) </li></ul><ul><li>platelets, enterochromaffin cells </li></ul><ul><li>increased vascular permeability </li></ul>
  30. 40. <ul><li>Plasma proteases </li></ul><ul><li>Complement C3a, C5a (C4a) </li></ul><ul><li>Anaphylatoxins increase vascular permeability/vasodilation (via histamine) </li></ul><ul><li>C5a chemotactic for PMN, monocytes, basophils </li></ul><ul><li>increase adhesion to endothelium (activates WBC) </li></ul><ul><li>C3b/bi opsonins </li></ul>
  31. 41. <ul><li>The complement system is a group of 20 plasma proteins which are activated in cascades by the classic or alternate pathways </li></ul>
  32. 42. <ul><li>Kinins (cascade activated by factor XIIa) </li></ul><ul><li>Bradykinin (increased permeability, vasodilation) </li></ul>
  33. 43. <ul><li>Bradykinin increases vascular permeability, dilates blood vessels, contracts non-vascular smooth muscle, and causes pain. </li></ul>
  34. 44. <ul><li>Clotting system </li></ul><ul><li>Thrombin (increased WBC adhesion) </li></ul><ul><li>Factor Xa (increased permeability, WBC exudation) </li></ul>
  35. 45. <ul><li>Fibrinolytic system </li></ul><ul><li>Fibrin split products (increased permeability) </li></ul>
  36. 46. <ul><li>Arachidonic acid metabolites </li></ul><ul><li>Cyclooxygenase pathway </li></ul><ul><li>prostaglandins (vasodilation, potentiate edema) </li></ul><ul><li>prostacyclins (vasodilation, plt aggreg) </li></ul><ul><li>thromboxane (vasoconstr, plt aggreg) </li></ul><ul><li>Lipoxygenase pathway </li></ul>
  37. 47. <ul><li>Prostaglandins : products of the cyclooxygenase pathway of arachidonic acid metabolism </li></ul>
  38. 48. <ul><li>Prostacyclin (PGI2), from the vessel wall, prevents platelet aggregation, dilates vessels </li></ul>
  39. 49. <ul><li>leukotrienes (increased permeability, vasoconstriction, bronchospasm) </li></ul>
  40. 50. <ul><li>Leukotrienes : products of the lipooxygenase pathway of arachidonic acid metabolism. They are produced by all of the inflammatory cells except lymphocytes </li></ul>
  41. 51. <ul><li>Platelet activating factor </li></ul><ul><li>vasodilation, increased permeability </li></ul><ul><li>Increased WBC adhesion (increased integrin binding) </li></ul><ul><li>chemotaxis </li></ul><ul><li>Platelets aggregation </li></ul>
  42. 52. <ul><li>Cytokines </li></ul><ul><li>Proteins produced by many cell types that modulate functions of other cells </li></ul><ul><li>interleukin1/ tumor necrosis factor </li></ul><ul><li>acute phase reaction (fever, neutrophilia) </li></ul><ul><li>endothelial activation </li></ul><ul><li>Nitric oxide </li></ul><ul><li>From macrophage/endothelium – vasodilatation </li></ul>
  43. 54. Outcomes of Acute Inflammation <ul><li>Complete resolution </li></ul><ul><li>Fibrosis </li></ul><ul><li>Granulation tissue </li></ul><ul><ul><li>capillaries </li></ul></ul><ul><ul><li>macrophages, fibroblasts </li></ul></ul><ul><li>Collagen-contracts to scar </li></ul><ul><li>Abscess </li></ul><ul><li>Chronic Inflammation </li></ul>
  44. 55. Granulation tissue, healing wound
  45. 56. LUNG ABSCESS
  47. 58. Myocardial Abscess
  48. 59. Chronic inflammation <ul><li>(&quot;late-phase inflammation&quot;) is a response to prolonged problems, orchestrated by T-helper lymphocytes. It may feature recruitment and activation of T- and B-lymphocytes, macrophages, eosinophils, and/or fibroblasts </li></ul>
  49. 60. Lymphocytes and Plasma cells
  50. 61. Eosinophils and Lymphocytes
  51. 62. Chronic inflammation-Lung <ul><li>Lymphoid nodule </li></ul><ul><li>Fibrosis </li></ul><ul><li>Alveolar spaces </li></ul>                                                     
  52. 63. Features of Chronic inflammation <ul><li>Mononuclear cell infiltration </li></ul><ul><li>Monocytes—transform to macrophages in connective tissue—“activated” macrophages </li></ul><ul><li>lymphocytes </li></ul><ul><li>plasma </li></ul>
  53. 64. Mixed inflammatory infiltrate (Plasma cell, Macrophages and Eosinophils)
  54. 65. Chronic cystitis
  55. 66. Chronic cystitis (lymphocytic cystitis)
  56. 67. <ul><li>Tissue destruction-repair granulation tissue </li></ul><ul><li>-formation of blood vessels (angiogenesis) </li></ul><ul><li>-fibroblast proliferation </li></ul><ul><li>Collagen deposition/scarring </li></ul>
  57. 68. Chronic nephritis, kidney is atrophied and fibrotic
  58. 69. <ul><li>Morphologic patterns of acute and chronic inflammation </li></ul><ul><li>Purulent, or suppurative: neutrophils (PMNs) predominate </li></ul><ul><li>Fibrinous: abundant fibrin, usually involving serosal surfaces, e.g. pericardium </li></ul><ul><li>Serous: abundant fluid ,e.g. skin blister </li></ul>
  59. 70. <ul><li>Systemic Effects of Inflammation </li></ul><ul><li>Fever (IL1, IL6, TNF, prostaglandins) </li></ul><ul><li>Malaise </li></ul><ul><li>Pain </li></ul><ul><li>Rapid Pulse </li></ul>
  60. 71. <ul><li>Labs Findings: </li></ul><ul><li>-neutrophilia in blood </li></ul><ul><li>-increased erythrocyte sedimentation rate ---increased acute phase reactants (e.g. </li></ul><ul><li> C reactive protein, complement) </li></ul>
  61. 72. Granulomatous inflammation <ul><li>A distinctive pattern of chronic inflammatory reaction in which the predominant cell type is an activated macrophage with a modified epithelial like (epithelioid) appearance. </li></ul><ul><li>a special kind of chronic inflammation which occurs in the presence of indigestible material and/or cell-mediated immunity (&quot;type IV hypersensitivity“) </li></ul>
  62. 73. <ul><li>A granuloma is a focal area of granulomatous inflammation. It consists of a microscopic aggregation of macrophages that are transformed into epithelium like cells (epithelioid cells) surrounded by a collar of mononuclear leukocytes. </li></ul>Granuloma
  63. 75. epithelioid cells
  64. 76. <ul><li>Granulomas can contain syncytial giant cells (polykaryons). For our purpose, there are two kinds of giant cells: </li></ul><ul><li>-Langhans giant cells have their nuclei </li></ul><ul><li>arranged in a horseshoe around the edge, </li></ul><ul><li>- foreign body giant cells , with nuclei </li></ul><ul><li>dispersed more or less evenly </li></ul>
  65. 77. Langhan’s giant cells Foreign body giant cells
  66. 78. Langhan’s type of giant cell
  67. 79. Granulomatous pneumonia, Langhans-type giant cell, epithelioid cells, lymphocytes, and fibrosis
  68. 80. Foreign body Granuloma
  69. 81. <ul><li>The classic granulomatous diseases include tuberculosis, leprosy, foreign body reactions (*  including the reactions to everything from sutures to schistosome eggs), the deep fungal infections, berylliosis, and the mysterious disease &quot;sarcoidosis&quot;. </li></ul>
  70. 82. <ul><li>Granulomas with suppuration (i.e., with pus in their centers; &quot;stellate microabscesses&quot;) are typical of those bacterial diseases with a propensity to involve lymph nodes. These are lymphogranuloma venereum, cat scratch fever, brucellosis, plague, tularemia, glanders-melioidosis, listeria, campylobacter, and yersinia infection </li></ul>
  71. 83. <ul><li>Granulomas with caseation are typical of certain fungal infections (histoplasmosis, blastomycosis, and coccidioidomycosis, as above) and of mycobacterial (&quot;fungus-like bacteria&quot;) infections (basically TB, leprosy, and &quot;atypical mycobacteria&quot;). </li></ul>
  72. 85. Granulomatous lymphadenitis (Histoplasmosis)
  73. 86. lung with tuberculosis
  74. 87. lung with tuberculosis
  75. 88. Granulomatous pneumonia (tuberculosis)
  76. 89. Granulomatous pneumonia (tuberculosis), area of central necrosis, Langhans-type giant cells, fibrosis, epithelioid cells
  77. 90. Caseous granulomatous inflammation-LUNG
  78. 91. gross appearance of caseous necrosis in a hilar lymph node infected with tuberculosis
  79. 92. Renal tuberculosis
  80. 93. Caseous granulomatous lymphadenitis
  81. 94. Carries Spine
  82. 95. <ul><li>Granulomas with foreign bodies : aspirated food, schistosome eggs, toxocara, silicone injections, splinters, sutures, windshield fragments, chalazions, ruptured epidermoid cysts, sea urchin spines, mucus plugs in cystic fibrosis, nitrogen bubbles (&quot;pneumatosis&quot;; &quot;tissue emphysema&quot;), </li></ul>
  83. 96. <ul><li>dead aspergillus fungi, dead filaria, ingrown hairs, talc in the lungs, metastatic calcification bits, uric acid crystals, sclerosing lipogranuloma of the penis, insect bites, &quot;actinic elastolytic granuloma of Mieschler&quot; (a foreign body reaction to your own elastic fibers), etc. </li></ul>
  84. 97. Cholesterol Granuloma
  85. 98. Silicotic Granuloma
  86. 99. Foreign Body Giant cell Granuloma
  87. 100. foreign body type giant cell at the upper left of center adjacent to a segment of vegetable material aspirated into the lung
  88. 101. Two foreign body giant cells are seen just to the right of center where there is a bluish strand of suture material
  89. 102. Other solid granulomas <ul><li>organic pneumoconioses, berylliosis, zirconium disease (the infamous &quot;armpit sarcoidosis&quot;), Wegener's granulomatosis, Lennert's lymphoma, sarcoidosis, Crohn's disease, primary biliary cirrhosis, Toxoplasmosis and Q-fever and cutaneous leishmaniasis etc </li></ul>
  90. 103. <ul><li>THE END </li></ul>