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Chronic inflamation

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Chronic inflamation

  1. 1. CHAPTER 2 Inflammation (5 OBJECTIVES)1) (Concept) Understand the chain, progression, or sequence of vascular and cellular events in the histologic evolution of acute inflammation
  2. 2. 2) (Rote?) Learn the roles of various“chemical mediators” of acuteinflammation3) Know the three possible outcomes ofacute inflammation4) Visualize the morphologic patterns ofacute inflammation5) Understand the causes, morphologicpatterns, principle cells, minor cells, ofchronic and granulomatousinflammation
  3. 3. SEQUENCE OF EVENTS• NORMAL HISTOLOGY • VASODILATATION • INCREASED VASCULAR PERMEABILITY • LEAKAGE OF EXUDATE • MARGINATION, ROLLING, ADHESION • TRANSMIGRATION (DIAPEDESIS) • CHEMOTAXIS • PMN ACTIVATION • PHAGOCYTOSIS: Recognition, Attachment, Engulfment, Killing (degradation or digestion) • TERMINATION • 100% RESOLUTION, SCAR, or CHRONIC INFLAMMATION are the three possible outcomes
  4. 4. ACUTE INFLAMMATION• “PROTECTIVE” RESPONSE•NON-specific
  5. 5. ACUTE INFLAMMATION• VASCULAR EVENTS• CELLULAR EVENTS (PMN or PolyMorphonuclear Neutrophil, Leukocyte?, “POLY”, Neutrophil, Granulocyte, Neutrophilic Granulocyte• “MEDIATORS”
  6. 6. ACUTEINFLAMMATION Neutrophil Polymorphonuclear Leukocyte, PMN, PML “Leukocyte” Granulocyte, Neutrophilic granulocyte “Poly-” Polymorph
  7. 7. HISTORICAL HIGHLIGHTS (Egypt, 3000 BC)RuborCalorTumorDolor5th (functio laesa)
  8. 8. STIMULI for acute inflammation• INFECTIOUS• PHYSICAL• CHEMICAL• Tissue Necrosis• Foreign Bodies (FBs)• Immune “responses”, or “complexes”
  9. 9. Vascular Changes• Changes in Vascular Flow and Caliber• Increased Vascular Permeability
  10. 10. INCREASED PERMEABILITY• DILATATION• Endothelial “gaps”• Direct Injury• Leukocyte Injury• Transocytosis (endo/exo)• New Vessels
  11. 11. LEAKAGE OFPROTEINACEOUS FLUID( EXUDATE, NOT TRANSUDATE)
  12. 12. EXTRAVASATION of PMNs• MARGINATION (PMN’s go toward wall)• ROLLING (tumbling and HEAPING)• ADHESION• TRANSMIGRATION (DIAPEDESIS)
  13. 13. ADHESION MOLECULES (glycoproteins) affectingADHESION and TRANSMIGRATION• SECRETINS (from endothelial cells)• INTEGRINS (from many cells)
  14. 14. CHEMOTAXISPMNs going to the site of “injury”AFTER transmigration
  15. 15. LEUKOCYTE “ACTIVATION”• “triggered” by the offending stimuli for PMNs to: – 1) Produce eicosanoids (arachidonic acid derivatives) • Prostaglandin (and thromboxanes) • Leukotrienes • Lipoxins – 2) Undergo DEGRANULATION – 3) Secrete CYTOKINES
  16. 16. PHAGOCYTOSIS• RECOGNITION• ENGULFMENT• KILLING (DEGRADATION/ DIGESTION)
  17. 17. CHEMICAL MEDIATORS• From plasma or cells• Have “triggering” stimuli• Usually have specific targets• Can cause a “cascade”• Are short lived
  18. 18. CLASSIC MEDIATORS • PLATELET• HISTAMINE ACTIVATING• SEROTONIN FACTOR (PAF)• COMPLEMENT • CYTOKINES• KININS • /CHEMOKINES• CLOTTING • LYSOSOME FACTORS CONSTITUENTS• EICOSANOIDS • FREE RADICALS• NITRIC OXIDE • NEUROPEPTIDES
  19. 19. HISTAMINE• Mast Cells, basophils• POWERFUL Vasodilator• Vasoactive “amine”• IgE on mast cell
  20. 20. SEROTONIN• (5HT, 5-Hydroxy- Tryptamine)• Platelets and EnteroChromaffin Cells• Also vasodilatation, but more indirect• Evokes N.O. synthetase (a ligase) from argenine
  21. 21. COMPLEMENT SYSTEM• >20 components, in circulating plasma• Multiple sites of action, but LYSIS is the underlying theme
  22. 22. KININ SYSTEM• BRADYKININ is KEY component, 9 aa’s• ALSO from circulating plasma• ACTIONS – Increased permeability – Smooth muscle contraction, NON vascular – PAIN
  23. 23. CLOTTING FACTORS• Also from circulating plasma• Coagulation, i.e., production of fibrin• Fibrinolysis
  24. 24. EICOSANOIDS(ARACHIDONIC ACID DERIVATIVES) • Part of cell membranes • 1) Prostaglandins (incl. Thromboxanes) • 2) Leukotrienes • 3) Lipoxins (new) MULTIPLE ACTIONS AT MANY LEVELS
  25. 25. Prostaglandins(thromboxanes included)• Pain• Fever• Clotting
  26. 26. Leukotrienes• Chemotaxis• Vasoconstriction• Increased Permeability
  27. 27. Lipoxins• INHIBIT chemotaxis• Vasodilatation• Counteract actions of leukotrienes
  28. 28. Platelet-Activating Factor (PAF)• Phospholipid• From MANY cells, like eicosanoids• ACTIVATE PLATELETS, powerfully
  29. 29. CYTOKINES/CHEMOKINES• CYTOKINES are PROTEINS produced by MANY cells, but usually LYMPHOCYTES and MACROPHAGES, numerous roles in acute and chronic inflammation –TNFα, IL-1, by macrophages• CHEMOKINES are small proteins which are attractants for PMNs (>40)
  30. 30. NITRIC OXIDE• Potent vasodilator• Produced from the action of nitric oxide synthetase from arginine
  31. 31. LYSOSOMAL CONSTITUENTS• PRIMARY • SECONDARY• Also called • Also called SPECIFIC AZUROPHILIC, or NON-specific • Lactoferrin • Lysozyme• Myeloperoxidase • Alkaline Phosphatase• Lysozyme (Bact.) • Collagenase• Acid Hydrolases
  32. 32. FREE RADICALS• O2 – (SUPEROXIDE)• H2O2 (PEROXIDE)• OH- (HYDROXYL RADICAL)• VERY VERY DESTRUCTIVE
  33. 33. NEUROPEPTIDES• Produced in CNS (neurons)• SUBSTANCE P• NEUROKININ A
  34. 34. OUTCOMES OF ACUTE INFLAMMATION• 1) 100% complete RESOLUTION• 2) SCAR• 3)CHRONIC inflammation
  35. 35. Morphologic PATTERNS of Acute INFLAMMATION (EXUDATE)• Serous (watery)• Fibrinous (hemorrhagic, rich in FIBRIN)• Suppurative (PUS)• Ulcerative
  36. 36. BLISTER, “Watery”, i.e., SEROUS
  37. 37. FIBRINOUS
  38. 38. PUS =PURULENT ABSCESS = POCKET OF PUS =NEUTROPHILS
  39. 39. PURULENT, FIBRINOPURULENT
  40. 40. ULCERATIVE
  41. 41. SEQUENCE OF EVENTS• NORMAL HISTOLOGY • VASODILATATION • INCREASED VASCULAR PERMEABILITY • LEAKAGE OF EXUDATE • MARGINATION, ROLLING, ADHESION • TRANSMIGRATION (DIAPEDESIS) • CHEMOTAXIS • PMN ACTIVATION • PHAGOCYTOSIS: Recognition, Attachment, Engulfment, Killing (degradation or digestion) • TERMINATION • 100% RESOLUTION, SCAR, or CHRONIC inflammation
  42. 42. CHRONIC INFLAMMATION (MONOS) “MONO”CYTELYMPHOCYTE MACROPHAGE
  43. 43. CAUSES ofCHRONIC INFLAMMATION • 1) PERSISTENCE of Infection • 2) PROLONGED EXPOSURE to insult • 3) AUTO-IMMUNITY
  44. 44. Cellular Players• LYMPHOCYTES• MACROPHAGES (aka, HISTIOCYTES)• PLASMA CELLS• EOSINOPHILS• MAST CELLS
  45. 45. MORPHOLOGY• INFILTRATION• TISSUE DESTRUCTION• HEALING
  46. 46. GRANULOMASGRANULOMATOUS INFLAMMATION 4 COMPONENTS FIBROBLASTS LYMPHS HISTIOS “GIANT” CELLS
  47. 47. GRANULOMASGRANULOMATOUS INFLAMMATION CASEATING (TB) NON-CASEATING
  48. 48. LYMPHATIC DRAINAGE• SITE REGIONAL LYMPH NODES
  49. 49. SYSTEMIC MANIFESTATIONS (NON-SPECIFIC)• FEVER, CHILLS• C-Reactive Protein (CRP)• “Acute Phase” Reactants, i.e., α1-α2• Erythrocyte Sedimentation Rate (ESR) increases• Leukocytosis• Pulse, Blood Pressure• Cytokine Effects, e.g., TNF(α), IL-1
  50. 50. NORMAL SPESerumProteinElectrophoresisIn ACUTEInflammationAlpha-1 & alpha-2are increased, i.e.,“acute phase”reactants.

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