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CHAPTER 2

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) (Rote?) Learn the roles of various “chemical mediators” of acute inflammation

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CHAPTER 2

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  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) (Rote?) Learn the roles of various “chemical mediators” of acute inflammation 3) Know the three possible outcomes of acute inflammation 4) Visualize the three morphologic patterns of acute inflammation 5) Understand the causes, morphologic patterns, principle cells, minor cells, of chronic and granulomatous inflammation

  3. ACUTE INFLAMMATION • “PROTECTIVE” RESPONSE • NON-specific

  4. ACUTE INFLAMMATION • VASCULAR EVENTS • CELLULAR EVENTS (PMN or PolyMorphonuclear Neutrophil, Leukocyte?, “POLY”, Neutrophil, Granulocyte, Neutrophilic Granulocyte • “MEDIATORS”

  5. ACUTE INFLAMMATION Neutrophil Polymorphonuclear Leukocyte, PMN, PML “Leukocyte” Granulocyte, Neutrophilic granulocyte “Poly-” Polymorph

  6. HISTORICAL HIGHLIGHTS (Egypt, 3000 BC) Rubor Calor Tumor Dolor 5th(functio laesa)

  7. STIMULI for acute inflammation • INFECTIOUS • PHYSICAL • CHEMICAL • Tissue Necrosis • Foreign Bodies (FBs) • Immune “responses”, or “complexes”

  8. Vascular Changes • Changes in Vascular Flow and Caliber • Increased Vascular Permeability

  9. INCREASED PERMEABILITY • DILATATION • Endothelial “gaps” • Direct Injury • Leukocyte Injury • Transocytosis (endo/exo) • New Vessels

  10. LEAKAGE OF PROTEINACEOUS FLUID (EXUDATE, NOT TRANSUDATE)

  11. EXTRAVASATION of PMNs • MARGINATION(PMN’s go toward wall) • ROLLING(tumbling and HEAPING) • ADHESION • TRANSMIGRATION(DIAPEDESIS)

  12. ADHESION MOLECULES(glycoproteins) affectingADHESION and TRANSMIGRATION • SECRETINS (from endothelial cells) • INTEGRINS (from many cells)

  13. CHEMOTAXIS PMNs going to the site of “injury” AFTER transmigration

  14. LEUKOCYTE“ACTIVATION” • “triggered” by the offending stimuli to: • Produce eicosanoids (arachidonic acid derivatives) • Prostaglandin (and thromboxanes) • Leukotrienes • Lipoxins • DEGRANULATION • CYTOKINESECRETION

  15. PHAGOCYTOSIS • RECOGNITION • ENGULFMENT • KILLING (DEGRADATION/DIGESTION)

  16. CHEMICAL MEDIATORS • From plasma or cells • Have “triggering” stimuli • Usually have specific targets • Can cause a “cascade” • Are short lived

  17. HISTAMINE SEROTONIN COMPLEMENT KININS CLOTTING FACTORS EICOSANOIDS NITRIC OXIDE PLATELET ACTIVATING FACTOR (PAF) CYTOKINES /CHEMOKINES LYSOSOME CONSTITUENTS FREE RADICALS NEUROPEPTIDES CLASSIC MEDIATORS

  18. HISTAMINE • Mast Cells • POWERFUL Vasodilator

  19. SEROTONIN • (5HT, 5-Hydroxy-Tryptamine) • Platelets and EnteroChromaffin Cells • Also vasodilatation, but more indirect

  20. COMPLEMENT SYSTEM • >20 components, in circulating plasma • Multiple sites of action, but LYSIS is the underlying theme

  21. KININ SYSTEM • BRADYKININ is KEY component • ALSO from circulating plasma • ACTIONS • Increased permeability • Smooth muscle contraction • PAIN

  22. CLOTTING FACTORS • Also from circulating plasma • Coagulation, i.e., production of fibrin • Fibrinolysis

  23. EICOSANOIDS(ARACHIDONIC ACID DERIVATIVES) • Part of cell membranes • Prostaglandins (incl. Thromboxanes) • Leukotrienes • Lipoxins (new) MULTIPLE ACTIONS AT MANY LEVELS

  24. Prostaglandins(thromboxanes included) • Pain • Fever • Clotting

  25. Leukotrienes • Chemotaxis • Vasoconstriction • Increased Permeability

  26. Lipoxins • INHIBIT chemotaxis • Vasodilatation • Counteract actions of leukotrienes

  27. Platelet-Activating Factor(PAF) • Phospholipid • From MANY cells, like eicosanoids • ACTIVATE PLATELETS, powerfully

  28. CYTOKINES/CHEMOKINES • CYTOKINES are PROTEINS produced by MANY cells, but usually LYMPHOCYTES and MACROPHAGES, numerous roles in acute and chronic inflammation • TNF, IL-1, by macrophages • CHEMOKINES are small proteins which are attractants for PMNs (>40)

  29. NITRIC OXIDE • Potent vasodilatator

  30. PRIMARY Also called AZUROPHILIC Myeloperoxidase Lysozyme (Bact.) Acid Hydrolases SECONDARY Also called SPECIFIC Lactoferrin Lysozyme Alkaline Phosphatase Collagenase LYSOSOMAL CONSTITUENTS

  31. FREE RADICALS • O2–(SUPEROXIDE) • H2O2(PEROXIDE) • OH- (HYDROXYL RADICAL) • VERY VERY DESTRUCTIVE

  32. NEUROPEPTIDES • Produced in CNS (neurons) • SUBSTANCE P • NEUROKININ A

  33. OUTCOMES OFACUTE INFLAMMATION • 100% complete RESOLUTION • SCAR • CHRONIC inflammation

  34. Morphologic PATTERNSof Acute INFLAMMATION(EXUDATE) • Serous (watery) • Fibrinous (hemorrhagic, rich in FIBRIN) • Suppurative (PUS) • Ulcerative

  35. BLISTER, “Watery”, i.e., SEROUS

  36. FIBRINOUS

  37. PUS = PURULENT ABSCESS = POCKET OF PUS

  38. PURULENT, FIBRINOPURULENT

  39. ULCERATIVE

  40. 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

  41. CHRONIC INFLAMMATION (MONOS) MONOCYTE MACROPHAGE HISTIOCYTE LYMPHOCYTE

  42. CAUSES ofCHRONIC INFLAMMATION • PERSISTENCE of Infection • PROLONGED EXPOSURE to insult • AUTO-IMMUNITY

  43. Cellular Players • LYMPHOCYTES • MACROPHAGES (aka,HISTIOCYTES) • PLASMA CELLS • EOSINOPHILS • MAST CELLS

  44. MORPHOLOGY • INFILTRATION • TISSUE DESTRUCTION • HEALING

  45. GRANULOMASGRANULOMATOUS INFLAMMATION 4 COMPONENTS FIBROBLASTS LYMPHS HISTIOS “GIANT” CELLS

  46. GRANULOMASGRANULOMATOUS INFLAMMATION CASEATING (TB) NON-CASEATING

  47. LYMPHATICDRAINAGE • SITE REGIONAL LYMPH NODES

  48. SYSTEMIC MANIFESTATIONS(NON-SPECIFIC) • FEVER, CHILLS • C-Reactive Protein (CRP) • “Acute Phase” Reactants • Erythrocyte Sedimentation Rate (ESR) increases • Leukocytosis • Pulse, Blood Pressure • Cytokine Effects, e.g., TNF(α), IL-1

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