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Ch2-Inflam (1).ppt
This document outlines the key events and processes in acute inflammation. It begins with vasodilation and increased vascular permeability, allowing fluid leakage and migration of neutrophils to the site of injury. Neutrophils are activated and undergo phagocytosis to eliminate pathogens. Chemical mediators like histamine, prostaglandins and cytokines further promote the inflammatory response. This sequence aims to resolve the trigger and heal tissue, and may result in full resolution, scarring, or progression to chronic inflammation characterized by lymphocytes and macrophages. The document also discusses chronic and granulomatous inflammation.
Ch2-Inflam (1).ppt
- 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
- 3. 2) (Rote?) Learnthe roles of various “chemical mediators” of acute inflammation 3) Know the three possible outcomes of acute inflammation 4) Visualize the morphologic patterns of acute inflammation 5) Understand the causes, morphologic patterns, principle cells, minor cells, of chronic and granulomatous inflammation
- 4. 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
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- 6. ACUTE INFLAMMATION •VASCULAR EVENTS •CELLULAREVENTS (PMN or PolyMorphonuclear Neutrophil, Leukocyte?, “POLY”, Neutrophil, Granulocyte, Neutrophilic Granulocyte ONE CELL!!!!! •“MEDIATORS”
- 7. ACUTE INFLAMMATION Neutrophil Polymorphonuclear Leukocyte, PMN, PML “Leukocyte” Granulocyte,Neutrophilic granulocyte “Poly-” Polymorph
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- 9. STIMULI for acute inflammation •INFECTIOUS(B>V) •PHYSICAL •CHEMICAL • Tissue Necrosis • Foreign Bodies (FBs) • Immune “responses”, or “complexes”, but usually CHRONIC
- 10. Vascular Changes • Changesin Vascular Flow and Caliber • Increased Vascular Permeability
- 11. INCREASED PERMEABILITY •DILATATION •Endothelial “gaps” •DirectInjury •Leukocyte Injury •Transocytosis (endo/exo) •New Vessels
- 12. LEAKAGE OF PROTEINACEOUS FLUID (EXUDATE,NOT TRANSUDATE)
- 13. EXTRAVASATION of PMNs • MARGINATION (PMN’sgo toward wall) • ROLLING (tumbling and HEAPING) • ADHESION • TRANSMIGRATION (DIAPEDESIS)
- 14. ADHESION MOLECULES (CAMs) (glycoproteins)affecting ADHESION and TRANSMIGRATION • SELECTINS (from endothelial cells): L,P,E • INTEGRINS (from many cells): ~8 types
- 15. CHEMOTAXIS PMNs going tothe site of “injury” AFTER transmigration
- 16. LEUKOCYTE “ACTIVATION” • “triggered” bythe offending stimuli for PMNs to: –1) Produce eicosanoids (arachidonic acid derivatives, 20 carbon chains) • Prostaglandin (and thromboxanes) • Leukotrienes • Lipoxins –2) Undergo DEGRANULATION –3) Secrete CYTOKINES (“STORM”)?
- 17. PHAGOCYTOSIS • RECOGNITION • ENGULFMENT •KILLING (DEGRADATION/ DIGESTION)
- 18. CHEMICAL MEDIATORS • Fromplasma or cells • Have “triggering” stimuli • Usually have specific targets • Can cause a “cascade” • Are short lived • Many are α-1 and α-2!
- 19. CLASSIC MEDIATORS • HISTAMINE •SEROTONIN • COMPLEMENT • KININS • CLOTTING FACTORS • EICOSANOIDS • NITRIC OXIDE • PLATELET ACTIVATING FACTOR (PAF) • CYTOKINES • /CHEMOKINES • LYSOSOME CONSTITUENTS • FREE RADICALS • NEUROPEPTIDES
- 20. HISTAMINE • Mast Cells, basophils •POWERFUL Vasodilator • Vasoactive “amine” • IgE on mast cell
- 21. SEROTONIN • (5HT, 5-Hydroxy- Tryptamine) •Platelets and EnteroChromaffin Cells • Also vasodilatation, but more indirect • Evokes N.O. synthetase (a ligase)
- 22. COMPLEMENT SYSTEM • >20 components, incirculating plasma • Multiple sites of action, but LYSIS is the underlying effect CASCADE!!!
- 23. KININ SYSTEM • BRADYKININis KEY component, 9 aa’s, from mast cells • ALSO from circulating plasma • ACTIONS – Increased permeability – Smooth muscle contraction, NON vascular –Produces PAIN !!!
- 24. CLOTTING FACTORS • Also fromcirculating plasma • Coagulation, i.e., production of fibrin • Fibrinolysis
- 26. EICOSANOIDS (ARACHIDONIC ACID DERIVATIVES) •Partof cell membranes •1) Prostaglandins (incl. Thromboxanes) •2) Leukotrienes •3) Lipoxins (new) MULTIPLE ACTIONS AT MANY LEVELS
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- 31. Platelet-Activating Factor (PAF) • Phospholipid •From MANY cells, like eicosanoids • ACTIVATE PLATELETS, powerfully
- 32. CYTOKINES/CHEMOKINES • CYTOKINES arePROTEINS 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)
- 33. NITRIC OXIDE • Potentvasodilator • Produced from the action of nitric oxide synthetase from arginine
- 34. LYSOSOMAL CONSTITUENTS • PRIMARY •Also called AZUROPHILIC, or NON-specific • Myeloperoxidase • Lysozyme (Bact.) • Acid Hydrolases • SECONDARY • Also called SPECIFIC • Lactoferrin • Lysozyme • Alkaline Phosphatase • Collagenase
- 35. FREE RADICALS • O2– (SUPEROXIDE) •H2O2 (PEROXIDE) •OH- (HYDROXYL RADICAL) •VERY VERY DESTRUCTIVE
- 36. NEUROPEPTIDES • Produced inCNS (neurons) • SUBSTANCE P • NEUROKININ A
- 37. OUTCOMES OF ACUTE INFLAMMATION •1) 100% complete RESOLUTION • 2) SCAR • 3)CHRONIC inflammation
- 38. Morphologic PATTERNS of AcuteINFLAMMATION (EXUDATE) •Serous (watery) •Fibrinous (hemorrhagic, rich in FIBRIN) •Suppurative (PUS) •Ulcerative
- 39. BLISTER, “Watery”, i.e.,SEROUS
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- 44. 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
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- 46. CAUSES of CHRONIC INFLAMMATION •1)PERSISTENCE of Infection •2) PROLONGED EXPOSURE to insult •3) AUTO-IMMUNITY
- 47. Cellular Players •LYMPHOCYTES •MACROPHAGES (aka, HISTIOCYTES) •PLASMA CELLS • EOSINOPHILS • MAST CELLS
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- 51. LYMPHATIC DRAINAGE (SPREAD?) • SITEREGIONAL LYMPH NODES SAME AS TUMOR!!!!!
- 52. 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
- 53. NORMAL SPE Serum Protein Electrophoresis In ACUTE Inflammation Alpha-1& alpha-2 are increased, i.e., “acute phase” reactants.