Acute & Chronic Inflammation PDF

AC U T E I N F L A M M AT I O N Causes Microbial infections Tissue necrosis Foreign bodies Hypersensitivity reaction Vascular & cellular changes Changes in vascular flow & caliber Increased vascular permeability Edema = exudate or transudate Contraction of endothelial cells Damage to endothelium Car...

AC U T E I N F L A M M AT I O N Causes Microbial infections Tissue necrosis Foreign bodies Hypersensitivity reaction Vascular & cellular changes Changes in vascular flow & caliber Increased vascular permeability Edema = exudate or transudate Contraction of endothelial cells Damage to endothelium Cardinal signs Rubor = redness Tumor = swelling Calor = heat Dolor = pain Function laesa = loss of function Migration & chemotaxis of leukocyte Chemotaxis = leukocytes emigrate towards site of injury along a chemical gradient of chemoattractants Stimuli that act as chemoattractant Exogenous = bacterial products Endogenous = complement, leukosis & chemokines Phagocytosis 1. Recognition & attachment 2. Engulfment & fusion of phagosome & lysosome 3. Killing & degradation of ingested material Mediators Local mediators mast cell = histamine Neutrophil / macrophage = lysosomal enzyme Platelet = serotonin Cell derived mediators Vasodilation = PGI2, PGE1, PGE2 & PGD2 Vasoconstriction = thromboxane A2, leukosis C4, D4 & E4 Increased vascular permeability = LTC4, LTD4 & LTE4 Chemotaxis & leukocyte adhesion = LTB4, 5-HETE Pain mediation & fever induction = PGE2 Patterns of inflammation Serous = outpouring of thin fluid Catarrhal = mucous hypersecretion, exclusively on mucous membranes Fibrinous = more severe, inflammation in lining of body cavities Purulent = production of pus Hemorrhagic inflammation = exudative & involves microvascular injury with bleeding Necrotizing/ulcerative = Produced by sloughing of inflammatory necrotic tissue C H RO N I C I N F L A M M AT I O N “Pathological inflammation of prolonged duration in which inflammation, tissue injury & the healing proceed simultaneously” Causes Persistent infection Prolonged exposure to causative agents Immune hyperresponsiveness Examples Cardiovascular disease RA IBD Type II diabetes Alzheimer’s Asthma Cancer Morphological features Infiltration with mononuclear cells = indicates persistent reaction to injury Tissue destruction = induced by inflammatory ells Repair involving angiogenesis & fibrosis = replace lost tissue & proliferation of fibroblasts and accumulation of excess extracellular matrix Key Immune cells Macrophages Activated by immune receptors (TLR) and cytokines (IFN-gamma) secreted by T-helper cells & NK cells When activated they're powerful phagocytic and secrete biologically active products: NO, protease, cytokines & growth factors Lymphocytes B-lymphocytes = mature to plasma cell & induce antibody mediates responses T-lymphocytes = cell mediated reactions, T-cytotoxic (CD8) & T-helper (CD4) Neutrophils = stimulated by presence of microbes Eosinophils = fight parasitic infections, mediated by IgE Mast cells = in connective tissue, binds Fc portion of IgE antibody in degranulation process MAST Censthtamine Ec IgE Granulatmous inflammation Pattern of chronic inflammatory reaction in which predominant cells are macrophages Granuloma = nodular aggregation of epithelioid macrophages surrounded by a cuff of lymphocytes focal area of granulomatous inflammation Immune granuloma Caused by insoluble particles that are capable of inducing a cell mediated immune response Macrophages are transformed into epithelioid cells & multinucleate giant cells Foreign body granulomas Epithelioid cells & giant cells are apposed to surface and encompass the foreign body Systemic Effects Fever = body temp increases 1-4 ‘C Elevated conc of acutephase proteins Leukocytosis Increased pulse & BP: rigor, chills & malaise Sepsis Sepsis Systemic vasodilation = tissue hypoperfusion & hemodynamic shock Disseminated intravascular coagulation Metabolic abnormalities: insulin resistance & hyperglycemia Multi organ failure H E A L I N G & R E PA I R Cellular proliferation 3 types of cell based on regenerative capacity Labile = continuously dividing= Stable = usually H0 but driven into G1 with rapid proliferation Permanent = non-dividing Factors influencing repair Local factors Infection Mechanical factors Foreign bodies Size Location General factors Nutrition diabetes mellites Circulatory stasis Steroid treatment Hydrogen peroxide treatment Growth factors Epidermal growth factor (EGF) = epithelial cells Fibroblast growth factor = fibroblasts Vascular endothelial growth factor (VEGF) = angiogenesis Transforming growth factor (TGF) = fibrinogenesis Platelet-derived growth factor (PDGF) = migration & proliferation of fibroblasts, smooth muscle & monocyte chemotaxis Extracellular matrix Provides turgor ,rigidity, support, adhesion substrate & reservoir Must remain intact for parenchyma healing 2 forms = interstitial matrix & basement membrane Protein components Collagen Adhesive glycoproteins Proteoglycans Elastin Tissue repair Basic features Inflammation Angiogenesis Migration & proliferation of fibroblasts Scar formation Connective tissue remodeling Scar formation