Overview Cardinal signs of inflammation rubor (redness) result of vasodilation specifically the arteriolar smooth muscle mediated by prostaglandins, bradykinin, and histamine dolor (pain) result of sensitization of pain nerve endings mediated by bradykinin and PGE2 calor (heat) result of vasodilation (increased blood flow) mediated by prostaglandins, bradykinin, and histamine tumor (swelling) result of increased permeability of post capillary venules leading to an exudate functio laesa (loss of function) Stages of Inflammation Fluid exudation endothelial injury ↑ post-capillary venule permeability vasodilation Leukocyte activation emigration chemotaxis (bacterial products, complement, chemokines) phagocytosis killing Potential outcomes restoration of normal structure granulation tissue highly vascularized and fibrotic abscess fibrosis surrounding pus fistula abnormal communication fibrosis/scarring collagen deposition resulting in altered structure and function Acute vs. Chronic Acute chemical mediators activation of Toll-like receptors (TLRs) by pathogen-associated molecular patterns (PAMPs) arachidonic acid metabolites prostaglandins and leukotrienes complement system hageman factor (Factor XII) defined by the effector cells neutrophils eosinophils antibodies rapid onset (seconds to minutes) may have long lasting "acute" inflammation Chronic defined by effector cells monocytes plasma cells characterized by persistent destruction and repair associated with blood vessel proliferation fibrosis granulomas are a subtype of chronic inflammation the body attemps to contain a substance that it perceives as foreign but is unable to eliminate formation is mediated by interferon-γ release from Th1 cells which activate macrophages macrophages release IL-12 which activates Th1 cells granuloma formation is maintained by IL-12 and TNF-alpha defining feature is the presence of epithelioid histiocytes presence of multinucleated giant cells is not required for a granuloma two types caseating presence of central necrotic zone e.g. TB, fungal infections noncaseating lack of central necrotic zone e.g. sarcoidosis, beryllium, Crohn disease, cat scratch disease (Bartonella), and Wegener's granulomatosis