Updated: 1/3/2021

Inflammation

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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

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