Acute Inflammation

  • Non-specific response to injury due to a number of different tissue insults which can be endogenous or exogenous e.g. infection, ishaemia (hypoxia), trauma, toxin exposure
    • Aim is the rid the cause and consequences of injury; however, inflammation can be harmful
  • Lasts minutes-days (longer than this is chronic inflammation)


  • Mediated by mostly chemical mediators e.g. bacterial toxins, histamine, serotonin, arachidonic acid, metabolites, cytokines, complement factors etc
    • The clotting system and inflammation are connected (bleeding causes inflammation)
    • The predominant cell type in acute inflammation is the neutrophil (macrophage is a cell of chronic inflammation).
  • Phases
    1. Widespread vasodilation (hyperaemia)
      1. Initially, if there is vascular injury, there is a rapid and transient vasoconstrictor response to avoid excess blood loss and to allow clot formation
      2. Platelet activation causes the release of various chemical mediators including prostaglandins, leukotrienes, histamine and serotonin
      3. Prostaglandins and nitrous oxide released cause widespread vasodilation, whilst serotonin, histamine and serotonin cause increased permeability
      4. They also cause recruitment of other cells involved, as well as activation of the complement cascade.
    2. Increased vascular permeability
      1. Immediate-transient response (occurs in every case)- only affects venules, in response to inflammatory mediators released in response to the insult.  Caused by contraction of the endothelial cells (causing larger intercellular gaps)
      2. Immediate-prolonged response- similar to transient but occurs when the stimulus is prolonged, causing a prolonged ‘immediate’ response.
      3. Delayed prolonged leakage- seen after hours or days.  Usually due to apoptosis of endothelial cells which opens up intercellular space to cause protein/fluid leak.  A good example is that of sunburn (delayed inflammation)
    3. Leucocyte extravasation and phagocytosis
      1. Margination- as blood flow decreases, leucocytes move from the centre to the edge of the vessel
      2. Rolling and adhesion (pavementing)- activated endothelial cells express intercellular adhesion molecules (e.g. ICAM-1), which bind to adhesion molecules on the leucocytes (integrins)
        1. Note ICAMs are upregulated in many inflammatory diseases and down-regulated in conditions such as diabetes, alcohol excess, steroid excess.
      3. Diapedesis or Emigration across the endothelium
      4. Chemotaxis/migration- attracted by complement factors and leukotrienes, amongst others (e.g. TGF; VEGF etc)
  • Note that neutrophils are the primary inflammatory cell recruited in the first 24 hours.  Macrophages become predominant after 48 hours.

Inflammatory mediators

  • See also complement
  • Kinin system
    • Activation of coagulation factor XII into factor XIIa sets off a series of enzyme reactions which results in the production of bradykinin.
    • Bradykinin is a potent vasodilator and increases vascular permeability.
  • Histamine and serotonin (mast cell/basophils and, to a smaller degree, platelets)
    • Release stimulated by C3a/C5a, bound IgE and IL1
    • Both are also potent vasodilators and increase vascular permeability.
  • Nitric Oxide (NO)
    • Produced by NO synthase by neurons, endothelial cells and the immune system
    • Acts to reduce intracellular calcium which causes smooth muscle dilatation, decreased cardiac contractility, reduced platelet and inflammatory cell activation
      • This can be protective in neurons and endothelial cells but can be pathological in acute inflammation (local vasodilator; bactericidal; downregulates neutrophil function but prolongs their lifespan; conversely induces apoptosis in macrophages)
  • Arachidonic Acid Derivatives
    • Arachidonic acid is present in cell membranes and is activated in acute inflammation by phospholipases which release it from the membrane.
    • It is then metabolised by one of two pathways
      • COX pathway to produce prostaglandins
        • These cause vasodilation, increased vascular permeability and can be hyperalgesic
      • Lipoxygenase pathway to produce Leukotrienes 
        • Cause increased permeability; constrict smooth muscle cells and act as a chemotactic agent to attract inflammatory cells
  • Other mediators include polypeptides, interferons (involved in protection against viral infection), interleukins (powerful chemotactic and proliferation agents), TNF-α, and free radicals (powerful enzymes used to break down invading/foreign cells)


  • Redness (rubor)
  • Swelling (tumor)
  • Heat (calor)
  • Pain (dolor)
  • Also loss of function and increased secretion

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