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  <head>
    <title>096-02 Inflammation, repair, fibrosis, environmental injury, and systemic response</title>
    <ownerName>Integrated Medical Foundations</ownerName>
  </head>
  <body>
    <outline text="Inflammation, repair, fibrosis, and environmental injury">
      <outline text="Purpose of inflammation">
        <outline text="Recognise danger, contain cause, prepare repair"/>
        <outline text="Pathological when excessive, prolonged, unresolved"/>
        <outline text="Inflammation is not the same as infection">
          <outline text="Sterile infarction, crystals, trauma, tumours"/>
        </outline>
      </outline>
      <outline text="Acute vascular and cellular events">
        <outline text="Minutes to days: vessels, proteins, neutrophils"/>
        <outline text="Sentinel cells detect danger patterns"/>
        <outline text="Arteriolar dilation causes warmth and redness"/>
        <outline text="Permeability leaks protein-rich fluid">
          <outline text="Swelling and slowed, concentrated flow"/>
        </outline>
        <outline text="Leukocytes marginate, roll, adhere, migrate"/>
        <outline text="Neutrophils arrive early">
          <outline text="Granules, oxidants, proteases, traps"/>
          <outline text="Kill microbes but damage host"/>
        </outline>
        <outline text="Monocytes become macrophages"/>
      </outline>
      <outline text="Exudates and mediators">
        <outline text="Serous: cell-poor fluid"/>
        <outline text="Fibrinous: fibrin may organise into adhesions"/>
        <outline text="Suppurative: pus">
          <outline text="Abscess may need drainage"/>
        </outline>
        <outline text="Ulcer: lost epithelium over inflammation"/>
        <outline text="Histamine: rapid dilation and leak"/>
        <outline text="Prostaglandins and leukotrienes"/>
        <outline text="Complement opsonises and recruits"/>
        <outline text="Tumour necrosis factor and interleukin one"/>
        <outline text="Blocking one pathway can impair defence"/>
      </outline>
      <outline text="Systemic response and resolution">
        <outline text="Fever via hypothalamic prostaglandins">
          <outline text="Chills generate heat to new set point"/>
        </outline>
        <outline text="Acute-phase proteins rise, albumin falls"/>
        <outline text="Severe activation causes leak and coagulopathy"/>
        <outline text="Resolution is active">
          <outline text="Remove stimulus, stop neutrophil recruitment"/>
          <outline text="Macrophages clear apoptotic neutrophils"/>
          <outline text="Failed resolution sustains injury"/>
        </outline>
      </outline>
      <outline text="Chronic and granulomatous inflammation">
        <outline text="Weeks to years: infiltration, destruction, repair"/>
        <outline text="Persistent infection, autoimmunity, toxins, tumours"/>
        <outline text="Macrophage programmes change with signals"/>
        <outline text="Granuloma: epithelioid and giant cells">
          <outline text="Infectious and non-infectious causes"/>
          <outline text="Caseation supportive, not specific"/>
          <outline text="Sparse organisms need integrated testing"/>
        </outline>
      </outline>
      <outline text="Regeneration and scar formation">
        <outline text="Regeneration needs proliferating cells and scaffold"/>
        <outline text="Scar when injury extensive or matrix lost"/>
        <outline text="Angiogenesis builds new capillaries"/>
        <outline text="Granulation tissue is not granulomatous"/>
        <outline text="Fibroblasts deposit matrix">
          <outline text="Type three collagen remodelled to type one"/>
        </outline>
        <outline text="Metalloproteinase balance">
          <outline text="Excess degradation weakens repair"/>
          <outline text="Excess synthesis produces fibrosis"/>
        </outline>
        <outline text="Myofibroblasts contract wounds"/>
      </outline>
      <outline text="Wound healing and complications">
        <outline text="Primary intention: apposed clean edges"/>
        <outline text="Secondary intention: more contraction and matrix"/>
        <outline text="Tensile strength rises slowly, rarely complete"/>
        <outline text="Impaired by infection, poor perfusion, glucocorticoids">
          <outline text="Vitamin C deficiency impairs hydroxylation"/>
        </outline>
        <outline text="Hypertrophic scar stays within wound"/>
        <outline text="Keloid extends beyond wound"/>
        <outline text="Adhesions and contractures"/>
      </outline>
      <outline text="Organ fibrosis">
        <outline text="Final pathway in chronic organ injury"/>
        <outline text="Repeated damage activates mesenchymal cells"/>
        <outline text="Transforming growth factor beta drives matrix"/>
        <outline text="Stiffness feeds back via mechanotransduction"/>
        <outline text="Cross-linking and parenchymal loss limit reversal"/>
      </outline>
      <outline text="Environmental injury">
        <outline text="Dose, route, duration, metabolism, susceptibility"/>
        <outline text="Particle size sets deposition site"/>
        <outline text="Fibres resist clearance"/>
        <outline text="Occupational history spans a lifetime"/>
        <outline text="Metabolic activation creates reactive intermediates"/>
        <outline text="Genotoxic carcinogens: no assumed safe dose"/>
        <outline text="Ionising radiation damages DNA">
          <outline text="Deterministic effects above thresholds"/>
          <outline text="Stochastic cancer risk is probabilistic"/>
        </outline>
        <outline text="Thermal, cold, electrical, pressure injury">
          <outline text="Electrical: deep necrosis, minor skin change"/>
        </outline>
      </outline>
      <outline text="Systemic inflammation and sepsis">
        <outline text="No single mediator or value diagnoses it"/>
        <outline text="Infection or sterile injury can trigger it"/>
        <outline text="Sepsis: dysregulated response with organ dysfunction"/>
        <outline text="Injury continues as microbes fall"/>
        <outline text="Defence and repair can themselves cause disease"/>
      </outline>
    </outline>
  </body>
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