--- module: 096-02 language: en chapter: 96 title: "General and Diagnostic Pathology: Patterns, Specimens, and Clinicopathological Reasoning" module_title: "Inflammation, repair, fibrosis, environmental injury, and systemic response" source_sha256: 669d83368d9830b2261f20fe71b43ace17efc8015aeec24ae0b2afbcdfc7ab9f --- # Inflammation, repair, fibrosis, and environmental injury ## Purpose of inflammation ### Recognise danger, contain cause, prepare repair ### Pathological when excessive, prolonged, unresolved ### Inflammation is not the same as infection #### Sterile infarction, crystals, trauma, tumours ## Acute vascular and cellular events ### Minutes to days: vessels, proteins, neutrophils ### Sentinel cells detect danger patterns ### Arteriolar dilation causes warmth and redness ### Permeability leaks protein-rich fluid #### Swelling and slowed, concentrated flow ### Leukocytes marginate, roll, adhere, migrate ### Neutrophils arrive early #### Granules, oxidants, proteases, traps #### Kill microbes but damage host ### Monocytes become macrophages ## Exudates and mediators ### Serous: cell-poor fluid ### Fibrinous: fibrin may organise into adhesions ### Suppurative: pus #### Abscess may need drainage ### Ulcer: lost epithelium over inflammation ### Histamine: rapid dilation and leak ### Prostaglandins and leukotrienes ### Complement opsonises and recruits ### Tumour necrosis factor and interleukin one ### Blocking one pathway can impair defence ## Systemic response and resolution ### Fever via hypothalamic prostaglandins #### Chills generate heat to new set point ### Acute-phase proteins rise, albumin falls ### Severe activation causes leak and coagulopathy ### Resolution is active #### Remove stimulus, stop neutrophil recruitment #### Macrophages clear apoptotic neutrophils #### Failed resolution sustains injury ## Chronic and granulomatous inflammation ### Weeks to years: infiltration, destruction, repair ### Persistent infection, autoimmunity, toxins, tumours ### Macrophage programmes change with signals ### Granuloma: epithelioid and giant cells #### Infectious and non-infectious causes #### Caseation supportive, not specific #### Sparse organisms need integrated testing ## Regeneration and scar formation ### Regeneration needs proliferating cells and scaffold ### Scar when injury extensive or matrix lost ### Angiogenesis builds new capillaries ### Granulation tissue is not granulomatous ### Fibroblasts deposit matrix #### Type three collagen remodelled to type one ### Metalloproteinase balance #### Excess degradation weakens repair #### Excess synthesis produces fibrosis ### Myofibroblasts contract wounds ## Wound healing and complications ### Primary intention: apposed clean edges ### Secondary intention: more contraction and matrix ### Tensile strength rises slowly, rarely complete ### Impaired by infection, poor perfusion, glucocorticoids #### Vitamin C deficiency impairs hydroxylation ### Hypertrophic scar stays within wound ### Keloid extends beyond wound ### Adhesions and contractures ## Organ fibrosis ### Final pathway in chronic organ injury ### Repeated damage activates mesenchymal cells ### Transforming growth factor beta drives matrix ### Stiffness feeds back via mechanotransduction ### Cross-linking and parenchymal loss limit reversal ## Environmental injury ### Dose, route, duration, metabolism, susceptibility ### Particle size sets deposition site ### Fibres resist clearance ### Occupational history spans a lifetime ### Metabolic activation creates reactive intermediates ### Genotoxic carcinogens: no assumed safe dose ### Ionising radiation damages DNA #### Deterministic effects above thresholds #### Stochastic cancer risk is probabilistic ### Thermal, cold, electrical, pressure injury #### Electrical: deep necrosis, minor skin change ## Systemic inflammation and sepsis ### No single mediator or value diagnoses it ### Infection or sterile injury can trigger it ### Sepsis: dysregulated response with organ dysfunction ### Injury continues as microbes fall ### Defence and repair can themselves cause disease