Wound Healing

Within seconds of vascular injury, vasoconstriction reduces blood loss. Subendothelial collagen exposes von Willebrand factor, which captures platelets via GP1b. Activated platelets aggregate via GP IIb/IIIa and fibrinogen. The coagulation cascade (intrinsic + extrinsic → common) generates thrombin, which converts fibrinogen to fibrin, stabilizing the platelet plug. Activated platelets release PDGF, TGF-β, and other growth factors that recruit inflammatory cells. Bleeding disorders (hemophilia, von Willebrand disease, platelet dysfunction) impair this phase.

Neutrophils arrive within hours via chemotactic gradients (IL-8, complement C5a) — phagocytose bacteria and debris with reactive oxygen species. Macrophages arrive at 48-72 hours and become the orchestrators: clear debris, secrete TGF-β, FGF, PDGF, VEGF to recruit fibroblasts and stimulate angiogenesis. M1 macrophages dominate early (proinflammatory); M2 macrophages dominate later (resolution and repair). Persistent inflammation due to bacterial biofilm, foreign body, or ischemia stalls healing — a hallmark of chronic wounds.

The pink, beefy, friable tissue filling a healing wound bed. Composed of new capillaries (angiogenesis driven by VEGF and FGF), fibroblasts depositing collagen III, and macrophages. Granulation tissue is granular in appearance from capillary loops. Its presence indicates healthy proliferation phase. Excess (exuberant granulation, "proud flesh") may need debridement or silver nitrate. Pale or absent granulation suggests poor perfusion or infection. Wounds heal by primary intention (sutured, minimal granulation) or secondary intention (open, fills with granulation then re-epithelializes).

Multifactorial. Peripheral neuropathy reduces protective sensation — repetitive trauma goes unnoticed. Microvascular disease and macroangiopathy reduce perfusion. Hyperglycemia impairs neutrophil function, reduces collagen synthesis, glycates matrix proteins, and feeds bacteria. ~25% of diabetics develop a foot ulcer in their lifetime; ~15% of ulcers progress to amputation. Management: glycemic control, off-loading (total contact cast), debridement, infection control, revascularization if indicated, advanced therapies (negative pressure wound therapy, growth factors, skin substitutes).

Both are excess scar from collagen overproduction. Hypertrophic scars: stay within original wound boundary, often regress over years, more common after burns and tension. Keloids: extend beyond wound margins, do not regress, more common in darker-skinned individuals and on chest, shoulders, earlobes. Treatment: intralesional triamcinolone, silicone sheeting, pressure garments, cryotherapy, surgical excision (high recurrence — combine with steroid injection or radiation), 5-fluorouracil, laser. Prevention: minimize tension, early scar massage and silicone.

Initial collagen III is laid down in disorganized bundles within days to weeks. Replacement with collagen I, cross-linking, and reorientation along stress lines proceeds for 1-2 years. Tensile strength rises from ~10% at 1 week to ~80% at 1-2 years — never reaches 100% of normal skin. Surgical scars are weakest at 1 week (suture removal timing); patients should avoid heavy lifting for 6 weeks postoperatively. Remodeling involves matrix metalloproteinases (MMPs) and tissue inhibitors (TIMPs) — imbalance contributes to chronic wounds and keloids.

Local: infection, foreign body, ischemia (venous insufficiency, peripheral arterial disease), pressure (decubitus ulcers), repeated trauma, irradiation. Systemic: diabetes (hyperglycemia, neuropathy, vasculopathy), malnutrition (especially protein and zinc), vitamin C deficiency (impairs collagen hydroxylation — scurvy reopens old wounds), smoking (vasoconstriction, hypoxia, reduced fibroblast function — major risk for surgical complications), glucocorticoids and immunosuppressants, advanced age, obesity. Optimization is critical before elective surgery.