Wound Healing & Surgical Complications
Phases of healing, impaired healing, NPWT, groin wounds, stump care, and advanced wound management for MRCS vascular surgery
Phases of Wound Healing
Four distinct sequential phases with characteristic cellular events, growth factors, and molecular signalling. Master this section—fundamental to understanding all wound complications in vascular surgery.
Phase 1: Haemostasis (Seconds to Minutes)
Vessel injury exposes subendothelial collagen and tissue factor. Immediate vascular response: vasoconstriction (thromboxane A2, endothelin-1) → reduced flow. Platelet adhesion via Von Willebrand factor (vWF) binding to glycoprotein Ib (GPIb); platelet activation via collagen (GPVI) and ADP → shape change + granule release (alpha-granules: fibrinogen, vWF, P-selectin; dense-granules: ADP, serotonin, calcium). Fibrinogen bridges GPIIb/IIIa forming platelet plug. Coagulation cascade: extrinsic (tissue factor + VIIa → Xa), intrinsic (XIIa → Xa), common (Xa + Va → thrombin → fibrin). Fibrin clot = physical barrier + biological scaffold. Growth factors released: PDGF (chemoattractant, mitogen), TGF-β (immunomodulator, matrix deposition), EGF (epithelialisation), VEGF (angiogenesis), FGF (angiogenesis, fibroblast mitogen). All growth factors trapped in fibrin matrix, creating microenvironment for subsequent phases.
Phase 2: Inflammation (Hours to Day 5)
Vasodilation (histamine, prostaglandins, nitric oxide, bradykinin) → increased endothelial permeability → exudate (plasma + fibrinogen + growth factors + immunoglobulins). Celsian signs: calor (heat), rubor (redness), tumor (swelling), dolor (pain), functio laesa (loss of function).
Neutrophil phase (0-48 hours): Selectin-mediated rolling → ICAM-1/LFA-1 firm adhesion → diapedesis → chemotaxis (IL-8, C5a, LTB4). Functions: oxidative burst (NADPH oxidase → superoxide → H2O2 + hypochlorous acid; kills bacteria), granule release (proteases, lactoferrin), phagocytosis. Apoptosis by day 5; signals anti-inflammatory switch.
Macrophage phase (day 3-5+): M1 macrophages (pro-inflammatory, kill bacteria) → M2 transition (anti-inflammatory, pro-healing; produce IL-10, TGF-β, VEGF, FGF, PDGF, HGF). Macrophages absolutely essential—depletion studies show failed healing, no angiogenesis, minimal collagen. Critical: M1→M2 transition via apoptotic neutrophil signals and reduced hypoxia. Macrophages = orchestrators of healing.
Phase 3: Proliferation (Day 3 to Week 3)
Fibroblasts recruited by PDGF, TGF-β, FGF. TGF-β master regulator: binds TGF-βR1/R2 → Smad2/3 → upregulates collagen genes. Type III collagen synthesised (immature, loose triple helix); procollagen peptidase removes propeptides → mature collagen. Critical biochemistry: Prolyl/lysyl hydroxylase require O2 + vitamin C + iron + α-ketoglutarate for hydroxylation; without it, collagen dissolves. TcPO2 >40 mmHg optimal; <20 mmHg failure. Angiogenesis: VEGF signalling → endothelial sprouting → capillary budding from wound edges → granulation tissue (pink/red, friable, bleeds easily, high macrophage + fibroblast + capillary content). Re-epithelialisation: keratinocytes from wound margin dedifferentiate → integrin-based adhesion to fibronectin/vitronectin → lamellipodia migration (needs moist environment, oxygen, EGF, HGF). Myofibroblasts (fibroblasts expressing α-SMA) appear day 6-7; mediate wound contraction (reduces surface area up to 40%). Oxygen absolutely required: collagen hydroxylation failure if hypoxic; fibroblast proliferation impaired; angiogenesis minimal; keratinocyte migration blocked.
Phase 4: Remodelling (Week 3 to 2 Years)
Type III collagen → Type I collagen transition (organized, strong). Lysyl oxidase (copper-dependent, requires vitamin C) oxidises lysine → aldehydes → spontaneous Schiff bases and aldol cross-links → covalent collagen cross-linking. Collagen bundles reorganise: random weave → parallel (stiffer). Tensile strength: week 3 = 20%, week 6 = 60%, week 12 = 80-90%, maximum ~80% (never fully restores—inherent scar weakness). Myofibroblasts undergo apoptosis; vessel regression; scar evolution: initial raised/red/firm → final flat/pale/soft (12-24 months). Hypertrophic scar: Raised, red, itchy; stays within boundaries; collagen parallel; resolves 12-24 months; risk factors: high-tension, dark skin, sternum. Management: pressure garment, silicone gel, intralesional steroid, laser. Keloid: Extends beyond boundary; dark skin (5-15× higher risk); does not regress; management: intralesional steroid, radiotherapy post-excision (50% keloid recurrence with excision alone; radiotherapy 12-15 Gy <24h post-op reduces to <10%).
Phases Summary Table
| Phase | Timing | Dominant Cells | Key Events | Key Mediators | Vascular Surgery Relevance |
|---|---|---|---|---|---|
| Haemostasis | Seconds–minutes | Platelets, coagulation factors | Vasoconstriction; platelet adhesion/activation; coagulation cascade; fibrin clot scaffold | TXA2, ET-1, vWF, thrombin, PDGF, TGF-β, VEGF, FGF | Rapid haemostasis essential; growth factor trapping initiates healing; haemostasis failure = shock; excessive clotting = graft thrombosis |
| Inflammation | Hours–day 5 | Neutrophils (0-48h), Macrophages (day 3-5+), T-cells (day 5+) | Vasodilation/exudate; Celsian signs; neutrophil killing; M1→M2 macrophage transition; resolution phase | IL-8, C5a, LTB4, TNF-α, IL-1, IL-10, TGF-β, PDGF, lipoxins, resolvins | Essential for debris/bacteria clearance; excessive inflammation = chronic wound; steroids/NSAIDs impair; macrophages absolutely essential (depletion = failed healing) |
| Proliferation | Day 3–week 3 | Fibroblasts, Myofibroblasts, endothelial cells, keratinocytes | Fibroblast migration/proliferation; Type III collagen; angiogenesis; granulation tissue; myofibroblast contraction (40% surface reduction); re-epithelialisation | PDGF, TGF-β, FGF, VEGF, EGF, HGF, α-SMA, HIF-1α, vitamin C, lysine | CRITICAL FOR VASCULAR SURGERY: ischaemia impairs fibroblast (ATP), collagen synthesis (O2-hydroxylation); infection destroys growth factors; malnutrition impairs collagen; requires TcPO2 >40 mmHg; vitamin C mandatory (smokers, steroid-treated, malnourished) |
| Remodelling | Week 3–2 years | Fibroblasts, myofibroblasts (apoptosis), resident cells | Type III→Type I; lysyl oxidase cross-linking; scar flattening/blanching; vessel regression; ECM reorientation | Lysyl oxidase, MMPs, TIMPs, TGF-β (sustained), apoptotic signals | Plateau ~80% strength (never fully restores); hypertrophic scar common in high-tension/delayed healing; keloid risk in dark skin; maturation 12-24m—premature return to activity = poor outcomes |
Oxygen Thresholds Critical for Vascular Surgery
TcPO2 assessment mandatory: >40 mmHg optimal healing (supports collagen hydroxylation, angiogenesis, immune function). 20-40 mmHg borderline (partial hydroxylation, slow healing, infection risk). <20 mmHg impaired (hydroxylation blocked, fibroblast arrest, minimal angiogenesis). Intraoperative perfusion assessment: Most reliable sign = bleeding at incision margin (“good bleeding = good healing”—indicates haemostasis in well-perfused tissue). Normal skin temperature, colour, capillary refill <3 sec, intact pulses support adequacy. ABI >0.8 generally permits healing; <0.5 very high risk. Management principle: Vascular surgeons must ensure revascularisation BEFORE wound closure in marginal perfusion. Never accept low TcPO2 for healing. HBOT (Hyperbaric Oxygen): 100% O2 at 2-2.5 ATA increases dissolved plasma O2 substantially. Indicated for chronic ischaemic wounds (TcPO2 20-40 mmHg), diabetic ulcers, radiation necrosis. Protocol: 90 min at 2-2.5 ATA, 20-40 sessions. Oxygen challenge test (TcPO2 before/after 20 min 100% O2) increase >10 mmHg predicts responders.