## Factors Impairing Wound Healing in the Proliferative Phase **Key Point:** The proliferative phase (days 3–21) depends on adequate oxygen, nutrients, and growth factor signaling. Most systemic and local factors that impair healing reduce these resources; increased oxygen tension and FiO₂ actually **enhance** healing and do not impair it. ### Systemic Factors Affecting Wound Healing | Factor | Effect on Healing | Mechanism | |--------|-------------------|----------| | Corticosteroids | ↓ Impairs | Suppresses fibroblast proliferation, inhibits collagen cross-linking, reduces angiogenesis | | Hyperglycemia (>180 mg/dL) | ↓ Impairs | Impairs neutrophil chemotaxis, reduces angiogenesis, increases infection risk | | **High oxygen tension / FiO₂** | **↑ Enhances** | **Promotes fibroblast activity, collagen synthesis, angiogenesis** | | Protein malnutrition | ↓ Impairs | Reduces amino acid substrate for collagen (proline, lysine, glycine) | | Vitamin C deficiency | ↓ Impairs | Blocks hydroxylation of proline and lysine; collagen becomes unstable | | Anemia (Hb <7 g/dL) | ↓ Impairs | Reduces oxygen delivery to wound | | Infection | ↓ Impairs | Consumes nutrients, triggers excessive inflammation | ### Why Option 3 Is Correct (Does NOT Impair Healing) **High-Yield:** Increased wound oxygen tension and supplemental FiO₂ are **beneficial**, not harmful, to wound healing. Oxygen is essential for: 1. Hydroxylation of proline and lysine in collagen (requires O₂ as a cofactor for prolyl and lysyl hydroxylases) 2. ATP production for fibroblast and endothelial cell function 3. Bacterial killing by neutrophils (oxidative burst) 4. Angiogenesis and neovascularization **Clinical Pearl:** Supplemental oxygen (FiO₂ 40–50%) is recommended perioperatively to reduce surgical site infection and promote healing, particularly in high-risk patients (diabetics, elderly, obese). ### Why the Other Options Impair Healing - **Option 1 (Corticosteroids):** Suppress fibroblast proliferation, inhibit collagen cross-linking, and reduce angiogenesis — well-documented mechanism of impaired healing. - **Option 2 (Hyperglycemia):** Impairs neutrophil chemotaxis and function, reduces angiogenesis, and increases infection risk — major risk factor in diabetic wound healing. - **Option 4 (Protein malnutrition):** Collagen is ~30% glycine, ~10% proline, ~1% lysine. Deficiency of these amino acids directly reduces collagen synthesis and tensile strength. **Mnemonic — CHIMPANZEES (Factors Impairing Wound Healing):** - **C**orticosteroids - **H**yperglycemia - **I**nfection - **M**alnutrition (protein, vitamin C, zinc) - **P**oor perfusion / anemia - **A**ge (elderly) - **N**ecrotic tissue - **Z**inc deficiency - **E**xcessive tension - **E**dema - **S**moking
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