Wound healing

 

Wound Healing: High-Yield Pathology

Tissue repair occurs via two processes: regeneration (replacement of damaged cells with the same cell type, leaving no scar) and repair (replacement of parenchymal tissue with fibrovascular connective tissue, resulting in a scar).

1. Phases of Cutaneous Wound Healing

Wound healing progresses through three overlapping phases that must occur in a coordinated temporal sequence:

Phase Timeline Key Cellular & Molecular Events
1. Inflammatory Up to 3 days Hemostasis: Immediate vasoconstriction, platelet aggregation, and fibrin clot formation.
Infiltration: Neutrophils arrive first to clear bacteria, followed by macrophages (the orchestrators of transition to the proliferative phase).
2. Proliferative Day 3 to 3 weeks Granulation Tissue: Fibroblasts deposit **Type III collagen** alongside endothelial angiogenesis.
Epithelialization: Basal cells proliferate and migrate across the wound bed.
Wound Contraction: Mediated by **myofibroblasts**.
3. Remodeling 3 weeks to 1 year+ Collagen Type Switch: Metalloproteinases (MMPs) degrade fragile Type III collagen and replace it with strong **Type I collagen**.
• Tensile strength increases progressively, peaking at roughly 70–80% of original unwounded skin strength by 3 months.

2. Primary vs. Secondary Intention

  • Primary Intention (First Intention): Occurs in clean, uninfected surgical incisions where edges are approximated by sutures, staples, or steri-strips. Minimal tissue loss, narrow granulation tissue zone, and minimal scarring.
  • Secondary Intention: Occurs in large defects, ulcerations, or infected wounds where edges cannot be approximated. Requires an extensive volume of granulation tissue to fill the defect, exhibits pronounced myofibroblast-mediated wound contraction, and results in a large, prominent scar.

3. Factors Modifying Wound Healing

Factor Pathophysiological Mechanism
Infection The most common local cause of delayed healing prolongs the inflammatory phase and increases tissue destruction.
Vitamin C Deficiency Inhibits the hydroxylation of proline and lysine residues required for stable collagen cross-linking (Scurvy).
Zinc Deficiency Impairs Matrix Metalloproteinases (MMPs), which require zinc ions as a cofactor to remodel collagen.
Glucocorticoids Inhibit **TGF-beta** production, reducing fibroblast collagen synthesis and leading to poor wound tensile strength.

4. Aberrant Wound Healing (Exam Staples)

[Image comparing a hypertrophic scar with a keloid]

  • Keloid vs. Hypertrophic Scar:
    • Hypertrophic scars contain parallel Type III collagen bundles that stay **confined within the boundaries** of the original wound and frequently regress over time.
    • Keloids feature disorganized, thick Type I and III collagen bands that **extend beyond the boundaries** of the original injury, fail to regress, and have an increased incidence in darker-pigmented skin.
  • Proud Flesh (Exuberant Granulation): Over-proliferation of granulation tissue that projects above the level of the surrounding skin and blocks proper epithelialization. Must be cauterized or surgically excised.
  • Dehiscence: Rupture of a wound, most frequently encountered following abdominal surgeries due to increased intra-abdominal pressure (e.g., from coughing or vomiting).