U01.04.017 Wound healing

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Learning Objectives

Master the three distinct phases of Wound Healing and the specific effector cells involved in each. Identify the roles of key Tissue Mediators (FGF, VEGF, TGF-$\beta$) and understand how nutritional deficiencies in Vitamin C, Copper, and Zinc impair the healing process.

1. Phases of Wound Healing

Wound healing is a dynamic process divided into three overlapping phases: inflammatory, proliferative, and remodeling. The transition from one phase to the next is essential for restoring tissue integrity and tensile strength.

Phase & Timing Effector Cells Key Characteristics
Inflammatory (0–3 days) Platelets, Neutrophils, Macrophages Clot formation; ↑ vessel permeability; neutrophils migrate first, followed by macrophages, to clear debris.
Proliferative (3 days–weeks) Fibroblasts, Myofibroblasts, Endothelial cells Granulation tissue and Type III collagen deposition; angiogenesis; wound contraction by myofibroblasts.
Remodeling (1 week–6+ months) Fibroblasts Type III collagen is replaced by Type I collagen; ↑ tensile strength. Collagenases require Zinc.

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2. Growth Factors and Tissue Mediators

Specific mediators coordinate cell recruitment and extracellular matrix synthesis.

Mediator Primary Role in Healing
FGF & VEGF Stimulate angiogenesis (new blood vessel formation).
TGF-\beta Promotes angiogenesis and fibrosis; triggers collagen production.
PDGF Vascular remodeling, smooth muscle migration, and fibroblast growth.
Metalloproteinases Essential for tissue remodeling (breaking down old matrix).
EGF Stimulates cell growth via tyrosine kinases (e.g., ErbB1).

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3. Nutritional Deficiencies & Complications

Healing can be significantly delayed or impaired by the lack of specific enzymatic cofactors.

Deficiency Mechanism of Impairment
Vitamin C Required for hydroxylation of proline/lysine residues in collagen (Scurvy).
Copper Required for lysyl oxidase, which cross-links collagen fibers.
Zinc Cofactor for collagenases (MMPs) in the remodeling phase.

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High-Yield Mnemonics & Tips:

  • Collagen Switch: Type III is “three-mporary” (seen in granulation tissue). Type I is “strong” (remodeling phase).
  • TGF-$\beta$ Paradox: It is anti-inflammatory in the late stages of acute inflammation but is the most important mediator for driving fibrosis (scarring) in chronic states.
  • Zinc & Remodeling: If an exam question mentions a patient with a surgical wound that hasn’t changed in months, check for zinc deficiency.

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