Wound healing and repair

Wound healing and repair

Wound healing and repair

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Tissue Repair - Regeneration vs. Scarface

Wound Healing Process: Inflammation, Granulation, Scarring

  • Regeneration: Perfect restoration of tissue architecture and function.

    • Occurs in labile (skin, gut) & stable tissues (liver).
    • Requires an intact extracellular matrix (ECM) scaffold.
  • Repair (Scarring): Replacement with a fibrous scar.

    • Occurs in permanent tissues (heart, neurons) or with severe ECM damage.
    • Provides stability but with functional loss.

⭐ The extracellular matrix (ECM) is the critical determinant. If the ECM scaffold is damaged, healing results in a scar, regardless of the tissue's regenerative capacity.

Healing Phases - From Mess to Success

  • 1. Inflammatory Phase (0-3 days)

    • Hemostasis: Platelet plug & fibrin clot formation.
    • Inflammation: Neutrophils arrive first (peak ~24h), followed by macrophages (peak ~48-72h), which are crucial for cleanup and transition to the next phase.
  • 2. Proliferative Phase (Day 3-Weeks)

    • Granulation tissue forms: Fibroblasts deposit Type III collagen, new capillaries grow (angiogenesis), and myofibroblasts cause wound contraction.
    • Epithelialization covers the wound.
  • 3. Remodeling Phase (Week 1-Months/Years)

    • Type III collagen is replaced by stronger Type I collagen (Collagenases require Zinc).
    • Tensile strength increases over time.

⭐ By 3 months, wound strength is approximately 70-80% of unwounded skin, a common point of failure in post-op recovery.

Mammalian wound healing phases: cells, vessels, collagen

Healing Intention - Stitches & Ditches

Primary vs. Secondary Intention Wound Healing

  • Primary Intention (Stitches)

    • Mechanism: Clean, surgical wound edges approximated by sutures.
    • Process: Minimal tissue loss, clot, and inflammation. Less granulation tissue forms.
    • Result: Rapid healing with a fine, linear scar.
  • Secondary Intention (Ditches)

    • Mechanism: Large, open wounds with significant tissue loss (e.g., ulcers, abscesses).
    • Process: Abundant granulation tissue fills the defect, followed by wound contraction.
    • Result: Slower healing, larger scar.

⭐ Myofibroblasts are the key cells responsible for wound contraction in secondary intention, significantly reducing the size of the defect over time.

Healing Factors - What Slows the Show

  • Systemic: Malnutrition (↓ Vit C, copper, zinc), Diabetes Mellitus (impaired leukocyte function, ↓ perfusion), corticosteroids (anti-inflammatory effects), smoking (vasoconstriction), advanced age.
  • Local: Infection, ischemia/hypoxia (↓ ATP for collagen synthesis), foreign body, excessive movement, poor tissue apposition.

⭐ Infection is the single most common cause of delayed wound healing, with Staphylococcus aureus being a frequent culprit.

Healing Complications - Scars & Problems

  • Hypertrophic Scar: Excess Type III collagen; raised but confined to original wound boundaries. Collagen fibers are parallel.
  • Keloid: Disorganized, thick Type I & III collagen bundles extending beyond wound borders. High recurrence rate. Common in individuals of African descent.
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  • Contracture: Exaggerated wound contraction via myofibroblasts, causing deformity (e.g., after burns) and limiting mobility.
  • Dehiscence: Premature bursting open of a previously closed wound.

⭐ Keloids are characterized by haphazardly arranged, thick bundles of Type I and III collagen, unlike the parallel fibers seen in hypertrophic scars.

High‑Yield Points - ⚡ Biggest Takeaways

  • Healing phases: Inflammatory (neutrophils, macrophages), Proliferative (fibroblasts, granulation tissue), and Remodeling (collagen maturation).
  • Secondary intention involves significant granulation, contraction by myofibroblasts, and results in a larger scar.
  • The critical collagen transition is from Type III collagen (weak) to Type I collagen (strong), a process dependent on Vitamin C.
  • TGF-β is the key cytokine driving fibrosis; VEGF and FGF are critical for angiogenesis.
  • Keloids consist of excessive collagen extending beyond the original wound borders, unlike hypertrophic scars.
  • Wound dehiscence is strongly associated with infection, malnutrition, and obesity.

Practice Questions: Wound healing and repair

Test your understanding with these related questions

A 55-year-old African American female presents to her breast surgeon for a six-month follow-up visit after undergoing a modified radical mastectomy for invasive ductal carcinoma of the left breast. She reports that she feels well and her pain has been well controlled with ibuprofen. However, she is frustrated that her incisional scar is much larger than she expected. She denies any pain or pruritus associated with the scar. Her past medical history is notable for systemic lupus erythematosus and multiple dermatofibromas on her lower extremities. She has had no other surgeries. She currently takes hydroxychloroquine. On examination, a raised hyperpigmented rubbery scar is noted at the inferior border of the left breast. It appears to have extended beyond the boundaries of the initial incision. Left arm range of motion is limited due to pain at the incisional site. Abnormal deposition of which of the following molecules is most likely responsible for the appearance of this patient’s scar?

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Flashcards: Wound healing and repair

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Microglia are activated in response to _____

TAP TO REVEAL ANSWER

Microglia are activated in response to _____

tissue damage

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