⚙️ Repair & healing overview
- Repair begins within hours of injury, overlapping with inflammation.
- Extracellular matrix (ECM) provides structural scaffold.
- Interstitial matrix (collagens, elastin, proteoglycans).
- Basement membrane (type IV collagen, laminin).
- Five overlapping processes:
- Hemostasis (platelets, coagulation cascade).
- Inflammation (neutrophils → macrophages → lymphocytes).
- Regeneration (stem cells + differentiated cells).
- Fibrosis (granulation tissue: fibroblasts, angiogenesis, type III collagen).
- Remodeling (macrophages, fibroblasts; type III → type I collagen conversion).
Hemostasis→
Inflammation→
Regeneration / Fibrosis→
Remodeling
- ECM components: collagens/elastins · proteoglycan gels · glycoproteins (fibronectin, laminin).
🧬 Regeneration capacity cell types
- Labile cells – continuously divide throughout life.
- Skin epithelia, mucosal lining, hematopoietic cells, germ cells.
- Stable cells – low basal replication; can divide when stimulated.
- Hepatocytes, renal tubular cells, endothelial cells, smooth muscle.
- Permanent cells – minimal to no replicative capacity.
- Neurons, cardiac myocytes, skeletal muscle (limited).
| Category | Examples | Regenerative capacity |
|---|---|---|
| Labile | Skin, GI mucosa, bone marrow | High (stem cell driven) |
| Stable | Liver, kidney tubules, pancreas | Moderate (can proliferate) |
| Permanent | Neurons, cardiac muscle | Virtually none |
- Injury to permanent cells → repair by fibrosis, not regeneration.
🧫 Scar formation fibrosis
- Scarring occurs when regeneration is insufficient.
- Key growth factors and their roles:
- VEGF, FGF → angiogenesis (new vessels).
- PDGF, FGF‑2, TGF‑β → fibroblast activation → granulation tissue.
- TGF‑β, PDGF, FGF → ECM deposition (collagen, proteoglycans).
- IL‑1, IL‑13 → stimulate collagen production.
- Granulation tissue components:
- Fibroblasts (produce collagen).
- New capillaries (angiogenesis).
- Inflammatory cells (macrophages, lymphocytes).
- Remodeling phase: conversion of type III collagen to type I (stronger).
VEGF/FGF→
Angiogenesis→
PDGF/TGF‑β→
Fibroblast activation→
ECM deposition
🩹 Wound healing types primary vs secondary
- Primary union (first intention) – edges opposed; minimal granulation.
- Examples: surgical incisions, clean lacerations.
- Secondary union (second intention) – wound left open; healing by contraction.
- Myofibroblasts at wound edge mediate contraction.
- Clinical decision factors: wound size, contamination, location, patient factors.
| Feature | Primary union | Secondary union |
|---|---|---|
| Wound closure | Sutures, staples, adhesive | Open, allowed to contract |
| Granulation tissue | Minimal | Prominent |
| Scar size | Narrow | Larger, may contract |
| Healing time | Faster | Slower |
🧠 Organ‑specific repair patterns
- Liver – mild injury: regeneration of hepatocytes; severe: regenerative nodules + fibrosis → cirrhosis.
- Brain – neurons do not regenerate; microglia clear debris; astrocytes proliferate → gliosis.
- Heart – no regeneration; repair by fibrosis (scar).
- Lung – type II pneumocytes proliferate and differentiate into type I pneumocytes.
- Peripheral nerves – distal axon degenerates (Wallerian); proximal axonal sprouts regrow along Schwann cell tubes.
- Gliosis = astrocyte proliferation in CNS after injury; not functional regeneration.
⚠️ Aberrations in healing complications
- Delayed healing – associated with:
- Infection, foreign body, ischemia, diabetes, malnutrition, scurvy (vitamin C deficiency).
- Hypertrophic scar – localized, within wound boundaries.
- Excess granulation tissue/collagen; common after burns.
- Keloid – genetic predisposition (higher in African Americans).
- Extends beyond original wound margins.
- Predilection: earlobes, face, neck, sternum, forearms.
- Excess collagen (predominantly type III).
- May become large, tumor‑like.
| Feature | Hypertrophic scar | Keloid |
|---|---|---|
| Extent | Within wound borders | Beyond wound margins |
| Genetics | Not typically | Strong familial / ethnic |
| Common sites | Any, especially burns | Earlobes, face, sternum, forearms |
| Collagen type | Mixed (I & III) | Predominantly type III |
- Keloids can recur after excision; adjunct therapy (steroids, pressure) often needed.