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Tissue repair — regeneration, scar and fibrosis
Damaged tissue is repaired by regeneration when its cells can divide and the tissue framework is intact, and by scarring when the damage is extensive or the cells do not divide — through granulation tissue, collagen deposition and contraction by myofibroblasts, with TGF-β as the central fibrogenic factor.
Why it matters in the exam
The bank asks about cell types, scar stages and defined mechanisms. Labile cells (skin, gut mucosa, bone marrow) divide continuously; stable cells (hepatocytes, renal tubular cells) divide when needed; permanent cells (neurons, cardiac myocytes) hardly divide, so damage to them is repaired by scar. Granulation tissue appears within 3–5 days: fibroblasts, new vessels driven by VEGF and loose matrix; it looks pink and granular. Later, type III collagen is replaced by type I collagen and the scar strengthens.
Wound strength is about 10% of normal skin at the end of the first week, rises rapidly over the following months and reaches about 70–80% after about 3 months, and never returns to 100%. Contraction of a large wound is caused by myofibroblasts — fibroblasts with smooth-muscle actin filaments. Vitamin C is needed for hydroxylation of proline and lysine in collagen by the enzymes prolyl and lysyl hydroxylase, and in its absence wounds heal slowly and vessels are fragile (scurvy).
Healing by "first intention" occurs in a clean incision with apposed edges, and healing by "second intention" in a wide wound with tissue loss, with more granulation tissue and contraction. The most important local factor delaying healing is infection; other factors: diabetes, steroids, malnutrition, ischaemia and foreign bodies. Complications: a hypertrophic scar that stays within the wound borders, a keloid that extends beyond them, exuberant granulation tissue and dehiscence. In organ fibrosis, for example in the liver, Ito (stellate) cells are activated by cytokines, become myofibroblasts and produce collagen.
Key points
- Regeneration with dividing cells and an intact framework; otherwise scar.
- Granulation tissue at 3–5 days, driven by VEGF.
- Strength: 10% at week 1, 70–80% after 3 months.
- Contraction: myofibroblasts; TGF-β is the central fibrogenic factor.
- Vitamin C is needed for hydroxylation of proline and lysine.
Summary table
| Topic | Fact | Mechanism | Pitfall |
|---|---|---|---|
| Cell types | Labile, stable, permanent | Capacity to divide | Thinking cardiac muscle regenerates |
| Granulation tissue | 3–5 days; fibroblasts and new vessels | VEGF | Confusing it with a granuloma |
| Wound strength | About 10% at week 1; 70–80% after 3 months | Replacement of collagen III by I | Thinking it returns to 100% |
| Wound contraction | Myofibroblasts | Actin filaments | Attributing it to collagen |
| Liver fibrosis | Activated Ito cells | TGF-β | Attributing it to hepatocytes |
A free exam question
גבר בן 28 ( מאושפז בגלל חום, שיעול וירידה ברמת החמצן בדם Hypoxemia ). בתרבית כיח צו מח Pseudomonas aeruginosa .. באנמנזה שלו הוא מספר על תיאבון תקין ועל יציאות מרובות משקלו 53 ק"ג. הוא נשוי מזה 3 שנים, ללא ילדים. בבירור פוריות בשנה האחרונה נמצאה Azoospermia . הוא מספר על אפיזודות של Chronic sinusitis וכן דלקות ריאה. המשקל שלו 55 ק"ג. למר ות טיפול אנטיביוטי תוך- ורידי ופיסיותרפיה נשימתית, מצבו מידרדר והוא נפטר לאחר שבוע בתמונה של דלקת ריאות סוערת ואי ספיקה נשימתית כל המימצאים הבאים קשור ים. למחלתו ,פרט ל: (the question as examined, in Hebrew)
- א. תסנינים דלקתיים ברירית המעי הגס עם Crypt abscesses
- ב. חוסר דו-צדדי ב- Vas deferens
- ג. הרחבה וחסימה של pancreatic ducts
- ד. ( סימפונות מורחבים Bronchiectasis ( ) ודלקת ריאות Bronchopneumonia )
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Sources
- Robbins and Cotran Pathologic Basis of Disease, 10th edition (2021) — Inflammation and repair — tissue repair
- Rubin's Pathology: Mechanisms of Human Disease, 8th edition (2020) — Repair, regeneration and fibrosis
- Gurtner GC et al. Wound repair and regeneration, Nature, 2008 — Phases of repair
Sources are given for further reading; the text is written afresh and not copied from them.
Reviewed by the Examqo AI Professor · 2026-11-06. The text may contain errors; when in doubt, check the source.