10.2 Inflammation, Wound Healing and Repair
Key Takeaways
- Acute inflammation begins with transient arteriolar vasoconstriction, then vasodilatation mediated by histamine and nitric oxide, then increased permeability, stasis and margination.
- Exudate is protein-rich with a high specific gravity and contains fibrinogen; transudate is protein-poor and does not clot.
- Arachidonic acid is released by phospholipase A2 and processed by cyclooxygenase to prostaglandins and thromboxane, and by 5-lipoxygenase to leukotrienes.
- Granulomatous inflammation features epithelioid macrophages and multinucleate giant cells and occurs in tuberculosis, sarcoidosis and orofacial granulomatosis.
- A hypertrophic scar stays within the original wound boundary and tends to regress, whereas a keloid extends beyond it and does not.
Last updated: September 2026
3. Acute versus Chronic Inflammation
Vascular Dynamics of Acute Inflammation
Acute inflammation is an immediate, transient vascular and cellular response designed to deliver leukocytes and plasma proteins to sites of injury:
- Transient Arteriolar Vasoconstriction: Lasts seconds, mediated by neurogenic reflex.
- Arteriolar Vasodilatation: Mediated by histamine and nitric oxide (NO), leading to increased blood flow (hyperaemia), manifesting clinically as redness (rubor) and heat (calor).
- Increased Microvascular Permeability: The hallmark of acute inflammation. Endothelial cell contraction in post-capillary venules creates intercellular gaps, allowing protein-rich fluid to escape into the extravascular tissues, producing inflammatory swelling (tumour / oedema).
- Stasis and Margination: Fluid loss concentrates erythrocytes, increasing blood viscosity and slowing flow (stasis). Leukocytes (predominantly neutrophils) fall out of the central axial stream toward the endothelial periphery (margination).
Exudate versus Transudate
| Characteristic | Transudate | Exudate |
|---|---|---|
| Pathological Mechanism | Increased hydrostatic pressure (e.g., heart failure) or reduced oncotic pressure (e.g., cirrhosis, nephrotic syndrome) | Increased microvascular permeability due to acute inflammation or tissue injury |
| Protein Content | Low (<30 g/L / <3.0 g/dL) | High (>30 g/L / >3.0 g/dL) |
| Specific Gravity | Low (<1.012) | High (>1.020) |
| Cellular Content | Few or no inflammatory cells | Abundant inflammatory cells (neutrophils, macrophages, cellular debris) |
| Fibrinogen / Coagulation | Absent; does not clot | Present; rich in fibrin, clots readily |
Chemical Mediators of Acute Inflammation
- Vasoactive Amines: Histamine (preformed in mast cells; drives immediate arteriolar vasodilation and venular permeability) and serotonin (platelets).
- Plasma Protease Systems: The kinin cascade generates bradykinin, which causes profound vasodilation, increases microvascular permeability, and stimulates sensory C-fibers, mediating pain (dolor).
- The Arachidonic Acid Cascade: Arachidonic acid is cleaved from membrane phospholipids by Phospholipase A2 (which is directly inhibited by systemic corticosteroids). It is then metabolised through two distinct enzymatic pathways:
Membrane Phospholipids ➔ (Phospholipase A2) ➔ Arachidonic Acid
Arachidonic Acid ➔ (Cyclooxygenase COX-1 / COX-2) ➔ Prostaglandins (PGE₂, PGD₂, PGF₂α), Prostacyclin (PGI₂), Thromboxane (TXA₂)
Arachidonic Acid ➔ (5-Lipoxygenase 5-LOX) ➔ Leukotriene B₄, Leukotrienes C₄, D₄, E₄
- COX Pathway: Produces Prostaglandin PGE2 (mediates vasodilation, sensitises nociceptors to bradykinin, and resets the hypothalamic thermostat to cause fever), Prostacyclin (PGI2) (vasodilator and inhibitor of platelet aggregation), and Thromboxane TXA2 (vasoconstrictor and promoter of platelet aggregation). NSAIDs (ibuprofen) non-selectively block COX-1 and COX-2.
- LOX Pathway: Produces Leukotriene LTB4 (potent chemoattractant for neutrophils) and the cysteinyl leukotrienes (LTC₄, LTD₄, LTE₄), which cause severe bronchoconstriction and marked vascular permeability.
Chronic Inflammation and Granulomatous Disease
When the acute inflammatory stimulus cannot be eliminated, the process transitions to chronic inflammation, defined by concurrent active inflammation, tissue destruction, and repair:
- Cellular Infiltrate: Dominated by macrophages, lymphocytes (T and B cells), and plasma cells. Macrophages adopt either an M1 phenotype (classically activated by IFN-γ and microbial LPS; pro-inflammatory, microbicidal, produces IL-1, TNF, ROS) or an M2 phenotype (alternatively activated by IL-4 and IL-13; anti-inflammatory, secretes TGF-β, PDGF, and VEGF, driving tissue repair, angiogenesis, and fibrosis).
- Granulomatous Inflammation: A specialized pattern of chronic inflammation characterized by microscopic aggregates of epithelioid macrophages (activated macrophages with abundant pink cytoplasm and vesicular nuclei resembling epithelial cells) surrounded by a collar of lymphocytes and plasma cells, often with multinucleated giant cells:
- Langhans Giant Cells: Nuclei arranged in a characteristic peripheral horseshoe or ring pattern; classically seen in tuberculosis.
- Foreign Body Giant Cells: Nuclei arranged haphazardly throughout the cytoplasm; seen surrounding foreign material (sutures, talc).
- Caseating Granulomas: Feature central eosinophilic acellular necrosis; diagnostic of Mycobacterium tuberculosis.
- Non-Caseating Granulomas: Lack central necrosis; characteristic of sarcoidosis, Crohn's disease, and Orofacial Granulomatosis (OFG) (which presents with persistent, painless labial enlargement and cobblestoning of the oral mucosa).
4. Principles of Wound Healing and Repair
Tissue repair proceeds through four overlapping phases: Haemostasis, Inflammation, Proliferation, and Remodelling.
[Haemostasis: Immediate]
➔ Platelet aggregation, fibrin clot formation
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[Inflammation: Days 1–3]
➔ Neutrophils (0–24h) ➔ Macrophages (48–72h: debridement & growth factors)
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[Proliferation: Days 3–14]
➔ Angiogenesis (VEGF) ➔ Fibroplasia (Type III Collagen) ➔ Myofibroblast Contraction
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[Remodelling: Week 2 – 1+ Year]
➔ Type III Collagen replaced by Type I Collagen (MMP/TIMP mediated)
➔ Tensile strength reaches ~70–80% of original unwounded tissue
Primary versus Secondary Intention
- Healing by Primary Intention (First Intention): Occurs in clean, uninfected surgical incisions with closely approximated wound edges (e.g., properly sutured mucoperiosteal flaps). Minimal tissue loss, thin clot, rapid re-epithelialisation (within 24–48 hours), minimal granulation tissue, negligible wound contraction, and a fine linear scar.
- Healing by Secondary Intention (Second Intention): Occurs in wounds with extensive tissue loss, irregular separated edges, or infected defects (e.g., an open tooth extraction socket, large aphthous ulcer, or un-sutured wound). Requires copious granulation tissue (histologically defined by proliferating endothelial capillaries, loose extracellular matrix, and plump active fibroblasts) to fill the defect. Marked wound contraction mediated by myofibroblasts (differentiated fibroblasts expressing α-smooth muscle actin) significantly reduces wound area, but results in prolonged healing and prominent scar tissue.
Aberrant Repair: Hypertrophic Scars vs Keloids
- Hypertrophic Scar: Raised, erythematous scar resulting from excessive collagen deposition that remains strictly confined within the original boundaries of the wound. Tends to regress spontaneously over months.
- Keloid: Exuberant collagenous overgrowth that extends beyond the anatomical borders of the original wound into adjacent normal tissue and does not regress spontaneously. Characterised by thick, hyalinised bundles of Type I and Type III collagen, resisting fibroblast apoptosis, with genetic predisposition in individuals of African and Asian ancestry.