Quick Answer
Inflammation and repair is a recurring 6 to 10 marker in NEET PG pathology, and the topic overlaps directly with surgery (wound management), orthopaedics (fracture healing) and dermatology (keloid). Master these six anchors.
- Acute inflammation — vascular (vasodilation, permeability) plus cellular (margination, rolling, adhesion, transmigration, chemotaxis). Neutrophils dominate the first 24 to 48 hours.
- Mediators — histamine, prostaglandins, leukotrienes, IL-1, TNF, IL-6, IL-8, complement C3a/C5a, bradykinin, PAF, ROS, NO.
- Chronic inflammation — macrophages, lymphocytes, plasma cells; granulomatous forms include TB (caseating) and sarcoidosis (non-caseating).
- Wound healing phases — haemostasis, inflammation (days 0 to 3), proliferation (days 4 to 21), remodelling (weeks to months).
- Primary vs secondary intention — clean surgical wound approximated vs open wound healing by granulation.
- Fracture healing — haematoma, inflammation, soft callus, hard callus, remodelling. Delayed union caused by infection, NSAIDs, smoking, steroids, malnutrition, inadequate immobilisation.
Inflammation is the body's stereotyped response to injury or infection — a coordinated cascade of vascular and cellular events designed to eliminate the offending agent and initiate repair. In NEET PG, examiners test three angles: the mediator you would find at each step, the microscopic difference between acute and chronic inflammation, and the wound healing timeline (day 3 macrophage predominance, day 5 fibroblast peak, day 21 remodelling onset).
This NEETPGAI deep dive walks you through acute inflammation mediators, chronic granulomatous patterns, all four wound healing phases, keloid versus hypertrophic scar and the full fracture healing sequence — with the India-specific twist (chronic non-healing diabetic ulcers, tetanus prophylaxis, keloid predisposition) that examiners love. Pair it with the cell injury and necrosis guide for the upstream injury that triggers every inflammatory response.
Acute inflammation — vascular and cellular events
Acute inflammation is short-lived (minutes to a few days), neutrophil-dominant and characterised by exudation of fluid and plasma proteins. It has two components — vascular and cellular.
Vascular events
- Transient vasoconstriction (seconds) followed by vasodilation of arterioles — the source of heat and redness.
- Increased vascular permeability — endothelial contraction (histamine, leukotrienes), endothelial injury (burns, toxins), leukocyte-mediated injury and transcytosis (VEGF). Protein-rich exudate leaves the vessel.
- Slowing of circulation and stasis as the packed cell volume rises with fluid loss.
- Margination of leukocytes — neutrophils align along the endothelium.
Cellular events (the leukocyte cascade)
- Margination — neutrophils move to the periphery.
- Rolling — mediated by selectins (E-selectin on endothelium, L-selectin on leukocytes, P-selectin from Weibel-Palade bodies) binding sialyl-Lewis X.
- Adhesion — firm arrest via integrins (LFA-1, VLA-4, Mac-1) binding endothelial ICAM-1 and VCAM-1. Leukocyte adhesion deficiency (LAD) type 1 is a defect in the beta-2 integrin subunit (CD18).
- Transmigration (diapedesis) — through endothelial junctions mediated by PECAM-1 (CD31).
- Chemotaxis — directed migration along gradients of C5a, IL-8 (CXCL8), leukotriene B4 and bacterial products (N-formylmethionyl peptides).
- Phagocytosis — recognition (opsonisation with IgG Fc, C3b, mannose-binding lectin), engulfment, and killing via the respiratory burst (NADPH oxidase generating superoxide, then hydrogen peroxide, then hypochlorite via myeloperoxidase) and non-oxygen-dependent mechanisms (lysozyme, lactoferrin, defensins, BPI).
- NETs (neutrophil extracellular traps) — decondensed chromatin studded with granule proteins that trap bacteria; also implicated in autoimmune disease.
Chemical mediators — the exam checklist
| Class | Key mediators | Actions |
|---|
| Vasoactive amines | Histamine (mast cells, basophils, platelets), serotonin (platelets) | Vasodilation, increased permeability |
| Arachidonic acid metabolites (COX) | PGE2, PGI2, PGD2, PGF2 alpha, TxA2 | Vasodilation, permeability, pain, fever; TxA2 vasoconstricts and aggregates platelets |
| Arachidonic acid metabolites (LOX) | LTB4 (chemotaxis), LTC4/D4/E4 (bronchospasm, permeability), lipoxins (resolution) | Neutrophil chemotaxis, bronchoconstriction |
| Cytokines | IL-1, TNF (fever, endothelial activation, acute-phase), IL-6 (acute-phase, CRP synthesis), IL-8 (neutrophil chemokine) | Systemic inflammation, chemotaxis |
| Complement | C3a, C5a (anaphylatoxins), C5a (chemotaxis), C3b (opsonisation), MAC (C5b-9) | Vasodilation, chemotaxis, killing |
| Kinins | Bradykinin | Vasodilation, pain, permeability |
| PAF | Platelet-activating factor | Vasodilation, permeability, chemotaxis |
| ROS and NO | Superoxide, hydroxyl, hydrogen peroxide, hypochlorite, nitric oxide | Microbial killing, host tissue damage |
| Neuropeptides | Substance P, CGRP | Pain, vasodilation, permeability |
Systemic effects of acute inflammation
- Fever — IL-1, TNF, IL-6 and prostaglandin E2 act on the hypothalamus.
- Leukocytosis — with a left shift (immature band forms) in bacterial infection; lymphocytosis in viral; eosinophilia in parasitic and allergic; neutropenia in typhoid and viral haemorrhagic fever.
- Acute-phase reactants — CRP, fibrinogen (increases ESR), haptoglobin, ferritin, hepcidin, serum amyloid A (precursor of AA amyloid), complement components.
- Septic shock — driven by TNF, IL-1 and IL-6; DIC, ARDS, hypotension and multi-organ dysfunction.
Chronic inflammation and granulomas
Chronic inflammation is prolonged (weeks to years), driven by persistent infection (TB, syphilis), autoimmunity (RA, IBD), foreign material (silica, sutures) or unresolved acute inflammation. The cellular hallmark is a mononuclear infiltrate of macrophages, lymphocytes, plasma cells and fibroblasts, with concurrent tissue destruction and attempted repair (angiogenesis, fibrosis).
Macrophage polarisation
- M1 (classically activated) — driven by IFN-gamma and microbial products; kills intracellular organisms via ROS, NO and pro-inflammatory cytokines.
- M2 (alternatively activated) — driven by IL-4 and IL-13; drives tissue repair and fibrosis; implicated in parasitic infection and asthma.
Granulomatous inflammation
A granuloma is a compact aggregate of activated macrophages (epithelioid cells) surrounded by lymphocytes, often with multinucleated giant cells and a fibrous rim.
| Type | Necrosis | Cause | India-specific note |
|---|
| Caseating | Central cheese-like necrosis with acid-fast bacilli | Tuberculosis (default answer in India), histoplasmosis, some fungi | India carries roughly one-quarter of global TB burden |
| Non-caseating | No central necrosis; asteroid and Schaumann bodies | Sarcoidosis, Crohn disease, berylliosis, leprosy (tuberculoid), foreign body | Rising sarcoidosis diagnosis in urban India |
| Suppurative | Central neutrophilic microabscesses within granulomas | Cat-scratch disease (Bartonella), lymphogranuloma venereum (Chlamydia), tularaemia | LGV a differential in Indian genital ulcer stems |
| Foreign-body | Around indigestible material (sutures, talc, silica) | Silica, sutures, talc from IV drug use | Silicosis in stone-cutting workers |
Giant cells — Langhans (peripheral horseshoe nuclei, in TB) versus foreign-body type (haphazardly arranged nuclei) versus Touton (central ring of nuclei with foamy periphery, in xanthomas).
Repair — regeneration and scar formation
Repair restores the original tissue architecture (regeneration) if the stem cell niche and basement membrane are intact, otherwise a fibrous scar fills the defect.
Cell replicative potential
- Labile cells — continuously dividing (skin epidermis, GI mucosa, bone marrow); rapid renewal after injury.
- Stable cells — quiescent but can re-enter cycle when needed (liver hepatocytes, kidney tubules, endothelium, smooth muscle). Liver can regenerate 70 percent of its mass after partial hepatectomy.
- Permanent cells — cannot divide (neurons, cardiac myocytes, skeletal muscle to a limited degree); injury results in scar, not regeneration. This is why post-MI healing is fibrous, not muscular.
Key growth factors and their targets
| Growth factor | Function |
|---|
| VEGF | Angiogenesis (endothelial proliferation) |
| FGF | Angiogenesis, epithelialisation, fibroblast proliferation |
| PDGF | Fibroblast, smooth muscle and macrophage chemotaxis and mitogenesis |
| TGF-beta | Fibroblast collagen deposition, angiogenesis; also immunosuppressive |
| EGF | Keratinocyte and epithelial proliferation |
| HGF | Hepatocyte and epithelial proliferation |
| IGF-1 | Cell proliferation and matrix production |
Wound healing — the four phases
Wound healing is stereotyped regardless of tissue type, though timelines vary.
Phase 1 — Haemostasis (minutes)
Vasoconstriction, platelet plug formation and fibrin clot formation. The clot provides a provisional scaffold and releases PDGF, TGF-beta and EGF that recruit inflammatory cells.
Phase 2 — Inflammation (days 0 to 3)
- Neutrophils dominate the first 24 to 48 hours, clearing bacteria and debris.
- Macrophages take over from day 3, phagocytosing dead cells, releasing growth factors and orchestrating the transition to proliferation. Day 3 macrophage predominance is a favourite NEET PG data point.
- Persistent neutrophil infiltration beyond day 5 signals infection.
Phase 3 — Proliferation (days 4 to 21)
- Angiogenesis — endothelial sprouting driven by VEGF and FGF; new capillaries form the pink granular surface known as granulation tissue.
- Fibroblast proliferation and migration — peak at day 5; lay down type III collagen initially.
- Re-epithelialisation — keratinocytes migrate over the wound from the edges and from hair follicles.
- Wound contraction — myofibroblasts (fibroblasts with smooth muscle actin) contract the wound margins.
Phase 4 — Remodelling (weeks to months, up to 2 years)
- Collagen switch — type III collagen (weaker, laid down first) is replaced by type I collagen (stronger).
- Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) balance collagen deposition and degradation.
- Tensile strength — reaches about 10 percent of unwounded skin at week 1, 30 percent at week 3, 70 to 80 percent by month 3, and never exceeds 80 percent long term.
Primary vs secondary intention
- Primary intention — clean surgical wound with edges approximated by sutures; minimal scar. Days 3 to 5 sutures out for face; longer for high-tension sites.
- Secondary intention — open wound (ulcer, burn, dehiscence) healing by granulation from the base upward; more scar, more contracture, higher infection risk.
- Tertiary (delayed primary) intention — wound left open initially for infection control, then closed at day 4 to 5 once contamination is controlled.
Local and systemic factors affecting wound healing
- Local — infection (single most important delaying factor), foreign bodies, mechanical stress, wound size and location, blood supply, tissue type.
- Systemic — age (elderly heal slower), nutrition (protein, vitamin C for collagen hydroxylation, vitamin A, zinc), metabolic (diabetes, uraemia), corticosteroids (inhibit inflammation and collagen synthesis), NSAIDs (inhibit prostaglandins), chemotherapy, radiotherapy, smoking, immunodeficiency.
Complications of wound healing
- Dehiscence — wound reopening; typical after abdominal surgery in the malnourished or steroid-treated.
- Hypertrophic scar — raised scar confined to the wound margin, often regresses.
- Keloid — scar extending beyond wound margin, no regression, high recurrence. More common in darker-skinned Indians; favours earlobe, sternum, deltoid, jawline. Treatment: intralesional triamcinolone, silicone gel, pressure, cryotherapy, laser, excision plus radiotherapy for recurrence.
- Contractures — exaggerated wound contraction limiting mobility; common after burns.
- Incisional hernia — through a weakened abdominal wall scar.
- Chronic non-healing ulcer — venous, arterial, diabetic (neuropathic + ischaemic), pressure. Diabetic foot ulcer is a huge India public-health issue, with delayed diagnosis and secondary infection driving amputation rates.
- Malignant transformation (Marjolin ulcer) — squamous cell carcinoma arising in a chronic wound or burn scar.
Fracture healing — the surgical parallel
Bone is the one tissue in the adult that regenerates without a scar. Healing takes 6 to 8 weeks in an uncomplicated diaphyseal fracture, longer in cortical or intra-articular bone.
- Haematoma formation (hours) — blood pooling at the fracture site.
- Inflammation (days 1 to 7) — cytokines (IL-1, IL-6, TNF, TGF-beta, BMPs) recruit mesenchymal stem cells.
- Soft callus (weeks 2 to 3) — fibrocartilage bridges the fracture ends.
- Hard callus (weeks 4 to 12) — endochondral ossification converts cartilage to woven bone.
- Remodelling (months to years) — woven bone is replaced with lamellar bone along Wolff law lines of mechanical stress.
Causes of delayed union or non-union — infection, inadequate immobilisation, fracture gap, poor blood supply (scaphoid waist, femoral neck, talus), NSAIDs (inhibit prostaglandin-driven callus), smoking, corticosteroids, diabetes, vitamin D and calcium deficiency, comminuted or open fractures, and interposed soft tissue.
India-specific and NEET PG traps
- Day 3 macrophage predominance — the pivotal day of the inflammatory to proliferative switch.
- Day 5 fibroblast peak — granulation tissue is well established.
- Type III collagen laid first, type I later — remodelling switch.
- Wound tensile strength maxes at 80 percent — never fully recovers.
- Diabetic foot ulcer — India carries the highest absolute diabetes burden and non-healing ulcers drive amputation; combined neuropathy plus arterial insufficiency plus infection.
- Keloid — genetically predisposed, common in darker Indian skin; earlobe classic; treat with intralesional steroid first.
- Marjolin ulcer — SCC in a chronic wound or burn scar.
- Chediak-Higashi syndrome — defective phagolysosome fusion; giant granules on peripheral smear.
- Chronic granulomatous disease — NADPH oxidase defect; recurrent catalase-positive infections (Staph, Aspergillus, Nocardia); positive DHR test replacing NBT.
- Leukocyte adhesion deficiency type 1 — CD18 defect; delayed umbilical cord separation, no pus formation despite infection, leukocytosis.
- Ehlers-Danlos and scurvy — defective collagen and poor wound healing; scurvy is still seen in urban Indian slums with vitamin C deficiency.
- Vitamin A deficiency — impaired epithelialisation.
- Zinc deficiency — poor wound healing.
- NSAIDs and fracture non-union — prostaglandins are essential for callus; NSAIDs are relatively contraindicated in the first 2 weeks after fracture in orthopaedic teaching.
- Non-caseating granuloma with hypercalcaemia and bilateral hilar lymphadenopathy — sarcoidosis; ACE elevated; treat with corticosteroids.
- Caseating granuloma with acid-fast bacilli — tuberculosis, default India answer.
- Aschoff body — pathognomonic of rheumatic fever; fibrinoid necrosis with Anitschkow cells and Aschoff giant cells.
- Tetanus prophylaxis in wound care — Td or Tdap for clean minor wounds if last booster more than 10 years ago; add TIG for tetanus-prone wounds if unimmunised.
- Rabies wound care — wash with soap and water for 15 minutes, apply povidone-iodine, do not suture immediately; rabies immunoglobulin plus vaccine schedule.
- Chronic inflammation and AA amyloidosis — a long-term complication of untreated rheumatoid arthritis, TB and bronchiectasis in India.
Frequently asked questions
What are the five cardinal signs of acute inflammation and their mediators?
Celsus described four cardinal signs — rubor (redness), tumor (swelling), calor (heat) and dolor (pain) — and Virchow added a fifth, functio laesa (loss of function). Rubor and calor come from arteriolar vasodilation mediated by histamine, prostaglandins (PGE2, PGI2), nitric oxide and bradykinin. Tumor comes from increased vascular permeability with plasma protein-rich exudate, driven by histamine, leukotrienes C4 D4 E4, PAF, bradykinin and C3a and C5a. Dolor is mediated by bradykinin and prostaglandins sensitising nociceptors, plus mechanical pressure from oedema. Functio laesa follows from swelling, pain and cytokine-driven metabolic disturbance. Recognising which mediator drives which sign is a frequent NEET PG single-best-answer format.
How do you distinguish a granuloma of tuberculosis from sarcoidosis?
A granuloma is a compact aggregate of activated macrophages (epithelioid cells), often with multinucleated Langhans giant cells, T lymphocytes and a fibrous rim. Tuberculosis produces caseating granulomas — central cheese-like acellular necrosis with acid-fast bacilli on Ziehl-Neelsen or auramine staining. Sarcoidosis produces non-caseating (non-necrotising) granulomas containing asteroid bodies and Schaumann bodies, with raised serum ACE, hypercalcaemia and bilateral hilar lymphadenopathy on chest X-ray. Other causes of granulomas include leprosy, syphilis (gummas), fungal infection (histoplasmosis, cryptococcosis), Crohn disease, granulomatosis with polyangiitis, foreign body reactions and berylliosis. In India, TB is the default answer unless the stem points elsewhere.
What are the four phases of wound healing and their timeline?
Wound healing has four overlapping phases. (1) Haemostasis (immediate, minutes) — vasoconstriction, platelet plug, fibrin clot. (2) Inflammation (days 0 to 3) — neutrophils dominate day 1 to 2, macrophages take over from day 3 to clear debris. (3) Proliferation (days 4 to 21) — fibroblasts lay down type III collagen, endothelial cells sprout new capillaries (angiogenesis) driven by VEGF and FGF, keratinocytes migrate to re-epithelialise, myofibroblasts contract the wound. Granulation tissue (pink, granular, capillary-rich) is the hallmark. (4) Remodelling (weeks to months, up to two years) — type III collagen is replaced by stronger type I collagen, tensile strength rises to about 80 percent of unwounded skin. Timing is a favourite NEET PG stem — day 3 macrophage predominance and day 5 fibroblast peak are both testable.
How do you distinguish a keloid from a hypertrophic scar?
A hypertrophic scar is raised and thick but stays confined within the boundary of the original wound; it often regresses spontaneously over 6 to 12 months. A keloid extends beyond the original wound margin like a claw, does not regress and frequently recurs after excision. Keloids are far more common in darker-skinned populations (African, Asian, Indian) and favour the earlobe, sternum, deltoid and jawline. Both show excessive collagen deposition, but keloids have thick, disorganised type I and III collagen bundles arranged haphazardly, whereas hypertrophic scars retain a parallel arrangement. Treatment options include intralesional triamcinolone (first line), silicone gel sheeting, pressure garments, cryotherapy, laser and, for keloids, excision combined with adjuvant radiotherapy to reduce recurrence.
What are the phases of fracture healing and what causes non-union?
Fracture healing proceeds through five phases. (1) Haematoma (hours) — blood pooling at the fracture site. (2) Inflammation (days 1 to 7) — cytokines and growth factors recruit stem cells. (3) Soft callus (weeks 2 to 3) — fibrocartilage bridges the fracture. (4) Hard callus (weeks 4 to 12) — endochondral ossification replaces cartilage with woven bone. (5) Remodelling (months to years) — woven bone is replaced with lamellar bone along Wolff law lines of stress. Causes of delayed union or non-union include infection, inadequate immobilisation, wide fracture gap, poor blood supply (scaphoid waist, femoral neck, talar body), NSAIDs (inhibit prostaglandins essential to callus formation), smoking, corticosteroids, diabetes, malnutrition (vitamin C, D, calcium, protein deficiency) and comminuted or pathological fractures.
This content is for educational purposes for NEET PG exam preparation. It is not a substitute for professional medical advice, diagnosis, or treatment. Clinical information has been reviewed by qualified medical professionals.
Written by: NEETPGAI Editorial Team
Reviewed by: Pending SME Review
Last reviewed: September 2026
