Inflammation and Repair
🟢 Lite — Quick Review (1h–1d)
Rapid summary for last-minute revision before your exam.
Inflammation and Repair — Key Facts for FMGE Core concept: Acute inflammation involves vasodilation, exudation, and leukocyte recruitment; chronic inflammation follows when injurious stimulus persists High-yield point: Cardinal signs of inflammation (Rubor, Calor, Tumor, Dolor, Functio laesa) result from vascular and cellular events ⚡ Exam tip: Distinguish acute vs chronic inflammation and know the different types of exudates
🟡 Standard — Regular Study (2d–2mo)
Standard content for students with a few days to months.
Inflammation and Repair — FMGE Study Guide
Acute Inflammation
Cardinal Signs (Celsus - 1st century AD)
- Rubor (Redness): Vasodilation (hyperemia)
- Calor (Heat): Increased blood flow, metabolic activity
- Tumor (Swelling): Edema, leukocyte infiltration
- Dolor (Pain): Nerve ending stimulation by mediators
- Functio laesa (Loss of function): Tissue damage, mediator effects (added by Galen)
Vascular Events
Transitory phase:
- Vasoconstriction (brief, 5 min) → then vasodilation
- Mediated by catecholamines, serotonin
Vascular permeability phase:
- Mechanisms:
- Immediate transient: Gap formation in venules (histamine, bradykinin)
- Immediate sustained: Direct endothelial damage (burns, toxins)
- Delayed sustained: Cytokine-mediated (IL-1, TNF-α) - most important
- Effects: Edema, swelling, exudate formation
Chemical Mediators
| Mediator | Source | Primary Action |
|---|---|---|
| Histamine | Mast cells, basophils | Vasodilation, permeability |
| Serotonin | Platelets | Vasoconstriction, permeability |
| Prostaglandins | Membrane phospholipids (COX pathway) | Vasodilation, pain, fever |
| Leukotrienes | Membrane phospholipids (LOX pathway) | Bronchoconstriction, permeability |
| Cytokines (IL-1, TNF) | Macrophages | Systemic effects (fever, leukocytosis) |
| Complement (C3a, C5a) | Plasma proteins | Chemotaxis, anaphylatoxins |
| Kinins (Bradykinin) | Plasma (Hageman factor) | Pain, vasodilation, permeability |
| Chemokines | Various cells | Leukocyte chemotaxis |
Important cascade: Hageman factor (Factor XII) → triggers kinin system, complement, coagulation, fibrinolysis
Cellular Events
Margination: WBCs move to periphery of vessels Rolling: Selectin-mediated loose adhesion Adhesion: Integrin-mediated firm adhesion (ICAM-1, VCAM-1) Transmigration (Diapedesis): Cross endothelium via cell junctions (CD31/Platelet endothelial cell adhesion molecule) Chemotaxis: Directed migration along chemical gradient (bacterial peptides, complement C5a, leukotriene B4)
Pseudopodia: Amoeboid movement of leukocytes
Leukocyte Types and Functions
Neutrophils (60-70%):
- First responders in acute inflammation
- Phagocytosis of bacteria, debris
- Release lysosomal enzymes → tissue damage ( collateral damage)
- Lifespan: 1-2 days
- Seen in: acute bacterial infections, early inflammation
Eosinophils (<3%):
- Kill parasites (major basic protein, eosinophil cationic protein)
- Modulate allergic reactions
- Elevated in: parasitic infections, allergic diseases, Hodgkin lymphoma
Basophils/Mast cells:
- Release histamine, heparin, leukotrienes
- Key in Type I hypersensitivity, anaphylaxis
Monocytes/Macrophages:
- Arrive after neutrophils (24-48 hours)
- Long lifespan; can proliferate locally
- Cleanup, antigen presentation, chronic inflammation
- Transformed from blood monocytes
Phagocytosis
Steps: Recognition → engulfment → killing/digestion
Opsonins: IgG, C3b coating bacteria → enhanced phagocytosis Oxygen-dependent killing: Respiratory burst (NADPH oxidase)
- Superoxide → Hydrogen peroxide → Hypochlorous acid (HOCl)
- Myeloperoxase in neutrophils converts H₂O₂ to HOCl Oxygen-independent killing: Lysozyme, lactoferrin, defensins, bactericidal permeability-increasing protein
Defects in phagocytosis:
- Chediak-Higashi syndrome (giant granules, defect in granule fusion)
- Chronic granulomatous disease (CGD) - defect in NADPH oxidase → recurrent infections with catalase-positive organisms
Exudate Types
- Serous: Clear, watery (烫伤, early inflammation)
- Fibrinous: Yellow-white, fibrin strands (diphtheria, rheumatic carditis, lobar pneumonia)
- Hemorrhagic: RBCs present (trauma, malignancy, hemorrhagic infarcts)
- Suppurative/Purulent: Creamy yellow pus (Staphylococcus, Streptococcus)
- Catarrhal: Mucoid (common cold, bronchitis)
- Pseudomembranous: Fibrinomembranous exudate (diphtheria, Clostridium difficile)
Fistula/Sinus: Pathological drainage tracts
Chronic Inflammation
Features
- Mononuclear infiltrate: Lymphocytes, plasma cells, macrophages
- Tissue destruction: By inflammatory cells
- Fibrosis: Healing by connective tissue replacement
- Angiogenesis: New blood vessel formation
Causes
- Persistent infections (TB, syphilis, parasitic infections)
- Autoimmune diseases (RA, SLE)
- Prolonged exposure to irritants (silica in lungs → silicosis)
- Unknown etiology (sarcoidosis)
Granulomatous Inflammation
Granuloma: Collection of epithelioid macrophages + lymphocytes + giant cells
Types of Giant Cells:
- Langhans giant cells: Nuclei arranged in horseshoe at periphery (TB, sarcoidosis)
- Foreign body giant cells: Nuclei scattered randomly (foreign bodies)
- Touton giant cells: Central cluster of nuclei with peripheral ring (Xanthoma)
Caseating granuloma: Central caseous necrosis (TB) Non-caseating granuloma: No necrosis (sarcoidosis, Crohn’s disease)
Granuloma formation requires: Persistent antigen + T-cell mediated immunity (Type IV hypersensitivity)
Causes of Granulomas
- Infections: Tuberculosis, leprosy, syphilis, cat-scratch disease, schistosomiasis, fungal infections
- Autoimmune: Sarcoidosis, Crohn’s disease, primary biliary cholangitis
- Foreign bodies: Sutures, silica (silicosis), berylliosis, talc
- Unknown: Sarcoidosis
Healing and Repair
Regeneration vs Repair
Regeneration: Replacement with identical cells (labile cells: skin, mucosa; stable cells: liver, kidney; limited: neurons, cardiac muscle)
Repair: Replacement with connective tissue → fibrosis (scar formation)
Phases of Healing
1. Hemostasis (immediate):
- Platelet plug formation
- Fibrin clot formation
- Vasoconstriction
2. Inflammatory phase (Day 1-3):
- Neutrophils predominate (first 24-48 hours)
- Macrophages appear by day 2-3 (cleanup debris)
- Release of cytokines, growth factors
3. Proliferative phase (Day 3-weeks):
- Angiogenesis: New vessel formation (VEGF, FGF)
- Fibroblast proliferation: Collagen synthesis
- Granulation tissue formation: Highly vascular, pink, fragile tissue
- Epithelialization: Keratinocytes migrate from wound edges
- Wound contraction: Myofibroblasts (days 5-15)
- Collagen synthesis: Cross-linking → strength
4. Remodeling phase (weeks to months):
- Collagen maturation and cross-linking
- Increased tensile strength (only 80% of original after 3 months)
- Wound contraction continues
Healing by Primary Intention (First intention)
- Clean surgical wound, edges approximated
- Minimal tissue loss
- Early epithelialization (24-48 hours)
- Scar formation with minimal contraction
- Steps: Hemostasis → inflammation → epithelialization → fibroplasia → contraction → remodeling
Healing by Secondary Intention (Second intention)
- Large tissue defects, infected wounds, ulcers
- Extensive granulation tissue formation
- Wound contraction (myofibroblasts reduce wound size by 80-90%)
- Large scar formation
- Takes longer, greater inflammation
Factors Affecting Wound Healing
Local factors:
- Blood supply (best wound healing in well-vascularized areas)
- Infection (most important factor)
- Foreign bodies
- Mechanical forces (movement delays healing)
- Size/location of wound
Systemic factors:
- Age (elderly heal slower)
- Nutrition (protein, vitamin C, zinc essential)
- Diseases (diabetes - impaired healing, peripheral vascular disease)
- Drugs (corticosteroids delay healing)
Complications of Wound Healing
- Dehiscence: Wound breakdown (common in abdominal surgery)
- Keloid: Excessive collagen deposition beyond wound margins (dark-skinned individuals, ears, chest)
- Hypertrophic scar: Excessive but within wound margins
- Contractures: Excessive wound contraction (burns - restrict joint movement)
- Impaired healing: Chronic wounds, diabetic foot ulcers
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