Inflammation and Repair

🟢 Lite — Quick Review (1h–1d)

Cardinal Signs of Inflammation:

“Rubor, calor, tumor, dolor, functio laesa”

• Rubor — Redness
• Calor — Heat
• Tumor — Swelling
• Dolor — Pain
• Functio laesa — Loss of function

Acute Inflammatory Mediators — Key Sources:

• Histamine (from mast cells, basophils, platelets) — EARLIEST mediator; causes vasodilation + increased vascular permeability
• TNF-α, IL-1, IL-6 — systemic effects (fever, leukocytosis)
• Prostaglandins — pain, fever (blocked by NSAIDs)
• Leukotrienes — bronchoconstriction, vasoconstriction (LTC4, LTD4, LTE4 = “slow reacting substance of anaphylaxis”)
• Lysosomal enzymes — tissue damage (from neutrophils)
• Complement (C3a, C5a) — chemotaxis, anaphylatoxins
• Kinins — pain, vasodilation (bradykinin)

---

🟡 Standard — Regular Study (2d–2mo)

Acute Inflammation — Sequence of Events:

1. Vasoconstriction (transient, seconds)
2. Vasodilation (arterioles → increased blood flow → redness/heat)
3. Increased vascular permeability (via endothelial cell contraction, direct injury, or leukocyte-dependent mechanisms)
4. Leukocyte adhesion and transmigration (diapedesis)
5. Chemotaxis — leukocytes migrate toward inflammatory stimulus

Leukocyte Adhesion Cascade:

Selectins → Integrins → Ig-superfamily (ICAM-1, VCAM-1)

• L-selectin — on leukocytes (constitutive)
• P-selectin, E-selectin — on endothelium (induced)
• CD11/CD18 (integrins) — on leukocytes; must be activated
• ICAM-1 (CD54) — ligand for LFA-1 (CD11a/CD18)

Defects in adhesion → Leukocyte adhesion deficiency (LAD) — recurrent infections, delayed wound healing, ↑ neutrophil count

Phagocytosis:

1. Recognition and attachment — opsonins (IgG, C3b), Fc receptors, complement receptors
2. Engulfment — pseudopods form, phagosome
3. Killing/degradation — respiratory burst, lysosomal enzymes

Respiratory Burst: NADPH oxidase → superoxide (O₂⁻) → H₂O₂ → HOCl (hypochlorous acid) — most important microbicidal mechanism

• Myeloperoxidase (MPO) — in neutrophils; converts H₂O₂ to HOCl
• Chronic Granulomatous Disease (CGD): Defect in NADPH oxidase → no respiratory burst → catalase-positive organisms (S. aureus, Aspergillus, Serratia, Nocardia, Burkholderia cepacia)

Neutrophil Extracellular Traps (NETs): Netosis — chromatin fibers decorated with antimicrobial peptides; traps pathogens

Outcomes of Acute Inflammation:

1. Resolution — complete return to normal (ideal outcome)
2. Suppuration — abscess formation (pus)
3. Chronic inflammation — if irritant persists
4. Fibrosis — healing by scar formation
5. Progression — calcification, ossification

Chronic Inflammation:

• Lymphocytes, plasma cells, macrophages dominate
• Granulomatous inflammation — type IV hypersensitivity
• Causes: Persistent infections (TB, leprosy, syphilis), foreign bodies, autoimmune diseases

Granuloma = Epithelioid macrophages + Langhans giant cells + lymphocytes surrounded by fibrosis

Types of Giant Cells:

• Langhans giant cell — horseshoe/wreath arrangement of nuclei (TB)
• Foreign body giant cell — haphazard nuclei arrangement
• Touton giant cell — foamy cytoplasm surrounded by nuclei (xanthoma)

Types of Granulomas:

• Caseating granuloma — TB (central cheese-like necrosis)
• Non-caseating granuloma — sarcoidosis, Crohn’s disease

---

🔴 Extended — Deep Study (3mo+)

Chemical Mediators — Complete Table:

Mediator	Source	Action
Histamine	Mast cells, basophils	Vasodilation, ↑ permeability
Serotonin	Platelets	Vasoconstriction, ↑ permeability
TNF-α, IL-1, IL-6	Macrophages	Systemic effects (fever, acute phase)
IL-8 (CXCL8)	Macrophages, endothelium	Neutrophil chemotaxis
MCP-1	Macrophages, endothelium	Monocyte chemotaxis
RANTES	T lymphocytes	Eosinophil chemotaxis
LTB4	Phospholipids (via 5-LOX)	Neutrophil chemotaxis
LTC4, LTD4, LTE4	Phospholipids (via 5-LOX)	Bronchoconstriction, ↑ vascular permeability
PAF	Mast cells, neutrophils	Platelet aggregation, bronchoconstriction
C3a, C5a	Complement cascade	Anaphylatoxins (mast cell degranulation), chemotaxis
C5a	Complement	Neutrophil chemotaxis, adhesion
Lysosomal enzymes	Neutrophils	Tissue destruction
Free radicals	Neutrophils (respiratory burst)	Bacterial killing, tissue damage
Coagulation factors	Endothelium	Fibrin formation

Arachidonic Acid Pathway:

Phospholipids → Arachidonic Acid (via PLA2)
├── COX pathway → Prostaglandins (PGD2, PGE2, PGF2α, PGI2) + TxA2
└── LOX pathway → Leukotrienes (LTA4 → LTB4, LTC4, LTD4, LTE4)

• NSAIDs inhibit COX → ↓ prostaglandins (analgesia, anti-inflammatory, antipyretic, antiplatelet)
• Corticosteroids induce lipocortin → inhibits PLA2 → ↓ arachidonic acid → ↓ both PG + LT
• Zileuton — 5-LOX inhibitor → ↓ leukotrienes (used in asthma)
• Montelukast/Zafirlukast — leukotriene receptor antagonists

Wound Healing — Phases:

1. Hemostasis (immediate): Platelet plug formation, fibrin clot
2. Inflammatory phase (Day 1-3): Neutrophils → macrophages (clean up debris, release growth factors)
3. Proliferative phase (Day 3-weeks):
   • Angiogenesis — new blood vessel formation (VEGF, FGF)
   • Fibroblast proliferation — granulation tissue
   • Keratinocyte migration — re-epithelialization
   • Collagen synthesis (Type III collagen initially)
4. Remodeling/Maturation (weeks to months):
   • Type III collagen → Type I collagen (cross-linking)
   • Tensile strength increases up to 80% of normal
   • Wound contraction (myofibroblasts)

Factors Affecting Wound Healing:

Promoters	Inhibitors
Youth	Advanced age
Good blood supply	Poor blood supply
Adequate nutrition (protein, Vit C, Zn)	Malnutrition, vitamin deficiencies
Clean wound	Infection
Minimal tension	Excessive tension

Wound Healing Complications:

1. Infection — most common cause of wound dehiscence
2. Dehiscence — wound reopening (↑ in elderly, malnourished, infected)
3. Keloid — pathological scar beyond wound boundaries (↑ in dark-skinned individuals; collagen type III → I)
4. Hypertrophic scar — within wound boundaries
5. Proud flesh — excessive granulation tissue
6. Contractures — flexion deformities (burns, injuries over joints)

Healing by Primary (First) Intention:

• Clean surgical incision, minimal tissue loss
• Minimal inflammation
• Fine scar formation
• Example: Sutured surgical wound

Healing by Secondary (Second) Intention:

• Large tissue defect, infection present
• Large granulation tissue, more inflammation
• Wound contraction (30-50% reduction in size)
• Larger scar
• Example: Untreated wounds, burns

Healing by Tertiary (Delayed Primary):

• Initially left open (to reduce infection), then closed surgically after 3-5 days

Angiogenesis Mechanisms:

• VEGF — most specific growth factor
• FGF (basic FGF)
• TNF-α (initial phase)
• Angiopoietins — vessel maturation
• Mechanism: Degradation of basement membrane → EC migration → proliferation → tube formation

Lab Findings in Acute Inflammation:

• ↑ ESR (elevated due to fibrinogen — acute phase reactant)
• ↑ CRP (C-reactive protein)
• Leukocytosis (↑ neutrophils in bacterial infection; ↑ eosinophils in parasitic/allergic)
• Neutrophil “left shift” (immature band forms)

Fever Mechanism:

• IL-1, TNF-α, IL-6 → induce cyclooxygenase in hypothalamic endothelial cells → ↑ PGE2 → raises thermoregulatory set point
• Antipyretics (paracetamol, NSAIDs) → inhibit COX → ↓ PGE2

Key NEET-PG Clinical Pearls:

• Anaphylaxis = Type I hypersensitivity; IgE-mediated; mast cell degranulation → histamine, tryptase, heparin
• Serotonin in platelets — contributes to hemostasis and vasoconstriction
• C5a is most potent chemotactic agent for neutrophils
• Henoch-Schönlein Purpura — IgA vasculitis; palpable purpura on buttocks/lower limbs; associated with upper respiratory infection
• Kawasaki disease — acute vasculitis of medium vessels; criteria: bilateral conjunctivitis, oral changes, rash, extremity changes, cervical lymphadenopathy
• Wegener’s granulomatosis (GPA) — necrotizing granulomatous vasculitis; c-ANCA positive (anti-PR3); affects respiratory tract + kidneys
• Churg-Strauss syndrome (EGPA) — eosinophil-rich granulomatous vasculitis; p-ANCA positive (anti-MPO); asthma + eosinophilia + vasculitis

---

Content adapted based on your selected roadmap duration. Switch tiers using the selector above.