BP104T • Unit 5Topic 3 of 4⏱ 5 Min Read

3. Acute Inflammation: Vascular & Cellular Events and Chemical Mediators

💡 Core Concept & Clinical Context:

Acute Inflammation is the immediate, protective homeostatic response of vascularized living tissue to infection, physical trauma, or tissue necrosis. The five cardinal clinical signs of inflammation (Celsus and Virchow) are: Rubor (redness), Calor (heat), Tumor (swelling), Dolor (pain), and Functio Laesa (loss of function). The process consists of coordinated Vascular Events (transient arteriolar vasoconstriction followed by persistent vasodilation, increased microvascular permeability, and exudate formation) and Cellular Events (Neutrophil Margination, Rolling, Stable Adhesion, Diapedesis/Emigration, Chemotaxis, and Phagocytosis).

Clinical Scenarios & Pharmacopoeial Examples:

1Cellular Leukocyte Extravasation & Phagocytosis Cascade

Step-by-step neutrophil recruitment to the infection site.

Step-by-Step Breakdown:

•1. Margination & Rolling:

•- Blood flow slows (stasis); neutrophils marginate along vascular endothelium.

•- Endothelial Selectins (P-selectin, E-selectin) bind to Sialyl-Lewis-X on leukocytes -> Low-affinity transient rolling.

•2. Stable Adhesion:

•- Pro-inflammatory cytokines (TNF-alpha, IL-1) activate endothelial ICAM-1 and VCAM-1.

•- Leukocyte Integrins (LFA-1, Mac-1) switch to high-affinity conformation -> Firm endothelial arrest.

•3. Diapedesis (Transmigration):

•- Leukocytes squeeze between endothelial junctions mediated by PECAM-1 (CD31).

•4. Chemotaxis:

•- Leukocytes migrate along chemical gradient toward injury site driven by Chemotactic Agents: Complement C5a, Leukotriene B4 (LTB4), Bacterial formyl peptides (fMLP), and IL-8.

•5. Phagocytosis & Microbial Killing:

•- Recognition & Opsonization: Pathogen coated with Opsonins (IgG, C3b).

•- Engulfment: Pseudopods engulf microbe into Phagosome -> Fuses with lysosome to form Phagolysosome.

•- Respiratory Burst (Oxygen-dependent killing): NADPH Oxidase converts O2 into Superoxide radical (.O2-) -> Superoxide dismutase converts to H2O2 -> Myeloperoxidase (MPO) in presence of Cl- generates Hypochlorous acid (HOCl - bleach) that rapidly kills bacteria.

📋Key Takeaways & Exam Highlights

Vascular Permeability Mediators: Histamine and Serotonin cause immediate transient endothelial contraction (gaps); Bradykinin, Leukotrienes (LTC4, LTD4, LTE4).
Pain (Dolor) Mediators: Bradykinin and Prostaglandin E2 (PGE2) sensitize nociceptors.
Fever (Pyrexia) Mediators: IL-1, TNF-alpha, and IL-6 stimulate hypothalamic synthesis of PGE2.
Anti-Inflammatory Drug Targets: NSAIDs (Aspirin, Ibuprofen) inhibit Cyclooxygenase (COX-1/COX-2), blocking Prostaglandin synthesis; Corticosteroids inhibit Phospholipase A2 via Lipocortin/Annexin A1.

🇮🇳 हिन्दी व्याख्या (3. Acute Inflammation: Vascular & Cellular Events and Chemical Mediators)

सूजन (Inflammation) के 5 मुख्य लक्षण हैं: लालिमा (Rubor), गर्मी (Calor), सूजन (Tumor), दर्द (Dolor) और अंग का काम न करना। न्यूट्रोफिल रक्त वाहिकाओं से निकलकर कीटाणुओं को ओप्सोनाइजेशन और फेगोसाइटोसिस द्वारा नष्ट करते हैं। एस्पिरिन जैसी NSAID दवाएं प्रोस्टाग्लैंडीन को रोककर दर्द और सूजन कम करती हैं।