BP104T • Unit 5Topic 1 of 4⏱ 5 Min Read

1. Etiology & Mechanisms of Reversible vs. Irreversible Cell Injury

💡 Core Concept & Clinical Context:

Cell injury occurs when environmental stresses exceed the adaptive capacity of the cell. The primary etiologies include Hypoxia (oxygen deprivation), Ischemia (loss of arterial blood supply), Reactive Oxygen Species (ROS / Free radicals), physical trauma, chemical toxins, and genetic defects. The critical biochemical point of no return distinguishing Reversible Injury from Irreversible Injury (cell death) is characterized by severe mitochondrial dysfunction with inability to regenerate ATP and massive breakdown of plasma membrane permeability allowing catastrophic influx of extracellular calcium ($Ca^{2+}$).

Clinical Scenarios & Pharmacopoeial Examples:

1Sequential Biochemical Cascade in Ischemic Cell Injury

From arterial occlusion to irreversible membrane rupture.

Step-by-Step Breakdown:

•1. Ischemia -> Deprives tissue of O2 -> Mitochondrial oxidative phosphorylation ceases -> ATP levels plummet.

•2. Loss of ATP causes failure of the plasma membrane Na+/K+ ATPase pump:

•- Intracellular Na+ and water accumulate -> Cellular Swelling (Hydropic degeneration / Cloudy swelling).

•- Intracellular K+ is lost.

•3. Switch to anaerobic glycolysis -> Rapid glycogen depletion -> Lactic acid accumulates -> Intracellular pH drops (Acidosis) -> Chromatin clumping.

•4. Detachment of ribosomes from rough ER -> Protein synthesis ceases.

•5. Point of No Return (Irreversible Injury):

•- Massive influx of extracellular Ca2+ into cytosol.

•- Ca2+ activates destructive intracellular enzymes: Phospholipases (destroy membrane lipids), Proteases (destroy cytoskeletal proteins), Endonucleases (fragment nuclear DNA), and ATPases (hasten ATP depletion).

•- Mitochondrial membrane permeability transition pore (MPTP) opens irreversibly -> Cytochrome C leaks out -> Necrotic lysis.

📋Key Takeaways & Exam Highlights

Reversible Injury Hallmark: Cellular swelling (hydropic change) and fatty change (steatosis).
Irreversible Injury Hallmark: Inability to restore mitochondrial function + Severe structural membrane disruption + Massive Ca2+ influx.
Nuclear Changes in Necrosis: Pyknosis (nuclear shrinkage and condensation) $\rightarrow$ Karyorrhexis (nuclear fragmentation) $\rightarrow$ Karyolysis (nuclear dissolution by DNases).

🇮🇳 हिन्दी व्याख्या (1. Etiology & Mechanisms of Reversible vs. Irreversible Cell Injury)

सेल इंजरी में ऑक्सीजन की कमी (Ischemia) से ATP खत्म हो जाता है और Na+/K+ पंप बंद होने से कोशिका में पानी भरकर वह सूज जाती है। अगर नुकसान बढ़ता है तो कैल्शियम (Ca2+) अंदर घुसकर कोशिका के अंगों को नष्ट कर देता है जिससे कोशिका की मृत्यु हो जाती है।