JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD Pharm. D II Year PATHOPHYSIOLOGY Previous Question Paper (October - 2020 - R08)

Cell injury is defined as any alteration in cell structure or function resulting from an abnormality in the cell's environment or internal metabolic processes, which exceeds the cell's ability to maintain homeostasis. It can be reversible or irreversible, potentially leading to cell death.

The pathogenesis of cell injury involves several key mechanisms:

1. ATP Depletion: Failure of energy-dependent pumps (like Na+/K+-ATPase) leads to cellular swelling, detachment of ribosomes, and anaerobic glycolysis, resulting in lactic acid accumulation and decreased intracellular pH.
2. Mitochondrial Damage: Caused by hypoxia, toxins, or oxidative stress, leading to the formation of the mitochondrial permeability transition pore, loss of membrane potential, and release of pro-apoptotic proteins like cytochrome c.
3. Calcium Influx: Increased cytosolic calcium activates enzymes (phospholipases, proteases, endonucleases, and ATPases) that damage cellular components and membranes.
4. Oxidative Stress: Accumulation of reactive oxygen species (ROS) causes lipid peroxidation, protein misfolding, and DNA damage.
5. Membrane Damage: Direct damage to plasma or lysosomal membranes leads to loss of cellular contents and leakage of lysosomal enzymes into the cytoplasm, triggering autodigestion.

The morphology of cell injury is categorized into reversible and irreversible changes:

• Reversible Injury: Characterized by cellular swelling (hydropic change) due to failure of ion pumps and fatty change (steatosis), particularly in hepatocytes, appearing as clear vacuoles in the cytoplasm.
• Irreversible Injury (Necrosis): Involves increased eosinophilia, nuclear changes including pyknosis (shrinkage), karyorrhexis (fragmentation), and karyolysis (dissolution), along with rupture of the plasma membrane and enzymatic digestion of the cell.
• Apoptosis: Characterized by cell shrinkage, chromatin condensation, and the formation of apoptotic bodies which are rapidly phagocytosed without eliciting an inflammatory response.