JAWAHARLAL NEHRU TECHNOLOGICAL UNIVERSITY HYDERABAD Pharm. D II Year PATHOPHYSIOLOGY Previous Question Paper (April/May - 2019 - R08)

Cell injury occurs when cells are stressed by stimuli that exceed their adaptive capacity. The pathogenesis primarily involves ATP depletion, mitochondrial damage, influx of intracellular calcium, accumulation of reactive oxygen species (ROS), and membrane permeability defects. ATP depletion leads to failure of Na+/K+ pumps, causing cellular swelling (hydropic change) and detachment of ribosomes. Mitochondrial damage leads to the formation of the mitochondrial permeability transition pore, resulting in loss of membrane potential and apoptosis. Increased cytosolic calcium activates enzymes like phospholipases and proteases that degrade cellular components.

The morphology of reversible injury includes cellular swelling and fatty change (steatosis). Under light microscopy, this appears as clear vacuoles in the cytoplasm. Irreversible injury (necrosis) is characterized by increased eosinophilia, nuclear changes such as pyknosis (shrinkage), karyorrhexis (fragmentation), and karyolysis (dissolution). Membrane integrity is lost, leading to the leakage of cellular contents into the extracellular space, which triggers an inflammatory response.

The pathogenesis of acute inflammation involves three main components: vascular changes, leukocyte recruitment, and chemical mediators. Vascular changes include vasodilation, which increases blood flow, and increased vascular permeability, allowing protein-rich fluid (exudate) to enter the interstitial space. Leukocyte recruitment follows a sequence: margination, rolling (mediated by selectins), adhesion (mediated by integrins), and transmigration (diapedesis) toward the chemotactic stimuli.

Chronic inflammation is a prolonged response (weeks to years) where inflammation, tissue injury, and attempts at repair coexist. It is characterized by the infiltration of mononuclear cells (macrophages, lymphocytes, and plasma cells) rather than neutrophils. Macrophages are central to this process; they accumulate via recruitment from the circulation and local proliferation. Chronic inflammation often leads to tissue destruction and fibrosis (scarring) due to the persistent release of cytokines and growth factors. Common causes include persistent infections, prolonged exposure to toxic agents, and autoimmune diseases. A distinct pattern is granulomatous inflammation, a specialized form characterized by aggregates of activated macrophages with epithelioid appearance, sometimes fused into giant cells, often surrounded by a collar of lymphocytes.