CELL INJURY

Question. Define the term Cell injury Answer. • Cell injury is any change in cell structure or function produced by stress that exceeds the cell’s capacity to adapt. • Results in reversible dysfunction if mild/short-lived or irreversible damage and cell death if severe/prolonged.

Question. Describe the causes of cell injury Answer. • Oxygen deprivation: ischemia, hypoxia (most common). • Physical agents: trauma, temperature extremes, radiation, electric shock. • Chemical agents and drugs: poisons, therapeutic drugs, environmental toxins. • Infectious agents: bacteria, viruses, fungi, parasites. • Immunologic reactions: hypersensitivity, autoimmune damage. • Genetic derangements: inborn errors, mutations affecting proteins/enzymes. • Nutritional imbalances: vitamin deficiencies, obesity, starvation. • Aging and metabolic disturbances.

Question. Describe the types of cellular response to injurious stimuli and stress Answer. • Adaptation (reversible structural/functional change to survive): atrophy, hypertrophy, hyperplasia, metaplasia. • Reversible injury: cellular swelling (hydropic change), fatty change, mild organelle damage — cell can recover if stress removed. • Irreversible injury: persistent membrane/mitochondrial damage → cell death. • Cell death: apoptosis (programmed) or necrosis (pathologic, proinflammatory).

Question. Describe the sequential biochemical and ultrastructural changes in reversible cell injury due to ischemia and hypoxia Answer. • step 1 → Oxygen depletion → oxidative phosphorylation fails → ATP falls. • step 2 → ATP depletion → Na+–K+ pump failure → intracellular Na+ and water ↑ → cell swelling (hydropic change). • step 3 → Anaerobic glycolysis ↑ → lactate ↑ → pH ↓ → chromatin clumping reversible. • step 4 → Ribosome detachment from RER → protein synthesis ↓ → cytoplasmic vacuolization. • step 5 → Mitochondria swell with small amorphous densities; cristae preserved (reversible stage). • step 6 → Plasma membrane blebbing, loss of microvilli; reversible if perfusion restored.

Question. Describe the sequential biochemical and ultrastructural changes in irreversible cell injury due to ischemia and hypoxia Answer. • step 1 → Prolonged ATP depletion → irreversible failure of ion pumps. • step 2 → Massive Ca2+ influx into cytosol and mitochondria → activation of phospholipases, proteases, endonucleases, ATPases. • step 3 → Mitochondrial permeability transition pore opening → collapse of membrane potential → further ATP loss and release of pro-apoptotic proteins (e.g., cytochrome c). • step 4 → Progressive membrane damage of plasma, lysosomal and organelle membranes → hydrolytic enzyme leakage. • step 5 → Nuclear changes: chromatin pyknosis (shrinkage) → karyorrhexis (fragmentation) → karyolysis (dissolution). • step 6 → Irreversible ultrastructural loss (severe mitochondrial disruption, membrane rupture) and cell death.

Question. Describe the pathogenesis of free radical mediated cell injury Answer. • Sources: mitochondrial electron transport leakage, oxidative burst of phagocytes, enzymatic reactions (cytochrome P450), ionizing radiation, redox cycling chemicals. • Free radicals (reactive oxygen species: O2•−, H2O2, •OH) damage via: lipid peroxidation of membranes; oxidation of proteins (loss of enzymatic function, structural damage); DNA strand breaks and base modifications. • Antioxidant defenses: superoxide dismutase, catalase, glutathione peroxidase, vitamins E/C, glutathione. • Pathogenesis: imbalance (excess ROS or decreased antioxidant) → membrane lipid peroxidation → increased permeability, enzyme inactivation, cell death.

Question. Enumerate the common morphologic forms of reversible cell injury Answer. • Hydropic change (cellular swelling) • Fatty change (steatosis) • Mild mitochondrial swelling, membrane blebs, ribosomal detachment, nuclear chromatin clumping

Question. Define the term Hydropic change Answer. • Hydropic change is intracellular accumulation of water causing cell swelling due to failure of ion pumps (especially Na+–K+ ATPase).

Question. Describe the etiopathogenesis of Hydropic change Answer. • Causes: ischemia/hypoxia, toxins, chemical injury, membrane pump failure. • Mechanism: ATP depletion → Na+–K+ pump failure → Na+ accumulation inside cell → osmotic water influx → swelling; RER cisternae dilate and ribosomes detach.

Question. Describe morphology of hydropic change with an example Answer. • Light microscopy: swollen cells, pale/eosinophilic cytoplasm, vacuolation (small clear vacuoles), nucleus often centrally located but may show reversible chromatin clumping. • Ultrastructure: mitochondrial swelling, plasma membrane blebs, dilated ER. • Example: proximal renal tubular epithelial cells after brief ischemia.

Question. Define the term Fatty change Answer. • Fatty change (steatosis) is abnormal intracellular accumulation of triglyceride-rich lipid vacuoles in parenchymal cells.

Question. Describe the etiopathogenesis of Fatty change Answer. • Mechanisms include increased fatty acid influx/synthesis, decreased beta-oxidation (mitochondrial injury), impaired apoprotein synthesis causing defective lipoprotein export, and toxin-induced mitochondrial dysfunction. • Common causes: alcohol, obesity, diabetes, toxins, hypoxia, protein malnutrition.

Question. Describe morphology of Fatty change in various organs Answer. • Liver: hepatocytes contain clear lipid vacuoles, micro- or macrovesicular steatosis, liver enlarged and yellow. • Heart: small vacuoles in myocytes (fatty change with cardiomyopathy). • Kidney: vacuolation of tubular epithelium. • Pancreas: fat infiltration in chronic conditions. • Note: macrovesicular steatosis = single large droplet displacing nucleus; microvesicular = multiple small droplets, may indicate severe mitochondrial dysfunction (e.g., Reye syndrome).

Question. Describe the types of mucoid change with examples Answer. • Mucoid/myxoid change: accumulation of mucopolysaccharide-rich ground substance in connective tissue. • Examples: myxoid degeneration of connective tissue (e.g., myxomatous degeneration of mitral valve), mucoid edema in joints, mucinous cysts.

Question. Describe the types of hyaline change with examples Answer. • Hyaline change = homogenous, glassy, eosinophilic appearance due to protein deposition intracellularly or extracellularly. • Intracellular examples: Mallory (Mallory-Denk) bodies in alcoholic hepatitis (aggregated cytokeratin filaments). • Extracellular examples: hyaline arteriolosclerosis in hypertension/diabetes (protein deposition in vessel walls), amyloid (distinct but can appear hyaline).

Question. List the morphological forms of irreversible cell injury Answer. • Necrosis (multiple patterns: coagulative, liquefactive, caseous, fat, fibrinoid, gangrenous) • Apoptosis (programmed cell death with characteristic shrinkage and apoptotic bodies)

Question. Define the term Necrosis Answer. • Necrosis is the spectrum of morphologic changes that follow cell death in living tissue, usually accompanied by loss of membrane integrity and leakage of cell contents provoking inflammation.

Question. Describe the types of Necrosis with examples Answer. • Coagulative necrosis — ischemic infarcts in solid organs (heart, kidney, spleen). • Liquefactive necrosis — focal bacterial infections, brain infarcts. • Caseous necrosis — tuberculosis and some fungal infections (granulomatous). • Fat necrosis — enzymatic fat destruction (acute pancreatitis) or traumatic fat necrosis. • Fibrinoid necrosis — immune complex-mediated vessel wall damage in vasculitis, malignant hypertension. • Gangrenous necrosis — extensive ischemic necrosis often of limb or bowel; may be dry, wet or gas.

Question. Describe the etiopathogenesis of coagulative necrosis Answer. • Caused by ischemia leading to loss of oxidative metabolism and denaturation of structural and enzymatic proteins. • Denaturation predominates over enzymatic digestion initially → tissue architecture preserved for days. • Subsequent inflammatory response and phagocytosis remove necrotic tissue.

Question. Describe the morphological features of coagulative necrosis in affected organs Answer. • Gross: pale, firm, sharply demarcated infarcted area (except when hemorrhagic). • Microscopy: preserved cell outlines (“ghost cells”), increased eosinophilia of cytoplasm, absent nuclei (pyknosis/karyorrhexis/karyolysis), eventual infiltration by neutrophils and macrophages, then granulation tissue and scar.

Question. Describe the etiopathogenesis of liquefactive necrosis Answer. • Caused by enzymatic digestion: in bacterial infections neutrophils release hydrolytic enzymes; in brain ischemia, abundant lipids and autolytic enzymes produce digestion. • Results in transformation into liquid viscous mass (pus in infection).

Question. Describe the morphological features of liquefactive necrosis in affected organs Answer. • Gross: soft, yellowish pus or cystic cavity formation. • Microscopy: loss of tissue architecture, abundant neutrophils (if infection), cell debris and fluid; later cystic cavity lined by gliotic tissue in brain.

Question. Enumerate differences between coagulative necrosis and liquefactive necrosis Answer. • Coagulative: tissue architecture preserved initially, firm; common in ischemic infarcts of solid organs. • Liquefactive: architecture destroyed, soft/liquid; common in brain infarcts and suppurative infections. • Cellular mechanism: protein denaturation (coagulative) vs enzymatic digestion (liquefactive).

Question. Describe the etiopathogenesis of caseous necrosis Answer. • Cell-mediated immune response to certain organisms (notably Mycobacterium tuberculosis) → granuloma formation with central necrosis. • Combination of enzymatic digestion and protein denaturation in a granulomatous milieu.

Question. Describe the morphological features of caseous necrosis in affected organs Answer. • Gross: soft, friable, friable yellow-white “cheesy” material. • Microscopy: amorphous granular eosinophilic debris without preserved cellular outlines, surrounded by epithelioid cells, Langhans-type giant cells and a rim of lymphocytes (granuloma).

Question. Describe the etiopathogenesis and morphological features of fat necrosis Answer. • Etiopathogenesis: pancreatic lipases released in acute pancreatitis or direct trauma to fatty tissue hydrolyze triglycerides to free fatty acids that combine with Ca2+ (saponification). • Morphology: focal areas of fat destruction with chalky white deposits grossly; microscopic fat cell necrosis with shadowy outlines, basophilic calcium deposits and inflammatory infiltration.

Question. Describe the etiopathogenesis and microscopic features of fibrinoid necrosis Answer. • Etiopathogenesis: immune complex deposition with complement activation or severe hypertension damaging vessel walls → leakage of plasma proteins including fibrin into vessel wall. • Microscopy: bright eosinophilic, fibrin-like (“fibrinoid”) deposits in vessel walls often accompanied by inflammatory cells and necrotic smooth muscle.

Question. Define the term Gangrene Answer. • Gangrene is ischemic coagulative necrosis of an extremity or portion of an organ that has become colonized or infected by putrefactive bacteria (when wet or gas gangrene), resulting in decomposition.

Question. State the types of gangrene Answer. • Dry gangrene (ischemic coagulative necrosis without infection). • Wet gangrene (superadded bacterial infection causing liquefaction). • Gas gangrene (Clostridial infection with gas production).

Question. Explain the etiopathogenesis and morphological features of dry gangrene with examples Answer. • Etiopathogenesis: slowly progressive arterial occlusion → ischemia → coagulative necrosis; limited bacterial invasion. • Morphology: dry, shriveled, dark brown/black tissue, clear demarcation from viable tissue, mummified appearance. • Example: limb ischemia from atherosclerosis or diabetes.

Question. Describe the etiopathogenesis and morphological features of wet gangrene with examples Answer. • Etiopathogenesis: severe ischemia with venous outflow obstruction and bacterial infection → rapid tissue necrosis and putrefaction. • Morphology: swollen, foul-smelling, soft, edematous tissue with liquefaction and blistering; systemic toxemia possible. • Example: bowel infarction with bacterial overgrowth, diabetic foot with infection.

Question. Enumerate the differences between dry gangrene and wet gangrene Answer. • Dry: ischemic only, mummified, slow spread, minimal systemic toxicity. • Wet: ischemia + infection, moist and foul, rapid spread, severe systemic toxicity and sepsis risk.

Question. Explain the etiopathogenesis and morphological features of gas gangrene Answer. • Etiopathogenesis: infection by clostridial species (e.g., C. perfringens) producing alpha toxin (lecithinase) and gas; often after deep contaminated wounds with devitalized tissue and poor oxygenation. • Morphology: crepitus from gas in tissues, rapidly spreading necrosis, marked hemolysis and systemic toxicity; microscopic muscle necrosis with gram-positive bacilli and gas vacuoles.

Question. Define the term Pathological calcification Answer. • Pathological calcification = abnormal deposition of calcium salts (principally calcium phosphate) in tissues, either in damaged tissues or systemically.

Question. Enumerate the types of pathological calcification Answer. • Dystrophic calcification — deposition in dead/dying tissues with normal serum calcium. • Metastatic calcification — deposition in otherwise normal tissues due to hypercalcemia.

Question. Describe the etiopathogenesis of dystrophic calcification with examples Answer. • Mechanism: localized tissue injury → membrane damage and release of phospholipids and denatured proteins that bind calcium → deposition of calcium phosphate crystals. • Examples: calcification of atherosclerotic plaques, calcified heart valves, caseous necrosis in granulomas, dead parasites.

Question. Describe the etiopathogenesis of metastatic calcification with examples Answer. • Mechanism: systemic hypercalcemia (primary hyperparathyroidism, bone destruction from malignancy, vitamin D intoxication, renal failure with secondary hyperparathyroidism) → calcium phosphate precipitates in interstitial tissues (lungs, kidneys, gastric mucosa, systemic arteries). • Examples: nephrocalcinosis, pulmonary calcification in hypercalcemia.

Question. Enumerate the differences between dystrophic calcification and metastatic calcification Answer. • Dystrophic: normal serum Ca2+, local tissue damage, common in necrotic lesions and atherosclerosis. • Metastatic: raised serum Ca2+, deposition in normal tissues, related to systemic metabolic derangement.

Question. Define the term Apoptosis Answer. • Apoptosis is energy-dependent, programmed cell death characterized by cell shrinkage, chromatin condensation, membrane blebbing, formation of apoptotic bodies that are phagocytosed without provoking inflammation.

Question. Describe the role of apoptosis in pathologic processes with examples Answer. • Physiologic roles: embryogenesis (digit separation), tissue homeostasis (turnover of cells), lymphocyte selection. • Pathologic roles: elimination of cells during viral infection, cell death in tumors after cytotoxic T-cell action, ischemic injury can trigger apoptosis, neurodegenerative diseases (excessive apoptosis), and autoimmune diseases (defective apoptosis). • Examples: apoptosis of hepatocytes in viral hepatitis; apoptosis in ischemia-reperfusion; loss of neurons in Alzheimer disease.

Question. Define the term Intracellular accumulations Answer. • Intracellular accumulations are abnormal deposits of substances within cells due to increased uptake, decreased breakdown, or defects in protein folding/transport.

Question. Enumerate the types of abnormal intracellular accumulations with examples Answer. • Lipids: fatty change in liver (steatosis), xanthomas (lipid-laden macrophages). • Proteins: excess reabsorption in renal tubules, Russell bodies (excess immunoglobulin in plasma cells), Mallory bodies (cytokeratin in alcoholic liver). • Glycogen: glycogen storage diseases, clear vacuoles in hepatocytes. • Pigments: exogenous (carbon/anthracosis) and endogenous (lipofuscin—brown atrophy; hemosiderin—iron overload). • Minerals: calcium in dystrophic/metastatic calcification.

Question. Define the terms Xanthomas, Russell bodies, Mallory body, Brown atrophy, Heart failure cells Answer. • Xanthomas — localized collections of lipid-laden macrophages in skin/subcutaneous tissue often associated with hyperlipidemia. • Russell bodies — eosinophilic, globular immunoglobulin inclusions within plasma cells due to excessive synthesis (chronic inflammation or plasma cell dyscrasias). • Mallory body — cytoplasmic eosinophilic inclusion composed of damaged cytokeratin filaments seen in alcoholic liver disease (also called Mallory-Denk bodies). • Brown atrophy — accumulation of lipofuscin pigment in long-lived cells (heart, liver) giving a brownish appearance associated with aging or chronic malnutrition. • Heart failure cells — hemosiderin-laden macrophages in alveoli resulting from chronic pulmonary venous congestion in left-sided heart failure.