BUC 2026 CELL INJURY

Introduction to Cell Injury (Dr. Yasin)

• Definition of Cell Injury: Morphological and/or functional changes of the cell in response to stress.

• Main Types of Cell Injury:

  • Reversible Cell Injury

  • Irreversible Cell Injury

• Causes of Cell Injury:

  • Genetic Causes: e.g., inborn errors of metabolism.

  • Acquired Causes:

  • Hypoxia and ischaemia

  • Physical agents: Mechanical or thermal trauma, electricity, and radiation.

  • Chemicals and drugs

  • Microbial agents

  • Immunologic agents

  • Nutritional imbalances

• Cellular Responses to Injury:

  • Cellular adaptation

  • Reversible cell injury

  • Irreversible cell injury

  • Intracellular accumulations

Types of Atrophy (Dr. Yasin)

• Definition: Decrease in the size of an organ resulting from a decrease in the size of individual cells with or without a decrease in the number of cells.

• Types of Atrophy:

  1. Atrophy of Disuse: e.g., immobilized skeletal muscles and bone when a fractured limb is put in a cast.

  2. Atrophy due to Denervation: Atrophy of muscle fibers that are no longer stimulated by nerves.

  3. Atrophy from Hormonal Loss: Physiological atrophy of endometrium, vaginal epithelium, and breast after menopause.

  4. Atrophy due to Malnutrition: e.g., severe muscle atrophy observed in marasmus.

  5. Pressure Atrophy: Caused by prolonged compression of tissue.

Types of Hyperplasia and Hypertrophy (Dr. Yasin)

• Hyperplasia Definition: Increase in size of an organ or tissue due to an increase in the number of its parenchymal cells.

• Types of Hyperplasia:

  • Occurs in tissues composed of labile and stable cells.

  • Labile Cells: Continuously dividing cells.

  • Stable Cells: Enter cell cycle only under certain circumstances (such as injury).

• Hypertrophy Definition: Increase in size of an organ or tissue due to an increase in the size of its parenchymal cells.

• Types of Hypertrophy:

  • Physiologic Hypertrophy: e.g., hypertrophied skeletal muscles in athletes.

  • Pathologic Hypertrophy: e.g., left ventricular hypertrophy in systemic hypertension and aortic valve disease.

• Types of Physiologic Hyperplasia:

  • Hormonal hyperplasia during puberty and pregnancy.

• Types of Pathologic Hyperplasia:

  • e.g., Endometrial hyperplasia due to increased estrogen without progesterone opposition.

  • Prostatic hyperplasia with age.

  • Thyroid hyperplasia (Goiter) due to increased TSH.

Metaplasia (Dr. Yasin)

• Definition: Reversible change in which one cell type is replaced by another cell type, often in response to abnormal stimuli such as chronic irritation and inflammation.

• Characteristics:

  • Typically reverts back to normal on removal of stimulus.

  • If stimulus persists, may predispose to malignant transformation.

• Types of Metaplasia:

  • Epithelial

  • Squamous

  • Columnar

  • Mesenchymal (Osseous, cartilaginous, myelogenic)

• Examples:

  • Squamous Metaplasia: From pseudostratified columnar epithelium in bronchi in chronic bronchitis and chronic smoking.

  • Columnar Metaplasia: Barrett's esophagus where squamous epithelium changes to columnar epithelium in response to chronic reflux esophagitis.

Morphology and Mechanisms of Cell Injury (Dr. Yasin)

• Reversible vs. Irreversible Cell Injury:

  • Reversible Cell Injury: Cellular adaptation and cell recovery capability following mild stress.

  • Irreversible Cell Injury: Leads to necrosis or apoptosis, marked by significant stress exceeding adaptive capabilities.

• Mechanisms of Cell Injury:

  1. Depletion of ATP

  2. Mitochondrial damage

  3. Influx of calcium

  4. Accumulation of oxygen-derived free radicals

  5. Membrane damage

  6. Nuclear damage

Types of Hydropic Change (Dr. Yasin)

• Hydropic Change Definition: Accumulation of water in the cytoplasm of the cell, also known as cloudy swelling or vacuolar degeneration.

• Pathogenesis: Results from intracellular accumulation of sodium and escape of potassium, causing rapid water influx into the cell.

• Morphology:

  • Grossly: Enlarged organs (e.g., kidneys, liver, pancreas, heart) appearing pale.

  • Microscopically: Cells swollen with compressed capillaries, small clear vacuoles (distended ER cisternae).

Types of Necrosis (Dr. Yasin)

• Necrosis Definition: Death of a group of cells or tissues within the living body, typically accompanied by an inflammatory reaction.

• Types of Necrosis:

  1. Coagulative Necrosis:

  • Commonly resulting from sudden cessation of blood flow (ischemia).

  • Affects solid organs (kidney, heart, spleen).

  • Grossly appears pale, firm and swollen, later becoming yellowish and softer.

  • Microscopically retains tissue architecture but loses cellular details.

  1. Liquefactive Necrosis:

  • Results from ischemic injury in the brain or pyogenic abscesses.

  • Characterized by degradation of tissues by hydrolytic enzymes.

  • Grossly shows soft, liquefied center with necrotic debris.

  • Microscopically contains cystic space of necrotic debris.

  1. Caseous Necrosis:

  • Occurs in tuberculous granulomas.

  • Grossly resembles dry cheese, soft and yellowish.

  • Microscopically structureless, eosinophilic foci with surrounding granulomatous inflammation.

  1. Fat Necrosis:

  • Occurs as enzymatic or traumatic necrosis, especially in breast tissue.

  • Clinically presents as a breast mass, potentially misdiagnosed as cancer.

  1. Fibrinoid Necrosis:

  • Occurs with fibrin deposition in blood vessel walls, often in arterioles in malignant hypertension.

  • Identified microscopically by brightly eosinophilic, hyaline-like deposits.

Apoptosis (Dr. Yasin)

• Definition: Programmed cell death, controlled and regulated by cell division rates. Activated under conditions such as deprivation of growth factors or irreparable DNA damage.

• Comparison with Necrosis:

  • Apoptosis:

  • Programmed and coordinated.

  • No inflammation; death of individual cells.

  • Characterized by cell shrinkage, blebs, chromatin condensation, and apoptotic body formation.

  • Features macrophage-mediated phagocytosis of apoptotic cells.

  • Necrosis:

  • Tissue degradation by hydrolytic enzymes.

  • Accompanied by an inflammatory response.

  • Loss of cellular integrity and subsequent release of cell debris.

Mechanisms of Apoptosis (Dr. Yasin)

• Physiologic Causes of Apoptosis:

  • Embryogenesis and fetal development.

  • Hormonal dependent involution, such as regression of the lactating breast.

  • Survival and elimination of self-reactive lymphocytes.

  • Cell death due to DNA damage from radiation or chemotherapy.

Pathways of Apoptosis (Dr. Yasin)

• Extrinsic Pathway:

  • Triggered by ligands such as FAS ligand presented by NK cells and T cytotoxic lymphocytes.

  • These ligands bind to death receptors, activating adaptor proteins, which lead to a caspase cascade, ultimately activating caspase 3.

• Intrinsic Pathway:

  • Governed by a balance of pro-apoptotic and anti-apoptotic proteins.

  • Disruption occurs when cells are deprived of growth factors or under stress, leading to the activation of pro-apoptotic molecules and cytochrome C release.

• Execution Phase:

  • Both pathways converge to activate caspases, leading to cytoskeletal destruction and endonuclease activation.

Gangrene (Dr. Yasin)

• Definition: Necrosis of tissue with superadded putrefaction.

• Types of Gangrene:

  1. Dry Gangrene:

  • Begins in distal limb due to ischemia, commonly caused by atherosclerosis.

  • Affected area appears dry, shrunken, and dark black, resembling a mummy's foot.

  1. Wet Gangrene:

  • Occurs in moist tissues like the mouth, lung, intestine.

  • Develops rapidly due to blockage of venous flow by thrombus or embolus, showing soft, swollen, putrid areas.

Differences Between Dry and Wet Gangrene (Dr. Yasin)

• Site:

  • Dry gangrene: Commonly limbs

  • Wet gangrene: Common in bowel, lung

• Mechanism:

  • Dry: Arterial occlusion

  • Wet: Venous obstruction; less often arterial occlusion

• Gross Appearance:

  • Dry: Shrunken, black

  • Wet: Soft, swollen, dark

• Putrefaction:

  • Dry: Minimal due to limited blood supply

  • Wet: Marked due to blood engorgement

• Line of Demarcation:

  • Dry: Present at junction of healthy and gangrenous tissue

  • Wet: No clear line of demarcation

• Bacteria:

  • Dry: Bacteria typically fail to survive

  • Wet: Numerous bacteria present

• Prognosis:

  • Dry: Generally better prognosis

  • Wet: Generally poor prognosis due to toxemia

Intracellular Accumulations (Dr. Yasin)

• Definition: Accumulation of substances in abnormal amounts within cells, primarily in the cytoplasm or nucleus.

• Classification:

  • Mild accumulation may lead to reversible injury.

  • Severe accumulation can lead to irreversible injury.

• Fatty Change:

  • Definition: Accumulation of neutral fat (triglyceride) in cytoplasm of parenchymal cells, commonly occurring in the liver.

  • Causes: Due to conditions like hyperlipidemia (obesity), alcoholic liver disease, starvation, and exposure to drugs, toxins, or hypoxia.

• Morphology of Fatty Change:

  • Gross Appearance: Enlarged, soft liver with rounded margins, bulging cut surfaces, pale yellow, greasy to the touch.

  • Microscopic Appearance: Non-staining vacuoles in the cytoplasm of hepatocytes, exhibiting signet ring appearance.

Pathological Calcification (Dr. Yasin)

• Definition: Deposition of calcium salts in tissues.

• Types:

  • Dystrophic Calcification: Occurs in dead or degenerate tissue.

  • Metastatic Calcification: Occurs in living tissues, often due to hypercalcemia.

• Normal Blood Calcium Level: 9-11 mg%

• Sites of Dystrophic Calcification: Dead tissues, including necrotic lung, degenerated valves, infarcted kidney.

• Causes of Dystrophic Calcification: Involves local alkalinity increases leading to calcium deposition in injured tissues.

• Causes of Metastatic Calcification: Elevated calcium levels in blood due to conditions like hyperparathyroidism and hypervitaminosis D.

• Morphology of Pathological Calcification:

  • Grossly: Appears chalky white and hard.

  • Microscopically: Appears as blue granules with H&E stain, indicating calcifications.