PA1.1-3,PA2.1-8 | Cell Injury, Adaptation & Cell Death — Glossary

Accumulation of inhaled carbon pigment in alveolar macrophages and lymph nodes; black pigmentation ubiquitous in urban dwellers; may cause progressive massive fibrosis (coal worker's pneumoconiosis) in heavy occupational exposure.

Regulated, energy-dependent programmed cell death occurring in single cells without membrane disruption or inflammation; apoptotic bodies are rapidly phagocytosed by neighbouring cells.

A macromolecular complex of cytochrome c, APAF-1, and pro-caspase-9 that activates initiator caspase-9 in the intrinsic apoptosis pathway.

Membrane-bound fragments containing condensed chromatin and organelles, formed during apoptosis by cytoplasmic blebbing; phagocytosed by adjacent cells and macrophages without eliciting inflammation.

Reduction in cellular adenosine triphosphate resulting from mitochondrial dysfunction; disables energy-dependent processes including the Na+/K+-ATPase pump, causing cellular swelling.

Decrease in cell size (and organ mass) due to reduced protein synthesis, enhanced degradation via the ubiquitin–proteasome pathway, and autophagy; caused by disuse, denervation, reduced blood supply, inadequate nutrition, or loss of endocrine stimulation.

Cellular self-digestion process where damaged organelles and proteins are sequestered in autophagosomes and degraded by lysosomes; provides energy during starvation and drives atrophy; generates lipofuscin as a residue.

Metaplastic replacement of oesophageal stratified squamous epithelium by specialised intestinal-type columnar epithelium with goblet cells, driven by chronic GORD; a pre-neoplastic lesion with ×30–40 increased risk of adenocarcinoma.

Pro-apoptotic BCL-2 family members that form pores in the outer mitochondrial membrane, releasing cytochrome c to initiate the intrinsic apoptosis pathway.

An anti-apoptotic protein that localises to the outer mitochondrial membrane and prevents cytochrome c release; overexpressed in follicular lymphoma due to t(14;18) translocation.

Regulatory proteins governing mitochondrial apoptosis: anti-apoptotic members (BCL-2, BCL-XL) prevent cytochrome c release; pro-apoptotic members (BAX, BAK) promote it; the ratio determines whether a cell undergoes apoptosis.

Cheese-like necrosis with amorphous granular debris and no preserved cellular outlines, surrounded by a granulomatous reaction; hallmark of tuberculosis.

A family of cysteine proteases that execute apoptosis; initiator caspases (8, 9) activate executioner caspases (3, 6, 7), which cleave structural and nuclear proteins.

The earliest and most common reversible morphological change in cell injury; caused by Na+/K+-ATPase failure leading to intracellular Na+ and water accumulation.

Graded spectrum of cervical dysplasia: CIN 1 (lower ⅓ thickness), CIN 2 (lower ⅔), CIN 3/CIS (full thickness); basement membrane remains intact; predominantly HPV-driven; CIN 3 has significant malignant potential.

Necrosis in which the cellular architecture is preserved as ghost cells because ischaemia denatures both structural proteins and lysosomal enzymes; prototype is myocardial infarction.

Apoptotic hepatocyte seen in viral hepatitis, appearing as a round acidophilic (deeply eosinophilic) structure in the sinusoids with no surrounding inflammatory infiltrate.

An electron transport chain protein released from mitochondria during intrinsic apoptosis; forms the apoptosome with APAF-1 and ATP to activate caspase-9.

Ischaemic coagulative necrosis with mummification of the affected part (usually distal limb); black, dry, shrunken, with a sharply demarcated line of separation; no bacterial superinfection.

Disordered epithelial growth characterised by cytological atypia (↑ N:C ratio, hyperchromatism, loss of polarity, abnormal mitoses) and architectural disorganisation; a pre-neoplastic lesion graded by depth of involvement.

Calcium deposition in dead or damaged tissue with normal serum calcium; examples include TB granulomas, atherosclerotic plaques, and psammoma bodies.

Cellular response to accumulation of misfolded or unfolded proteins in the ER lumen; triggers the unfolded protein response (UPR) and, if unresolved, pro-apoptotic signalling.

Activated macrophages in granulomas with abundant pale eosinophilic cytoplasm and elongated 'footprint-shaped' nuclei; cannot phagocytose but secrete cytokines to contain organisms.

The cause or origin of a disease, encompassing both genetic (intrinsic) and acquired (extrinsic) factors.

A death receptor on cell surfaces that, when bound by FasL, recruits FADD and initiates the extrinsic apoptosis pathway via caspase-8 activation.

Focal death of adipose tissue due to lipase-mediated hydrolysis of neutral fat into fatty acids that bind calcium to form chalky saponification deposits; classic in acute pancreatitis.

Reversible accumulation of lipid vacuoles within parenchymal cells, predominantly hepatocytes, due to impaired lipoprotein export or excessive fatty-acid delivery.

Vessel wall necrosis characterised by deposition of fibrin, immune complexes, and necrotic protein, appearing as brightly eosinophilic homogeneous material; seen in immune vasculitis and malignant hypertension.

Macrophage engorged with oxidised LDL-derived cholesterol esters; pale, foamy cytoplasm on H&E; key cellular component of atherosclerotic plaques and xanthomas.

Large-scale clinical necrosis of a limb or hollow organ, often complicated by superimposed bacterial infection; classified as dry, wet, or gas.

Pale eosinophilic remnants of dead cells retaining their architectural silhouette after coagulative necrosis; nuclei are absent but cell shape persists.

Golden-yellow, coarse iron-containing granules derived from ferritin micelles; stains blue with Perl's Prussian blue; accumulates locally in haematomas and pulmonary macrophages ('heart failure cells') or systemically in haemosiderosis.

Widespread deposition of haemosiderin in multiple organs (liver, spleen, bone marrow, skin) without parenchymal damage, caused by haemolysis, multiple transfusions, or dietary iron overload.

Earliest form of reversible cell injury; cells enlarge with pale watery cytoplasm due to failure of the Na⁺/K⁺-ATPase and influx of Na⁺ and water; nucleus remains intact.

Increase in cell number in a tissue driven by growth factors or hormones in cells capable of division; growth ceases when the stimulus is removed, distinguishing it from neoplasia.

Increase in cell size without change in cell number, typically in post-mitotic cells such as cardiac myocytes and skeletal muscle fibres, driven by mechanical stretch and neurohormonal signals activating PI3K/Akt and calcineurin-NFAT pathways.

Inadequate oxygen availability at the cellular level; can result from reduced O2 delivery (anaemia, cardiorespiratory disease) or impaired O2 utilisation (cyanide poisoning).

Induced pluripotent stem cell — an adult somatic cell reprogrammed to an embryonic-like pluripotent state; the basis of personalised regenerative medicine.

Interruption of blood supply to a tissue; more injurious than hypoxia alone because metabolic waste (lactic acid, CO2) also accumulates and cannot be cleared.

Paradoxical additional cell death occurring on restoration of blood flow to ischaemic tissue; mediated by xanthine oxidase-generated ROS burst, Ca2+ overload, neutrophil activation, and MPT.

Dissolution of the nuclear chromatin due to DNase activation; the nucleus fades and disappears; the final nuclear change in necrosis.

Fragmentation of the condensed nucleus into basophilic granules; follows pyknosis in necrotic cells.

Cells that continuously divide throughout life, never leaving the cell cycle (e.g., epidermis, gut mucosa, bone marrow); capable of full regeneration if stem cell pool is preserved.

Multinucleated giant cell formed by fusion of epithelioid macrophages with nuclei arranged in a horseshoe (peripheral semicircle) pattern; characteristic of TB granulomas.

Insoluble yellow-brown granules ('wear-and-tear pigment') accumulating in non-dividing cells (neurons, cardiac myocytes) with ageing; composed of oxidised lipid-protein complexes generated by autophagy; a marker of cellular senescence.

Necrosis in which enzymatic digestion converts tissue to a liquid or creamy mass; occurs in brain infarction and pyogenic abscesses.

Eosinophilic intracytoplasmic inclusions in hepatocytes composed of aggregated cytokeratins 8 and 18; hallmark of alcoholic hepatitis, also seen in NASH and Wilson's disease.

Reversible replacement of one differentiated cell type by another, arising from reprogramming of stem cells; associated with chronic irritation; carries a risk of malignant transformation if the causative stimulus persists.

Calcium deposition in normal viable tissues due to hypercalcaemia; affects sites of alkaline pH such as renal tubules, gastric mucosa, and pulmonary alveoli.

Opening of a non-selective mega-channel in the inner mitochondrial membrane, dissipating the proton gradient; an early reliable marker of irreversible cell injury.

Structural alteration in cells or tissues detectable at gross, histological, or ultrastructural level; the diagnostic signature of a disease process.

N-acetyl-p-benzoquinone imine — the toxic metabolite of paracetamol overdose that depletes glutathione and causes centrilobular hepatocyte necrosis via ROS accumulation.

Programmed necrosis mediated by RIPK3 and MLKL when caspases are blocked; morphologically resembles necrosis but is genetically regulated and triggers inflammation.

A form of cell death characterised by swelling, membrane rupture, and release of intracellular contents, always triggering an inflammatory response; invariably pathological.

An imbalance between ROS production and the cell's antioxidant defences, resulting in cumulative molecular damage.

Firm, pale-tan, wedge-shaped area of coagulative necrosis in a solid organ (kidney, heart, spleen) resulting from arterial occlusion; base faces the capsule, apex the hilum.

The sequence of cellular and molecular events by which an etiological agent produces the structural and functional manifestations of disease.

The scientific study of structural, biochemical, and functional changes in cells, tissues, and organs that underlie disease; the bridge between basic science and clinical medicine.

Terminally differentiated cells that cannot divide after maturity (e.g., cardiac myocytes, neurons); irreversible loss leads to replacement by fibrosis.

Protein homeostasis — the balance of protein synthesis, folding (chaperones), and degradation (proteasome, autophagy); declines with ageing, causing accumulation of misfolded protein aggregates central to neurodegeneration.

Concentric laminated calcified spherule representing focal dystrophic calcification in papillae of papillary thyroid carcinoma, papillary serous ovarian carcinoma, and meningioma.

Nuclear condensation with intense basophilia; an early sign of irreversible injury and a histological marker of necrosis or apoptosis.

Inflammasome-mediated programmed cell death driven by gasdermin D pore formation, releasing IL-1β and IL-18; contributes to host defence and inflammatory disease.

Chemically reactive molecules containing oxygen (superoxide O2•−, H2O2, hydroxyl radical •OH) that cause oxidative damage to lipids, proteins, and DNA when produced in excess.

Dark red infarct occurring in organs with dual blood supply or collaterals (lung, bowel) or after reperfusion; blood re-enters the necrotic zone producing haemorrhagic discolouration.

Permanent cell cycle arrest (G1) triggered by critically short telomeres or DNA damage, mediated by p53-p21 and p16-Rb pathways; a tumour-suppressive mechanism that also contributes to tissue ageing.

Large eosinophilic intracytoplasmic inclusions in plasma cells, representing distended endoplasmic reticulum packed with immunoglobulin that cannot be secreted.

Conversion of fat into calcium soaps when lipase-released fatty acids bind free calcium ions in fat necrosis; produces chalky-white deposits visible grossly in pancreatitis.

Pro-inflammatory cytokine milieu (IL-6, IL-8, MMPs) secreted by senescent cells; propagates inflammation and tissue dysfunction in aged tissues; links cellular senescence to systemic ageing.

Normally quiescent (G0) cells that can re-enter the cell cycle when stimulated (e.g., hepatocytes, renal tubular epithelium); regenerate if the extracellular matrix scaffold is intact.

Abnormal accumulation of triglycerides within parenchymal cells, most prominently hepatocytes; appears as clear cytoplasmic vacuoles on H&E (lipid dissolved during processing); seen in alcoholism, obesity, diabetes, and malnutrition.

Repetitive TTAGGG sequences capping chromosome ends; shortened by 50–200 bp per mitotic cycle; critical shortening triggers p53-mediated replicative senescence; maintained by telomerase in germ cells and most cancers.

Intracellular proteolytic system in which proteins tagged with ubiquitin chains are degraded by the 26S proteasome; central to atrophy, particularly muscle wasting.

Ischaemic necrosis with superimposed bacterial infection producing a liquefactive component; moist, swollen, foul-smelling, no clear line of demarcation; risk of sepsis.

An enzyme (converted from xanthine dehydrogenase during ischaemia) that generates superoxide when O2 is reintroduced, driving the ROS burst in reperfusion injury.

Carbol-fuchsin-based stain that colours acid-fast mycobacteria (including M. tuberculosis) bright red against a blue counterstain; the confirmatory stain for TB in caseous necrosis.