Cell Injury, Adaptation and Cell Death for NEET PG Pathology: Apoptosis vs Necrosis, Necrosis Types, Calcification

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🎯 Exam priority: High. Expect: name the adaptation, apoptosis vs necrosis, caspases and the two apoptosis pathways, the newer death types (necroptosis, pyroptosis, ferroptosis), which necrosis goes with which cause, and dystrophic vs metastatic calcification.

CBME mapping: PA 1.1–1.3, 2.1–2.8. Cell-death terms follow the Nomenclature Committee on Cell Death (NCCD, 2018).

Apoptosis vs necrosis, regulated cell death, necrosis patterns and calcification. Drawn by TrackNation.

Adaptations

Barrett oesophagus (squamous replaced by columnar epithelium after reflux) can progress to oesophageal adenocarcinoma.

Why Cells Get Hurt

• Ischaemia (poor perfusion) and hypoxia (low oxygen). Free radicals such as reactive oxygen species have an unpaired electron and damage DNA, RNA and proteins. Reperfusion injury: harm when blood flow returns after ischaemia.

• Cell cycle: G0 resting; G1 12 h to days; S (DNA synthesis) 2–4 h. Telomeres shorten with each division; senescence is permanent growth arrest without death, triggered by DNA damage or oxidative stress. Cancer cells use telomerase.

How Cells Die

• Accidental cell death is instant destruction by severe physical, chemical or mechanical insults; regulated cell death uses dedicated machinery and can be modified by drugs or genes.

• Apoptosis: shrinkage, chromatin condensation (pyknosis), nuclear fragmentation (karyorrhexis), membrane blebbing and apoptotic bodies that neighbouring cells eat. The membrane stays intact. DNA is cut at regular internucleosomal sites. It balances mitosis.

• Intrinsic pathway: stress (DNA damage, growth-factor loss, ROS) → mitochondrial outer-membrane permeabilisation (MOMP), controlled by the BCL2 family → cytochrome c + APAF1 + caspase 9 form the apoptosome. Extrinsic pathway: death receptors (FAS with FAS ligand, TRAIL receptors) → caspase 8. Both end in executioner caspase 3, which exposes phosphatidylserine. Caspases are cysteine proteases that cut after aspartate.

• Necrosis (classical type III): no apoptotic features, and the debris is not cleared by phagocytes. Necroptosis: RIPK3 and MLKL; swelling and membrane rupture. Pyroptosis: inflammasome, caspase 1, gasdermin pores, inflammation. Ferroptosis: iron-dependent lipid peroxidation, controlled by GPX4. Dying cells release danger signals (DAMPs). Autolysis: tissue breakdown by its own enzymes.

Patterns of Necrosis and Gangrene

• Liquefactive: alkali ingestion — saponification, deep transmural damage. Coagulative: acid ingestion — proteins denature and capillaries thrombose, which limits penetration.

• Caseous: tuberculosis — cheese-like granulomatous necrosis with epithelioid granulomas.

• Fat necrosis: fats split into fatty acids and glycerol; in the breast after injury, surgery or radiation it can form a firm, round lump.

• Gangrene: death and putrefaction of tissue from lost blood supply. Gas gangrene: Clostridium (C. perfringens in over 80%) spreading from a contaminated wound into healthy muscle. Infarction: necrosis from local ischaemia, usually thrombus or embolus.

Accumulations, Pigments and Calcification

• Fatty liver: triglyceride droplets make the liver yellow. Lipofuscin: lipid pigment that builds up with age. Haemosiderosis: excess stainable iron in liver and macrophages without tissue damage. Hyalin: clear, homogeneous, eosinophilic material. Melanin protects skin from UV.

• Calcification: dystrophic occurs with normal serum calcium and phosphate (the commonest type in connective tissue disease); metastatic comes from high phosphate depositing calcium phosphate, as in chronic kidney disease. Vessel calcification accompanies atherosclerotic plaques. Psammoma bodies are concentric calcified rings in some tumours.

Traps the Examiner Sets

• Hypertrophy = bigger cells; hyperplasia = more cells.

• Alkali = liquefactive (deeper); acid = coagulative (shallower).

• Apoptosis keeps the membrane intact; necroptosis and pyroptosis rupture it.

• Intrinsic = caspase 9 (mitochondria); extrinsic = caspase 8 (FAS); both → caspase 3.

• Dystrophic = normal calcium; metastatic = deranged calcium–phosphate.

Memory Hooks & Shortcuts

Shortcuts to lock in this article's numbers and lists. Each one only re-packages facts proven above.

• 🧠 Hyper-TROPHY = Trophy-sized cells; Hyper-PLASIA = Plenty of cells — hypertrophy vs hyperplasia

• 🧠 Apoptosis is a tidy suicide: Shrink, Shatter, get Swallowed — apoptosis morphology

• 🧠 Nine from the mitochondria, Eight from the doorbell (FAS), Three finishes the job — caspases 9, 8, 3

• 🧠 Pyro = fire = Inflammasome and caspase 1 — pyroptosis

• 🧠 Ferro = iron = rusting lipids — ferroptosis

• 🧠 ALKali = ALL the way through (liquefactive) — alkali vs acid necrosis

• 🧠 Dystrophic = Damaged tissue, normal blood; Metastatic = Minerals high — calcification

Rapid-Revision Cards

• Atrophy

  Shrinkage — ischaemia, malnutrition, hormones.

• Hypertrophy vs hyperplasia

  Bigger cells vs more cells.

• Metaplasia

  Adult cell type swapped — Barrett.

• Dysplasia

  Abnormal cells, not yet cancer.

• Reperfusion injury

  Damage when flow returns after ischaemia.

• Free radicals

  Unpaired electron; damage DNA, proteins.

• S phase

  DNA synthesis, 2–4 h.

• Senescence

  Permanent arrest, cell alive.

• Apoptosis morphology

  Shrinkage, pyknosis, karyorrhexis, blebs, apoptotic bodies.

• Apoptosis membrane

  Intact; cleared by phagocytes.

• Intrinsic pathway

  MOMP (BCL2) → cytochrome c + APAF1 → caspase 9.

• Extrinsic pathway

  FAS/TRAIL → caspase 8.

• Executioner

  Caspase 3; exposes phosphatidylserine.

• Necroptosis

  RIPK3, MLKL; rupture.

• Pyroptosis

  Inflammasome, caspase 1, gasdermin.

• Ferroptosis

  Iron, lipid peroxides, GPX4.

• Alkali vs acid

  Liquefactive deep vs coagulative shallow.

• Caseous

  TB; cheese-like.

• Fat necrosis

  Fatty acids + glycerol; breast lump.

• Gas gangrene

  C. perfringens > 80%.

• Lipofuscin

  Ageing pigment.

• Haemosiderosis

  Iron, no damage.

• Dystrophic vs metastatic

  Normal Ca/P vs high phosphate.

• Psammoma bodies

  Concentric calcified rings.

Sources

Facts in this article were checked against these documents.

• Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018 — Galluzzi L et al., Cell Death Differ 25:486–541, 2018 (link)

• Medical Subject Headings (MeSH) scope notes — US National Library of Medicine, accessed 2026 (link)

• NCI Dictionary of Cancer Terms — National Cancer Institute, accessed 2026 (link)

• MSD Manual Professional: Tuberculosis; GERD; Hyperphosphatemia; Cellular and Molecular Basis of Cancer — Merck & Co. (MSD Manuals), reviewed 2025–26 (link)

• Post-Caustic Esophagitis: Updated Clinical Insights (J Clin Med, CC BY) — Europe PMC PMC12693313, 2025 (link)

• Calcinosis Cutis Universalis: A Review (CC BY); Phosphate: An Anion Controlling Metabolic Functions (CC BY) — Europe PMC PMC12897785; PMC13467933, 2026 (link)

• Competency Based Undergraduate Curriculum, Pathology (PA 1–2) — National Medical Commission, 2024

Test Yourself: Practice Questions

Thirty-three questions in NEET PG style, most of them clinical vignettes.

Practice Questions (NEET PG pattern)

Original questions written in the style of the exam: +4 for a correct answer, −1 for a wrong one. Every answer was checked against the sources listed above. NEET PG papers are not published by NBEMS, so these are not past-paper questions.

Q1. A tissue shrinks because of long-standing malnutrition and poor blood supply. This change is

• (a) metaplasia

• (b) atrophy

• (c) hyperplasia

• (d) hypertrophy

Q2. An organ enlarges because its cells grow bigger, without any increase in cell number. This is

• (a) dysplasia

• (b) hyperplasia

• (c) hypertrophy

• (d) metaplasia

Q3. An increase in the number of normal-looking cells in a tissue, without a tumour, is

• (a) atrophy

• (b) hyperplasia

• (c) anaplasia

• (d) hypertrophy

Q4. A man with long-standing acid reflux has columnar epithelium replacing the squamous lining of the distal oesophagus. This is

• (a) hyperplasia only

• (b) dysplasia

• (c) normal ageing

• (d) metaplasia (Barrett oesophagus), which can lead to adenocarcinoma

Q5. A biopsy shows abnormal cells that are not cancer but may become cancer. The term is

• (a) atrophy

• (b) metaplasia

• (c) dysplasia

• (d) hyperplasia

Q6. Blood flow returns to a tissue after a period of ischaemia, and further damage follows. This is

• (a) apoptosis only

• (b) reperfusion injury

• (c) autolysis

• (d) atrophy

Q7. Reactive oxygen species damage cells because they

• (a) are enzymes that cut DNA

• (b) block caspases

• (c) are free radicals with an unpaired electron

• (d) are antibodies

Q8. In the cell cycle, DNA is synthesised during

• (a) G1

• (b) S phase (usually 2–4 h)

• (c) M phase

• (d) G0

Q9. Cells that have permanently stopped dividing but are still alive, after DNA damage or oxidative stress, are in

• (a) mitosis

• (b) necrosis

• (c) apoptosis

• (d) senescence

Q10. A cell shrinks, its chromatin condenses, the nucleus fragments and small membrane-bound bodies are eaten by neighbouring cells. This is

• (a) necrosis

• (b) autolysis

• (c) apoptosis

• (d) liquefaction

Q11. A feature that distinguishes apoptosis from necrosis is that in apoptosis the

• (a) lysosomes are not involved

• (b) debris is never removed

• (c) plasma membrane stays intact and the cell is cleared by phagocytes

• (d) cell swells and bursts

Q12. In apoptosis, genomic DNA is cut

• (a) at regularly spaced internucleosomal sites

• (b) only at telomeres

• (c) randomly

• (d) by lysosomal enzymes after death

Q13. In the intrinsic (mitochondrial) pathway of apoptosis, the committing step is

• (a) mitochondrial outer membrane permeabilisation, controlled by the BCL2 family

• (b) activation of caspase 1

• (c) lipid peroxidation

• (d) binding of FAS ligand

Q14. Cytochrome c released from mitochondria joins APAF1 to form the apoptosome, which activates

• (a) RIPK3

• (b) caspase 8

• (c) caspase 1

• (d) caspase 9

Q15. A cell dies after FAS ligand binds its FAS receptor. The initiator caspase is

• (a) caspase 9

• (b) caspase 1

• (c) caspase 8 (extrinsic pathway)

• (d) caspase 3 alone

Q16. Caspases are

• (a) lipases

• (b) serine proteases

• (c) DNA polymerases

• (d) cysteine proteases that cut after an aspartic acid residue

Q17. Regulated cell death that depends on RIPK3 and MLKL and ends in cell swelling and membrane rupture is

• (a) necroptosis

• (b) autophagy

• (c) ferroptosis

• (d) apoptosis

Q18. A cell infected by an intracellular pathogen dies with inflammasome formation, caspase 1 activation and cytokine release. This is

• (a) pyroptosis

• (b) necroptosis

• (c) apoptosis

• (d) ferroptosis

Q19. Cell death driven by iron-dependent lipid peroxidation and blocked by iron chelators is

• (a) autolysis

• (b) ferroptosis (controlled by GPX4)

• (c) apoptosis

• (d) pyroptosis

Q20. Breakdown of tissue after death by the cells' own enzymes is called

• (a) autolysis

• (b) apoptosis

• (c) caseation

• (d) heterolysis by bacteria

Q21. A child swallows a strong alkali. The type of necrosis expected in the oesophagus is

• (a) coagulative necrosis limited to the surface

• (b) fat necrosis

• (c) caseous necrosis

• (d) liquefactive necrosis with deep, transmural injury

Q22. Strong acid ingestion produces which type of necrosis, and why is it shallower?

• (a) liquefactive — saponification

• (b) coagulative necrosis — capillary thrombosis limits penetration

• (c) fibrinoid — immune complexes

• (d) caseous — granulomas

Q23. A lymph node biopsy shows epithelioid granulomas with cheese-like necrotic centres. This necrosis is typical of

• (a) acid burns

• (b) gas gangrene

• (c) acute pancreatitis

• (d) tuberculosis (caseous necrosis)

Q24. A woman notices a firm breast lump months after breast surgery; biopsy shows dead fat tissue. This is

• (a) fat necrosis

• (b) caseous necrosis

• (c) gangrene

• (d) liquefactive necrosis

Q25. A contaminated wound develops infection spreading into healthy muscle. The organism in most cases is

• (a) Streptococcus pneumoniae

• (b) Mycobacterium tuberculosis

• (c) Staphylococcus aureus

• (d) Clostridium perfringens (gas gangrene)

Q26. Death and putrefaction of tissue due to loss of blood supply is

• (a) autolysis

• (b) gangrene

• (c) atrophy

• (d) metaplasia

Q27. An infarct is

• (a) fat accumulation

• (b) apoptosis from hormone loss

• (c) necrosis from local ischaemia, usually due to a thrombus or embolus

• (d) calcification of normal tissue

Q28. A lipid pigment that accumulates in normal tissues and increases with age is

• (a) haemosiderin

• (b) bilirubin

• (c) lipofuscin

• (d) melanin

Q29. A patient has increased stainable iron in the liver and macrophages without organ damage. This is

• (a) lipofuscinosis

• (b) fatty liver

• (c) haemosiderosis

• (d) haemochromatosis with cirrhosis

Q30. A patient with a connective tissue disease has calcium deposits in the skin with normal serum calcium and phosphate. The type is

• (a) metastatic calcification

• (b) dystrophic calcification

• (c) ossification

• (d) calciphylaxis only

Q31. A dialysis patient with persistently high phosphate develops hard calcium deposits in soft tissues. This is

• (a) dystrophic calcification

• (b) psammoma body formation

• (c) metastatic calcification

• (d) fat necrosis

Q32. Microscopy of a tumour shows small laminated calcified bodies with concentric rings. These are

• (a) Heinz bodies

• (b) Russell bodies

• (c) psammoma bodies

• (d) apoptotic bodies

Q33. A liver biopsy shows hepatocytes filled with lipid droplets, single large or many small; the liver looks yellow. The lipid is mainly

• (a) cholesterol esters only

• (b) lipofuscin

• (c) triglyceride (fatty liver)

• (d) glycogen

Active Recall

From memory: define the four adaptations with an example of metaplasia; explain reperfusion injury and senescence; describe apoptosis morphology and the intrinsic and extrinsic pathways with their caspases; contrast necroptosis, pyroptosis and ferroptosis; match each necrosis pattern to a cause; and distinguish dystrophic from metastatic calcification.