Q2 LONG ANSWER 10M ★ High-yield

Define necrosis. Describe its types with examples. Compare necrosis with apoptosis.

Pathology · 2nd Professional — Para-Clinical

Definitions

Necrosis is the morphological appearance of cell death following denaturation of proteins and enzymatic digestion, occurring in a living organism.

Apoptosis is an actively regulated, energy-dependent process of individual cell suicide, occurring in both physiological and pathological states.

Nuclear Changes in Necrosis

Change	Appearance
Pyknosis	Shrinkage of the nucleus with increased basophilia
Karyorrhexis	Fragmentation of the pyknotic nucleus
Karyolysis	Fading and dissolution of chromatin by DNase

Cytoplasm becomes intensely eosinophilic, from loss of ribosomal RNA and denatured protein
Nuclear changes take 4 to 12 hours to appear, which is why very early infarcts look normal under the microscope

Types of Necrosis

Type	Appearance	Typical sites
Coagulative	Architecture preserved as "ghost outlines"; firm; denaturation exceeds digestion	Infarcts of all organs except the brain — heart, kidney, spleen
Liquefactive	Complete digestion to a viscous fluid; a cyst may result	Brain infarcts; abscesses (bacterial and fungal)
Caseous	Cheesy, white, friable; amorphous granular debris within a granuloma; architecture lost	Tuberculosis; some fungal infections
Fat necrosis	Chalky white deposits; saponification of released fatty acids with calcium	Acute pancreatitis; trauma to the breast
Fibrinoid	Bright pink amorphous material in vessel walls; immune complexes with fibrin	Malignant hypertension, vasculitis, rheumatic fever, Arthus reaction
Gangrenous	Not a distinct type — coagulative necrosis with superimposed putrefaction	Limbs and bowel

Dry gangrene — arterial occlusion, tissue is dry, shrunken and black, with a clear line of demarcation; little infection
Wet gangrene — venous obstruction or superadded infection; moist, swollen, foul, no clear line; far more dangerous, with systemic toxaemia
Gas gangrene — Clostridium perfringens; crepitus from gas in the tissues

CLINICAL PEARL

Why is the brain the exception? Because it is rich in lipid and in lysosomal enzymes but poor in structural protein and connective tissue. Denaturation therefore cannot outpace digestion, so cerebral infarcts undergo liquefactive rather than coagulative necrosis and end as a fluid-filled cyst.

Apoptosis

Physiological

Embryogenesis — interdigital webs, involution of the paramesonephric ducts
Hormone-dependent involution — endometrium, lactating breast after weaning
Deletion of self-reactive lymphocytes
Cell turnover in proliferating populations such as the gut crypts

Pathological

DNA damage from radiation and cytotoxic drugs
Accumulation of misfolded proteins
Viral infection, both directly and by cytotoxic T cells
Duct obstruction causing atrophy of pancreas or kidney

Mechanisms of Apoptosis

Intrinsic (mitochondrial) pathway — the commoner → Loss of survival signals or DNA damage → BAX and BAK exceed bcl-2 → Mitochondrial permeability rises → cytochrome C released → Forms the apoptosome with APAF-1 → activates caspase 9 → extrinsic (death receptor) pathway — FAS–FAS ligand or TNF binding → Activates caspase 8 → Both converge on the executioner caspases 3 and 6 → Endonuclease activation → DNA fragmentation; cytoskeletal breakdown → apoptotic bodies formed and phagocytosed — NO inflammation

Necrosis and Apoptosis Compared

Feature	Necrosis	Apoptosis
Nature	Always pathological	Physiological OR pathological
Extent	Groups of cells	Single cells
Cell size	Enlarged (swelling)	Shrunken
Plasma membrane	Disrupted	Intact, but altered orientation of lipids
Cell contents	Leak out	Retained in apoptotic bodies
DNA breakdown	Random, diffuse smear	Internucleosomal — a "ladder" on electrophoresis
Energy	Not required (ATP depleted)	ATP-dependent
Inflammation	Present	Absent
Regulation	Passive, unregulated	Genetically programmed

Applied Aspects

Caseous necrosis is virtually diagnostic of tuberculosis in the right clinical setting, and is the reason a Ghon focus and cold abscess behave as they do
Fat necrosis of the breast follows trauma and forms a hard, fixed lump with skin tethering that mimics carcinoma clinically and on imaging
Excessive apoptosis contributes to neurodegenerative disease and to ischaemic injury; too little allows cancer and autoimmunity
P53 triggers apoptosis in cells with irreparable DNA damage; its loss is the commonest genetic abnormality in human cancer
Most chemotherapy and radiotherapy work by inducing apoptosis, which is why tumours with defective apoptotic pathways are resistant
Bcl-2 overexpression from the t(14;18) translocation blocks apoptosis and is the basis of follicular lymphoma — a cancer of failure to die rather than excess division
Councilman bodies in viral hepatitis and apoptotic bodies in the gut in graft-versus-host disease are apoptosis seen down the microscope
Gangrene of the foot in diabetes combines large-vessel disease, microangiopathy, neuropathy and infection, and is the commonest reason for non-traumatic amputation in India
Apoptosis is recognised histologically as a shrunken, deeply eosinophilic cell with a condensed fragmented nucleus, without any surrounding inflammatory reaction
Phosphatidylserine flips to the outer leaflet of the apoptotic cell membrane and acts as the "eat me" signal for phagocytes; it is the basis of the annexin V assay
Necroptosis is a regulated form of necrosis, morphologically necrosis but genetically programmed, now recognised in several diseases

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