Outline of Lecture
Necrosis
Definition: Localized death of cell or tissue occurring in the living body.
Necrosis
Severe tissue damage
Metabolism stops
Structure destroyed
Function lost
Classification:
necrosis & apoptosis
Necrosis
Irreversible
Local cell death & cellular dissolution in living tissue.
Comprises self/auto digestion & lysis.
Release of catalytic enzymes from lysosome → autolysis/hydrolysis.
Types of cell death
Necrosis morphological changes seen in dead tissue within viable tissue
Autolysis dissolution of dead cells by own enzymes
Apoptosis programmed cell death. Physiological, cell regulation.
Ultrastructural changes
Margination or progressive loss of nuclear chromatin
Focal rupture of the nuclear membrane
Breakdown of the plasma membrane.
Development of flocculent densities in mitochondria.
Changes in the nucleus.
Pyknosis: condensation of chromatin of chromatin and shrinkage of the nucleus.
Karyorrhexis: fragmentation of the nucleus.
Karyolysis: dissolution of the nucleus.
Changes in cytoplasm staining
Positive staining with vital dyes such as Trepan blue which reflects abnormal membrane permeability.
Opacification: denaturation of proteins lead to aggregation with resultant opacification of the cytoplasm.
Eosinophilia: exposure of basic amino groups results in increased affinity for acidic dyes such as eosin.
Biochemical changes
Release of K+ by dead cells.
Release of enzymes into the blood. e. g. increased plasma levels of creatine kinases, lactic dehydrogenase and aspartate aminotransferase.
Release of protein or protein breakdown products into the blood.
Postmortem change: degeneration autolysis of normal tissues occurring in dead body, generally distinguished from necrosis by being diffuse and not associated with inflammatory response.
Autolysis: Digestion of cell by enzymes released from lysosome; occurs after cell dies.
Morphological ∆ in necrosis are due to
Enzymatic digestion of cells
Denaturation of protein
Types of necrosis
Coagulative, hemorrhagic, liquifactive, caseous ,fat necrosis ,gummatous necrosis & fibrinoid necrosis.
Steps/sequel of necrosis
Autolysis
Phagocytosis
Organization / fibrous repair
Dystrophic calcification.
Necrosis
cytoplasm morphologic changes
Denaturation of protein & enzymatic digestion.
Histological evidence of myocardial necrosis after 4-6 hrs.
↑ eosinophilia due to
↓ cytoplasmic RNA &
denatured cytoplasmic protein forming aggregates of fluffy material.
↑ glassy appearance due ↓ glycogen.
Vacuolated cytoplasm after digestion.
Myelin figures are whorled phospholipid masses derived from cell membrane.
Dystrophic calcification of residual fatty acids.
Necrosis
Coagulative
Hemorrhagic
Caseous
Gummatous
Liquifactive
Fibrinoid
Fatty
Pattern of tissue necrosis
COAGULATIVE NECROSIS
architecture of dead tissue preserved for some days. due to denaturation of enzymes.
Ischemia → coagulative necrosis except in brain.
Infarct is localized area of coagulative necrosis.
LIQUEFACTIVE NECROSIS
digestion of dead cells → liquid mass.(infections & hypoxic death in CNS)
GANGRENOUS NECROSIS.
Clinical term for ischemic necrosis of lower limb involving multiple tissue planes with superadded bacterial infections.
Pattern of tissue necrosis
Caseous necrosis
Cheese-like in tuberculosis.
Fat necrosis
focal area of fat destruction. (pancreatic lipase digest cell membrane → fatty acid +calcium →white deposits.)
Fibrinoid necrosis
deposition of immune complexes & fibrin in arterial wall. Artrial wall show amorphous pink circumferential necrosis with inflammation.
(3) Types:
① Coagulative necrosis:
Gross features: The necrosis area is swollen, firm and pale.
LM: cell detail is lost, but architecture preserved. The dead cells retain their outline but only indistinctly.
This type of necrosis is frequently caused by lack of blood supply and is exemplified well in infarcts of solid organs, e. g. heart, spleen, kidney.
Coagulative necrosis
Commonest ischemic
Infarction in heart ,kidney & adrenal is firm in texture
↑ ICF Ca
Denaturation of all protein including enzymes.
Histology
Preservation of tissue architecture & cell outline.
Necrotic area stain ↑ eosinophilic often devoid of nuclei
Contraction band necrosis
Coagulative necrosis acute myocardial infection
Coagulative necrosis
acute myocardial infarction
Coagulative necrosis acute tubular necrosis kidney
Coagulative Necrosis of Skin
Coagulative necrosis skin
Epidermolysis bullosa
Embryonal Rhabdomyosarcoma
Tumor coagulative necrosis
Coagulative necrosis
Testis
Massive hepatic necrosis
Coagulative necrosis
massive hepatic necrosis
Caseous necrosis:
Gross features: soft, granular, and friable a cream-cheesy appearance.
LM: granular, eosinophilic.
architecture completely destroyed.
example Tuberculosis, syphilis, some fungal infection.
Caseous necrosis
Gross
Cheese-like
Histology
Granuloma is localized collection of modified macrophges
Central cheesy material rimmed by epitheloid cells & giant cells (FB/Langhan)
In tuberculosis coagulative necrosis modified by capsule of lippopolysacchiride of TB bacili
Caseaous necrosis
② Liquefactive necrosis:
Soft and liquid grossly.
Enzymes digest the cell and convert it to a formless proteinaceous mass. Ultimately, discharge of the contents forms a cystic space. i. e. central nervous system after ischemic injury; abscesses.
Liquifactive necrosis
Autolysis predominates resulting in liquified mass. Cerebral infarction, Abscess in any tissue.
Brain cells ↑ hydrolases. These make neural tissue soft & liquid.
Abscess hydrolase from neutrophil liquefy tissue.
GBM
liquifactive Necrosis
GBM
liquifactive tumor necrosis
Liquifactive necrosis
Medulloblastoma
Haemorrhagic Necrosis
Ischemic tissue necrosis in organs with dual blood supply like, portal & systemic. One patent vascular channel results in haemorrhagic morphology.
Liver
Spleen
Intestine
Lung is supplied by bronchial &pulmonary artery.
CVN
Centrilobular haemorrhagic hepatic necrosis
Spleenic infarction
haemorrhagic necrosis
Fat necrosis:
Grossly: Opaque and chalky
LM: outline of necrotic fat cells filled with amorphous basophilic material (calcium soaps).
e. Digestion of peritoneal fat by pancreatic enzymes in pancreatic inflammation.
Fat necrosis
Types
Truamatic fat necrosis→FB giant cell + foamy histiocytes→calcification →hard lump.
Acute pancreatits released enzymes digest fat
Adipose tissue →TG + FFA →saponification + calcification.
Fat necrosis breast
Fat necrosis
Gangrene
Necrosis + putrifaction by saprophytes
Wet gangrene coagulative necrosis by ischemia + liquifactive necrosis by superimposed infection.
Dry gangrene. Drying of dead tissue associated with P vascular disease.
Necrosis is separated from viable tissue by line of demarcation.
Gass gangrene gass produced in necrotic tissue by anerobic bacteria clostridium perfringes.
Gangrene
Definition: necrosis of big tissue with superadded putrefaction, black, foul-smelling appearance.
Necrosis of big tissue → putrefactive → black, green colour.
(black or green due to breakdown of haemoglobin)
Dry gangrene:
Conditions: only occurs on the skin surface following arterial obstruction. It is particularly liable to affect the limbs, especially the toes.
Character: mummification
b. Wet gangrene:
Conditions: Both arterial and venous obstruction; wet in environment;
Character: wet swollen, foul-smelling, black or green.
Commonly in small intestine, appendix, lung, and uterus, also in limbs.
c. Gas gangrene:
Conditions: deep contaminated wounds in which there is considerable muscle damaged by gas formation bacteria.
Character: swollen obviously, gas bubbles formation. The infection rapidly spreads and there is associated severe toxaemia.
Only occasionally in civilian practice but is a serious complication of war wounds.
Definition: This is not a true degeneration but a strongly eosinophilic stain like fibrin.
Location: interstitial collagen and blood vessels (small artery and arteriole)
Nature: one kind of necrosis.
e. g. in allergic reactive diseases: active rheumatism, polyarteritis nodose.
in non-allergic reactive diseases: malignant hypertension.
Fibrinoid necrosis renal glomerulus
Fibrinoid necrosis lung
Fibrinoid necrosis Muscle
(4) Consequences of necrosis
① Acute or chronic inflammation
② Immunological reactions to sub cellular components released by dead tissue or self-antigens altered by denaturation.
After cell death
Leakage of enzymes & protein into ECF useful in diagnosis
CK-NAC, Troponin in MI
ALT in hepatitis
ALK PO4ase in biliary obstruction
Dead cells →myelin figures →FFA →calcifications
