Morphologic features of necrosis- cytoplasmic changes
Early phase: cytoplasm becomes homogenous pink in HE section
increased eosinophilia due to loss of RNA. (nb: RNA is responsible for cytoplasmic basophilia) and consolidation of cytoplasmic components upon cell collapse; degradation of cytoplasmic proteins--> ghost like appearance of cell.
Necrotic cells "individualize"- they lose adherence to basement membrane and adjacent cells- they're found free in tubules, alveoli, follicles and other lumen surfaces
Late phase: cell rupture with loss of integrity and release of cell contents.
Morphologic features of necrosis: nuclear changes
Pyknosis: nucleus is shrunken, dark, homogenous and round
Karyorrhexis: nuclear membrane is ruptured and dark fragments of the nucleus are released in the cytoplasm
Karyolysis: nuclear outline is extremely pale due to dissolution of chromatin (caused by action of DNAses)
Types of oncotic necrosis
Oncotic necrosis- typical feature of cell injury is swelling
Coagulation necrosis: ischemic or toxin-induced in liver, heart and kidneys
Liquefactive necrosis: ischemic or toxin-induced necrosis in CNS
Caseous necrosis: associated with mycobacterial infections (TB)
Gangrenous necrosis: dry/moist/gas gangrene caused by bacterial toxins, other toxic agents, ischemia
Enzymatic necrosis: typically necrosis of adipose tissue caused by leakage of pancreatic enzymes (lipases) subsequent to exocrine acinar tissue injury.
preservation of the basic outline of necrotic ceels
cytoplasm: homogenous eosinophilc appearance due to coagulation of cellular proteins
Injury or subsequent cellular acidosis denatures both structural proteins and enzymes
Nuclei: pyknotic/karyhorrhectic/karyolitic or absent
Occurs in any tissue, except brain parenchyma,
Common causes of coagulation necrosis
Gross and histo appearance of coagulation necrosis
example: bovine renal infarct
gross: pale area of central necrosis, hemorrhagic periphery
Histo: presence of detached necrotic cells within tubules ("individualized"); v. dense shrunken hyperbasophilic nuclei (pyknosis) and karyorrhexis; tubular necrosis with increased cytoplasmic eosinophilia; no nuclei detected in some necrotic cells.
Coagulation necrosis can be caused by nephrotoxic substances
Plants: oak, acorn, oxalates (cows); easter lily (cats); red maple (horses); raisins/grapes (dogs)
Heavy metals: mercury and lead
Chemicals: ethylene glycol
Therapeutic drugs: ABX (gentamycin and cephalosporins), some chemotherapeutics
Pigments: hemoglobin and myoglobin
Necrotic cells and tissues transformed into a granular, friable material grossly resembling cottage cheese
Necrotic focus= coagulum of nuclear and cytoplasmic debris
Typical of TB and cornyebacterium pseudotuberculosis (small ruminants)
Any tissues affected; necrotic debris is mainly dead leukocytes
dystrophic calcification commonly occurs at later stages
Comparison of coagulation necrosis with caseating necrosis
Caseous necrosis is an older (chronic) lesion often associated with poorly degradable lipid substances of bacterial origin.
Delayed degradation of bacterial wall components-->formation of a focal caseous necrosis--> surrounded by granulomatous inflammation and a peripheral fibrous capsule.
Bovine TB lesions
LN has multifocal granulomas with central caseation necrosis
Mycobacterium bovis gets inahled-->bacilli within alveolar spaces in the lung-->phagocytosed by alveolar macrophages. Either 1) bacteria is killed and infection is stopped or 2) macrophage bactericidal activity is inhibited and macrophages get killed and the bacteria spread.
Sheep/goat caseous lymphadenitis
Chronic suppurative (pus) lymphadenitis
Intracellular bacterium cornyebacterium pseudotuberculosis (c. ovis)
Bacteria enters through shearing wounds, arthropod bites
Spread by ruptured abscesses and oral and nasal secretions
Incubation period of 3 months
Ill-thrift, carcass condemnation.
inspissated (thickened/congealed) pus centrally with a pale, peripheral fibrous capsule.
Usual type of necrosis in CNS
Individual neurons initially show coagulation necrosis, followed by a liquefactive process affecting neuroparenchyma
Hypoxia or toxin induced neuronal necrosis--> enzymatic dissolution of the neuropil (brain parenchyma)
There's little to no fibrous connective tissue in the CNS-->lack of support to necrotic tissue, no fibrotic reaction to replace tissue necrosis and loss.
The resulting cavity is filled with fluid and debris of neuronal membrane lipids--> debris cleared up by macrophages (gitter cells)
Liquefactive necrosis in tissues other than CNS
pyogenic bacteria cause liquefactive necrosis--> recruitment of inflammatory cells (neutrophils)-->release of lytic enzymes--> destruction of bacteria + degeneration and necrosis of neutrophil--> abscess (pus-filled cavity) can be considered to be a type of liquefactive necrosis.
With dehydration--> pus inspissates--> caseous necrosis
Example of liquefactive necrosis
Spinal cord compression:
histo features: "malacia" (grey and white matter- generalized softening of tissue)- ischemic neurons, necrosis, hemorhage, edema, liquefaction, pallor (rarefaction of brain parenchyma)
Fibrocartilagenous embolic myelopathy: infarction due to blockage of spinal cord vessels. Multifocal extensive areas of reddish-brown discoloration, softening and cavitation representing hemorrhage, "malacia" (necrosis) and loss of substance
initial lesion is coagulation necrosis which progresses with specific mechanisms and morphologic patterns
area of necrotic tissue (coagulation necrosis) further degraded by saprophytic bacteria (microorganisms living on dead organic matter)--> causes putrefaction
typically observed with: ischemic necrosis of extremities (tight bandage); penetrating injury to arterial blood supply; lung necrosis caused by aspiration.
Gross and microscopic appearance of moist gangrene
Necrotic tissue becomes soft, moist, reddish-brown to black.
Saprophytic bacteria produce gas--> gas bubbles and putrid smell from resulting H2S, ammonia and mercaptans
Tissue liquefaction caused by saprophytic bacteria and infiltrating neutrophils
Coagulation necrosis secondary to ischemia/infarction followed by mummification.
Limited putrefaction and bacteria fail to survive
Observed on lower portions of an extremity i.e. leg, tail, ears, udder
Caused by: 1) ingested toxins (ergot and fescue)-->peripheral arteriolar vasoconstriction and damage to capillaries--> thrombosis and infarction
2) cold (frost bite): direct cell freezing and disruption by intra/extra-ceullar ice crystal formation, vascular damage leading to ischemia and infarction
Gross appearance: shriveled, dry, brown-black tissue.
anaerobic bacteria proliferating and producing toxins in necrotic tissue (Clostridium perfringens and clostridium septicum)
bacteria introduced by penetrating wounds into muscles or subcutis
necrotic tissue-->anaerobic medium fro growth of the clostridia
Clostridium chauvoei (black leg): bacteria NOT introduced by penetrating wound, but from spores spread hematogenously from intestine and lodged in muscle. Once trauma/necrosis occurs and anaerobic conditions predominate, spores germinate and bacteria proliferate.
Gross and histo appearance of gas gangrene
Gross: tissues are dark red to black with gas bubbles and a fluid exudate that may contain blood; lesions are characterized by coagulation necrosis of muscle with a sero-hemorrhagic exudate and gas bubble formation.
Saponification caused by enzymatic leakage due to pancreatitis.
Fat necrosis (type of enzymatic necrosis due to lipase): traumatic: crushed fat- pelvic fat in dystocia, sternal fat in recumbent animals
Abdominal fat necrosis of cattle: necrotic fat in mesentery, omentum and retroperitoneum
Important disease conditions characterized by necrosis
Infectious bovine rhinotracheitis:
Canine parvovirus enteritis
Canine infectious hepatitis/canine adenovirus
Infectious bovine rhinotracheitis
diffuse necrosis of tracheal mucosa
-transient, acute febrile illness with severe hypermia and focal necrosis of nasal, pharyngeal, laryngeal, tracheal (+/- bronchial) mucosae
-thick plaques of fibrinonecrotic exudate (diphtheritic membranes) cover the laryngeal and tracheal mucosae (due to secondary bacterial infection), necrosis and exfoliation of ciliated epithelial cells followed by repair.
Canine parvovirus enteritis
Flaccid, dilated, segmentally reddened intestine with serositis, granular necrotic appearance
Initial multiplication in lymphoid tissue--> viremia--> villous atrophy results from inability to replace enterocytes from crypts. Necrosis of crypt epithelial cells lead to crypt dilatation.
Canine infectious hepatitis/canine adenovirus
Liver enlarged and friable, will often see fibrin on capsular surface, granular appearance of serosal surface; fibrin tags on liver lobs; gall bladder wall thickened by oedema; hepatocyte necrosis and loss; intranucelar inclusions in hepatocytes.
Sequelae to oncotic necrosis
Inflammatory reaction within viable tissue: band of leukocytes, hyperemia
Digestion and liquefaction of necrotic tissue: phagocytosis by macrophages; diffusion by blood or lymphatics
Regeneration of normal tissue or fibrous scarring.
highly coordinated and active process/sequence leading to programmed cell death
Physiological: involution of tissues during embryonic development, age-related involution/atrophy of thymus
Pathological: irreversible cell injury with different underlying causes--infectious agents, ionizing radiation, chemicals, etc.
Apoptosis due to action of specific enzymes: Caspases (Cys-Asp cleaving proteins) and nucleases
Reduced cell size, fragmentation of nucleus into nucleosome-size fragments, intact plasma membrane with altered structure, intact cellular contents (may be released in apoptotic bodies), no adjacent inflammation; often physiologic.
Intrinsic (mito pathway): withdrawal of growth factors, hormones. Lack of survival signals or irradiation (DNA damage)--> activation of sensors--> activation of Bax/Bak channel--> leakage of cytochrome C, other proteins--> cytochrome C + APAF1 "Apoptosome"--> activation of caspase 9--> apoptosis
Extrinsic (death-receptor mediated): ligand activated fas or tnfr 1--> activate Bid
Possible connection btwn intrinsic and extrinsic pathway via caspase 8- mediated activation of the pro-apoptotic factor Bid.