Ch2 Cell Death EC Flashcards
Necrosis
Death of groups of cells + inflammation
Coagulative necrosis
Preservation of structural outlines
Mechanism of coagulative necrosis
Denaturation of enzymes and structural proteins (lactate, heavy metals, ionizing radiation)
Inactivation of intracellular enzymes
Microscopic features of coagulative necrosis
Indistinct outlines of cells within dead tissue
Nuclei absent
Infarction
Gross manifestation of coagulative necrosis due to sudden occlusion of a vessel
Pale (ischemic) infarcts
Dense tissue
heart, kidney, spleen
Hemorrhagic (red) infarcts
Loose tissue
lung, bowel, testicle
Dry gangrene
Toes in DM is a form of infarction that results from ischemia with coagulation necrosis
When is an infarction less likely to occur?
Dual blood supply (lungs)
Collateral circulation (arcade system of superior/inferior mesenteric arteries)
Preexisting disease
Mechanism of liquefactive necrosis
Release of lysosomal enzymes by necrotic cells or by the release of hydrolytic enzymes by neutrophils
Examples of liquefactive necrosis
Cerebral infarction (via hydrolytic enzymes from neuroglial cells) Abscess in bacterial infection (via hydrolytic enzymes released by neutrophils)
Wet gangrene
Predominantly liquefactive necrosis
Dry gangrene + superimposed anaerobic infection (C. perfringens)
Mechanism of caseous necrosis
Produced by lipid from cells walls of mycobacterium and fungi after immune destruction by macrophages in granulomas
other granulomas as noncaseating because they lack excessive amounts of lipid
Gummatous necrosis
Type of coagulation necrosis
Associated with spirochetal disease (syphilis)
Hypersensitivity directed against spirochetes
Mechanism of enzymatic fat necrosis
Activation of pancreatic lipase causes hydrolysis of TGs in fat cells
Calcium combines with fatty acids via saponification
Traumatic fat necrosis
Necrosis in fatty tissue as a result of trauma
Non-enzymatic (unlike pancreas)
Fibrinoid necrosis
Necrosis that may occur in small muscular arteries, arterioles, venules, glomerular capillaries, valve leaflets, myocardium, and subcutaneous tissue
Mechanism of fibrinoid necrosis
Deposition of pink-staining proteinaceous material in damaged tissue
Necrosis of immune-mediated disease
Extrinsic apoptosis pathway (death receptor pathway)
TNFR1 binds TNF-alpha
Fas-R binds Fas-Ligand
(Perforin and granzyme B in immune cells)
Activation of initiator caspases (8&10)
Activation of effector caspases
~Protease destroys cytoskeleton
~Endonuclease causes pyknosis of nucleus
Intrinsic apoptosis pathway (mitochondrial pathway)
BCL-2 stabilizes cytochrome c in mito. membrane (anti-apoptotic)
BAX/BAK form channels in mito. membrane (pro-apoptotic)
Cytochrome C complexes with another protein activating initiator caspase 9
Activation of effector caspases
~Protease destroys cytoskeleton
~Endonuclease causes pyknosis of nucleus
Microscopic appearance of apoptotic cells
Deeply eosinophilic
Nucleus pyknotic, fragmented, or absent
Minimal inflammation
Pyroptosis
Proinflammatory cell death using caspase-1
Monocyte cell destruction of Salmonella, Shigella, Legionella
What are some examples of pathologic activation of caspase-1?
MI Neurodegenerative disease IBD Cerebral ischemia Endotoxic shock
Aspartate aminotransferase (AST) diagnostic use
Marker of diffuse liver cell necrosis
Mitochondrial enzyme preferentially increased in alcohol-induced liver disease
