Chapter 1. Cell Injury - Injury to Cellular Organelles Flashcards
mitochondrial injury; what happens and what causes it?
release of cyt c from injured mitochondria initiates apoptosis by activating caspases in cytosol
- alcohol, salicylates, increased cytosolic Ca++
- -salicylates and alcohol produce megamitochondria with destruction of cristae
how can the SER be damaged? what happens? what causes it?
- induction of enzymes of liver cytochrome P-450 system
- causes hyperplasia and decreased drug detox with lower-than-expected therapeutic drug levels
- caused by alcohol, barbiturates, phenytoin - inhibition of enzymes of cytochrome P-450 system
- causes decreased drug detox with higher-than-expected therapeutic drug levels
- caused by proton receptor blockers, macrolides, and histamine blockers
what is inclusion (I)-cell disease?
rare inherited condition with defect in post-translational modification of lysosomal enzymes in Golgi
- mannose on lysosomal enzymes coming from RER are NOT phosphorylated due to phosphotransferase deficiency
- vesicles that pinch off Golgi empty unmarked enzymes in ECS to be degraded in blood stream
- undigested substrates accumulate in cytosol
- psychomotor retardation and early death
what is Gaucher’s diease?
deficiency of glucocerebrosidase causes accumulation of glucocerebrosides in lysosome
what is Pompe’s disease?
deficiency of alpha-1,4-glucosidase causes accumulation of glycogen in lysosome
what is Chediak-Higashi syndrome
AR with defects in lysosomal transport protein affecting synthesis, maintenance, and storage of secretory granules in various cells
- granules fuse to become megagranules
- defect in microtubule function in neutrophils and monocytes that prevents fusion of lysosomes with phagosomes to make phagolysosomes, producing bactericidal defect
- -increased susceptibility to getting S. aureus infections
- -defects in chemotaxis
what do etoposide and bleomycin do to the cytoskeleton?
cause defects in synthesis of tubulin in G2 phase of cell cycle
what can cause mitotic spindle defects in M phase of cell cycle?
- vinca alkaloids and colchicine bind to tubulin in microtubules
- interfere with assembly of mitotic spindle - paclitaxel enhances tubulin polymerization
- interferes with disassembly of mitotic spindle
what happens in intermediate filament defects?
- ubiquitin binds to damaged IF for destruction
- Mallory bodies form (ubiquinated cytokeratin IF in hepatocytes in alcoholic liver disease)
- Lewy bodies form (ubiquinated neurofilaments in Parkinson’s, or eosinophilic cytoplasmic inclusions in degenerating substantia nigra neurons)
what happens if bilirubin is accumulated endogenously?
kernicterus - fat soluble, unconjugated bilirubin from Rh hemolytic disease of newborn
-bilirubin enters basal ganglia nuclei of brain to cause permanent damage
what happens if cholesterol is accumulated endogenously?
- xanthelasma - yellow plaque on eyelid (cholesterol in macrophages)
- atherosclerosis - cholesterol-laden smooth muscle cells and macrophages (components of fibrofatty plaques)
what happens if glycogen is accumulated endogenously?
- DM - increased glycogen in proximal renal tubule cells (insensitive to insulin and become overloaded)
- von Gierke’s glycogenosis - deficiency in glucose-6-phosphatase causes excess glycogen in hepatocytes and renal tubular cells
what happens if hematin is accumulated endogenously?
melena - blood is exposed to gastric acid, so Hb is converted into black pigment (hematin) for tarry stools showing upper GI bleed
what happens in pulmonary congestion?
in left-sided heart failure, there is pulmonary hemorrhage with phagocytosis of RBCs by alveolar macrophages
-hemosiderin is breakdown product in “heart failure cells” responsible for rusty-colored sputum
what happens if melanin is accumulated endogenously?
Addison’s disease
-destruction of adrenal cortex causes increase in ACTH (melanocyte-stimulating properties) causing excess melanin synthesis and diffuse pigmentation of skin and mucus membranes
