cellular injury

General mechanisms of cell injury: Pathology: 1) reactive oxygen metabolites 2) loss of calcium homeostasis - activation of Ca⁺²-dependent proteases - activation of Ca⁺²-dependent phospholipases - activation of Ca⁺²-dependent ATPases - activation of Ca⁺²-dependent endonucleases 3) ATP depletion 4) defects in membrane permeability 5) genetic aberrations Sequence of events (hypoxic & ischemic cellular injury): 1) compromise of mitochondrial oxidative phosphorylation a) decreased cellular ATP - failure of plasma-membrane Na⁺/K⁺ ATPase b) increased glycolysis - diminished glycogen stores - accumulation of lactic acid c) increased inorganic phosphate d) decreased creatine phosphate stores 2) cellular edema - dilation of the endoplasmic reticulum - loss of cellular polarity 3) ribosomal disruption - detachment of ribosomes from endoplasmic reticulum - dissociation of polysomes into monosomes 4) formation of blebs 5) loss of microvillae 6) mitochondrial swelling 7) injury to lysosomal membranes. The duration of ischemia require to produce irreversible cell injury varies with tissue: 1) hepatocyte: 1-2 hours 2) neuron: 3-5 minutes Morphologic changes: 1) light microscopy - cellular swelling - fatty change 2) electron microscopy a) plasma membrane alterations - blebbing - distortion of microvilli - formation of myelin figures - loosening of intercellular attachments - alterations in the cytoskeleton b) mitochondrial changes - swelling - rarefaction - appearance of small amorphous phospholipid-rich amorphous densities c) ribosomal disruption - dilation of the endoplasmic reticulum - detachment of ribosomes from endoplasmic reticulum - dissociation of polysomes into monosomes 4) nucleolar alterations

References

Cotran et al Robbins Pathologic Basis of Disease, 5th ed. W.B. Saunders Co, Philadelphia, PA 1994 pg 4-9