POINTS MIGHT HELPP YOU... MECHANISMS OF CELL INJURY IN HYPOXIC INJURY. • reversible cell injury Hypoxia first causes loss of phosphorylation in mitochondria- results in decrease of production of energy rich-ATP - loss of ATP (which is a energy source) has widespread effects on many systems in the cell- for example-heart muscle stops to contract within 60 seconds after coronary occlusion (noncontractility does not mean the cell death) the decrease in cellular ATP stimulates increase of anaerobic glycolysis= the other source how to generate energy for the cell glycogen is rapidly depleted, glycolysis results in accumulation of lactic acids - it reduces pH intracellularly - at this point, there is also early clumping of nuclear chromatin energy-dependent sodium pump slows down the activity - sodium pump keeps normally the concentration of potassium (K+) significantly higher intracellularly. Failure of active transport through the cell membrane causes that sodium (Na+) accumulates within the cell and potassium diffuses out of the cell - it leads to important movement of water intracellularly= morphologic changes in reversible cell injury -cellular swelling -due to accumulation of catabolites of metabolism and water intracellularly -loss of microvilli -blebs swelling of cisternae of endoplasmic reticulum -detachment of ribosomes from the granular ER due to disruptions of energy-dependent interactions between membranes myelin figures- derived from plasma or from membranes of organelles. They are thought to results from dissociation of lipoproteins. All the above mentioned changes are reversible if oxygenation is restored. • irreversible cell injury -if ischemia persists, irreversible injury develops. Irreversible injury is marked by severe mitochondrial vacuolization, extensive damage to plasma membranes, swelling of ribosomes, swelling of ribosomes. Injury to lysosomal membranes leads to leakage of lysosomal enzymes into the cytoplasm, there is no universal biochemical point of no return, transitions from reversible injury to cell death. critical events for irreversible cell injury: -1- ATP depletion inability to reverse mitochondrial dysfunction (lack of oxidative phosphorylation and production of energy ) -2- Cell membrane demage -the earliest phase of irreversible injury is associated with functional and structural defects in cell membranes -great deal of evidence indicates that cell membrane damage is a central factor in the pathogenesis of irreversible injury -intact cell membranes are essencial to the maintenance of normal cell permeability and volume- loss of membrane integrity causes massive influx of calcium from the extracellular space- resulting in mitochondrial dysfunction, inhibition of intracellular enzymes, denaturation of proteins ..........Reversible cell injury: cell swelling, detachment of ribosomes from granular e.r. and dissociation of polysomes into monosomes. Fatty change encountered in cells invloved in fat metabolism (hepatocyte, myocardium). Histologically characterized by pallor, hydropic change, vacuolar degeneration. EM: plasma membrane blebbing, blunting, villous distortion, myelin figures, mitochondrial swelling, rarefaction, nuclear disaggregation of granular and fibrillar elements. Irreversible cell injury: mitochondria swell, lysosomes swell, damage to plasma membrane and lysosomal membranes leads to enzyme leakage; acidosis somewhat protective by inhibiting enzymatic reactions.
Posted on: Thu, 29 May 2014 08:39:51 +0000
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