s Dead cell Mechanisms of Cell Injury Depletion of ATP Mitochondrial Damage Influx of Intracellular Calcium and Loss of
Calcium Homeostasis Accumulation of Oxygen-Derived free radical (Oxidative stress) Defects in Membrane Permeability Morphology of Cell Injury and Necrosis Cell Injury Reversible
Irreversible Cell Death Necrosis Apoptosis Cell Injury and Death Reversible Injury Cell swelling develops when cells are incapable of fluid an ion homeostasis (ed function of ATP
dependant pumps). o Fatty change the accumulation of lipid vacuoles in the cytoplasm. o Irreversible injury (Necrosis) o
Two basic processes underlie the morphologic changes of necrosis Denaturation of protein Enzymatic digestion of cell components Ischemic injury Cell injury and death
Reversible hypoxic/ ischemic injury Loss of ATP generation by mitochondria initially results in reversible events: o Na+/K+ ATPase membrane pump leads to a loss of ionic and osmotic gradient ( edCa+2+ Na+, ed K+ and osmotic gain of water) resulting cell swelling & ER dilatation) o ed anaerobic glycolysis results in glycogen depletion
and lactate accumulation (ed pH). o Reduced protein synthesis due to ribosome detachment from the RER Cell Injury and Death Irreversible hypoxic/ ischemic injury These changes are reversible if O2 and flow are reinstated, the
transition to irreversible injury depends on the extent of ATP depletion and membrane dysfunction especially of mitochondria. ATP depletion results in MPT with loss of the H+ gradient ATP depletion releases cytochrome c that can induce apoptosis edCa+2 activates o membrane phospholipases with resulting membrane damage o Intracellular proteases leading to cytoskeletal degradation Phospholipid degradation products that accumulate are directly toxic
to the cell Reversible vs irreversible cell injury Reversible injury * Decreased ATP levels * Ion imbalance * Swelling
Decreased pH Fatty change (liver) Irreversible injury * Amorphous densities in mitochondria * Severe membrane damage
* Lysosomal rupture Extensive DNA damage Mechanisms of Cell Injury Ischemic injury
Morphology of Cell Injury Reversible Injury Cellular swelling Fatty change
Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 19 October 2005 05:51 PM) 2005 Elsevier Hydropic change or vacuolar degereration. Appears whenever cells are incapable of maintaining ionic and fluid homeostasis. The first manifestation of almost all forms of sell injury.
Reversible injury. Gross Findings Pallor, increased turgor, and increased in weight.
Micro Findings 1. Cell swelling, cytoplasm contains coarse granules. 2. Nucleus not affected in light microscopy.. 3. Pigmented cast, hyaline cast. D. Others:
1. The first manifestation of cell injury and is reversible. 2. Increasing hydration of the cell due to alteration in ion transport at cell membrane. 3. Cause: infection, physico-chemical injury ( toxic ), ischemia
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