Cell Injury and Cell Death LO Describe the

Cell Injury and Cell Death LO  Describe the

Cell Injury and Cell Death LO Describe the pathogenesis of irreversible cell injury with ischemia Identify morphology of reversible cell injury Differentiate between reversible and

irreversible cell injury Overview Normal cell Injury Reversibly injured cell

Irreversibly Injured cell + Stress - Stress Adapted

Cell +Stres s Stress Apoptosi s Necrosi

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

Plasma membrane alteration Mitochondrial Changes Dilation of Endoplasmic reticulum Nuclear Alteration Fatty liver

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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