Cell can't do oxidative phosphorylation. Intracellular ADP increases, glycolysis increases greatly, lactic acid builds up and drops the cell pH, and proteins denature. This lets water, sodium and calcium into, and potassium and various marker enzymes (LDH, SGOT, or whatever, depending on the cell) out of, the cells. Water-and-lipid phases separate as layers ("myelin figures", dumb name). The cell and its rough-endoplasmic-reticulum may swell with water ("cloudy swelling"). This is still reversible. When hypoxia is bad enough, the calcium precipitates the phosphates in the mitochondria ("mitochondrial densities") which kills the cell (irreversible injury). If that doesn't happen, then sometimes the change in pH or whatever lets calcium that's tied-up by proteins loose in the cytoplasm, where it activates phospholipases. Lysosomes may burst, and freed fatty acids can act as detergents. A neuron is probably permanently damaged by zero-blood-flow in about 15 seconds, i.e., it's lost spines. A neuron is likely to die if deprived of oxygen for 3 minutes. Heart muscle cells last 30 minutes. Liver and kidney epithelial cells last maybe 2 hours. Glia may last a few hours. A leg can last maybe six hours. Histotoxic hypoxia: The cytochromes are inactivated, i.e., cyanide. Anemic hypoxia: Not enough hemoglobin to carry oxygen. Hypoxic hypoxia: Low arterial pO2. Ischemic hypoxia: Not enough blood to the area. Reperfusion injury: When blood is restored to an ischemic area, more calcium and oxygen (etc.) get into the cells and hurts them worse.
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The causes of hypoxia
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Ischemia ("ischemic hypoxia"; "stagnant hypoxia"): Loss of arterial blood flow (literally, "holding back the blood")
Local causes
-- Occlusion of the arteries that bring in fresh blood
-- Occlusion of the veins which allow blood to leave, so that fresh blood can flow in
-- Shunting of arterial blood elsewhere ("steal syndromes"; "Robin Hood" syndromes)
Systemic causes
-- Failure of the heart to pump enough blood
Hypoxemia: Too little oxygen in the blood
Oxygen problems ("hypoxic hypoxia")
-- Too little oxygen in the air
-- Failure to properly ventilate the lungs
-- Failure of the lungs to properly oxygenate the blood
-- Failure of the heart to pump enough blood through the lungs
-- Tremendously increased dead space (i.e., pulmonary thromboembolus)
Hemoglobin problems ("anemic hypoxia")
-- Inadequate circulating red cell mass ("anemia")
-- Inability of hemoglobin to carry the oxygen (carbon monoxide poisoning, methemoglobinemia)
-- "High affinity" hemoglobins that will not give up their oxygen to the tissues
Failure of the cytochromes ("histotoxic hypoxia")
Cyanide poisoning
Rotenone poisoning
Dinitrophenol poisoning
Other curious poisons
I wish I had time to review blood gases here....
Note: Copyrights: "The Pathology Guy" - Ed Friedlander MD. Reproduced with permission.
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