Reduced tissue perfusion, or perfusion that is inadequate to meet the metabolic demands of the tissues (such as exercising muscle), results in an inadequate supply of oxygen and a change from oxidative metabolism (the end products of which are CO2 and H2O) to anaerobic metabolism. The end product of anaerobic glycolysis is lactic acid, which is normally metabolized (to CO2 and H2O) by the liver or used in the synthesis of glucose (gluconeogenesis). The normal plasma [lactate] is less than 1mmoll~1 but may increase 10-fold in extreme exercise. When the ability to metabolize lactate is exceeded, either by increased production, or reduced delivery to the liver (in, for example, circulatory shock) or in the presence of impaired liver function, accumulation results in metabolic acidosis. Thus, lactic acidosis may occur in a variety of conditions, including circulatory shock, severe diabetic ketoacidosis, as a consequence of drugs (for example, the oral hypo-glycemic agent metformin that inhibits gluconeogen-esis and lactate transport), chronic liver disease, and poisoning (including ethanol and methanol).
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