Lactic acidosis--emphasis on the carbon precursors and buffering of the acid load.

We have compared the capacity of major organs to produce lactic acid from endogenous sources relative to their ability to buffer that proton load. We deduced that the ultimate source for the rapid production of a very large amount of lactic acid must be hepatic and/or muscle glycogen or exogenous glucose, because the quantity of endogenous glucose is quite small and the rate of net protein catabolism is too slow. Of the organs examined, only the liver of fed persons can produce sufficient lactic acid to markedly overwhelm its own buffer capacity plus that of the ECF and other tissues. Moreover, it is important to realize that a fasted (low hepatic glycogen) subject who lacks the stimulus for muscle glycogenolysis can only develop a modest degree of acute lactic acidosis owing to a limited precursor availability; under these circumstances, hypoglycemia and/or localized tissue necrosis could be the major threats to that patient. We present two examples with more chronic lactic acidosis without hypoxia emphasizing that tissue catabolism may be necessary to support high rates of lactic acid production, and we suggest that a high plasma lactate concentration need not be present to observe a large turnover of this metabolite.