1. The effects of varying Pco2 on lactate uptake and intracellular pH (pHl) were studied in the isolated rat liver perfused with differing concentrations of lactate.

2. In general, pHl and lactate uptake are inversely related to Pco2, and pHl and lactate uptake are directly related to each other, but the quantitative aspects and significance of these relationships vary with the availability of lactate. A model of hepatic lactate metabolism is proposed which may account for the quantitative variation.

3. The metabolism of lactate within the hepatocyte exerts a destabilizing effect on hepatocyte cell pH, in contrast to the buffering effect seen in predominantly glycolytic tissues.

4. An attempt is made to relate the findings to the disturbances of lactate metabolism in clinical respiratory failure.

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