Last word on point:counterpoint: lactate is/is not the only physicochemical contributor to the acidosis of exercise.

TO THE EDITOR: This debate (1, 4) focused on whether the increase in plasma [lactate] was the sole contributor to the acidosis associated with exercise at sufficiently high intensities to generate increased plasma [lactate ]. It remains puzzling that many physiologists continue to compare plasma “acidbase” status (pH, PCO2, [HCO3 ]) with whole blood (not plasma) measures of [lactate ], thus equating the decrease in plasma [HCO3 ] with the increase in whole blood [lactate ]. This crosscompartment comparison does not contribute to describing or understanding the origins of the acidosis within the plasma compartment, per se. It is also incapable of providing an accounting of each of the independent variables that determine acid-base status within any physiological system, of which [lactate ] is only one. Several respondents mistakenly placed the debate within the context of the intracellular environment of skeletal muscle, in contrast to the extracellular environment as layed out by Böning and Maassen (1). These comments, while not supportive of the physicochemical approach, also do not refute it and rather point to limitations with current ways of thought and understanding. The parsing of proton production/appearance within biochemical reactions is a mathematics exercise whose purpose is to provide charge balance and to generate biochemical equations consistent with measured changes in pH, or [H ], nothing more and nothing less. It is unfortunate that many physiologists prefer to ignore the physical and chemical properties of water that have been well understood for nearly a century (2, 3). Acid-base physiology is founded on these principles, and they should be embraced, understood, and used. Because ALL strong and weak ions, as well as carbon dioxide, affect the dissociation of water, the effect of a change in any one of the strong or weak ions or of PCO2 will be manifest as changes in [H ] and [OH ]. The concentrations of all of the major ions and CO2 can be measured with reasonably high accuracy and precision, and changes in their concentrations are well described in the literature. Why should we not use our knowledge of these changes and of their independent effects on water to help us to understand acid-base balance? It is also apparent that many view the physiochemical approach as an attempt to be able to predict the dependent variables pH and [HCO3 ] from a large number of measures of independent variables, each of which contributes error to a “predicted” acid-base status. This is a misrepresentation of the physicochemical approach. In contrast to this notion, no one that uses the physicochemical approach to acid-base balance uses the equations developed by Stewart (5) to predict pH or acid-base status. Rather, the physicochemical approach is used as an objective, quantitative, and powerful tool that allows us to determine the contributions to any acid-base disturbance within a physiological compartment, regardless of how complex or varied in origins.