Moving More Closely to Acid-Base Relationships in the Body as a Whole

MOVING MORE CLOSELY TO ACID-BASE RELATIONSHIPS IN THE BODY AS A WHOLE JAMES L. GAMBLE, JR. * This article reviews two topics in acid-base physiology: the first a "metabolic " relationship of large quantitative importance, but of little general recognition; the second, a "respiratory" relationship, widely recognized, but easily misconstrued. If we can bring to die fore die importance of the first, and improve interpretation of the second, we can do much to overcome roadblocks to understanding in this field of medicine. The Metabolic Event In metabolic acidosis, buffering in tissues other than blood is not controlled by changes in extracellular pH. THE UNEXPECTED RELATIONSHIP For the bettert part of tiiis century, introduction into acid-base physiology has included detailed presentation ofthe relationship in isolated blood, and in tiiis system, predominant weighting is given to the importance of change in pH. The large contribution of buffering by hemoglobin occurs as a strict function of change in pH, and most of die teaching diagrams give pH the position of primacy on die abscissa. But now, as we turn from whole blood to whole body, we encounter a different story. Buffering in metabolic acidosis in tissues other than blood appears not to depend on change in pH. Such a concept of nondependency must appear almost as a contradiction in terms; and adding to die difficulty, we are unable at this time to decipher the mechanism of tiiis buffering. There is a bit of irony here. Academic confidence and allegiance to the blood relationships stems from our uninhibited admiration of the elegant and comprehensive study which Van Slyke, Wu, and McLean were able to carry out in China and to publish in 1923 [I]. However, six years earlier, *Dept. ofPhysiology,Johns Hopkins University School ofMedicine, 715 N. Wolfe St., Baltimore , MD 21205.© 1996 by The University of Chicago. All rights reserved. 0031-5982/96/390_O962$01.00 Perspectives in Biology and Medicine, 39, 4 ¦ Summer 1996 | 593 and on this occasion working with the whole body rather than with isolated blood, Palmer and Van Slyke identified change in plasma bicarbonate rather than change in pH as the key measure of abnormality in metabolic acidosis in the whole body [2]. For the clinician, decrease in plasma bicarbonate has always provided a reliable measure of disorder in metabolic acidosis, and as shown by the Van Slyke report, utilization of this buffer, which is wholly predominate in the extracellular fluids, accurately reflects die change in total body water. It follows that die external change must also measure the internal: that the abnormal accumulation of acid in the large intracellular "tissue" compartment can be deduced on the basis of the decrease in the extracellular concentration of bicarbonate. What then of the relation of change in pH to the intracellular (nonblood ) buffering? Here we encounter the unexpected. We know that die intracellular fluids contain an abundance of proteins and organic phosphate compounds as potential pH-reactive buffering agents, and yet neutralization of acid in the intracellular fluids in metabolic acidosis is surprisingly independent of change in pH, or at least change in external, extracellular pH. The evidence for this anomalous relationship has been presented previously [3, 4] and is reviewed briefly here. It is useful to introduce this problem with reference to reported experimental findings and to results of student laboratory experiments [3, 5] . After an infusion into an animal of an equivalence of HCl sufficient to react witii all of the extracellular bicarbonate (i.e., 6 meq/kg), only about half of the acid will, in fact, be neutralized in the extracellular compartment —a portion by blood buffers, but chiefly by the ECF bicarbonate. The ECF bicarbonate will fall to close to 50 percent of the initial value (i.e., from 24 to 12 meq/liter). The remaining halfof the infused acid will enter body tissues (perhaps muscle or bone) to become neutralized by intracellular buffering systems. Now for the anomaly. This intracellular, non-blood, or "tissue" buffering does not appear to be closely related to, or controlled by, changes in extracellularpH. To illustrate: if, as a second part of the experiment, the animal should be hyperventilated to lower the Pco2 sufficiently to return the pH to...