Abstract
The study of acid-base regulation may be seen as a continuation of research focused on physiological homeostasis, a concept first formulated early in the nineteenth century and spelled out by Bernard. Complexities of electrolyte-solution chemistry led Henderson and Hasselbalch to develop the empirical approximations embodied in the Henderson-Hasselbalch equation, which stills serves admirably for acid-base analysis. More recent attempts to reformulate the approach to acid-base and electrolyte analysis, such as the "strong ion diference " method, require much the same kinds of approximations, and offer no significant improvement. The development of electrolyte chemistry was also important to understanding protein behavior in physiological solutions. The idea that constant protein ionization was important in understanding acid-base homeostasis was formulated in the 1920s, formalized by Reeves as the "alphastat" model, and is here reexamined in light of recent physiological and biochemical data. A modified charge-maintenance, or "Z -stat, " model is suggested as a refinement. Current trends in acid-base physiology point to a concentration in the future on cellular and molecular aspects.
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