Whole Body Buffers in the Regulation of Acid-Base Equilibrium

Twenty-five years ago John P. Peters with Donald D. Van Slyke wrote one of the most precise, lucid, and comprehensive accounts of acid-base equilibrium that has ever appeared in scientific literature, namely, Chapter 18 in Volume I, Interpretations, of Quantitative clinical chemistry." This account rested on the basic experimental work of Van Slyke and other investigators and especially on the classic work of Lawrence J. Henderson'"" who in 1908 first delineated in a unified manner the physicochemical and physiological mechanisms for the maintenance of neutrality of the fluids of the body. In the quarter of a century since the appearance of Quantitative clinical chemnistry, although much research activity has taken place in this field, no major revision has had to be made of the fundamental concepts as set forth in that work. Nevertheless, the investigative efforts of this subsequent period have greatly enhanced our understanding of both the physicochemical and the physiological mechanisms involved. This is true especially as regards (i) the linked transfers of ions which participate in the functioning of buffer systems, (ii) the r6le of the kidney in acid-base regulation, and (iii) the relationship of disease processes to disturbances of acid-base equilibrium. The first of these three categories is the subject of this paper; the other two are treated in part in some of the following contributions. The first defense of body fluid neutrality is the physicochemical mechanism of the buffer systems. The buffer systems of the body consist of weak acids and their salts which react with strongly dissociated acids to form a neutral salt and a slightly dissociated weak acid, thus minimizing changes in hydrogen ion concentration. These systems are principally bicarbonates, phosphates, and proteins, and function according to circumstances as either donors or acceptors of hydrogen ions or protons. Once these buffer systems had been identified by Henderson, the attention of investigators was focussed primarily on the buffering activity of the blood.8" 53 "' This is easily understandable since blood is such a readily accessible portion of the