Transport processes in urinary acidification

Abstract

The transport processes that underly the reabsorption of bicarbonate and the excretion of acid by the kidney have long been of interest to renal physiologists. Working models of the cellular mechanisms of transport were based on the transport functions of the sum of all segments of all nephrons, and remained useful for many years because of their simplicity. Several mechanisms for tubular acidification have been proposed on the basis of such studies. They involve either secretion of H + ions or reabsorption of buffer anions. The classical work of Pitts and Alexander [1] showed that reabsorption of filtered alkaline phosphate alone could not account for urinary acidification and provided one of the first indications of H + ion secretion by tubular cells. The origin of the secreted H + ions has been ascribed to CO 2 hydration in the tubular cell or to water splitting by a redox pump located at the luminal membrane with subsequent neutralization of the OH ­ ion in the cell by CO 2 [2, 3]. On the other hand, it was recognized that bicarbonate reabsorption could be due either to H + secretion or to reabsorption of HCO 3 ­ as such [2, 3]. It was also suggested that H + secretion would be difficult to distinguish from a sequence of events in which CO 2 diffuses into the lumen and becomes hydrated, and in which only the HCO ­ 3 species of the hydrated pair is reabsorbed [4, 5]. With the advent of new techniques for the study of individual tubule segments in vivo , it is now becoming feasible to explore the transport processes under conditions in which the individual forces and flows can be estimated and monitored. The ideal of controlling the electrochemical forces on both sides of the epithelial cell layer has been approached more closely in vitro , in sheet preparations of certain urinary bladders mounted in Lucite chambers. As a result of these developments, some of the described working hypotheses have been tested and many observations have been made that require a new framework of interpretation. What is the origin of the so-called disequilibrium pH which is present in the distal tubule under ordinary conditions and in the proximal tubule during carbonic anhydrase inhibition? Is it caused by a disequilibrium concentration of carbonic acid or an elevated PCO 2 of the tubular fluid? If CO 2 is formed in the tubular fluid from the reaction between secreted H + and filtered HCO 3 - , large quantities of CO 2 will be formed, the diffusion of which could well be delayed as a function of the permeability of the tubular cells. Another important question is the regulation of acidification in metabolic and respiratory acid-base disorders. What are the major factors controlling the net rate of acidification? Although it is impossible to examine the effects of ambient pH, PCO 2 and HCO 3 ­ separately, a number of interesting studies have been undertaken in the tubule and in the turtle bladder. It appears that the results are influenced primarily by differences in the passive permeability of these structures. The distal tubule, collecting duct and turtle bladder are considerably tighter epithelia than the proximal tubule. Among the subjects reviewed in this paper are the nature of the transported ion species in acidification, the question of whether or not H + secretion is coupled directly to the transport of Na + and other electrolytes, the behavior of active and passive components of transport during acidification against an electrochemical gradient and the factors that are rate determining for each of the transport rates. After an exploration of these questions in an epithelial membrane that is capable of urinary acidification in vitro , we shall examine the transport processes of acidification in kidney tubules by microelectrode and microperfusion techniques. Despite differences between these urinary structures, it is evident that some of the general principles that have been forthcoming from recent studies may ultimately simplify our understanding of the transport processes of urinary acidification.