Basic mechanisms of urinary acidification.

This article has examined the process of urinary acidification from the perspective of events occurring at the cellular and single nephron level. Accordingly, the reabsorption of filtered HCO3- and the titration of urine buffers can be ascribed to the fundamental process of H+ secretion. The precise mechanism of H+ secretion by the tubule cells, the rate by which this occurs, and the factors regulating transport differ between nephron segments. Despite these differences, the cellular process of urinary acidification can be viewed as the extrusion of H+ against an electrochemical gradient across the luminal cell membrane and the movement of an HCO3- equivalent across the basolateral cell membrane. In the proximal tubule (convoluted and straight portions) approximately 90 per cent of the filtered load of HCO3- is reabsorbed. This occurs without the development of large lumen-to-blood pH gradients. The secretion of H+ across the luminal membrane occurs primarily via an electrically neutral Na-H exchange mechanism. Since it is the lumen-to-cell Na+ gradient which provides the energy, the secretion of H+ is a "secondary active" process dependent on the function of the Na-K-ATPase located in the basolateral cell membrane. During the elaboration of an acid urine, the distal nephron (distal convoluted tubule and collecting duct) reabsorbs that portion of the filtered HCO3- escaping proximal reabsorption, titrates luminal buffers, and lowers urine pH. The secretion of H+ occurs by a "primary active" mechanism, which involves the extrusion of H+ across the luminal cell membrane by an electrogenic H+ pump driven by the hydrolysis of ATP. The rate at which H+ is secreted depends on the electrochemical gradient for H+ across the luminal membrane. Thus, changes in both lumen pH and potential will effect H+ secretion, with low lumen pH inhibiting transport and large lumen-negative potentials stimulating transport. In some animals, depending on their homeostatic needs, secretion of HCO3- by the distal nephron can also occur. This process is localized to the distal convoluted tubule and the cortical collecting duct and appears to represent a transport system distinct from that responsible for H+ secretion.