Mechanisms of renal tubular acidification

Both bicarbonate retrieval from the filtrate as well as the net excretion of acid depend upon hydrogen ion secretion by the tubular epithelium. Hydrogen ion secretion is mediated either by sodium-hydrogen exchange, an electroneutral and secondary active process, or by hydrogen ion secretion, a directly electrogenic and primary active process. Extrusion of hydrogen ions across the apical cell membrane is accompanied by electrogenic bicarbonate transfer across the basolateral cell membrane. Both luminal and peritubular pH exert a strong influence upon acidification by altering the gradient against which hydrogen transport or base exit occur. In the distal nephron, both hydrogen ion secretion and bicarbonate secretion may occur. These transport operations have been shown to be mediated by subgroups of intercalated cells in which hydrogen pumps and bicarbonate-chloride exchange processes are located either in the apical or basolateral cell membranes. Regulation of acidification involves several factors: the rate of luminal buffer delivery, sodium and chloride delivery, the luminal and peritubular pH and pCO2, the electrical potential, mineralocorticoids and the state of the potassium balance.