The kidneys respond to changes in acid-base balance through both immediate and longer-term mechanisms. In the case of metabolic acidosis, H+ secretion is stimulated by various means, depending on the specific segment of the nephron. Firstly, acidosis leads to a decrease in intracellular pH, creating a more favorable gradient for H+ secretion across the apical membrane. Secondly, the decrease in pH can cause changes in the kinetics of transport proteins. Lastly, transporters may be moved from intracellular vesicles to the membrane. In cases of long-term acidosis, the abundance of transporters increases through increased transcription of relevant genes or translation of transporter mRNA.

There is a type of intercalated cell that exhibits characteristics of both H+-secreting and HCO3 −-secreting intercalated cells. The precise role of this cell type in acid-base transport is not fully understood. In addition to acid-base transport, intercalated cells (B type) are now known to be involved in NaCl reabsorption. The reabsorption of NaCl occurs through the combined action of an apical membrane Cl−/HCO3 − antiporter (pendrin) and an apical membrane Na+/HCO3 −/2Cl− antiporter (NDCBE). Thiazide diuretics inhibit this mechanism of NaCl reabsorption.

Figure 37.4 illustrates the cellular mechanisms involved in the reabsorption and secretion of HCO3− by intercalated cells in the distal tubule and collecting duct. Only the primary H+ and HCO3− transporters are depicted. ATP represents adenosine triphosphate, and CA stands for carbonic anhydrase.

Figure 37.5 provides examples of cellular H+ and HCO3− sensors. The abbreviations ATP, cAMP, GPCR, IRR, Pyk2, and sAC stand for adenosine triphosphate, cyclic adenosine monophosphate, G protein–coupled receptor, insulin receptor–related receptor, nonreceptor tyrosine kinase, and soluble adenylyl cyclase, respectively. This information has been adapted from the work of Levin et al. (2015) in the Annual Review of Physiology (Vol. 77, p. 347).
The response of the kidneys to changes in acid-base balance includes both immediate changes in the activity and/or number of transporters in the membrane and longer-term changes in the synthesis of transporters. For example, with metabolic acidosis, H+ secretion is stimulated by multiple mechanisms, depending on the particular nephron segment. First, the decrease in intracellular pH that occurs with acidosis will create a more favorable cell-to–tubular fluid H+ gradient and thereby make secretion of H+ across the apical membrane more energetically favorable. Second, the decrease in pH may lead to allosteric changes in transport proteins, thereby altering their kinetics. Lastly, transporters may be shuttled to the membrane from intracellular vesicles. With long-term acidosis the abundance of transporters increases, either by increased transcription of appropriate transporter genes or by increased translation of transporter mRNA.
eA third group of intercalated cells shares features of both H+-secreting and HCO3 −-secreting intercalated cells. The precise function of this cell type in acid-base transport is not fully understood. fTraditionally it was believed that intercalated cells were only involved in acid-base transport. There is now good evidence that NaCl reabsorption is also carried out by intercalated cells (B type). Reabsorption of NaCl occurs by the tandem operation of an apical membrane Cl−/HCO3 − anti-porter (pendrin) and an apical membrane Na+/HCO3 −/2Cl− antiporter (NDCBE). This mechanism of NaCl reabsorption is inhibited by thiazide diuretics.
•Fig. 37.4 CellularmechanismsforreabsorptionandsecretionofHCO3− byintercalatedcellsofthedistaltubuleandcollectingduct.OnlytheprimaryH+ andHCO3− transportersareshown.ATP,adenosinetriphosphate;CA,carbonicanhydrase.
•Fig. 37.5 ExamplesofcellularH+ andHCO3− sensors.ATP,adenosinetriphosphate;cAMP,cyclicadenosinemonophosphate;GPCR,Gprotein–coupledreceptor;IRR,insulinreceptor–relatedreceptor;Pyk2,nonreceptortyrosinekinase;sAC,solubleadenylylcyclase.(Adaptedfrom:LevinLR,BuckJ.Annu Rev Physiol 2015;77:347.)