The Collecting Duct Can Secrete Protons and Generate Acidic Urine

In contrast to the proximal tubule, which is a high-capacity, low-gradient system of H⁺ secretion, the collecting duct has a lower capacity for H⁴ secretion but can generate a steep H’ concentration gradient.

Acid secretion in most of the collecting duct system is a function of a specialized group of cells, the intercalated cells (see Figure 42-12). Intercalated cells are present in the con­necting segment, cortical collecting duct, and medullary col­lecting duct. Intercalated cells contain abundant cytoplasmic carbonic anhydrase, which catalyzes the formation of intracellular H* and HCO₅ from intracellular H₂O and CO₂. H⁴ is secreted into the tubule fluid across the apical plasma membrane of intercalated cells by the electrogenic proton pump, H⁺-ATPase, or by the electrically neutral H ^,,K^t-ATPase pump. HCO₃^- is transported across the basolateral plasma membrane to the blood side of the cell by a C17HCO₃^ exchanger similar to the C17HCO₃ exchanger in red blood cell membranes (Figure 44-3). The acid-secreting intercalated cells alter the rate of H' secretion by altering the numbers of proton pumps in the apical plasma membrane. The insertion or removal of proton pump-containing membrane vesicles causes structural changes that reflect the physiological response (Figure 44-4). Furthermore, in some species the C17HCO₃^- exchanger is translocated from intracellular compart­ments to the basolateral plasma membrane in acidosis. In this way, the acid-secreting intercalated cells respond to changes in the acid load and alter acid secretion accordingly.

The activity of the H⁺JC-ATPase pump is enhanced by hypokalemia (low serum K* level), and thus the contribution of the H,IC-ATPase pump to renal acidification is augmented during potassium restriction. Mineralocorticoid hormones, such as aldosterone, also enhance acidification in the collecting duct. It has been postulated that this increase in H⁴ secre­tion results from an increase in the numbers of proton transporters—either H⁺-ATPase or H∖K^,-ATPase, or both—in the apical plasma membrane of the acid-secreting inter­calated cells, which is similar to the adaptive response seen in acidosis.

The terminal segments of the inner medullary collecting duct, where there are few or no intercalated cells, also can secrete acid. An Na⁺∕H⁺ exchanger, an electrogenic proton pump, a H⁺,K⁺-ATPase pump, and substitution of NH/ for K⁴ on the basolateral Na',Kⁱ-ATPase all may participate in acid secretion in this region, but the relative importance of these mechanisms is currently unclear.