The small amount of HCO3- that is not reabsorbed by the proximal tubule and loop of Henle is reabsorbed by the distal tubule and collecting duct. Fig. 37.4 illustrates how intercalated cells in these segments transport H+/HCO3-. There are two types of intercalated cells. The A- or α-intercalated cell secretes H+ and reabsorbs HCO3-. Within this cell, CO2 is hydrated to produce H+ and HCO3-, catalyzed by carbonic anhydrase (CA-II). H+ is secreted into the tubular fluid through an apical membrane H+-ATPase (V-type) and an H+-K+-ATPase similar to those in the stomach and colon (HKα1 and HKα2), which also allows for H+ secretion and K+ reabsorption. HCO3- exits the cell through the basolateral membrane in exchange for Cl- via a Cl-/HCO3- antiporter (AE-1) and enters the peritubular capillary blood. The B- or β-intercalated cells secrete HCO3- into the tubular fluid. In these cells, the H+-ATPase (V-type) is located in the basolateral membrane, and the Cl-/HCO3- antiporter is located in the apical membrane, known as pendrin. The HCO3--secreting intercalated cell becomes more active during metabolic alkalosis to excrete excess HCO3-. However, under most conditions, H+ secretion predominates in these segments. The apical membrane of collecting duct cells is not very permeable to H+ , resulting in a highly acidic tubular fluid (pH = 4.0–4.5). In comparison, the proximal tubule has higher permeability to H+ and HCO3-, resulting in a lower tubular fluid pH (pH = 6.5). The ability of the collecting duct to lower the pH of the tubular fluid is crucial for excreting urinary titratable acids and NH4+. The secretion of H+ and reabsorption of filtered HCO3- in the nephron is regulated by various factors, with changes in systemic acid-base balance being the primary factor. Acidosis stimulates H+ secretion, while alkalosis reduces it.
The distal tubule and collecting duct reabsorb the small amount of HCO3 − that escapes reabsorption by the proximal tubule and loop of Henle.
Fig. 37.4 shows the cellular mechanism of H+/HCO3 − transport by the intercalated cells located within these segments (see also
One type of intercalated cell secretes H+ (reabsorbs HCO3 −) and is called the A-or α-intercalated cell. Within this cell, H+ and HCO3 − are produced by hydration of CO2; this reaction is catalyzed by carbonic anhydrase (CA-II). H+ is secreted into the tubular fluid via two mechanisms. The first involves an apical membrane H+-ATPase (V-type). The second couples secretion of H+ with reabsorption of via an H+-K+-ATPase similar to those found in the stomach and colon (HKα1 and HKα2). HCO3 − exits the cell across the basolateral membrane in exchange for Cl− (via a Cl−/HCO3 − antiporter, AE-1) and enters the peritubular capillary blood.
A second population of intercalated cells secretes HCO3 − rather than H+ into the tubular fluid (also called B-or dHere and in the remainder of the chapter we focus on the function of intercalated cells. The early portion of the distal tubule, which does not contain intercalated cells, also reabsorbs HCO3 − . The cellular mechanism appears to involve an apical membrane Na+/H+ antiporter (NHE2) and a basolateral Cl−/HCO3 − antiporter (AE2).
β-intercalated cells).
In these cells the H+-ATPase (V-type) is located in the basolateral membrane and the Cl−/HCO3 − antiporter is located in the apical membrane (see
Fig. 37.4).
However, the apical membrane Cl−/HCO3 − antiporter is different from the one found in the basolateral membrane of the H+-secreting intercalated cells and has been identified as pendrin. The activity of the HCO3 −-secreting intercalated cell is increased during metabolic alkalosis, when the kidneys must excrete excess HCO3 − . However, under most conditions (e.g., ingestion of a meat-containing diet) H+ secretion predominates in these segments.
The apical membrane of collecting duct cells is not very permeable to H+ , and thus the pH of tubular fluid can become quite acidic. Indeed, the most acidic tubular fluid along the nephron (pH = 4.0–4.5) is produced there. In comparison the permeability of the proximal tubule to H+ and HCO3 − is much higher, and the tubular fluid pH falls to only 6.5 in this segment. As explained later the ability of the collecting duct to lower the pH of the tubular fluid is critically important for excretion of urinary titratable acids and NH4 + .
Regulation of H+ Secretion
A number of factors influence secretion of H+ and thus reabsorption of filtered HCO3 − by the cells of the nephron. From a physiological perspective the primary factor that regulates H+ secretion by the nephron is a change in systemic acid-base balance. Thus acidosis stimulates RNAE, whereas RNAE is reduced during alkalosis.