Renal Bicarbonate Excretion
- Because bicarbonate is not secreted by the tubule, the rate of renal bicarbonate excretion is ultimately determined by the balance between its rate of glomerular filtration and tubular resorption. Because the rate of glomerular filtration is maintained at a fairly constant level, specific regulation of bicarbonate excretion is principally achieved by modulation of its tubular resorption rate.
- The vast majority (85%) of the filtered bicarbonate is resorbed in the proximal tubule with 10% resorbed in the thick ascending loop of Henle and the remainder in the early distal tubules. The luminal tubular epithelial cell membrane does not display significant permeability to bicarbonate and thus a complex cyclical mechanism is employed to resorb bicarbonate, as discussed below.
- The cyclical process of tubular bicarbonate resorption can be thought of beginning with the secretion of free hydrogen ions into the tubular lumen. Here, cytosolic hydrogen ions are secreted via luminal NaH Antiporters which utilize the inward concentration gradient of for sodium to actuate secondary active transport of they hydrogen ions into the lumen. Once inside the lumen, hydrogen ions combine with tubular bicarbonate to form gaseous CO2 which can readily diffuse across the luminal membrane of epithelial cells. Consequently, luminal resorption of bicarbonate in reality occurs in the form of carbon dioxide gas. Once inside the tubuar epithelial cell the generated CO2 molecule is re-converted to H+ and HCO3- by carbonic anhydrase. The generated H+ is simply re-transported into the lumen whereas the bicarbonate molecule is transported past the basolateral membrane and into the ECF. Consequently, cyclical transport of hydrogen allows for unidirectional resorption of bicarbonate.
- The rate of bicarbonate resorption is linked to the pH of the extracellular fluid and thus blood pH. In contexts of acidosis when ECF pH is excessively low, nearly all of the filtered bicarbonate is resorbed thus preventing further drops in the ECF pH. In contrast, in contexts of alkalosis, when ECF pH is excessively high, there will be significant urinary loss of bicarbonate, thus helping lower the ECF pH. Interestingly, the regulatory link between ECF pH and renal bicarbonate excretion does not depend on neuroendocrine mechanisms but results from the dependence of bicarbonate excretion on cyclical hydrogen ion secretion. The rate of cyclical hydrogen ion secretion changes with the general availability of ECF hydrogen ions. Consequently, when ECF pH is low and thus there is excessive ECF hydrogen ions, cyclical hydrogen ion secretion is highly effective and nearly all of the bicarbonate is resorbed. In contrast, when ECF pH is high and thus there is a deficiency in ECF hydrogen ions, cyclical hydrogen ion secretion is low and thus much of the urinary bicarbonate cannot be resorbed, yielding urinary bicarbonate excretion.