The Mechanism of Bicarbonate Reabsorption in the Proximal and Distal Tubules of the Kidney*

Abstract

Considerable evidence (1-6) has been adduced to support the hypothesis that the reabsorption of filtered HCO3-by the kidney is mediated by a single mechanism, operative in both the proximal and distal portions of the nephron, which involves the secretion of cellular He in exchange for luminal Na+. The secreted Ho reacts with filtered HC03-to form H2CO3, which then decomposes to C02 and H20.Difficulties arise, however, when the details of the process are examined. In the steady state, the rate at which the H2CO3 is removed from the luminal fluid must equal the rate at which H+ is secreted. Walser and Mudge (7) have estimated that for the uncatalyzed dehydration of H2C03 to account for the observed rates of HC03-reabsorption, the steady-state concentration of H2C03 in luminal fluid must be at least tenfold greater than the concentration that would exist were H2C03 in equilibrium with the C02 tension of luminal fluid and plasma. As a result of the excess H2C03, the steady-state pH would be approximately 1 pH U lower than would be predicted from the luminal concentration of HC03-and the C02 tension of plasma, assuming complete equilibration of luminal H2C03 with plasma C02. A marked disequilibrium pH ' would exist.Two lines of evidence have been advanced to support the presence of a disequilibrium pH in the proximal tubule. Rector and Carter (8) perfused single proximal tubules with NaHCO3 * Submitted for publication July 27, 1964; accepted October 29, 1964. Supported in part by a grant from the American Heart Association and in part by grants 5 TI AM-5028 and 5 TI HE-5469 from the National Institutes of Health.'The difference between the actual pH, under conditions where C02 and H2CO0 are not in equilibrium, and the calculated equilibrium pH will be termed "disequilibrium" pH. and estimated the steady-state intraluminal pH from the change in color of various acid-base indicators. The pH was found to be about 1.5 U lower than the predicted equilibrium pH. However, since the color change could result from loss of dyes by either reabsorption or binding to cell proteins, the validity of these results may be questioned. Bank and Aynedjian (9) measured intratubular pH by aspirating tubular fluid into quinhydrone microelectrodes and comparing the readings while the electrode was still in the tubular lumen with the values obtained when the fluid was removed from the tubule and permitted to reach equilibrium. With this technique, they found the intratubular pH to be 2.0 to 2.5 pH U below the equilibrium pH. These results, however, are open to the serious objection that a disequilibrium pH of this magnitude would require the generation of H2CO3 at a rate 10 to 50 times greater than is theoretically possible, as judged from the rate of HC03-reabsorption.The presence of a disequilibrium pH, however, is not a necessary consequence of the hypothesis that H+ secretion mediates HC03-reabsorption. An equilibrium pH could obtain if H2CO3 were rapidly removed from the tubular urine by either of two mechanisms: 1) nonionic diffusion...

Role of tubular secretion and carbonic anhydrase in vertebrate renal sulfate excretion

“…In mammals, H ϩ secretion indirectly drives proximal tubular HCO 3 Ϫ reabsorption, and 40% of tubular HCO 3 Ϫ reabsorption is CA dependent (67). Proximal tubular CA is also required for a fraction (50%) of tubular SO 4 2Ϫ reabsorption in chickens (22).…”

Hydrogen ion secretion by the collecting duct as a determinant of the urine to blood PCO2 gradient in alkaline urine.

“…The disequilibrium pH method (pHdq = pHi, -pHeq) has been used by several investigators to demonstrate delayed dehydration, and thus H+ secretion in other nephron segments (18,19). Recently, we have used newly developed microelectrode techniques to measure Pco2, in situ pH (pHij), and equilibrium pH (pHeq).…”

Factors modifying renal tubular bicarbonate reabsorption in the dog

“…In the present work, by contrast, the dogs' plasma HC03-was raised above 24 mequiv/l., and a drop of 'proximal' pH and HC03-concentration below the plasma level was only seen if water reabsorption from the tubules was restricted by mannitol. Rector, Carter & Seldin (1965) acutely induced a state of metabolic alkalosis by i.v. infusion of NaHCO3 in rats used for micropuncture, and found in most proximal fluid samples a pH and HC03-concentration higher than in the plasma.…”