Evidence against bicarbonate reabsorption in the ascending limb, particularly as disclosed by free water clearance studies

D. W. Seldin, J. M. Rosin, F. C. Rector

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3 Scopus citations


Bicarbonate reabsorption in the thick ascending limb of Henle's loop was examined by studies of free water clearance (C(H2O)) and free water reabsorption (T(c H2O)). During maximal water diuresis in the dog, C(H2O)/GFR was taken as an index of sodium reabsorption in, and urine flow (V/GFR) as an index of delivery of filtrate to, this segment. Three different procedures, infusion of hypotonic sodium bicarbonate, infusion of a nonreabsorbable solute (hypotonic mannitol) and administration of an inhibitor of bicarbonate reabsorption (acetazolamide), all increased C(H2O)/GFR per unit V/GFR to a similar extent, but less than that achieved with hypotonic saline infusion. This suggests that sodium bicarbonate is not reabsorbed in the ascending limb. Rather, it is the sodium chloride, swept out of the proximal tubule by osmotic diuresis due to nonreabsorbed mannitol or sodium bicarbonate, that is reabsorbed in the ascending limb thereby increasing C(H2O), whereas the nonreabsorption of mannitol and sodium bicarbonate results in a depressed C(H2O) per unit V when compared with hypotonic saline. V/GFR is not a satisfactory index of delivery to the ascending limb during osmotic diuresis, since it includes water obligated by nonreabsorbable solutes. When a better index of delivery, the sum of the clearances of chloride (C(Cl)) and free water (C(H2O)) is used, hypotonic bicarbonate infusion, hypotonic mannitol infusion and acetazolamide administration increase C(H2O)/GFR per unit delivery to the same extent as does hypotonic saline infusion. Studies in dogs and rats on T(c H2O) also indicate that sodium bicarbonate is an impermeant solute in the ascending limb. Osmotic diuresis due to sodium bicarbonate diuresis, produced either by inhibition of sodium bicarbonate reabsorption (acetazolamide, L lysine monohydrochloride) or infusion of sodium bicarbonate, or mannitol diuresis both produced marked chloruresis and increased T(c H2O) to the same extent as did hypertonic saline infusion. If chloride excretion was almost eliminated by hemodialysis against a chloride free dialysate (dogs) or prolonged feeding of a salt free diet (rats), T(c H2O) formation was unimpaired if hypertonic saline was infused but virtually obliterated during mannitol or sodium bicarbonate diuresis. Sodium reabsorption in the ascending limb, therefore, appears to be dependent upon chloride as the accompanying anion. At any given rate of bicarbonate excretion, more chloride is delivered out of the proximal tubule (as estimated from C(Cl) + C(H2O)) with hypotonic sodium bicarbonate infusion than with acetazolamide administration. This suggests that magnitude of the chloruresis accompanying bicarbonate diuresis depends, not only on osmotic diuresis due to nonreabsorbed sodium bicarbonate, but also on the extent to which concomitant changes in effective extracellular volume influence overall sodium chloride reabsorption.

Original languageEnglish (US)
Pages (from-to)337-347
Number of pages11
JournalYale Journal of Biology and Medicine
Issue number4
StatePublished - Dec 1 1975

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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