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Institut National de la Santé et de la Recherche Médicale Unité 467, Necker Faculty of Medicine, F-75015 Paris, France
Since anaerobic glycolysis
yields two lactates for each glucose consumed and since it is reported
to be a major source of ATP for inner medullary (IM) cell maintenance,
it is a likely source of "external" IM osmoles. It has long been
known that such an osmole source could theoretically contribute to the
"single-effect" of the urine concentrating mechanism, but there was
previously no suggestion of a plausible source. I used numerical
simulation to estimate axial gradients of lactate and glucose that
might be accumulated by countercurrent recycling in IM vasa recta
(IMVR). Based on measurements in other tissues, anaerobic glycolysis
(assumed to be independent of diuretic state) was estimated to consume ~20% of the glucose delivered to the IM. IM tissue mass and axial distribution of loops and vasa recta were according to reported values
for rat and other rodents. Lactate (PLAC) and
glucose (PGLU) permeabilities were varied over a
range of plausible values. The model results suggest that
PLAC of 100 × 10
5 cm/s
(similar to measured permeabilities for other small solutes) is
sufficiently high to ensure efficient lactate recycling. By contrast,
it was necessary in the model to reduce PGLU to
a small fraction of this value (1/25th) to avoid papillary glucose
depletion by countercurrent shunting. The results predict that IM
lactate production could suffice to build a significant steady-state
axial lactate gradient in the IM interstitium. Other modeling studies (Jen JF and Stephenson JL. Bull Math Biol 56: 491-514,
1994; and Thomas SR and Wexler AS. Am J Physiol Renal Fluid
Electrolyte Physiol 269: F159-F171, 1995) have shown that
20-100 mosmol/kgH2O of unspecified external,
interstitial, osmolytes could greatly improve IM concentrating ability.
The present study gives several plausible scenarios consistent with
accumulation of metabolically produced lactate osmoles, although only
to the lower end of this range. For example, if 20% of entering
glucose is consumed, the model predicts that papillary lactate would
attain about 15 mM assuming vasa recta outflow is increased 30% by
fluid absorbed from the nephrons and collecting ducts and that this
lactate gradient would double if IM blood flow were reduced by
one-half, as may occur in antidiuresis. Several experimental tests of
the hypothesis are indicated.
glucose; descending vasa recta; blood flow; urine concentrating mechanism; anaerobic glycolysis
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