Inner medullary lactate production and accumulation: a vasa recta model

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 ( P LAC) and glucose ( P GLU) permeabilities were varied over a range of plausible values. The model results suggest that P LAC 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 P GLU 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.