Permeability Criteria for Effective Function of Passive Countercurrent
Multiplier.
Layton, H. E., Mark A. Knepper, and Chung-Lin Chou.
Department of Mathematics, Duke University, Durham, North Carolina 27708-
0320; Laboratory of Kidney and Electrolyte Metabolism, National Heart, Lung,
and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-
1598
APStracts 2:0157F, 1995.
The urine concentrating effect of the mammalian renal inner medulla has been
attributed to countercurrent multiplication of a transepithelial osmotic
difference arising from passive absorption of NaCl from thin ascending limbs
of long loops of Henle. This study assesses, both mathematically and
experimentally, whether the permeability criteria for effective function of
this passive hypothesis are consistent with transport properties measured in
long loops of Henle of chinchilla. Mathematical simulations incorporating
loop-of-Henle transepithelial permeabilities idealized for the passive
hypothesis generated a steep inner medullary osmotic gradient, confirming the
fundamental feasibility of the passive hypothesis. However, when
permeabilities measured in chinchilla were used, no inner medullary gradient
was generated. A key parameter in the apparent failure of the passive
hypothesis is the long-loop descending limb (LDL) urea permeability, which
must be small to prevent significant transepithelial urea flux into inner
medullary LDL. Consequently, experiments in isolated perfused thin LDL were
conducted to determine whether the urea permeability may be lower under
conditions more nearly resembling those in the inner medulla. LDL segments
were dissected from 30-70% of the distance along the inner medullary axis of
the chinchilla kidney. The factors tested where NaCl concentration (125-400 mM
in perfusate and bath), urea concentration (5-500 mM in perfusate and bath),
calcium concentration (2-8 mM in perfusate and bath), and protamine
concentration (300 micrograms per ml in perfusate). None of these factors
significantly altered the measured urea permeability, which exceeded 20 X 10{-
5} cm/s for all conditions. Simulation results show that this moderately high
urea permeability in LDL is an order of magnitude too high for effective
operation of the passive countercurrent multiplier.
Received 2 January 1994; accepted in final form 15 May 1995.
APS Manuscript Number F31-5.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 September 1995.