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Transport efficiency and workload distribution in a mathematical model of the thick ascending limb.

Authors
  • Nieves-González, Aniel
  • Clausen, Chris
  • Layton, Anita T
  • Layton, Harold E
  • Moore, Leon C
Type
Published Article
Journal
American journal of physiology. Renal physiology
Publication Date
Mar 15, 2013
Volume
304
Issue
6
Identifiers
DOI: 10.1152/ajprenal.00101.2012
PMID: 23097466
Source
Medline
License
Unknown

Abstract

The thick ascending limb (TAL) is a major NaCl reabsorbing site in the nephron. Efficient reabsorption along that segment is thought to be a consequence of the establishment of a strong transepithelial potential that drives paracellular Na(+) uptake. We used a multicell mathematical model of the TAL to estimate the efficiency of Na(+) transport along the TAL and to examine factors that determine transport efficiency, given the condition that TAL outflow must be adequately dilute. The TAL model consists of a series of epithelial cell models that represent all major solutes and transport pathways. Model equations describe luminal flows, based on mass conservation and electroneutrality constraints. Empirical descriptions of cell volume regulation (CVR) and pH control were implemented, together with the tubuloglomerular feedback (TGF) system. Transport efficiency was calculated as the ratio of total net Na(+) transport (i.e., paracellular and transcellular transport) to transcellular Na(+) transport. Model predictions suggest that 1) the transepithelial Na(+) concentration gradient is a major determinant of transport efficiency; 2) CVR in individual cells influences the distribution of net Na(+) transport along the TAL; 3) CVR responses in conjunction with TGF maintain luminal Na(+) concentration well above static head levels in the cortical TAL, thereby preventing large decreases in transport efficiency; and 4) under the condition that the distribution of Na(+) transport along the TAL is quasi-uniform, the tubular fluid axial Cl(-) concentration gradient near the macula densa is sufficiently steep to yield a TGF gain consistent with experimental data.

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