title: Urine-concentrating mechanism in the inner medulla: function of the thin limbs of the loops of Henle.
abstract: The ability of mammals to produce urine hyperosmotic to plasma requires the generation of a gradient of increasing osmolality along the medulla from the corticomedullary junction to the papilla tip. Countercurrent multiplication apparently establishes this gradient in the outer medulla, where there is substantial transepithelial reabsorption of NaCl from the water-impermeable thick ascending limbs of the loops of Henle. However, this process does not establish the much steeper osmotic gradient in the inner medulla, where there are no thick ascending limbs of the loops of Henle and the water-impermeable ascending thin limbs lack active transepithelial transport of NaCl or any other solute. The mechanism generating the osmotic gradient in the inner medulla remains an unsolved mystery, although it is generally considered to involve countercurrent flows in the tubules and vessels. A possible role for the three-dimensional interactions between these inner medullary tubules and vessels in the concentrating process is suggested by creation of physiologic models that depict the three-dimensional relationships of tubules and vessels and their solute and water permeabilities in rat kidneys and by creation of mathematical models based on biologic phenomena. The current mathematical model, which incorporates experimentally determined or estimated solute and water flows through clearly defined tubular and interstitial compartments, predicts a urine osmolality in good agreement with that observed in moderately antidiuretic rats. The current model provides substantially better predictions than previous models; however, the current model still fails to predict urine osmolalities of maximally concentrating rats.
authors.affiliation: Department of Physiology, College of Medicine, University of Arizona, Tucson, Arizona; and dantzler@Email.arizona.edu.
authors.forename: William H
authors.initials: WH
authors.lastname: Dantzler
authors.affiliation: Department of Mathematics, Duke University, Durham, North Carolina.
authors.forename: Anita T
authors.initials: AT
authors.lastname: Layton
authors.affiliation: Department of Mathematics, Duke University, Durham, North Carolina.
authors.forename: Harold E
authors.initials: HE
authors.lastname: Layton
authors.affiliation: Department of Physiology, College of Medicine, University of Arizona, Tucson, Arizona; and.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Pannabecker
mesh_terms: D000818:Animals; D004058:Diffusion; D007671:Kidney Concentrating Ability; D007679:Kidney Medulla / Q000098:blood supply* / Q000502:physiology*; D008138:Loop of Henle / Q000502:physiology*; D008954:Models, Biological; D009994:Osmolar Concentration; D010539:Permeability; D051381:Rats; D012079:Renal Circulation; D065608:Renal Reabsorption; D015203:Reproducibility of Results; D012965:Sodium Chloride / Q000378:metabolism*
chemical_list: D012965:Sodium Chloride
references.citation: Bull Math Biol. 1994 May;56(3):491-514
references.pmid: 8087079
references.citation: Am J Physiol Renal Physiol. 2008 Dec;295(6):F1744-51
references.pmid: 18842821
references.citation: Am J Physiol Renal Physiol. 2008 Nov;295(5):F1271-85
references.pmid: 18495796
references.citation: Cell Tissue Res. 1991 May;264(2):269-81
references.pmid: 1878946
references.citation: Am J Physiol. 1992 Sep;263(3 Pt 2):F417-26
references.pmid: 1415570
references.citation: Pflugers Arch. 1969;310(4):297-317
references.pmid: 5817589
references.citation: BMC Physiol. 2002;2:4
references.pmid: 11914159
references.citation: Am J Physiol. 1991 Mar;260(3 Pt 2):F384-94
references.pmid: 2000955
references.citation: Kidney Int. 1991 Mar;39(3):370-81
references.pmid: 2062030
references.citation: Kidney Int. 1982 Apr;21(4):653-5
references.pmid: 7098276
references.citation: Am J Physiol Renal Physiol. 2011 Nov;301(5):F1047-56
references.pmid: 21753076
references.citation: Am J Physiol Renal Physiol. 2004 Jan;286(1):F38-45
references.pmid: 14519595
references.citation: Am J Physiol. 1959 Apr;196(4):927-36
references.pmid: 13637248
references.citation: Compr Physiol. 2012 Jul;2(3):2063-86
references.pmid: 23723033
references.citation: Am J Physiol Renal Physiol. 2008 Jun;294(6):F1306-14
references.pmid: 18417543
references.citation: Am J Physiol Renal Physiol. 2010 Jul;299(1):F273-9
references.pmid: 20392799
references.citation: Am J Physiol Renal Physiol. 2000 Sep;279(3):F468-81
references.pmid: 10966926
references.citation: Am J Physiol. 1973 Mar;224(3):659-68
references.pmid: 4691283
references.citation: J Clin Invest. 1973 Mar;52(3):612-23
references.pmid: 4685086
references.citation: Am J Physiol Renal Physiol. 2010 Jul;299(1):F265-72
references.pmid: 20392798
references.citation: Am J Physiol. 1982 Aug;243(2):F167-72
references.pmid: 6287850
references.citation: J Am Soc Nephrol. 2003 Mar;14(3):611-9
references.pmid: 12595496
references.citation: Am J Physiol Renal Physiol. 2004 Oct;287(4):F767-74
references.pmid: 15187004
references.citation: Helv Physiol Pharmacol Acta. 1951 Jun;9(2):196-207
references.pmid: 14849950
references.citation: Am J Physiol Renal Physiol. 2006 Jun;290(6):F1355-66
references.pmid: 16380456
references.citation: Am J Physiol. 1995 May;268(5 Pt 2):R1087-100
references.pmid: 7539594
references.citation: J Clin Invest. 1974 Feb;53(2):393-402
references.pmid: 11344552
references.citation: Am J Physiol. 1993 Feb;264(2 Pt 2):F337-43
references.pmid: 8447443
references.citation: Am J Physiol. 1996 May;270(5 Pt 2):F900-11
references.pmid: 8928853
references.citation: Kidney Int. 1972 Oct;2(4):214-23
references.pmid: 4657922
references.citation: Am J Physiol. 1965 Jun;208:1119-28
references.pmid: 14301367
references.citation: Am J Physiol Renal Physiol. 2005 Dec;289(6):F1346-66
references.pmid: 15914776
references.citation: Am J Physiol Renal Physiol. 2011 Feb;300(2):F356-71
references.pmid: 21068086
references.citation: Am J Physiol Renal Physiol. 2012 Mar 1;302(5):F591-605
references.pmid: 22088433
references.citation: Pflugers Arch. 1985;405 Suppl 1:S28-32
references.pmid: 4088836
references.citation: Am J Physiol Renal Physiol. 2003 Mar;284(3):F433-46
references.pmid: 12556362
references.citation: Am J Physiol Renal Physiol. 2011 Feb;300(2):F372-84
references.pmid: 21068088
references.citation: Am J Physiol Renal Physiol. 2012 Apr 1;302(7):F830-9
references.pmid: 22160770
references.citation: Kidney Int. 1972 Aug;2(2):85-94
references.pmid: 4671532
references.citation: Am J Physiol Renal Physiol. 2014 Jan 1;306(1):F123-9
references.pmid: 24197065
references.citation: Am J Physiol Renal Physiol. 2003 Jan;284(1):F65-81
references.pmid: 12388411
references.citation: Am J Physiol. 1998 Feb;274(2):F413-24
references.pmid: 9486237
references.citation: Am J Physiol Renal Physiol. 2007 Sep;293(3):F696-704
references.pmid: 17609288
references.citation: Anat Embryol (Berl). 1999 Jul;200(1):117-21
references.pmid: 10395012
references.citation: Physiology (Bethesda). 2009 Aug;24:250-6
references.pmid: 19675356
references.citation: J Physiol. 1971 Mar;213(2):291-309
references.pmid: 5574830
references.citation: Math Biosci. 1993 Aug;116(2):169-96
references.pmid: 8369598
references.citation: J Am Soc Nephrol. 2006 Jan;17(1):77-88
references.pmid: 16319188
references.citation: Am J Physiol. 1991 Mar;260(3 Pt 2):F368-83
references.pmid: 2000954
references.citation: Am J Physiol Renal Physiol. 2013 Feb 1;304(3):F308-16
references.pmid: 23195680
references.citation: Kidney Int. 1974 May;5(5):337-47
references.pmid: 4427415
references.citation: Am J Physiol. 1975 Jan;228(1):71-9
references.pmid: 1147030
references.citation: Am J Physiol Renal Physiol. 2010 Apr;298(4):F973-87
references.pmid: 20053796
references.citation: Am J Physiol Renal Physiol. 2004 Oct;287(4):F816-39
references.pmid: 15213067