Mammalian Renal Medulla Models

Anita Layton and Harold Layton


It has been shown that the organization of nephrons and vasa recta in the mammalian outer medulla is highly structured. Nephrons and vasa recta are positioned around the vascular bundles, which are tightly packed bundles containing descending vasa recta and ascending vasa recta, arranged in a checkerboard pattern. It has been proposed that this structural organization may results in preferential interactions among nephrons and vasa recta, which may in turn contribute to solute recycling in the medulla and to the urine concentrating mechanism.

The goal of our study is to develop a mathematical model of the mammalian outer medulla that incorporates the findings of anatomic studies and recently obtained epithelial transport parameters. Our model is formulated as a dynamic boundary-value problem, consisting of a large system of coupled ordinary differential equations (ODEs), representing water conservation, and partial hyperbolic partial differential equations (PDEs), representing solute conservation. Unliked previous central core models, this model includes the representation of vasa recta. By representing the relative positions of the medullary structures, the model captures preferential interactions among the structures.

Model Configuration Configuration of the Outer Medulla Model

Our outer medulla model (see above figure) represents a short loop of Henle that reaches to the end of the outer medulla, a long loop of Henle that reaches into the inner medulla, continuously distributed vasa recta that turn at differing levels of the outer medulla, a long vas rectum that reaches into the inner medulla, a collecting duct, and two central regions of merged capillaries, interstitial spaces, and interstitial cells. The loops of Henle, vasa recta, and collecting duct interact in the central regions; two central regions are included to simulate the preferential interactions among tubules vessels that have been suggested by the complex structural features revealed in anatomical studies of the mammalian renal medulla. Such preferential interactions have been interpreted to contribute to more efficient countercurrent exchange or multiplication, to the cycling and accumulation of urea in the inner medulla, and to the sequestration of urea or NaCl in tubular segments.

In most mammalian species, descending vasa recta (DVR) and ascending vasa recta (AVR) are incorporated into tightly packed vascular bundles in the inner stripe of the outer medulla. The innermost central region, denoted by R1, represents a intrabundle region. DVR on the periphery of the bundles peel off to supply the dense capillary plexus of the outer medulla. Thus, these vasa recta are represented by continuously distributed vasa recta, with a vas rectum reaching to each level of the outer medulla. Centrally located DVR traverse the axis of the bundles to supply blood flow to the inner medulla. Thus, vasa recta that are destined for the inner medulla are represented by a single vas rectum that reaches past the end of the outer medulla.


Related Publications

  • Anita T. Layton and Harold E. Layton, `` A Region-based Model Framework for the Rat Urine Concentrating Mechanism the Urine Concentrating Mechanism,'' Bulletin of Mathematical Biology, Vol. 65, No. 5, pp. 859-901, 2003.
  • Anita T. Layton, Thomas L. Pannabecker, William H. Dantzler, and Harold E. Layton, "Two Modes for Concentrating Urine in the Rat Inner Medulla," American Journal of Physiology Renal Physiology, Vol. 287, pp. F816-F839, 2004.
  • Anita T. Layton and Harold E. Layton, ``A Region-based Mathematical Model of the Urine Concentrating Mechanism in the Rat Outer Medulla: I. Formulation and Base-case Results,'' American Journal of Physiology Renal Physiology, Vol 289, pp. F1346-F1366, 2005.
  • Anita T. Layton and Harold E. Layton, ``A Region-based Mathematical Model of the Urine Concentrating Mechanism in the Rat Outer Medulla: II. Parameter Sensitivity and Tubular Inhomogeneity,'' American Journal of Physiology Renal Physiology, Vol 289, pp. F1367-F1381, 2005.
  • S. Randall Thomas, Anita Layton, Harold Layton, and Leon Moore, Kidney modelling: status and perspectives, Proceedings of the IEEE, Vol. 94 No. 4, pp. 740-752, 2006.
  • Anita T. Layton, "Role of UTB urea transporters in the urine concentrating mechanism of the rat kidney," Bull. Math. Biol., Vol. 69, No. 3, pp. 887-929, 2007.
  • Thomas L. Pannabecker, William H. Dantzler, Harold E. Layton, and Anita T. Layton, "Role of three-dimensional architecture in the urine concentrating mechanism of the rat renal inner medulla," Am. J. Physiol. Renal Physiol., Vol. 295, pp. F1271-F1285, 2008.
  • Anita T. Layton, Harold E. Layton, William H. Dantzler, and Thomas L. Pannabecker, "The mammalian urine concentrating mechanism: hypotheses and uncertainties," Physiol., Vol. 24, pp. 250-256, 2009.
  • Anita T. Layton, Thomas L. Pannabecker, William H. Dantzler, and Harold E. Layton, "Functional implications of the three-dimensional architecture of the rat renal inner medulla," Am. J. Physiol. Renal Physiol., Vol. 298, pp. F973-F987, 2010.
  • Anita T. Layton, Thomas L. Pannabecker, William H. Dantzler, and Harold E. Layton, "Hyperfiltration and inner-stripe hypertrophy may explain findings by Gamble and co-workers," Am. J. Physiol. Renal Physiol., Vol. 298, pp. F962-F972, 2010.
  • William H. Dantzler, Thomas L. Pannabecker, Anita T. Layton, and Harold E. Layton, "Urine concentrating mechanism in the inner medulla of the mammalian kidney: Role of three-dimensional architecture," Acta Physiologica, in press, 2010.


Last updated: September 3, 2006