Two fluid compartments in the renal inner medulla: a view through the keyhole of the concentrating process

Abstract

Approximately four decades ago, the countercurrent theory became influential in studies on the concentrating process in the mammalian kidney. The theory successfully represented the concentrating process in the outer medulla, but the problem of the concentrating mechanism in the inner medulla, as defined by Homer Smith has remained essentially intractable. In a recent comprehensive review by Knepper and coworkers of various theories and models, attention was refocused on the possible role of hyaluronate (HA) in the inner medullary concentrating process. The authors proposed a hypothesis that HA can convert hydrostatic pressure to concentrating work.Here, we briefly survey the earlier ideas on the role imputed to HA and present a new hypothesis which is different from that of Knepper and coworkers. We estimate that the hydrostatic pressures available in the inner medulla can account only for a very small fraction of the concentrating work. We hypothesize that the role of HA is tied up with extravasated plasma albumin and suggest that owing to the property of HA solutions to exclude other macromolecules, extravasated plasma albumin and HA constitute two fluid compartments in the interstitium in the inner medulla. In this proposed two-compartment model, the Gibbs-Donnan distribution influences the movement of ions and water between the HA and the extravasated albumin compartment. To relate the hypothetical role of HA to the concentrating process, we briefly describe new results obtained by other investigators on the accumulation of urea in the inner medulla. This subject has been critically reviewed recently by Yang & Bankir.Many processes have been identified as contributing to the concentrating process in the mammalian inner medulla. We speculate that among these many processes, the primary responsibility for the final concentration of the excreted urine may be portioned out differently in different mammalian species.

Modeling transport in the kidney: investigating function and dysfunction

“…This would in turn raise the luminal osmolality above that of the interstitium and generate a single effect for concentration of urine. However, thermodynamic analysis of this process indicates that the pressures exerted on the inner medullary tissue can only account for a small fraction of the concentrating work in the inner medulla (70,100). Very recently, Pinter and Shohet (69) suggested that pelvic contractions could contribute to the IM osmolality gradient via a different mechanism, one based on the Gibbs-Donnan effect between two interstitial compartments, one containing hyaluronan and the other extravasated plasma albumin.…”

An Inner Medullary Concentrating Process Actuated by Renal Pelvic/Calyceal Muscle Contractions: Assessment and Hypothesis

“…The extravasated albumin molecules are mobile and, driven by solvent drag, move rapidly through their EPA compartment and re-enter into the ascending vasa recta [17, 18]. We estimated [10] that the EPA compartment constitutes approximately 15–20% of the interstitial volume, and cited experimental data [19, 20] indicating that the concentration of albumin molecules in this compartment is about one third to one half of that in circulating plasma.…”

“…Knepper et al [9] proposed that a macromolecule, hyaluronan (HA), played the role of a mechano-osmotic transducer in the process. In an earlier paper [10] we discussed the role of macromolecules in the inner medulla and argued that by considering the thermodynamic equivalence between mechanical and osmotic work, the work exerted by the pelvic muscles seemed disproportionately small to account for the increase of solute concentration occurring in the inner medulla. The hypothesis developed here provides a possible resolution of this discrepancy.…”

“…We have previously proposed [10] that in the inner medullary interstitium of the mammalian kidney there are 2 fluid compartments: the HA compartment and the extravasated plasma albumin (EPA) compartment. Although these compartments are not separated by a membrane, the separation is the result of molecular exclusion, a phenomenon described by Ogston, Laurent and associates [11,12,13] as it relates specifically to hyaluronan and albumin.…”

Hormona antidiurética, 2014

“…El lector interesado puede recurrir a la bibliografía sobre el tema. [21][22][23] b. L a a c c i ó n d e l a v a s o p r e s i n a s o b r e el receptor V2 extrarrenal estimula la producción de factores de la coagulación: factor VIIIc y Von Willebrandt. Sus niveles aumentan dos a tres veces sobre los basales.…”