Urine concentrating mechanism in the inner medulla of the mammalian kidney: role of three‐dimensional architecture

Abstract

The urine concentrating mechanism in the mammalian renal inner medulla (IM) is not understood, although it is generally considered to involve countercurrent flows in tubules and blood vessels. A possible role for the three-dimensional relationships of these tubules and vessels in the concentrating process is suggested by recent reconstructions from serial sections labelled with antibodies to tubular and vascular proteins and mathematical models based on these studies. The reconstructions revealed that the lower 60% of each descending thin limb (DTL) of Henle’s loops lacks water channels (aquaporin-1) and osmotic water permeability and ascending thin limbs (ATLs) begin with a prebend segment of constant length. In the outer zone of the IM (i) clusters of coalescing collecting ducts (CDs) form organizing motif for loops of Henle and vasa recta; (ii) DTLs and descending vasa recta (DVR) are arrayed outside CD clusters, whereas ATLs and ascending vasa recta (AVR) are uniformly distributed inside and outside clusters; (iii) within CD clusters, interstitial nodal spaces are formed by a CD on one side, AVR on two sides, and an ATL on the fourth side. These spaces may function as mixing chambers for urea from CDs and NaCl from ATLs. In the inner zone of the IM, cluster organization disappears and half of Henle’s loops have broad lateral bends wrapped around terminal CDs. Mathematical models based on these findings and involving solute mixing in the interstitial spaces can produce urine slightly more concentrated than that of a moderately antidiuretic rat but no higher.

Isolated interstitial nodal spaces may facilitate preferential solute and fluid mixing in the rat renal inner medulla

“…Model results of the present study support our hypothesis, described in previous reviews (7,24,33), that the countercurrent system in the CD cluster mixes NaCl absorbed from ATLs with absorbate from the CDs (which consists mostly of water, urea, and NaCl) to produce isolated sites of high osmolality that will promote water withdrawal from CDs. By isolating CDs from DVR, which carry relatively dilute fluid, the INSs increase water reabsorption from the CDs and raise the osmolality of its tubular fluid.…”

“…In the context of a countercurrent system, we have previously suggested (7,24,33) that the absorbate from the CDs and ATL is carried via the AVR to higher levels within the CD cluster, where the local absorbate will likely have lower solute concentrations and lower osmolality and where the ascension in AVR fluid that is concentrated relative to local fluid would raise the osmolality of the CD tubular fluid and contribute to an optimization of concentrating efficiency. The model predicts that AVR fluid is hypotonic relative to tubular fluid in loops of Henle, CDs, and DVR.…”

“…In previous reviews (7,24,33), we hypothesized that such repeating microdomains may facilitate interstitial solute and fluid mixing and thus play an important role in generating the IM osmotic gradient. Assuming that the ATLs bordering the INS have low urea permeability and high NaCl permeability, NaCl is reabsorbed from the ATL segments.…”

Vascular endothelial growth factor signaling is necessary for expansion of medullary microvessels during postnatal kidney development

“…The renal medulla contributes significantly to systemic blood pressure control through regulation of sodium excretion and fetal programming includes enhanced salt sensitivity of blood pressure (2,12). Normal salt excretion is a function that relies partly on the unique architecture and close tubulovascular relationship of the renal medulla (10). However, the contribution of renal medullary developmental changes to the programming effect of adult hypertension is not known.…”

The importance of the thick ascending limb of Henle’s loop in renal physiology and pathophysiology

“…2,3 A similar arrangement of the surrounding vessels prevents osmotic gradient dissipiation. 4 Electron microscopy studies demonstrated the presence of two distinct cell types in the TAL, differing in the configuration of the apical membrane: rough-surface cells (R cells), characterized by abundant apical microvilli, and smooth-surface cells (S cells) with no microprojections, but with several subapical vesicles. 5 The former is abundant in the cortex, and the latter in the medulla.…”