Role of three-dimensional architecture in the urine concentrating mechanism of the rat renal inner medulla

Abstract

Recent studies of three-dimensional architecture of rat renal inner medulla (IM) and expression of membrane proteins associated with fluid and solute transport in nephrons and vasculature have revealed structural and transport properties that likely impact the IM urine concentrating mechanism. These studies have shown that 1) IM descending thin limbs (DTLs) have at least two or three functionally distinct subsegments; 2) most ascending thin limbs (ATLs) and about half the ascending vasa recta (AVR) are arranged among clusters of collecting ducts (CDs), which form the organizing motif through the first 3-3.5 mm of the IM, whereas other ATLs and AVR, along with aquaporin-1-positive DTLs and urea transporter B-positive descending vasa recta (DVR), are external to the CD clusters; 3) ATLs, AVR, CDs, and interstitial cells delimit interstitial microdomains within the CD clusters; and 4) many of the longest loops of Henle form bends that include subsegments that run transversely along CDs that lie in the terminal 500 microm of the papilla tip. Based on a more comprehensive understanding of three-dimensional IM architecture, we distinguish two distinct countercurrent systems in the first 3-3.5 mm of the IM (an intra-CD cluster system and an inter-CD cluster system) and a third countercurrent system in the final 1.5-2 mm. Spatial arrangements of loop of Henle subsegments and multiple countercurrent systems throughout four distinct axial IM zones, as well as our initial mathematical model, are consistent with a solute-separation, solute-mixing mechanism for concentrating urine in the IM.

Architecture of the human renal inner medulla and functional implications

“…The AQP1-positive DTLs lie predominantly within the vascular bundles alongside the UT-B-positive DVR (Fig. 9), in the vascular bundle regions that are spatially separate from regions occupied by CDs, in an ar- (40). Thus the close association of long-loop DTLs with CDs in the outer medulla undergoes an anatomic transition as DTLs descend from the outer medulla into and through the inner medulla, where they tend to lie distant from CDs.…”

“…Formation of both gradients reflects, in part, the tubulovascular architecture. The thin limbs of Henle, CDs, and blood vessels partition NaCl, urea, oxygen, water, and other molecules into and out of the multiple medullary compartments in a manner dependent upon their transepithelial or transendothelial permeability characteristics and gradients in addition to overall architecture (5,20,40). Consequently, the tubulovascular architecture can promote or constrain medullary countercurrent systems and other intercompartmental fluid, solute, and oxygen flows.…”

Urea and Ammonia Metabolism and the Control of Renal Nitrogen Excretion

“…UT-A4 is the N-terminal 25% of UT-A1 spliced to the C-terminal 25% (11). UT-B1 protein is expressed in red blood cells (11,16,17) and in nonfenestrated endothelial cells that are characteristic of descending vasa recta, especially in those that are external to collecting duct clusters (18).…”

A mathematical model of the urine concentrating mechanism in the rat renal medulla. I. Formulation and base-case results

“…countercurrent system; NaCl transport; urea transport; kidney DURING PERIODS OF WATER DEPRIVATION, the mammalian urine concentrating mechanism, which is localized in the renal medulla, stabilizes the osmolality of blood plasma by producing a urine that has an osmolality that substantially exceeds that of blood plasma. However, despite decades of sustained experimental and theoretical investigation (24,37,54,58), the nature of the urine concentrating mechanism in the inner medulla (IM) of the mammalian kidney remains controversial.Anatomic studies have revealed a highly structured organization of tubules and vasa recta in the outer medulla (OM) of some mammalian kidneys (2, 29), with tubules and vessels organized concentrically around vascular bundles, tightly packed clusters of parallel vessels, and tubules containing mostly vasa recta. Recent studies of the three-dimensional architecture of the rat IM and expression of membrane proteins associated with fluid and solute transport in nephrons and vasculature have revealed transport and structural properties that likely impact the IM urine concentrating mechanism in the rat kidney.…”

“…countercurrent system; NaCl transport; urea transport; kidney DURING PERIODS OF WATER DEPRIVATION, the mammalian urine concentrating mechanism, which is localized in the renal medulla, stabilizes the osmolality of blood plasma by producing a urine that has an osmolality that substantially exceeds that of blood plasma. However, despite decades of sustained experimental and theoretical investigation (24,37,54,58), the nature of the urine concentrating mechanism in the inner medulla (IM) of the mammalian kidney remains controversial.…”