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

2008 ◽  
Vol 295 (5) ◽  
pp. F1271-F1285 ◽  
Author(s):  
Thomas L. Pannabecker ◽  
William H. Dantzler ◽  
Harold E. Layton ◽  
Anita T. Layton
Keyword(s):  
Three Dimensional ◽  
Cluster System ◽  
Urea Transporter ◽  
Comprehensive Understanding ◽  
Concentrating Mechanism ◽  
Vasa Recta ◽  
Collecting Ducts ◽  
Renal Inner Medulla ◽  
Urine Concentrating Mechanism

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 μm 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.

Inner medullary lactate production and urine-concentrating mechanism: a flat medullary model

2003 ◽  
Vol 284 (1) ◽  
pp. F65-F81 ◽  
Author(s):  
Stéphane Hervy ◽  
S. Randall Thomas
Keyword(s):  
Collecting Duct ◽  
Lactate Production ◽  
Osmotic Gradient ◽  
Osmotic Effect ◽  
Concentrating Mechanism ◽  
Urea Permeability ◽  
Vasa Recta ◽  
Renal Inner Medulla ◽  
High Lactate ◽  
Urine Concentrating Mechanism

We used a mathematical model to explore the possibility that metabolic production of net osmoles in the renal inner medulla (IM) may participate in the urine-concentrating mechanism. Anaerobic glycolysis (AG) is an important source of energy for cells of the IM, because this region of the kidney is hypoxic. AG is also a source of net osmoles, because it splits each glucose into two lactate molecules, which are not metabolized within the IM. Furthermore, these sugars exert their full osmotic effect across the epithelia of the thin descending limb of Henle's loop and the collecting duct, so they are apt to fulfill the external osmole role previously attributed to interstitial urea (whose role is compromised by the high urea permeability of long descending limbs). The present simulations show that physiological levels of IM glycolytic lactate production could suffice to significantly amplify the IM accumulation of NaCl. The model predicts that for this to be effective, IM lactate recycling must be efficient, which requires high lactate permeability of descending vasa recta and reduced IM blood flow during antidiuresis, two conditions that are probably fulfilled under normal circumstances. The simulations also suggest that the resulting IM osmotic gradient is virtually insensitive to the urea permeability of long descending limbs, thus lifting a longstanding paradox, and that this high urea permeability may serve for independent regulation of urea balance.

scholarly journals Functional implications of the three-dimensional architecture of the rat renal inner medulla

2010 ◽  
Vol 298 (4) ◽  
pp. F973-F987 ◽  
Author(s):  
Anita T. Layton ◽  
Thomas L. Pannabecker ◽  
William H. Dantzler ◽  
Harold E. Layton
Keyword(s):  
Collecting Duct ◽  
Three Dimensional ◽  
Outer Region ◽  
Free Water ◽  
Model Calculations ◽  
Concentrating Mechanism ◽  
Vasa Recta ◽  
Renal Inner Medulla ◽  
Inner Region ◽  
Surprising Finding

A new, region-based mathematical model of the urine concentrating mechanism of the rat renal inner medulla (IM) was used to investigate the significance of transport and structural properties revealed in recent studies that employed immunohistochemical methods combined with three-dimensional computerized reconstruction. The model simulates preferential interactions among tubules and vessels by representing two concentric regions. The inner region, which represents a collecting duct (CD) cluster, contains CDs, some ascending thin limbs (ATLs), and some ascending vasa recta; the outer region, which represents the intercluster region, contains descending thin limbs, descending vasa recta, remaining ATLs, and additional ascending vasa recta. In the upper portion of the IM, the model predicts that interstitial Na+ and urea concentrations (and osmolality) in the CD clusters differ significantly from those in the intercluster regions: model calculations predict that those CD clusters have higher urea concentrations than the intercluster regions, a finding that is consistent with a concentrating mechanism that depends principally on the mixing of NaCl from ATLs and urea from CDs. In the lower IM, the model predicts that limited or nearly zero water permeability in descending thin limb segments will increase concentrating effectiveness by increasing the rate of solute-free water absorption. The model predicts that high urea permeabilities in the upper portions of ATLs and increased contact areas of longest loop bends with CDs both modestly increase concentrating capability. A surprising finding is that the concentrating capability of this region-based model falls short of the capability of a model IM that has radially homogeneous interstitial fluid at each level but is otherwise analogous to the region-based model.

Quantitative analysis of functional reconstructions reveals lateral and axial zonation in the renal inner medulla

2008 ◽  
Vol 294 (6) ◽  
pp. F1306-F1314 ◽  
Author(s):  
Thomas L. Pannabecker ◽  
Cory S. Henderson ◽  
William H. Dantzler
Keyword(s):  
Surface Area ◽  
Three Dimensional ◽  
Outer Zone ◽  
Vasa Recta ◽  
Collecting Ducts ◽  
Exponential Decrease ◽  
Renal Inner Medulla ◽  
Distance Mapping ◽  
Definition Of ◽  
Quantitative Definition

Three-dimensional functional reconstructions of descending thin limbs (DTLs) and ascending thin limbs (ATLs) of loops of Henle, descending vasa recta (DVR), ascending vasa recta (AVR), and collecting ducts (CDs) permit quantitative definition of lateral and axial zones of probable functional significance in rat inner medulla (IM). CD clusters form the organizing motif for loops of Henle and vasa recta in the initial 3.0–3.5 mm of the IM. Using Euclidean distance mapping, we defined the lateral boundary of each cluster by pixels lying maximally distant from any CD. DTLs and DVR lie almost precisely on this independently defined boundary, placing them in the intercluster interstitium maximally distant from any CD. ATLs and AVR lie in a nearly uniform pattern throughout intercluster and intracluster regions, which we further differentiated by a polygon around CDs in each cluster. Loops associated with individual CD clusters show a similar axial exponential decrease as all loops together in the IM. Because ∼3.0–3.5 mm below the IM base CD clusters cease to form the organizing motif, all DTLs lack aquaporin 1 (AQP1), and all vasa recta are fenestrated, we have designated the first 3.0–3.5 mm of the IM the “outer zone” (OZ) and the final 1.5–2.0 mm the “inner zone” (IZ). We further subdivided these into OZ-1, OZ-2, IZ-1, and IZ-2 on the basis of the presence of completely AQP1-null DTLs only in the first 1 mm and on broad transverse loop bends only in the final 0.5 mm. These transverse segments expand surface area for probable NaCl efflux around loop bends from ∼40% to ∼140% of CD surface area in the final 100 μm of the papilla.

scholarly journals The urea transporter UT-A1 plays a predominant role in a urea-dependent urine-concentrating mechanism

2020 ◽  
Vol 295 (29) ◽  
pp. 9893-9900 ◽  
Author(s):  
Xiaoqiang Geng ◽  
Shun Zhang ◽  
Jinzhao He ◽  
Ang Ma ◽  
Yingjie Li ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Urine Output ◽  
Urine Osmolality ◽  
Urine Concentration ◽  
Urea Transporter ◽  
Predominant Role ◽  
Concentrating Mechanism ◽  
Daily Urine ◽  
Urine Concentrating Mechanism ◽  
Daily Urine Output

Urea transporters are a family of urea-selective channel proteins expressed in multiple tissues that play an important role in the urine-concentrating mechanism of the mammalian kidney. Previous studies have shown that knockout of urea transporter (UT)-B, UT-A1/A3, or all UTs leads to urea-selective diuresis, indicating that urea transporters have important roles in urine concentration. Here, we sought to determine the role of UT-A1 in the urine-concentrating mechanism in a newly developed UT-A1–knockout mouse model. Phenotypically, daily urine output in UT-A1–knockout mice was nearly 3-fold that of WT mice and 82% of all-UT–knockout mice, and the UT-A1–knockout mice had significantly lower urine osmolality than WT mice. After 24-h water restriction, acute urea loading, or high-protein (40%) intake, UT-A1–knockout mice were unable to increase urine-concentrating ability. Compared with all-UT–knockout mice, the UT-A1–knockout mice exhibited similarly elevated daily urine output and decreased urine osmolality, indicating impaired urea-selective urine concentration. Our experimental findings reveal that UT-A1 has a predominant role in urea-dependent urine-concentrating mechanisms, suggesting that UT-A1 represents a promising diuretic target.

Outer medullary anatomy and the urine concentrating mechanism

1998 ◽  
Vol 274 (2) ◽  
pp. F413-F424 ◽  
Author(s):  
X. Wang ◽  
S. R. Thomas ◽  
A. S. Wexler
Keyword(s):  
Structural Model ◽  
Comparative Anatomy ◽  
Urine Concentration ◽  
Vascular Bundles ◽  
Vasa Recta ◽  
Collecting Ducts ◽  
Outer Stripe ◽  
Physiological Values ◽  
Modeling Representation ◽  
Urine Concentrating Mechanism

In earlier work, mathematical models of the urine concentration mechanism were developed incorporating the features of renal anatomy. However, several anatomic observations showed inconsistencies in the modeling representation of the outer stripe (OS) anatomy. In this study, based on observations from comparative anatomy and morphometric studies, we propose a new structural model of outer medullary anatomy, different from that previously presented [A. S. Wexler, R. E. Kalaba, and D. J. Marsh. Am. J. Physiol. 260 ( Renal Fluid Electrolyte Physiol. 29): F368–F383, 1991]. The modifications include the following features of rat outer medullary anatomy, for example, 1) in the OS, the limbs of long loops of Henle surround the descending and ascending vasa recta that develop into the vascular bundles in the inner stripe (IS), whereas the limbs of short loops are close to the collecting ducts; and 2) the descending limbs of short loops shift from the tubular region in the OS to near the vascular bundle in the IS, whereas the limbs of long loops are situated away from the vascular bundles in the tubular region. The sensitivity of the concentrating process to the relative position of loops and vessels was investigated in the different medullary regions. With these modifications, the model predicts a more physiological, axial osmolarity gradient in both outer and inner medulla with membrane parameters that are all in the range of measured physiological values, including the urea permeabilities of descending vasa recta reported by Pallone and co-workers (T. L. Pallone, J. Work, R. L. Myers, and R. L. Jamison. J. Clin.Invest. 93: 212–222, 1994).

Micropuncture study of the mammalian urinary concentrating mechanism: evidence for the countercurrent hypothesis

1959 ◽  
Vol 196 (4) ◽  
pp. 927-936 ◽  
Author(s):  
Carl W. Gottschalk ◽  
Margaret Mylle
Keyword(s):  
Sodium Chloride ◽  
Antidiuretic Hormone ◽  
Osmotic Diuresis ◽  
Concentrating Mechanism ◽  
Vasa Recta ◽  
Multiplier System ◽  
Collecting Ducts ◽  
Micropuncture Study ◽  
Proximal Tubular

The osmolality was determined of fluid collected by micropuncture from proximal and distal convolutions, loops of Henle, collecting ducts and vasa recta of kidneys of various rodents with and without osmotic diuresis. Proximal tubular fluid was isosmotic; in the presence of antidiuretic hormone, early distal fluid was hypo-osmotic due to the prior reabsorption of sodium chloride, and late distal fluid again isosmotic. The hyperosmotic concentration of the urine is established in the collecting ducts, apparently as a consequence, in part at least, of the hyperosmotic reabsorption of sodium chloride in the loops of Henle. Fluid from the bends of loops of Henle, and from collecting ducts and vasa recta at the same level were equally hyperosmotic, consistent with the hypothesis that the mammalian nephron functions as a countercurrent multiplier system. The vasa recta are believed to play an important role in the concentration of the urine by functioning as countercurrent diffusion exchangers.

scholarly journals Loop of Henle interaction with interstitial nodal spaces in the renal inner medulla

2008 ◽  
Vol 295 (6) ◽  
pp. F1744-F1751 ◽  
Author(s):  
Thomas L. Pannabecker
Keyword(s):  
Total Population ◽  
Outer Zone ◽  
Wistar Rat ◽  
Clear Understanding ◽  
Vasa Recta ◽  
Structural Relationships ◽  
Equivalent Length ◽  
Collecting Ducts ◽  
Renal Inner Medulla ◽  
Periodic Changes

Understanding dynamics of NaCl reabsorption from loops of Henle, and cellular and physiological consequences, requires a clear understanding of the structural relationships of loops with other functional elements of the inner medulla (IM). Pathways taken by ascending thin limbs (ATLs) and prebend segments along the corticopapillary axis were evaluated for the outer zone of the IM of the Munich-Wistar rat. Connectivity between these segments and microdomains of interstitium adjacent to collecting ducts (CDs) and abutting ascending vasa recta (interstitial nodal spaces) was assessed by evaluating their physical contacts. For each secondary CD cluster, the number of contacts made between the total population of ATLs and interstitial nodal spaces declines as a function of depth below the outer medulla (OM)-IM boundary at near the same exponential rate that loop number declines. The proportion of each loop that makes contact with nodal spaces is inversely related to loop length. Prebend and postbend equivalent length ATL segments lie in contact with an interstitial nodal space along nearly their entire lengths. The number of contacts made by the total population of prebend or postbend segments exhibits a marked, periodic increase and decrease as a function of depth below the OM-IM boundary; this number of contacts correlates with equivalent periodic changes in prebend number. Simulations of loop distribution indicate that small discontinuities in loop distribution contribute to periodic changes in prebend number. Convergence of IM loop bends within CD clusters likely plays an essential role in NaCl compartmentalization by promoting NaCl reabsorption near interstitial regions lying adjacent to CDs and ascending vasa recta.

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