Two modes for concentrating urine in rat inner medulla

Pannabecker, Thomas L.; Dantzler, William H.; Layton, Harold E.

doi:10.1152/ajprenal.00398.2003

Cited by 72 publications

(135 citation statements)

References 74 publications

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“…As in previous studies (38,40), this loop configuration is represented by continuously distributed loops that have bends at all IM levels (39). The fraction of loops remaining at the medullary level x is given by…”

Section: Parametersmentioning

confidence: 94%

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

Layton

2011

American Journal of Physiology-Renal Physiology

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Layton AT. A mathematical model of the urine concentrating mechanism in the rat renal medulla. I. Formulation and base-case results. Am J Physiol Renal Physiol 300: F356 -F371, 2011. First published November 10, 2010 doi:10.1152/ajprenal.00203.2010.-A new, region-based mathematical model of the urine concentrating mechanism of the rat renal medulla was used to investigate the significance of transport and structural properties revealed in anatomic studies. The model simulates preferential interactions among tubules and vessels by representing concentric regions that are centered on a vascular bundle in the outer medulla (OM) and on a collecting duct cluster in the inner medulla (IM). Particularly noteworthy features of this model include highly urea-permeable and water-impermeable segments of the long descending limbs and highly urea-permeable ascending thin limbs. Indeed, this is the first detailed mathematical model of the rat urine concentrating mechanism that represents high long-loop urea permeabilities and that produces a substantial axial osmolality gradient in the IM. That axial osmolality gradient is attributable to the increasing urea concentration gradient. The model equations, which are based on conservation of solutes and water and on standard expressions for transmural transport, were solved to steady state. Model simulations predict that the interstitial NaCl and urea concentrations in adjoining regions differ substantially in the OM but not in the IM. In the OM, active NaCl transport from thick ascending limbs, at rates inferred from the physiological literature, resulted in a concentrating effect such that the intratubular fluid osmolality of the collecting duct increases ϳ2.5 times along the OM. As a result of the separation of urea from NaCl and the subsequent mixing of that urea and NaCl in the interstitium and vasculature of the IM, collecting duct fluid osmolality further increases by a factor of ϳ1.55 along the IM. 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 th...

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Section: Parametersmentioning

confidence: 94%

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

Layton

2011

American Journal of Physiology-Renal Physiology

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“…Over the past 10 years, we have developed a series of mathematical models of the urine-concentrating mechanism in the IM, which have incorporated the new information on the three-dimensional relationships of the vessels and tubules, the sites of transporters and channels, and the tubule permeabilities as this information became available (24,48,(56)(57)(58). Here, we consider only the most recent version of these models (46).…”

Section: Mathematical Model Relating Structural and Permeability Findmentioning

confidence: 99%

“…Wexler and colleagues explored, without significant Figure 1. | Diagram of a single vas rectum and single long-looped nephron, illustrating how classic countercurrent multiplication could produce the osmotic gradient in the outer medulla, and how the "passive mechanism" was proposed to produce the osmotic gradient in the inner medulla (23,24). In the outer medulla, active transport of NaCl out of the water-impermeable thick ascending limb (indicated by solid arrows and black dots) creates the small osmotic pressure difference between that limb and the descending limb sufficient for classic countercurrent multiplication to generate the osmotic gradient (approximate osmolalities for rat kidney given by numbers in the black boxes).…”

Section: Introductionmentioning

confidence: 99%

“…Our preliminary studies also indicate that rodent and human inner medullary architecture share fundamental similarities. Finally, we have developed several mathematical models to determine how these physiologic and structural features might relate to the concentrating mechanism (24,(46)(47)(48). In this paper, we briefly review some of the main findings and put them into context with regard to the concentrating mechanism.…”

Section: Introductionmentioning

confidence: 99%

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Urine-Concentrating Mechanism in the Inner Medulla

Dantzler

Layton

et al. 2014

Clinical Journal of the American Society of Nephrology

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SummaryThe ability of mammals to produce urine hyperosmotic to plasma requires the generation of a gradient of increasing osmolality along the medulla from the corticomedullary junction to the papilla tip. Countercurrent multiplication apparently establishes this gradient in the outer medulla, where there is substantial transepithelial reabsorption of NaCl from the water-impermeable thick ascending limbs of the loops of Henle. However, this process does not establish the much steeper osmotic gradient in the inner medulla, where there are no thick ascending limbs of the loops of Henle and the water-impermeable ascending thin limbs lack active transepithelial transport of NaCl or any other solute. The mechanism generating the osmotic gradient in the inner medulla remains an unsolved mystery, although it is generally considered to involve countercurrent flows in the tubules and vessels. A possible role for the three-dimensional interactions between these inner medullary tubules and vessels in the concentrating process is suggested by creation of physiologic models that depict the threedimensional relationships of tubules and vessels and their solute and water permeabilities in rat kidneys and by creation of mathematical models based on biologic phenomena. The current mathematical model, which incorporates experimentally determined or estimated solute and water flows through clearly defined tubular and interstitial compartments, predicts a urine osmolality in good agreement with that observed in moderately antidiuretic rats. The current model provides substantially better predictions than previous models; however, the current model still fails to predict urine osmolalities of maximally concentrating rats.

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“…With the development of digital techniques, three-dimensional (3D) representations of the tubule segments of nephrons were performed to a limited extent at the proximal tubules (PT) (5), distal tubule (6), and at the thin limbs (TL) of the LLN in the inner medulla (IM) (7) of rats. Two mathematical regionalbased models combining morphologic and immunohistochemical findings have been set up to simulate the urine concentration mechanism in rat medulla (8).…”

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confidence: 99%

Three-Dimensional Reconstruction of the Mouse Nephron

Zhai¹,

Thomsen

Birn³

et al. 2006

Journal of the American Society of Nephrology

103

116

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Renal function is crucially dependent on renal microstructure which provides the basis for the regulatory mechanisms that control the transport of water and solutes between filtrate and plasma and the urinary concentration. This study provides new, detailed information on mouse renal architecture, including the spatial course of the tubules, lengths of different segments of nephrons, histotopography of tubules and vascular bundles, and epithelial ultrastructure at well-defined positions along Henle's loop and the distal convolution of nephrons. Three-dimensional reconstruction of 200 nephrons and collecting ducts was performed on aligned digital images, obtained from 2.5-m-thick serial sections of mouse kidneys. Important new findings were highlighted: (1) A tortuous course of the descending thin limbs of long-looped nephrons and a winding course of the thick ascending limbs of short-looped nephrons contributed to a 27% average increase in the lengths of the corresponding segments, (2) the thick-walled tubules incorporated in the central part of the vascular bundles in the inner stripe of the outer medulla were identified as thick ascending limbs of long-looped nephrons, and (3) three types of short-looped nephron bends were identified to relate to the length and the position of the nephron and its corresponding glomerulus. The ultrastructure of the tubule segments was identified and suggests important implications for renal transport mechanisms that should be considered when evaluating the segmental distribution of water and solute transporters within the normal and diseased kidney. T he renal architecture is arranged elaborately to fulfill the physiologic demands for reabsorption of filtered substances and for urine concentration. The architecture includes the formation of the renal zones, the population of short-looped nephrons (SLN) and long-looped nephrons (LLN), the distribution of the tubule segments of nephrons, the tubular-vascular histotopography in medulla, and the epithelial configurations of the different tubule segments.From the 1960s to the 1980s, Kriz and others studied the renal microstructure, including the distribution of nephrons, the tubular-vascular relations in the medullary zones, and the ultrastructure of the epithelia along Henle's loop. Simultaneously, the diversities in renal structure were demonstrated between different species, including rat, mouse, hamster, and rabbit (1-3). In the late 1980s, a standard nomenclature for the kidney structure, which has been widely adopted, was published (4). With the development of digital techniques, three-dimensional (3D) representations of the tubule segments of nephrons were performed to a limited extent at the proximal tubules (PT) (5), distal tubule (6), and at the thin limbs (TL) of the LLN in the inner medulla (IM) (7) of rats. Two mathematical regionalbased models combining morphologic and immunohistochemical findings have been set up to simulate the urine concentration mechanism in rat medulla (8).At present, a large body of basic nephrol...

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Two modes for concentrating urine in rat inner medulla

Cited by 72 publications

References 74 publications

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

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

Urine-Concentrating Mechanism in the Inner Medulla

Three-Dimensional Reconstruction of the Mouse Nephron

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