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).

A region-based mathematical model of the urine concentrating mechanism in the rat outer medulla. II. Parameter sensitivity and tubular inhomogeneity

2005 ◽  
Vol 289 (6) ◽  
pp. F1367-F1381 ◽  
Author(s):  
Anita T. Layton ◽  
Harold E. Layton
Keyword(s):  
Mathematical Model ◽  
Boundary Conditions ◽  
Rat Kidney ◽  
Vascular Bundles ◽  
Thick Ascending Limb ◽  
Outer Medulla ◽  
Model Calculations ◽  
Concentrating Mechanism ◽  
Vasa Recta ◽  
Urine Concentrating Mechanism

In a companion study (Layton AT and Layton HE. Am J Physiol Renal Physiol 289: F1346–F1366, 2005), a region-based mathematical model was formulated for the urine concentrating mechanism (UCM) in the outer medulla (OM) of the rat kidney. In the present study, we quantified the sensitivity of that model to several structural assumptions, including the degree of regionalization and the degree of inclusion of short descending limbs (SDLs) in the vascular bundles of the inner stripe (IS). Also, we quantified model sensitivity to several parameters that have not been well characterized in the experimental literature, including boundary conditions, short vasa recta distribution, and ascending vasa recta (AVR) solute permeabilities. These studies indicate that regionalization elevates the osmolality of the fluid delivered into the inner medulla via the collecting ducts; that model predictions are not significantly sensitive to boundary conditions; and that short vasa recta distribution and AVR permeabilities significantly impact concentrating capability. Moreover, we investigated, in the context of the UCM, the functional significance of several aspects of tubular segmentation and heterogeneity: SDL segments in the IS that are likely to be impermeable to water but highly permeable to urea; a prebend segment of SDLs that may be functionally like thick ascending limb (TAL); differing IS and outer stripe Na+ active transport rates in TAL; and potential active urea secretion into the proximal straight tubules. Model calculations predict that these aspects of tubular of segmentation and heterogeneity generally enhance solute cycling or promote effective UCM function.

scholarly journals Countercurrent multiplication may not explain the axial osmolality gradient in the outer medulla of the rat kidney

2011 ◽  
Vol 301 (5) ◽  
pp. F1047-F1056 ◽  
Author(s):  
Anita T. Layton ◽  
Harold E. Layton
Keyword(s):  
Alternative Explanation ◽  
Rat Kidney ◽  
Vascular Bundles ◽  
Outer Medulla ◽  
Anatomic Structure ◽  
Physical Separation ◽  
Nacl Absorption ◽  
Vasa Recta ◽  
Osmotic Water ◽  
Collecting Ducts

It has become widely accepted that the osmolality gradient along the corticomedullary axis of the mammalian outer medulla is generated and sustained by a process of countercurrent multiplication: active NaCl absorption from thick ascending limbs is coupled with the counterflow configuration of the descending and ascending limbs of the loops of Henle to generate an axial osmolality gradient along the outer medulla. However, aspects of anatomic structure (e.g., the physical separation of the descending limbs of short loops of Henle from contiguous ascending limbs), recent physiologic experiments (e.g., those that suggest that the thin descending limbs of short loops of Henle have a low osmotic water permeability), and mathematical modeling studies (e.g., those that predict that water-permeable descending limbs of short loops are not required for the generation of an axial osmolality gradient) suggest that countercurrent multiplication may be an incomplete, or perhaps even erroneous, explanation. We propose an alternative explanation for the axial osmolality gradient: we regard the thick limbs as NaCl sources for the surrounding interstitium, and we hypothesize that the increasing axial osmolality gradient along the outer medulla is primarily sustained by an increasing ratio, as a function of increasing medullary depth, of NaCl absorption (from thick limbs) to water absorption (from thin descending limbs of long loops of Henle and, in antidiuresis, from collecting ducts). We further hypothesize that ascending vasa recta that are external to vascular bundles will carry, toward the cortex, an absorbate that at each medullary level is hyperosmotic relative to the adjacent interstitium.

scholarly journals Architecture of vasa recta in the renal inner medulla of the desert rodent Dipodomys merriami: potential impact on the urine concentrating mechanism

2012 ◽  
Vol 303 (7) ◽  
pp. R748-R756 ◽  
Author(s):  
Tadeh Issaian ◽  
Vinoo B. Urity ◽  
William H. Dantzler ◽  
Thomas L. Pannabecker
Keyword(s):  
Water Channel ◽  
Wistar Rat ◽  
Vascular Bundles ◽  
Dipodomys Merriami ◽  
Kangaroo Rat ◽  
Concentrating Mechanism ◽  
Architectural Features ◽  
Vasa Recta ◽  
Desert Rodent ◽  
Urine Concentrating Mechanism

We hypothesize that the inner medulla of the kangaroo rat Dipodomys merriami, a desert rodent that concentrates its urine to over 6,000 mosmol/kg H2O, provides unique examples of architectural features necessary for production of highly concentrated urine. To investigate this architecture, inner medullary vascular segments in the outer inner medulla were assessed with immunofluorescence and digital reconstructions from tissue sections. Descending vasa recta (DVR) expressing the urea transporter UT-B and the water channel aquaporin 1 lie at the periphery of groups of collecting ducts (CDs) that coalesce in their descent through the inner medulla. Ascending vasa recta (AVR) lie inside and outside groups of CDs. DVR peel away from vascular bundles at a uniform rate as they descend the inner medulla, and feed into networks of AVR that are associated with organized clusters of CDs. These AVR form interstitial nodal spaces, with each space composed of a single CD, two AVR, and one or more ascending thin limbs or prebend segments, an architecture that may lead to solute compartmentation and fluid fluxes essential to the urine concentrating mechanism. Although we have identified several apparent differences, the tubulovascular architecture of the kangaroo rat inner medulla is remarkably similar to that of the Munich Wistar rat at the level of our analyses. More detailed studies are required for identifying interspecies functional differences.

Urinary concentrating ability: insights from comparative anatomy

1985 ◽  
Vol 249 (6) ◽  
pp. R643-R666 ◽  
Author(s):  
L. Bankir ◽  
C. de Rouffignac
Keyword(s):  
Water Conservation ◽  
Comparative Anatomy ◽  
Renal Medulla ◽  
Urine Concentration ◽  
Vascular Bundles ◽  
High Concentration ◽  
Morphological Adaptations ◽  
Time Required ◽  
Urinary Concentrating Ability ◽  
Coherent Picture

It appears difficult to build a coherent picture of the concentrating system of the mammalian renal medulla. This may be due to the diversity of the factors involved and to considerable interspecies differences. Several morphological adaptations that may be critical in the improvement of water conservation are described. They include variations in the length of the papilla, number of nephrons, percentage of long-looped nephrons, nephron heterogeneity, development of pelvic fornices, confluence of collecting ducts, vascular bundles in the inner stripe of the outer medulla, thin descending limb epithelium, and relative development of the three medullary zones. The organization of the medullary circulation is described; the medulla includes several functionally different compartments favoring preferential exchanges by the juxtaposition of certain tubules and vessels. This may improve the efficiency of certain recycling routes and hence the insulation of the different compartments. As discussed in section III, a better inner medullary insulation may be key, not (or not only) in achieving a high urine concentration but mainly in reducing the time required to reach this high concentration. This overview of the multiple interspecies variations in medullary organization underlines the importance, among other factors, of the inner stripe architecture and of the internephron differences in the process of urine concentration.

scholarly journals Comparative physiology and architecture associated with the mammalian urine concentrating mechanism: role of inner medullary water and urea transport pathways in the rodent medulla

2013 ◽  
Vol 304 (7) ◽  
pp. R488-R503 ◽  
Author(s):  
Thomas L. Pannabecker
Keyword(s):  
Water Channel ◽  
Urine Concentration ◽  
Structure And Function ◽  
Transport Pathways ◽  
Regulatory Pathways ◽  
Concentrating Mechanism ◽  
Vasa Recta ◽  
And Function ◽  
Tissue Compartments ◽  
Urine Concentrating Mechanism

Comparative studies of renal structure and function have potential to provide insights into the urine-concentrating mechanism of the mammalian kidney. This review focuses on the tubular transport pathways for water and urea that play key roles in fluid and solute movements between various compartments of the rodent renal inner medulla. Information on aquaporin water channel and urea transporter expression has increased our understanding of functional segmentation of medullary thin limbs of Henle's loops, collecting ducts, and vasa recta. A more complete understanding of membrane transporters and medullary architecture has identified new and potentially significant interactions between these structures and the interstitium. These interactions are now being introduced into our concept of how the inner medullary urine-concentrating mechanism works. A variety of regulatory pathways lead directly or indirectly to variable patterns of fluid and solute movements among the interstitial and tissue compartments. Animals with the ability to produce highly concentrated urine, such as desert species, are considered to exemplify tubular structure and function that optimize urine concentration. These species may provide unique insights into the urine-concentrating process. 1

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.

Vasoconstriction of outer medullary vasa recta by angiotensin II is modulated by prostaglandin E2

1994 ◽  
Vol 266 (6) ◽  
pp. F850-F857 ◽  
Author(s):  
T. L. Pallone
Keyword(s):  
Angiotensin Ii ◽  
Prostaglandin E2 ◽  
Regional Blood Flow ◽  
Renal Medulla ◽  
Hydraulic Pressure ◽  
Vascular Bundles ◽  
Ang Ii ◽  
Vasa Recta ◽  
Anatomical Arrangement

Vasa recta were dissected from outer medullary vascular bundles in the rat and perfused in vitro. Examination by transmission electron microscopy reveals them to be only outer medullary descending vasa recta (OM-DVR). To establish a method for systematic examination of vasoconstriction, OMDVR were perfused at 5 nl/min with collection pressure increased to 5 mmHg. Under these conditions, transmembrane volume flux was found to be near zero, and the transmural hydraulic pressure gradient was found to be < 15 mmHg. Over a concentration range of 10(-12) to 10(-8) M, abluminal application of angiotensin II (ANG II) caused graded focal vasoconstriction of OMDVR that is blocked by saralasin. Luminal application of ANG II over the same concentration range was much less effective. Abluminal application of prostaglandin E2 (PGE2) shifted the vasoconstrictor response of OMDVR to higher ANG II concentrations. PGE2 reversibly dilated OMDVR that had been preconstricted by ANG II. These results demonstrate that OMDVR are vasoactive segments. Their anatomical arrangement suggests that they play a key role in the regulation of total and regional blood flow to the renal medulla.

Amino acid transport by juxtamedullary nephrons: distal reabsorption and recycling

1988 ◽  
Vol 255 (3) ◽  
pp. F397-F407 ◽  
Author(s):  
W. H. Dantzler ◽  
S. Silbernagl
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Amino Acid Transport ◽  
Acid Transport ◽  
Acidic Amino Acids ◽  
Vasa Recta ◽  
Collecting Ducts ◽  
Distal Site

Amino acid transport by juxtamedullary (JM) nephrons and its relationship to transport by superficial cortical (SC) nephrons and to function of vasa recta and collecting ducts were examined in vivo and in situ by free-flow micropuncture of Henle's loops, collecting ducts, and vasa recta and by continuous microinfusion of Henle's loops in exposed rat papillae. Fractional deliveries (FDs) of six neutral amino acids, two acidic amino acids, and taurine to tips of Henle's loops of JM nephrons could be substantially below those to early distal loops of SC nephrons, indicating that reabsorption before loop tips could be greater in JM than in SC nephrons. FDs to collecting ducts lower than to JM loop tips suggested reabsorption distal to loop tips. This was confirmed by continuous microinfusion of ascending limbs of Henle's loops. Distal site of reabsorption is unknown, but amino acids may move passively out of the thin ascending limb and be recycled into vasa recta and descending limb. Recycling of amino acids was supported by high FDs to tips of Henle's loops (sometimes greater than 1.0), higher concentrations in ascending than in descending vasa recta at same papilla level, and high mean concentrations in vasa recta.

scholarly journals Inhibition of calcium signaling in descending vasa recta endothelia by ANG II

2000 ◽  
Vol 278 (4) ◽  
pp. H1248-H1255 ◽  
Author(s):  
Thomas L. Pallone ◽  
Erik P. Silldorff ◽  
Zhong Zhang
Keyword(s):  
Collecting Duct ◽  
No Production ◽  
Vascular Bundles ◽  
Thick Ascending Limb ◽  
Ang Ii ◽  
Vasomotor Tone ◽  
Medullary Thick Ascending Limb ◽  
Vasa Recta ◽  
Medullary Collecting Duct ◽  
Peak Phase

The intracellular calcium ([Ca2+]i) response of outer medullary descending vasa recta (OMDVR) endothelia to ANG II was examined in fura 2-loaded vessels. Abluminal ANG II (10− 8 M) caused [Ca2+]i to fall in proportion to the resting [Ca2+]i ( r =0.82) of the endothelium. ANG II (10− 8 M) also inhibited both phases of the [Ca2+]i response generated by bradykinin (BK, 10− 7 M), 835 ± 201 versus 159 ± 30 nM (peak phase) and 169 ± 26 versus 103 ± 14 nM (plateau phase) (means ± SE). Luminal ANG II reduced BK (10− 7 M)-stimulated plateau [Ca2+]i from 180 ± 40 to 134 ± 22 nM without causing vasoconstriction. Abluminal ANG II added to the bath after luminal application further reduced [Ca2+]i to 113 ± 9 nM and constricted the vessels. After thapsigargin (TG) pretreatment, ANG II (10− 8 M) caused [Ca2+]i to fall from 352 ± 149 to 105 ± 37 nM. This effect occurred at a threshold ANG II concentration of 10− 10 M and was maximal at 10− 8 M. ANG II inhibited both the rate of Ca2+ entry into [Ca2+]i-depleted endothelia and the rate of Mn2+ entry into [Ca2+]i-replete endothelia. In contrast, ANG II raised [Ca2+]i in the medullary thick ascending limb and outer medullary collecting duct, increasing [Ca2+]i from baselines of 99 ± 33 and 53 ± 11 to peaks of 200 ± 47 and 65 ± 11 nM, respectively. We conclude that OMDVR endothelia are unlikely to be the source of ANG II-stimulated NO production in the medulla but that interbundle nephrons might release Ca2+-dependent vasodilators to modulate vasomotor tone in vascular bundles.

Renal medullary blood flow: its measurement and physiology

1986 ◽  
Vol 64 (7) ◽  
pp. 873-880 ◽  
Author(s):  
W. A. Cupples
Keyword(s):  
Blood Flow ◽  
Renal Medulla ◽  
Vascular Bundles ◽  
Medullary Blood Flow ◽  
Vasa Recta ◽  
Countercurrent Exchange ◽  
Renal Medullary Blood Flow ◽  
Urinary Concentrating Ability ◽  
Velocity Tracking ◽  
Uptake Method

The vasculature of the mammalian renal medulla is complex, having neither discrete input nor output. There is also efficient countercurrent exchange between ascending and descending vasa recta in the vascular bundles. These considerations have hampered measurement of medullary blood flow since they impose pronounced constraints on methods used to assess flow. Three main strategies have been used: (i) indicator extraction; (ii) erythrocyte velocity tracking; and (iii) indicator dilution. These are discussed with respect to their assumptions, requirements, and limitations. There is a consensus that medullary blood flow is autoregulated, albeit over a narrower pressure range than is total renal blood flow. When normalized to gram tissue weight, medullary blood flow in the dog is similar to that in the rat, on the order of 1 to 1.5 mL∙min−1∙g−1. This is considerably greater than estimated by the radioiodinated albumin uptake method which has severe conceptual and practical problems. From both theoretical and experimental evidence it ssems that urinary concentrating ability is considerably less sensitive to changes in medullary blood flow than is often assumed.

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