Three-dimensional functional reconstruction of inner medullary thin limbs of Henle's loop

Pannabecker, Thomas L.; Abbott, Diane E.; Dantzler, William H.

doi:10.1152/ajprenal.00285.2003

Cited by 83 publications

(108 citation statements)

References 24 publications

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“…The ATL is assumed to contribute to the higher osmolality in the middle to deep IM by passive NaCl absorption, urea permeability, and water impermeability (41,42). This assumption is corroborated by the findings from a study in 3D functional reconstruction of the IM in rats (43).…”

Section: Discussionmentioning

confidence: 66%

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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Section: Discussionmentioning

confidence: 66%

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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“…Tissue embedded in Spurr resin was cut into 1-m-thick sections with a Leica EM UC6 or Leica Ultracut UCT ultramicrotome. Tissue em- Immunofluorescence histochemistry was performed as previously described (37)(38)(39). Before antibody application, Spurr resin was etched by applying to each slide 300 l of a solution of 5 g NaOH, 5 ml 100% ethanol, and 5 ml propylene oxide for 3 min (24), followed by extensive washing, first with ethanol and then with distilled water.…”

Section: Methodsmentioning

confidence: 99%

Architecture of the human renal inner medulla and functional implications

Wei

Rosen

Dantzler

et al. 2015

American Journal of Physiology-Renal Physiology

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The architecture of the inner stripe of the outer medulla of the human kidney has long been known to exhibit distinctive configurations; however, inner medullary architecture remains poorly defined. Using immunohistochemistry with segment-specific antibodies for membrane fluid and solute transporters and other proteins, we identified a number of distinctive functional features of human inner medulla. In the outer inner medulla, aquaporin-1 (AQP1)-positive long-loop descending thin limbs (DTLs) lie alongside descending and ascending vasa recta (DVR, AVR) within vascular bundles. These vascular bundles are continuations of outer medullary vascular bundles. Bundles containing DTLs and vasa recta lie at the margins of coalescing collecting duct (CD) clusters, thereby forming two regions, the vascular bundle region and the CD cluster region. Although AQP1 and urea transporter UT-B are abundantly expressed in long-loop DTLs and DVR, respectively, their expression declines with depth below the outer medulla. Transcellular water and urea fluxes likely decline in these segments at progressively deeper levels. Smooth muscle myosin heavy chain protein is also expressed in DVR of the inner stripe and the upper inner medulla, but is sparsely expressed at deeper inner medullary levels. In rodent inner medulla, fenestrated capillaries abut CDs along their entire length, paralleling ascending thin limbs (ATLs), forming distinct compartments (interstitial nodal spaces; INSs); however, in humans this architecture rarely occurs. Thus INSs are relatively infrequent in the human inner medulla, unlike in the rodent where they are abundant. UT-B is expressed within the papillary epithelium of the lower inner medulla, indicating a transcellular pathway for urea across this epithelium.

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“…They tend to lie about as far as possible from any CD in any cluster. This arrangement continues as tubules and blood vessels descend along the corticopapillary axis (Figure 3, B-D) (35,37,39,41,42). In contrast, the ATLs and ascending vasa recta (AVR) are arranged both inside (intracluster region) and outside (intercluster region) each CD cluster (Figures 2, 4, and 5A) (39,40).…”

Section: Three-dimensional Lateral and Vertical Relationships Of Tubumentioning

confidence: 97%

“…Second, the chloride channel ClC-K1 (the rat homolog of human ClC-Ka) begins to be expressed abruptly in the AQP1-negative portion of each DTL about 150-200 mm above the bend, thereby defining a prebend segment, and continues to be expressed throughout the ATL ( Figure 2) (37). The expression of ClC-K1 throughout each ATL apparently reflects the extremely high chloride permeability found in this segment (16).…”

Section: Three-dimensional Reconstructions Of Thin Limbs Of the Loopsmentioning

confidence: 99%

“…Although, as noted above, an earlier model failed to demonstrate the significance of the three-dimensional structure (28), this model was based on very limited knowledge of that structure. Therefore, during the past decade, we have worked to develop a detailed understanding of the three-dimensional relationships of the tubules and vessels in the IM of the rat kidney by analysis of digital reconstructions of these structures produced from 1-mm serial sections (35)(36)(37)(38)(39)(40)(41)(42). For this purpose, we labeled the various tubules and vessels with antibodies to structure-and segment-specific proteins, usually transporters or channels.…”

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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Three-dimensional functional reconstruction of inner medullary thin limbs of Henle's loop

Cited by 83 publications

References 24 publications

Three-Dimensional Reconstruction of the Mouse Nephron

Three-Dimensional Reconstruction of the Mouse Nephron

Architecture of the human renal inner medulla and functional implications

Urine-Concentrating Mechanism in the Inner Medulla

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