Identifying renal medullary neighborhoods--when do distances matter?

Identifying renal medullary neighborhoods--when do distances matter?
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识别肾髓质邻近区域——距离何时很重要?

DOI:
10.1152/ajprenal.00692.2012
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发表时间:
2013
期刊:
American journal of physiology. Renal physiology
影响因子:
--
通讯作者:
Weinstein,AlanM
Weinstein,AlanM
中科院分区:
--
文献类型:
--
作者:
Weinstein,AlanM

文献摘要

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RENAL ANATOMISTS are special: few in number, but capable of providing enduring scientific contributions. Memorable contributions include the comparative biology by Sperber, the ultrastructural anatomy of tubules by Maunsbach or Pfaller, and of glomeruli by Kriz, or the injection studies defining renal vascular anatomy by Beeuwkes. There is little doubt that each of these workers believed that their obsession with anatomic detail was fueled by the conviction that understanding function begins with delineating structure. To this roster, I would add Pannabecker and colleagues, who have, over the last decade, provided an extraordinary view of the renal inner medulla. That view derives from the combination of immunohistochemical staining of structures within medullary slices, as developed in the Wade laboratory (7), and computer reconstruction to derive a full axial image (8). I confess to showing our medical students their early images with this technique (9), simply because it is such a tour de force. There is also no doubt that Pannabecker and colleagues believed that their effort serves the cause of deciphering the urine concentrating mechanism (UCM). The classic view of the renal inner medulla recognizes steep axial concentration gradients, but relatively homogenous interstitial composition at any given level. This view was rooted in the micropuncture observations of Gottschalk (3), who documented osmotically identical fluids within blood vessels, descending Henle limbs (DHL), and collecting ducts (CD) at any single inner medullary level within the antidiuretic kidney. This observation provided a crucial simplifying assumption in the central core model of Stephenson (10), in which all tubule segments experienced the same environment, namely, a wellmixed vascular and interstitial compartment. This view propagated into subsequent medullary models from other workers. Unfortunately, the UCM field has been plagued by an inability to devise medullary simulations, which can rationalize the steep axial medullary gradient while also being true to measured tubule properties. Contemporaneous with the anatomic studies of Pannabecker et al., the Laytons began to develop medullary simulations that could accommodate this new level of detail. They fashioned an outer medullary model, in which each slice was comprised of four distinct regions, each containing different tubular and vascular structures, and with a distinct interstitial solute composition (4, 5). In collaboration with Pannabecker and Dantzler, they fashioned an inner medulla model with two distinct regions (6). However, with respect to the UCM, outer medullary regionalization provided only a 16% increase in CD osmolality, and inner medullary regionalization actually diminished concentrating ability. A notable turn in this story came when Edwards focused attention on microvascular oxygen transport. In the outer medullary model, it turned out that regionalization of oxygen was huge, predicting a 40-to 50-mmHg PO2 gradient between the vascular bundle and the tubules (1, 2). There is as yet no O2 transport model for the inner medulla.