Physiological and Clinical Implications of Medullary Hypoxia

Epstein, F. H.; Brezis, Mayer; Silva, P.; Rosen, Seymour

doi:10.1111/j.1525-1594.1987.tb02711.x

Cited by 26 publications

(21 citation statements)

References 16 publications

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“…Anatomic findings (18,19) have revealed a highly structured organization of tubules and vessels in the rat outer medulla, in which the vasa recta form tightly packed vascular bundles that appear to dominate the histotopography of the outer medulla, especially in the inner stripe, and in which collecting ducts and mTALs are found distant from the vascular bundles. As a result, under experimental conditions resulting in reduced medullary O 2 tension, mTALs are the most injured segments (7,8). Taken together, the high metabolic demands of the mTAL and the low oxygen tension make the efficiency of NaCl transport an important issue.…”

Section: Discussionmentioning

confidence: 99%

Transport efficiency and workload distribution in a mathematical model of the thick ascending limb

Nieves‐Gonzalez

Clausen

Layton

et al. 2013

American Journal of Physiology-Renal Physiology

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The thick ascending limb (TAL) is a major NaCl reabsorbing site in the nephron. Efficient reabsorption along that segment is thought to be a consequence of the establishment of a strong transepithelial potential that drives paracellular Na ϩ uptake. We used a multicell mathematical model of the TAL to estimate the efficiency of Na ϩ transport along the TAL and to examine factors that determine transport efficiency, given the condition that TAL outflow must be adequately dilute. The TAL model consists of a series of epithelial cell models that represent all major solutes and transport pathways. Model equations describe luminal flows, based on mass conservation and electroneutrality constraints. Empirical descriptions of cell volume regulation (CVR) and pH control were implemented, together with the tubuloglomerular feedback (TGF) system. Transport efficiency was calculated as the ratio of total net Na ϩ transport (i.e., paracellular and transcellular transport) to transcellular Na ϩ transport. Model predictions suggest that 1) the transepithelial Na ϩ concentration gradient is a major determinant of transport efficiency; 2) CVR in individual cells influences the distribution of net Na ϩ transport along the TAL; 3) CVR responses in conjunction with TGF maintain luminal Na ϩ concentration well above static head levels in the cortical TAL, thereby preventing large decreases in transport efficiency; and 4) under the condition that the distribution of Na ϩ transport along the TAL is quasi-uniform, the tubular fluid axial Cl Ϫ concentration gradient near the macula densa is sufficiently steep to yield a TGF gain consistent with experimental data. tubuloglomerular feedback; autoregulation; NaCl transport; cell volume regulation ALONG THE THICK ASCENDING limb (TAL) of a short loop of Henle in a rat kidney, active transport of Na ϩ reduces luminal NaCl concentration from ϳ250 to 300 mM at the loop bend to ϳ25 mM at the end of the cortical TAL (cTAL; Refs. 2, 37, 40). Given the low availability of oxygen within the renal medulla and the high metabolic demands of the medullary TAL (mTAL), it appears essential that TAL Na ϩ transport be efficient. TAL cells are believed to attain that efficiency by means of apical Na ϩ uptake that is mediated by the electroneutral NaϪ cotransporter (NKCC2; Refs. 1, 11). Back diffusion of K ϩ through apical K ϩ channels produces a lumen-positive transepithelial potential that drives passive Na ϩ reabsorption through cation-permeable tight junctions. It is thought that this reduces net ATP utilization to a level much lower than what would be required if Na ϩ transport were solely transcellular. However, the above scheme is complicated by several factors. As tubular Na ϩ concentration ([Na ϩ ]) decreases along the TAL, the transepithelial Na ϩ chemical potential reduces, or perhaps reverses, the driving force for paracellular Na ϩ transport. Also, the distribution of Na ϩ transport along the TAL likely influences transport efficiency, especially if luminal [Na ϩ ] approaches low static-head lev...

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Section: Discussionmentioning

confidence: 99%

Transport efficiency and workload distribution in a mathematical model of the thick ascending limb

Nieves‐Gonzalez

Clausen

Layton

et al. 2013

American Journal of Physiology-Renal Physiology

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“…The major site of endothelial cell injury in our model of liver IR predominantly affects the 'outer stripe' of the outer medulla corresponding to the S3 segments of proximal tubule, which is located precisely at the corticomedullary junction. 28,29 The production of several proinflammatory cytokines and adhesion molecules after hepatic IR contributes to the pathophysiology of liver injury. 1,30 We show that as expected, all of the proinflammatory mRNAs examined (TNF-a KC, MCP-1, MIP-2, and ICAM-1) show enhanced expression in liver and kidney after hepatic IR.…”

Section: Discussionmentioning

confidence: 99%

Selective intrarenal human A1 adenosine receptor overexpression reduces acute liver and kidney injury after hepatic ischemia reperfusion in mice

Park

Chen

Kim

et al. 2010

Laboratory Investigation

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“…In many but not all patients, renal blood flow continues to be depressed for several days after completion of the surgery (10 -12). If the decrease in renal blood flow is significant, then injury to the S3 segment of the proximal tubule and the medullary thick ascending limb in the outer medulla may result (13). Ischemia to the outer medulla, coupled with the subsequent reperfusion phase, may injure tubular cells by depleting intracellular ATP; disrupting intracellular calcium homeostasis; generating free radicals; and causing cellular changes that destroy the integrity of the tight junction, apical-basolateral polarity, and cytoskeletal structure.…”

Section: Renal Vasoconstrictionmentioning

confidence: 99%

Could Uric Acid Have a Role in Acute Renal Failure?

Ejaz¹,

Mu²,

Kang³

et al. 2007

Clinical Journal of the American Society of Nephrology

173

111

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Acute renal failure (ARF), induced by either toxins or ischemia, is associated with significant morbidity. The pathogenesis of ARF is complex and is characterized by renal vasoconstriction and oxidative stress in association with tubular and microvascular injury and interstitial inflammation. In many situations, ARF is associated with a rise in serum uric acid as a result of both increased generation and decreased excretion. Although it is widely recognized that markedly elevated levels of uric acid can cause ARF via supersaturation within the tubules with crystallization and intrarenal obstruction ("acute urate nephropathy"), the possibility that uric acid may affect renal outcomes at concentrations that do not lead to tubular obstruction have not been considered. This article reviews both the salutary and the adverse effects of uric acid on biologic processes and presents the hypothesis that hyperuricemia, particularly if chronic and marked, likely represents a true risk factor for ARF. Hyperuricemia also may account for the paradoxic lack of benefit of diuretics in the management of ARF. It is suggested that studies are needed to investigate the role of chronic hyperuricemia on renal outcomes after acute tubular injury.Clin J Am Soc Nephrol 2: 16 -21, 200716 -21, . doi: 10.2215 A cute renal failure (ARF) is observed most commonly after major surgeries; in patients with sepsis; in patients who receive chemotherapy for various malignancies; and after the administration of various nephrotoxins, such as contrast agents or antibiotics. The development of ARF has a significant effect on prognosis. For example, whereas the acute operative and postoperative mortality rate after cardiovascular surgery varies between 1 and 2%, this increases to 10 to 38% if renal insufficiency occurs and to Ͼ50% if dialysis is required (1,2). Therefore, identifying who is at risk for developing ARF and how to prevent it from happening are of paramount interest.

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Physiological and Clinical Implications of Medullary Hypoxia

Cited by 26 publications

References 16 publications

Transport efficiency and workload distribution in a mathematical model of the thick ascending limb

Transport efficiency and workload distribution in a mathematical model of the thick ascending limb

Selective intrarenal human A1 adenosine receptor overexpression reduces acute liver and kidney injury after hepatic ischemia reperfusion in mice

Could Uric Acid Have a Role in Acute Renal Failure?

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