Layton Anita T, Vallon Volker, Edwards Aurélie
Department of Mathematics, Duke University, Durham, North Carolina;
Departments of Medicine and Pharmacology, University of California San Diego, La Jolla, California, and San Diego Veterans Affairs Healthcare System, San Diego, California.
Am J Physiol Renal Physiol. 2016 Dec 1;311(6):F1378-F1390. doi: 10.1152/ajprenal.00293.2016. Epub 2016 Oct 5.
The goal of this study was to investigate water and solute transport, with a focus on sodium transport (T) and metabolism along individual nephron segments under differing physiological and pathophysiological conditions. To accomplish this goal, we developed a computational model of solute transport and oxygen consumption (Q ) along different nephron populations of a rat kidney. The model represents detailed epithelial and paracellular transport processes along both the superficial and juxtamedullary nephrons, with the loop of Henle of each model nephron extending to differing depths of the inner medulla. We used the model to assess how changes in T may alter Q in different nephron segments and how shifting the T sites alters overall kidney Q Under baseline conditions, the model predicted a whole kidney T/Q , which denotes the number of moles of Na reabsorbed per moles of O consumed, of ∼15, with T efficiency predicted to be significantly greater in cortical nephron segments than in medullary segments. The T/Q ratio was generally similar among the superficial and juxtamedullary nephron segments, except for the proximal tubule, where T/Q was ∼20% higher in superficial nephrons, due to the larger luminal flow along the juxtamedullary proximal tubules and the resulting higher, flow-induced transcellular transport. Moreover, the model predicted that an increase in single-nephron glomerular filtration rate does not significantly affect T/Q in the proximal tubules but generally increases T/Q along downstream segments. The latter result can be attributed to the generally higher luminal [Na], which raises paracellular T Consequently, vulnerable medullary segments, such as the S3 segment and medullary thick ascending limb, may be relatively protected from flow-induced increases in Q under pathophysiological conditions.
本研究的目的是调查水和溶质转运,重点关注不同生理和病理生理条件下单个肾单位各节段的钠转运(T)和代谢。为实现这一目标,我们建立了一个大鼠肾脏不同肾单位群体溶质转运和氧消耗(Q)的计算模型。该模型代表了浅表肾单位和近髓肾单位上皮细胞及细胞旁的详细转运过程,每个模型肾单位的亨氏袢延伸至髓质内层的不同深度。我们使用该模型评估T的变化如何改变不同肾单位节段的Q,以及T位点的转移如何改变整个肾脏的Q。在基线条件下,该模型预测全肾的T/Q(表示每消耗1摩尔O所重吸收的Na摩尔数)约为15,预计皮质肾单位节段的T效率显著高于髓质节段。浅表肾单位和近髓肾单位节段的T/Q比值总体相似,但近端小管除外,浅表肾单位的T/Q比近髓肾单位高约20%,这是由于近髓近端小管管腔内流量较大,导致流量诱导的跨细胞转运增加。此外,该模型预测单肾单位肾小球滤过率的增加不会显著影响近端小管的T/Q,但通常会增加下游节段的T/Q。后一结果可归因于管腔内较高的[Na],这会增加细胞旁转运。因此,在病理生理条件下,诸如S3节段和髓质厚升支等脆弱的髓质节段可能相对免受流量诱导的Q增加的影响。