Modeling Solute Transport and Urine Concentrating Mechanism in the Rat Kidney

描述(申请人提供)：模拟大鼠肾脏中的溶质转运和尿液浓缩机制本研究的目的是使用数学模型来研究肾脏转运和动力学的各个方面，最终目的是更好地了解哺乳动物的尿液浓缩机制和溶质循环。肾小管和微血管的数学模型以及求解微分方程组的显式分析和数值方法将用于下列研究：(I)将建立一个代表肾小管和血管相对位置的大鼠肾脏髓质的尿液浓缩机制模型，并用于检验假设：大鼠肾内髓质的尿液浓缩机制是由间质中的溶质混合引起的，该机制可能由四个逆流系统组成，基于肾小管和血管之间特定的三维关系。(Ii)内髓内三维组织的一个特殊方面将被考虑：由集合管、上升的直肠血管和上升的细长肢体为边界的间质结节空间。一个隔室模型将被用来检验这样的假设，即这些微域可能是特定溶质的靶向传递和相互作用的基本混合节点。(Iii)建立尿液浓缩机制的动力学模型，用于跟踪溶质(特别是尿素)的循环，研究溶质的停留时间，并研究尿素负荷的瞬时影响。最终目的是为了更好地了解尿素在肾髓质中的循环，以及在生理和病理生理条件下，髓质三维结构和逆流肾小管充血在尿素管理中的作用。(4)用大鼠外髓内纹层的切片模型，结合粗大升肢细胞上皮运输过程的详细描述，来研究粗大升肢的能量供应和钠的运输。 公共卫生相关性：模拟大鼠肾脏的溶质转运和尿液浓缩机制的意义。这项提议旨在更全面和定量地了解肾脏产生比血浆更集中的尿液的方法(即，单位体积含有比血浆更多的溶质)。这项基础研究与公众健康相关，因为已知肾脏尿液浓缩能力的异常会引起、促成、作为一系列重要的紊乱和疾病的后果或与之一起发生，包括体内水和盐的异常滞留或丧失。

DESCRIPTION (provided by applicant): Modeling Solute Transport and Urine Concentrating Mechanism in the Rat Kidney The goal of this proposal is to use mathematical modeling to investigate aspects of the renal trans- port and dynamics, with an ultimate goal of gaining a better understanding of the mammalian urine concentrating mechanism and solute cycling. Mathematical models of renal tubules and microvessels, coupled with explicit analysis and numerical methods for solving dierential equations, will be used in the following studies: (I) A model of the urine concentrating mechanism of the renal medulla in the rat kidney that represents the relative positions of the tubules and vessels will be developed and used to test the hypothesis: the urine concentrating mechanism of the renal inner medulla of the rat kidney arises from solute mixing in the interstitium, and that mechanism may be comprised of four countercurrent systems, based on the specic 3-dimensional relationships among tubules and vessels. (II) A specic aspect of the 3-dimensional organization in the inner medulla will be considered: interstitial nodal spaces that are bordered by collecting ducts, ascending vasa recta, and ascending thin limbs. A compartment model will be used to test the hypothesis that these microdomains may be essential mixing nodes for targeted delivery and interaction of specic solutes. (III) A dynamic model of the urine concentrating mechanism will be developed and used to track solute (urea, in particular) cycling, to study residence times of solutes, and to study the transient eects of urea loads. The ultimate goal is to gain a better understanding of urea recycling in the renal medulla, and the role of medullary 3-dimensional structure and countercurrent tubular conguration in urea management under physiologic and pathophysiologic conditions. (IV) A slice model of the inner stripe of the rat outer medulla, together with a detailed representation of the epithelial transport processes of the thick ascending limb cell, will be used to study the energy eciency and sodium transport of the thick ascending limbs. PUBLIC HEALTH RELEVANCE: Modeling Solute Transport and Urine Concentrating Mechanism of the Rat Kidney Significance. This proposal aims to provide a more complete and quantitative understanding of the means by which the kidney can produce urine that is more concentrated than blood plasma (i.e., that contains more solute per unit volume than does blood plasma). This basic research is relevant to public health, because abnormalities of the kidney's urine concentrating capability are known to cause, contribute to, be a consequence of, or occur along with, a number of important disorders and diseases, including abnormal body water and salt retention or loss.