Modeling Solute Transport and Urine Concentrating Mechanism in the Rat Kidney

描述（由申请人提供）：大鼠肾脏中溶质运输和尿液浓缩机制的建模本提案的目标是使用数学建模来研究肾脏运输和动力学的各个方面，最终目标是更好地理解哺乳动物尿液浓缩机制和溶质循环。肾小管和微血管的数学模型，结合明确的分析和求解微分方程的数值方法，将用于以下研究：(I)将建立大鼠肾脏肾髓质的尿液浓缩机制模型，该模型代表了小管和血管的相对位置，并用于验证假设：大鼠肾内髓质的尿浓缩机制源于间质溶质的混合，基于小管和血管之间特定的三维关系，该机制可能由四个逆流系统组成。（II）将考虑髓质内三维组织的一个特定方面：由集合管、上升的直血管和上升的细肢包围的间质淋巴结空间。一个隔室模型将用于测试这些微域可能是特定溶质靶向递送和相互作用的基本混合节点的假设。（III）将开发尿液浓缩机制的动态模型，并用于跟踪溶质（特别是尿素）循环，研究溶质的停留时间，并研究尿素负荷的瞬时效应。最终目的是为了更好地了解肾髓质的尿素循环，以及在生理和病理生理条件下，肾髓的三维结构和逆流小管凝聚在尿素管理中的作用。（IV）采用大鼠外髓内条纹切片模型，详细描述厚升肢细胞上皮转运过程，研究厚升肢的能量效率和钠转运。

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.