Modeling Fluid Dynamics and Solute Transport in the Kidney

该项目的总体目标是利用分析和计算数学来更好地理解肾小管流动对肾中水和溶质运输的复杂流体动力学的影响。采用浸入式边界方法，建立数学模型来表示近端微绒毛边缘微管周围的流体动力学，并表示乳头状集管中发生蠕动收缩的管状流动。所得到的模型将用于研究双向流固相互作用对沿近端小管和沿收集管的溶质和水输送的影响。此外，非线性优化技术将通过评估各种调节机制在稳态恢复中的有效性，进一步用于细胞稳态的生理研究。如果一个人被困在海里好几天，他应该喝海水来解渴吗？答案取决于这个对象是人（不要！）还是老鼠（没问题，喝吧！）原因是海水的渗透压（即总溶质浓度）高于人体所能产生的最大尿液渗透压。相比之下，一只小老鼠的尿液浓度是海水的两倍。这可能很难相信，但一些哺乳动物产生高浓度尿液的机制尚不清楚。该项目将使用数学分析和计算技术来回答肾脏生理学中的一些基本和重要问题：肾乳头的蠕动收缩如何影响肾脏的浓缩机制？沿部分肾单位（肾中的小管）发现的刷状边缘微绒毛如何影响肾脏中的溶质运输？为了在不断变化的环境中生存，肾细胞改变其运输特性的最有效方法是什么？这些问题的答案对于全面了解肾脏生理学、肾脏病理生理学和其他自动调节机制至关重要。

The overall goal of this project is to use analysis and computational mathematics to gain a better understanding of the effects of the complex fluid dynamics, frequently exhibited by renal tubular flows, on renal transport of water and solutes. Using the immersed boundary approach, mathematical models will be built to represent the fluid dynamics around the proximal tubule brush border microvilli, and to represent the tubular flow in a papillary collecting duct undergoing peristaltic contractions. The resulting models will be used to study the effects of the two-way fluid-structure interactions on solute and water transport along the proximal tubule and along the collecting duct. Additionally, nonlinear optimization techniques will be used to further the physiological investigation of cellular homeostasis, by assessing the effectiveness of various regulatory mechanisms in homeostatic recovery.If one is stranded in the ocean for days, should one drink the sea water to quench one's thirst? The answer depends on whether the subject is a person (don't!) or a rat (no problem, drink away!). The reason is that the osmolality (i.e., total solute concentration) of sea water is higher than the maximum urine osmolality that can be produced by a human. In contrast, a little rat can produce a urine twice as concentrated as sea water. It may be hard to believe, but the mechanism by which some mammals produce highly concentrated urine is not well understood. This project will use mathematical analysis and computational techniques to answer a number of basic and important questions in renal physiology: How do the peristaltic contractions of the renal papilla impact the concentrating mechanism of the kidney? How do the brush border microvilli, which are found along portions of the nephrons (little tubules in the kidney), affect solute transport in the kidney? What are the most effective ways for kidney cells to change aspects of its transport properties in order to survive in its ever-changing surroundings? The answers to those questions are crucial in an overall understanding of renal physiology, renal pathophysiology, and other autoregulatory mechanisms.