PHYSICO-CHEMICAL ASPECTS OF RENAL TRANSPORT PROCESSES

拟议的研究旨在发展准确的和 肾功能两要素的预测理论。其中的第一个 涉及肾小球毛细血管选择性限制的机制 对某些大分子的过滤。蛋白尿由一种 这种滤过屏障的破坏是肾脏疾病的一个标志，而且 更好地理解正常和改变的肾小球选择性 承诺提供对潜在疾病机制的洞察，以及 从而为监测患者的病情发展提供新的方法。 理论模型将被开发或扩展以描述 不同大小、电荷和分子构型的大分子通过 多孔膜。膜将被表示为阵列或 圆柱状毛孔或纤维网络。体外实验将是 用来检验这些理论的要素，并用来表征测试 大分子。这些理论将被用来解释 肾小球选择性在大鼠实验性肾脏疾病研究中的应用 在各种人类肾小球疾病中。 对过滤后的碳酸氢盐重新吸收速度的调整 肾脏为人体提供了一种主要的防御系统 酸碱平衡。二氧化碳分压的最新测量 (二氧化碳)在大鼠肾脏中的含量已经提出了一些重要的问题 关于肾内处理二氧化碳和碳酸氢盐的问题， 为拟议的研究提供第二个重点。理论模型将 旨在使观察到的二氧化碳浓度差异合理化 管周毛细血管和动脉血，以及小管和动脉之间 肾皮质表面的微血管。这些模型将涉及 详细考虑传质、化学动力学和化学 血管和肾小管的平衡。两个版本的比较 大鼠实验结果的理论预测应该能提供 对当前关于重碳酸盐重吸收的假设的敏感测试。 拟议的研究将涉及化学工程师之间的合作， 肾脏生理学家和临床肾病学家。

The proposed research is aimed at the development of accurate and predictive theories for two elements of renal function. The first of these concerns the mechanisms whereby glomerular capillaries selectively restrict the filtration of certain macromolecules. Proteinuria resulting from a disruption of this filtration barrier is a hallmark of kidney disease, and a better understanding of normal and altered glomerular selectivity promises to provide insight into the underlying disease mechanisms, as well as to offer new methods for monitoring the progress of patients. Theoretical models will be developed or extended to describe movement of macromolecules of varying size, charge and molecular configuration through porous membranes. The membranes will be represented either as an array or cylindrical pores or as a network of fibers. In vitro experiments will be used to examine elements of these theories and to characterize test macromolecules. The theories will be used to interpret measurements of glomerular selectivity in studies of experimental renal disease in rats, and in various human glomerulopathies. Adjustments in the rate at which filtered bicarbonate is reabsorbed by the kidney provide one of the body's major defenses against disruptions of acid-base balance. Recent measurements of carbon dioxide partial pressure (PCO2) in the rat kidney have raised a number of important questions concerning the intrarenal handling of carbon dioxide and bicarbonate, which provide a second focus for the proposed research. Theoretical models will be developed to rationalize observed differences in PCO2 between peritubular capillary and arterial blood, and among tubules and microvessels on the surface of the renal cortex. These models will involve detailed consideration of mass transfer, chemical kinetics, and chemical equilibria in blood vessels and renal tubules. Comparison of the theoretical predictions with experimental results in the rat should provide a sensitive test of current hypotheses concerning bicarbonate reabsorption. The proposed research will involve collaboration among chemical engineers, renal physiologists and clinical nephrologists.