MECHANISM OF RENAL ACID-BASE HOMEOSTASIS

这项建议中概述的研究的主要目标是 更全面地阐明肾脏在全身性疾病中的整体作用 酸碱同源异型藻。在过去的几年里，研究一直是 设计调查的基本机制(S)负责 尿酸化及其在几种疾病中的调节作用 肾节段，维持升高的二氧化碳压力在 肾皮质，以及尿Cos张力作为一种 终末肾单位H+分泌的定性指标。这个 本申请书建议继续对……进行调查 酸化过程的基本机制，但地方 重视对精神损害机制的研究 实验性神经性酸中毒模型的尿酸 碱和/或电解质平衡。为了实现这些目标 目标提出四个具体项目：1)评估 远端肾实验模型中的酸化参数 小管性酸中毒和选择性醛固酮缺乏症。2) 髓内节段性氨转运的评价 皮质肾单位确定氨转移的作用 尿氨中Henle到集合管的环 体内钾平衡变化时的排泄， 盐皮质激素缺乏和输尿管梗阻。3) 跨上皮pH梯度在血管内皮细胞损伤中的作用 近曲小管对H+分泌的调节。4) 细菌H+分泌机制和动力学的研究进展 人刷状缘膜囊泡的体外培养及比较 这些发现适用于其他哺乳动物物种。一个重要的 本研究中提出的体内微穿孔研究的优势 应用程序是我们实验室中扩展这些功能的能力 通过调查观察到孤立的类似问题 体外灌流小管。维持酸碱平衡的方法是 肾脏的一个重要的生理作用。对这一切的控制 必须理解过程才能充分阐明这些功能。 疯狂酸化模型的研究，如肾脏 小管性酸中毒，可能会提高我们对本病的认识 人类，并提高我们早期诊断这种情况的能力 疾病的病程。

The primary objective of the studies outlined in this proposal is to elucidate more fully the overall role of the kidney in systemic acid-base homeostais. During previous years studies have been designed to investigate the basic mechanism(s) responsible for urinary acidification and the regulation of this process in several nephorn segments, the maintenance of elevated CO2 tensions in the renal cortex, and the utility of urinary COs tension as a qualitative index of H+ secretion by the terminal nephron. The present application proposes to continue our investigation of fundamental mechanisms of the acidification process, but places major emphasis on investigation of the mechanism of impaired urinary acidification in experimental models of deranged acid- base and/or electrolyte balance. In order to accomplish these goals four specific projects are proposed: 1) Evaluation of acidification parameters in experimental models of distal renal tubular acidosis and selective aldosterone deficiency. 2) Evaluation of segmental ammonia transport in medullary and cortical nephrons to determine the role of ammonia transfer from the loop of Henle to the collecting duct in urinary ammonium excretion during changes in systemic potassium balance, mineralocorticoid deficiency and ureteral obstruction. 3) Evaluation of the role of transepithelial pH gradients in the regulation of H+ secretion by the proximal convoluted tubule. 4) Evaluation of the mechanism and kinetics of H+ secretion in human brush border membrane vesicles in vitro and to compare these findings with other mammaliam species. An important advantage of the in vivo micropuncture studies proposed in this application is the capability in our laboratory of extending these observations by investigation similar questions in the isolated perfused tubule in vitro. The maintenance of acid-base balance is an essential physiological role of the kidney. The control of this process must be understood to fully elucidate these functions. The study of models of deranged acidification, such as renal tubular acidosis, may enhance our understanding of this disease in humans, and improve our ability to diagnose this condition early in the course of the disease.