MECHANISM OF RENAL ACID-BASE HOMEOSTASIS

本建议中概述的研究的主要目标是 更充分地阐明肾脏在全身性疾病中的整体作用， 酸碱平衡 在过去的几年里， 旨在调查负责的基本机制 尿酸化和调节这一过程中的几个 nephorn段，维持高CO2紧张局势， 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。 的 本申请建议继续我们的研究， 酸化过程的基本机制，但地方 主要侧重于研究受损的机制， 在实验性酸紊乱模型中的尿酸化- 碱和/或电解质平衡。 为了完成这些 提出了四个具体项目：1）评估 远端肾动脉实验模型中的酸化参数 肾小管性酸中毒和选择性醛固酮缺乏。 （二） 延髓节段性氨转运的评价 皮质肾单位，以确定氨转移的作用， 尿氨中Henle袢至集合管 在全身钾平衡变化期间的排泄， 盐皮质激素缺乏和输尿管梗阻。 第三章 评价跨上皮pH梯度在 通过近曲小管调节H+分泌。 四、 H ~+分泌的机制和动力学评价 人刷状缘膜囊泡体外培养及比较 这些发现与其他的紫菀属物种。 一个重要 本研究中提出的体内微穿刺研究的优点 应用是我们实验室的能力， 通过调查观察到的孤立的类似问题 体外灌流小管。 酸碱平衡的维持是 肾脏的重要生理作用。 控制该 必须理解过程以充分阐明这些功能。 研究紊乱性酸化模型，如肾 肾小管性酸中毒，可能会提高我们对这种疾病的理解， 人类，并提高我们早期诊断这种疾病的能力， 疾病的进程。

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.