MECHANISM OF RENAL ACID-BASE HOMEOSTASIS

肾酸碱平衡机制

• 批准号: 3229559
• 负责人: THOMAS D DUBOSE
• 金额: $ 7.75万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-07-01 至 1991-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3229559
• 关键词: acid base balance; acidity /alkalinity; acidosis; aldosterone; amiloride; bicarbonates; carbon dioxide tension; carbonate dehydratase; homeostasis; hydrogen transport; kidney metabolism; kidney pharmacology; laboratory rat; lithium; microcalorimetry; microelectrodes; micropuncture; perfusion; renal tubular transport; renal tubule acidosis; respiratory acidosis

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.

本提案中概述的研究的主要目标是 更全面地阐明肾脏在全身系统中的总体作用 酸碱稳态。 在前几年的研究中 旨在研究负责的基本机制 尿酸化以及该过程在几个方面的调节 肾段，维持升高的二氧化碳张力 肾皮质，以及尿 CO 张力作为 终末肾单位 H+ 分泌的定性指标。 这 本申请建议继续我们的调查 酸化过程的基本机制，但地方 重点关注损伤机制的研究 酸紊乱实验模型中的尿液酸化 碱和/或电解质平衡。 为了实现这些 目标提出了四个具体项目： 1) 评估 远端肾实验模型中的酸化参数 肾小管酸中毒和选择性醛固酮缺乏。 2） 髓质和髓质节段氨转运的评价 皮质肾单位确定氨转运的作用 尿铵中亨利氏环至集合管 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。 3） 评估跨上皮 pH 梯度在 近曲小管对 H+ 分泌的调节。 4） H+分泌机制和动力学的评估 人刷状缘膜囊泡体外培养及比较 这些发现与其他哺乳动物物种有关。 一个重要的 本文提出的体内微穿刺​​研究的优点 应用程序是我们实验室扩展这些的能力 通过调查孤立的类似问题来观察 体外灌注肾小管。 酸碱平衡的维持是 肾脏的重要生理作用。 对此的控制 必须理解过程才能充分阐明这些功能。 酸化紊乱模型的研究，例如肾模型 肾小管性酸中毒可能会增强我们对这种疾病的了解 人类，并提高我们早期诊断这种疾病的能力 病程。