THEORETICAL ANALYSIS OF SOLUTE & H2O TRANSPORT IN KIDNEY

溶质的理论分析

• 批准号: 3230155
• 负责人: JOHN L STEPHENSON
• 金额: $ 24.73万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1984
• 资助国家: 美国
• 起止时间: 1984-01-01 至 1993-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3230155
• 关键词: aldosterone; ammonia; apical membrane; basolateral membrane; biological fluid transport; body fluid osmolarity; carbonate dehydratase; diuretics; electrical potential; electrolyte balance; excretion; glucose; hormone regulation /control mechanism; hydrostatic pressure; ion transport; kidney circulation; mathematical model; membrane permeability; model design /development; nonblood rheology; radiotracer; renal cortex; renal medulla; renal tubular transport; scintillation cameras; solute; urea; vasopressins; water; water flow

The overall aim in this continuing project is to integrate experimental data on water and solute transport at the membrane level into a predictive model of whole kidney function that is useful in both experimental design and patient management. During this period the focus is on the handling of Na, K, urea, and water and their control by ADH and aldosterone. The specific aims are: 1. To model thick ascending limb of Henle's loop (TAHL). This model, based on models to toad bladder and proximal tubule (PT), will include both cellular and paracellular pathways and the following variables: Na+, K+, C1-, urea, hydrostatic pressure, electric potential, and volume flow; it may also include the additional variables H+, HCO3+, HPO42-, H2PO4-, NH4+, and glucose and will utilize a linear non-equilibrium thermodynamic (NET) formalism to describe fluxes. A primary objective will be to understand transmural fluxes of Na+, K+, C1- and NH4+ in terms of apical and basolateral membrane transport systems. Another will be to model the target action of ADH and diuretics on the apical co-transport system. 2. To incorporate the TAHL model together with the PT model into a central core model of the cortex and outer medulla. The extended model will be used to interpret cortical micropuncture data and certain clearance data, particularly from the isolated perfused kidney. 3. To model the cortical collecting tubule (CCT). By including the carbonic anhydrase (CA)-rich intercalated cell, this will be the first model of a cellularly heterogeneous epithelium. The model will be used to explore K+ handling, H+ secretion, HCO3- secretion, water absorption and their control and interaction in the experimentally isolated and perfused tubule, and will also be incorporated into the central core model of a cortical nephron. 4. To develop models of descending (DHL) and ascending (AHL) thin limbs of the loop of Henle that include cellular and paracellular pathways. These models will be used to explore the hypothesis that cycling of potassium from AHL to DHL generates the inner medullary concentration gradient. 5. To extend a two nephron model of the medulla to a) include the extended segmental models and b) to incorporate additional details of the architectural organization of the medulla; and to develop and to utilize new methods of parameter estimation.

这个持续项目的总体目标是整合 水和溶质在膜中迁移的实验数据 进入全肾功能的预测模型，即 在实验设计和病人管理方面都很有用。 在此期间，重点放在处理钠、钾、尿素和 水以及ADH和醛固酮对水的控制。 具体目标是： 1.建立粗大的Henle氏环升支模型(TAHL)。这 模型，以蟾蜍膀胱和近端小管(PT)模型为基础， 将包括细胞和细胞旁途径，以及 以下变量：Na+、K+、Cl-、尿素、静水压力、 电势和体积流量；它还可以包括 附加变量H+、HCO3+、HPO42-、H2PO4-、NH4+和 葡萄糖和将利用线性非平衡热力学 (NET)形式主义来描述通量。主要目标将是 了解Na~+、K~+、C_1~-和NH_4~+的跨壁通量 顶端和基底侧膜运输系统的术语。 另一种是模拟ADH和利尿剂的靶向作用 在心尖联合传输系统上。 2.将TAHL模型与PT模型结合起来 形成皮质和外髓的中央核心模型。这个 将使用扩展模型来解释皮质微穿刺术 数据和某些净空数据，特别是来自孤立的 灌流的肾脏。 3.建立大脑皮层集合管模型。通过包括 富含碳酸酐酶(CA)的嵌入细胞，这将是 细胞异质上皮的第一个模型。这个 模型将用于探索K+的处理、H+的分泌、HCO3- 细菌的分泌、吸水及其调控和相互作用 实验中分离和灌流的小管，也将 合并到皮质肾单位的中央核心模型中。 4.建立DHL模型和AHL模型。 亨勒环的细枝，包括细胞和 细胞旁通路。这些模型将用于探索 假设钾从AHL循环到DHL产生 髓内浓度梯度。 5.将延髓的双肾单位模型推广到a)包括 扩展的分段模型以及b)合并其他 延髓的建筑组织的细节；以及 开发和利用参数估计的新方法。