THEORETICAL ANALYSIS OF SOLUTE & H2O TRANSPORT IN KIDNEY

这个持续项目的总体目标是整合 水和溶质在膜上传输的实验数据 水平进入整个肾功能的预测模型，即 对于实验设计和患者管理都很有用。 在此期间，重点是 Na、K、尿素和 水及其受 ADH 和醛固酮的控制。 具体目标是： 1. 模拟亨利氏袢升肢粗（TAHL）。 这个 模型，基于蟾蜍膀胱和近端小管（PT）模型， 将包括细胞和细胞旁途径以及 以下变量：Na、K、C1-、尿素、静水压、 电势和体积流量；它还可能包括 附加变量 H 、 HCO3 、 HPO42- 、 H2PO4- 、 NH4 和 葡萄糖并将利用线性非平衡热力学 (NET) 描述通量的形式主义。 主要目标是 了解 Na 、 K 、 C1- 和 NH4 的跨壁通量 顶膜和基底外侧膜运输系统的术语。 另一个是模拟 ADH 和利尿剂的目标作用 关于心尖协同运输系统。 2. 将TAHL模型与PT模型合并 形成皮质和外髓质的中央核心模型。 的 扩展模型将用于解释皮质微穿刺 数据和某些清除数据，特别是来自隔离的数据 灌注肾脏。 3. 模拟皮质集合管（CCT）。 通过包括 富含碳酸酐酶（CA）的嵌入细胞，这将是 第一个细胞异质上皮模型。 的 模型将用于探索 K 处理、H 分泌、HCO3- 分泌、吸水及其控制和相互作用 实验分离和灌注的小管，也将 纳入皮质肾单位的中央核心模型。 4. 开发降序（DHL）和升序（AHL）模型 亨利环的细肢，包括细胞和 细胞旁路。 这些模型将用于探索 假设钾从 AHL 循环到 DHL 产生 内髓浓度梯度。 5. 将髓质的两个肾单位模型扩展到 a) 包括 扩展分段模型和 b) 纳入额外的 髓质结构组织的细节；并到 开发和利用新的参数估计方法。

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.