THEORETICAL ANALYSIS OF SOLUTE & H2O TRANSPORT IN KIDNEY

这个持续项目的总体目标是将实验 关于膜水平上的水和溶质输送到一个可预测的 在两个实验设计中都有用的全肾功能模型 和病人管理。在此期间，重点是处理 钠、钾、尿素和水分及其受ADH和醛固酮的调控。 具体目标是： 1.建立粗大的Henle氏环升支模型(TAHL)。这个模型， 基于蟾蜍膀胱和近端小管(PT)的模型，将包括两者 细胞和细胞旁通路和下列变量：Na+，K+， 氯离子、尿素、静水压力、电势和体积流量；它 还可包括附加变量H+、HCO3+、HPO42-、H2PO4-、NH4+、 和葡萄糖，并将利用线性非平衡热力学(净) 形式主义来描述通量。主要目标将是了解 Na~+、K~+、Cl~-和NH_4~+在根尖和壁上的跨壁通量 基侧膜转运系统。另一个将是为 ADH和利尿剂对心尖共转运系统的靶向作用。 2.将TAHL模型和PT模型合并为一个中央 皮质和外髓的核心模型。扩展的模型将是 用于解释皮质微穿孔数据和某些间隙数据， 尤其是来自隔离的灌流肾。 3.建立大脑皮层集合管模型。通过包括 富含碳酸酐酶(CA)的嵌合细胞，这将是第一个 细胞异质上皮的模型。该模型将用于 探索K+的处理，H+的分泌，HCO3-的分泌，水分的吸收和 它们在实验隔离和灌流中的控制和相互作用 微管，也将被纳入中央核心模型的一个 皮质肾单位。 4.建立DHL模型和AHL模型。 亨勒环的细肢，包括细胞和细胞旁 小路。这些模型将被用来探索骑自行车的假设 从AHL到DHL的钾产生内髓内浓度 渐变。 5.将延髓的双肾单位模型推广到a)包括扩展的 分段模型和b)纳入 延髓的建筑组织；以及开发和利用 参数估计的新方法。

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+, Cl-, 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+, Cl- 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.