THEORY OF SOLUTE AND WATER TRANSPORT ACROSS EPITHELIA

跨上皮的溶质和水运输理论

• 批准号: 3229080
• 负责人: ALAN M WEINSTEIN
• 金额: $ 10.1万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-08-01 至 1993-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3229080
• 关键词: biological fluid transport; carbonates; chloride channels; computer simulation; epithelium; gallbladder; glucose transport; hydrogen channel; ionophores; mathematical model; membrane permeability; membrane potentials; micropuncture; osmosis; phosphates; potassium channel; renal tubular transport; sodium channel; solute; urea; water

Mathematical models are formulated that represent an epithelium as a system of compartments and bounding membranes and permit the computer simulation of normal and pathological states. This project also undertakes the analysis of simplified, approximate, mathematical models, which may be used in the interpretation of experimental data. Comparison of the approximate analytical models with the detailed computer simulation is used to assess the range of applicability of the simpler models. The major aim for the next period of investigation is the completion of a model of the proximal nephrovascular unit - including proximal tubule, glomerulus, and peritubular capillary. The model tracks the concentrations and fluxes of Na+, K+, H+, Cl-, carbonate ion, secondary hydrogen phosphate ion, primary hydrogen phosphate ion, glucose and urea. The primary focus of this simulation is the study of the proximal tubule sodium reabsorption: the transepithelial pathways and driving forces of sodium transport and the mechanisms by which physical factors modulate this reabsorption. In particular, this is an effort to quantify the effects of luminal and peritubular factors which mediate the balance between glomerular filtration and proximal reabsorption. The second focus is the representation of proximal tubule bicarbonate reabsorption: mechanisms of transport defined in cell membrane systems are to be examined in the context of a tubule model, in simulations of the acid-base disturbances. Of particular interest is the role of the proximal nephron in the maintenance of metabolic alkalosis - defining the interplay of decreased glomerular filtration rate, extracellular volume depletion, and increased peritubular pH. A second aim for the next investigational period is the representation of the cortical collecting tubule. This model will be developed in a step-wise fashion from simulations of toad and turtle urinary bladder. It will be used to explore the interaction of tubule flow, acid-base states, and sodium avidity on potassium transport by this nephron segment.

建立了将上皮细胞表示为系统的数学模型 隔室和边界膜，并允许计算机模拟 正常的和病态的。该项目还承担了 分析可能使用的简化的、近似的数学模型 在解释实验数据时。近似值的比较 使用带有详细计算机模拟的分析模型来评估 较简单模型的适用范围。的主要目标是 下一阶段的调查是完成近端的模型 肾血管单位--包括近端小管、肾小球和 肾小管周围毛细血管。该模型跟踪了大气中的 Na+，K+，H+，Cl-，碳酸盐离子，二次磷酸氢离子，初级 磷酸氢离子、葡萄糖和尿素。这件事的主要焦点是 模拟是近端小管钠重吸收的研究： 跨上皮细胞钠转运途径和驱动力与血管内皮细胞 物理因素调节这种重吸收的机制。在……里面 具体地说，这是一项努力，以量化卢米纳和 调节肾小球滤过平衡的肾小管周围因子 和近端的重吸收。第二个焦点是 近端小管重吸收碳酸氢盐：明确的转运机制 在细胞膜系统中，将在小管的背景下进行检查 模型，用于酸碱紊乱的模拟。特别的 兴趣是近端肾单位在维持肾功能中的作用。 代谢性碱中毒--定义肾小球减少的相互作用 滤过率、细胞外容量耗竭和肾小管周围增加 PH值。下一个调查期的第二个目标是代表 大脑皮层集合管。这一模型将在一个 从模拟蟾蜍和乌龟的膀胱开始循序渐进的方式。它 将被用来探索小管流、酸碱状态、 钠亲和力对肾单位段钾离子转运的影响。