THEORETICAL ANALYSIS OF SOLUTE & WATER TRANSPORT IN MAMMALIAN KIDNEYS

溶质的理论分析

• 批准号: 6411699
• 负责人: JOHN STEPHENSON
• 金额: $ 1.29万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-12-01 至 2001-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6411699
• 关键词: biological products; biomedical resource; computers; proteins; technology /technique

The overall goal of this work is to synthesize experimental data at the membrane and molelcular level into predictive mathematical models of the mammalian kidney that are useful in understanding both its normal and diseased function. The mammalian kidney consists of a large number of units, the nephrons, operating in parallel. Each nephron is a tube approximately 1 cm long and 10 to the -3 power cm in diameter. The closed end is wrapped around a specialized knot of capillaries to form the glomerulus; the open ends merge to empty into the ureter and thence the bladder. The first step in urine formation is the expression of a protein and cell-free filtrate of blood. As this glomerular filtrate flows down the nephron it is modified by the selective reabsorption of most of the solutes and water and the selective secretion of other solutes to form the final urine. By varying the composition of the final urine, the composition of the interstitial fluid bathing the cells of the body is maintained within the narrow limits compatible with life. From experiments on isolated perfused tubules, a great deal is known about the transport properties of the individual renal tubules, and from whole animal experiments a great deal is known about overall function of the kidney. Lacking is a coherent theory that links microscopic function with overall function. The general method we have devised for modeling this intricate system is to solve the differential equations describing volume and solute flow in the individual tubules against assumed values of solute concentrations and hydrostatic pressure in the vascular interstitial space. Transmural solute and water fluxes computed for the tubes are then substituted into the differential equations for the space. If these are satisfied to some specified tolerance, we have a solution. If not, a correction to the assumed concentrations is computed by a Newton type method. The scheme is iterated until a satisfactory solution is obtained. Our current research is evolving toward more realistic models along two parallel paths: l) Incorporation of more details of the renal anatomy. Here we are moving from models in which the interstitial space is assumed to be radially well mixed toward models in which both the radial and axial distribution of structures are considered. 2) Incorporation of more details of transtubular transport. Our current kidney models describe fluxes of solute and water from tubular lumen to surrounding interstitial space by treating the tubular wall as a single membrane and describing fluxes through it by the phenomenology of irreversible thermodynamics. In models of individual segments this description has been replaced by one that considers the details of transport through cells and intracellular space. These detailed tubular models are being introduced into the whole kidney models.

这项工作的总体目标是综合实验数据 在膜和分子水平上， 哺乳动物肾脏的模型，有助于理解 它的正常和病态功能。 哺乳动物的肾脏由 大量的单位，肾单位，并行运作。 每个 肾单位是一个长约1厘米，直径为10的-3次方厘米的管 直径. 封闭端缠绕在一个特殊的结上， 毛细血管形成肾小球;开放的末端合并成 输尿管和膀胱 尿液形成的第一步 是血液中蛋白质和无细胞滤液的表达。 作为 肾小球滤液向下流到肾单位， 大多数溶质和水的选择性重吸收， 其他溶质的选择性分泌形成最终的尿液。 通过 改变最终尿液的组成， 沐浴身体细胞的间质液维持在 与生命相容的狭窄界限。 从孤立的实验 灌流小管，大量的是已知的运输性能 的个体肾小管，并从整个动物实验， 关于肾脏的整体功能，我们知道很多。 缺 将微观功能与整体功能联系起来的连贯理论 功能 我们设计的建模的一般方法 复杂的系统是解决微分方程描述 体积和溶质流量在个别小管对假设 的溶质浓度和静水压力的值， 血管间隙 土壤溶质和水通量 然后将为管计算的值代入差分， 空间的方程。 如果这些满足某些特定的 宽容，我们有一个解决方案。 如果不是，则对假设的 通过牛顿型方法计算浓度。 该方案 迭代直到得到满意的解。 我们目前 研究正沿着沿着两条平行的方向朝着更现实的模型发展 路径：l）并入肾解剖的更多细节。 这里 我们从假设间隙空间 径向混合良好的模型，其中径向和 考虑结构的轴向分布。 2)掺入 更多经前庭转运的细节。 我们目前的肾脏模型 描述溶质和水从管腔到周围的通量 通过将管状壁处理为单个膜 并通过不可逆的现象学来描述通过它的通量 热力学 在单个段的模型中，该描述具有 被一个考虑运输细节的方法所取代， 细胞和细胞内空间。 这些详细的管状模型是 被引入到整个肾脏模型中。