MATHEMATICAL MODELS OF RENAL DYNAMICS

肾脏动力学的数学模型

• 批准号: 2444034
• 负责人: HAROLD E LAYTON
• 金额: $ 14.07万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-01-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2444034
• 关键词: electrolyte balance; fluidity; glomerular filtration; juxtaglomerular apparatus; kidney circulation; kidney function; mathematical model; model design /development; oscillatory blood flow; renal glomerulus; renal medulla; renal tubular transport; renal tubule; sensory feedback

This proposal is for the continuation of several research projects that use mathematical modeling to integrate and interpret experimental findings so that a better understanding of kidney function be can attained. More specifically, this proposal is directed to understanding renal processes that exhibit complex dynamic behaviors and/or complex spatial interactions, at the levels of microvessels, tubules, and nephron populations. Hypotheses for renal hemodynamic control will be tested by analyzing the coupling of the tubuloglomerular feedback (TGF) oscillator with vasomotion of the afferent arteriole (AA) and with adjoining TGF oscillators, by constructing a minimal dynamic and spatially distributed model of the AA to study the coordination and propagation of vasoconstriction arising from major determinants of vaso-activity, and by constructing a detailed model of nitric oxide action on vessel walls to determine its role in maintaining total segmental resistance. Hypotheses for the urine concentrating mechanism will be tested by analyzing the single-solute avian mechanism and by investigating potential mammalian inner medullary mechanisms that operate via descending limb hypertonicity. The principal mathematical methods that will be employed are explicit analysis, numerical methods for solving ordinary and partial differential equations, and the immersed boundary technique. The nature of the inner medullary urine concentrating mechanism remains an unsolved mystery of normal renal function. Many disorders of whole-body water balance result from inappropriate or deranged regulation of the concentrating mechanism. The afferent arteriole and the juxtaglomerular apparatus are major regulatory sites for blood flow and nephron load. A more complete analysis of the influences that come to bear at these sites, and their interactions, could greatly enrich our understanding of blood pressure control and renal electrolyte management. Moreover, these intrarenal control processes are deranged in several important renal diseases, including hypertension and diabetes, which are major causes of chronic renal failure in humans.

该建议是为了继续进行几个研究项目 使用数学建模来整合和解释实验发现 这样就可以更好地了解肾脏功能。 更多的 具体而言，该提案旨在理解肾脏过程 表现出复杂的动态行为和/或复杂的空间 相互作用，微血管，小管和肾单位的水平 人群。 通过分析肾脏血流动力学控制的假设将测试 与血管舒张症的肾小管晶状体反馈（TGF）振荡器的耦合 通过传入小动脉（AA）和与毗邻的TGF振荡器 构建AA的最小动态和空间分布的模型 研究血管收缩的协调和传播 血管活性的主要决定因素，并通过构建详细的模型 一氧化氮在容器壁上的作用，以确定其在 保持总节段阻力。 尿液的假设 浓缩机制将通过分析单层测试 通过研究潜在的哺乳动物内髓质 通过降肢高渗性运行的机制。 校长 将要使用的数学方法是明确的分析， 用于求解普通和部分微分方程的数值方法， 和沉浸的边界技术。 内髓质尿液浓缩机制的性质仍然是一种 正常肾功能的未解决的奥秘。 全身的许多疾病 水平平衡是由于不适当或失调的调节 集中机制。 传入小动脉和近链球菌 设备是血流和肾载负荷的主要调节部位。 一个 对在这些站点上产生的影响的更完整分析， 他们的互动可以极大地丰富我们对血液的理解 压力控制和肾脏电解质管理。 而且，这些 培育内控制过程在几个重要的肾脏中被扰乱 疾病，包括高血压和糖尿病，这是主要原因 人类的慢性肾衰竭。