Studies in Renal Hemodynamics

肾血流动力学研究

• 批准号: 0616345
• 负责人: E Bruce Pitman
• 金额: $ 21.67万
• 依托单位: SUNY at Buffalo
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0616345&HistoricalAwards=false
• 关键词: Studies; Renal; Hemodynamics

The principal functional unit of the kidney is the nephron, a capillary tuft connected to a renal tubule. There are about 1 million nephrons in the human kidney, and a significant fraction of these may be closely coupled through the microvasculature. Through computational and analytical methods, two major research questions will be addressed: how does coupling of a large number of nephrons affect the dynamics of the collective system, and how can uncertainty, in modeling paradigms and in the parameters inherent in modeling, be incorporated into computational simulations of renal blood flow. Coupling arises in vivo, and must be included in models. Uncertainty in model parameters is a recognized consequence of our limited knowledge of the systems under study; uncertainty regarding the limitations of the very models used in our studies may alter major findings identified in the analysis. Answering these two questions will provide important steps in linking simulations with experiment. Because of the nephron's role in filtering blood, it is frequently assumed, either explicitly or implicitly, that the behavior observed in a single nephron is representative of whole kidney function. This assumption has proven valid and useful in many contexts. However, the coupling of two individual nephrons is known to induce dynamics of the pair that is not present in the individual. Massive coupling of nephrons, as it is thought to occur in the kidney, will likely elicit collective behavior from the system that cannot be guessed beforehand. Likewise, idealized modeling and specification of model parameters may not accurately reflect the environment in which the nephron exists in vivo. This project brings new mathematical ideas to the study of renal blood flow regulation, a complex biological system that plays an important role in human health.

肾脏的主要功能单元是肾单位，是连接到肾小管的毛细管簇。人肾脏中大约有100万个肾单位，其中很大一部分可能通过微脉管系统紧密结合。通过计算和分析方法，将解决两个主要的研究问题：大量肾接的耦合如何影响集体系统的动力学，以及在建模范式和建模固有的参数中如何将不确定性纳入肾血流的计算模拟中。耦合在体内产生，必须包括在模型中。模型参数的不确定性是我们对正在研究的系统的有限了解的公认结果；关于我们研究中使用的模型的局限性的不确定性可能会改变分析中确定的主要发现。回答这两个问题将为将模拟与实验联系起来提供重要步骤。 由于肾单位在过滤血液中的作用，经常被认为是明确或隐式的，在单个肾单位中观察到的行为代表了整个肾脏功能。 在许多情况下，这一假设已被证明有效且有用。 但是，已知两个单独的肾单位的耦合会诱导个人中不存在的这对动力学。人们认为在肾脏中发生的大规模肾结核可能会引起无法事先猜测的系统的集体行为。同样，模型参数的理想化建模和规范可能无法准确反映在体内存在肾单位的环境。该项目将新的数学思想带入了肾脏血流调节的研究，这是一种复杂的生物系统，在人类健康中起着重要作用。