Mathematical Models of Renal Dynamics

肾脏动力学的数学模型

基本信息

批准号：
7367019
负责人：
HAROLD E LAYTON
金额：
$ 24.05万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1990
资助国家：
美国
起止时间：
1990-01-01 至 2010-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7367019
关键词：
3-Dimensional Affect Basic Science Behavior Blood Pressure Blood Vessels Blood flow Body Water Cells Characteristics Chemicals Collaborations Compatible Complex Constriction procedure Coupled Coupling Data Decompression Sickness Dependence Diabetes Mellitus Disease Distal Duct (organ) structure Equation Equilibrium Event Exhibits Feedback Frequencies Henle&apos s loop Heterogeneity High Blood Pressure Injury to Kidney Ions Kidney Lateral Limb structure Liquid substance Localized Macula densa Measures Mediating Methods Modeling Movement Nature Nephrons Numbers Osmolalities Pathway interactions Physiological Plasma Population Potential Energy Prevalence Process Public Health Radial Rate Rattus Rectum Reflex action Relative (related person)Renal tubule structure Research Personnel Research Project Grants Resistance Role Series Signal Transduction Site Smooth Muscle Sodium Chloride Solutions Structure of descending limb of Henle&apos s loop Study models Sum System Thick Time Trees Tubular formation Universities Urea Urine Vasocon Water absorption base cell type experimental analysis glomerular filtration hemodynamics heterodyning ilium mathematical model normotensive pressure research study response sensor solute three dimensional structure tongue papilla transmission process vasomotion

项目摘要

This proposal is for the continuation of research projects that use mathematical modeling to gain a more complete understanding of two regulatory mechanisms found in the kidney: the tubuloglomerular feedback (TGF) mechanism and the urine concentrating mechanism. Mathematical models of renal tubules and microvessels, coupled with explicit analysis and methods for solving differential equations, will be used to investigate the following hypotheses: (I) vascular coupling between nephrons increases the propensity for oscillatory dynamics and serves as a regulatory mechanism for increasing NaCI delivery to the distal nephron; (II) irregular TGF-mediated oscillations found in the nephrons of hypertensive rats emerge from multiple oscillatory modes; from lability, in key parameters, that episodically and significantly impacts otherwise regular oscillations; and from coupling between nephrons soaffected; (III) the urine concentrating mechanism of the renal inner medulla arises from passive solute mixing in the interstitium; this mechanism is made effective by specialized axial segmentation in descending limbs of loops of Henle, by a loop of Henle cascade, and by specific three-dimensional relationships among tubules and vessels. Significance. This proposal aims to provide a more complete and quantitative understanding of the means by which blood flow is controlled and regulated within the kidney and of the means by which the kidney can produce urine that is more concentrated than blood plasma (i.e., that contains more solute per unit volume than does blood plasma). This basic research is relevant to public health, because disordered blood flow control by the kidney, and abnormalities of the kidney's urine concentrating capability, are known to cause, contribute to, be a consequence of, or occur along with, a number of important disorders and diseases, including abnormal body water and salt retention or loss, high blood pressure, diabetes, and injury to the kidney.

该建议是为了继续使用数学建模来获得更多的研究项目对肾脏中发现的两种调节机制的完全了解：微管反馈（TGF）机制和尿液浓缩机制。肾小管和微血管的数学模型，再加上明确的分析和方法求解微分方程将用于研究以下假设：（i）肾单位之间的血管耦合增加了振荡动力学的倾向，并充当将NACI递送到远端肾单位的调节机制；（ii）在高血压大鼠的肾脏中发现的不规则TGF介导的振荡来自多个振荡模式；从不稳定，关键参数中，会发作和显着影响否则常规振荡；并通过所谓的肾词之间的耦合；（iii）肾脏内髓质的尿液浓缩机制来自被动溶质混合间质；该机制是通过在降肢中的专门轴向分割而有效的 Henle的循环，通过Henle Cascade的循环，以及通过特定的三维关系小管和容器。意义。该建议旨在提供对血液的手段的更完整和定量的理解流量受到控制和调节，在肾脏内以及肾脏可以产生尿液的手段这比血浆更集中（即，每单位体积的溶质比血液含有更多的溶质等离子体）。这项基础研究与公共卫生有关，因为已知肾脏尿液浓缩能力的肾脏和异常是造成的，有助于与许多重要的疾病和疾病一起发生的结果，包括异常体内水和盐的保留或损失，高血压，糖尿病和肾脏受伤。