Mathematical Models of Renal Dynamics

肾脏动力学的数学模型

• 批准号: 7097752
• 负责人: HAROLD E LAYTON
• 金额: $ 26.27万
• 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 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7097752
• 关键词: animal data; glomerular filtration; hemodynamics; kidney circulation; kidney function; mathematical model; model design /development; oscillatory blood flow; renal glomerulus; renal medulla; renal tubular transport; renal tubule; saluresis; urine

DESCRIPTION (provided by applicant): 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 so affected; (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.

描述（由申请人提供）：该建议是用于继续使用数学建模的研究项目，以更完整地理解肾脏中发现的两种调节机制：肾小管胶质细胞反馈（TGF）机制和尿液浓度机制。肾小管小管和微血管的数学模型，再加上求解微分方程的明确分析和方法，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，并将其作为将NACI递送的调节机制增加到远端naci递送到远端NEPHRON，以增加对远端NEPHRON的递送； （ii）在高血压大鼠的肾单位中发现的不规则TGF介导的振荡来自多种振荡模式；从不稳定，在关键参数中，这些偶发性和显着影响定期振荡。以及受到影响的肾单位之间的耦合； （iii）肾脏内髓质的尿液浓缩机制来自间质中的被动溶质混合；该机制是通过在Henle环，Henle Cascade的循环以及小管和血管之间特定的三维关系中的专门轴向分割而有效的。意义。该提案旨在提供对肾脏在肾脏中控制和调节血流的手段的更完整和定量的理解，以及肾脏可以产生比血浆更浓缩的尿液的手段（即，每单位量含有比血浆更高的单位溶质溶质）。这项基础研究与公共卫生有关，因为肾脏的血流控制失调以及肾脏尿液浓缩能力的异常是众所周知，会导致，导致，导致或发生多种重要疾病和疾病，包括多种重要的疾病和疾病，包括异常体内水和盐的疾病或盐保留或流失，高血压，糖尿病和糖尿病和受伤。