MATHEMATICAL MODELS OF RENAL DYNAMICS

肾脏动力学的数学模型

• 批准号: 6634955
• 负责人: HAROLD E LAYTON
• 金额: $ 22万
• 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 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6634955
• 关键词: angiotensin /renin /aldosterone hypertension; electrolyte balance; glomerular filtration; juxtaglomerular apparatus; kidney circulation; mathematical model; model design /development; oscillatory blood flow; renal glomerulus; renal medulla; renal tubular transport; renal tubule; urine

DESCRIPTION (Adapted from the Applicant's Abstract): This proposal is for the continuation of research projects that use the technique of mathematical modeling to gain a more complete understanding of 2 regulatory mechanisms found in the kidney: the tubuloglomerular feedback (TGF) mechanism and the urine concentrating mechanism. Mathematical models of renal tubules and micro-vessels will be used to investigate the following hypotheses: (I) regular, sustained TGF-mediated oscillations in tubular flow differentially regulate sodium and water delivery to the distal tubule and enhance sodium excretion; and the emergence of TGF-mediated oscillations is mediated and regulated through its integration with other intrarenal control mechanisms, notably the renin-angiotensin-aldosterone system; (II) under appropriate conditions, irregular TGF-mediated oscillations emerge from excitation of multiple oscillatory modes and tend to enhance sodium and water delivery to the distal tubule and sodium excretion; and (III) tubular heterogeneity in renal tubules (notably, the large fraction of thin limbs of loops of Henle that exhibit alternating subsegments of differing morphological and functional type) have an important functional role in the urine concentrating mechanism of the renal inner medulla. The principal mathematical methods that will be employed in these studies are explicit analysis and numerical methods for solving differential equations. The TGF system, which includes functional aspects of the afferent arteriole and the juxtaglomerular apparatus, is a critical regulatory mechanism for renal blood flow and nephron load. A more complete understanding of this system would enrich our understanding of blood pressure control and renal electrolyte management which are deranged in several important renal diseases, including hypertension and diabetes. 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 urine concentrating mechanism.

描述（根据申请人的摘要改编）：此提案是针对的 继续使用数学技术的研究项目 建模以获得对发现2种调节机制的更完整理解 在肾脏中：肾小管斜体反馈（TGF）机制和尿液 集中机制。肾小管和微容器的数学模型 将用于调查以下假设：（i）常规，持续 TGF介导的管状流量差异调节钠和 水向远端小管输送并增强钠排泄；和 TGF介导的振荡的出现是通过其介导和调节的 与其他肾内控制机制集成，尤其是 肾素 - 血管紧张素 - 醛固酮系统； （ii）在适当条件下， TGF介导的不规则TGF介导的振荡来自多个的激发 振荡模式，并倾向于增强钠和水向远端的递送 小管和钠排泄物； （iii）肾小管中的管状异质性 （值得注意的是，显示出亨的薄环的狭窄四肢很大一部分 不同形态和功能类型的交替亚侦查）具有 在肾脏的尿液浓缩机制中的重要功能作用 内髓。将采用的主要数学方法 这些研究是用于解决的明确分析和数值方法 微分方程。 TGF系统，其中包括传入小动脉的功能方面 近距离腔，是肾脏的关键调节机制 血流和肾载负荷。对该系统的更完整的理解将 丰富我们对血压控制和肾脏电解质的理解 在几种重要的肾脏疾病中被危险的管理 高血压和糖尿病。内髓质的本质 浓缩机制仍然是正常肾功能的未解决的奥秘。 全身水平平衡的许多疾病是由于不适当或 尿液浓缩机制的混乱调节。