肾微血管滤过的流体动力学模型:生理和血流动力学变化对肾小球大小选择性的影响

IF 1.9 4区 医学 Q3 HEMATOLOGY Microcirculation Pub Date : 2022-07-25 DOI:10.1111/micc.12779
Numpong Punyaratabandhu, Panadda Dechadilok, Wannapong Triampo, Pisut Katavetin
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引用次数: 1

摘要

目的肾尿形成的第一步是超滤过肾小球屏障。其纳米结构的变化与肾病综合征有关。通过采用低雷诺数流体动力学和阻碍转运理论的数学模型,研究了与糖尿病肾病(DN)相关的生理和血流动力学因子改变对肾小球过电选择性的影响。方法将肾小球毛细血管表示为具有多层壁的圆柱形管网络。肾小球基底膜(GBM)是一种纤维介质,具有双峰纤维大小。上皮狭缝纤维间距遵循对数正态分布,基于报道的电子显微图具有最高的分辨率。内皮窗内充满糖胺聚糖(GAGs)大小的纤维。包括纤维-大分子的空间和水动力相互作用的影响。针对糖尿病肾病,在计算中采用的生理和血流动力学因素是已报道的健康人和早期但明显的糖尿病肾病患者的生理和血流动力学因素。大分子浓度以对流扩散方程的有限元解的形式得到。结果沿毛细管长度计算的平均筛分系数与在大多数溶质半径的人类研究中得到的筛分系数吻合得很好。GBM增厚和狭缝膈的丧失几乎不影响肾小球的透性选择性。然而,内皮腔内GAG体积分数的降低显著增加了大分子滤过。肾血浆流速(RPF)升高、肾小球高血压和管腔渗透压降低导致筛分系数轻微降低。这些效应随着大分子大小的增加而被放大。结论肾小球高血压和肿瘤压降低可降低肾小球大分子滤过。然而,与DN相关的RPF减少和肾小球屏障结构的改变增加了溶质筛分。高血糖引起的gag损伤可能是影响肾小球大小选择性的最重要因素。
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Hydrodynamic model for renal microvascular filtration: Effects of physiological and hemodynamic changes on glomerular size-selectivity

Objective

The first step in renal urine formation is ultrafiltration across the glomerular barrier. The change in its nanostructure has been associated with nephrotic syndromes. Effects of physiological and hemodynamic factor alterations associated with diabetic nephropathy (DN) on glomerular permselectivity are examined through a mathematical model employing low-Reynolds-number hydrodynamics and hindered transport theory.

Methods

Glomerular capillaries are represented as networks of cylindrical tubes with multilayered walls. Glomerular basement membrane (GBM) is a fibrous medium with bimodal fiber sizes. Epithelial slit fiber spacing follows a lognormal distribution based on reported electron micrographs with the highest resolution. Endothelial fenestrae are filled with fibers the size of glycosaminoglycans (GAGs). Effects of fiber-macromolecule steric and hydrodynamic interactions are included. Focusing on diabetic nephropathy, the physiological and hemodynamic factors employed in the computation are those reported for healthy humans and patients with early-but-overt diabetic nephropathy. The macromolecule concentration is obtained as a finite element solution of the convection-diffusion equation.

Results

Computed sieving coefficients averaged along the capillary length agree well with ficoll sieving coefficients from studies in humans for most solute radii. GBM thickening and the loss of the slit diaphragm hardly affect glomerular permselectivity. GAG volume fraction reduction in the endothelial fenestrae, however, significantly increases macromolecule filtration. Increased renal plasma flow rate (RPF), glomerular hypertension, and reduction of lumen osmotic pressure cause a slight sieving coefficient decrease. These effects are amplified by an increased macromolecule size.

Conclusion

Our results indicate that glomerular hypertension and the reduction in the oncotic pressure decreases glomerular macromolecule filtration. Reduction of RPF and changes in the glomerular barrier structure associated with DN, however, increase the solute sieving. Damage to GAGs caused by hyperglycemia is likely to be the most prominent factor affecting glomerular size-selectivity.

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来源期刊
Microcirculation
Microcirculation 医学-外周血管病
CiteScore
5.00
自引率
4.20%
发文量
43
审稿时长
6-12 weeks
期刊介绍: The journal features original contributions that are the result of investigations contributing significant new information relating to the vascular and lymphatic microcirculation addressed at the intact animal, organ, cellular, or molecular level. Papers describe applications of the methods of physiology, biophysics, bioengineering, genetics, cell biology, biochemistry, and molecular biology to problems in microcirculation. Microcirculation also publishes state-of-the-art reviews that address frontier areas or new advances in technology in the fields of microcirculatory disease and function. Specific areas of interest include: Angiogenesis, growth and remodeling; Transport and exchange of gasses and solutes; Rheology and biorheology; Endothelial cell biology and metabolism; Interactions between endothelium, smooth muscle, parenchymal cells, leukocytes and platelets; Regulation of vasomotor tone; and Microvascular structures, imaging and morphometry. Papers also describe innovations in experimental techniques and instrumentation for studying all aspects of microcirculatory structure and function.
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