Curry Fitzroy E, Michel C Charles
Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, Davis, CA, United States.
Department of Bioengineering, Imperial College London, London, United Kingdom.
Front Cell Dev Biol. 2021 Aug 12;9:729873. doi: 10.3389/fcell.2021.729873. eCollection 2021.
The primary purpose of these investigations is to integrate our growing knowledge about the endothelial glycocalyx as a permeability and osmotic barrier into models of trans-vascular fluid exchange in whole organs. We describe changes in the colloid osmotic pressure (COP) difference for plasma proteins across the glycocalyx after an increase or decrease in capillary pressure. The composition of the fluid under the glycocalyx changes in step with capillary pressure whereas the composition of the interstitial fluid takes many hours to adjust to a change in vascular pressure. We use models where the fluid under the glycocalyx mixes with sub-compartments of the interstitial fluid (ISF) whose volumes are defined from the ultrastructure of the inter-endothelial cleft and the histology of the tissue surrounding the capillaries. The initial protein composition in the sub-compartments is that during steady state filtration in the presence of a large pore pathway in parallel with the "small pore" glycocalyx pathway. Changes in the composition depend on the volume of the sub-compartment and the balance of convective and diffusive transport into and out of each sub-compartment. In skeletal muscle the simplest model assumes that the fluid under the glycocalyx mixes directly with a tissue sub-compartment with a volume less than 20% of the total skeletal muscle interstitial fluid volume. The model places limits on trans-vascular flows during transient filtration and reabsorption over periods of 30-60 min. The key assumption in this model is compromised when the resistance to diffusion between the base of the glycocalyx and the tissue sub-compartment accounts for more than 1% of the total resistance to diffusion across the endothelial barrier. It is well established that, in the steady state, there can be no reabsorption in tissue such as skeletal muscle. Our approach extends this idea to demonstrate that transient changes in vascular pressure favoring initial reabsorption from the interstitial fluid of skeletal muscle result in much less fluid exchange than is commonly assumed. Our approach should enable critical evaluations of the empirical models of trans-vascular fluid exchange being used in the clinic that do not account for the hydrostatic and COPs across the glycocalyx.
这些研究的主要目的是将我们对作为通透性和渗透屏障的内皮糖萼的不断增长的认识，整合到全器官跨血管液体交换模型中。我们描述了毛细血管压力升高或降低后，血浆蛋白跨糖萼的胶体渗透压（COP）差异的变化。糖萼下液体的成分随毛细血管压力同步变化，而组织间液的成分需要数小时才能适应血管压力的变化。我们使用的模型中，糖萼下的液体与组织间液（ISF）的子隔室混合，这些子隔室的体积由内皮细胞间裂的超微结构和毛细血管周围组织的组织学确定。子隔室中的初始蛋白质组成是在存在与“小孔”糖萼途径平行的大孔途径的稳态过滤过程中的组成。成分的变化取决于子隔室的体积以及进出每个子隔室的对流和扩散运输的平衡。在骨骼肌中，最简单的模型假设糖萼下的液体直接与一个组织子隔室混合，该子隔室的体积小于骨骼肌组织间液总体积的20%。该模型对30 - 60分钟内的瞬态过滤和重吸收过程中的跨血管流量设定了限制。当糖萼底部与组织子隔室之间的扩散阻力占内皮屏障总扩散阻力的1%以上时，该模型的关键假设就会受到影响。众所周知，在稳态下，骨骼肌等组织中不会有重吸收。我们的方法扩展了这一观点，以证明血管压力的瞬态变化有利于骨骼肌组织间液的初始重吸收，但导致的液体交换比通常假设的要少得多。我们的方法应该能够对临床中使用的不考虑跨糖萼的静水压和COP的跨血管液体交换经验模型进行批判性评估。
