Abstract
The semipermeable capillary walls not only enable the removal of excess body water and solutes during hemodialysis (HD) but also provide an essential mechanism for maintaining cardiovascular homeostasis. Here, we investigated transcapillary transport processes on the whole-body level using the three-pore model of the capillary endothelium with large, small and ultrasmall pores. The transcapillary transport and cardiovascular response to a 4-h hemodialysis (HD) with 2 L ultrafiltration were analyzed by simulations in a virtual patient using the three-pore model of the capillary wall integrated in the whole-body compartmental model of the cardiovascular system with baroreflex mechanisms. The three-pore model revealed substantial changes during HD in the magnitude and direction of transcapillary water flows through small and ultrasmall pores and associated changes in the transcapillary convective transport of proteins and small solutes. The fraction of total capillary hydraulic conductivity attributed to ultrasmall pores was found to play an important role in the transcapillary water transport during HD thus influencing the cardiovascular response to HD. The presented model provides a novel computational framework for a detailed analysis of microvascular exchange during HD and as such may contribute to a better understanding of dialysis-induced changes in blood volume and blood pressure.
Highlights
The semipermeable capillary walls enable the removal of excess body water and solutes during hemodialysis (HD) and provide an essential mechanism for maintaining cardiovascular homeostasis
The changes in water filtration across ultrasmall pores are opposite to those for small pores, which is due to the fact that the reduced leakage of negatively charged proteins during HD entails the increased transcapillary flow of “other anions”, which in the model are assumed to move according to the electroneutrality condition—this leads to the extra osmotic pressure gradient developing across ultrasmall pores, which draws more vascular water through this transport channel
As far as we know, the model presented in this study is the first compartmental model of the human cardiovascular system with baroreflex regulation integrated with the model of whole-body water and solute transport that takes into account the structural properties of the capillary endothelium
Summary
The semipermeable capillary walls enable the removal of excess body water and solutes during hemodialysis (HD) and provide an essential mechanism for maintaining cardiovascular homeostasis. The fraction of total capillary hydraulic conductivity attributed to ultrasmall pores was found to play an important role in the transcapillary water transport during HD influencing the cardiovascular response to HD. On the whole-body level, under steady-state conditions, there is a net filtration of water and solutes (including proteins) from the blood to the tissues, which is compensated by the equivalent lymphatic absorption of interstitial fluid and its transport back to the circulation in the form of lymph[2,3]. During hemodialysis (HD), when relatively large quantities of water and solutes are removed from the patient’s body over a few hours, the normal transcapillary filtration becomes progressively reduced and eventually reverses into absorption of fluid from the interstitial space in order to compensate for the reduced blood volume to maintain cardiovascular stability (vascular refilling m echanism[4,5,6,7]). Under non-steady conditions, such as during HD, the magnitude and direction of water and solute flow through different pores may vary substantially
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