Modeling Loss of Microvascular Wall Homeostasis during Glycocalyx Deterioration and Hypertension that Impacts Plasma Filtration and Solute Exchange

Abstract

Abstract:The fiber matrix of the surface glycocalyx layer internally coating the endothelial cells and plugging the intercellular clefts is crucial for microvascular wall homeostasis. Disruption of the glycocalyx is found in clinical conditions characterized by microvascular and endothelial dysfunction such as atherosclerosis, diabetes mellitus, chronic renal failure and cerebrovascular disease. Shedding of its components may also occur during oxidative stress and systemic inflammatory states including septis. In this work, we investigate the effects of glycocalyx degradation, either due to enzymatic digestion or to agonist recruitment, on plasma filtration and solute extravasation. We also take into account the possibility of a physiological or pathological increase in blood pressure, as in hypertensive zones such as pre-and post-stenotic blood vessels. Our mathematical model shows that a seriously damaged glycocalyx produces an augmentation of flux of both solvent and solute, thus losing its role of transport barrier and macro-molecular sieve, in agreement with experimental evidence. Similarly, hypertension causes an increase in both volume and solute fluxes, also according to physiological findings. The combination of glycocalyx deterioration and hypertension further raises plasma and solute fluxes, potentially leading in most severe cases to edema and hemorrhage, as in the case of diabetes.

Vascular refilling coefficient is not a good marker of whole-body capillary hydraulic conductivity in hemodialysis patients: insights from a simulation study

“…The classic approach allowed us to refer directly to the discussed works by Tabei et al as well as to other studies mentioned above, all of which employed the classic Starling principle. In order to reflect the extended Starling principle, our model would need to be substantially extended by either: (1) adding a sub-glycocalyx compartment (or possibly more sub-compartments of the interstitial fluid, as proposed by Curry and Michel 21 ) with the description of convection and diffusion of macromolecules between that compartment and the interstitial fluid, which would depend on the flow rate (velocity) of the filtration flow through the orifices in the junction strand, or (2) employing a spatially distributed model of pressure and protein concentration fields behind the glycocalyx, as done by Hu and Weinbaum 28 , or (3) modelling the capillary wall as a two-membrane system (glycocalyx + endothelium), as done by Facchini et al 49 , 50 . Any of the above approaches would increase substantially the level of complexity of our already relatively complex model, but, more importantly, as outlined below, we believe that the possible error introduced by using the classic approach should not affect our conclusions with respect to the deficiencies of Kr.…”

A time-dependent multi-layered mathematical model of filtration and solute exchange, the revised Starling principle and the Landis experiments

“…In our recent work, we showed that in order to properly model transport of proteins across microvessel walls and the loss of the barrier effect consequent to glycocalyx damage, a two-layer model should be used, with the internal layer representing the glycocalyx and the external one the endothelial cells. 26,39 However, in applications, a single-layer model is typically used, requiring the definition of equivalent properties encapsulating the effects of both glycocalyx and of the surrounding endothelial cells. To properly address the single-layer case we suggest computing the reflection coefficient by means of the expression proposed by Sugihara-Seki and Fu: 10 (16) while ℓ p eq and ℓ d eq are obtained by imposing that at the initial steady-state condition volumetric and solute fluxes are the same in the two-layer model, considered here with discontinuous (step) transition of the physical properties, and in the single-layer homogeneous equivalent model: (17) where (p c ,Π c ) and (p o ,Π o ) are the initial values of the pressures at r = 0 and within the interstitium at r = 1, respectively.…”