The Revised Starling Hypothesis: Modeling the impact of the glycocalyx on vascular refilling during ultrafiltration in humans

Abstract

The glycocalyx lines systemic capillaries and influences the distribution of osmotic forces across the capillary between the intravascular and interstitial compartments. By creating a pericapillary space between the capillary and the interstitium with a low osmotic pressure, the predicted and measured water flux at the distal end of systemic capillaries is outward under physiological conditions – contrary to the prediction of the traditional Starling model of capillary fluid transport. This has led to a ‘revised’ Starling model in which the predicted the movement of water from the capillary into the interstitium is consistently outward, and the return of water from the interstitial compartment necessary to maintain intravascular volume occurs nearly exclusively through the lymphatic system. We developed a methematicl model of the revised Starling Hypothesis that is applicable to the whole body in the special circumstance of hemodialysis, where the contributions of renal function to blood volume regulation may be ignored, and the total input and output of water and solutes are controlled and measured as part of the process of hemodialysis. We created a revised, two compartment (vascular+interstitial space), Starling model using the quantitative model of Facchini et al. (Microvasc. Res. 94:52-63, 2014) that describes capillary transport through the glycocalyx (albeit as normalized dimensionless values). We modelled the return of interstitial water to the vascular space through lymphatic flow based on the interstitial pressure (Possenti et al., Micro. Vasc. Res. 122:101-110, 2019), and we estimated the interstitial pressure based upon the formulation of Chapple et al. (Comp. Meth, and Prog. In Biomed. 41: 33-54,1993). We used the two-compartment model (intravascular and extravascular spaces) developed by de los Reyes et al. (J. Theoret. Biol. 390:146-155, 2016) to analyze transcapillary fluxes based on the traditional Starling model, and we embedded the description of fluxes across glycocalyx developed by Facchini et al. to decribe the fluxes of solutes and water across the glycocalyx and peri-glycocalyx/sub-capillary space and added control of lymphatic function within this two-compartment model to create a revised Starling model. The traditional and revised models were evaluated using data from periods of ultrafiltration in which the hematocrit (Crit-line), body weight and measured fluid input or ultrafiltrate removed were measured, and we compared the predicted fluxes of solvent and solutes across the capillary and through the lymphatic system between the traditional and revised Starling models. The two models lead to dramatically different predictions—all of the fluid transported out of the capillary must come back via the lymphatics according to the revised Starling model. This places vital importance upon the lymphatic flow during vascular refilling when blood volume is reduced and must be repleted to maintain stable cardiac function. Partially funded by the Renal Research Institute This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.