Modeling the impact of the revised starling hypothesis on vascular refilling during ultrafiltration in humans

The physical attributes of continuous capillaries, the glycocalyx, and endothelial tight junctions, influence the distribution of forces that affect transcapillary solvent and solute transport. The traditional Starling hypothesis does not account for the effects of transcapillary solvent flux on the protein content of the pericapillary space, whereas the "Revised" Starling model (RSM) incorporates the impact of the glycocalyx and endothelial tight junctions on transcapillary solute flux, which results in an inhomogeneous distribution of oncotic pressures across the capillary wall. We compared the regulation of intravascular volume during dialysis using two, 2-compartment models: one based on the traditional Starling model (TSM) and the other based on the RSM. We evaluated the two models using data from two patients undergoing hemodialysis during which the ultrafiltration rate was varied to perturb the system and reveal the dynamics of transcapillary and lymphatic solvent and solute (protein) fluxes. Both models fit the observed changes in hematocrit and calculated changes in plasma and interstitial volumes well. However, the predicted mechanisms whereby intravascular volume and mass balance were maintained differed significantly: the RSM predicted that all interstitial fluid and protein were returned to the intravascular space by lymphatic flow, whereas the TSM predicted that interstitial fluid and protein were returned to the intravascular space from both lymphatic flow and fluxes of solvent and protein from the interstitial space into the venous end of the capillary. Thus, the RSM emphasizes the central role of lymphatic return on the rate of vascular refilling from the interstitial space when ultrafiltration reduces blood volume.NEW & NOTEWORTHY A novel computer model of vascular refilling, which incorporated the impact of glycocalyx and endothelial tight junctions, demonstrated that fluid and protein leave the vascular space through the capillary wall and return to the circulation exclusively through lymphatic mechanisms during ultrafiltration during dialysis. The vascular refill rate, capillary exit + ultrafiltration, and lymphatic return can be estimated during ultrafiltration to compare predicted vascular dynamics in either the traditional or revised Starling hypothesis.