Modelling the fluid drainage through primary lymphatic valves

Abstract

This study investigates the fluid flow through tissues where lymphatic drainage occurs. Lymphatic drainage relies on two unidirectional valve systems, primary and secondary. The primary system is located in the initial lymphatics with, it is presumed, overlapping endothelial cells around the circumferential lining of lymphatic capillaries which act as unidirectional valves. The secondary lymphatic system is located in the lumen of the collecting lymphatics and is well studied in contrast to the primary system. We propose two models for the drainage of fluid by the lymphatic system that includes the primary valve system. The analysis identifies four key areas that affect lymphatic drainage. These are: the regular tissue deformations, the mechanics of the primary lymphatic valves, the fluid flow through the interstitium and that through the walls of blood capillaries. The models outline a new way of modelling the primary valve system that appears to be more relevant to experimental studies than previous models. The first model presented in this thesis describes a permeable membrane around a blood capillary, an elastic primary lymphatic valve and the interstitium lying between the two. Here we pay special attention to the mechanics of the primary valve system, by assuming that lymphatic endothelial cells (primary valve system) deflect into the lumen (allowing fluid drainage) in response to pressure differences between the interstitium and the lumen. The model predicts a piecewise linear relation between the drainage flux and the pressure difference between the blood and lymphatic capillaries. The second model presented in this thesis includes the regular tissue deformations in modelling lymphatic drainage. We propose a 'sliding door' theory of how lymphatic drainage occurs, which we base upon the premise that when the interstitium expands (due to excess fluid)the surrounding matrix pulls open the lymphatic valves creating a gap for the interstitial flid to drain into the lumen. The model predicts that after a certain number of valve cycles (close to open to close)the system relaxes to a steady state, in which the lymphatic valve stays open.

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ORCID for Tiina Roose: orcid.org/0000-0001-8710-1063

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