Multi-scale computer models of lymphatic pumping
File(s)
Author(s)
Morris, Christopher James
Type
Thesis
Abstract
The lymphatic system maintains fluid homeostasis by returning interstitial fluid to the veins. Lymphatics pump fluid locally with contracting segments of the vessel (lymphangions) bounded by valves. Contractions are generated by specialized muscle exhibiting phasic and tonic contractions. Deficient pumping can result in accumulation of interstitial fluid, called lymphoedema. Lymphoedema treatments have limited effectiveness, partially attributable to a lack of understanding of contractions. A lumped parameter computational model of lymphangion pumping has previously been developed in the group. In this thesis I detail development of two multiscale models of lymphatic pumping to facilitate improved treatments for lymphoedema.
The first model captures subcellular mechanisms of lymphatic muscle contraction. This model is based on the sliding filament model and its smooth muscle adaptation. Contractile elements are combined with passive viscoelastic elements to model a cell. Many arrangements were trialled but only one behaved physiologically. The muscle model was then combined with the lymphangion model for comparison with experiments. This model captures mechanical and energetic aspects of both contraction types. I show that the model provides results similar to published experiments from rat mesenteric lymphatics. The model predicted a peak efficiency of 35%, in the upper range from other muscle types. In the range of frequencies and amplitudes simulated, the direct effect of calcium oscillations can increase lymphangion outflow by up to 40% of the flow in their absence.
The second model aims to improve our understanding of lymphangion interaction in large networks through computational homogenisation. In this model we do not directly simulate all lymphangions but sample lymphangions at evenly spaced intervals to reduce the computational intensity. We show through this model that increased external pressure at the network inlet collapses lymphangions and that this disruption of pumping for a few lymphangions reduces the outflow from the entire network.
The first model captures subcellular mechanisms of lymphatic muscle contraction. This model is based on the sliding filament model and its smooth muscle adaptation. Contractile elements are combined with passive viscoelastic elements to model a cell. Many arrangements were trialled but only one behaved physiologically. The muscle model was then combined with the lymphangion model for comparison with experiments. This model captures mechanical and energetic aspects of both contraction types. I show that the model provides results similar to published experiments from rat mesenteric lymphatics. The model predicted a peak efficiency of 35%, in the upper range from other muscle types. In the range of frequencies and amplitudes simulated, the direct effect of calcium oscillations can increase lymphangion outflow by up to 40% of the flow in their absence.
The second model aims to improve our understanding of lymphangion interaction in large networks through computational homogenisation. In this model we do not directly simulate all lymphangions but sample lymphangions at evenly spaced intervals to reduce the computational intensity. We show through this model that increased external pressure at the network inlet collapses lymphangions and that this disruption of pumping for a few lymphangions reduces the outflow from the entire network.
Version
Open Access
Date Issued
2021-07
Date Awarded
2022-04
Copyright Statement
Creative Commons Attribution NonCommercial Licence
License URL
Advisor
Moore, James
Publisher Department
Bioengineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)