Lumped-parameter modelling of fluid transport in the lymphatic system
File(s)
Author(s)
Jamalian Ardakani, Seyedeh Samira
Type
Thesis
Abstract
Any disruption of the lymphatic system due to trauma or injury can lead to oedema. There is no effective cure for lymphedema, partly because predictive knowledge of lymphatic system reactions to interventions is lacking. A well-developed model of the system could greatly improve our understanding of its function. The system is required to pump viscous fluid against gravity and pressure. In contrast to the blood circulatory system, there is no primary pump in the lymphatic network. Lymphangions, defined as the vessel segment between two intraluminal valves, are the individual pumping units.
We first aimed to identify the key parameters that affect the flow output of the system using a sensitivity analysis in a lumped-parameter model of lymphangions in series. Our results indicated that further experiments to estimate valve resistance more accurately are necessary. Moreover, the existence of an optimal value of transmural pressure may provide additional guidelines for increasing pumping in areas affected by oedema. In the next step, we expanded our model of contracting lymphangions in series to study pumping activity of physiologic lymphatic networks. We quantified the pumping capability of the system under increasing levels of steady transmural pressure and outflow pressure for different network sizes. Larger network models are valuable for translating experimental measurements from the single lymphangion level to tissue and organ scales. Finally, we demonstrated the suction effect in collecting lymphatic vessels by combining measurements of intraluminal pressure and diameter in isolated contracting lymphatic vessels with our mathematical model of lymphatic pumping. These findings provide insight on the mechanism for fluid entry from interstitial beds at sub-atmospheric pressure to the lymphatic system.
Collectively, these results improve our knowledge of lymphatic function and demonstrate the power of experimentally informed mathematical models to address physiological questions to develop better therapeutics and improve patient outcomes.
We first aimed to identify the key parameters that affect the flow output of the system using a sensitivity analysis in a lumped-parameter model of lymphangions in series. Our results indicated that further experiments to estimate valve resistance more accurately are necessary. Moreover, the existence of an optimal value of transmural pressure may provide additional guidelines for increasing pumping in areas affected by oedema. In the next step, we expanded our model of contracting lymphangions in series to study pumping activity of physiologic lymphatic networks. We quantified the pumping capability of the system under increasing levels of steady transmural pressure and outflow pressure for different network sizes. Larger network models are valuable for translating experimental measurements from the single lymphangion level to tissue and organ scales. Finally, we demonstrated the suction effect in collecting lymphatic vessels by combining measurements of intraluminal pressure and diameter in isolated contracting lymphatic vessels with our mathematical model of lymphatic pumping. These findings provide insight on the mechanism for fluid entry from interstitial beds at sub-atmospheric pressure to the lymphatic system.
Collectively, these results improve our knowledge of lymphatic function and demonstrate the power of experimentally informed mathematical models to address physiological questions to develop better therapeutics and improve patient outcomes.
Version
Open Access
Date Issued
2016-06
Date Awarded
2016-11
Copyright Statement
Attribution NoDerivatives 4.0 International Licence (CC BY-ND)
Advisor
Moore Jr., James E.
Publisher Department
Bioengineering
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)