Lymphatic Fluid Mechanics: An In Situ and Computational Analysis of Lymph Flow

The lymphatic system is an extensive vascular network responsible for the transport of fluid, immune cells, proteins and lipids. It is composed of thin-walled vessels, valves, nodes and ducts, which work together to collect fluid, approximately 4 L/day, from the interstitium transporting it back to the systemic network via the great veins. The failure to transport lymph fluid results in a number of disorders and diseases. Lymphedema, for example, is a pathology characterized by the retention of fluid in limbs creating extreme discomfort, reduced mobility and impaired immunity. In general, there are two types of edema: primary edema, being those cases that are inherited (i.e. genetic predisposition), and secondary edema, which develop post-trauma or injury of the lymphatic vessels. With the onset of breast cancer and radiation therapies, the prevalence of secondary edema is on the rise. Clinical studies have shown that up to 80% of women who undergo nodal-dissection surgery develop lymphedema in their arms within 3-5 years of the surgery. Unfortunately, there is no cure or remedy for lymphedema stemming from our lack of understanding of the lymphatic system. The goal of this study was to evaluate lymph flow both experimentally and analytically to better understand the mechanisms regulating lymph transport. In particular we investigated the effects of pressure, volume loads and valve resistance on lymphatic function in the rat mesentery. Our experimental results were then used to develop computational and constitutive models to emulate the dynamic behavior of lymph transport. Collectively, the data illustrate the mechanics of lymphatic contractility and lymph flow. In particular, lymph flow and pumping significantly increased post edemagenic stress in the rat model. Furthermore, lymphangions exhibited highly nonlinear pressure-diameter responses at low pressures between 3-5 cmH2O. These experimental results strongly suggest the regulation of lymph flow via changes in pressure, shear stress and vessel diameter. Furthermore, the computational and constitutive models from this study provide great insight into lymphatic function characterizing the mechanical properties of a single pumping unit (i.e. lymphangion). These models will serve as valuable tools to further lymphatic research