The lymphatic system has many recognized important roles in normal physiology and in a variety of disease conditions. In addition to returning fluid from interstitial tissue spaces to the blood circulation, it also serves as an important transport route for immune cells and cancer metastases. All of the deadliest forms of cancer spread through the lymphatic system. Despite the importance in so many causes of death and disability, little is actually known about transport mechanisms in this obscure system.
We have quantified various aspects of lymphatic system pumping based on a multiscale modeling approach combined with a unique experimental skill set. In addition to the general insight on lymphatic pumping, we have elucidated the phenomena by which the lymphatic system is able to generate negative interstitial tissue pressures while still generating positive fluid flow out of those tissues. This resolves a decades-old mystery of basic physiology.
Along the pathway back to the blood vessels, all lymph must pass through at least one lymph node. These are highly compartmentalized structures in which leukocytes process antigens and tumor cells. There are also specialized direct communication ports with the blood circulation in which fluid and cells can traverse in either direction. Our studies of flow patterns and mass transport in lymph nodes reveal that under basal conditions only about 10% of the incoming flow passes through the cortex, or the innermost part of the node where the T and B cells reside. Upon antigen recognition, nodes quickly adapt their flow resistance to send more of the flow through the cortex. These flow patterns are also important for shaping chemokine concentration gradients.
The long term goals of this research include developing better strategies for treating fluid balance disorders such as lymphedema, and also contributing to the knowledge base of other lymphatic disorders with the insight provided by mass transport analysis.