Modelling the lymphatic system: challenges and opportunities

Abstract

The lymphatic system is a vital part of the circulatory and immune systems, and plays an important role in homeostasis by controlling extracellular fluid volume and in combating infection. Nevertheless, there is a notable disparity in terms of research effort expended in relation to the treatment of lymphatic diseases in contrast to the cardiovascular system. While similarities to the cardiovascular system exist, there are considerable differences in their anatomy and physiology. This review outlines some of the challenges and opportunities for those engaged in modelling biological systems. The study of the lymphatic system is still in its infancy, the vast majority of the models presented in the literature to date having been developed since 2003. The number of distinct models and their variants are few in number, and only one effort has been made thus far to study the entire lymphatic network; elements of the lymphatic system such as the nodes, which act as pumps and reservoirs, have not been addressed by mathematical models. Clearly, more work will be necessary in combination with experimental verification in order to progress and update the knowledge on the function of the lymphatic system. As our knowledge and understanding of its function increase, new and more effective treatments of lymphatic diseases are bound to emerge.

Figure 1.

The lymphatic system. Adapted with permission from Quere [9].

Figure 2.

Lymphangion. This schematic diagram cannot encompass the wide variation of vessel aspect ratio observed at different anatomical sites; and while the distension shown in the figure is perhaps exaggerated, lymphangions have been reported to double or triple their diameter during diastole [15,16]. Reproduced with permission from Quere [9].

Figure 3.

Schematic diagram of a collecting vessel and a trunk/duct of the human head and neck from a cadaveric study. It appears that, at this anatomical site in humans, the intervalvular distance is roughly the same. However, this is not a general case [18]. Reproduced with permission from Pan et al. [17].

Figure 4.

(a) Schematic diagram of a lymph node. Lymph flows around the lymphoid compartment and part of it enters the paracortex and follicles, where cells of the immune system remove pathogens and foreign material. Reproduced with permission from Roozendaal et al. [25]. (b) Illustration of a node cross section. Red and blue denote arteries and veins, respectively. Yellow arrows indicate lymph flow. SS, subcapsular sinuses; LL, lymphatic labyrinth; F, follicle; MS, medullary sinuses; IS, intermediate sinuses; Af, afferent; Ef, efferent. Reproduced with permission from Ohtani & Ohtani [24].

Figure 5.

Model of a lymphangion.