Multiscale Modelling of Lymphatic Drainage - Multiscale Computer Modeling in Biomechanics and Biomedical Engineering - page 148

number of experimental studies of molecular and micromechanical factors con-
trolling lymphatics. Although these studies have greatly increased our knowledge
of different aspects of the lymphatic system there is a need to integrate these
studies to produce quantitative models of the functioning of the lymphatic system.
In particular such models should aim to explain the effect of the lymphatics on the
macroscale, i.e., organ and body scale, in terms of the system's microscopic and
molecular properties. As well as providing a framework for interpreting experi-
mental results and highlighting interesting avenues for new experimental studies,
in the long term such modelling can lead to new ways of treating important
medical conditions.
The fundamental role of the lymphatic system is to collect excess interstitial
fluids, tissue waste products and plasma proteins from tissue and return them to the
blood. Tissues require fluid and nutrients and these are supplied to them by blood
vessels. After the fluid has performed its function it is reabsorbed either by the
lymphatics or by postcapillary venules, with the dominant contribution in most
cases being due to the lymphatics. Thus when the lymphatic system is unable to
function the interstitial pressure becomes heightened and the tissues become
swollen. In addition, as in most cases reabsorption drives the flow of fluids through
tissues, failure of the lymphatic system results in much slower, mainly diffusive,
movement of nutrients into tissues and the accumulation of waste products in the
tissues. In order to perform its important task, the lymphatic system has evolved
into an elaborate, highly branched, highly valved, unidirectional drainage network.
We can distinguish three main parts of the lymphatic system; the primary lymph
system, comprising passive microcapiliary ducts which drain the interstitial tissue
and feed into the secondary lymphatic ducts or lymphangions, larger vessels with
active, contractile walls and interspersed with simple valves, forming a distributed
pumping system. Secondary lymph vessels combine to feed larger vessels draining
whole areas of the body. Finally, lymph nodes are distributed through the system at
intervals, whose function is to process the lymph fluid as it passes through. In
addition to its primary task the lymphatic system also plays an important part in
the immune system. In particular, lymphocytes that reside and multiply in the
lymphatic system clean lymph fluid of bacteria and other contaminants. Thus
diseases of the lymphatic system often result in compromised immune compe-
tence. The lymph nodes play a critical part in the body's response to infection, and
in the spread of cancer and HIV.
Many medical conditions have now been linked to a malfunctioning of the
lymphatic system, for example lymphedema, Melkersson-Rosenthal-Meischer
syndrome, Kaposi sarcoma, lymphatic filariasis. Lymphatic filariasis is a parasitic
disease that is thought to be globally the second leading cause of permanent and
long-term disability [ 20 ]. In recent years, the lack of lymphatic function in solid
tumours has been identified as one cause for hindered delivery of chemothera-
peutic drugs to solid tumours [ 19 ]. Tumour metastasis is also thought to involve
lymphatics as one, if not the primary, pathway [ 7 , 47 , 48 ].