Lymph flow, valves and why lymph loading is so important

Recent findings that lymph flow influences the formation and maintenance of the valves in lymph collectors is a valuable piece in the jigsaw puzzle that is our understanding of lymph formation and transportation. For me it was one of those pieces that just slotted into a little gap and suddenly explains a lot.

The paper I'm referring to is on the genes involved in embryonic development and postnatal maintenance of valves in mice Yang et al (1). The results elucidate the role of adherin (molecules that help cells attach to one another) in valve formation and function, and while the paper is available open access, you'll need a molecular biology degree to read it. Click here read the paper.

Fortunately there is also a good summary in the USF Health News and an excellent webinar by one of the authors on the LE&RN website. The first half of the webinar is an overview of how lymph vessels are formed and function and worth watching for that alone. By half way though I felt myself go cross-eyed and skipped to the conclusion at the end. View the webinar.

“We knew that lymph flow was required for the valves to form and function throughout life, but we did not know how the endothelial cells that make up the inner lining of lymphatic vessels can ‘sense’ the flow" Joshua Scallan PhD

Another paper by Li and colleagues (2) describes the effect of lymph flow on lymphatic smooth muscle contractions. This is an in vitro model of a single lymphangion, so still not in humans, but they seem to have included a lot of known variants into the model. Models like this are important in developing hypotheses that can be further investigated and this model suggests that the co-ordination of the relaxation and contraction phases of the lymphangion are influenced by lymph flow. Cyclical fluctuations in nitric oxide (NO) and calcium ions (Ca++) have a similar effect on smooth muscle in lymph and blood vessels, NO relaxes the muscle and promotes dilatation (filling) and Ca++ stimulates smooth muscle contractions (emptying).

So with the rider that molecular biology is NOT my area of expertise, here is my attempt to put both these findings together and work out what that means for our understanding of the effects of MLD on lymphmotoricity.

The endothelial cells that line all lymph vessels are sensitive to stretch and shear forces and these conditions influence the levels of NO and Ca++ and other cytokines released into the lymph. The molecules that influence valve formation and function have their effect on adherins, which are the molecules that join the endothelial cells together. At the initial lymph vessel end of the system they form button junctions which allow gaps for lymph formation to occur. Further along in the collectors the cell junctions are in a zipper formation to restrict movement across the vessel wall. In the valves they have something to do with the stiffness or flexibility of the valve flap. Valves are generally held in an open state.

The effect of NO and Ca++ on smooth muscle within a single lymphangion, particularly in the pre-valve and post-valve regions can be seen in this video from the model created by Li and colleagues which shows the effect of fluctuating NO and Ca++ on smooth muscle contraction within a single lymphangion. Lymph is propelled forward by a sudden forceful contraction and passes through a few valves which are held open. Then as the lymph flow slows the chemical levels reset (watch the graphs at the top falling) eventually reaching threshold and another contraction is initiated. Just prior to contraction the angion relaxes fully and some re-fluxing lymph is pulled back though the open valves. This increases the load within the angion triggering the stretch receptor mediated contraction and increasing the force and amplitude of the contraction. This video is cropped to 1 contraction, view the full 9 minute video here.

This video is an ICG image of lymph vessels in the ankle showing how this oscillating pattern of lymph flow looks over a chain of angions. We can see the 'parcels' of lymph being propelled along through a number of angions and then as the parcel slows you can see the load reflux a little to distend the angion wall, initiating the next propulsion of lymph along the chain of angions.

This diagram is the pathological changes occurring in the collector vessels during lymphoedema. Under constant stress and protein exposure all layers of the vessel wall succumb to fibrosis. I can see now how the interruption in lymph flow will result in the loss of valves and this will contribute to further interruption in lymph flow, it's a downward spiral from there. The ageing lymph vessels as described by Shang et al is the most readable references for today (3). It is a fascinating account of the changes in lymph-motoricity and valve function really helps make the new findings relevant. Please do read this paper.

Reviewing these three papers has highlighted the importance of continued lymph loading to maintain collector vessel health. If the oscillating nature of lymph flow is essential in normal vessel maintenance, then it must be crucial in recovery after acute damage or chronic stress.
So how does this all relate to Dr Vodders' MLD?

Keeping in mind that these studies were not on the effects of MLD, I can still use the findings to further my understanding of the way in which the Vodder method of MLD increases lymphatic pumping. Our current understanding of how the precise movements of the skin stimulate lymph motoricity is very mechanistic (see also my previous post on the effects of different techniques). Basically, we move the loose connective tissue without compression to enable lymph formation at the initial lymph plexus which loads the system. We also apply stretching and shearing forces to the lymph collectors which initiates stretch receptor mediated contractions of the smooth muscle. Systemically the reduction in sympathetic tonus dilates the lymph vessels allowing for increased filling which in turn increases the force and amplitude of the next contraction.

Maybe now we also need to consider the effect of MLD of levels of molecules like NO which are increased in response to shearing forces and have the effect of dilating the lymph angion?

Lymph vessels that are damaged during surgery or traumatic injury, and which do not reconnect or develop collateral pathways will deteriorate, and this understanding of the importance of lymph flow in valve maintenance and muscle contraction may explain how that happens. MLD can help a newly damaged system to recover by loading the lymph vessels to encourage the establishment of new pathways and maintain valve health. In chronic oedema, using MLD to load the vessels may help to reverse some of the damage to vessels and valves, or at least prevent further deterioration.

Unfortunately most of us are not lucky enough to receive a full MLD treatment every day, so we need to find other activities which can promote lymph loading to keep our systems healthy. Deep breathing, exercise, self massage, dry brushing, appropriate compression and meticulous skin care will all support normal lymphatic function and help a damaged system to recover.

  1. Yang, Y., et al. (2019). "VE-cadherin is required for lymphatic valve formation and maintenance." Cell reports 28(9): 2397-2412. e2394.

  2. Li, H., et al. (2019). "The effects of valve leaflet mechanics on lymphatic pumping assessed using numerical simulations." Scientific Reports 9(1): 1-17.

  3. Shang, T., et al. (2019). "Pathophysiology of aged lymphatic vessels." Aging (Albany NY) 11(16): 6602.

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