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Why MLD should be started as early as possible.

Updated: Mar 26, 2023

There's nothing quite so satisfying as reading a well written paper which summarises everything interesting that we know about the lymph system.

Wix stock image

In this regard, the recent paper by Weber et al (1) is a good read for anyone fascinated by lymphatics, regardless of academic ability. Personally I can't help but make connections with the descriptions given, and what I know about lymphatic physiology and the effects of MLD.

It's also very affirming when new understandings in lymphology, support the basic tenets and mechanisms of MLD.

 

"...the lymphatic system in health and disease has become a hot topic in vascular research."

 

Firstly, the authors give us a summary of recent discoveries that have sparked increased interest in research on lymphatics, and describe the 'positive feedback loop' that is the chronic progression of lymphoedema.

Samples of lymph collector vessels were studied to determine the histopathological changes affecting the lymph vessels in lymphoedema. There are some excellent images and descriptions showing how the vessels become fibrosed, sclerosed and eventually completely obliterated in advanced disease.

The main aim of the article is to highlight the potential and considerations in surgical procedures such as lympho-venous anastomosis (LVA). However, I will review the histological results with relevance to the stage of lymphoedema and to highlight how important it is to start MLD* as soon as possible when there is lymphatic overload.

 

Normal lymphatic anatomy

In the section on normal anatomy of the lymph vessels we are given reference images of healthy lymph vessels showing the layers of endothelium and smooth muscle.

FIG. 1.Semithin sections stained with toluidine blue of two superficial lymphatic collecting vessels of the human thigh (a, b); scale bar 100 μm. (c, d) Enlargements of the same vessels showing the two different layers of the media: the inner (i) longitudinal and the outer (o) circular layer. Scale bar 50 μm.

I read with interest the role of mast cells in regulating lymphatic vascular function. I've always know they were involved in regulating inflammation, but I hadn't realised how closely they were located to the initial lymph vessels or the role they play in vessel permeability and contractility.

Likewise I've been teaching how the vasa vasorum supply the smooth muscle in the blood vessel walls, so of course the lymphatic smooth muscle needs them too, and the paper has a great image of these lymph collector vasa vasorum.

FIG. 3.Semithin sections stained with toluidine blue. (a) Network of blood microvessels surrounding this lymphatic collecting vessel of the human thigh. Scale bar 100 μm. (b) Vasa vasorum (arrows) penetrate deep into the media of this vessel reaching as far as the subendothelial space. Scale bar 50 μm.

Next comes a description of the development and maintenance of valves, which fits with previous reports on the influence of lymph flow in valve formation, direction, and health. Read my previous post on lymph flow and valves.

FIG. 2.Semithin section (a; scale bar 100 μm) and transmission electron microscopy (b) of a valve (scale bar 5 μm). The valve leaflets are made of a connective tissue core covered on both sides by endothelial cells. At the valve buttress (*), the inner muscular coat is disrupted whereas the outer (o) circular layer is still present.

And this is where I start to connect the dots with MLD*, and why it is so very important in the early stages of lymphatic dysfunction - valve health depends on it!

Shear-stress activated mechanisms are responsible for formation and maintenance of the valves and the endothelial cell junctions.

So much of this tallies with our primary goal in performing MLD, which is to stimulate lymphatic pumping and increase lymph flow*. To achieve this we apply very precise stretching forces across and along the lymph collector vessels. We've always been focussed on how this affects lymph-motoricity, but it may also be beneficial in maintaining valve function and endothelial integrity in lymphatic disease. Read more posts on the importance of gentle shear forces including in tissue repair.

 

Lymph vessel changes in lymphoedema

As with the connective tissue changes, early changes in lymph vessels are happening before the lymphoedema itself becomes apparent. When the lymph pathway is obstructed by something like lymph node removal, the supplying vessels become dilated and the walls become thin and leaky.

This is the stage where we have the best - and in fact any chance at all - of assisting the system to recover full function.

FIG. 4.Masson's trichrome staining, red: lymphatic muscle cells, blue: collagen fibers. (a) Ectasis type vessel: the lumen is dilated and the wall is thin; (b) contraction type vessel: the lumen is restricted, and the wall is mainly made of lymphatic muscle cells stained red by Masson's trichrome; (c) sclerosis type vessel: the lumen is almost completely occluded, the inner longitudinal layer of the media is stained blue by Masson's trichrome, whereas the outer circular layer is stained in red. Scale bar 100 μm

MLD* improves lymph flow and if applied early enough can increase the formation of new lymph vessels in the damaged area.

This reinforces recommendations that MLD be applied as early as possible once lymph vessels have been damaged in any way.

The next stage in the damaged lymph vessels correlates to the middle stages of lymphoedema, which are typified by fat and fibre induration in the connective tissues.

FIG. 6.Schematic drawing of the histopathological changes of the lymphatic wall in lymphedema.

Similar changes occur in the vessel walls. Under a high lymph load the smooth muscle layers thicken which reduces the size of the lumen (the inside of the vessel). Normally there 1-3 layers of smooth muscle in the vessel wall, but in this intermediate stage of disease there can be up to 10 layers as the system tries to compensate for the obstruction in lymph flow.

Collagen is deposited under the endothelium and in the advanced stages the vessels become sclerosed and cease to work at all.

 

The role of MLD in lymph vessel health and recovery

Can these changes in lymph vessel pathology be reversed? This paper doesn't offer any answers as to the potential for disease reversal, other than the observation that

Interrupting this viscous cycle seems imperative.

Clinically we know that MLD improves lymph flow*, which is essential in maintaining vessel health and at least slowing disease progression. MLD will have the best effect in the early or mild stages of disease.

Since the pathological changes to the vessels and connective tissue are happing before there is any visible swelling, MLD should be applied before any obvious swelling appears.

There is a small window of opportunity after surgical damage to re-establish lymph flow across the scar and MLD should be used as soon as possible to maximise this repair process. Read more on the effects of MLD.

Once fibrosis and fatty changes have begun it is much more difficult to reverse these connective tissue change, so likely more difficult to reverse pathological changes in the vessels too. In the advanced stages we are left with trying to prevent progression and manage symptoms.

So the main message remains the same, MLD should be applied as soon as there is any lymphatic damage, be it from lymph node removal or other surgery, radiation damage, traumatic injury or obesity (which is the fastest growing cause of lymphoedema globally).

Since inflammation is both an initiator and promoter of lymph vessel disease, improving lymph flow and clearing these molecules from the tissue is still one of the best mechanism we have for slowing lymphoedema progression. I don't know of a better way to do this without drugs, than to apply MLD, which has been shown to reduce inflammation systemically*. Read more on inflammation and MLD.


* Effects of MLD on lymphatic pumping apply only to the Vodder method of MLD, these effects are not shown in lymphatic effleurage techniques, read more on these differences here.


1) Elisabetta Weber MA, Eugenio Bertelli, Guido Gabriele, Paolo Gennaro, and Virginia Barone. Lymphatic Collecting Vessels in Health and Disease: A Review of Histopathological Modifications in Lymphedema. Lymphatic research and biology 2022; 20: 468-477. DOI: 10.1089/lrb.2021.0090.

Lymphatic Collecting Vessels in Health and Disease: A Review of Histopathological Modifications in Lymphedema

Abstract

Secondary lymphedema of the extremities affects millions of people in the world as a common side effect of oncological treatments with heavy impact on every day life of patients and on the health care system. One of the surgical techniques for lymphedema treatment is the creation of a local connection between lymphatic vessels and veins, facilitating drainage of lymphatic fluid into the circulatory system. Successful results, however, rely on using a functional vessel for the anastomosis, and vessel function, in turn, depends on its structure. The structure of lymphatic collecting vessels changes with the progression of lymphedema. They appear initially dilated by excess interstitial fluid entered at capillary level. The number of lymphatic smooth muscle cells in their media then increases in the attempt to overcome the impaired drainage. When lymphatic muscle cells hyperplasia occurs at the expenses of the lumen, vessel patency decreases hampering lymph flow. Finally, collagen fiber accumulation leads to complete occlusion of the lumen rendering the vessel unfit to conduct lymph. Different types of vessels may coexist in the same patient but usually the distal part of the limb contains less affected vessels that are more likely to perform efficient lymphatic–venular anastomosis. Here we review the structure of the lymphatic collecting vessels in health and in lymphedema, focusing on the histopathological changes of the lymphatic vessel wall based on the observations on segments of the vessels used for lymphatic–venular anastomoses.



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