What is Lymphoedema?

For many years, the movement of fluid from the vascular system to the interstitium (all soft tissues outside of the vascular system) was explained by the Starlings model. It said that 100% of vascular fluid that left the capillaries, was 90% re-absorbed by the venous system and 10 % by the lymphatic system. Because of this model, most of the research on oedema and lymphoedema was based on this premise. The movement of fluid however could never be explained mathematically by this model. This all changed with the discovery of GLYCOCALYX.

Glycocalyx is a highly hydrated fibrous meshwork of carbohydrates that projects out and covers the membrane of endothelial cells, many bacteria and other cells. Proteoglycans and glycoproteins are generic structural components of a glycocalyx. (GE Kapellos et al 2013) Endothelial cells of the entire vascular system is covered by glycocalyx but of varying composition depending on the function required. Pictures of glycocalyx has only recently surfaced after the development of new imaging methods(Van den Berg 2003).

Image from The Endothelial Glycocalyx Protects Against Myocardial Edema
Bernard M. van den Berg, Hans Vink, and Jos A.E. Spaan

Figure 1. A, Electron microscopic overview of an Alcian blue 8GX–stained rat left ventricular myocardial capillary (bar=1 μm). B, After hyaluronidase treatment, before Alcian blue staining (bar=1 μm). C, Detailed pictures of glycocalyx on normal (left) and of hyaluronidase-treated (right) capillaries (bar=0.5 μm).

Figure 2. Distribution of glycocalyx thickness within normal capillaries (no treatment) and hyaluronidase-treated capillaries. Box plots indicate median values with 5th and 95th percentiles. *P<0.001 by means of Mann-Whitney U nonparametric test. Enzymatic degradation of the endothelial glycocalyx had no effect on endothelial cell thickness. With a mean endothelial cell thickness of 0.18±0.04 μm (n=270) and 0.16±0.03 μm (n=124) in normal and hyaluronidase-treated capillaries, respectively, these cells were well within the normal range.9 However, the interstitial space between capillaries and their surrounding tissue was significantly (P<0.001) affected on treatment with hyaluronidase (Figures 3A and 3B). Although most of the normal vessels were surrounded by an interstitium with a median dimension of 0.28 μm (Figure 3A), distribution of the interstitial space in hyaluronidase-treated capillaries was clearly shifted to the right and resulted in a median value of 0.46 μm (Figure 3B).

Figure 3. Normalized frequency distribution of pericapillary spaces of normal (no treatment) and hyaluronidase-treated capillaries. Difference in pericapillary space between normal and hyaluronidase-treated capillaries was assessed by means of Mann-Whitney U nonparametric test.

Once scientists were aware of Glycocalyx, they were prompted to find a new model to explain fluid movement. Michel and Weinbaum then pioneered the new model which mathematically explained fluid exchange. The Glycocalyx model (or Michel-Weinbaum model) now is widely accepted and says that:

For most of the body, 100% of the interstitial fluid is absorbed via the lymphatic system. When primary lymphatics absorb interstitial fluid, it follows lymphatic vessels to lymph nodes where 50% is re-absorbed into the vascular system. The rest enters the vascular system at the subclavian vein. This information is of major importance for the patient and therapist as therapy now targets a  different organ! If the lymphatic system has to manage 100% of interstitial fluid, it leaves us with two possible causes of lymphoedema:

  • Obstructive Lymphoedema and
  • Non-obstructive Lymphoedema.

Obstructive lymphoedema  – Here lymphoedema is secondary to Radiation, CA infiltration or surgery which permanently obstructs lymphatic flow and there is very little relief for these patients. Lymphatic pathways are permanently destroyed and fluid removal is achieved with difficulty via interstitial pathways which requires high and sustained compression.

Non-obstructive lymphoedema is where lymphoedema is secondary to venous insufficiency or perhaps inflammatory disease. The major lymphatic pathways are largely intact but over production of interstitial fluid and other factors (EG sedentary lifestyle) overwhelms the lymphatic system and lymphoedema develops. These patients respond much better to compression therapy as their lymphatics respond well to compression therapy.

The new Glycocalyx model therefor has now placed lymphoedema therapy on a pedestal and emphasized the role of the Lymphoedema therapist. Therapists will now better understand the response to therapy and be able to offer the more appropriate treatment.