The lymphatic system is an incredibly complex network of tissues and organs. Together, this network regulates fluid balance, transports fatty acids from the gastrointestinal tract, and contributes to the immune system.¹ Dysfunction in the lymphatic system can lead to lymphedema and tumor development. Although it is common to treat wounds and lymphatic dysfunction as separate conditions, there can be many benefits in viewing these conditions as interrelated.² The lymphatic system is an essential component of the vascular system and is made up of a thoracic duct that receives fluid from smaller lymph vessels and lymph nodes that are grouped around several areas of the body, including the knees, hips, shoulders, elbows, abdomen, spine, between the ribs, and at the neck.

Brain lymphatics were newly discovered in 2017, thus leaving whole new areas for research into the effect of the lymphatic system on the nervous system and its diseases.³ There are several other primary lymphatic organs, including the spleen, thymus, appendix, bone marrow, and tonsils. Lymph fluid, which is composed of intercellular fluid, larger molecules, protein, blood waste, and immune products, moves within interstitial space, or space that is not an organ or a vessel.⁴

The Lymphatic System and Wounds

Wound healing is a complex process that includes coagulation, the conscription of inflammatory cells to the injured area, and formulation of granulation tissue. Chronic wounds are a complication of several diseases or conditions, such as diabetes, chronic venous insufficiency, poor circulation, mechanical pressure, or a weakened immune system.⁵ Recent studies have shown that the regeneration of lymphatic vessels plays an important role in wound healing. This impact includes the following:⁶

• Vascular endothelial growth factor 3 (VEGFR3)–expressing lymphatic vessels were found in the granulation tissue followed by regression at later stages.
• A ligand for VEGFR3, VEGFC, increases in response to tissue injury.
• The VEGFR3 ligand VEGFD can delay the recovery of a wound.
• Macrophages from diabetic mice have been found to promote the recovery of tissue when activated with interleukin-1ß.

Given the interrelationships between wounds and the lymphatic system, care and management of all lymphatic system disorders and abnormalities are central to the prevention and long-term care of venous and lymphatic wounds. Lymphatic ulcers are also negatively affected by delayed wound healing.⁷

The Impact of Compromised Lymphatic Function on Wounds

The presence of lymphatic dysfunction or lymphedema can greatly increase the risk of wound formation. Lymph fluid that drains from wounds can also increase the risk of infection and potentially even contribute to delayed healing. Identification of lymphatic dysfunction can be challenging when assessing a wound. Patients with mild edema or edema that is present only around the periwound area are generally not thought to have a lymphatic system impairment because some edema is a normal part of wound healing in its initial stages. However, the prolonged presence of edema can impair blood flow and decrease the ability to deliver or remove nutrients such as oxygen and carbon dioxide as a result of the impaired diffusion.

Additionally, the accumulation of interstitial fluid can increase bacterial colonization and trap growth factors and other peptides and matrix proteins. All of these factors contribute to delayed healing and can cause a further decline in lymphatic function,² thereby leaving the patient in a continuing state of decline. This process can be demonstrated in chronic venous insufficiency associated with venous hypertension. A high-filtration pressure is created in this condition, causing an increase in tissue fluid, which increases the lymphatic load. Initially, this is a low-protein edema, but as it goes untreated, the lymphatic vessels become dysfunctional in response to prolonged lymphatic hypertension. Tissue fibrosis occurs, and chronic inflammation contributes to an ongoing negative impact on the lymphatic system and its functions. When chronic wounds are present in this condition, the chronic inflammation impairs their ability to heal adequately.²

Conclusion

The lymphatic system is an active and integral component of the immune system and the wound healing process. Treating lymphatic disorders and wounds jointly requires a treatment plan with goals for both modalities. Compression therapy can be beneficial in treating both the wound itself and a lymphatic disorder. Care should also be taken to select the proper padding and dressings for patients with edema because edema can cause limbs to be shaped unusually.² In patients with early venous or lymphatic ulcerations, treatment can include application of an Unna boot, elevation, topical antiseptics, and systemic antibiotics while encouraging patient compliance with the plan of care. If healing does not progress, more specialized wound care treatment may be sought.⁷

An interdisciplinary approach with a Certified Lymphedema Therapist can provide decongestive exercise and manual lymphatic therapy to support wound healing.

References

1. Hancock DG, Potezny TM, White PM. Immune regulation by the peripheral lymphatics and its implications for wound healing and infection control in lymphoedema. Wound Pract Res. 2016;24(2):76-83.

2. Ehmann S. Incorporating specialized lymphedema therapy & the wound clinic. Today’s Wound Clinic. 2015;9(6). https://www.todayswoundclinic.com/articles/incorporating-specialized-ly…. Accessed May 6, 2019.

3. Absinta M, Ha SK, Nair G, et al. Human and nonhuman primate meninges harbor lymphatic vessels that can be visualized noninvasively by MRI. Elife. 2017;6:e29738.

4. Wolfson J. Wound care basics: understanding lymphedema and the lymphatic system. WoundSource; 2017. https://www.woundsource.com/blog/wound-care-basics-understanding-lymphe…. Accessed May 6, 2019.

5. Frykberg RG, Banks J. Challenges in the treatment of chronic wounds. Adv Wound Care. 2015;4(9):560-582.

6. Lee SJ, Park C, Lee JY, et al. Generation of pure lymphatic endothelial cells from human pluripotent stem cells and their therapeutic effects on wound repair. Sci Rep. 2015;5:11019.

7. Stanley DG, Dieter RA Jr, Dieter RA III. Venous and Lymphatic Diseases. New York, NY: McGraw-Hill Medical; 2011.