Lymphedema at the Cellular Level
What tissues are affected by Lymphedema?
With lymphedema, the lymph fluid accumulates in the space between various tissues and cells including:
SKIN TISSUE
FAT TISSUE
MUSCLE TISSUE
NERVOUS TISSUE
Major Affected Areas and Cellular Pathways
Lymphedema and the Skin
There are several common skin changes that are associated with lymphedema. These can be directly or indirectly related to lymphedema, caused by a combination of effects, associated with the disease that is causing lymphedema, or caused by therapies. Primarily, the accumulation of lymphatic fluid leads to swelling which causes inflammation and scarring of the skin. The top skin layer is highly prone to becoming dry and cracked, which increases the risk of recurrent skin infections. Skin inflammation also causes an increased risk of wounds through warts, foot ulcers and pressure injuries (1). Also in the long-term, the pressure and inflammation from the lymphedema can lead to skin changes such as hyperkeratosis which involves thickening of the upper skin layer, and muscular fascia which is the tightening of skin (2).
Lymphedema and Adipose Tissue
The common symptom of lymphedema, tissue swelling, was originally thought to be caused solely by the accumulation of fluid, however, there is substantial evidence that it can also be caused by the deposition of fat in tissues (2). Studies have found that there is an excess of adipose tissue in these affected areas. Adipose tissue is known to be composed of fat cells which stores fat from nutrients. A defective lymphatic system and lymphatic flow increases the storage of fat as adipose tissue. Getting a better understanding of the relationship between lymphedema and adipose or fat tissue allows for better therapies to be developed. Treatments such as liposuction help to remove fat from these affected areas (3). This really helps clear up excess lymphatic fluid more efficiently, and reduce several symptoms.
Lymphedema and Fibrosis
Fibrosis is the thickening and scarring of various tissues. Due to the prolonged swelling from lymphedema, the immune system triggers inflammation across affected tissues (2). The lymph fluid in those specific areas begins to gather and attract fat cells. These fat cells begin to bind to the surface of different tissue types and eventually the tissue hardens into a gel-like or solid structure, this is known as scarring. Scarring further prevents lymph fluid from being circulated or excreted properly, which causes lymphedema symptoms to worsen. Targeting this fibrosis helps to improve and decrease the progression of lymphedema.
References
(1) Fife, C. E., Farrow, W., Hebert, A. A., Armer, N. C., Stewart, B. R., Cormier, J. N., & Armer, J. M. (2017). Skin and Wound Care in Lymphedema Patients. Advances in Skin & Wound Care, 30(7), 305–318. https://doi.org/10.1097/01.asw.0000520501.23702.82
This article outlines skin disorders that can be associated with lymphedema. Many skin disorders and infections can be prevented through proper skin care.
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(2) Azhar, S. H., Lim, H. Y., Tan, B.-K., & Angeli, V. (2020). The Unresolved Pathophysiology of Lymphedema. Frontiers in Physiology, 11. https://doi.org/10.3389/fphys.2020.00137
This article discusses lymphedema at a physiological level focusing on data that proves tissue swelling that occurs in lymphedema is not solely caused by an accumulation of protein fluid but also an accumulation of fat deposition. The article also outlines fibrosis in lymphedema.
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(3) Hoffner, M., Peterson, P., Månsson, S., & Brorson, H. (2018). Lymphedema Leads to Fat Deposition in Muscle and Decreased Muscle/Water Volume After Liposuction: A Magnetic Resonance Imaging Study. Lymphatic Research and Biology, 16(2), 174–181. https://doi.org/10.1089/lrb.2017.0042
This paper outlines adipose tissue and how lymphedema can lead to adipose tissue deposition. A technique discussed in the study is used to quantify and localize fat and water is called water-fat magnetic resonance imaging (MRI).
Media References
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(1) Riches, P. (2019). Lymphedema: Symptoms, Treatments, and Causes. www.medicalnewstoday.com. https://www.medicalnewstoday.com/articles/180919
This article gives a general overview of what lymphedema is, the symptoms, and mainly how it can be treated. Specifically, this was useful in providing an image to associate with common lymphedema symptoms, skin changes and inflammation.
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(2) Tashiro, K., Feng, J., Wu, S.-H. ., Mashiko, T., Kanayama, K., Narushima, M., Uda, H., Miyamoto, S., Koshima, I., & Yoshimura, K. (2017). Pathological changes of adipose tissue in secondary lymphoedema. British Journal of Dermatology, 177(1), 158–167. https://doi.org/10.1111/bjd.15238
This article outlines a study focusing on understanding the pathophysiology of lymphedema. The objective of the study is to characterize skin and adipose tissue for secondary lymphedema, with the main goal to develop a treatment in the future.
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(3) Kataru, R. P., Wiser, I., Baik, J. E., Park, H. J., Rehal, S., Shin, J., & Mehrara, B. J. (2019). Fibrosis and secondary lymphedema: chicken or egg? Translational Research: The Journal of Laboratory and Clinical Medicine, 209, 68–76. https://doi.org/10.1016/j.trsl.2019.04.001
This article takes an indepth look at the pathophysiology of lymphedema. Recent studies have discovered that chronic inflammation-induced fibrosis plays a key role in pathophysiology of this disease.
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