Lymphedema is a chronic condition, which may either be caused due to abnormal development of the lymphatic system or due to the injury to the lymphatic vasculature. The abnormal development of the lymphatic system is denoted as primary lymphedema, whereas, the injury to the lymphatic vasculature is termed as secondary lymphedema. The condition, most commonly involves the extremities, but genitals may also be involved. It is a progressive condition in which the area enlarges due to poor lymphatic drainage. The chronic interstitial fluid accumulation can cause fibrosis, inflammation & fat deposition leading to hypertrophy of the affected area. This can result in severe infections, skin changes, functional disability, morbidity & malignant transformation. In the United States alone, there are about 5 million individuals & 1 in every 1000 American suffering from lymphedema. Currently, about 200 million people suffer from lymphedema, all across the world.
Is Lymphedema Related To Obesity?
There have been clinical evidences that link severe obesity to being a major risk factor in the development of secondary lymphedema due to damage of the lymphatic vasculature. In most cases, lymphedema is secondary to breast cancer treatment. Other risk factor of lymphedema includes weight gain post-surgery & extreme weight gain with body mass index (BMI) of over 50. BMI of over 50 has been linked to lower extremity lymphedema. The greater chance of lower body lymphedema might be related to preferential fat tissue deposition in the lower extremities in comparison to the upper extremities along with the positioning of the lower extremities leading to impairment of lymphatic drainage against gravity.
Researches have also pointed toward profound changes in lymphatic function secondary to obesity & dietary changes. Animal Researches have shown that defective APOE (apolipoprotein E) gene is related to abnormally high levels of circulating cholesterol & eventually develop defects in lymphatic system, including decreased interstitial fluid transport capacity, abnormal lymphatic valves & impaired concentration of immune cells. These animals, when fed with high fat diet were modestly obese with decreased lymphatic transport, reduced lymph node uptake of interstitial fluid & abnormal lymph node architecture. These changes are reversible, which are consistent with reports demonstrating improvement in lymphedema symptoms with persistent weight loss regimen.
Pathophysiology Of Lymphedema In Relation To Obesity
The pathophysiology of lymphedema in obese individuals is largely unknown, although there is a clear link between lymphedema & obesity in post-surgical patients.
Although, there exists a clear relation between the two, it is still not clear whether obesity causes lymphedema due to increased production of lymph from an enlarging limb leading to disturbance in the lymphatic drainage, or due to compression of the lymphatics due to adipose tissue deposition, or due to direct injury in the lymphatic endothelium by changes in diet or body weight. However, research in mice has suggested inflammation & up-regulation of adipocyte differentiation genes including peroxisome proliferator-activated receptor gamma (PPAR) & CCAAT enhancer-binding protein alpha (CEPB) & increased activity of adipokines (hormones produced by adipose tissues) in individuals with impaired lymphatic flow.
Interrelation Between Lymphedema & Obesity
Recent researches have proposed that lymphedema & obesity are reciprocally interrelated to each other. This means that not only obesity leads to lymphedema, but lymphedema might also cause obesity due to increased adipose tissue deposition. Researches have shown that lymphedema associated fat deposition is caused by both hypertrophy & proliferation of local adipocytes (fat cells) & is similar to that found in fat depots in obese patients. In addition to fat depots similar to those found in obese patients, lymphedema associated fat deposition tissue also shows “crown like structures”, which increased the aggressive behavior & chances of malignancies of these lymphedema tissues.
Lymphedema can be managed by weight management programs that might include nutritional counseling &/or surgical weight loss options to reduce the rate or severity of lymphedema in at-risk patients. These approaches might lead to improved lymphatic function & increased clearance of interstitial fluid.
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