Lymphedema: A Practical Approach and Clinical Update

Samih Bittar, MD; Richard Simman, MD; Fedor Lurie, MD


Wounds. 2020;32(3):86-92. 

In This Article

Abstract and Introduction


The lymphatic system is arguably the most neglected bodily system. As a result, its contribution to human health and disease is not well understood. In this review, the clinical approaches based on new knowledge and developments of the lymphatic system are covered. The lymphatic system has 3 major functions: (1) the preservation of fluid balance; (2) a nutritional function, as intestinal lymphatics are responsible for fat absorption; and (3) host defense. Lymph vessels return the capillary ultrafiltrate and escaped plasma proteins from most tissues back, ultimately, to the blood circulation. Hence, lymphatics are responsible for maintaining tissue (and plasma) volume homeostasis. Impaired lymph drainage results in peripheral edema (lymphedema) and may have more far-reaching effects on cardiovascular disease, in particular hypertension and atherosclerosis. Lymphatics have an important immune surveillance function, as they represent the principal route of transport from tissues for antigen and immune cells. Intestinal lymphatics (lacteals) are responsible for most fat absorption, first documented by Gaspare Aselli in 1627, when the lymphatic system was discovered. A relationship between fat and lymphatics may exist well beyond the gut alone. Fat deposition is a defining clinical characteristic of lymphedema. Suction-assisted lipectomy of lymphedema has shown the swelling is not just fluid but is dominated by fat. Lymphatics are the preferred route for the metastatic spread of cancer. Accordingly, the lymphatic system may be important for defense against cancer by generating immune responses to malignant cell antigens. Preventing lymphatic entry and propagation of malignant metastasis would effectively render the cancer nonfatal. As one can see, the lymphatic circulation is fundamentally important to cardiovascular disease, infection and immunity, cancer, and, in all likelihood, obesity — 4 of the major challenges to health care in the 21st century.


Edema is the presence of an excess of interstitial fluid and is an important sign of poor health in clinical medicine. It may occur in the lungs (pulmonary edema), abdominal cavity (ascites), and other body cavities (synovial, pericardial, and pleural effusions), but the most common site is within the peripheral subcutaneous adipose tissue.[1]

In medical practice, peripheral edema is often classified according to possible systemic causes, such as heart failure, nephrotic syndrome, and venous obstruction.[1] This clinical approach fails to appreciate that (a) more than 1 cause may contribute to the development of edema and (b) the central role of lymphatic drainage is tissue fluid balance. Consequently, the clinician's approach to treating chronic edema is often misguided and inappropriate as, for example, when diuretics are empirically prescribed for patients with lymphedema.[2]

Peripheral edema develops when the microvascular (capillary and venular) filtration rate exceeds lymph drainage for a prolonged period because the microvascular filtration rate is high, lymph flow is low, or a combination of both.[3] Filtration rate is governed by the Starling principle of fluid exchange. In simple terms, microvascular filtration of fluid from capillary into interstitium is driven by the hydraulic (water) pressure gradient across the blood vessel wall (Pc – Pi, in which Pc indicates capillary pressure and Pi indicates interstitial pressure) and is opposed by the osmotic pressure gradient (πp – πi, in which πp indicates plasma osmotic pressure and πi indicates interstitial osmotic pressure from tissue proteins), which is the suction force retaining fluid within the vessel (Figure 1).[4]

Figure 1.

Summary of the lymphatic fluid flow from the interstitial space to the central venous system.

Tissue fluid balance thus critically depends upon lymphatic function in most tissues. By returning the capillary ultrafiltrate and filtered plasma proteins to the bloodstream, lymphatic vessels complete the extravascular circulation of fluid and protein and maintain tissue and, to some extent, plasma volume homeostasis.[4] If lymphatic drainage fails to cope with the excessive microvascular filtration caused by increased Pc (eg, heart failure, chronic venous insufficiency), or with reduced plasma colloid osmotic pressure (eg, nephrotic syndrome, malnutrition, liver disease, or inflammation), a filtration edema occurs.[5]

All chronic edema indicates an inadequacy or failure of lymph drainage; therefore, a clinical approach to peripheral (ie, subcutaneous) edema should begin with a consideration of lymphatic function to assess whether this is a primary impairment or normal lymphatic circulation is simply overloaded by high microvascular filtration (ie, heart failure, tricuspid regurgitation, pulmonary hypertension, venous hypertension or insufficiency, etc). There are many clinical circumstances in which more than 1 physiological factor contribute to chronic peripheral edema. For example, in heart failure, edema initially is caused by high microvascular filtration from high venous pressures that overwhelm lymph drainage capacity.[5] However, with chronicity, the sustained microvascular filtration exhausts lymph drainage so that eventually, even when heart failure is controlled, permanent damage to lymphatic vessels results in lymphedema. Therefore, a clinical approach should consider all possible physiologic factors influencing both lymph drainage and microvascular filtration, rather than relying upon a diagnosis confined to a single clinical category such as heart failure. Arguably, it may be better to consider the presence of chronic edema as synonymous with the presence of lymphedema, as chronic edema most often represents relative lymph drainage failure.[6]

In this review, the authors cover the topic of lymphedema as an external manifestation of lymphatic system insufficiency and dysfunctional transport marked by the accumulation of interstitial fluid, protein-rich fluid, cellular debris, and fibroadipose tissue that most commonly affects the limbs.