Lymphedema : Medical and Physical Therapy

Structure and Function of the Lymphatic System

The lymphatic system is a closed vascular system composed of endothelial-lined channels that parallel the arterial and venous systems. The lymphatics originate in the tissue interstitium as specialized capillaries. These capillaries are remarkably porous and readily permit the entry of even large macromolecules, including albumin. Lymphatic capillaries have been observed also to be intimately associated with fine strands of reticular fibers and collagen that are connected to surrounding tissues. These anchoring filaments provide a direct anatomic connection between the lymphatic capillaries and the adjoining tissues. As interstitial fluid increases, the collagen fibers are pulled apart. This exerts traction on the lymphatic anchoring filaments and centrifugal pull on lymphatic capillaries that keeps the lumens patent even in the presence of increasing interstitial pressure and interstitial edema.

Beyond the lymphatic capillaries are the terminal lymphatic vessels. The walls of these vessels are devoid of any smooth muscle; however, intraluminal bicuspid valves are present. The valves partition the vessels into discrete contractile segments termed lymphangions. Eventually these vessels merge to form larger lymphatic collector vessels and lymphatic trunks that contain smooth muscle in their walls. Contraction of the smooth muscle propels the lymphatic fluid through the peripheral lymphatic vessels that eventually connect with the thoracic duct or right lymphatic duct. These latter lymphatic vessels join the venous system in the left and right cervical regions, respectively.

There is both a superficial and a deep collecting system of lymphatics in the extremities. Lymphatics from the skin and adjacent subcutaneous connective tissues drain into the superficial system. Lymph from the lymphatics in the fascial planes surrounding skeletal muscles drains predominantly into the deep lymphatic collecting system. The distribution of fluid between the blood vascular system and the tissues depends on the transcapillary balance between hydrostatic and protein osmotic pressure gradients.

Normally there is a slight hydrodynamic imbalance favoring a small excess amount of fluid, salt, and macromolecules in the tissue spaces. This filtrate, or lymph, is collected by the lymphatics and returned to the venous system. Thus, a primary function of the lymphatic system is to return to the circulation not only fluid but also large-molecular-weight substances such as protein and particulate matter that cannot reenter the blood capillaries directly.

The lymphatic system acts also as a safety valve or buffer in the event of fluid overload and therefore helps to prevent edema from forming. As interstitial fluid volume increases, interstitial fluid pressure increases. The result is a marked increase in local lymph flow. Unlike blood, which is pumped by the heart, lymph is propelled predominantly by spontaneous intrinsic contractions of the lymphangions and lymphatic trunks. Skeletal muscle contraction, active and passive range of motion, respiration, and blood vessel pulsation also aid significantly in the centripetal movement of lymph by external compression of lymphatic vessels.

Pathophysiology

When lymphatic blockage occurs secondary to cancer infiltration of lymph nodes, lymphadenectomy, or radiation-induced lymph node fibrosis, blood capillary hemodynamic forces and permeability characteristics usually remain normal. Intralymphatic pressure distal to the site of the blockage increases. Lymphatic vessels dilate and their valves become incompetent. Increased intralymphatic pressure also dilates lymphatic capillaries and results in incompetence in endothelial cellular junctions. These junctions normally serve as inlet valves. Their incompetence results in a reduction in lymph influx and an increase in tissue fluid volume.

Lymphedema may be categorized as either high-lymph-output failure or low-lymph-output failure. High-lymph-output failure results from an overproduction of capillary filtrate and leads to a greatly expanded extracellular fluid space. Examples of this state are decompensated heart failure, ascites from hepatic cirrhosis, and the nephrotic syndrome. Low-lymph-output failure of the lymphatic circulation is characterized by a decreased rate of lymph absorption and results from deficient or obliterated lymphatics.

Interstitial fibrosis is often a significant complication of lymphedema. This phenomenon often is recognized as the brawny, nonpitting form of soft tissue swelling. Although the exact mechanism of this scarring is unknown, there is a strong association between the high protein content of lymph and the proliferation of fibroconnective tissue. It has been postulated that fibrin or other specialized protein complexes dispersed throughout the interstitial matrix form an intricate lattice-template facilitating the deposition of collagen.

Fibrosis can also result from the inability of local macrophages to digest the excessive protein load. The accumulation of protein promotes chronic inflammation and scar formation even under conditions of adequate lymphatic drainage and normal capillary permeability. Activation of tissue macrophages should enhance scavenger function and interrupt the cycle of progressive protein accumulation and fibroplasia in tissue.

The proteolysis of tissue macromolecules into component amino acids can result in lower-molecular-weight fragments being reabsorbed into the blood stream, which relieves the load on the lymphatic system. Once the osmotic force created by the extravascular tissue protein is eliminated, excess salt and water diffuse back into the intravascular compartment. As the protein-rich tissue swelling regresses, the dynamic balance between collagen deposition and resorption shifts toward proteolysis, and the fibrous tissue recedes.

Primary and Secondary Lymphedema

Primary or idiopathic lymphedema is caused by a developmental abnormality in the lymphatic system (e.g., aplasia, hypoplasia, or hyperplasia of lymphatic vessels) or fibrotic occlusion of lymphatic vessels or lymph nodes. Secondary lymphedema results from a well-defined disease process that causes obstruction or injury to the lymphatic system. In North America and Europe, the most common cause of secondary lymphedema is surgical excision and radiation treatment of axillary or inguinal lymph nodes for the treatment of an underlying malignancy, such as breast or prostate cancer or malignant melanoma. The reported incidence of secondary lymphedema is variable. Development of post–breast cancer surgery upper extremity lymphedema has been reported to be approximately 25%. Other causes of secondary lymphedema include tumors invading the lymphatic vessels, such as those found in metastatic ovarian, testicular, colorectal, pancreatic, or liver cancers. Additional etiologies include bacterial and fungal infections, lymphoproliferative diseases, and trauma.

Grades of Lymphedema

Regardless of etiology, lymphedema has been classified as follows:

• Grade 0: Latent or subclinical condition where edema is not evident despite impaired lymph transport. It can exist months or years before overt edema occurs.

• Grade I: The edema pits in response to pressure and is reduced significantly by elevation. There is no clinical evidence of fibrosis.

• Grade II: Edema does not pit in response to pressure and is not reduced by elevation. Moderate to severe fibrosis is evident on clinical examination.

• Grade III: Lymphedema is irreversible and develops as a result of repeated inflammatory insults. Fibrosis and sclerosis of the skin and subcutaneous tissues is present. This stage of edema is known also as lymphostatic elephantiasis.

Each grade may be subclassified as mild, moderate, or severe.