Lymphedema—the accumulation of lymph in the interstitial spaces, principally in the subcutaneous fatty tissues—is caused by a defect in the lymphatic system. It is marked by an abnormal collection of excess tissue proteins, edema, chronic inflammation, and fibrosis. 1 Understanding why it develops requires a familiarity with the lymphatic system, 1 of the 3 vascular systems in the body.
PATHOPHYSIOLOGY OF LYMPHEDEMA
The lymphatic system consists of superficial or primary lymphatic vessels that form a complex dermal network of capillary-like channels that drain into larger, secondary lymphatic vessels located in the subdermal space. These primary and secondary lymphatic vessels parallel the superficial veins and drain into a third, deeper layer of lymphatic vessels located in the subcutaneous fat adjacent to the fascia. A muscular wall and numerous valves aid active, unidirectional lymphatic flow in secondary and subcutaneous lymphatic vessels. Primary lymphatic vessels lack a significant muscular wall and do not have valves. An intramuscular system of lymphatic vessels that parallels the deep arteries and drains the muscular compartment, joints, and synovium also exists.
Although there is evidence that the superficial and deep lymphatic systems communicate near lymph nodes, they probably function independently, except in abnormal states. 2 Lymph drains from the lower limbs into the lumbar lymphatic trunk, which joins the intestinal lymphatic trunk and cisterna chyli to form the thoracic duct that empties into the left subclavian vein. The lymphatic vessels of the left arm drain into the left subclavian lymphatic trunk, then into the left subclavian vein. Right arm lymph channels drain into the right subclavian lymphatic trunk, then into the right subclavian vein.
One function of the lymphatic system is to return excess fluid and protein from interstitial spaces to the blood vascular system. Because lymphatic vessels often lack a basement membrane, they can reabsorb molecules too large for venous uptake. Mechanisms of clinical edema include increased arteriovenous capillary filtration and reduced interstitial fluid absorption. Causes of increased capillary filtration include increased hydrostatic pressure in capillaries, decreased tissue pressure, and increased membrane permeability. Reduced interstitial fluid resorption can be caused by decreased plasma oncotic pressure, increased oncotic pressure of tissue fluid, and lymphatic obstruction.
Lymphedema is categorized as either primary or secondary. Primary lymphedema is caused by congenital absence or abnormalities of lymphatic tissue and is relatively rare. Secondary lymphedema is generally caused by obstruction or interruption of the lymphatic system, which usually occurs at proximal limb segments (ie, lymph nodes) due to infection, ligation, malignancy, or scar tissue. 1 The pelvic and inguinal nodes in the lower extremities and the axillary nodes of the upper extremities are the primary sites of obstruction.
TRANSIENT VS. CHRONIC LYMPHEDEMA
Lymphedema can be transient or chronic. Transient lymphedema is a temporary condition that lasts less than 6 months and is associated with pitting edema with tactile pressure and lack of brawny skin changes. 1 The following factors may place the patient at increased risk for transient lymphedema with an acute onset:
•surgical drains with extravasation of protein into the site of the surgical procedure.
- inflammation following injury, radiation, or infection leading to increased capillary permeability.
- immobility of the extremity or extremities that results in decreased external compression by the musculature
- proximal venous occlusion by thrombosis or phlebitis
- reversal of equilibrium at the capillary bed resulting in accumulation of third-space fluid.
Chronic lymphedema is more difficult to reverse because of its pathophysiology. A cycle is started, in which the limb’s deficient lymphatic system cannot compensate for the increased demand for fluid drainage. This condition may occur subsequent to any of the following:
- tumor recurrence or progression in the nodal area
- infection and/or injury of lymphatic vessels
- radiation injury to lymphatic structures
- unsuccessful management of early lymphedema
- venous obstruction due to thrombosis.
Early in the course of developing lymphedema, the patient experiences soft, pitting edema that may be easily improved by limb elevation, gentle exercise, and elastic support. Continual and progressive lymphostasis, however, causes dilation of the lymph vessels and backflow of fluid to the tissue beds. Collagen proteins accumulate, further increasing colloid osmotic tissue pressure, leading to enhanced fluid flow from the vascular capillaries into the interstitial space. The stasis of fluid and protein stimulates inflammation and macrophage activity as the body attempts to degrade the excess proteins. Fibrosis of the interstitial connective tissue by fibrinogen and fibroblasts causes the development of the brawny, stiff, nonpitting lymphedema that no longer responds to elevation, gentle exercise, or elastic compression garments. Chronic lymphedema gradually becomes nonpitting.
Lymphedematous tissues have lower oxygen content, a greater distance between lymph vessels due to fluid accumulation and swelling, impaired lymphatic clearance, and depressed macrophage function, rendering patients at increased risk of infection and cellulitis. Treatment for patients with advanced lymphedema with chronic fibrosis is more difficult than when treated earlier. Additionally, once these tissues are stretched, edema recurs more readily.
Because of its pathophysiology, chronic lymphedema is more difficult to reverse than transient lymphedema.
ASSESSMENT AND DIAGNOSIS
Unlike patients with arterial or venous disease, most patients with lymphedema do not report symptoms other than heaviness or fullness related to the weight of the limb. Ambulation is affected because of the limb size and weight, causing an inability to wear clothing. However, because of the lower incidence of pedal edema, patients with lymphedema are less likely than patients with edema from venous disease to complain of an inability to wear shoes. Oozing fluids may cause pruritus.
Patient assessment includes a history and physical examination. The history should include information about past operations, postoperative complications, radiation treatment, the time interval from radiation or surgery to the onset of symptoms, and intervening variables in the presence or severity of symptoms. The quality and behavior of the edema (fluctuation with position, progression over time) should be assessed. History of trauma or infection should be determined. In addition, information concerning current medications may be important. 1 Edema is not detectable clinically until the interstitial volume exceeds 30% above normal.
The following scale may be clinically useful in assessing edema:
- 1+: 1 cm indentation
- 2+: 2 cm indentation
- 3+: 3 cm indentation
- 4+: 4 cm or greater indentation.
When in doubt, chemical evaluation of the protein content of the edema fluid within the extremity can help establish the proper diagnosis. A tissue fluid analysis with a protein content between 1.0 and 5.5 g/dL usually indicates lymphedema; 0.1 to 0.9 g/dL is more consistent with venous or cardiac edema. The albumin to globulin ratio is usually higher than serum in lymphedema. A complete blood count, plasma protein, albumin, urinalysis, and urine protein can help diagnose the source for the edematous limb. Under unusual circumstances, a chromium chloride test can be obtained to assess for abnormal protein losses resulting in extremity edema. 3
Tissue loss or ulceration related to lymphatic obstruction with subsequent lymphedema is unusual. Tissue loss occurs because of a concurrent secondary pathologic process. Patients with lymphatic obstruction are prone to infectious complications in the affected extremity. These infections can be bacterial but commonly are fungal in origin. Intertriginous folds should be frequently inspected for ulcers and infections. Cutaneous fungal or bacterial infections are not unusual in patients with lymphatic obstruction. If transcutaneous weeping or oozing from a small abrasion occurs, the fluid can cause pruritus.
Early conservative treatment is the treatment of choice for patients with lymphedema. A multimodality approach, including elevation, exercise, compression garments, manual lymphatic drainage, compression pumps, and preventing infection, is recommended. 4–7 Patients with lymphedema frequently require a higher degree of compression than those with venous insufficiency. Pressures should be 50 to 60 mm Hg for lymphedema, compared with 30 to 40 mm Hg, which is the norm for venous insufficiency.
A lymph pump is recommended for more rapid reduction of lymphatic fluid to reduce edema in the affected extremity. The extremity is placed into a long inflatable sleeve that is connected to a pump that inflates the sleeve to a predetermined pressure. Continued elevation of the extremity is also necessary. In patients with reducible lymphedema, long-term use of a compression pump is the treatment of choice; however, adherence to therapy may be a problem.
Manual lymphatic drainage is a therapeutic technique used to increase lymph flow. It consists of movement of the therapist’s hands over the patient’s skin and subcutaneous tissue. The pressure applied is very gentle, and the movements are slow to correspond with the slow lymphatic pulsations. The massage sequence begins at the center of the body and moves to the periphery. The rationale for this is that the lymph nodes must be emptied before they can receive more lymph from the periphery. Each maneuver is performed in a distal to proximal direction.
Manual lymphatic decompression is effective in selected patients, but it is often difficult to find a qualified specialist. Lymphedema pumps are more widely available; however, many insurance companies do not pay for this equipment.
Once the extremity reaches its smallest obtainable size, a static compression garment is fitted. Between pump uses, the extremity should be wrapped with elastic compression bandage or have temporary compression garments applied to reduce recurrence of lymph in the extremity. It may take months to obtain a demonstrable reduction in the size of the extremity.
It may take months to obtain a demonstrable reduction in the size of the extremity in a patient with lymphedema.
Lymphedema has fewer surgical options than the treatment of arterial or venous disease. Patients with severe lymphedema and minimal improvement with compression therapy may benefit from a lymph-reducing surgical procedure. These procedures fall under 3 broad categories:
- excisional procedures
- excisional therapy and skin grafting
- drainage procedures.
Excisional therapy involves removing a large section of skin and subcutaneous tissue down to the muscle fascia and reapproximating the wound edges. The net result is the equivalent of reducing the hem on a waistline. Problems associated with this procedure relate to the undermining of residual tissue necessary for approximation of wound edges, which can delay healing. In addition, this method does not treat the underling problem of lymphatic outflow obstruction. 7
Excisional therapy and skin grafting can be performed and may also be used to treat lymphedema. This technique usually involves completely degloving the overlying tissue on the affected extremity and split-thickness grafting directly onto the muscular bed. By removing all overlying lymphatic tissue within the dermal and subcutaneous space down to the muscle bed, lymphedema in the area of grafting is no longer a concern. The result is one of marked reduction in the size of the extremity, but any tissue distal to this is left with more exaggerated lymphedema than in the preoperative state. Skin grafts have a 5% to 10% incidence of failure, and when they fail, long-term healing can be a problem. A frequent complication of excisional procedures is a protracted lymph leak, which interferes with the healing process and wound healing.
A drainage procedure for lymphatic obstruction may be considered for patients with lymphatic obstruction at the level of the upper leg or more proximal extremity and for those who have short-segment obliteration of lymphatic channels. The procedure is contraindicated for patients with distal or obliterative disease, and those with combined pelvic and distal obliterative disease.
The drainage procedure currently favored for the treatment of limited lymphatic obstruction is a surgical lymphovenous anastamosis. 8 In this procedure, a lymph channel, usually at the level of the inguinal region, is anastomosed in an end-to-side fashion to the deep venous system of the leg. This requires a microvascular anastomosis. The size disparity between the wall of the lymph channel and that of the wall of the vein is great; for this reason, these procedures have a high failure rate. However, when they succeed, lymphatic outflow from the extremity is increased and good results can be obtained as long as the lymphovenous anastomosis stays patent. These patients still need to wear compression garments for life.
As with most chronic problems, the responsibility for managing lymphedema falls to the patient. Education about the etiology of lymphedema and principles for management are the first and most important part of patient education. Usually, when patients know what is behind the pathology of their condition, they can devise creative ways to deal with the manifestations of the disease, or at the very least, figure out a way to work the treatment into a schedule that maintains function for as long as possible.
Specific points to teach patients with lymphedema include the following:
•keep the affected extremity elevated higher than the heart whenever possible
•use the lymph pump on a schedule to maintain reduced edema
• wear compression garments between lymph pump treatments.
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