Lymphedema

Description

Lymphedema involves blockage of the lymph vessels, with a resulting accumulation of lymphatic fluid in the interstitial tissues of the body. The lymphatic system consists of lymph vessels and lymph nodes throughout the body. The lymph vessels collect lymphatic fluid, which consists of protein, water, fats, and wastes from cells. The lymph vessels transport the fluid to the lymph nodes, where waste materials and foreign materials are filtered out from the fluid. The fluid is then returned to the blood. When the vessels are damaged or missing, the lymph fluid cannot move freely throughout the system but accumulates. This accumulation of fluid results in abnormal swelling of the arm(s) or leg(s), and occasionally swelling in other parts of the body.

Lymphedema is a very serious condition. There is no cure for lymphedema and once it develops, it can be a long-term, uncomfortable, and sometimes painful condition requiring daily treatment. When lymphedema is not treated, the protein-rich fluid continues to accumulate, leading to even more swelling and hardening (referred to as fibrosis) of the tissues. This fluid is a good culture medium for bacteria, thus resulting in reoccurring infections when there are injuries to the skin, decrease or loss of functioning of the affected limbs, and skin breakdown. Infections, referred to lymphangitis, can affect the connective tissue under the skin. Repeated infections may result in scarring, which in turn makes the tissue susceptible to more swelling and infection. Over time, these infections result in tissue hardening (i.e., fibrosis), which is a characteristic of advanced chronic lymphedema. In very severe cases, untreated lymphedema may even result in a rare form of lymphatic cancer called lymphangiosarcoma.

Lymphedema affects approximately 100 million people worldwide, including at least 3 million people in the United States.

Symptoms of lymphedema include:

• swelling of an affected limb, which may develop gradually or suddenly
• tightness of the skin and a feeling of heaviness in the affected area
• discomfort or a feeling of "pins and needles" in the affected area
• pitting edema, which can be identified by observing a temporary indentation in the swollen area when pressure is placed on the affected area
• aching in the adjacent shoulder or hip due to the increasing weight of the swelling limb
• tight fitting of a ring, wristwatch, or bracelet, without a gain in weight.

In 90% of the cases, lymphedema is diagnosed through observations, measurements, and symptoms. The remaining 10% require the use of more complex diagnostic tests such as lymphoscintigraphy. Lymphoscintigraphy is a technique in which a radioactive substance that concentrates in the lymphatic vessels is injected into the affected tissue and is mapped using a gamma camera, which images the location of the radioactive tracer. Magnetic resonance imaging (MRI), computed tomography (CT) scanning, and duplex ultrasound are imaging techniques that are also sometimes used as diagnostic tools for lymphedema.

There are three stages of lymphedema:

• Stage 1 (spontaneously reversible)—tissue is still at the pitting stage and soft to the touch. Upon waking in the morning, the limbs or affected areas are of normal or almost normal size
• Stage 2 (spontaneously irreversible)—tissue is non-pitting and no longer soft to the touch, fibrosis begins to form, and the limbs increase in size
• Stage 3 (lymphostatic elephantiasis )—swelling is irreversible and the affected areas are very swollen. The skin hardens and begins to break down, fibrosis is more extensive, and patients may need surgery to remove some of the swollen tissues.

Causes

Primary lymphedema is an inherited condition, where the patient is born without lymph vessels and nodes. The swelling associated with primary lymphedema usually occurs during adolescence and affects the foot or calf. A rare form of primary lymphedema, called Milroy's Disease, occurs in pregnancy. However, secondary lymphedema, or acquired lymphedema, develops as a result of an injury to the lymph system. Specific causes include surgical treatments for certain types of cancers, especially those cancers that currently require the removal of lymph nodes. Radiation treatment for cancer or for some AIDs-related diseases such as Kaposi-Sarcoma may also result in lymphedema, as radiation may damage or destroy lymph nodes or cause the formation of scar tissue that can interrupt the normal flow of the lymphatic fluid. Specific cancers and their treatment that may result in lymphedema include malignant melanoma, breast (in both women and men), gynecological, head and neck, prostate, testicular, bladder, and colon cancer. Other causes of lymphedema include trauma to the lymphatic system from burns, liposuction, tattooing, injuries, surgery, radiation, obesity, heart or circulatory disease, and multiple sclerosis. Lymphedema in people at risk may not develop the condition immediately, but develop the condition weeks, months, or even years later. Aircraft travel has been linked to the development of lymphedema in patients after cancer surgery, possible due to the decreased cabin pressure.

In Western countries, one of the most common causes of lymphedema is mastectomy with axillary dissection (removal of the breast and underarm lymph tissue for treatment of breast cancer ), which may result in lymphedema of the breast, underarm, or arm on the side of the surgery in 10-20% of patients. This occurs because the lymphatic drainage of the arm passes through the axilla (armpit), and tissue in the axilla is removed during the mastectomy. To reduce the risk of developing lymphedema after breast cancer treatment, there is an alternative treatment that avoids axillary lymph node dissection. Sentinel lymph node biopsy is a new diagnostic procedure used to determine whether the breast cancer has spread (metastasized) to axillary lymph nodes. A sentinel lymph node biopsy requires the removal of only one to three lymph nodes for close review by a pathologist. If the sentinel nodes do not contain tumor (cancer) cells, this may eliminate the need to remove additional lymph nodes in the axillary area. Early research on this technique indicates that sentinel lymph node biopsy may be associated with less pain and fewer complications than standard axillary dissection. Because the procedure is so new, long term data are not yet available. However, there is still a risk for developing lymphedema because of follow-up radiation treatments or chemotherapy, which may also damage the lymph nodes.

Persons who have developed lymphedema after cancer treatment should be checked for a possible reoccurrence of cancer if they experience a sudden increase of swelling, for the tumor growth may be responsible for blocking lymphatic flow.

Treatments

Lymphedema is a chronic condition that cannot be cured, but it can be improved with treatment. There are several major components of a lymphedema treatment program, which should be administered by the health care provider in cooperation with a physical therapist trained in lymphedema treatment. Complete Decongestive Therapy (CDT; also referred to as Complex Decongestive Therapy (CDT) or as Complete Decongestive Physiotherapy (CDP)) combines manual lymph drainage (MLD) with compression techniques and with patient education on self-care needs. The goals of the treatment program are to:

• remove the stagnant lymph fluids out of the tissues
• reduce and help control swelling
• soften fibrotic tissue
• improve the overall health of the patient.

However, some lymphedema specialists feel that lymphedema patients with metastatic cancer should not be treated with CDT, to prevent the spreading of the cancer.

MLD was developed in 1932 in Denmark by a doctor and his wife. It was widely used in Europe and now is accepted as a therapy for lymphedema patients in the United States. In MLD a series of rhythmic, light strokes are made in a specific sequence along the lymphatic vessels and the adjoining tissues. These movements remove the lymph fluids from the tissues and return them to the circulatory system, thus reducing swelling in the affected area.

Compression techniques include the use of compression garments, compression aids, and compression bandages. These techniques encourage natural drainage and prevent swelling by supporting tissues in a way that aids in drainage. Compression garments are knit, stretch sleeves or stockings. Compression aids are custom-fitted sleeves, stockings, or pads made of fabric-covered foam. Bandages are an effective and flexible means of compression. They work when the patient is active or is resting and can easily be adjusted to fit changing limb sizes. However, the bandage should be a special type of short-stretch bandage and not the long-stretch bandage that is commonly known as Ace bandages. Only persons who are trained in lymphedema therapy should tape or wrap swollen areas.

Self-care techniques are practiced by the patient or his or her caregiver at home, between visits to the therapist. Self-care techniques include self-massage, skin care to maintain healthy tissue, nutritious diet, and exercise to increase lymph flow, increase mobility, and to improve the patient's general health.

Exposure to extreme heat has the potential to increase lymphedema swelling, so an affected person or a person at risk of developing lymphedema should avoid hot tubs, saunas, and steam rooms.

To keep the affected extremities as healthy as possible, a person with lymphedema should keep the swollen areas clean and avoid heavy lifting and pulling as well as avoid any type of trauma, such as cuts, bruises, sunburn or other burns, injections, sports injuries, insect bites, or cat scratches. Some doctors and lymphedema therapists recommend that a person with lymphedema use a preventative course of antibiotics when having dental treatment, that is, starting antibiotics several days before the appointment and continuing several days afterwards. A person at risk of developing lymphedema (for example, a woman who has been treated for breast cancer) should also observe the same type of precautions to prevent the development of the condition.

If infections occur, then all treatments for lymphedema should be discontinued while the infection is present, and the infection treated with antibiotics.

Surgery is sometimes used to remove excess tissue ("debulking") if the swollen limb becomes so large and heavy as to interfere with movement.

Exercise is important for a person with lymphedema, but only in moderation. If the extremity starts to ache, the person should lie down and elevate the swollen limb. Recommended exercises include walking, swimming, light aerobics, bike riding, and yoga.

Persons with lymphedema should wear a lymphedema alert bracelet or necklace for safety during a medical emergency, explaining the risk of infections. They may also benefit from counseling and membership in support groups to deal with the psychological impact of the disease. Sometimes patients with lymphedema will be denied insurance coverage for treatment; as a result patient advocacy groups in 2005 are attempting to get a law passed through the U.S. Congress guaranteeing insurance coverage for lymphedema.

Alternative and complementary therapies

The use of clinical aromatherapy in conjunction with CDT may improve the quality of life for persons with lymphedema. Clinical aromatherapy involves the use of essential oils to improve the functioning of the immune system, for the immune system is closely associated with the lymphatic system. Also a massage oil comprised of a blend of frankincense, grapefruit, hyssop, and lavender, may be used to soften scarred and fibrotic tissues. Radiation treatments can cause skin contractures, which can be helped by massage with a blend of cajeput, frankincense, hyssop, lavender, sage, and tea tree. Radiation can also have adverse effects on the bowel, resulting in poor bowel functioning, scarring, and activity restrictions. Massaging the abdomen with a blend of grapefruit, fennel, helichrysum, lavender, myrrh, and sage may improve intestinal functions. When compression techniques are used, the underlying skin can be treated with a blend of bay laurel, chamomile, geranium, helchrysum, lavender, patchouli, and vetiver in a combination of castor oil, safflower oil, and grapeseed oil as carrier oils. Good skin care is important in preventing infections. Body oils that contain cajeput, cypress, lavender, marjoram, and rosewood can be applied after bathing to keep the skin moist and healthy. Finger nail beds can be a portal of entry for infections, so can be kept moist with an essential oil blend of chamomile, geranium, lavender, lemon, sage, tea tree, and ylang ylang.

Resources

BOOKS

Burt, Jeannie, and White, Gwen. Lymphedema: A Breast Cancer Patient's Guide to Prevention and Healing. Berkeley, CA: Publisher's Group West, 1999.

French, Ramona Moody. Milady's Guide to Lymph Drainage Massage. Clifton Park, NY: Milady Publishing, 2003.

Kelly, Deborah G. A Primer on Lymphedema. Essex, United Kingdom: Pearson Education, 2001.

Parker, James N. and Parker, Philip M.. San Diego, CA: Icon Health Publications, 2004.

PERIODICALS

Heckathorn, Peg. "Use of Aromatherapy in Lymphedema Management." Lymph Link. Oct-Dec. 2003, Vol. 15, No. 4, 6-12

OTHER

Lymph Notes, an online information resource and support group for those with lymphedema and for the family, friends, and therapists who care for them. Web site: 〈www.lymphnotes.com/index.php〉

National Lymphedema Network, Latham Square Building, Suite 1111, 1611 Telegraph Avenue, Oakland, CA 94612-2138. Telephone: (800) 541-3259. Fax: (510) 208-3110. Web site: 〈www.lymphnet.org〉

Lymphedema People. Web site: 〈www.lymphedemapeople.com/〉

Lymphatic Research Foundation. 〈http://www.lymphaticresearch.org〉

Lymphedema Awareness Foundation. 〈http://www.elymphnotes.com/〉

KEY TERMS

Axillary nodes— Lymph nodes found in the armpit that drain the lymph channels from the breast.

Clinical aromatherapy— Aromatherapy is the therapeutic use of plant-derived, aromatic essential oils to promote physical and psychological well-being. It is sometimes used in combination with massage and other therapeutic techniques as part of a holistic treatment approach.

Debulking— General term used for surgeries in which subcutaneous tissue is removed from lymphodemous limb.

Fibrosis— Formation of fibrous tissue as a reaction or as a repair process; may occur due to treatment and/or disease. in lymphedema condition known as hardening of the limb with resulting restriction of circulatory flow, increased infection, and weeping sores.

Fibrotic— Pertaining to or characterized by fibrosis. In dermatological description, "fibrotic" would be used to describe leathery, bound-down, or thickened, scarred skin.

Interstitial fluid— The fluid between cells in tissues. Referred to as the liquid subtance of the body.

Interstitial space— The fluid filled areas that surround the cells of a given tissue; also known as tissue space.

Long-stretch bandages— Specialized bandages, similar to an Ace bandage, that have 100 to 200% stretch.

Low-stretch bandage— Specialized bandages, with 30 to 90% stretch, that are used to obtain the correct compression during the treatment of lymphedema; also known as short-stretch bandages.

Lymph— The almost colourless fluid that bathes body tissues and is found in the lymphatic vessels that drain the tissues of the fluid that filters across the blood vessel walls from blood. Lymph carries antibodies and lymphocytes (white blood cells that help fight infection) that have entered the lymph nodes from the blood.

Lymph nodes— Small bean-shaped organs of the immune system, distributed widely throughout the body and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells.

Lymph System— When sickness or infection invades the body, the immune system is the first line of defense. A big part of that defense is the lymph system. Lymph is carried through the body by lymph vessels that have valves and muscles to help move the fluid. Along the route are lymph nodes that serve as filters for harmful substances. This network of vessels and nodes together is called the lymph system.

Lymphatic fluid— The clear fluid found outside the cells which bathes the tissues. It is collected, filtered, and transported by the lymphatic system from around the tissues to the blood circulatory system. Fluid that collects as a result of lymphedema.

Nail beds— The underlying connective tissue that nourishes the finger and toenails.

Pitting edema— When a swollen area is pressed, the pressure leaves an indentation (pit) that takes time to fill back in.

Sentinel node biopsy— A newer procedure performed in order to determine whether breast cancer has spread to auxiliary (underarm) lymph nodes. A blue radioactive tracer and/or blue dye is injected into the area of the breast tumor. The lymphatic vessels carry the dye or radioactive material, to a "sentinel node". This sentinel node is thought to be the first lymph node receiving fluid from the tumor and the one most likely to contain cancer cells if the cancer has spread. Only if the sentinel node contains cancer cells are more lymph nodes removed.

Skin contracture— A permanent tightening of the skin that prevents normal movement of the associated body part and that can cause permanent deformity. A contracture develops when the normally elastic connective tissues are replaced by inelastic fibrous tissue. This makes the affected area resistant to stretching and prevents normal movement.

Lymphatic System

Lymphocytes

Lymph Nodes

Lymphatic Vessels

Other Lymphatic Organs

Lymphatic Diseases

Resources

The lymphatic system is the body’s network of organs, ducts, and tissues that filter harmful substances out of the fluid that surrounds body tissues. Lymphatic organs include the bone marrow, thymus, spleen, appendix, tonsils, adenoids, lymph nodes, and Peyer’s patches (in the small intestine). The thymus and bone marrow are called primary lymphatic organs, because lymphocytes are produced in them; the others are secondary lymphatic organs.

Lymphocytes are a type of white blood cell that is highly concentrated in lymphatic fluid. This clear fluid, also called lymph, travels through the lymphatic vessels, which connect the lymphatic organs. The terminal lymphatic vessels feed into the thoracic duct that returns body fluids to the heart prior to blood reoxygenation. The reincorporated fluid originates in the bloodstream, bathes organs and tissues, and returns to the bloodstream after passing through lymphatic filters that function as part of the body’s defense system against infection and cancer.

Lymph nodes, clustered primarily in the neck, armpits, and pelvic area, are the system’s battle stations against infection. Lymph nodes are connected to one another by lymphatic vessels. It is in the nodes and other secondary organs where white blood cells engulf and destroy debris to prevent them from reentering the bloodstream. Of the other two major secondary lymphatic organs, the spleen removes dead red blood cells, and Peyer’s patches remove intestinal antigens (foreign or harmful substances in the body).

Lymphocytes

Lymphocytes are the lymphatic system’s foot soldiers, identifying enemy particles and attempting to destroy them. Lymphocytes fall into two general categories: T lymphocytes (T cells) and B lymphocytes (B cells). T cells form in the thymus (in the chest), and B cells form in the bone marrow of the long, thick

bones of the thigh, arm, spine, or pelvis. While T cells primarily attack viral antigens, B cells attack bacterial antigens. Both travel in lymph, through lymphatic vessels, and into lymph nodes.

T cells are further divided into three primary classes: helper T cells (T-H cells), cytotoxic T cells (ctx T cells), and T suppressor T cells. T-H cells augment B cell responses to bacterial antigens. Cytotoxic T cells attack viral antigens and some early cancer cells. And suppressor T cells halt immune cell functions, allowing the body to rest.

B cells produce antibodies. According to their basic immunoglobulin type, antibodies are subdivided into five classes: IgM, IgD, IgG, IgE, and IgA. B cell antibodies recognize specific bacterial invaders and destroy them. Certain antibodies are more concentrated in areas of the body where they are most needed. For example, IgA-producing B cells are most concentrated in the Peyer’s patches, where they sample intestinal contents for potential antigens that could signal an infectious invasion of food-borne bacteria.

Lymph Nodes

Lymph nodes are pockets of lymph that orchestrate the removal of foreign material (including bacteria, viruses, and cancerous cells) from the lymph. They vary in size from microscopic to about 0.16 inch (0.394 cm) in diameter. Some nodes cluster at key sites where the limbs join the torso. Lymph nodes are named after their locations in the body. The nodes at the arm are called axial and brachial, those under the jaw are called subclavian, and those in the groin are called inguinal. Fibrous connective tissue covers the lymphatic tissue inside the lymph node.

Each node, also called a lymph gland, has both arterial blood supply and venous drainage. Lymphocytes drain out of the arteries into the node interior, usually through a high endothelial venule that facilitates their entry. This venule (small vein) derives its name from the higher-than-usual tightly joined endothelial cells that line it.

Before they can enter the lymph node, lymphocytes are carefully selected from other blood cells. They are recognized and distinguished by a lymphocyte-cell surface protein called E-selectin. Receptors on the endothelial cells bind the E-selectin positive lymphocytes and slowly roll them toward a gap between adjacent cells. Then the lymphocyte is fed through this area much the way film is fed into a camera. The lymphocytes emerge on the interior of the node.

The internal lymph node tissue is separated into lobes. The lobe end at the center of the node is called the medulla, whereas the wider lobe end toward the perimeter of the node is called the cortex. The lobe area just next to the cortex is called the paracortex. Surrounding the lobes is an area called the medullary sinus. T cells are concentrated in the paracortex, whereas B cells primarily are concentrated in the cortex in structures called primary follicles. Lymphocytes first travel to the medullary sinus before migrating to the cortical and paracortical regions.

In addition to lymphocytes, several other kinds of antigen-fighting white blood cells are contained within the nodes. Macrophages destroy and devour foreign antigens under direction from lymphocytes. Within the cortex, a large wbc called an interdigitating dendritic cell actually gathers the foreign antigen and presents it to the T cells that, in turn, trigger the antigen’s destruction. This system is carefully controlled to avoid destroying host cells. Within the paracortex, follicular dendritic cells present antigens to B cells in a region of the follicles called the germinal centers. Within germinal centers, memory B cells are formed that are specifically primed to launch an attack against an antigen if it is encountered again. Like seasoned soldiers who know how to fight a particular enemy, memory B cells are molecularly armed to combat a known antigen.

Foreign antigens are constantly being destroyed; however, when a particularly strong infection occurs, the lymph nodes will sometimes swell with the influx of backup troops (more white blood cells) sent in to help fight a particular molecular attacker. Eventually, the lymphocytes leave the node through the efferent lymphatic vessel.

Lymphatic Vessels

Lymphatic vessels infiltrate tissues that are bathed in fluid released from blood into those tissues. Pockets of fluid collect in the tissues, and increased pressure allows the fluid to seep into the lymphatic vessels. Whereas blood vessels return deoxygenated blood to the heart to be pumped to the lungs for oxygen, lymphatic vessels return fluid that has leaked out of the capillaries into various tissues. However, before this lymphatic fluid is rejoined with venous fluid at the thoracic duct, it is filtered through the lymph nodes to remove infectious agents.

Lymphatic vessels are made of single-cell epithelial layers that drain fluid away from tissue. Smooth muscles controlled by the autonomic nervous system direct the fluid away from tissues toward the lymph nodes and, eventually, the heart. The vessels contain one-way valves that close behind fluid traveling back to the heart so that lymphatic fluid cannot go backward. Lymphatic fluid is usually returned to the circulation within 24 hours. When the lymphatic vessels become clogged, stopped up, or blocked, severe edema (bloating due to water retention) can result in a condition known as lymphedema.

Other Lymphatic Organs

Of the remaining lymphatic system components, the thymus, bone marrow, spleen, and Peyer’s patches have fairly unique roles. Both the bone marrow and thymus introduce “virgin” lymphocyte to the lymphatic system. The spleen filters old red blood cells from the blood and fights infections with lymphocytes and monocytes (cells that engulf and devour antigens). And the Peyer’s patches are lymph tissue pockets under raised intestinal projections that examine intestinal contents for foreign antigens. Although the spleen’s role is important, the human body is capable of functioning without it if it becomes injured or diseased.

Although the thymus is critical for T cell development in children, it begins to shrink as they progress toward adulthood and thereafter plays an increasingly reduced role. T cells are “educated” in the thymus to recognize “self” versus “nonself” (foreign) antigens. Without the ability to recognize self-antigens, T cells would target a person’s own tissues in a very destructive manner. The thymus is also responsible for fostering maturation of T cells into their various subclasses. T cells function in a cell-mediated way such that they only recognize antigens presented to them by other cells; hence, T cell immunity is called cell-mediated immunity.

Both T cells (before branching off to develop in the thymus) and B cells originate in the pluripotential stem cells of the bone marrow or the fetal liver. Pluripotential stem cells are the body’s cellular sculpting clay. They can be shaped into any cell—including lymphocytes, red blood cells, macrophages, and numerous other blood constituents—and become increasingly specialized as they reach maturity. The B cells can generate an infinite number of antibodies in response to a multitude of foreign antigens. This amazing diversity arises from the many combinations of antibody components that can be rearranged to recognize individual antigens. Once a B cell identifies a particular enemy, it undergoes a process called clonal expansion. During this process, it makes many clones (copies) of itself to fight several invaders of a single type. This highly sophisticated molecular process destroys infections wherever they arise in the body.

One specialized form of antibody, IgA, detects antigens in the gastrointestinal tract at Peyer’s patches. IgA contained within small projections called lamina propriae extend into the small intestine to test the intestinal lining for pathogens. The IgA binds to the foreign antigen, returns to exit the patch at its efferent lymphatic vessel, and travels to a mesenteric lymph node that gears up to fight the invader. IgA antibodies are also passed to nursing babies in their mothers’ milk, because newborns do not synthesize IgAs until later.

Lymphatic Diseases

Although lymph nodes commonly enlarge to fight infection, an overwhelming infection can leave a lymph node and travel through the lymphatic system to other nodes and even to other body tissues. Cancer can spread very easily through the lymph system, but different cancers vary in how soon they attack the nodes. Lymphedema, fluid accumulation, can occur when the movement of fluid in a lymphatic region is blocked. Although lymphedema is rare, limbs are the most commonly affected areas.

The unregulated growth of cells and tissues of the lymphatic system can lead to lymphoma, or lymph cancer. Lymphomas are classified into two types, Hodgkin’s or non-Hodgkin’s. Hodgkin’s disease is marked by enlargement of lymph nodes. Symptoms include chronic fatigue, depressed immune function, weight loss, night sweats, and pain after drinking alcohol. Hodgkin’s is diagnosed by lymph node biopsy, with identification confirmed by the presence of large, multi-nucleated Reed-Sternberg cells. Hodgkin’s is further categorized as lymphocyte predominant, nodular sclerosis, mixed cellularity, or lymphocyte-depleted depending on cell populations present in the biopsy sample. Hodgkin’s disease can be treated and cured with radiation or chemotherapy if it is caught in its early stages.

Although the cause of Hodgkin’s is unknown, males, caucasians, people of higher socioeconomic status, the well-educated, and people with certain blood types are more prone to develop it. Hodgkin’s most often affects people in their 20s or 70s for unknown reasons. People who work with certain chemicals, such as benzene and rubber products, also seem to be more prone to develop the disease.

Non-Hodgkin’s lymphoma is also diagnosed through lymph tissue biopsy. Several lymphomas have been identified, but have little in common. Burkitt’s lymphoma, prevalent among central African children, is characterized by enlarged subclavian lymph nodes. In contrast with most lymphomas whose causes are unclear, Burkitt’s lymphoma has been linked to infection with the Epstein-Barr virus. Mycosis fungoides is a rare T cell lymphoma that affects the skin. Non-Hodgkin’s lymphomas are further classified as lymphocytic or histiocytic. Lymphocytic lymphomas may be poorly

KEY TERMS

Lymph —Lymphatic fluid, rich in white blood cells, that runs through the lymphatic vessels, lymph nodes, and other lymphatic organs.

Lymph node —Region of lymphoid tissue along lymph vessels that filters harmful antigens from the blood and some tissues.

Lymphocyte —A cell that functions as part of the lymphatic and immune systems by attacking specific invading substances.

differentiated (according to the extent to which they have evolved from the pluri potential stem cell); they may also be nodular (concentrated) or diffuse.

Symptoms for most lymphomas are similar. Many patients experience enlargement of the liver and spleen as well as the lymph nodes. Some patients have bloody stools or vomit blood. Tiredness, itching, weight loss, fever, and general immunosuppression may also be present. The symptoms may abate and intensify over several months before a diagnosis is made. Sometimes, a bone marrow biopsy is also performed. Treatment includes radiation or chemotherapy with effectiveness varying according to severity of the lymphoma at the time of diagnosis. Bone marrow transplants have been effective against some advanced-stage lymphomas. The “cure” rate for non-Hodgkin’s lymphomas is generally poorer than for Hodgkin’s lymphomas.

See also Antibody and antigen; Immune system.

Resources

BOOKS

Alberts, B., D. Bray, J. Lewis, M. Raff, K. Roberts, and J. Watson, eds. Molecular Biology of the Cell. 3d ed. New York: Garland Publishing, 1994.

Marieb, Elaine Nicpon. Human Anatomy & Physiology. 5th Edition. San Francisco: Benjamin/Cummings, 2000.

OTHER

Lymph Notes. “Understanding the Lymphatic System” <http://www.lymphnotes.com/article.php/id/151/> (accessed December 2, 2006).

Lymphoma Information Network. “The Lymphatic System” <http://www.lymphomainfo.net/lymphoma/lymphsys.html> (accessed December 2, 2006).

Louise Dickerson

Lymphatic system

The lymphatic system is the body's network of organs, ducts, and tissues that filter harmful substances out of the fluid that surrounds body tissues. Lymphatic organs include the bone marrow, thymus, spleen, appendix, tonsils, adenoids, lymph nodes, and Peyer's patches (in the small intestine). The thymus and bone marrow are called primary lymphatic organs, because lymphocytes are produced in them. The other lymphatic organs are called secondary lymphatic organs.

Lymphocytes are a type of white blood cell (wbc), which is highly concentrated in lymphatic fluid. This clear fluid, also called lymph, travels through the lymphatic vessels, which connect the lymphatic organs. The terminal lymphatic vessels feed into the thoracic duct that returns body fluids to the heart prior to blood reoxygenation. The reincorporated fluid originates in the bloodstream, bathes organs and tissues, and is returned to the bloodstream after passing through lymphatic filters that function as part of the body's defense system against infection and cancer .

Lymph nodes, primarily clustered in the neck, armpits, and pelvic area, are the system's battle stations against infection. Lymph nodes are connected to one another by lymphatic vessels. It is in the nodes and other secondary organs where wbcs engulf and destroy debris to prevent them from reentering the bloodstream. Of the other two major secondary lymphatic organs, the spleen removes dead red blood cells (rbcs), and Peyer's patches remove intestinal antigens (foreign or harmful substances in the body).

Lymphocytes

Lymphocytes are the lymphatic system's foot soldiers. These cells identify enemy particles and attempt to destroy them. Lymphocytes fall into two general categories: T lymphocytes (T cells ) and B lymphocytes (B cells). T cells form in the thymus (in the chest), and B cells form in the bone marrow of the long, thick bones of the thigh, arm, spine, or pelvis. While T cells primarily attack viral antigens, B cells attack bacterial antigens. Both T and B cells travel in lymph, through lymphatic vessels, and into lymph nodes.

T cells are further divided into three primary classes: helper T cells (T-H cells), cytotoxic T cells (ctx T cells), and T suppressor T cells. T-H cells augment B cell responses to bacterial antigens. Cytotoxic T cells attack viral antigens and some early cancer cells. And suppressor T cells halt immune cell functions, allowing the body to rest.

B cells produce antibodies. According to their basic immunoglobulin type, antibodies are subdivided into five classes (IgM, IgD, IgG, IgE, and IgA). B cell antibodies recognize specific bacterial invaders and destroy them. Certain antibodies are more concentrated in areas of the body where they are most needed. For example, IgA-producing B cells are most concentrated in the Peyer's patches where they sample intestinal contents for potential antigens that could signal an infectious invasion of food-borne bacteria .

Lymph nodes

Lymph nodes are pockets of lymph that orchestrate the removal of foreign material (including bacteria, viruses, and cancerous cells) from the lymph. They vary in size from microscopic to about 0.16 in (0.394 cm) in diameter. Some nodes cluster at key sites where the limbs join the torso. Lymph nodes are named after their locations in the body. The nodes at the arm are called axial and brachial, those under the jaw are called subclavian, and those in the groin are called inguinal. Fibrous connective tissue covers the lymphatic tissue inside the lymph node.

Each node, also called a lymph gland, has both arterial blood supply and venous drainage. Lymphocytes drain out of the arteries into the node interior, usually through a high endothelial venule that facilitates their entry. This venule (small vein) derives its name from the higher-than-usual tightly joined endothelial cells that line it.

Before they can enter the lymph node, lymphocytes are carefully selected from other blood cells. They are recognized and distinguished by a lymphocyte-cell surface protein called E-selectin. Receptors on the endothelial cells bind the E-selectin positive lymphocytes and slowly roll them toward a gap between adjacent cells. Then the lymphocyte is fed through this area much the way film is fed into a camera. The lymphocytes emerge on the interior of the node.

The internal lymph node tissue is separated into lobes. The lobe end at the center of the node is called the medulla, whereas the wider lobe end toward the perimeter of the node is called the cortex. The lobe area just next to the cortex is called the paracortex. Surrounding the lobes is an area called the medullary sinus. T cells are concentrated in the paracortex, whereas B cells primarily are concentrated in the cortex in structures called primary follicles. Lymphocytes first travel to the medullary sinus before migrating to the cortical and paracortical regions.

In addition to lymphocytes, several other kinds of antigen-fighting wbcs are contained within the nodes. Macrophages destroy and devour foreign antigens under direction from lymphocytes. Within the cortex, a large wbc called an interdigitating dendritic cell actually gathers the foreign antigen and presents it to the T cells that, in turn, trigger the antigen's destruction. This system is carefully controlled to avoid destroying host cells. Within the paracortex, follicular dendritic cells present antigens to B cells in a region of the follicles called the germinal centers. Within germinal centers, memory B cells are formed that are specifically primed to launch an attack against an antigen if it is encountered again. Like seasoned soldiers who know how to fight a particular enemy, memory B cells are molecularly armed to combat a known antigen.

Foreign antigens are constantly being destroyed; however, when a particularly strong infection occurs, the lymph nodes will sometimes swell with the influx of backup troops (more wbcs) sent in to help fight a particular molecular attacker. Eventually, the lymphocytes leave the node through the efferent lymphatic vessel.

Lymphatic vessels

Lymphatic vessels infiltrate tissues that are bathed in fluid released from blood into those tissues. Pockets of fluid collect in the tissues, and increased pressure allows the fluid to seep into the lymphatic vessels. Whereas blood vessels return deoxygenated blood to the heart to be pumped to the lungs for oxygen , lymphatic vessels return fluid that has leaked out of the capillaries into various tissues. However, before this lymphatic fluid is rejoined with venous fluid at the thoracic duct, it is filtered through the lymph nodes to remove infectious agents.

Lymphatic vessels are made up of single-cell epithelial layers that drain fluid away from tissue. Smooth muscles controlled by the autonomic nervous system direct the fluid away from tissues toward the lymph nodes and, eventually, the heart. The vessels contain one-way valves that close behind fluid traveling back to the heart so that lymphatic fluid cannot go backward. Lymphatic fluid is usually returned to the circulation within 24 hours. When the lymphatic vessels become clogged, stopped up, or blocked, severe edema (bloating due to water retention) can result in a condition known as lymphedema.

Other lymphatic organs

Of the remaining lymphatic system components, the thymus, bone marrow, spleen, and Peyer's patches have fairly unique roles. Both the bone marrow and thymus introduce "virgin" lymphocyte to the lymphatic system. The spleen filters old rbcs from the blood and fights infections with lymphocytes and monocytes (cells that engulf and devour antigens). And the Peyer's patches are lymph tissue pockets under raised intestinal projections that examine intestinal contents for foreign antigens. Although the spleen's role is important, the human body is capable of functioning without it if it becomes injured or diseased.

Although the thymus is critical for T cell development in children, it begins to shrink as they progress toward adulthood and thereafter plays an increasingly reduced role. T cells are "educated" in the thymus to recognize "self" versus "nonself" (foreign) antigens. Without the ability to recognize self-antigens, T cells would target a person's own tissues in a very destructive manner. The thymus is also responsible for fostering maturation of T cells into their various subclasses. T cells function in a cell-mediated way such that they only recognize antigens presented to them by other cells; hence, T cell immunity is called cell-mediated immunity.

Both T cells (before branching off to develop in the thymus) and B cells originate in the pluripotential stem cells of the bone marrow or the fetal liver. Pluripotential stem cells are the body's cellular sculpting clay. They can be shaped into any cell-including lymphocytes, rbcs, macrophages, and numerous other blood constituentsand become increasingly specialized as they reach maturity. The B cells can generate an infinite number of antibodies in response to a multitude of foreign antigens. This amazing diversity arises from the many combinations of antibody components that can be rearranged to recognize individual antigens. Once a B cell identifies a particular enemy, it undergoes a process called clonal expansion. During this process, it makes many clones (copies) of itself in order to fight several invaders of a single type. This highly sophisticated molecular process destroys infections wherever they arise in the body.

One specialized form of antibody, IgA, detects antigens in the gastrointestinal tract at Peyer's patches. IgA contained within small projections, called lamina propriae, that extend into the small intestine test the intestinal lining for pathogens . The IgA binds to the foreign antigen, returns to exit the patch at its efferent lymphatic vessel, and travels to a mesenteric lymph node that gears up to fight the invader. IgA antibodies are also passed to nursing babies in their mothers' milk, because newborns do not synthesize IgAs until later.

Lymphatic diseases

Although lymph nodes commonly enlarge to fight infection, an overwhelming infection can leave a lymph node and travel through the lymphatic system to other nodes and even to other body tissues. Cancer can spread very easily through the lymph system, but different cancers vary in how soon they attack the nodes. Lymphedema, fluid accumulation, can occur when the movement of fluid in a lymphatic region is blocked. Although lymphedema is rare, limbs are the most commonly affected areas.

The unregulated growth of cells and tissues of the lymphatic system can lead to lymphoma, or lymph cancer. Lymphomas are classified into two types, Hodgkin's or non-Hodgkin's, both of which can be malignant. Hodgkin's disease is marked by enlargement of lymph nodes, usually those in the neck. Symptoms of Hodgkin's include chronic fatigue, depressed immune function, weight loss, night sweats, and pain after drinking alcohol . Hodgkin's is diagnosed by lymph node biopsy, with identification confirmed by the presence of Reed-Sternberg cells, large multinucleated cells. Hodgkin's is further categorized as lymphocyte predominant, nodular sclerosis, mixed cellularity, or lymphocyte-depleted on the basis of the cell populations present in the biopsy sample. Hodgkin's can be successfully treated and cured with radiation or chemotherapy if it is caught in its early stages. Although the cause of Hodgkin's is unknown, males, Caucasians, people of higher socioeconomic status, the well-educated, and people with certain blood types are more prone to develop it. Hodgkin's most often affects people in their 20s or 70s for unknown reasons. People who work with certain chemicals, such as benzene and rubber products, also seem to be more prone to develop the disease .

Non-Hodgkin's lymphoma is also diagnosed through lymph tissue biopsy. Several lymphomas have been identified, but have little in common. Burkitt's lymphoma, prevalent among Central African children, is characterized by enlargement of the lymph nodes under the jaw. In contrast with most lymphomas whose causes are unclear, Burkitt's lymphoma has been linked to infection with the Epstein-Barr virus . Mycosis fungoides is a rare T cell lymphoma that affects the skin.

Non-Hodgkin's lymphomas are further classified as lymphocytic or histiocytic. Lymphocytic lymphomas may be poorly differentiated (according to the extent to which they have evolved from the pluri potential stem cell); they may also be nodular (concentrated) or diffuse.

Symptoms for most lymphomas are similar. Many patients experience enlargement of the liver and spleen as well as the lymph nodes. Some patients have bloody stools or vomit blood. Tiredness, itching, weight loss, fever, and general immunosuppression may also be present. The symptoms may abate and intensify over several months before a diagnosis is made. Sometimes, a bone marrow biopsy is also performed. Treatment includes radiation or chemotherapy with effectiveness varying according to severity of the lymphoma at the time of diagnosis. Bone marrow transplants have been effective against some advanced-stage lymphomas. The "cure" rate for non-Hodgkin's lymphomas is generally poorer than for Hodgkin's lymphomas.

See also Antibody and antigen; Immune system.

Resources

books

Alberts, B., D. Bray, J. Lewis, M. Raff, K. Roberts, and J. Watson, eds. Molecular Biology of the Cell. 3d ed. New York: Garland Publishing, 1994.

Marieb, Elaine Nicpon. Human Anatomy & Physiology. 5th ed. San Francisco: Benjamin/Cummings, 2000.

Louise Dickerson

KEY TERMS

Lymph

—Lymphatic fluid, rich in white blood cells, that runs through the lymphatic vessels, lymph nodes, and other lymphatic organs.

Lymph node

—Region of lymphoid tissue along lymph vessels that filters harmful antigens from the blood and some tissues.

Lymphocyte

—A cell that functions as part of the lymphatic and immune systems by attacking specific invading substances.

Lymphatic system

Definition

The lymphatic system is composed of a network of vessels that collects fluid and plasma proteins that leak out of capillaries and into the interstitial space. Lymphatic vessels return the lymph (fluid and plasma protein) back to the circulatory system through the veins.

Description

The lymphatic system is a secondary system of vessels that is distinct both in anatomy and function from the blood vessel capillaries of the circulatory system. Small lymphatic vessels (or "lymphatics") called lymphatic capillaries are found in almost all organs of the body except superficial layers of the skin, the central nervous system , endomysium of muscles, and the bone. These exceptions have a system of smaller vessels called prelymphatics. Fluid from prelymphatics returns to nearby lymphatic vessels, or the cerebral spinal fluid in the case of the central nervous system.

Lymphatic capillaries are made up of a single layer of endothelial cells. They are anchored to the surrounding connective tissue by special filaments called anchoring filaments. The system begins as a series of sacs. Each sac has a low hydrostatic pressure relative to the outside of the sac. At the end of the lymphatic capillaries there are endothelial valves. The valves form as a result of the slight overlap of the endothelial cells, and the overlapping edge has the ability to open inward. The valves open enough to allow fluid and plasma protein to pass into the lymphatic capillary.

Inside the lymph vessels are valves that prevent the backflow of lymph, a general name for the slightly opalescent fluid picked up by the lymphatics. Surrounding the lymphatics are smooth muscles that contract involuntarily to assist in the movement of lymph through the system. The lymphatic capillaries converge into larger lymph vessels. The larger lymph vessels pass through swellings called lymph nodes and then empty into one of two large lymph ducts. The lymph ducts empty into the venous circulatory system through either the right or left subclavian veins. Lymph from the right side of the head, arm and chest empties into the right subclavian vein. Lymph collected from the lower part of the body, and lymph from the left side of the head, arm and chest empties into the left subclavian vein. Both subclavian veins are located within the thorax underneath the clavicles, the thin bones located on the top part of the chest.

At approximately 600 sites in the human body, lymphatic vessels converge into bundles of tissue called lymph nodes. The shape of a lymph node resembles a kidney bean and ranges in size from a few millimeters to a few centimeters. They are mostly found at the base of extremities such as the arms, legs and head. Many afferent lymphatics or vessels lead the lymph into the node at the larger curve of the bean shape and efferent lymphatics, fewer in number, take the lymph away from the node at the hilum, the depressed region of the bean shape. All nodes have a blood supply from the circulatory system running through them. The blood vessels enter and exit at the hilum. Inside the nodes are a honeycomb of lymphfilled sinuses that have macrophages and groupings of lymphocytes that produce antibodies.

As mentioned, lymph is the fluid flowing through the lymphatic system and originates from the interstitial spaces of the organs and tissues. Another element of the lymph is a type of cell of the immune system called a lymphocyte, which is a type of white blood cell. Lymphocytes mature in either the thymus (T-lymphocytes) or the bone marrow (B-lymphocytes), which are primary lymphoid organs The blood supply transports lymphocytes from their site of maturation (the thymus or bone marrow) to secondary lymphoid organs such as the lymph nodes, spleen, and tonsils. All lymphocytes in the adult originate in the bone marrow.

Function

Fluid enters organs and tissues from the arterial capillaries, and is eventually reabsorbed by the venous capillaries. However, not all of the fluid is reabsorbed by blood capillaries. About one tenth of the fluid is returned to the blood vessels via the lymphatic system. The lymphatic system reabsorbs about 2–4 qt (l) of fluid per day. Lymph composition is different depending on the site of origin. For example lymph collected from the gastrointestinal tract is high in fat that has been absorbed during digestion, and lymph collected from the bone marrow and thymus is high in lymphocyte concentration.

Lymph is collected when the pressure of the interstitial fluid and plasma proteins increases in the organs and tissues. Lymph pushes against the outside of the lymphatic valves and flows into the lymphatic capillary. This is called bulk flow. Valves are located throughout the lymphatic system approximately 0.15 in (38 mm) apart. Backflow is not possible in the lymphatics because the

valves open in only one direction. Therefore, the lymphatic system runs in only one direction.

There are several factors the affect the rate at which lymph is collected. Interstitial fluid pressure affects the rate of flow of fluid into the lymphatic capillaries. Elevated capillary pressure, increased interstitial fluid pressure, and increased capillary permeability all contribute to an increase in the amount of interstitial pressure and the rate of lymph flow.

Smooth muscles around the lymphatic vessels act as lymphatic pumps, and their involuntary contractions affect the rate of lymph flow. As the lymphatic vessel swells with fluid, the smooth muscle around that portion senses the stretch and automatically contracts, pushing the lymph through the valve to the next chamber. The valve prevents backwards flow as the smooth muscle in the chamber contracts to send the lymph through the next valve into the next chamber. This process continues along the entire vessel until the lymph passes through the lymph nodes and into the subclavian vein.

Factors outside of the lymphatic system can also affect the rate of lymph flow by assisting in the pumping of lymph through the system. The following eternal factors can increase lymph flow: contraction of close skeletal muscles , movements made by other parts of the body, nearby arterial pulses, and compression of tissues by items outside of the body. Therefore, during periods of exercise , the lymphatic system is extremely active and the flow rate is high.

The terminal end of the lymphatic capillary also has a pump that can affect the rate of lymph flow. When the interstitial fluid pressure is high, the surrounding tissue expands. The anchoring filaments that are attached to the endothelial cells at the terminal end of the lymphatic capillary and to the connective tissue pull the capillary valves open, allowing inward flow of interstitial fluid. Then the internal lymphatic capillary pressure causes the valves to close and the smooth muscle in the first compartment to contract and push the lymph into the next chamber.

Contractile actomyosin filaments are also present in the end terminal of the lymphatic vessels. These filaments cause the rhythmic contraction of the terminal end of the lymphatic capillary. Therefore, they contribute to part of the initial pumping of lymph through the system.

KEY TERMS

B-lymphocytes (B-cells) —A type of white blood cell that originates in the bone marrow and recognizes foreign antigens (or proteins), secreting antibodies in an immune response.

Interstitial space —The spaces found within organs and tissues.

Lymph —The slightly opalescent fluid found within the lymphatic system.

Lymph nodes —Bean shaped swellings along the lymphatic vessels that contain macrophages and lymphocytes.

Lymphatics —The system of lymphatic vessels.

T-lymphocytes (T-cells) —A type of white blood cell that originates in the thymus and attaches themselves to foreign organisms, secreting lymphokines that kill the foreign organisms.

Tonsil —A collection of lymphocytes that form a mass in the back of the pharynx.

Role in human health

The lymphatic system has a variety of roles in human health ranging from returning fluid from organs back to the circulatory system, to an important part in the human immune response , to absorbing lipids from the intestines. The defining role of the lymphatic vessels is to return any fluid that has leaked from the capillaries and into the interstitial space back to the circulatory system through the veins. This is important because if fluid was retained in the tissues, the result in reduced blood volume and swelling of the tissues.

Another important role of the lymphatic system is the ability of plasma proteins to fit through the lymphatic valves and into the lymphatic capillary. Since most proteins have such a high molecular weight, they are unable to be reabsorbed by venous capillaries. With out the reabsorption of the plasma proteins, humans can die within 24 hours.

The lymphatic system also has an essential role in the process of digestion. Primarily, the lymphatic capillaries in the gastrointestinal tract are one of the main routes for fats to be absorbed. Fats enter the lymphatics before entering the blood stream.

High molecular weight proteins are not the only large substances that are absorbed. Microorganisms such as bacteria can also fit between the endothelial cells of the terminal end of the lymphatic capillary. As this occurs and the bacteria are transported to the next lymph node, the meshwork of the node and sinuses with in the node act as a filter, catching and trapping the foreign organisms. Once trapped, microorganisms can be attacked by the concentrated cells of the immune system. Macrophages may consume disease-causing bacteria, Blymphocytes may come into contact with the antigens on the surface of the microorganism and stimulate antibodies, and T-lymphocytes called "killer" cells that attach themselves to the foreign organism and release a substance to destroy the organism. The destructive nature of the "killer" cells is enhanced by another T-lymphocyte called "helper" cells (T-helper cells also assist B-cells). If this system fails, then microorganisms are not destroyed, resulting in the spread of infection though the lymphatic system and extreme infection possibly leading to death.

Cancer cells that have lost adherence to, and break away from, the primary tumor are collected by the lymphatic system and filtered by latticework within the lymph nodes. Within the lymph node T-cells release substances called lymphokine (e.g. gamma interferor and interleukin 2) that may help destroy the cancer cells. Doctors use the lymph nodes as one factor of evaluation when determining the stage of the cancer. In other words, when determining how far the cancer has progressed at the time of diagnosis, the lymph nodes can be dissected to determine if cancer has spread (metastisized) from the original tumor or not. If cancer cells are present in the lymph nodes, then the cancer receives a higher stage and a less-optimistic diagnosis. In cancers that metastasize via the lymphatics, the lymph nodes where cancer cells are present are often removed. This is even more common when the lymph nodes in question are adjacent to the tumor, when the lymph nodes are located on the only lymphatic vessel present in the area of the tumor, or if no other lymphatics will be damaged during the removal.

Common diseases and disorders

Since the lymphatic system is responsible for draining excess fluid from tissues and organs, the most common symptom of diseases and disorders of the lymphatic system is swelling. For example, a disease known as elephantiasis, which is caused by a filarial worm infestation, involves the blockage of the lymphatics. When the lymphatics are blocked, fluid cannot be drained and swelling occurs in the affected areas. Administering ethyl-carbamazine drugs, elevating the area and wearing a compression stocking can treat elephantiasis.

Tonsillitis is another disease of the lymphatic system. Tonsillitis usually involves a bacterial or viral infection located within the tonsils. The tonsils are swollen, and the patient experiences a fever , sore throat , and difficulty swallowing. This can be treated by the use of antibiotics or through a surgical procedure called a tonsillectomy.

A condition common among individuals following surgery for breast cancer or prostate cancer is lymphedema. It is caused by blockage of lymph vessels or lymph nodes located near the surgical site and can result in swollen arms or legs. If microorganisms cause the swelling, then antibiotics are used as treatment. If microorganisms are not the cause, then compression garments and message therapy are used as treatment.

There are also cancers called lymphosarcomas and cancers of the lymph nodes that can affect the lymphatic system. The causes of these cancers are not known and there is not a consensus on what preventative measures can be taken to reduce the risk of developing these cancers. Symptoms of cancers affecting the lymphatic system include loss of appetite, energy, and weight, as well as swelling of the glands. As with many cancers, treatment includes surgical removal followed by adjuvant radiation and chemotherapy .

Resources

BOOKS

Braunwald, Eugene, et al. Harrison's Principles of Internal Medicine, 15th ed. New York: McGraw-Hill, 2001.

Lee, Richard G. M.D., et al. Wintrob's Clinical Hematology, 10th ed. Philadelphia: Lippincott Williams & Wilkins, 1999.

Vander, Arthur. Human Physiology: The Mechanisms of Body Function, Seventh ed. New York: WBC McGraw-Hill, 1998.

ORGANIZATIONS

Lymphatic Research Foundation. 941 N.E. 19th Avenue, Suite 305, Ft. Lauderdale, Florida, 33304-3071. (954)525-3510. <http://www.lymphaticresearch.org/>.

Sally C. McFarlane-Parrott

Lymphatic System

Definition

The lymphatic system is composed of a network of vessels that collects fluid and plasma proteins that leak out of capillaries and into the interstitial space. Lymphatic vessels return the lymph (fluid and plasma protein) back to the circulatory system through the veins.

Description

The lymphatic system is a secondary system of vessels that is distinct both in anatomy and function from the blood vessel capillaries of the circulatory system. Small lymphatic vessels (or "lymphatics") called lymphatic capillaries are found in almost all organs of the body except superficial layers of the skin, the central nervous system, endomysium of muscles, and the bone. These exceptions have a system of smaller vessels called prelymphatics. Fluid from prelymphatics returns to nearby lymphatic vessels, or the cerebral spinal fluid in the case of the central nervous system.

Lymphatic capillaries are made up of a single layer of endothelial cells. They are anchored to the surrounding connective tissue by special filaments called anchoring filaments. The system begins as a series of sacs. Each sac has a low hydrostatic pressure relative to the outside of the sac. At the end of the lymphatic capillaries there are endothelial valves. The valves form as a result of the slight overlap of the endothelial cells, and the overlapping edge has the ability to open inward. The valves open enough to allow fluid and plasma protein to pass into the lymphatic capillary.

Inside the lymph vessels are valves that prevent the backflow of lymph, a general name for the slightly opalescent fluid picked up by the lymphatics. Surrounding the lymphatics are smooth muscles that contract involuntarily to assist in the movement of lymph through the system. The lymphatic capillaries converge into larger lymph vessels. The larger lymph vessels pass through swellings called lymph nodes and then empty into one of two large lymph ducts. The lymph ducts empty into the venous circulatory system through either the right or left subclavian veins. Lymph from the right side of the head, arm and chest empties into the right subclavian vein. Lymph collected from the lower part of the body, and lymph from the left side of the head, arm and chest empties into the left subclavian vein. Both subclavian veins are located within the thorax underneath the clavicles, the thin bones located on the top part of the chest.

At approximately 600 sites in the human body, lymphatic vessels converge into bundles of tissue called lymph nodes. The shape of a lymph node resembles a kidney bean and ranges in size from a few millimeters to a few centimeters. They are mostly found at the base of extremities such as the arms, legs and head. Many afferent lymphatics or vessels lead the lymph into the node at the larger curve of the bean shape and efferent lymphatics, fewer in number, take the lymph away from the node at the hilum, the depressed region of the bean shape. All nodes have a blood supply from the circulatory system running through them. The blood vessels enter and exit at the hilum. Inside the nodes are a honeycomb of lymphfilled sinuses that have macrophages and groupings of lymphocytes that produce antibodies.

As mentioned, lymph is the fluid flowing through the lymphatic system and originates from the interstitial spaces of the organs and tissues. Another element of the lymph is a type of cell of the immune system called a lymphocyte, which is a type of white blood cell. Lymphocytes mature in either the thymus (T-lymphocytes) or the bone marrow (B-lymphocytes), which are primary lymphoid organs The blood supply transports lymphocytes from their site of maturation (the thymus or bone marrow) to secondary lymphoid organs such as the lymph nodes, spleen, and tonsils. All lymphocytes in the adult originate in the bone marrow.

Function

Fluid enters organs and tissues from the arterial capillaries, and is eventually reabsorbed by the venous capillaries. However, not all of the fluid is reabsorbed by blood capillaries. About one tenth of the fluid is returned to the blood vessels via the lymphatic system. The lymphatic system reabsorbs about 2-4 quarts (liters) of fluid per day. Lymph composition is different depending on the site of origin. For example lymph collected from the gastrointestinal tract is high in fat that has been absorbed during digestion, and lymph collected from the bone marrow and thymus is high in lymphocyte concentration.

Lymph is collected when the pressure of the interstitial fluid and plasma proteins increases in the organs and tissues. Lymph pushes against the outside of the lymphatic valves and flows into the lymphatic capillary. This is called bulk flow. Valves are located throughout the lymphatic system approximately 0.15 in (38 mm) apart. Backflow is not possible in the lymphatics because the valves open in only one direction. Therefore, the lymphatic system runs in only one direction.

There are several factors the affect the rate at which lymph is collected. Interstitial fluid pressure affects the rate of flow of fluid into the lymphatic capillaries. Elevated capillary pressure, increased interstitial fluid pressure, and increased capillary permeability all contribute to an increase in the amount of interstitial pressure and the rate of lymph flow.

Smooth muscles around the lymphatic vessels act as lymphatic pumps, and their involuntary contractions affect the rate of lymph flow. As the lymphatic vessel swells with fluid, the smooth muscle around that portion senses the stretch and automatically contracts, pushing the lymph through the valve to the next chamber. The valve prevents backwards flow as the smooth muscle in the chamber contracts to send the lymph through the next valve into the next chamber. This process continues along the entire vessel until the lymph passes through the lymph nodes and into the subclavian vein.

Factors outside of the lymphatic system can also affect the rate of lymph flow by assisting in the pumping of lymph through the system. The following eternal factors can increase lymph flow: contraction of close skeletal muscles, movements made by other parts of the body, nearby arterial pulses, and compression of tissues by items outside of the body. Therefore, during periods of exercise, the lymphatic system is extremely active and the flow rate is high.

The terminal end of the lymphatic capillary also has a pump that can affect the rate of lymph flow. When the interstitial fluid pressure is high, the surrounding tissue expands. The anchoring filaments that are attached to the endothelial cells at the terminal end of the lymphatic capillary and to the connective tissue pull the capillary valves open, allowing inward flow of interstitial fluid. Then the internal lymphatic capillary pressure causes the valves to close and the smooth muscle in the first compartment to contract and push the lymph into the next chamber.

Contractile actomyosin filaments are also present in the end terminal of the lymphatic vessels. These filaments cause the rhythmic contraction of the terminal end of the lymphatic capillary. Therefore, they contribute to part of the initial pumping of lymph through the system.

Role in human health

The lymphatic system has a variety of roles in human health ranging from returning fluid from organs back to the circulatory system, to an important part in the human immune response, to absorbing lipids from the intestines. The defining role of the lymphatic vessels is to return any fluid that has leaked from the capillaries and into the interstitial space back to the circulatory system through the veins. This is important because if fluid was retained in the tissues, the result in reduced blood volume and swelling of the tissues.

Another important role of the lymphatic system is the ability of plasma proteins to fit through the lymphatic valves and into the lymphatic capillary. Since most proteins have such a high molecular weight, they are unable to be reabsorbed by venous capillaries. With out the reabsorption of the plasma proteins, humans can die within 24 hours.

The lymphatic system also has an essential role in the process of digestion. Primarily, the lymphatic capillaries in the gastrointestinal tract are one of the main routes for fats to be absorbed. Fats enter the lymphatics before entering the blood stream.

High molecular weight proteins are not the only large substances that are absorbed. Microorganisms such as bacteria can also fit between the endothelial cells of the terminal end of the lymphatic capillary. As this occurs and the bacteria are transported to the next lymph node, the meshwork of the node and sinuses with in the node act as a filter, catching and trapping the foreign organisms. Once trapped, microorganisms can be attacked by the concentrated cells of the immune system. Macrophages may consume disease-causing bacteria, B-lymphocytes may come into contact with the antigens on the surface of the microorganism and stimulate antibodies, and T-lymphocytes called "killer" cells that attach themselves to the foreign organism and release a substance to destroy the organism. The destructive nature of the "killer" cells is enhanced by another T-lymphocyte called "helper" cells (T-helper cells also assist B-cells). If this system fails, then microorganisms are not destroyed, resulting in the spread of infection though the lymphatic system and extreme infection possibly leading to death.

Cancer cells that have lost adherence to, and break away from, the primary tumor are collected by the lymphatic system and filtered by latticework within the lymph nodes. Within the lymph node T-cells release substances called lymphokine (e.g. gamma interferor and interleukin 2) that may help destroy the cancer cells. Doctors use the lymph nodes as one factor of evaluation when determining the stage of the cancer. In other words, when determining how far the cancer has progressed at the time of diagnosis, the lymph nodes can be dissected to determine if cancer has spread (metastisized) from the original tumor or not. If cancer cells are present in the lymph nodes, then the cancer receives a higher stage and a less-optimistic diagnosis. In cancers that metastasizes via the lymphatics, the lymph nodes where cancer cells are present are often removed. This is even more common when the lymph nodes in question are adjacent to the tumor, when the lymph nodes are located on the only lymphatic vessel present in the area of the tumor, or if no other lymphatics will be damaged during the removal.

Common diseases and disorders

Since the lymphatic system is responsible for draining excess fluid from tissues and organs, the most common symptom of diseases and disorders of the lymphatic system is swelling. For example, a disease known as elephantiasis, which is caused by a filarial worm infestation, involves the blockage of the lymphatics. When the lymphatics are blocked, fluid cannot be drained and swelling occurs in the affected areas. Administering ethyl-carbamazine drugs, elevating the area and wearing a compression stocking can treat elephantiasis.

Tonsillitis is another disease of the lymphatic system. Tonsillitis usually involves a bacterial or viral infection located within the tonsils. The tonsils are swollen, and the patient experiences a fever, sore throat, and difficulty swallowing. This can be treated by the use of antibiotics or through a surgical procedure called a tonsillectomy.

A condition common among individuals following surgery for breast cancer or prostate cancer is lymphedema. It is caused by blockage of lymph vessels or lymph nodes located near the surgical site and can result in swollen arms or legs. If microorganisms cause the swelling, then antibiotics are used as treatment. If microorganisms are not the cause, then compression garments and message therapy are used as treatment.

There are also cancers called lymphosarcomas and cancers of the lymph nodes that can affect the lymphatic system. The causes of these cancers are not known and there is not a consensus on what preventative measures can be taken to reduce the risk of developing these cancers. Symptoms of cancers affecting the lymphatic system include loss of appetite, energy, and weight, as well as swelling of the glands. As with many cancers, treatment includes surgical removal followed by adjuvant radiation and chemotherapy.

KEY TERMS

B-lymphocytes (B-cells)— A type of white blood cell that originates in the bone marrow and recognizes foreign antigens (or proteins), secreting antibodies in an immune response.

Interstitial space— The spaces found within organs and tissues.

Lymph— The slightly opalescent fluid found within the lymphatic system.

Lymph nodes— Bean shaped swellings along the lymphatic vessels that contain macrophages and lymphocytes.

Lymphatics— The system of lymphatic vessels.

T-lymphocytes (T-cells)— A type of white blood cell that originates in the thymus and attaches themselves to foreign organisms, secreting lymphokines that kill the foreign organisms.

Tonsil— A collection of lymphocytes that form a mass in the back of the pharynx.

Resources

BOOKS

Braunwald, Eugene, et. al. Harrison's Principles of Internal Medicine, 15th ed. New York: McGraw-Hill, 2001.

Lee, Richard G., M.D. et. al. Wintrob's Clinical Hematology, 10th ed. Philadelphia: Lippincott Williams & Wilkins, 1999.

Vander, Arthur. Human Physiology: The Mechanisms of Body Function, Seventh ed. New York: WBC McGraw-Hill, 1998.

ORGANIZATIONS

Lymphatic Research Foundation. 941 N.E. 19th Avenue, Suite 305, Ft. Lauderdale, Florida, 33304-3071. (954)525-3510. 〈http://www.lymphaticresearch.org/〉.