Introduction
The lymphatic system, or lymphoid system, is a component of the circulatory system and serves a critical role in immune function and the drainage of surplus extracellular fluid. (see Image. Lymphatic System). Components of the lymphatic system include lymph, lymphatic vessels and plexuses, lymph nodes, lymphatic cells, and various lymphoid organs. The pattern and form of lymphatic channels are more variable and complex, but generally parallel those of the peripheral vascular system. The lymphatic system partly functions to convey lymphatic fluid, or lymph, through a network of lymphatic channels, filter it through lymph nodes, and return it to the bloodstream, where it is eventually eliminated. Nearly all body organs, regions, and systems have lymphatic channels that collect the various byproducts that require elimination (see Images. Axillary Lymph Nodes, Lymphatics of the Lower Limb). The liver and intestinal lymphatics account for about 80% of the body's lymph volume.[1]
Notable body regions that do not appear to contain lymphatics include the bone marrow, epidermis, and other tissues lacking blood vessels. The central nervous system was long considered to be devoid of lymphatic vessels until they were recently identified in the cranial meninges.[2][3] Moreover, a vessel with lymphatic features was also observed in the eye.[4][5] The lymphatic system is critical in a clinical context, particularly because it is a major route for cancer metastasis and because inflammation of lymphatic vessels and lymph nodes is an indicator of pathology.
Structure
The lymphatic system includes numerous structural components, including lymphatic capillaries, afferent lymphatic vessels, lymph nodes, efferent lymphatic vessels, and various lymphoid organs. Lymphatic capillaries are tiny, thin-walled vessels that originate blindly within the extracellular space of various tissues. Lymphatic capillaries tend to be larger in diameter than blood capillaries and are interspersed among them to enhance their ability to collect interstitial fluid efficiently. They are critical for the drainage of extracellular fluid, allowing it to enter the closed capillaries but not exit due to their unique morphology. Lymphatic capillaries at their blind ends are composed of a thin endothelium without a basement membrane. The endothelial cells at the closed end of the capillary overlap but shift to open the capillary end when interstitial fluid pressure exceeds intra-capillary pressure. This process permits lymphocytes, interstitial fluid, bacteria, cellular debris, plasma proteins, and other cells to enter the lymphatic capillaries. Special lymphatic capillaries called lacteals are present in the small intestine to facilitate the absorption of dietary fats. Lymphatics in the liver contribute to a specialized role in transporting hepatic proteins into the bloodstream.[1] The body's lymphatic capillaries form large networks of channels called lymphatic plexuses, which converge to form larger lymphatic vessels.
Lymphatic vessels convey lymph, or lymphatic fluid, through their channels. Afferent (toward) lymphatic vessels convey unfiltered lymphatic fluid from the body tissues to the lymph nodes, and efferent (away) lymphatic vessels convey filtered lymphatic fluid from lymph nodes to subsequent lymph nodes or into the venous system. The various efferent lymphatic vessels in the body eventually converge to form 2 major lymphatic channels: the right lymphatic duct and the thoracic duct.
The right lymphatic duct drains most of the right upper quadrant of the body, including the right upper trunk, right upper extremity, and right head and neck (see Image. Lymphatics of the Oral and Nasal Cavity). The right lymphatic trunk is a visible channel in the right cervical region just anterior to the anterior scalene muscle. Its origin and termination are variable in morphology, typically forming as the convergence of the right bronchomediastinal, jugular, and subclavian trunks, extending 1 to 2 centimeters in length before returning its contents to the systemic circulation at the junction of the right internal jugular, subclavian, and/or brachiocephalic veins.
The thoracic duct, also known as the left lymphatic duct or the van Hoorne canal, is the largest of the body's lymphatic channels. It drains most of the body except for the territory of the right superior thorax, head, neck, and upper extremity served by the right lymphatic duct. The thoracic duct is a thin-walled tubular vessel measuring 2 to 6 mm in diameter. The length of the duct ranges from 36 to 45 cm. The thoracic duct is highly variable in form but typically arises in the abdomen at the superior aspect of the cisterna chyli, around the level of the twelfth thoracic vertebra (T12). The cisterna chyli, from which it extends, is an expanded lymphatic sac that forms at the convergence of the intestinal and lumbar lymphatic trunks extending along the L1-L2 vertebral levels. The cisterna chyli is present in approximately 40-60% of the population, and in its absence, the intestinal and lumbar lymphatic trunks communicate directly with the thoracic duct at the T12 level.[6][7]
As a result, the thoracic duct receives lymphatic fluid from the lumbar lymphatic trunks and chyle, composed of lymphatic fluid and emulsified fats, from the intestinal lymphatic trunk. Initially, the thoracic duct is located just to the right of the midline and posterior to the aorta. It exits the abdomen and enters the thorax via the aortic hiatus formed by the right and left crura of the diaphragm, side by side with the aorta. The thoracic duct then ascends in the thoracic cavity just anterior and to the right of the vertebral column between the aorta and the azygos vein. At about the level of the fifth thoracic vertebra (T5), the thoracic duct typically crosses to the left of the vertebral column and posterior to the esophagus. From here, it ascends vertically and usually empties its contents into the junction of the left subclavian and left internal jugular veins in the cervical region.
To prevent the backward flow of lymph, collecting and larger lymphatic vessels have 1-way valves. These valves are absent in lymphatic capillaries. These lymphatic valves permit the continued advancement of lymph through the lymphatic vessels, aided by a pressure gradient created by vascular smooth muscle, skeletal muscle contraction, and respiratory movements. However, it is important to note that lymphatic vessels also communicate with the venous system through various anastomoses.
Lymph nodes are small bean-shaped tissues situated along lymphatic vessels. Lymph nodes receive lymphatic fluid from afferent lymphatic vessels and convey lymph away through efferent lymphatic vessels. Lymph nodes serve as filters and monitor the composition of lymphatic fluid/blood, drain excess tissue fluid and leaked plasma proteins, engulf pathogens, augment an immune response, and eradicate infection.
Several organs in the body are considered lymphoid or lymphatic organs because of their role in producing lymphocytes. These include the bone marrow, spleen, thymus, tonsils, lymph nodes, and other tissues. Lymphoid organs can be categorized as primary or secondary lymphoid organs. Primary lymphoid organs are those that produce lymphocytes, such as the bone marrow and thymus. Bone marrow is the primary site of lymphocyte production. The thymus is a glandular organ located anterior to the pericardium. It serves to mature and develop T cells, or thymus cell lymphocytes, in response to an inflammatory process or pathology. As individuals age, both their bone marrow and thymus decrease in size and accumulate fat. Secondary lymphoid organs serve as territories in which immune cells function and include the spleen, tonsils, lymph nodes, and various mucous membranes, such as those in the intestines. The spleen is a purplish, fist-sized organ in the left upper abdominal quadrant that contributes to immune function by filtering blood, storing lymphocytes in its white pulp, and serving as a site for an adaptive immune response to antigens. The lingual tonsils, palatine tonsils, and pharyngeal tonsils, or adenoids, work to prevent pathogens from entering the body. Mucous membranes in the gastrointestinal, respiratory, and genitourinary systems also function to prevent pathogens from entering the body.
Lymph
Lymphatic fluid, or lymph, is similar to blood plasma and is typically watery, transparent, and yellowish. Extracellular fluid leaks out of blood capillary walls due to pressure from the heart or to osmotic pressure at the cellular level. As interstitial fluid accumulates, it is absorbed by the tiny lymphatic capillaries, along with other substances, forming lymph. This fluid then passes through the lymphatic vessels and lymph nodes and finally enters the venous circulation. As the lymph passes through the lymph nodes, both monocytes and lymphocytes enter it. Lymph is composed primarily of interstitial fluid with variable amounts of lymphocytes, bacteria, cellular debris, plasma proteins, and other cells. In the GI tract, lymphatic fluid is called chyle and has a milk-like appearance, chiefly due to the presence of cholesterol, glycerol, fatty acids, and other fat products. The vessels that transport lymphatic fluid from the GI tract are called lacteals.
Embryology
The development of the lymphatic system has been studied in both human and animal models, especially mouse models. The lymphatic vessels form after the development of blood vessels, around 6 weeks post-fertilization. The endothelial cells that serve as precursors to the lymphatics arise from the embryonic cardinal veins.[8] The process by which lymphatic vessels form is similar to that of blood vessels and produces lymphatic-venous and intra-lymphatic anastomoses, but the origins of components of lymphatic vessel formation differ across regions.[9][10][11][12]
Six primary lymph sacs develop and are apparent about 8 weeks post-fertilization. These include, from caudal to cranial, 1 cisterna chyli, 1 retroperitoneal lymph sac, 2 iliac lymph sacs, and 2 jugular lymph sacs. The jugular lymph sacs are the first to develop, initially appearing next to the jugular part of the cardinal vein.[12] Lymphatic vessels then form adjacent to the blood vessels and connect the various lymph sacs. The lymphatic vessels primarily arise from the lymph sacs through self-proliferation and polarized sprouting.[13]
Stem/progenitor cells play a major role in forming lymphatic tissues and vessels by contributing to sustained growth and, postnatally, differentiating into lymphatic endothelial cells.[13] Lymphatic channels from the developing gut connect with the retroperitoneal lymph sac and the cisterna chyli, situated just posteriorly. The lymphatic channels of the lower extremities and inferior trunk communicate with the iliac lymph sacs. Finally, lymphatic channels in the head, neck, and upper extremities drain to the jugular lymph sacs. Additionally, the right and left thoracic ducts form, connect the cisterna chyli to the jugular lymph sacs, and establish anastomoses that eventually produce the typical adult form. The lymph sacs then produce groups of lymph nodes in the fetal period. Migrating mesenchyme enters the lymph sacs and produces lymphatic networks, connective tissue, and other layers of the lymph nodes.
Clinical Significance
Leaks of lymphatic fluid occur when the lymphatic vessels are damaged. In the abdomen, lymphatic vessel damage may occur during surgery, especially during retroperitoneal procedures such as repairing an abdominal aortic aneurysm. These leaks tend to be mild, and the vessels in the peritoneum and mesentery eventually absorb the lymphatic fluid or chyle. However, when the thoracic duct is injured in the chest, the chyle leak can be extensive. In most cases, conservative care with a no-fat diet (medium-chain triglycerides) or total parenteral nutrition is ineffective. In most cases, if the injury to the thoracic duct was surgical, a surgical procedure is required to tie off the duct. If the thoracic duct is injured in the cervical region, inserting a drainage tube and adopting a low-fat diet can help seal the leak. However, thoracic duct injury in the chest cavity usually requires drainage and surgery. It is rare for the thoracic segment of the thoracic duct to seal on its own.[16][17][18] In terms of accumulation of chyle in the thorax (ie, chylothorax), if a patient has an injury to the thoracic duct below the T5 vertebral level, then fluid collects in only the right pleural cavity. If the injury is to the thoracic duct in the thorax above the T5 vertebral level, then fluid appears in both pleural cavities.
Other Issues
The lymphatic system is prone to disorders, as are the venous and arterial circulatory systems. Developmental or functional defects of the lymphatic system cause lymphedema. When this occurs, the lymphatic system is unable to adequately drain lymphatic fluid, leading to its accumulation and swelling of the affected area. Lymphedema, this swelling due to the accumulation of lymph, is classified as primary or secondary.
Primary lymphedema is an inherited disorder in which lymphatic system development is disrupted, leading to absent or malformed lymphatic tissues. This condition often presents soon after birth, but some conditions may present later in life (eg, at puberty or later adulthood). There are no effective treatments for primary lymphedema. Past surgical treatments were found to be mutilating and are no longer implemented. The current treatment focuses on compression stockings, pumps, and constrictive garments.[19][20][21]
Secondary lymphedema is an acquired disorder involving lymphatic system dysfunction that may result from many causes, including cancer, infection, trauma, or surgery. The treatment of secondary lymphedema depends on the cause. Oncological and other surgeries may result in secondary lymphedema due to the removal or biopsy of lymph nodes or lymphatic vessels. Non-surgical lymphedema may result from malignancies, obstruction within the lymphatic system, infection, or deep vein thrombosis. In most cases of obstructive secondary lymphedema, the drainage resumes if the inciting cause is removed, although some individuals may need to wear compressive stockings permanently. Also, physical therapy may help alleviate lymphedema when the extremities are involved. There is no absolute cure for lymphedema, but diagnosis and careful management can help to minimize complications.[22]
Lymphomas are cancers that arise from the cells of the lymphatic system. There are numerous types of lymphoma, but they are grouped into Hodgkin lymphoma and non-Hodgkin lymphoma.[23] Lymphomas usually arise from the malignant transformation of specific lymphocytes in the lymphatic vessels or lymph nodes in the gastrointestinal tract, neck, axilla, or groin. Symptoms of lymphoma may include night sweats, fever, fatigue, itching, and weight loss. Cancers originating outside of the lymphatic system often spread via the lymphatic vessels and may involve regional lymph nodes serving the impacted organs or tissues.
Lymphadenitis occurs when the lymph nodes become inflamed or enlarged. The cause is usually an adjacent bacterial infection, but it may also involve viruses or fungi. The lymph nodes usually enlarge and become tender.
Lymphatic filariasis, or elephantiasis, is a very common mosquito-borne disorder caused by a parasite found in tropical and subtropical regions worldwide, including Africa, Asia, the Pacific, the Caribbean, and South America. This condition involves parasitic microscopic nematodes (roundworms) that infect the lymphatic system, rapidly multiply, and disrupt lymphatic function.[24] Many infected individuals may have no outward symptoms, although the kidneys and lymphatic tissues may be damaged and dysfunctional. Symptomatic individuals may present with disfigurement due to severe lymphedema and elephantiasis (thickening of the skin, particularly the extremities). The parasite may also cause a hydrocele, an enlargement of the scrotum due to fluid accumulation, which may result from obstruction of the lymph nodes or vessels in the groin. Individuals presenting with symptoms have poorly draining lymphatics, often involving the extremities, resulting in huge extremities and marked disability. Lymphatic filariasis is the most common cause of disfigurement in the world, and it is the second most common cause of long-term disability.[24]
