The lymphatic system is part of the circulatory system, comprising a network of lymphatic vessels that carry a clear fluid called lymph (from Latin lympha meaning water) directionally towards the heart. The lymphatic system was first described in the seventeenth century independently by Olaus Rudbeck and Thomas Bartholin. Unlike the cardiovascular system the lymphatic system is not a closed system. The human circulatory system processes an average of 20 litres of blood per day through capillary filtration which removes plasma while leaving the blood cells. Roughly 17 litres of the filtered plasma get reabsorbed directly into the blood vessels, while the remaining 3 litres are left behind in the interstitial fluid. One of the main functions of the lymph system is to provide an accessory route for these excess 3 litres per day to get returned to the blood.
The other main function is that of defense in the immune system. Lymph is very similar to blood plasma but contains lymphocytes and other white blood cells. It also contains waste products and debris of cells together with bacteria and protein. Associated organs composed of lymphoid tissue are the sites of lymphocyte production. Lymphocytes are concentrated in the lymph nodes. The spleen and the thymus are also lymphoid organs of the immune system. The tonsils are lymphoid organs that are also associated with the digestive system. Lymphoid tissues contain lymphocytes, and also contain other types of cells for support. The system also includes all the structures dedicated to the circulation and production of lymphocytes (the primary cellular component of lymph), which also includes the bone marrow, and the lymphoid tissue associated with the digestive system.
The blood does not come into direct contact with the parenchymal cells and tissues in the body, but constituents of the blood first exit the microvascular exchange blood vessels to become interstitial fluid, which comes into contact with the parenchymal cells of the body. Lymph is the fluid that is formed when interstitial fluid enters the initial lymphatic vessels of the lymphatic system. The lymph is then moved along the lymphatic vessel network by either intrinsic contractions of the lymphatic passages or by extrinsic compression of the lymphatic vessels via external tissue forces (e.g. the contractions of skeletal muscles), or by lymph hearts in some animals. The organization of lymph nodes and drainage follows the organization of the body into external and internal regions; therefore, the lymphatic drainage of the head, limbs, and body cavity walls follows an external route, and the lymphatic drainage of the thorax, abdomen, and pelvic cavities follows an internal route. Eventually, the lymph vessels empty into the lymphatic ducts, which drain into one of the two subclavian veins, near their junction with the internal jugular veins.
Structure
The lymphatic system consists of lymphatic organs, a conducting network of lymphatic vessels, and the circulating lymph.
The tertiary lymphoid tissue typically contains far fewer lymphocytes, and assumes an immune role only when challenged with antigens that result in inflammation. It achieves this by importing the lymphocytes from blood and lymph.)
The thymus and the bone marrow constitute the primary lymphoid organs involved in the production and early clonal selection of lymphocyte tissues. Bone marrow is responsible for the creation of both T cells, and the production and maturation of B cells. From the bone marrow B cells immediately join the blood system and travel to secondary lymphoid organs in search of pathogens. T cells on the other hand travel from the bone marrow to the thymus where they are allowed to develop further. Mature T cells join B cells in search of pathogens. The other 95% of T cells begin a process of apoptosis (programmed cell death).
The central or primary lymphoid organs generate lymphocytes from immature progenitor cells.
Secondary or peripheral lymphoid organs which include lymph nodes and the spleen, maintain mature naive lymphocytes and initiate an adaptive immune response. The peripheral lymphoid organs are the sites of lymphocyte activation by antigen. Activation leads to clonal expansion and affinity maturation. Mature lymphocytes recirculate between the blood and the peripheral lymphoid organs until they encounter their specific antigen.
Secondary lymphoid tissue provides the environment for the foreign or altered native molecules (antigens) to interact with the lymphocytes. It is exemplified by the lymph nodes, and the lymphoid follicles in tonsils, Peyer's patches, spleen, adenoids, skin, etc. that are associated with the mucosa-associated lymphoid tissue (MALT).
In the gastrointestinal wall the appendix has a mucosa resembling that of the colon, but here it is heavily infiltrated with lymphocytes.
Thymus
The thymus is a primary lymphoid organ and is the site of the T cells, the lymphocytes of the adaptive immune system.
Spleen
The spleen synthesizes antibodies in its white pulp and removes antibody-coated bacteria and antibody-coated blood cells by way of blood and lymph node circulation. A study published in 2009 using mice found that the spleen contains, in its reserve, half of the body's monocytes within the red pulp. These monocytes, upon moving to injured tissue (such as the heart), turn into dendritic cells and macrophages while promoting tissue healing. The spleen is a center of activity of the mononuclear phagocyte system and can be considered analogous to a large lymph node, as its absence causes a predisposition to certain infections.
Like the thymus, the spleen only has efferent lymphatic vessels. Both the short gastric arteries and the splenic artery supply it with blood.
The germinal centers are supplied by arterioles called penicilliary radicles.
Up to the fifth month of prenatal development the spleen creates red blood cells. After birth the bone marrow is solely responsible for hematopoiesis. As a major lymphoid organ and a central player in the reticuloendothelial system, the spleen retains the ability to produce lymphocytes. The spleen stores red blood cells and lymphocytes. It can store enough blood cells to help in an emergency. Up to 25% of lymphocytes can be stored at any one time.
Lymph nodes
A lymph node is an organized collection of lymphoid tissue, through which the lymph passes on its way back to the blood. Lymph nodes are located at intervals along the lymphatic system. Several afferent lymph vessels bring in lymph, which percolates through the substance of the lymph node, and is then drained out by an efferent lymph vessel. There are between five and six hundred lymph nodes in the human body, many of which are grouped in clusters in different regions as in the underarm and abdominal areas.
The substance of a lymph node consists of lymphoid follicles in an outer portion called the "cortex." The inner portion of the node is called the "medulla," which is surrounded by the cortex on all sides except for a portion known as the "hilum." The hilum presents as a depression on the surface of the lymph node, which makes the otherwise spherical lymph node, bean-shaped or ovoid. The efferent lymph vessel directly emerges from the lymph node here. The arteries and veins supplying the lymph node with blood enter and exit through the hilum.
There is a region of the lymph node called the paracortex that immediately surrounds the medulla. Unlike the cortex, which has mostly immature T cells, or thymocytes, the paracortex has a mixture of immature and mature T cells. Lymphocytes enter the lymph nodes through specialised high endothelial venules found in the paracortex.
A lymph follicle is a dense collection of lymphocytes, the number, size and configuration of which change in accordance with the functional state of the lymph node. For example, the follicles expand significantly when encountering a foreign antigen. The selection of B cells also called B lymphocytes, occurs in the germinal center of the lymph nodes.
Lymph nodes are particularly numerous in the mediastinum in the chest, neck, pelvis, axilla (armpit), inguinal (groin) region, and in association with the blood vessels of the intestines.
Other lymphoid tissue
Lymphoid tissue associated with the lymphatic system is concerned with immune functions in defending the body against infections and the spread of tumors. It consists of connective tissue formed of reticular fibers, with various types of leukocytes, (white blood cells), mostly lymphocytes enmeshed in it, through which the lymph passes. Regions of the lymphoid tissue that are densely packed with lymphocytes are known as lymphoid follicles. Lymphoid tissue can either be structurally well organized as lymph nodes or may consist of loosely organized lymphoid follicles known as the mucosa-associated lymphoid tissue.
Lymphatics
The lymphatic vessels also sometimes called lymph vessels, conduct lymph between different parts of the body. They include the tubular vessels of the lymph capillaries, the collecting lymphatic vessels, the right lymphatic duct and the thoracic duct, also called the left lymphatic duct. The lymph vessels transport lymph back to the blood ultimately replacing the volume lost from the blood during the formation of the interstitial fluid. These vessels are also called the lymphatic channels or simply lymphatics.
The lymphatics are responsible for maintaining the balance of the body fluids. Its network of capillaries and collecting lymphatic vessels, work to efficiently drain and transport extravasated fluid back to the cardiovascular system Fluid, along with proteins and antigens are captured and returned to the blood circulation. There are numerous intraluminal valves in place to ensure a unidirectional flow without reflux.Two valve systems are used to achieve this one directional flowâ€"a primary and a secondary valve system. The capillaries are blind ended and the valves here use specialised junctions together with anchoring filaments to allow a unidirectional flow to the primary vessels. The collecting lymphatics are however seen to act to propel the lymph through to the blood circulation by the combined actions of the intraluminal valves and lymphatic muscle cells.
Development
Lymphatic tissues begin to develop by the end of the fifth week of embryonic development. Lymphatic vessels develop from lymph sacs that arise from developing veins, which are derived from mesoderm.
The first lymph sacs to appear are the paired jugular lymph sacs at the junction of the internal jugular and subclavian veins. From the jugular lymph sacs, lymphatic capillary plexuses spread to the thorax, upper limbs, neck and head. Some of the plexuses enlarge and form lymphatic vessels in their respective regions. Each jugular lymph sac retains at least one connection with its jugular vein, the left one developing into the superior portion of the thoracic duct.
The next lymph sac to appear is the unpaired retroperitoneal lymph sac at the root of the mesentery of the intestine. It develops from the primitive vena cava and mesonephric veins. Capillary plexuses and lymphatic vessels spread from the retroperitoneal lymph sac to the abdominal viscera and diaphragm. The sac establishes connections with the cisterna chyli but loses its connections with neighboring veins.
The last of the lymph sacs, the paired posterior lymph sacs, develop from the iliac veins. The posterior lymph sacs produce capillary plexuses and lymphatic vessels of the abdominal wall, pelvic region, and lower limbs. The posterior lymph sacs join the cisterna chyli and lose their connections with adjacent veins.
With the exception of the anterior part of the sac from which the cisterna chyli develops, all lymph sacs become invaded by mesenchymal cells and are converted into groups of lymph nodes.
The spleen develops from mesenchymal cells between layers of the dorsal mesentery of the stomach. The thymus arises as an outgrowth of the third pharyngeal pouch.
Function
The lymphatic system has multiple interrelated functions:
- It is responsible for the removal of interstitial fluid from tissues
- It absorbs and transports fatty acids and fats as chyle from the digestive system
- It transports white blood cells to and from the lymph nodes into the bones
- The lymph transports antigen-presenting cells (APCs), such as dendritic cells, to the lymph nodes where an immune response is stimulated.
Function of the fatty acid transport system
Lymph vessels called lacteals are present in the lining of the gastrointestinal tract, predominantly in the small intestine. While most other nutrients absorbed by the small intestine are passed on to the portal venous system to drain via the portal vein into the liver for processing, fats (lipids) are passed on to the lymphatic system to be transported to the blood circulation via the thoracic duct. (There are exceptions, for example medium-chain triglycerides (MCTs) are fatty acid esters of glycerol that passively diffuse from the GI tract to the portal system.) The enriched lymph originating in the lymphatics of the small intestine is called chyle. The nutrients that are released to the circulatory system are processed by the liver, having passed through the systemic circulation.
Immune function
Clinical significance
The study of lymphatic drainage of various organs is important in diagnosis, prognosis, and treatment of cancer. The lymphatic system, because of its physical proximity to many tissues of the body, is responsible for carrying cancerous cells between the various parts of the body in a process called metastasis. The intervening lymph nodes can trap the cancer cells. If they are not successful in destroying the cancer cells the nodes may become sites of secondary tumors.
Lymphadenopathy
Lymphadenopathy refers to one or more enlarged lymph nodes. Small groups or individually enlarged lymph nodes are generally reactive in response to infection or inflammation. This is called local lymphadenopathy. When many lymph nodes in different areas of the body are involved, this is called generalised lymphadenopathy. Generalised lymphadenopathy may be caused by infections such as infectious mononucleosis, tuberculosis and HIV, connective tissue diseases such as SLE and rheumatoid arthritis, and cancers, including both cancers of tissue within lymph nodes, discussed below, and metastasis of cancerous cells from other parts of the body, that have arrived via the lymphatic system.
Lymphedema
Lymphedema is the swelling caused by the accumulation of lymph, which may occur if the lymphatic system is damaged or has malformations. It usually affects limbs, though the face, neck and abdomen may also be affected. In an extreme state, called elephantiasis the edema progresses to the extent that the skin becomes thick with an appearance similar to the skin on elephant limbs.
Causes are unknown in most cases, but sometimes there is a previous history of severe infection, usually caused by a parasitic disease, such as lymphatic filariasis.
Lymphangiomatosis is a disease involving multiple cysts or lesions formed from lymphatic vessels.
Lymphedema can also occur after surgical removal of cancerous lymph nodes in the armpit (causing the arm to swell due to poor lymphatic drainage) or groin (causing swelling of the leg). Treatment is by massage, and is not permanent.
Cancer
Cancer of the lymphatic system can be primary or secondary. Lymphoma refers to cancer that arises from lymphatic tissue. Lymphoid leukemias and lymphomas are now considered to be tumors of the same type of cell lineage. They are called "leukemia" when in the blood or marrow and "lymphoma" when in lymphatic tissue. They are grouped together under the name "lymphoid malignancy".
Lymphoma is generally considered as Hodgkin's lymphoma and Non-Hodgkin's lymphoma. Hodgkin's lymphoma is characterised by a particular type of cell, called a Reedâ€"Sternberg cell, visible under microscope. It is associated with past infection with the Epstein-Barr Virus, and generally causes a painless "rubbery" lymphadenopathy. It is staged, using Ann Arbor staging. Chemotherapy generally involves the ABVD and may also involved radiotherapy. Non-Hodgkin's lymphoma is a cancer characterised by increased proliferation of B-cells or T-cells, generally occurs in an older age group than Hodgkin's lymphoma, It is treated according to whether it is high-grade or low-grade, and carries a poorer prognosis than Hodgkin's lymphoma.
Lymphangiosarcoma is a malignant soft tissue tumor, whereas lymphangioma is a benign tumor occurring frequently in association with Turner syndrome. Lymphangioleiomyomatosis is a benign tumor of the smooth muscles of the lymphatics that occurs in the lungs.
History
Hippocrates was one of the first people to mention the lymphatic system in 5th century BC. In his work On Joints, he briefly mentioned the lymph nodes in one sentence. Rufus of Ephesus, a Roman physician, identified the axillary, inguinal and mesenteric lymph nodes as well as the thymus during the 1st to 2nd century AD. The first mention of lymphatic vessels was in 3rd century BC by Herophilos, a Greek anatomist living in Alexandria, who incorrectly concluded that the "absorptive veins of the lymphatics," by which he meant the lacteals (lymph vessels of the intestines), drained into the hepatic portal veins, and thus into the liver. The findings of Ruphus and Herophilos were further propagated by the Greek physician Galen, who described the lacteals and mesenteric lymph nodes which he observed in his dissection of apes and pigs in the 2nd century AD.
In the mid 16th century, Gabriele Falloppio (discoverer of the fallopian tubes), described what are now known as the lacteals as "coursing over the intestines full of yellow matter." In about 1563 Bartolomeo Eustachi, a professor of anatomy, described the thoracic duct in horses as vena alba thoracis. The next breakthrough came when in 1622 a physician, Gaspare Aselli, identified lymphatic vessels of the intestines in dogs and termed them venae alba et lacteae, which is now known as simply the lacteals. The lacteals were termed the fourth kind of vessels (the other three being the artery, vein and nerve, which was then believed to be a type of vessel), and disproved Galen's assertion that chyle was carried by the veins. But, he still believed that the lacteals carried the chyle to the liver (as taught by Galen). He also identified the thoracic duct but failed to notice its connection with the lacteals. This connection was established by Jean Pecquet in 1651, who found a white fluid mixing with blood in a dog's heart. He suspected that fluid to be chyle as its flow increased when abdominal pressure was applied. He traced this fluid to the thoracic duct, which he then followed to a chyle-filled sac he called the chyli receptaculum, which is now known as the cisternae chyli; further investigations led him to find that lacteals' contents enter the venous system via the thoracic duct. Thus, it was proven convincingly that the lacteals did not terminate in the liver, thus disproving Galen's second idea: that the chyle flowed to the liver. Johann Veslingius drew the earliest sketches of the lacteals in humans in 1647.
The idea that blood recirculates through the body rather than being produced anew by the liver and the heart was first accepted as a result of works of William Harveyâ€"a work he published in 1628. In 1652, Olaus Rudbeck (1630â€"1702), a Swede, discovered certain transparent vessels in the liver that contained clear fluid (and not white), and thus named them hepatico-aqueous vessels. He also learned that they emptied into the thoracic duct, and that they had valves. He announced his findings in the court of Queen Christina of Sweden, but did not publish his findings for a year, and in the interim similar findings were published by Thomas Bartholin, who additionally published that such vessels are present everywhere in the body, and not just the liver. He is also the one to have named them "lymphatic vessels." This had resulted in a bitter dispute between one of Bartholin's pupils, Martin Bogdan, and Rudbeck, whom he accused of plagiarism.
Galen's ideas prevailed in medicine until the 17th century. It was believed that blood was produced by the liver from chyle contaminated with ailments by the intestine and stomach, to which various spirits were added by other organs, and that this blood was consumed by all the organs of the body. This theory required that the blood be consumed and produced many times over. Even in the 17th century, his ideas were defended by some physicians.
Etymology
The adjective used for the lymph-transporting system is "lymphatic." The adjective used for the tissues where lymphocytes are formed is "lymphoid."
Lymphatic comes from the Latin word lymphaticus, meaning "connected to water."
