Lymphatic system

Lymphatic System

An image displaying the lymphatic system.

Latin systema lymphoideum

The lymphatic system is the part of the immune system comprising a network of conduits
called lymphatic vessels that carry a clear fluid called lymph (from Latin lympha "water"[1])
unidirectionally toward the heart. Lymphoid tissue is found in many organs, particularly the
lymph nodes, and in the lymphoid follicles associated with the digestive system such as the
tonsils. The system also includes all the structures dedicated to the circulation and production
of lymphocytes, which includes the spleen, thymus, bone marrow and the lymphoid tissue
associated with the digestive system.[2] The lymphatic system as we know it today was first
described independently by Olaus Rudbeck and Thomas Bartholin.
The blood does not directly come in 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).

Functions
The lymphatic system has multiple interrelated functions:[3]

 it is responsible for the removal of interstitial fluid from tissues

 it absorbs and transports fatty acids and fats as chyle from the circulatory system

 it transports immune cells to and from the lymph nodes in to the bones

 The lymph transports antigen-presenting cells (APCs), such as dendritic cells, to the
lymph nodes where an immune response is stimulated.

Lymphatic tissue is a specilized connective tissue - reticular connective, that contains large
quantities of lymphocytes

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

Lymphoid tissue
Lymphoid tissue associated with the lymphatic system is concerned with immune functions
in defending the body against the infections and spread of tumors. It consists of connective
tissue with various types of white blood cells enmeshed in it, most numerous being the
lymphocytes.

The lymphoid tissue may be primary, secondary, or tertiary depending upon the stage of
lymphocyte development and maturation it is involved in. (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
Primary lymphoid organs

The central or primary lymphoid organs generate lymphocytes from immature progenitor
cells.

The thymus and the bone marrow constitute the primary lymphoid tissues involved in the
production and early selection of lymphocytes

Secondary lymphoid organs

Secondary or peripheral lymphoid organs 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

Lymph nodes
For more details on this topic, see lymph node.

A lymph node showing afferent and efferent lymphatic vessels

A lymph node is an organized collection of lymphoid tissue, through which the lymph passes
on its way to returning 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 drained out by an efferent lymph vessel.

The substance of a lymph node consists of lymphoid follicles in the outer portion called the
"cortex", which contains the lymphoid follicles, and an inner portion called "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 or ovoid lymph node bean-shaped. 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.

Lymph follicles are 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 upon encountering a foreign antigen. The selection of B cells
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.[2]

Lymphatics
Main article: Lymph vessel

lymphatic system

Tubular vessels transport back lymph to the blood ultimately replacing the volume lost from
the blood during the formation of the interstitial fluid. These channels are the lymphatic
channels or simply called lymphatics.[6]

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. As the blood circulates, fluid leaks out into the body tissues. This fluid is
important because it carries food to the cells and waste back to the bloodstream. The nutrients
that are released to the circulatory system are processed by the liver, having passed through
the systemic circulation. The lymph system is a one-way system, transporting interstitial fluid
back to blood.

Diseases of the lymphatic system

Lymphedema is the swelling caused by the accumulation of lymph fluid,[7] which may occur
if the lymphatic system is damaged or has malformations. It usually affects the limbs, though
face, neck and abdomen may also be affected.

Some common causes of swollen lymph nodes include infections, infectious mononucleosis,
and cancer, e.g. Hodgkin's and non-Hodgkin lymphoma, and metastasis of cancerous cells via
the lymphatic system. In elephantiasis, infection of the lymphatic vessels cause a thickening
of the skin and enlargement of underlying tissues, especially in the legs and genitals. It is
most commonly caused by a parasitic disease known as lymphatic filariasis.
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.

Development of lymphatic tissue

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.

History
Hippocrates was one of the first persons 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.[8] 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.[8] Findings of Ruphus and Herophilos findings 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.[8][9]

Until the 17th century, ideas of Galen were most prevalent. Accordingly, it was believed that
the 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. His ideas had remained unchallenged until the 17th century, and
even then were defended by some physicians.[9]

Olaus Rudbeck in 1696

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."[8] In
about 1563 Bartolomeo Eustachi, a professor of anatomy, described the thoracic duct in
horses as vena alba thoracis.[8] 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).
[10]
He also identified the thoracic duct but failed to notice its connection with the lacteals.[8]
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.[8][10] 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.
[10]
Johann Veslingius drew the earliest sketches of the lacteals in humans in 1647.[9]

Thomas Bartholin

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 Harvey—a work he
published in 1628. In 1652, Olaus Rudbeck (1630–1702), 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.[10] He announced his findings in the court of Queen Christina of Sweden,
but did not publish his findings for a year,[11] 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".[10] This had resulted in a bitter dispute between one of Bartholin's pupils,
Martin Bogdan,[12] and Rudbeck, whom he accused of plagiarism.[11]