The lymphoid system is a part of circulatory system and immune system. It is a network of tissue and organs that help rid the body of toxins, waste and other unwanted materials. The cells of the body are bathed in interstitial (tissue) fluid, which leaks constantly out of the bloodstream through the permeable walls of blood capillaries. Hence the fluid is very similar in composition to blood plasma. Some tissue fluid returns through capillaries end (capillaries venous end) and reminder diffuse through the more permeable walls of the lymph capillaries, forming lymph.
(Fig-01 A. Major parts of the lymphatic system. B. Regional drainage of lymph).
FUNCTION OF LYMPHATIC SYSTEM
Around 21 liters of fluid from plasma, escape from the arterial end of the capillaries into the tissues, that contain dissolved substance and some amount of plasma protein. Most of the fluid return back to the bloodstream via capillary venous end, but about 3-4 liters of fluid is drained away by the lymphatic vessels.
Absorption in the small intestine
Fat and fat soluble materials e.g. the fat soluble vitamins are absorbed into central lacteals (lymphatic vessels) of the villi.
The white blood cells responsible for immunity, the lymphocytes which is produced in the bone marrow, that are concerned with the production of immunity.
Lymph is a clear watery fluid, similar composition to plasma capillaries beds and also carries away larger particles e.g. bacteria and cell debris from damaged tissues, which can then filtered out and destroyed by lymph nodes. The lymph contains lymphocytes, which circulate in the lymphatic system to prevent disease produced by antigen or any internal injury in the body organs.
These originate as blind-end tubes in the interstitial space. They have same structure as blood capillaries (single layer of endothelial cells), but their walls are more permeable to all interstitial fluid constituents, including protein and cell debris. The tiny capillaries join up to form large lymph vessels. Nearly all tissues have a network of lymphatic vessels (exception central nervous system, cornea of eye, bones superficial layer of skin).
(Fig-02. The origin of a lymph capillary.)
Large lymph vessels
It is found alongside the arteries and veins serving the area. Their walls are about same as veins (i.e. same thickness, same layers of tissue i.e. fibrous covering a middle layer of smooth muscle and elastic tissue and as inner lining of endothelium).
(Fig-03. A lymph vessel cut open to show valves.)
There is no pump, but the muscle layer in the walls of large lymph vessel has an intrinsic ability to contract rhythmically (lymphatic pump). Lymph vessels become larger as they join together eventually forming two ducts, Thoracic duct and Right lymphatic ducts.
Duct begins at the Cisterna chyli, which is a dilated lymph channel situated in front of the bodies first two lumbar vertebrae. The duct is about 40 cm long and opens into left subclavian vein in the root of the neck. It drains lymph from both legs, the pelvic and abdominal cavities, the left half of the thorax, head and neck and the left arm.
Right lymphatic duct
This is a dilated lymph vessel about 1 cm long. It lies in the root of the neck and open into the right subclavian vein. It drains lymph from the right half of the thorax, head, neck and right arm.
Lymphatic tissue mainly consist of lymphocytes in a mesh-like framework of connective tissue.
Lymph nodes and nodules
Lymph nodes and nodules are masses of lymphatic tissue. Nodes and nodules differ with respect to size and location. Nodes are usually larger, 10 to 20 mm in length, and are encapsulated; nodules range from a fraction of a millimeter to several millimeters in length and do not have capsules.
Lymph nodes structure
Lymph nodes have an outer capsule of fibrous tissue that dips down into the node substance forming partitions, or trabeculae. The main substance of the node consists of reticular and lymphatic tissue containing many lymphocytes and macrophages.
As many as four or five afferent lymph vessels may enter a lymph node while only one efferent vessel carries lymph away from the node. Each node has a concave surface called the hilum where an artery enters and a vein and the efferent lymph vessel leave.
Fig-04. Lymphatic vessels to cardiovascular system
The large numbers of lymph nodes situated in strategic positions throughout the body are arranged in deep and superficial groups. Lymph from the head and neck passes through deep and superficial cervical nodes.
Lymph from the upper limbs passes through nodes situated in the elbow region, then through the deep and superficial axillary nodes.
Lymph from organs and tissues in the thoracic cavity drains through groups of nodes situated close to the mediastinum, large airways, oesophagus and chest wall. Most of the lymph from the breast passes through the axillary nodes.
Lymph from the pelvic and abdominal cavities passes through many lymph nodes before entering the cisterna chyli. The abdominal and pelvic nodes are situated mainly in association with the blood vessels supplying the organs and close to the main arteries, i.e. the aorta and the external and internal iliac arteries.
The lymph from the lower limbs drains through deep and superficial nodes including groups of nodes behind the knee and in the groin (inguinal nodes).
Filtering and phagocytosis
Lymph is filtered by the reticular and lymphoid tissue as it passes through lymph nodes. Particulate matter may include bacteria, dead and live phagocytes containing ingested microbes, cells from malignant tumours, worn-out and damaged tissue cells and inhaled particles. Organic material is destroyed in lymph nodes by macrophages and antibodies. Some inorganic inhaled particles cannot be destroyed by phagocytosis. These remain inside the macrophages, either causing no damage or killing the cell. In some cases where phagocytosis of bacteria is incomplete they may stimulate inflammation and enlargement of the node (lymphadenopathy).
Proliferation of lymphocytes
Activated T- and B-lymphocytes multiply in lymph nodes. Antibodies produced by sensitized B-lymphocytes enter lymph and blood draining the node.
Spleen is the largest lymph organ and it contains reticular and lymphatic tissues.
Position and morphology
The spleen lies in the left hypochondriac region of the abdominal cavity between the fundus of stomach and the diaphragm. It is the purplish in colour and varies in size in different individuals, but is usually about 12 cm long, cm wide and 2.5 cm thick. It weight about 200g.
Organs associated with the spleen
Superiorly and posteriorly – diaphragm
Inferiorly – left colic flexure of the large intestine
Anteriorly – fundus of the stomach
Medially – pancreas and the left kidney
Laterally – separated from the 9th, 10th and 11th ribs and the intercostal muscles by the diaphragm
The spleen is slightly oval in shape with the hilum on the lower medial border. The anterior surface is covered with peritoneum. It is enclosed in a fibroelastic capsule that dips into the organ, forming trabeculae. The cellular material, consisting of lymphocytes and macrophages, is called splenic pulp, and lies between the trabeculae. Red pulp is the part suffused with blood and white pulp consists of areas of lymphatic tissue where there are sleeves of lymphocytes and macrophages around blood vessels.
(Fig-07. A section through the spleen)
The structures entering and leaving the spleen at the hilum are:
- Splenic artery, a branch of the coeliac artery
- Splenic vein, a branch of the portal vein
- Lymph vessels (efferent only)
Blood passing through the spleen flows in sinusoids, which have distinct pores between the endothelial cells, allowing it to come into close association with splenic pulp.
As described previously, old and abnormal erythrocytes are mainly destroyed in the spleen, and the breakdown products, bilirubin and iron, are transported to the liver via the splenic and portal veins. Other cellular material, e.g. leukocytes, platelets and bacteria, is phagocytosed in the spleen. Unlike lymph nodes, the spleen has no afferent lymphatics entering it, so it is not exposed to diseases spread by lymph.
Storage of blood
The spleen contains up to 350 ml of blood, and in response to sympathetic stimulation can rapidly return most of this volume to the circulation, e.g. in haemorrhage.
The spleen contains T- and B-lymphocytes, which are activated by the presence of antigens, e.g. in infection. Lymphocyte proliferation during serious infection can cause enlargement of the spleen (splenomegaly).
The spleen and liver are important sites of fetal blood cell production, and the spleen can also fulfil this function in adults in times of great need.
The thymus gland lies in the upper part of the mediastinum behind the sternum and extends upwards into the root of the neck. It weighs about 10 to 15 g at birth and grows until puberty, when it begins to atrophy. Its maximum weight, at puberty, is between 30 and 40 g and by middle age it has returned to approximately its weight at birth.
Fig-08. The thymus gland in the adult, and related structures.
Organs associated with the thymus
Anteriorly – sternum and upper four costal cartilages
Posteriorly – aortic arch and its branches, brachiocephalic veins, trachea
Laterally – lungs
Superiorly – structures in the root of the neck
Inferiorly – heart
The thymus consists of two lobes joined by areolar tissue. The lobes are enclosed by a fibrous capsule which dips into their substance, dividing them into lobules that consist of an irregular branching framework of epithelial cells and lymphocytes.
Lymphocytes originate from stem cells in red bone marrow. Those that enter the thymus develop into activated T-lymphocytes.
Thymic processing produces mature T-lymphocytes that can distinguish ‘self’ tissue from foreign tissue, and also provides each T-lymphocyte with the ability to react to only one specific antigen from the millions it will encounter. T-lymphocytes then leave the thymus and enter the blood. Some enter lymphoid tissues and others circulate in the bloodstream. T-lymphocyte production, although most prolific in youth, probably continues throughout life from a resident population of thymic stem cells.
The maturation of the thymus and other lymphoid tissue is stimulated by thymosin, a hormone secreted by the epithelial cells that form the framework of the thymus gland. Shrinking of the gland begins in adolescence and, with increasing age, the effectiveness of the T-lymphocyte response to antigens declines.
Mucosa-associated lymphoid tissue (MALT)
Throughout the body, at strategically placed locations, are collections of lymphoid tissue which, unlike the spleen and thymus, are not enclosed within a capsule. They contain B- and T-lymphocytes, which have migrated from bone marrow and the thymus, and are important in the early detection of invaders. However, as they have no afferent lymphatic vessels, they do not filter lymph, and are therefore not exposed to diseases spread by lymph. MALT is found throughout the gastrointestinal tract, in the respiratory tract and in the genitourinary tract, all systems of the body exposed to the external environment. The main groups of MALT are the tonsils and aggregated lymphoid follicles (Peyer’s patches).
These are located in the mouth and throat, and will therefore destroy swallowed and inhaled antigens.
Aggregated lymphoid follicles (Peyer’s patches)
These large collections of lymphoid tissue are found in the small intestine, and intercept swallowed antigens.
Lymph vessel pathology
|Lymphangitis||Inflammation of lymph vessels|
|Lymphadenitis||Infection of lymph nodes|
|Lymphadenopathy||Enlargement of lymph nodes|
|Splenomegaly||Enlargement of the spleen|
|Lymphoedema||Swelling in tissues whose lymphatic drainage has been obstructed in some way|
Spread of disease
The materials most commonly spread via the lymph vessels from their original site to the circulating blood are fragments of tumours and infected material.
Tumour cells may enter a lymph capillary draining a tumour, or a larger vessel if a tumour has eroded its wall. Cells from a malignant tumour, if not phagocytosed, settle and multiply in the first lymph node they encounter. There may then be further spread to other lymph nodes, to the bloodstream and to other parts of the body via the blood. In this sequence of events, each new metastatic tumour becomes a source of malignant cells that may spread by the same routes.
Infected material may enter lymph vessels from infected tissues. If phagocytosis is not effective the infection may spread from node to node, and eventually reach the bloodstream.
This occurs in some acute bacterial infections in which the microbes in the lymph draining from the area infect and spread along the walls of lymph vessels, e.g. in acute Streptococcus pyogenes infection of the hand, a red line may be seen extending from the hand to the axilla. This is caused by an inflamed superficial lymph vessel and adjacent tissues. The infection may be stopped at the first lymph node or spread through the lymph drainage network to the blood.
When a lymph vessel is obstructed, lymph accumulates distal to the obstruction (lymphoedema). The amount of resultant swelling and the size of the area affected depend on the size of the vessel involved. Lymphoedema usually leads to low-grade inflammation and fibrosis of the lymph vessel and further lymphoedema. The most common causes are tumours and following surgical removal of lymph nodes.
A tumour may grow into, and block, a lymph vessel or node, obstructing the flow of lymph. A large tumour outside the lymphatic system may cause sufficient pressure to stop the flow of lymph.
In some surgical procedures lymph nodes are removed because cancer cells may have already spread to them. This aims to prevent growth of secondary tumours in local lymph nodes and further spread of the disease via the lymphatic system, e.g. axillary nodes may be removed during mastectomy, but it can lead to obstruction of lymph drainage.
Diseases of lymph nodes
Acute lymphadenitis (acute infection of lymph nodes) is usually caused by microbes transported in lymph from other areas of infection. The nodes become inflamed, enlarged and congested with blood, and chemotaxis attracts large numbers of phagocytes. If lymph node defences (phagocytes and antibody production) are overwhelmed, the infection can cause abscess formation within the node. Adjacent tissues may become involved, and infected materials transported through other nodes and into the blood. Acute lymphadenitis is secondary to a number of conditions.
Infectious mononucleosis (glandular fever)
This is a highly contagious viral infection, usually of young adults, spread by direct contact. During the incubation period of 7 to 10 days, viruses multiply in the epithelial cells of the pharynx. They subsequently spread to cervical lymph nodes, then to lymphoid tissue throughout the body. Clinical features include tonsillitis, lymphadenopathy and splenomegaly. A common complication is myalgic encephalitis. Clinical or subclinical infection confers lifelong immunity.
Minor lymphadenitis accompanies many infections and indicates the mobilization of normal protective mechanisms, e.g. proliferation of defense cells. More serious infection occurs in, e.g. measles, typhoid and cat-scratch fever, and wound or skin infections. Chronic lymphadenitis occurs following unresolved acute infections, in tuberculosis, syphilis and some low-grade infections.
These are malignant tumours of lymphoid tissue and are classified as either Hodgkin’s or non-Hodgkin’s lymphomas.
In this disease there is progressive, painless enlargement of lymph nodes throughout the body, as lymphoid tissue within them proliferates. The superficial lymph nodes in the neck are often the first to be noticed. The disease is malignant and the cause is unknown. The prognosis varies considerably but the pattern of spread is predictable because the disease spreads to adjacent nodes and to other tissues in a consistent way. The effectiveness of treatment depends largely on the stage of the disease at which it begins. The disease leads to reduced immunity, because lymphocyte function is depressed, and recurrent infection is therefore common. As lymph nodes enlarge, they may compress adjacent tissues and organs. Anaemia and changes in leukocyte numbers occur if the bone marrow is involved.
These tumours, e.g. multiple myeloma and Burkitt’s lymphoma, may occur in any lymphoid tissue and in bone marrow. They are classified according to the type of cell involved and the degree of malignancy, i.e. low, intermediate or high grade. Low-grade tumours consist of well-differentiated cells and slow progress of the disease, death occurring after a period of years. High-grade lymphomas consist of poorly differentiated cells and rapid progress of the disease, death occurring in weeks or months. Some low- or intermediate-grade tumours change their status to high grade with increased rate of progress. The expanding lymph nodes may compress adjacent tissues and organs. Immunological deficiency leads to increased incidence of infections, and if the bone marrow or spleen (or both) is involved there may be varying degrees of anaemia and leukopenia.
Metastatic tumours develop in lymph nodes in any part of the body. Lymph from a tumour may contain cancer cells that are filtered out by the lymph nodes. If not phagocytosed, they multiply, forming metastatic tumours. Nodes nearest the primary tumour are affected first but there may be further spread through the sequence of nodes, eventually reaching the bloodstream.
Diseases of the spleen
This is enlargement of the spleen, and is usually secondary to other conditions, e.g. infections, circulatory disorders, blood diseases, malignant neoplasms.
The spleen may be infected by blood-borne microbes or by local spread of infection. The red pulp becomes congested with blood and there is an accumulation of phagocytes and plasma cells. Acute infections are rare.
Some chronic non-pyogenic infections cause splenomegaly, but this is usually less severe than in the case of acute infections. The most commonly occurring primary infections include:
- Typhoid fever
- Brucellosis (undulant fever)
- Infectious mononucleosis.
Splenomegaly due to congestion of blood occurs when the flow of blood through the liver is impeded by, e.g., fibrosis in liver cirrhosis, or portal venous congestion in right-sided heart failure.
Splenomegaly may be caused by blood disorders. The spleen enlarges to deal with the extra workload associated with removing damaged, worn out and abnormal blood cells in, e.g., haemolytic and macrocytic anaemia, polycythaemia and chronic myeloid leukaemia. Splenomegaly may itself cause blood disorders. When the spleen is enlarged for any reason, especially in portal hypertension, excessive and premature haemolysis of red cells or phagocytosis of normal white cells and platelets leads to marked anaemia, leukopenia and thrombocytopenia.
Benign and primary malignant tumours of the spleen are rare but blood-spread tumour fragments from elsewhere in the body may cause metastases. Splenomegaly caused by infiltration of malignant cells is characteristic of some conditions, especially chronic leukemia, Hodgkin’s disease and non- Hodgkin’s lymphoma.
Diseases of the thymus gland
Enlargement of the gland is associated with some autoimmune diseases, such as thyrotoxicosis and Addison’s disease. Tumours are rare, although pressure caused by enlargement of the gland may damage or interfere with the functions of adjacent structures, e.g. the trachea, oesophagus or veins in the neck. In myasthenia gravis, most patients have either thymic hyperplasia (the majority) or thymoma (a minority), although the role of thymic function in this disorder is not understood.
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