A much-deprived topic in some anatomy textbooks and hence often a poorly understood area of anatomy and clinical practice. This post aims to highlight the function of the lymphatic system, explore the key components and give examples of its clinical significance. If you are wanting a brief version of this post, focusing on lymph drainage, then read on from the subheading titled “General drainage patterns”.
The lymphatic system consists of four main components, lymph fluid, vessels, lymphatic tissue (follicles, nodes and organs) and red marrow. These structures do not form a complete circuit as compared with the cardiovascular system, this is because the lymphatic capillaries end blindly in the tissues. In the cardiovascular system blood moves to and away from the heart, in the lymphatic system, lymph is only moving towards the heart. The cardiovascular system has a quad chambered pump, the lymphatic system has no intrinsic pump.
The lymphatics permeate every area of the body except for the CNS*, eyeball, the internal ear, epidermis of the skin, cartilage, bone marrow and placenta. The lymphatic system has three major functions, drain and recycle excessive interstitial fluid AKA extracellular fluid back into the cardiovascular circulation (hence helping to maintain circulatory volume), transport dietary lipids and it forms an integral part of the immune system, providing white cells with a conduit to traverse the body. Clinically an understanding of the main vessels and groups of nodes is important in appreciating how a disease may spread from one region to another, in particular, infection and malignant disease.
What is lymph?
Lymph consists of white blood cells (in particular lymphocytes), “used” extracellular fluid, and chyle. Extracellular fluid (also referred to as interstitial fluid) consists of the liquid which is found between (interstitial spaces) cells; it is formed in capillary beds, a product of the balance between hydrostatic and oncotic pressure between the arterial and venous end of a capillary bed. Once extracellular (interstitial) fluid enters the lymph vessels, it is referred to as lymph.
Chyle is component added to lymph fluid from the intestinal lymphatic vessels known as lacteals. Chyle is a whitish liquid (lymph elsewhere is a clear yellowish liquid) found in intestinal lymphatics, rich in protein and lipids from absorption in the small bowel microvilli.
Lymph is carried through the lymphatics and finally drains into the venous system via the right lymphatic duct and the thoracic duct on the left. Both ducts drain into their respective junctions between the internal jugular and subclavian veins on each side of the body.
Components of the lymphatic system
The key components other than lymph fluid are vessels, lymphatic tissue and red marrow. Lymph vessels start off as single endothelial cell walled lymphatic capillaries, these vessels are highly permeable, allowing large molecules and interstitial fluids to flow in, but preventing them from flowing out through their walls. These lymphatic capillaries are anchored to the surrounding tissue by elastic anchoring filaments. When excessive interstitial fluid causes tissues to swell, the anchoring filaments are pulled taut, opening the gaps wider between the endothelial cells and encouraging interstitial fluid to enter into the lymphatic capillaries. In the small intestines, the lymphatic capillaries are specialised for the absorption of lipids and are known as lacteals.
Figure 1 Schematic representation of lymph flow through the lymphatic system
Lymphatic capillaries interconnect to form lymphatic plexuses, which eventually converge to form larger lymphatic vessels, these larger vessels are similar to veins having valves and have a beaded appearance due to the presence of intermittent lymph nodes. Once the lymph has passed through at least one lymph node, it eventually passes through lymphatic vessels which then converge to form large lymphatic trunks, see Figure 1. These trunks include the lumbar (left and right), intestinal (single), bronchomediastinal (left and right), subclavian (left and right) and jugular trunks (left and right). The lumbar trunks drain their respective lower limb, pelvic wall and viscera, abdominal wall, kidneys and adrenal glands. The intestinal trunk drains most of the abdominal viscera, including parts of the liver. The bronchomediastinal trunks drain lymph from the thoracic walls, lungs and heart. The jugular trunks drain their respective sides of the head & neck and as do the subclavian trunks their respective upper limbs.
The left and right lumbar trunks and the intestinal trunk drain into a dilated lymph sac like vessel known as the cisterna chyli, located just below the aortic hiatus in the diaphragm; this marks the beginning of the thoracic duct, which ascends into the thorax through the aortic hiatus and is joined by the left bronchomediastinal, subclavian and jugular trunks before it finally drains into the junction of the left internal jugular and subclavian vein. You may be asking what about the right bronchomediastinal, subclavian and internal jugular? Well, they drain into the right lymphatic duct, which drains into the junction between the right subclavian and internal jugular veins, Thus there is a distinct asymmetry in terms of general drainage of lymph between the left and right side of the body.
Lymphatic tissues can be split into two broad categories, primary and secondary lymphatic organs & tissues. Primary includes organs and tissues where stem cells divide and become immunocompetent. These include red bone marrow and the thymus (an organ). Secondary organ and tissue sites are where immunocompetent B & T cells mount an immune response. These sites include follicles (nodules), nodes and the spleen.
Follicles (sometimes referred to as nodules in some texts) are the small aggregation of lymphatic tissue, specifically B cell lymphocytes or plasma cells found throughout mucosa located in the gastrointestinal, respiratory and urinary tract, often referred to as mucosa-associated lymphatic tissue (MALT). Some of these aggregations form larger clumps such as the tonsils (Waldeyer’s ring), the Appendix and Peyer’s patches in the intestinal ileum. Follicles (nodules) are not considered organs, because they lack a connective tissue capsule. Follicles can be arranged in a structure with an outer capsule – these are nodes, discussed next.
The nodes are small kidney-bean shaped structures located along lymph vessels, we have over 600 of them spread throughout the body. Each node consists of groups of follicles (parenchyma) encapsulated and divided by connective tissue (stroma). The node is generally divided into a cortex and medulla regions. The cortex contains follicles containing resident B cells; the medulla contains visiting (from other tissues) T cells and dendritic cells. Nodes have afferent vessels bringing lymph in (convex surface of the node) and efferent vessels taking lymph out (hilum or concave surface of the node). The nodes act as sites where foreign antigens are presented to lymphocytes, and hence where immune responses are mounted. Lymph nodes also act as physical filtration systems, trapping bacteria, cancer cells and foreign material. A large number of nodes are found in the inguinal, axillary and head & neck regions, which are easily palpated when enlarged, the thorax, abdomen and pelvis contain many deeper nodes as well, often adjacent to arteries.
The thymus and spleen have a similar function to the smaller nodes. Remember though the thymus is a primary lymphatic organ and is therefore also responsible for immunocompetent cells being created from stem cells. Immature T cells migrate from red bone marrow sites to enter the thymus to undergo maturation. The thymus is a bilobed organ located in the anterior aspect of the superior mediastinum and extending into the anterior aspect of the inferior mediastinum, in front of the upper edge of the heart. The functional portion of the thymus is significantly larger in early life than it is in the adult.
The spleen is a secondary lymphatic organ and is the largest lymphatic organ. It is located on the left side, under the diaphragm, within the ribcage and beneath ribs 9, 10 and 11. The spleen has an external capsule, which extends into the organ itself, this constitutes the stroma. The functional tissue (parenchyma) consists of white and red pulp.
The white pulp is mainly tissue made up of lymphocytes and macrophages arranged around central arteries (branches of the splenic artery) and carries out functions akin to the nodes, mounting immune responses to foreign antigens and destroying pathogens. The red pulp is made splenic tissue known as Billroth’s cords, and blood filled venous sinuses, as blood travels through this region, the red pulp macrophages break down and remove old and defective red blood cells and platelets. The spleen is also an important store for platelets and during foetal life is a location for red blood cell production.
General drainage patterns
Lymph, in general, will pass through at least one node before it returns to the venous system. Once lymph enters a major collecting vessel with valves, its direction is fixed, before this lymph follows the path of least resistance, hence why it is common to find differences in lymph drainage patterns from organs.
As described previously, the lymph from the right half of the thorax, right arm and right side of the head and neck all drain into the right lymphatic duct, which then empties into the junction between the right internal jugular and subclavian vein. The rest of the body drains into the thoracic duct and then into the junction between the left internal jugular and left subclavian vein.
Unlike the cardiovascular system, there is no pump like the heart to help push lymph through the lymphatic system. Instead, the flow of lymph relies on the squeezing action of surrounding muscles and respiratory effort. The changes in intrathoracic pressure occurring during respiration, for example during inhalation, intrathoracic pressure drops, aiding venous and lymphatic return. During exhalation, the valves in lymphatic vessels prevent the reversal of flow.
Looking at deep lymph vessels, we see that they tend to run adjacent to the arteries supplying this tissues. Therefore the testicles are supplied by the testicular arteries, which arise from the aorta. The testicular lymph vessels follow the testicular arteries back towards the aorta, towards the aortic nodes (paraaortic to be specific). Consider foregut abdominal organs, each organ will have their own cluster of deep nodes, however, they will all drain back to the coeliac nodes (foregut arterial supply is from the coeliac axis). The midgut would be similar, midgut organs would have their own cluster of deep nodes, but they would all converge and drain into the superior mesenteric nodes.
Superficial lymph drainage in the upper and lower limbs follows superficial veins, which can help to serve as a reminder as to where superficial nodes and vessels drain, see examples below.
Lymph drainage examples
When asked to consider which nodes cancer may metastasise to or an infection will affect, you will need to take into account the original site of pathology. As stated above, if it’s superficial skin in the upper and lower limbs, then lymph will follow superficial veins draining that area of skin. If it’s a deeper structure (in the torso and or limbs), e.g. in the testicles, then the lymph vessels run along aside the arterial supply to the specific organ being considered.
Let’s take testicular cancer, the closest nodes may be the superficial inguinal nodes, however, the testicular lymph drainage runs adjacent to the testicular artery which comes directly off the abdominal aorta. Hence the lymphatic drainage will be to the paraaortic nodes. Though, if the testicular cancer spreads locally and invades the skin of the scrotum, metastasis will cause enlargement of the superficial inguinal nodes.
How about the ovaries? The blood supply to ovaries is via the ovarian arteries (via the suspensory ligaments), therefore drainage would also be to the paraaortic nodes. The ovary is also connected to the uterus by the ovarian ligament, of which a continuation is the round ligament, we know this ligament extend outs of the deep and superficial inguinal rings, and into the mons pubic, therefore metastasis can spread via this route into pelvic nodes and also into inguinal nodes.
Lymphatic capillaries in the breast tissue form various plexuses which eventually drain to the axillary lymph nodes and internal thoracic nodes (internal thoracic artery). Approximately 75% of the lymph drainage from the breast drains towards the lateral quadrants (the breasts are divided into four quadrants, the upper lateral quadrant includes the tail of the breast tissue) of the breast. The lymph from these lateral quadrants drain to the axillary complex of nodes; a useful mnemonic to remember the nodes which make up the axillary complex is the word APICAL. Anterior, Posterior, Infraclavicular, Central, Apical and Lateral. Most breast cancers occur in the upper lateral quadrant of the breast, this region, in particular, tends to drain to the anterior nodes of the axillary group. The medial quadrants tend to drain to the internal thoracic nodes, potentially also allowing spread to the adjacent sides internal thoracic nodes and breast tissue also.
In the general section above we have already looked at the lymph drainage of the gastrointestinal tract, a slightly more complicated example to consider is the rectum and anal canal. The rectum and the anal canal are supplied by three arteries, the rectum and the first half of the anal canal are supplied by the superior rectal artery and some branches of the middle rectal arteries. The former arises from the inferior mesenteric artery, the latter the internal iliac arteries. Lymphatic drainage is therefore to the inferior mesenteric nodes, but also to the internal iliac nodes. In the anal canal, the pectinate line demarcates the halfway point between the part of the canal derived from the hindgut (endoderm) with the lower half of the canal derived from the proctodeum (ectoderm), thus the lower half is more akin to the external skin. The blood supply to the lower half of the anal canal arises from both branches of the middle rectal arteries, as well as the inferior rectal arteries. Hence, lymph will drain to the internal iliac nodes, as well as the superficial inguinal nodes due to the region not strictly being a hindgut derivative.
The uterus drains to multiple groups of nodes, consider its blood supply, essentially an anastomosis of the uterine and ovarian arteries. The uterine artery is a division of the internal iliac artery so lymph will drain to the iliac nodes, the ovarian artery comes off the aorta, therefore lymph will also drain towards the paraaortic nodes. Remember the round ligament? Well, lymph will therefore also drain to the superficial inguinal nodes too.
Your patient has enlarged, tender superficial inguinal nodes; you suspect an infection, but where do you look? You need to consider which structures drain to this region, start with superficial structures, so skin covering the groin, perineum, lower limb and leg. If there was no swelling of the superficial inguinal nodes, instead you notice enlarged tender popliteal nodes behind the knee. You should then suspect pathology in the posterolateral aspect of the leg, in particular, the heel, why this area? Consider the superficial venous drainage, the short saphenous vein drains the posterolateral aspect of the leg, into the popliteal vein, the superficial lymph also drains in this direction, into the popliteal nodes, behind the knee. Deep infection of the foot would drain to the deep inguinal nodes. The deep inguinal nodes drain the deep lymphatics of the entire lower limb and leg but also drain the penis and the clitoris.
Consider the upper limb, infections of the thumb typically cause initially swelling of the inferior clavicular nodes (deltopectoral nodes), the lymph drainage following the cephalic vein, while infection of the ulnar side of the hand will typically cause the supratrochlear node to swell first, following the basilic vein.
In cases of supraclavicular lymph node enlargement which tissues drain to these regions? The axillary nodes drain the upper limb and breast, so pathology in these regions may cause right or left supraclavicular node enlargement. The right side is only receiving lymph from the right arm, the right half of the thorax and head & neck, but the left is also receiving lymph drainage from the entire abdomen, pelvis and both legs. So abdominal malignancy may present with enlarged left sided supraclavicular lymphadenopathy, remember Virchow’s node/ Troisier’s sign?
Lymphadenopathy, lymphangitis, lymphoedema and lymphoma
Lymphadenopathy is when lymph nodes increase in size, reacting to infection (reactive lymphadenopathy), this can be localised to a small cluster or generalised throughout of the body, depending on the spread of infection. Lymph glands may also enlarge due to the metastatic spread of cancers, this tends to follow the lymph drainage patterns of the tissues affected. Lymphadenopathy can also occur in autoimmune conditions. Lymphadenopathy due to infection and autoimmune conditions tends to cause the lymph nodes to become tender, they often remain soft and movable, as opposed to lymph nodes affected by metastasis, these tend to be non-tender, firm and fixed. Lymphangitis occurs when lymph vessels become inflamed or infected (commonly Streptococcus pyogenes), causing an inflammatory reaction in the overlying skin, indicated by swelling, erythema and tenderness.
Lymphoedema is the swelling of tissues due to excessive interstitial fluid not being removed due to impaired lymphatic drainage (filtration exceeds reabsorption). This is often seen in clinical practice, where lymph nodes have been removed post breast cancer surgery or where due to severe venous damage (e.g. due to chronic deep vein thrombosis in the leg), there is excessive interstitial fluid, which is overwhelming the lymphatic systems ability to reabsorb interstitial fluid. Regardless of the cause, it is difficult to treat and does not respond to diuretics and often requires uncomfortable compression stockings. It can cause some patients great distress and patients should be managed by the local lymphoedema service.
Lymphoma refers to a malignancy that arises from either B, T or NK (natural killer) cells within discrete areas of lymphatic tissue, as opposed to Lymphocytic leukaemia, which arises from the same cells, but presentations typically involve the bone marrow and peripheral blood. The lymphomas are broadly split into two main groups, Hodgkins and Non-Hodgkins lymphomas. Virtually all Hodgkins and 2/3 of Non-Hodgkins lymphomas present with an enlarged non-tender lymph node.
*Lymphatic drainage of the CNS is an ongoing area of research, recent research has shown the existence of lymphatic vessels in the meninges which interact with the cerebrospinal fluid.
Clinical Anatomy by Regions, Richard Snell
Principles of Human Anatomy, Gerard Tortora, Mark Nielson
Robbins and Cotran Pathologic Basis of Disease, Kumar, Abbas, Aster