THE LYMPHATIC SYSTEM
HOW THE LYMPHATIC SYSTEM WORKS
Modern Lymphology is a new, rapidly developing, medical discipline, which deals with the physiology and diseases of the Lymphatic System. It is not a stand-alone specialty, but it is an integral part of practically every other clinical specialty. At the same time, it has its own experimental and clinical research area.
The Lymphatic System consists of an architectural structure formed of an interstitial space, lymph vessels, lymph, organized lymphatic tissue, and lymphatic nodes, which are all closely interrelated. Further, from a functional point of view, it is linked to the nervous and endocrine systems.
When analyzing physiological and pathological processes, the system of lymphatic vessels and the lymph should not be separated from lymphatic cells. Indeed, the cellular and non-cellular components of the lymphatic system are functionally interdependent. For example, the physiopathological mechanisms underlying lymphedema cannot be understood without accepting the modern definition of the lymphatic system, which comprises the lymphatic pathways, lymph, and lymphatic cells that work in an integrated manner.
Lymphatic circulation acts as a regulator of tissue fluid volume and chemical composition (between cells and the extracellular environment), in charge of transporting filtered plasma proteins and cellular products (enzymes, hormones, etc.), removingdetritus, waste, mutated or tumor cells, and carrying bacteria, viruses, fungi, inorganic particles to lymphoid organs, such as lymph nodes, the spleen, and the bone marrow.
From an embryological point of view, the Lymphatic System begins to develop at around the end of the 5th week of gestation, two weeks after the cardiovascular system. Just like the venous system, lymphatic vessels originate out of thin perivenous mesenchymal fissures. They are independent of embryonal veins and, initially, do not communicate with them. Between the 6thand 9th week, 6 dilations begin to develop along lymphatic vessel pathways, corresponding to the 6 main lymphatic sacs: 2 jugular, 2 iliac sacs, 1 retroperitoneal sac, and the chylous cyst. Initially, they form discreet lymphatic territories. Lymph vessels originate out of these sacs and develop along the pathways of the main veins.
The chylous cyst communicates with the jugular sac by means of two large – right and left – thoracic collectors, which later on join together through an anastomotic branch.
The thoracic duct develops from the caudal portion of the right thoracic duct and from the anastomotic branch and cranial portion of the left thoracic duct.
The right lymphatic duct develops from the cranial portion of the right thoracic duct.
Finally, the thoracic duct flows into the intersection between the jugular vein and the left subclavian vein.
This brief description of lymphangiogenesis is important to understand the high anatomic complexity of the lymphatic structures, and, the potential for variability particularly, of the thoracic duct pathway.
Anatomy and Physiopathology
The Lymphatic System consists of:
- Lymphatic capillaries (or initial lymphatics), featuring blind ending canaliculi, formed by a single-layer endothelial cells, without basal membrane. Seamless areas between the cells allow interstitial fluid to pass through.
- Lymphatic vessels, distributed all over the body, in each organ, except for the central nervous system, consisting of an endothelial layer, resting on a basal membrane. The tunica media consists of more or less scattered smooth muscle fiber cells. The adventitia consists of a connective tissue sheath.
Lymphatic collectors have a high number of valves, which, along a caudo-cranial line, become progressively less numerous but thicker, thus conferring a moni-liniform appearance to lymphatic vessels.
Lymph nodes, which are the lymph circulation relays, are organized into lymph node chains along the course of major veins. Afferent lymphatic vessels enter into the lymph node capsule and drain the lymph into the marginal sinus. The lymph fluid, through the cortical sinus, flows into the medullary sinus, and is drained by efferent collectors at the level of the hilum. The number of afferent lymph vessels is always greater than efferent ones, which, however, have bigger cross-sections.
Lymph nodes have an arteriolar-capillary-venous blood supply, which, under pathologic conditions, may allow for intranodal lymph-venous communication.
Lymph vessels receive the lymph from adjacent regions, organs, and viscera, according to a relatively constant anatomic distribution, which has major clinical implications, especially in case of tumors and peripheral and visceral lymph stasis diseases.
Lymphatic vessels receive the lymph from adjacent regions, organs, and viscera, according to a relatively constant anatomic distribution, that has major clinical implications, especially in case of tumors and peripheral and visceral lymph stasis diseases.
The lymphatics converge in the abdomen towards the commencement of the thoracic duct at the level of the cisterna chyli, into which several chylous vessels also flow. The cisterna chyli is most commonly located at the level of the 2nd lumbar vertebra. Therefore, the thoracic duct traverses the diaphragm, running to the right side of the aorta. Anterior to the spine, it runs medially and surpasses the median line, then moves to the left and ascends along the posterior-internal surface of the subclavian artery, to empty into the junction of the left subclavian vein and left jugular, at the root of the neck. There is one, or more, highly efficient, valves at the level of its outlet, in charge of the almost constant reflux toward afferent lymphatics, thus causing, during podal lymphography, a frequent opacization of supraclavicular lymph nodes.
The thoracic duct drains 3/4 of the body’s lymph; namely all subdiaphragmatic lymph, part of the thoracic lymph, the lymph from the upper left limb, the left half of the neck and the left side of the face.
The right lymphatic duct or the right end portion of a duplicate thoracic duct receives part of the thoracic lymph and the lymph from the upper right limb, the right half of the neck, and the right side of the face. It drains into a vein of the right supraclavicular fossa.
These strict anatomic correlations between the lymphatic collectors and viscera account for the consequences of loco-regional diseases on lymph circulation and, viceversa, repercussions caused by lymphatic obstruction on organs and tissues upstream the obstacle.
The lymph derives from extracellular fluid, which is constantly exchanged with blood. Around 20 liters of fluid flow every day in interstitial tissues through blood capillaries: 90% is taken up by the venous system, and 10% by lymphatic roots, to form the lymph. Water, electrolytes, and small diameter molecules enter into the lymphatics by diffusion. Larger molecules, entering the interstitial tissues from the blood flow, are partially collected by the lymphatic circulation, together with by-products of their metabolism. Re-absorption occurs in intercellular spaces of lymphatic capillaries, by means of a mechanic process, whereby these spaces simply open up. Initial lymphatic vessels fill up according to a passive process, that depends on tissue pressure. The lymph pushed into a lymph vessel beyond a first valve, empties the capillary, thus allowing it to absorb more interstitial fluid again. Casley-Smith described this process as the “capillary pump”.
In the lymphatics, the lymph is clear, colorless, transparent, and coagulable. Owing to a higher concentration of diffusible ions, it has a higher osmotic pressure than the plasma.
Many Authors have tried to compare lymph and plasma composition. However, lymph composition changes depending on the examined territory. Each territory feeds the lymph with products of specific local metabolism: for example, intestinal chyliferous vessels, draining chyle (a white, dense, milky fluid), have a lipid concentration, which depends on digestion stage and diet. The lymphatic system is the most important way in which intestinal fats are absorbed.
The lymph also consists of a cellular component: erythrocytes and lymphocytes that derive from the interstitial tissue. Erythrocytes are present in low numbers in the lymph, but are more numerous than lymphocytes in the initial lymphatics.
The number of lymphocytes gradually increases while the lymph flows through various lymph nodes. Hence, the lymph in the thoracic duct contains from 2,000 to 20,000 lymphocytes mm3, namely a concentration 2 to 10 times higher than in the blood. Lymphocytosis varies in healthy individuals, depending on the number of lymph nodes, temperature, digestion stage, and endocrine condition.
Concentration of clotting factors in lymphatics is 20 to 60% lower than in the blood; however, the lymph in the thoracic duct may clot.
While it flows forward in the lymphatics, the lymph becomes progressively more and more concentrated, due to the leak of fluids through the walls of lymphatic vessels.
Lymphatic flow is slow. The presence of valves prevents, under normal conditions, gravitational lymphatic reflux. Lymph progress particularly depends on the action of smooth muscle fiber cells in the lymphatic vessel wall, and is due to the opening and closing of valves, muscle activity, endo-abdominal pressure, respiratory movements, and thoracic inspiration.
Lymph nodes tend to slow down circulation only in part.
Lymphatic pressure varies depending on the territory where it is measured and on digestion stage. It increases during inhaling and drops while exhaling.
Peripheral endolymphatic pressure, under normal conditions, ranges between 10 and 22 mm H2O. The flow is negligible during complete rest.
Lymphatic pressure inside the thoracic duct, which is higher than venous pressure, promotes lymphatic drainage into the venous system, due to a negative pressure gradient.
The immunologic, circulatory, and metabolic functions are the main functions of the lymphatic system:
- Immunologic function – Lymph nodes play a fundamental role, by promoting exchanges with the reticular-endothelial system. The lymph, by flowing through lymph nodes, becomes rich in lymphocytes and antibodies. Also, the lymph nodes act as a filter and barrier against the spread of infections or tumors. With regard to venous return, they play the same function as the lungs and the liver.
- Circulatory function – in parallel with the venous system, that drains 90% of interstitial fluid, the lymphatic system drains the remaining 10%.
- Metabolic function – The lymphatic system is involved in general metabolism: of proteins (proteins are present in the lymph in lower concentration than in the plasma), and of lipids (during digestion). The lymphatic system transports the majority of lipids to the thoracic duct, in the form of chylomicrons and lipoproteins. Chyle is the lymph of the thoracic duct.
From a physiopathological point of view, as far as lymphedema is concerned, primary deficiency in lymph transport may be due to a low output failure of the lymphatic system: in other words, there is an overall reduction in lymph transport. In any case, the common factor is the fact that lymph transport falls below the level needed to handle the microvascular filtration load, which includes plasma and cell proteins, that normally enter the interstitium from blood circulation. On the other hand, lymphatic circulation high output failure occurs, when healthy or increased output is overwhelmed by an excessive load of capillary blood filtration products: for example, in the case of liver cirrhosis (ascites), nephrosic syndrome (anasarca), and deep venous insufficiency of the lower limbs (post-thrombophlebitic syndrome). Finally, lymphatic valve failure may imply a gravitational lymphatic-chylous reflux and subsequent correlated syndromes (chyledema, chylothorax, chyloperitoneum, chyluria, etc.).