Modern lymphology is a new, rapidly evolving medical discipline that deals with the physiology and diseases of the Lymphatic System. It does not represent an entity in its own right, but is, instead, an integral part of every clinical specialty and, moreover, has its own experimental and clinical research area. The Lymphatic System consists of an architectural structure composed of the interstitial space, lymphatic vessels, lymph, organized lymphatic tissue and lymph nodes, closely related to each other. It is also functionally connected to the nervous and endocrine systems.
Separating the system of lymph and lymphatic collectors from the lymphatic cells active in the process of analyzing physiological and pathological phenomena is incorrect. The cellular and non-cellular components of the lymphatic system are functionally interdependent. For example, the pathophysiological mechanisms of lymphedema cannot be understood without accepting the modern definition of the lymphatic system, which includes lymphatic pathways, lymph and lymphatic cells functioning in an integrated manner. Lymphatic circulation plays the role of regulating the volume and chemical composition of the tissue fluid (between cells and the extracellular environment); the role of transport of filtered plasma proteins and cellular products (enzymes, hormones, etc.), removal of debris, waste, mutated cells or tumor cells; and to convey bacteria, viruses, fungi, and inorganic particles to the lymphoid organs, such as lymph nodes, spleen, and bone marrow.
From an embryological point of view, the development of the lymphatic system begins at the end of the 5th week of gestation, 2 weeks after the cardiovascular system. As with the venous system, the lymphatic vessels derive from thin perivenous mesenchymal slits. They are independent of the embryonic veins and initially there is no communication between these vessel types. Between the 6th and 9th week, 6 dilatations appear (they are localized along the course of the lymphatic vessels), corresponding to the 6 main lymphatic sacs: 2 jugular, 2 iliac, 1 retroperitoneal, and the cisterna chyli. These represent initially separate lymphatic territories. The lymphatic vessels originate from these pockets and develop along the course of the main veins.The cisterna chyli communicates with the jugular sac by means of two large left and right thoracic collectors, which are then joined by 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 emerges in the angle formed by the internal jugular veins and the left subclavian.This synthetic description of the process of lymphangiogenesis allows us to understand the extreme anatomical variability of the lymphatic structures and, in particular, of the thoracic duct along its course.
The lymphatic system is composed of:1. Lymphatic (or initial lymphatic) capillaries, represented by blind-ended canaliculi, consisting of a single layer of endothelial cells without a basal membrane. Regions of continuous solutions between these cells favor exchanges with the interstitial fluid;2. Lymphatic vessels are distributed throughout the body, in each organ (but have not been demonstrated in the central nervous system) consisting of an endothelial layer that rests on a basal membrane. The tunica media is composed of more or less discontinuous smooth muscle cells (scattered). The adventitia is represented by a connective lamina sheath.The lymphatic collectors have a large number of valves, which progressively become less and less numerous, but thicker, in a caudo-cranial sense, providing a vermicular (moniliform) appearance to the lymphatic vessels.The lymph nodes, relays of the lymphatic circulation, are organized in lymph node chains along the course of the main veins. The afferent lymphatic collectors penetrate the lymph node capsule and drain the lymph into the marginal sinus. The lymph is passed through the cortical sinus to the medullary one, to be drained from efferent collectors at the hilum. There are aways more afferent vessels than efferent lymphatics but the efferent vessels have a larger diameter.The lymph nodes have an arteriolo-capillary-venous blood support system, which, under pathological conditions, may allow intranodal lymphatic-venous communication.The lymphatic vessels receive lymph from adjacent regions, organs and viscera, according to a relatively constant anatomical distribution. This has important clinical implications, especially in the oncological field and in peripheral and visceral lymphostatic diseases.The lymphatics converge in the abdomen towards the origin of the thoracic duct in correspondence to the cisterna chyli, to which numerous chyliferous collectors are found, situated at the level of the second lumbar vertebrae. The thoracic duct then crosses the diaphragm, running to the right of the aorta. It is located in front of the vertebral column, moves medially and crosses the midline in order to move to the left, and ascends the postero-internal surface of the subclavian artery, until it reaches the venous jugular- in the left corner at the base of the neck. The mouth of the thoracic duct contains one or more valves, which is very efficient but also potentially responsible for reflux towards the lymphatics afferent to the duct, determining an opacification of supraclavicular lymph nodes during a bipodal lymphangiography.
Anatomical abnormalities of the thoracic duct are frequent. Plexiform dilatations and duplications can sometimes be observed along its course, more frequently between T4 and T6. Accessory trans-diaphragmatic lymphatics drain, almost constantly, the submicroscopic lymph towards the mediastinal, intertracheobronchial and laterotracheobronchial lymph nodes.The thoracic duct drains 3/4 of the body’s lymph: all the subdiaphragmatic lymph, part of the thoracic lymph, the lymph from the left upper limb, the left half of the neck, and the left side of the face.The right lymphatic duct or the right terminal part of the duplicated thoracic duct receives part of the thoracic lymph and the lymph resulting from the right upper limb, right half of the neck, and the right side of the face. This lymph drains into a vein in the right supraclavicular fossa.The close anatomical correlations between lymphatic collectors and the viscera explain the consequences of loco-regional pathologies for the lymphatic circulation and, vice versa, the repercussions of a lymphatic obstruction on the organs and tissues upstream of the obstacle.The lymph derives from the extracellular fluid, in constant exchange with the blood. About 20 liters of liquid pass into the interstitial tissues through the blood capillaries every day: 90% is absorbed by the venous system and 10% by the lymphatic capillaries, forming the lymph. Water, electrolytes and small-diameter molecules enter the lymphatic vessels by diffusion. The large molecules, which pass into the interstitial tissues from the blood circulation stream, are partly reabsorbed by the lymphatic circulation, together with products deriving from their metabolism. The reabsorption occurs in the intercellular spaces of the lymphatic capillaries, through a mechanical phenomenon of a simple opening of these spaces. The filling of the initial lymphatics is a passive process, dependent on tissue pressure. The lymph pushed inside a lymphatic vessel over the first valve, empties the capillary, allowing it to further reabsorb the interstitial fluid. Casley-Smith described this phenomenon as a “capillary pump”.In the lymphatic vessels, the lymph is clear, colorless, transparent, and coagulable. As a result of the higher concentration of diffusible ions, the osmotic of lymph is higher than that of plasma.
Many authors have tried to compare the composition of the lymph to that of the plasma. However, the composition of the lymph varies according to the territory examined. Each area contributes the specific products of the local metabolism: just think of the intestinal chiliferous vessels, which drain the chylo (white, opaque, with a milky appearance), whose lipid concentration depends on the digestive phase and also the diet. The lymphatic system is the most important route of absorption of intestinal fats. The lymph also consists of a cellular component: erythrocytes and lymphocytes, initially deriving from interstitial tissue. Erythrocytes are present in low numbers in the lymph, but are more numerous than lymphocytes within the initial lymphatics.Gradually, after passing through various lymph node stations, the number of lymphocytes increases. Thus, the lymph in the thoracic duct contains from 2,000 to 20,000 lymphocytes per mm3; i.e., a concentration 2 to 10 times greater than blood. This lymphocytosis varies in normal subjects depending on the number of lymph nodes, temperature, digestive phase, and endocrine status.The lymphatic concentration of coagulation factors is 20 to 60% lower than that of blood, but the lymph of the thoracic duct can coagulate.During its progression along the lymphatic pathways, the lymph becomes progressively more concentrated due to the loss of liquids through the walls of the lymphatic vesselsLymphatic flow is slow. The presence of valves prevents, under normal conditions, gravitational lymphatic reflux. The progression of the lymph occurs, in particular, from the action of smooth muscle fibrocellules of the lymphatic wall, with the opening and closing of the valves, by muscular activity, by the intra-abdominal pressure, by respiratory movements, and by thoracic aspiration. Lymph nodes tend only to slow down the circulation.The lymphatic pressure varies according to the territory in which it is measured and the digestive phase. It increases during expiration and decreases during inspiration.The peripheral endolymphatic pressure, under normal conditions, varies between 10 and 22 mm H2O. The flow is negligible during complete rest.The lymphatic pressure inside the thoracic duct is greater than the venous pressure and thus promotes lymphatic drainage into the venous system. The main functions of the lymphatic system are immunological, circulatory, and metabolic:1. Immunological function: Lymph nodes play a fundamental role by favoring exchanges with the reticuloendothelial system. When lymph moves through the lymph nodes, it is enriched with lymphocytes and antibodies. The lymph nodes, moreover, act as a filter and barrier to the spread of infections or tumors. They perform the same function as that of the lungs and the liver with regard to the venous return system.• Circulatory function: in parallel to the venous system, which drains 90% of the interstitial fluid, the lymphatic system drains the remaining 10%.• Metabolic function: The lymphatic system participates in the general metabolism: protein (the proteins are present in the lymph in lower concentration compared to the plasma) and lipid (during digestion). The lymphatic system transports most of the lipids to the thoracic duct, in the form of chylomicrons and lipoproteins. The lymph of the thoracic duct is chylous. From the pathophysiological point of view, with regards to lymphedema, the central disturbance is represented by a low-flow failure (low output failure) of the lymphatic system: in other words, there is a general reduction of lymphatic transport. However, the common denominator is the fact that lymphatic transport falls below the capacity needed to manage the microvascular filtrate load, made up of plasma proteins and cells, which normally enter the interstitium from the bloodstream. On the other hand, a high output failure of the lymphatic circulation occurs when a normal or increased transport capacity is overwhelmed by an excessive load of filtrated capillary blood: for example, in cases of cirrhosis of the liver (ascites), nephrotic syndrome (anasarca), and deep venous insufficiency of the lower limbs (post-thrombophlebitic syndrome). Finally, a lymphatic valvular insufficiency may result in a gravitational lymphatic-chylous reflux and the consequent development of correlated syndromes (chyledema, chylothorax, chyloperitoneum, chyluria, etc.).
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