Anatomy and physiology of the lymphatic system
- Removes water, electrolytes, low-molecular-weightmoieties (polypeptides, cytokines, growth factors) and macromolecules (fibrinogen, albumen, globulins, coagulation and fibrinolytic factors) from the interstitial space and returns them to the circulation.
- Permits the circulation of lymphocytes and other immune cells.
- Intestinal lymph (chyle) transports cholesterol, long-chain fatty acids, triglycerides and the fat soluble vitamins (A, D, E and K) directly to the circulation, bypassing the liver.
Development and macroanatomy
In the embryo, the lymphatic system develops from four cystic spaces, located one on either side of the neck and one in each groin. These cisterns enlarge and develop communications (lymphatic vessels) that permit lymph from the lower limbs and abdomen to drain via the cisterna chyli, lying between the aorta and azygos vein, into the thoracic duct. This duct is a major lymph channel which passes cephalad on the left of the bodies of the thoracic vertebrae to enter the left side of the neck, where it drains into the left internal jugular vein at its confluence with the left subclavian vein. Lymph from the head and right arm drains via a separate lymphatic trunk, the right lymphatic duct, into the right internal jugular vein. Lymph nodes develop as condensations along the course of these lymphatic highways.
Lymphatics accompany veins everywhere in the body except in the cortical bony skeleton and central nervous system, although the brain and retina possess analogous systems (cerebrospinal fluid and aqueous humour, respectively). The lymphatic system comprises lymphatic channels, lymphoid organs (lymph nodes, spleen, Peyer’s patches, thymus, tonsils) and circulating elements (lymphocytes and other mononuclear immune cells).
Microanatomy and physiology
Lymphatics originate within the interstitial space either from specialised endothelialised capillaries (initial lymphatics) or from nonendothelialised precapillary channels such as in the liver (spaces of Disse). Initial lymphatics capillaries are unlike arteriovenous capillaries in that they:
• are blind-ended;
• are much larger (50 micron);
• allow the entry of molecules up to 1000 kDa in size because the basement membrane is fenestrated, tenuous or even absent and the endothelium itself possesses intra and intercellular pores.
• The abluminal surface of the endothelium is intimately related to the interstitial matrix through anchoring collagen and elastic filaments. In the resting state initial lymphatic capillaries are collapsed. When interstitial fluid volume and pressure increase, the space expands and the lymphatic capillaries and their pores are held open by these filaments to facilitate increased lymphatic drainage.
Lymphatic capillaries drain into terminal (collecting) lymphatics which possess bicuspid valves and endothelial cells rich in the contractile protein actin. Larger collecting lymphatics are innervated and surrounded by smooth muscle. Valves partition the lymphatic into segments termed lymphangions which are believed to contract sequentially in order to propel lymph into the lymph trunks. The area of skin drained by a single terminal lymphatic is termed an areola. Although there is some overlap between adjacent areolata, there are lymphatic watersheds and there is limited capacity for bypass flow when a main collecting duct or lymph trunk is blocked.
Terminal lymphatics lead to lymph trunks which have a structure that is similar to veins: a single layer of endothelial cells, lying on a basement membrane overlying a media comprised of smooth muscle cells that are innervated with sympathetic, parasympathetic and sensory nerve endings. About 10 per cent of lymph arising from a limb is transported in deep lymphatic ducts that accompany the main neurovascular bundles. The majority of lymph, however, is conducted, in epifascial lymph ducts, against venous flow from the core of the limb to the surface. Superficial ducts form lymph bundles of various sizes which ate located within strips of adipose tissue and tend to follow the course of the major superficial veins.
The distribution of fluid and protein between the vascular and interstitial spaces depends on the balance of hydrostatic and oncotic pressures between the two compartments (Starling’s forces), together with the relative impermeability of the blood capillary membrane to molecules over 70 kDa. In health there is net capillary filtration into the interstitial space of 2—4 litres per 24 hours which is removed by the lymphatic system. Disease processes which disturb Starling’s forces lead primarily to oedema that is low in protein, whereas diseases which primarily impair lymphatic drainage lead to high-protein oedema (lymphoedema).
Transport of particles
Particles enter the initial lymphatics through interendothelial openings and vesicular transport through intraendothelial pores. In contradistinction to arteriovenous capillaries, the larger the particles the greater the lymphatic uptake. Large particles are actively phagocytosed by macrophages and transported through the lymphatic system intracellularly.
Mechanisms of lymph transport
Whereas resting pressures in the interstitial fluid compartments of the skin and subcutaneous tissues are negative (—2 to —6 mmH2O) pressures within lymphatics are positive, indicating that lymph flows against a small pressure gradient. It is believed that prograde lymphatic flow depends on two mechanisms:
• transient increases in interstitial pressure secondary to muscular contraction and external compression;
• the generation of alternating suction and propulsive forces through the sequential contraction and relaxation of lymphangions separated by valves that prevent retrograde flow.
Lymphangions respond to increased lymph flow in much the same way as the heart responds to increased venous return, in that they increase their contractility and stroke volume. Contractility is also enhanced by noradrenaline, serotonin, certain prostaglandins and thromboxanes, and endothelin-1. Pressures of up to 30—50 mmHg have been recorded in normal lymph trunks and up to 200 mmHg in severe lymphoedema. Lymphatics modulate their own contractility through the production of nitric oxide. Contractility appears to be inhibited by haemoglobin, haem-containing proteins and oxygen-derived free radicals.
Transport in the thoracic and right lymph ducts is also dependent on the changes in intrathoracic pressure that occur with respiration, as well as changes in central venous pressures through the cardiac cycle. Cardiac and respiratory disease may, therefore, have an adverse effect on lymphatic function.
Lymphovenous communications were first observed on lymphangiography and were thought to act as safety valves that would allow decompression of a hypertensive lymphatic system. While lymphscintigraphy may reveal lymphovenous communications in normal limbs, they have been reported to be absent in some cases of lymphoedema, for example post-mastectomy. The pathophysiological importance of this observation remains uncertain.
In summary, in the normal limb, lymph flow is largely due to intrinsic lymphatic contractility, although exercise, limb movement and external compression do increase lymphatic return. However, in lymphoedema, where the lymphatics are constantly distended with lymph, these forces assume a much more important functional role and this explains the success of physical therapy.