Anatomy
and physiology of the lymphatic system
Functions
2. Permits the circulation of
lymphocytes and other immune cells.
3. 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.
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,
Microanatomy
and physiology
Lymphatic
capillaries
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.
Terminal
lymphatics
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:
• 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
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.