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11.1.1 Introduction

The lymphatic system is a significant pathway for the drainage of fluid, large protein molecules and white blood cells from the interstitial spaces within capillary beds. Lymphatic capillaries lie in the dermis and subcutaneous fat, in the fascial planes between muscles and in perivascular tissues. Lymphatic vessels transport lymph from these areas through regional lymph nodes towards the thoracic duct. Lymph returns to the venous circulation via the termination of the thoracic duct at the left internal jugular vein close to its junction with the left subclavian vein. The system plays a major immunologi-cal role, with the regional lymph nodes processing antigens presented to them by white blood cells from the peripheries. Antigen-specific lymphocytes proliferate in the lymph nodes and are then released into the circulation via the main lymph ducts and also through small lym-phovenous connections within the lymph nodes themselves. Impaired drainage of lymph from a limb, usually due to obstruction of the system, leads to the accumulation of fluid and protein in the subcutaneous tissues with eventual irreversible fibrosis and swelling, known as lymphoedema [8]. Capillary Microcirculation

Fluid and protein fluxes in the capillary bed follow both hydrostatic and colloid osmotic pressure gradients. Since hydrostatic pressure outside the capillary is negligible, hydrostatic pressures tend to force fluid out of the capillary lumen into the tissues, whereas colloid osmotic pressures generated by intravascular proteins tend to draw fluid back into the vessel lumen. White cells pass through gaps in the capillary endothelium by an active process of diapedesis, drawn towards sites of inflammation by che-moattractant molecules. Fluid, proteins and white blood cells are delivered to the tissues at the arterial end of the capillary bed, where the hydrostatic pressure at around 32 mmHg exceeds the colloid osmotic pressure. Fluid and proteins, particularly albumin, globulin and fibrinogen, pass through the capillary wall along the hydrostatic pressure gradient. The majority of the fluid returns to the capillary lumen at the venous end, where the intralumi-nal hydrostatic pressure has fallen to around 15 mmHg and is now overcome by the colloid osmotic pressure. The latter increases as fluid leaves the capillary at the arterial end, increasing the concentration of colloids within the vessel lumen and drawing fluid back into the capillary. Very little protein returns via the capillary, with up to 95% of it entering the lymphatics along with some fluid. The lymphatic endothelium is poorly organized with gaps between the cells and little basement membrane, so fluid and proteins enter via a combination of passive and active transport. Overall around 20 l of fluid and up to 200 g of protein pass through the capillary bed every day, with 2-4 l of fluid and the majority of the protein returning to the circulation via lymphatic pathways [3].

Once within the lymphatic vessels, there is very little leakage of fluid and protein back out. Lymph vessels contain both valves in the lumen and smooth muscle cells in their walls. Intrinsic contraction of the vessel walls pushes lymph proximally through the valves. Skeletal muscle contraction increases the extrinsic pressure on the lymph and also drives it through the valves, and negative pressure within the thorax encourages proximal flow. As lymph flow is relatively sluggish, it can be impeded by the effects of gravity and by any increase in central venous pressure which limits egress of lymph from the thoracic duct. The lymph nodes also act as filters of the lymph, increasing resistance to flow along the drainage pathway.

An understanding of the capillary microcirculation is important when considering the differential diagnosis of lymphoedema, as limb swelling can result when any component of the system malfunctions or becomes diseased. Capillary Circulation and Limb Oedema

Conditions which affect the hydrostatic or colloid osmotic pressure gradients in the capillary beds may lead to accumulation of fluid (Table 11.1.1).

Venous Hypertension

• Venous hypertension, whether superficial or deep, will increase the intraluminal hydrostatic pressure at the venous end of the capillary so that it resists the colloid osmotic pressure and reduces the force drawing fluid from the tissues into the capillaries.

• Fluid then accumulates within the tissues causing oedema.

Table 11.1.1 Causes of limb oedema


Superficial venous incompetence Deep vein insufficiency Deep vein thrombosis Deep vein occlusion Extrinsic venous compression


Excess intravenous fluid Heart failure Caval obstruction Aortocaval fistula


Malnutrition Renal failure Liver failure

Capillary damage

Anaphylaxis Septicaemia


Paralysis Orthopnoea Ischaemic rest pain Air travel


Primary lymphoedema Secondary lymphoedema

• malignant infiltration

• radiotherapy

• block dissection


Dependency Constricting band


• As protein clearance by the lymphatics is not affected, the fluid is low in protein and fibrotic changes are slow to develop, so the oedema remains pitting and can be reversed by increasing the tissue's hydrostatic pressure with externally applied compression gradients using graduated compression stockings.

• Likewise the intraluminal hydrostatic pressure can be reduced by elevating an affected limb and reversing gravitational pressures, thus encouraging fluid to follow colloid osmotic pressure back into the capillary at the venous end.

• Other causes of high venous pressure, such as extrinsic compression of iliac veins by a pelvic mass, deep venous thrombosis or heart failure, will have the same effect on the capillary circulation and lead to tissue oedema.

Low Intravascular Colloid Osmotic Pressure

• Intravascular colloid osmotic pressure at the venous end of the capillary bed may fall in patients with low levels of plasma proteins due to malnutrition, liver failure or renal failure.

• In such patients, although hydrostatic forces remain low, they become sufficient to impede the deficient colloid osmotic pressure and leave fluid within the tissues.

• The capillary walls may become leaky through damage from anaphylactic reactions or septicaemia.

• Dependency of a limb, particularly when it is immobile, impairs the mechanisms of venous and lymphatic drainage by increasing gravitational pressures and impairing extrinsic muscle pump activity, causing an increased intraluminal hydrostatic pressure and impairing fluid movement back into both capillaries and lymphatics.

• Such patients may be wheelchair bound after a stroke or an amputation, they may be paraplegic or they may sit and sleep with their legs dependent because of or-thopnoea or ischaemic rest pain.


• Obstruction to the lymphatic system will impair fluid drainage from a limb in a mechanical way, as a result of either poor lymphatic development or damage to the lymphatic channels by infection, malignancy surgery or radiotherapy.

• Some patients with hysteria may hold their limb in a dependent position with resistance to any movement or may apply constricting bands around a limb, causing either increased gravitational pressure or venous and lymphatic obstruction.

Idiopathic Oedema

• There is also a group of patients who develop idiopath-ic oedema for whom no cause is found, although the swelling in such patients is usually mild.

11.1.2 Definition of Lymphoedema

• Lymphoedema is an abnormal accumulation of protein rich fluid in the tissues.

• The proteins raise the colloid osmotic pressure within the tissues and so more fluid is attracted.

• Fibroblast proliferation occurs, causing the subcutaneous tissues to thicken and the oedema becomes nonpitting as a result.

11.1.3 Aetiology/Epidemiology

• Lymphoedema may be either primary [10], due to intrinsic abnormalities of the lymph vessels, or secondary [2].

• Secondary lymphoedema is commoner and arises from pathological or iatrogenic damage to lymph nodes. Primary Lymphoedema

• Primary lymphoedema was initially classified as congenital when present at birth, praecox when it started in early life and tarda when the onset was after the age of 35 years.

• Current definitions focus more on whether the lymphoedema arises from either obliteration or hyperplasia of the lymphatics.

• Over 90% of patients have the obliterative version and of these a small number are born with developmental aplasia of lymphatics (Milroy disease, Fig. 11.1.1).

• The genetic basis of congenital forms of primary lymphoedema is currently the subject of active re-

Fig. 11.1.1 A child with bilateral congenital lymphoedema (Milroy disease)

search [6]. The most common type of primary, familial lymphoedema is that first described by Meige (isolated pubertal-onset lymphoedema), but to date no locus has been reported. The gene for Milroy disease (congenital familial lymphoedema) has recently been mapped to chromosome 5q35.3 and probable causative mutations have been found in the VEGFR3 gene.

• Lymphoedema-distichiasis syndrome is a rare, primary lymphoedema of pubertal onset, associated with distichiasis. Distichiasis is a congenital anomaly in which accessory eyelashes occur along the posterior border of the lid margins. Lymphoedema-distichiasis has been mapped to chromosome 16q24 with a high incidence of mutations in the FOXC2 gene [1,5].

• Aside from these rare forms of congenital lymphoedema, obliterative lymphoedema maybe broken down into three clinical sub-groups.

• The first of these, distal obliteration, occurs when thelymphatic vesselsofthe thighare hypoplastic, being narrow and reduced in number (Fig. 11.1.2a,b). The lymphoedema is often bilateral, below the knee and mild, occurs mainly in women with an onset in their teenage years and is not usually progressive provided the pelvic lymphatics are normal.

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