3rd April 2024

Peripheral Oedema

Peripheral Oedema

Introduction

Expansion of fluid volume within the interstitial space leads to detectable swelling known as peripheral oedema. This is a common finding in routine medical practice, occurring in both outpatient and inpatient scenarios. Oedema can present in various forms including unilateral, bilateral, localised or generalised oedema. It is associated with older age, female sex, low socioeconomic status, obesity, diabetes, and mobility limitations. The most common cause in those > 50 years of age is venous insufficiency. It is vital to assess the mechanism of oedema formation to understand how it relates to disease pathophysiology, clinical presentation, and treatment.

Pathophysiology

Total body water can be divided into two general categories namely intracellular fluid and extracellular fluid. Of these categories, the extracellular fluid is further divided into interstitial and intravascular fluid. This fluid is maintained in appropriate concentrations in the various compartments of the body through a variety of regulatory mechanisms and forces. Peripheral oedema occurs when these regulatory mechanisms and forces are disrupted.

Factors that control the directional flow of fluid between compartments include hydrostatic pressure, oncotic pressure, endothelial integrity and the lymphatic systems.  Hydrostatic pressure is defined as the pressure of any fluid enclosed in a space. It is primarily generated by the heart as it pumps blood through the circulatory system. It is also influenced by factors such as blood volume, viscosity and peripheral resistance. Osmotic pressure, on the other hand, is determined by solute concentration gradients, that is, the difference in the solute to water concentrations in the blood and tissue fluid. An area with greater solute concentration attracts water through a semipermeable membrane from an area with higher water concentration.

Under normal circumstances, a balance exists between the hydrostatic pressure in the capillaries and the oncotic pressure, resulting in a constant vascular volume with allowance of a small percentage of fluid being filtered into the interstitium. This filtration exceeds reabsorption by roughly 10%, with the excess non-reabsorbed filtrate being returned to the vascular system via lymphatics. Factors that raise hydrostatic pressures, reduce oncotic pressure, increase endothelial permeability or impair lymphatic drainage will result in oedema.

Major causes of oedema by primary mechanism 

The major causes of the development of oedema are divided into four categories based on the underlying mechanism as shown below:

Table 1 outlines the main categories of developing oedema with the mechanism and causes

Unilateral and localised oedema is often secondary to DVT or infection like cellulitis, while more generalised or bilateral oedema is likely a result of one of the systemic conditions listed above. In heart failure, left sided heart failure results in fluid accumulation in lungs leading to pulmonary oedema while right sided heart failure causes raised JVP, hepatomegaly, peripheral oedema and ascites. In acute heart failure, there is a decrease in cardiac output resulting in pulmonary oedema but peripheral oedema is not seen as capillary hydrostatic pressure is low peripherally at that point and it takes time for compensatory mechanisms like sodium retention to cause peripheral oedema.

Investigations

To determine the cause of peripheral oedema, essential investigations include renal, liver, and thyroid function tests, brain natriuretic peptide (BNP) evaluation, echocardiogram and urinalysis. 

Pro BNP has become an important diagnostic tool to identify patients with heart failure. It is a hormone released by the heart when there is heightened wall stretching, neurohormonal activation, and hypoxia.  BNP then causes fluid and sodium loss in the urine and has a mild vasodilator effect. If BNP is normal it rules out heart failure (high negative predictive value). However, it is important to remember that conditions like PE, sepsis, COPD, diabetes, liver cirrhosis, age >70 and eGFR <60 ml/min can all increase BNP levels. 

Cardiac magnetic resonance imaging (CMR) is a reliable and reproducible investigation to assess the structure and function of the heart. It is costly and would rarely be considered first line.

Management

Chronic oedema can cause pain, heaviness, weakness, discomfort, negative body image and limitations in mobility. Therefore, attention to treatment is necessary for improvement in quality of life. Management of oedema consists of reversal of the underlying disorder (if possible), dietary modifications, physical measures and diuretic therapy. 

Dietary modification advice is given to consider decreasing dietary sodium intake to 2 g/dL and increasing protein intake to 1g/kg/dL if hypoalbuminemia exists. Fluid restriction is also advised in patients with heart failure, renal failure and liver failure. Compression stockings are known to be effective in reducing peripheral oedema by increasing tissue pressure and venous blood flow. It is usually indicated in treating patients with Lymphoedema and varicose veins. Elevating the legs above heart level for 30 minutes three or four times a day can help alleviate leg, ankle, and foot oedema. While this approach may suffice for individuals with mild venous disease, those with more severe cases may need additional interventions to reduce oedema.

Diuretics specifically loop diuretics, such as furosemide, bumetanide, and torsemide can reduce oedema by promoting diuresis. The choice of diuretics will depend on the underlying cause, for example, loop diuretics are preferred in renal failure while spironolactone is favoured in liver disease. Furosemide is the most commonly used loop diuretic, whereas bumetanide is a more potent option in patients who are unresponsive to furosemide. Furosemide at a dosage of 40mg is roughly equal to bumetanide at 1mg. However, as the dosage of bumetanide increases, this equivalence ratio diminishes. Bumetanide potency is lower in terms of urinary potassium excretion. Caution needs to be taken when using diuretics as they can cause electrolyte imbalances, including hypokalaemia, hypomagnesemia, hypocalcaemia, hyponatraemia and hyperuricaemia. Adverse effects of spironolactone include hyperkalaemia, renal injury and gynaecomastia.

Pulmonary oedema is the only form of oedema that is life-threatening and requires immediate therapy with intravenous diuretics. In most other oedematous states, removal of the excess fluid can proceed more gently since it usually is of no immediate danger to the patient.

References

• Smith, C. (2023) Clinical manifestations and evaluation of edema in adults, UpToDate. Edited by M.D. Aronson, M. Emmett, and K. Law. 
• Rosenthal, L. and Cumbler, E. (2022). Assessment of peripheral oedema. [online] BMJ Best Practice.
• Goyal A, Cusick AS, Bhutta BS. Peripheral Edema. [Updated 2023 Aug 17]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan
• Darwish A, Lui F. Physiology, Colloid Osmotic Pressure. [Updated 2023 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan.