Edema, commonly referred to as swelling, is a widespread finding with multiple potential etiologies. Weight gain generally occurs prior to edema formation as the body’s total water stores increase. In most cases, edema first occurs symmetrically in the lower extremities. This is due to gravity’s role in increasing the hydrostatic (fluid) pressure in the lower extremity veins and is referred to as dependent edema. However, edema can be generalized (referred to as anasarca), asymmetric, or it can be localized to the lungs (pulmonary edema), peritoneal cavity (ascites), or pleural cavity (hydrothorax).
The regulation of the body’s water stores is complex. One third of the total body water is extracellular, of which three quarters is extravascular. This relationship is governed by a complex interaction of fluid pressure, proteins, and vessel wall permeability referred to as the Starling forces. The hydrostatic (fluid) pressure in the vasculature and the colloid oncotic (protein) pressure in the interstitium promote efflux of fluid from the vascular to the extravascular space. The hydrostatic interstitial pressure and the intravascular colloid oncotic pressure sustain intravascular volume. Intact lymphatic drainage and capillary endothelial integrity are essential for maintaining fluid homeostasis. Any changes in this delicate balance favoring increased extravascular fluid accumulation lead to the formation of edema.
Congestive heart failure is a common cause of edema. The weakened heart results in an increase in hydrostatic pressure in the lungs and venous vasculature in left and right heart failure, respectively. Additionally, as blood flow to the kidneys is reduced, neurohormonal changes take place that lead to fluid and sodium retention increasing the body’s total water stores. The combination of increased venous capillary pressure and increased total body water leads to an egress of fluid to the extravascular space. Edema develops as interstial fluid accumulation outpaces the lymphatic system’s ability to drain. Additionally, patients with constrictive pericarditis or restrictive cardiomyopathy may develop peripheral edema via similar mechanisms. In these conditions, the heart’s ability to relax and fill during diastole is impaired. This leads to systemic venous hypertension (i.e., increased hydrostatic pressure).
Chronic venous insufficiency is another frequent cause of edema. This occurs as a result of venous valvular incompetence. It is most often secondary to the sequelae of deep venous thromboses (blood clots). Lower extremity edema develops, usually asymmetrically, then varicosities, induration, pigment changes, and fibrosis. In severe cases, venous stasis ulcers can develop around the medial malleoli (ankle).
Hypoproteinemia, low blood protein, leads to edema because the decreased intravascular protein concentration shifts the Starling forces in favor of interstitial fluid accumulation. Hypoproteinemia can occur through a variety of mechanisms. These include severe nutritional deficiency, severe liver disease with decreased protein synthesis, protein-losing gastrointestinal diseases, and nephrotic syndrome.
Cirrhosis, end-stage liver disease, results in edema by many mechanisms. Portal hypertension increases venous hydrostatic pressure and decreases the “effective” circulating volume thereby leading to decreased kidney perfusion. This stimulates neurohormonal changes that result in increased renal sodium and water retention. Additionally, protein synthesis is often impaired and decreases plasma oncotic pressure.
Initially, fluid accumulation in cirrhosis develops in the peritoneal cavity with ascites.
Lymphedema results from impaired lymphatic drainage. Secondary lymphedema is usually caused by lymph node surgery, radiation, or cancerous invasion. Primary lymphedema is most commonly lymphedema praecox (10: 1 female-to-male ratio). It is usually limited to the foot and calf and it occurs in young women often at the time of menarche or first pregnancy.
Pregnancy is a unique situation. Edema is the norm occurring in approximately 80% of all pregnancies. Most weight gain occurs after 20 weeks with approximately 70% due to water. Total body water increases from 7 L to 9 L. This occurs secondary to neurohormonal changes associated with pregnancy. Postpartum the fluid is quickly eliminated once the neurohormonal milieu returns to the prepregnancy state.
Edema in menstruating females in the absence of cardiac, hepatic, or renal disease is referred to as idiopathic edema. Initially, it occurs premenstrually, but often becomes persistent. The exact etiology of this phenomenon is uncertain, but it is felt to be caused by exaggerated volume depletion with standing secondary to venous pooling. This increases hydrostatic pressure and promotes extracellular fluid accumulation. The neurohormonal milieu then shifts to favor sodium retention further promoting edema. Additional potential etiologies for idiopathic edema include refeeding and diuretic-induced edema. In refeeding edema, weightconscious individuals drastically reduce caloric intake for a period of time. At the end of the diet, increased caloric intake increases insulin release promoting sodium retention. In diuretic-induced edema, minor ankle edema leads to initiation of a diuretic. This activates neurohormonal changes favoring edema formation. Once diuretics are withdrawn, edema develops secondary to these neurohormal changes, which take some time to resolve. The mistaken assumption is then made that long-term diuretic therapy is necessary.
Many medications are well known to cause edema. Common culprits include calcium channel blockers, minoxidil, diazoxide, thiazolidinediones, estrogens/ progesterones (including oral contraceptives), corticosteroids, and nonsteroidal anti-inflammatory agents. Cessation of the offending agent results in resolution of the edema. Other etiologies of edema include allergic reactions, angioedema, severe burns, and idiopathic edema where edema formation is secondary to altered capillary endothelial permeability. Myxedema occurs most commonly in hypothyroidism and its genesis is not fully understood, but altered capillary endothelial permeability is known to play a role.
The treatment of edema depends upon the etiology. The mainstays of therapy generally include sodium restriction and diuretic therapy. Support hose is an important and often overlooked tool to aid in the management of lower extremity edema particularly in patients with venous insufficiency. Edema in pregnancy is treated primarily with sodium restriction and support hose. In myxedema, correction of the underlying endocrine abnormality is necessary to eliminate edema.
SEE ALSO: Cardiovascular disease, Chest pain, Chronic obstructive pulmonary disease, Congestive heart failure, Hepatitis, Pregnancy, Thyroid diseases, Weight control
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- Chou, S., & Atwood, J. E. (2002). Peripheral edema. American Journal of Medicine, 113, 580—586.
- Davidson, J. M. (1997). Edema in pregnancy. Kidney International, 51(S59), S90-S96.
- Rose, B. D. (1999, October 18). Idiopathic edema. Up To Date. Version 11.1.
- refeeding edema
- What Causes Interstitial Edema
- Starling Forces and Edema
- Lower Extremity Edema in Pregnancy
- asymmetric edema
- proteins role in edema
- pathophysiology of edema formation in pregnant women
- lower limb edema hydrostatic pressure
- lower extremity swelling pregnancy