What causes anasarca?

Causes of Anasarca

Anasarca results from severe generalized fluid accumulation in the interstitial space, most commonly caused by cardiac failure, renal failure (particularly nephrotic syndrome), or hepatic cirrhosis through mechanisms involving increased intravascular hydrostatic pressure, decreased plasma oncotic pressure, or both. 1, 2

Cardiac Causes

• Acute and chronic heart failure is a leading cause of anasarca, resulting from sodium and water retention due to reduced cardiac output and neurohormonal activation of the renin-angiotensin-aldosterone system. 1, 2
• The fluid retention reflects congestion from elevated filling pressures, though peripheral edema may not always correlate with intravascular volume status. 1
• Elevated jugular venous pressure improves the specificity of edema as a sign of cardiac congestion rather than other causes of fluid shifts. 1, 2
• Natriuretic peptides are secreted in response to volume and pressure overload, helping distinguish cardiac from non-cardiac causes of anasarca. 1, 2
• Infective endocarditis may precipitate acute heart failure with subsequent anasarca development. 1

Renal Causes

• Nephrotic syndrome is characterized by severe proteinuria (>3.5 g/day), hypoalbuminemia, and anasarca, representing the predominant clinical manifestation of renal amyloidosis. 1, 2
• Approximately 70% of patients with AL amyloidosis develop renal involvement presenting with nephrotic syndrome, significant proteinuria, and anasarca. 1, 2
• Renal failure from any cause can lead to anasarca through impaired sodium and water excretion, particularly when combined with hypoalbuminemia. 1
• Systemic vasculitides including granulomatosis with polyangiitis (GPA) cause renal involvement through pauci-immune necrotizing crescentic glomerulonephritis with ANCA-mediated glomerulonephritis and necrotizing vasculitis of renal vessels. 2
• PR3-ANCA is present in 80-90% of GPA cases and is highly specific for this diagnosis; without treatment, GPA has a mean survival of only 5 months. 2, 3
• Eosinophilic granulomatosis with polyangiitis (EGPA) can also cause renal involvement leading to anasarca, with ANCA positivity detectable in 30-40% of patients. 4, 1

Hepatic Causes

• Liver cirrhosis produces anasarca through multiple mechanisms including decreased albumin synthesis, portal hypertension, and secondary hyperaldosteronism. 1, 2
• Pre-existing edema of hepatic origin should be distinguished from cardiac-related fluid overload when assessing patients. 1, 2
• Chronic liver disease combined with acute-on-chronic renal failure, circulatory failure, and sepsis can result in severe anasarca requiring aggressive fluid removal. 5

Vascular and Venous Disorders

• Superior or inferior vena cava obstruction can cause regional anasarca in the distribution of the affected venous system. 1, 2
• Chronic venous insufficiency produces localized lower extremity edema that must be distinguished from systemic causes of anasarca. 1, 2

Perioperative and Critical Illness

• Postoperative anasarca occurs in approximately 30% of patients following major abdominal surgery, with risk factors including age >60 years, high NRS 2002 score, low albumin levels, and raised leukocyte counts. 6
• Severe anasarca complicates the course of acute respiratory distress syndrome (ARDS) secondary to sepsis or systemic inflammatory response syndrome, particularly in children. 7
• Postoperative anasarca is a significant predictor of poor prognosis with higher Clavien-Dindo complication grades. 6

Critical Diagnostic Pitfalls

• Anasarca may reflect extravascular volume shifts from low plasma oncotic pressure or high vascular permeability rather than elevated filling pressures, requiring assessment of multiple parameters including jugular venous pressure to distinguish cardiac from non-cardiac causes. 1, 2
• Pre-existing edema from non-cardiac causes (hepatic, renal, venous) should be documented to avoid misattributing chronic edema to acute cardiac decompensation. 1, 2
• In patients with unexplained anasarca and bilateral pleural effusions, consider lymphatic disorders when cardiac, renal, and liver workup is unremarkable. 8
• When vasculitis is suspected as the cause of anasarca, urgent recognition is critical as untreated GPA has a median survival of only 5 months. 2, 3