What causes anasarca?

What Causes Anasarca?

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

Cardiac Causes

• 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 1, 2
• Infective endocarditis may precipitate acute heart failure with subsequent anasarca development 1

Renal Causes

• Nephrotic syndrome is characterized by severe proteinuria, 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 cause renal involvement through pauci-immune necrotizing crescentic glomerulonephritis, with ANCA-mediated glomerulonephritis and necrotizing vasculitis of renal vessels 2, 3
• PR3-ANCA is present in 80-90% of granulomatosis with polyangiitis cases and is highly specific for this diagnosis 2, 3

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

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

Less Common Causes

• Severe iron deficiency anemia with hypoalbuminemia from excessive cow's milk intake can cause anasarca, particularly in infants 4
• TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis, organomegaly) can present with acute kidney injury and subsequent nephrotic syndrome 5
• Drug-induced anasarca can occur with calcium channel blockers like amlodipine, though this is rare 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 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
• Without treatment, granulomatosis with polyangiitis has a mean survival of only 5 months, making urgent recognition critical when vasculitis is suspected as the underlying cause 2, 3