What causes anasarca?

Causes of Anasarca

Primary Pathophysiologic Mechanisms

Anasarca results from severe fluid accumulation in the interstitial space, most commonly caused by cardiac, renal, or hepatic failure through mechanisms involving either increased intravascular hydrostatic pressure, decreased plasma oncotic pressure, or both. 1

The three major organ system failures account for the vast majority of anasarca cases, though the clinical presentation requires careful assessment to distinguish between elevated filling pressures versus extravascular volume shifts from low plasma oncotic pressure or high vascular permeability. 1

Cardiac Etiologies

• Acute and chronic heart failure represents a leading cause through sodium and water retention resulting from reduced cardiac output and neurohormonal activation of the renin-angiotensin-aldosterone system. 1

• The fluid retention reflects congestion from elevated filling pressures, though peripheral edema may not always correlate with intravascular volume status. 1

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

• Elevated jugular venous pressure improves the specificity of edema as a sign of cardiac congestion rather than other causes of fluid shifts. 1

• Natriuretic peptides are secreted in response to volume and pressure overload, helping distinguish cardiac from non-cardiac causes. 1

Renal Etiologies

Nephrotic Syndrome

• Nephrotic syndrome is characterized by severe proteinuria, hypoalbuminemia, and anasarca, representing the predominant clinical manifestation of renal amyloidosis. 1

• Approximately 70% of patients with AL amyloidosis develop renal involvement presenting with nephrotic syndrome, significant proteinuria, and anasarca. 1

• Bronchiectasis-associated systemic amyloidosis can cause profound proteinuria (up to 82.9 g/day documented) with advanced renal disease and anasarca. 2

Glomerulonephritis and Vasculitis

• Systemic vasculitides including granulomatosis with polyangiitis (GPA) cause renal involvement through pauci-immune necrotizing crescentic glomerulonephritis, a hallmark manifestation with ANCA-mediated glomerulonephritis and necrotizing vasculitis of renal vessels. 1, 3

• PR3-ANCA is present in 80-90% of GPA cases and is highly specific for this diagnosis. 3, 4

• Eosinophilic granulomatosis with polyangiitis can also cause renal involvement leading to anasarca. 1

• TAFRO syndrome (thrombocytopenia, anasarca, fever, reticulin fibrosis, organomegaly) can present with acute kidney injury initially showing minor proteinuria, followed by nephrotic syndrome with membranoproliferative glomerulonephritis-like glomerulopathy. 5, 6

General Renal Failure

• Renal failure from any cause can lead to anasarca through impaired sodium and water excretion, particularly when combined with hypoalbuminemia. 1

Hepatic Etiologies

• Liver cirrhosis produces anasarca through multiple mechanisms including decreased albumin synthesis, portal hypertension, and secondary hyperaldosteronism. 1

• Chronic liver disease with acute-on-chronic renal failure, circulatory failure, and sepsis can result in severe anasarca requiring massive fluid removal (up to 71 liters documented via continuous hemofiltration). 7

• Pre-existing edema of hepatic origin should be distinguished from cardiac-related fluid overload when assessing patients. 1

Vascular and Venous Disorders

• Superior or inferior vena cava obstruction can cause regional anasarca in the distribution of the affected venous system. 1

• Chronic venous insufficiency produces localized lower extremity edema that must be distinguished from systemic causes of anasarca. 1

Postoperative Anasarca

• Postoperative anasarca occurs in approximately 30% of patients following major abdominal surgery, with pedal edema as an early sign progressing to generalized edema and potential multiple organ dysfunction. 8

• Risk factors include: higher NRS 2002 score, low albumin levels, age >60 years, and raised leukocyte counts. 8

• Postoperative anasarca is a significant predictor of poor prognosis with higher Clavien-Dindo complication grades. 8

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

• Pre-existing edema from non-cardiac causes (hepatic, renal, venous) should be documented to avoid misattributing chronic edema to acute cardiac decompensation. 1

• In GPA, nasal biopsies often lack sufficient specific features to confirm diagnosis, requiring biopsies from other involved organs. 9

• Without treatment, GPA has a mean survival of only 5 months, making urgent recognition critical when vasculitis is suspected. 3, 4

• Tissue edema itself plays a pathophysiological role in the downward spiral of hepato-renal and cardio-renal dysfunction, and very large volumes of tissue fluid can be safely removed with continuous renal replacement therapy to permit recovery of organ function. 7