What are the causes of anasarca?

Causes of Anasarca

Anasarca is most commonly caused by conditions that lead to severe hypoalbuminemia, heart failure, renal disease, or systemic vasculitis, with the underlying pathophysiology involving fluid redistribution or retention that overwhelms the body's compensatory mechanisms.

Definition and Pathophysiology

Anasarca refers to severe, generalized edema characterized by massive subcutaneous fluid accumulation throughout the body. Unlike localized edema, anasarca involves extensive swelling affecting the entire body, including the face, trunk, extremities, and can be accompanied by fluid accumulation in body cavities (pleural effusions, ascites).

Major Causes of Anasarca

1. Cardiovascular Causes

• Severe heart failure: Reduced cardiac output leads to activation of the renin-angiotensin-aldosterone system, causing sodium and water retention 1
• High-output heart failure: Conditions like beriberi heart disease (thiamine deficiency) can cause anasarca through increased cardiac output and peripheral vasodilation 2
• Constrictive pericarditis: Restricts cardiac filling and raises venous pressure

2. Renal Causes

• Nephrotic syndrome: Characterized by massive proteinuria (>3.5g/day), hypoalbuminemia, and edema
• Acute or chronic kidney failure: Impaired sodium and water excretion 1
• Glomerulonephritis: Particularly forms with significant protein loss 1
• Diabetic nephropathy: Can cause severe proteinuria leading to hypoalbuminemia and anasarca 2

3. Hepatic Causes

• Liver cirrhosis: Decreased albumin synthesis and portal hypertension 1
• Chronic liver disease: Impaired protein synthesis leading to hypoalbuminemia 3
• Budd-Chiari syndrome: Hepatic venous outflow obstruction

4. Nutritional and Metabolic Causes

• Severe protein malnutrition: Kwashiorkor, severe malnutrition after divorce or other life events 2
• Protein-losing enteropathy: GI loss of protein leading to hypoalbuminemia
• Severe iron deficiency anemia: Particularly in infants with excessive cow's milk intake 4
• Beriberi: Thiamine deficiency leading to high-output heart failure 2

5. Inflammatory and Autoimmune Causes

• Systemic vasculitis:
  • Granulomatosis with polyangiitis (GPA): ANCA-associated vasculitis 1
  • Eosinophilic granulomatosis with polyangiitis (EGPA): Can cause anasarca through cardiac involvement 1
• Systemic lupus erythematosus: With lupus nephritis causing nephrotic syndrome 1
• Sarcoidosis: Can affect kidneys leading to proteinuria and edema 1

6. Iatrogenic Causes

• Excessive fluid administration: Particularly in critically ill patients 3
• Medication side effects: Certain medications like calcium channel blockers, NSAIDs, thiazolidinediones
• Inappropriate hormone replacement: In adrenal insufficiency 5
• Post-surgical anasarca: Following major abdominal surgeries, associated with poor nutritional status 6

7. Other Causes

• Severe hypoalbuminemia from any cause (serum albumin <2.0 g/dL)
• Capillary leak syndrome: Increased vascular permeability
• Lymphatic obstruction: Severe lymphedema
• Venous insufficiency: When severe and bilateral

Risk Factors for Developing Anasarca

• Age >60 years: Higher risk for post-surgical anasarca 6
• Poor nutritional status: Low albumin levels, high NRS 2002 score 6
• Leukocytosis: Marker of inflammation associated with anasarca 6
• Multiple comorbidities: Higher Charlson Comorbidity Index 6
• Prolonged immobility: Contributing to fluid redistribution

Clinical Assessment

When evaluating a patient with anasarca, key clinical findings to assess include:

• Presence of jugular venous distention (suggests cardiac etiology)
• Hepatomegaly or other signs of liver disease
• Proteinuria (suggests renal etiology)
• Blood urea nitrogen (BUN) levels (may reflect congestion and fluid retention) 1
• Serum albumin levels (hypoalbuminemia <2.5 g/dL strongly associated with anasarca)
• Cardiac function assessment (echocardiography)
• ANCA testing if vasculitis is suspected 1

Diagnostic Approach

The diagnostic approach should focus on identifying the underlying cause:

1. Laboratory evaluation:

   • Complete blood count (anemia, leukocytosis)
   • Comprehensive metabolic panel (liver and kidney function)
   • Serum albumin and total protein
   • Urinalysis (proteinuria)
   • BNP/NT-proBNP (for heart failure) 1
   • ANCA testing if vasculitis suspected 1

2. Imaging:

   • Chest X-ray (cardiomegaly, pleural effusions)
   • Echocardiography (cardiac function)
   • Abdominal ultrasound (liver disease, ascites)
   • CT scan if indicated for specific conditions

3. Tissue sampling:

   • Kidney biopsy if glomerular disease suspected
   • Liver biopsy if liver disease etiology unclear

Treatment Considerations

Treatment must address the underlying cause while managing the fluid overload:

• Diuretic therapy: Often high-dose loop diuretics
• Ultrafiltration/hemofiltration: For severe cases unresponsive to diuretics 3, 2
• Albumin infusion: In cases of severe hypoalbuminemia
• Sodium restriction: To reduce fluid retention
• Specific therapy for the underlying condition (immunosuppression for vasculitis, thiamine for beriberi, etc.)

Conclusion

Anasarca represents the end result of severe fluid imbalance from various pathological processes. Identifying and treating the underlying cause is essential for effective management and preventing recurrence.