Why are albumin levels decreased in patients with cirrhosis?

Why Albumin is Decreased in Cirrhosis

Albumin levels are decreased in cirrhosis primarily due to reduced hepatic synthesis, increased catabolism, and dilutional effects from fluid retention, leading to both quantitative and qualitative albumin deficiency.

Pathophysiological Mechanisms of Hypoalbuminemia in Cirrhosis

1. Reduced Hepatic Synthesis

• Cirrhosis causes progressive loss of functional hepatocyte mass, directly reducing the liver's capacity to synthesize albumin 1
• Albumin is synthesized exclusively by the liver, making cirrhosis patients particularly vulnerable to hypoalbuminemia 2
• The severity of hypoalbuminemia typically correlates with the degree of hepatic dysfunction and disease progression

2. Increased Albumin Catabolism

• Cirrhosis leads to increased albumin degradation, with studies showing that up to 58% of infused albumin is rapidly degraded in cirrhotic patients 3
• Increased inflammatory state in cirrhosis accelerates albumin breakdown
• A 15% increase in serum albumin can lead to a disproportionate 39% increase in degradation, demonstrating the body's tendency to break down excess albumin in cirrhosis 3

3. Dilutional Effects

• Portal hypertension in cirrhosis leads to profound hemodynamic derangements and splanchnic vasodilation 3
• This results in decreased effective circulating blood volume despite increased total body fluid
• Fluid retention and third-spacing (particularly ascites) dilute plasma proteins including albumin

4. Qualitative Albumin Deficiency

• In advanced cirrhosis, albumin undergoes post-transcriptional modifications that impair its functional properties 1
• The relative abundance of native, intact albumin (effective albumin) is significantly reduced as disease severity increases 1
• Oxidative damage creates dysfunctional albumin isoforms such as human nonmercaptalbumin and nitrosoalbumin 4

Clinical Implications of Hypoalbuminemia in Cirrhosis

Consequences of Low Albumin

• Reduced oncotic pressure leading to ascites and edema
• Impaired binding and transport of drugs, toxins, and endogenous substances
• Compromised antioxidant and scavenging activities 1
• Increased risk of complications including hepatorenal syndrome and spontaneous bacterial peritonitis 3

Therapeutic Considerations

• Albumin infusion is indicated for specific complications:
  • Large-volume paracentesis (>5L) at 6-8g per liter of fluid removed 5
  • Spontaneous bacterial peritonitis management 3
  • Hepatorenal syndrome treatment (in combination with vasoconstrictors) 3
• Long-term albumin administration may modify disease course in decompensated cirrhosis by reducing new complications 4

Monitoring and Management

• Serum albumin levels should be regularly monitored in cirrhosis patients
• The concept of "effective albumin concentration" (native intact albumin) is more relevant than total serum albumin concentration 1
• Albumin infusion should target specific indications rather than being used as a "one size fits all" approach 2
• Potential adverse effects of albumin therapy include volume overload, pulmonary edema, and coagulation derangements 4

Understanding the complex mechanisms behind hypoalbuminemia in cirrhosis is essential for appropriate management of these patients and for targeting albumin therapy to those most likely to benefit.