What causes ascites in cirrhosis?

Pathophysiology of Ascites in Cirrhosis

Ascites in cirrhosis is primarily caused by portal hypertension combined with splanchnic arterial vasodilation, leading to decreased effective arterial blood volume and activation of sodium-retaining systems, resulting in renal sodium retention and fluid accumulation in the peritoneal cavity. 1

Primary Pathophysiological Mechanisms

• Portal hypertension is a prerequisite for ascites development in cirrhosis and occurs due to structural changes in liver architecture from progressive collagen deposition and nodule formation 1

• Increased resistance to portal flow occurs from:

  • Architectural distortion of the liver vasculature in cirrhosis 1
  • Activated hepatic stellate cells dynamically regulating sinusoidal tone 1
  • Reduced nitric oxide production/bioavailability in the cirrhotic liver (accounting for approximately 25% of increased resistance) 1

• Splanchnic arterial vasodilation is triggered by:

  • Elevated portal pressure sensed by intestinal microvasculature 1
  • Production of vasodilators including nitric oxide, prostacyclin and endocannabinoids 1
  • This vasodilation leads to "effective hypovolemia" despite total body fluid overload 1

Sodium and Water Retention Cascade

• Decreased effective arterial blood volume activates compensatory mechanisms: 1

  • Sympathetic nervous system activation (promoting sodium reabsorption in proximal, distal tubules, loop of Henle and collecting duct) 1
  • Renin-angiotensin-aldosterone system activation (promoting sodium absorption from distal tubule and collecting duct) 1, 2
  • Non-osmotic release of arginine vasopressin (promoting water retention) 1

• The resulting positive sodium balance leads to: 1

  • Expansion of extracellular fluid volume 1
  • Accumulation of fluid in the peritoneal cavity 1
  • Portal hypertension acting as a compartmentalizing factor for the expanded fluid volume 1

Role of Inflammation and Bacterial Translocation

• Recent evidence suggests bacterial translocation associated with portal hypertension contributes to: 1
  • Systemic inflammation via pathogen-associated molecular pattern activation 1
  • Release of proinflammatory cytokines 1
  • Production of reactive oxygen and nitrogen species 1
  • Further worsening of vasodilation and organ dysfunction 1

Clinical Implications

• Ascites is the most common complication of cirrhosis, developing in 5-10% of compensated cirrhotic patients annually 1, 3
• Development of ascites marks significant disease progression, reducing 5-year survival from 80% in compensated cirrhosis to approximately 30% 1, 4
• Ascites predisposes to additional complications including spontaneous bacterial peritonitis, restrictive ventilatory dysfunction, and abdominal hernias 1, 4

Diagnostic Considerations

• Diagnostic paracentesis is essential for all patients with new-onset grade 2-3 ascites 1
• Serum-ascites albumin gradient (SAAG) ≥1.1 g/dL confirms portal hypertension as the cause with 97% accuracy 1, 4
• Neutrophil count, culture, and total protein concentration should be assessed to evaluate for spontaneous bacterial peritonitis and infection risk 1

Important Caveats

• Portal hypertension alone is insufficient to cause ascites - patients with presinusoidal portal hypertension without cirrhosis rarely develop ascites unless there is an additional insult to liver function 1
• The development of ascites should prompt consideration for liver transplantation evaluation, as it offers the most definitive treatment 1, 4
• While sodium restriction and diuretics are first-line therapy, approximately 10% of patients develop refractory ascites requiring more advanced interventions 5