From the Guidelines
Refractory ascites in cirrhosis is primarily caused by portal hypertension, sodium and water retention, and systemic inflammation.
Causes of Refractory Ascites
- Portal hypertension: increased sinusoidal pressure and resistance to portal flow, leading to fluid accumulation in the peritoneal cavity 1
- Sodium and water retention: renal sodium retention due to activation of sodium-retaining systems, such as the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system, resulting in a positive fluid balance and extracellular fluid volume expansion 1
- Systemic inflammation: bacterial translocation and activation of innate immune responses, contributing to vasodilatation and release of proinflammatory cytokines, reactive oxygen and nitrogen species, leading to organ dysfunction 1
Pathogenesis
The development of refractory ascites is associated with a complex interplay of factors, including:
- Arterial splanchnic vasodilation: decreased effective arterial blood volume, activation of vasoconstrictor and sodium-retaining systems, and renal sodium retention 1
- Hepatorenal syndrome (HRS): a frequent and grave complication of refractory ascites, characterized by rapid decline in renal function and poor prognosis 1
- Cirrhosis progression: decompensation of liver disease, leading to increased risk of complications, such as dilutional hyponatremia, refractory ascites, HRS, and spontaneous bacterial peritonitis 1
From the Research
Causes of Refractory Ascites in Cirrhosis
The causes of refractory ascites in cirrhosis are multifactorial and involve significant volume and hormonal dysregulation in the setting of portal hypertension 2. The key factors contributing to refractory ascites include:
- Severe sinusoidal portal hypertension and hepatic insufficiency, leading to circulatory dysfunction characterized by arterial vasodilation, arterial hypotension, high cardiac output, and hypervolemia 3
- Splanchnic arterial vasodilation, which impairs systemic hemodynamics and renal function, and alters hemodynamics in the splanchnic microcirculation 3
- Increased synthesis of local vasodilators in the splanchnic circulation, leading to arterial vasodilation 3
- Renal sodium and water retention, which perpetuates ascites formation 3
- Progressive liver disease, leading to loss of compensatory cardiac output and further splanchnic vasodilation, resulting in compromised kidney function and severe sodium retention 4
Pathophysiology of Refractory Ascites
The pathophysiology of refractory ascites involves the development of ascites as a result of portal hypertension, leading to water-sodium retention and renal failure 5. The mechanisms underlying refractory ascites include:
- Increased hydrostatic pressure in the splanchnic capillaries, leading to an excessive production of splanchnic lymph over lymphatic return 3
- Lymph leakage from the liver and other splanchnic organs, resulting in fluid accumulation in the abdominal cavity 3
- Continuous renal sodium and water retention, which perpetuates ascites formation 3
Clinical Implications
Refractory ascites is a serious complication of cirrhosis, associated with a poor quality of life and high mortality rate 5. The development of refractory ascites is a sign of advanced liver disease, and its management is crucial to improve patient outcomes. The choice of treatment modality for refractory ascites depends on various factors, including the condition of the patient 5.