What is the pathophysiology of ascites (accumulation of fluid in the peritoneal cavity)?

From the Guidelines

Ascites formation is primarily driven by portal hypertension and sodium retention, with the pathophysiology involving a complex interplay of increased resistance to blood flow, splanchnic vasodilation, and activation of the renin-angiotensin-aldosterone system, as described in the 2021 guidelines on the management of ascites in cirrhosis 1. The development of ascites is a multifactorial process, with key factors including:

• Portal hypertension, which is essential for the development of ascites, as fluid accumulation does not develop at portal pressure gradient below 8 mm Hg 1
• Retention of sodium and water, which is driven by the activation of the renin-angiotensin-aldosterone system and antidiuretic hormone, leading to sodium and water retention 1
• Increased lymph production from the liver surface, which exceeds the lymphatic drainage capacity, further contributing to fluid accumulation 1
• Local inflammation and increased vascular permeability, particularly in cases with spontaneous bacterial peritonitis, which exacerbate fluid leakage 1 These mechanisms create a vicious cycle where worsening portal hypertension and sodium retention progressively increase ascites formation, making it a common and challenging complication of advanced liver disease. The diagnosis and management of ascites involve a range of strategies, including:
• Grading the amount of fluid accumulated in the abdominal cavity and classifying the response to treatment 1
• Using dietary sodium restriction and diuretic therapy to manage ascites, with the goal of achieving a weight loss of 0.5 kg per day in patients without peripheral edema, and up to 1 kg per day in those with edema 1
• Monitoring laboratory parameters, such as serum electrolyte concentrations, and assessing 24-hour urinary sodium excretion to guide therapy 1 Overall, the management of ascites requires a comprehensive approach that takes into account the underlying pathophysiology and the individual patient's needs and circumstances.

From the FDA Drug Label

1. 2 Pharmacodynamics Aldosterone antagonist activity: Increased levels of the mineralocorticoid, aldosterone, are present in primary and secondary hyperaldosteronism. Edematous states in which secondary aldosteronism is usually involved include congestive heart failure, hepatic cirrhosis, and nephrotic syndrome By competing with aldosterone for receptor sites, Spironolactone provides effective therapy for the edema and ascites in those conditions.

The pathophysiology of ascites involves edematous states and secondary aldosteronism, which can be caused by conditions such as congestive heart failure, hepatic cirrhosis, and nephrotic syndrome.

• Aldosterone plays a key role in the development of ascites by promoting sodium and water retention.
• Spironolactone works by competing with aldosterone for receptor sites, providing effective therapy for edema and ascites in these conditions 2. The exact mechanism of ascites development is complex and involves multiple factors, but aldosterone antagonism is a key aspect of its treatment 2.

From the Research

Pathophysiology of Ascites

The pathophysiology of ascites is complex and involves multiple factors, including:

• Portal hypertension, which is the primary driver of ascites formation 3, 4, 5
• Splanchnic vasodilatation, which leads to arterial vascular underfilling and compensatory activation of the renin-angiotensin-aldosterone system (RAAS), sympathetic nervous system (SNS), and arginine vasopressin (AVP) 4, 5
• Liver insufficiency and cardiovascular dysfunction, which contribute to the development of ascites 3
• Sodium retention, which occurs due to the activation of antinatriuretic factors and the increased activity of the RAAS and SNS 4

Mechanisms of Ascites Formation

The mechanisms of ascites formation involve:

• Severe sinusoidal portal hypertension, which causes marked splanchnic arterial vasodilation and a forward increase in the splanchnic production of lymph 5
• Splanchnic arterial vasodilation, which produces arterial vascular underfilling, arterial hypotension, and compensatory activation of the RAAS, SNS, and AVP 5
• Continuous sodium and water retention, leading to ascites formation 5

Clinical Practice Guidelines

Clinical practice guidelines for the diagnosis and management of portal hypertension and ascites have been issued by several international and national societies, including the Italian Association for the Study of the Liver (AISF) 6

• These guidelines aim to provide updated guidance on the clinical management of portal hypertension and ascites, taking into account national regulations and resources, local circumstances and settings, infrastructure, and cost/benefit strategies 6
• The guidelines are based on a systematic review of the literature and are developed using the PICO format (Population, Intervention, Comparison, Outcomes) 6