What is the cause of hyponatremia (low sodium levels) in liver cirrhosis?

From the Guidelines

Hyponatremia in liver cirrhosis is primarily caused by dilutional hyponatremia, where excess water retention dilutes serum sodium levels, as stated in the 2021 practice guidance by the American Association for the Study of Liver Diseases 1. The primary cause of hyponatremia in liver cirrhosis is dilutional hyponatremia, which occurs due to excess water retention diluting serum sodium levels. This happens because cirrhosis leads to portal hypertension, triggering splanchnic vasodilation and reduced effective arterial blood volume. The body perceives this as volume depletion, activating compensatory mechanisms including increased antidiuretic hormone (ADH) secretion, which promotes water retention in the kidneys. Additionally, the renin-angiotensin-aldosterone system becomes activated, further contributing to sodium and water retention. Some key points to consider in the management of hyponatremia in liver cirrhosis include:

• Fluid restriction to 1,000 mL/day and cessation of diuretics is recommended in the management of moderate hyponatremia (120-125 mEq/L) 1
• The use of vasopressin receptor antagonists can raise serum sodium during treatment, but should be used with caution only for a short term (≤30 days) 1
• The goal rate of increase of serum sodium is 4-6 mEq/L per 24-hour period, not to exceed 8 mEq/L per 24-hour period to ameliorate the risk of osmotic demyelination syndrome (ODS) 1 Impaired free water clearance by the kidneys exacerbates the problem, as damaged liver function reduces metabolism of ADH. Ascites formation and the use of diuretics (especially thiazides) in cirrhosis management can worsen hyponatremia. Many cirrhotic patients also have decreased dietary sodium intake due to prescribed salt restrictions, while continuing to consume free water. The severity of hyponatremia typically correlates with the progression of liver disease and is associated with worse outcomes in cirrhotic patients, as noted in the 2018 clinical practice guidelines for liver cirrhosis 1.

From the Research

Causes of Hyponatremia in Liver Cirrhosis

• Hyponatremia in liver cirrhosis is mostly dilutional hyponatremia, defined as a serum sodium concentration below 130 meq/L 2
• The primary cause of hyponatremia in cirrhosis is increased release of arginine vasopressin, leading to excessive renal retention of water relative to sodium due to reduced solute-free water clearance 3
• Portal hypertension, diuretics, large volume paracentesis without albumin, infection, and multiple medications are also connected with the development or worsening of hyponatremia 4
• Impaired renal sodium handling due to renal hypoperfusion and increased arginine-vasopressin secretion secondary to reduced effective volemia due to peripheral arterial vasodilation represent the main mechanisms leading to dilutional hyponatremia in this setting 5

Associated Factors

• Hyponatremia is associated with increased mortality in cirrhotic patients, those with end-stage liver disease (ESLD) on transplant waiting lists, and, in some studies, posttransplantation patients 3
• Hyponatremia is also associated with numerous complications in liver disease patients, including severe ascites, hepatic encephalopathy, infectious complications, renal impairment, increased severity of liver disease in cirrhosis, and increased hospital stay and neurologic/infectious complications posttransplant 3
• The presence of hyponatremia frequently complicates the management of the cirrhotic patient 4
• Hyponatremia is common in cirrhosis, particularly advanced cirrhosis, and is associated with complications and increased mortality 2, 6, 5