Why does cirrhosis cause hyponatremia?

Pathophysiology of Hyponatremia in Cirrhosis

Cirrhosis causes hyponatremia primarily through dilutional mechanisms driven by portal hypertension, systemic vasodilation, and impaired free water excretion due to non-osmotic release of antidiuretic hormone (ADH/vasopressin). 1, 2

Primary Mechanism: Portal Hypertension and Systemic Vasodilation

Portal hypertension in advanced cirrhosis triggers a cascade of hemodynamic changes that ultimately lead to hyponatremia 1:

• Splanchnic vasodilation occurs due to portal hypertension, causing marked arterial vasodilation in the splanchnic circulation 1, 3
• This vasodilation leads to decreased effective circulatory volume despite increased total plasma volume, creating a state of relative hypovolemia 1, 3
• The body perceives this as true volume depletion, triggering compensatory mechanisms 1

Activation of Sodium and Water-Retaining Systems

The perceived volume depletion activates multiple neurohumoral systems 1, 2:

• Renin-angiotensin-aldosterone system (RAAS) activation causes excessive sodium and water reabsorption in the kidneys 1, 2
• Sympathetic nervous system activation further promotes sodium retention 1
• Non-osmotic ADH (arginine vasopressin) secretion occurs despite low serum osmolality, which is the key mechanism for hyponatremia 1, 2, 4

Impaired Free Water Excretion

The critical pathophysiologic defect in cirrhotic hyponatremia is the kidney's inability to excrete solute-free water 1, 2:

• ADH acts on V2 receptors in the kidney collecting tubules, increasing solute-free water retention 2, 4
• This leads to disproportionate water retention relative to sodium retention, resulting in dilutional hyponatremia 1, 3
• The result is hypervolemic hyponatremia: low serum sodium, increased total body water, ascites and edema, but decreased effective plasma volume 3

Clinical Characteristics of Cirrhotic Hyponatremia

Hyponatremia in cirrhosis is defined as serum sodium <130 mmol/L and is mostly dilutional in nature 2, 5:

• Occurs in approximately 49.4% of cirrhotic patients (sodium <135 mEq/L) and 21.6% have sodium ≤130 mEq/L 5
• Represents hypervolemic hyponatremia in 90% of cases, with hypotonic/hypovolemic hyponatremia accounting for only 10% 3
• Associated with advanced cirrhosis and portal hypertension 1, 2

Contributing Factors

Several factors can worsen hyponatremia in cirrhotic patients 5:

• Diuretic therapy (particularly loop diuretics and thiazides) 5
• Large volume paracentesis without albumin replacement 5
• Infections (particularly spontaneous bacterial peritonitis) 5
• Multiple medications that can impair water excretion 5

Clinical Significance and Complications

Hyponatremia in cirrhosis is associated with significantly increased morbidity and mortality 1, 2, 4:

• Increased risk of spontaneous bacterial peritonitis (OR 3.40) 6
• Increased risk of hepatorenal syndrome (OR 3.45) 6
• Increased risk of hepatic encephalopathy (OR 2.36) 6
• Poor prognostic marker both before and after liver transplantation 1, 4
• Associated with increased hospital stay and neurologic/infectious complications post-transplant 4