Hyponatremia in cirrhosis: Pathogenesis, clinical significance, and management

Abstract

Hyponatremia is a frequent complication of advanced cirrhosis related to an impairment in the renal capacity to eliminate solute-free water that causes a retention of water that is disproportionate to the retention of sodium, thus causing a reduction in serum sodium concentration and hypo-osmolality. The main pathogenic factor responsible for hyponatremia is a nonosmotic hypersecretion of arginine vasopressin (or antidiuretic hormone) from the neurohypophysis related to circulatory dysfunction. Hyponatremia in cirrhosis is associated with increased morbidity and mortality. There is evidence suggesting that hyponatremia may affect brain function and predispose to hepatic encephalopathy. Hyponatremia also represents a risk factor for liver transplantation as it is associated with increased frequency of complications and impaired short-term survival after transplantation. The current standard of care based on fluid restriction is unsatisfactory. Currently, a new family of drugs, known as vaptans, which act by antagonizing specifically the effects of arginine vasopressin on the V2 receptors located in the kidney tubules, is being evaluated for their role in the management of hyponatremia. The short-term treatment with vaptans is associated with a marked increase in renal solute-free water excretion and improvement of hyponatremia. Long-term administration of vaptans seems to be effective in maintaining the improvement of serum sodium concentration, but the available information is still limited. Treatment with vaptans represents a novel approach to improving serum sodium concentration in cirrhosis.

Influence of Serum Sodium on MELD-Based Survival Prediction in Alcoholic Hepatitis

“…Hypersecretion of vasopressin in turn is thought to occur because of circulatory dysfunction that is common in patients with cirrhosis, a concept commonly referred to as the underfilling hypothesis. 22 This excessive volume overload in the absence of increased uptake of Na causes a hypo-osmolar state and is reflected as hyponatremia. Because the degree of hyponatremia reflects the degree of circulatory dysfunction, hyponatremia predicts survival in patients with cirrhosis.…”

Model for end-stage liver disease-Na score or Maddrey discrimination function index, which score is best?

“…Low sodium levels are related to the impairment of renal solute-free water excretion most likely due to an increased vasopressin secretion, which results in increased sodium retention and reduced renal free water clearance, which predispose to life threatening conditions in the cirrhotic such as HRS and refractory ascites [36] . Also, hyponatremia represents an independent risk factor for brain edema, a fatal complication of acute liver failure [37,38] .…”

Management of cirrhotic ascites in children. Review and recommendations. Part 2: Electrolyte disturbances, nonelectrolyte disturbances, therapeutic options

“…64,65 In general, it is accompanied with an increase of intravascular volume. 8,66 Although it has been described a s h y p e r v o l e m i c o r d i l u t i o n a l hyponatremia (HH) in the literature regarding the adult population, 6,10,12,13,67 the first term is preferred in pediatrics because excess water relative to sodium also occurs in euvolemic or hypovolemic hyponatremia. 16 As cirrhosis progresses, circulatory dysfunction induces non-osmotic ADH secretion with greater water retention relative to sodium and HH develops.…”

“…A minority of patients have hypovolemic hyponatremia, 5,8,66,67 in general, secondary to diuretic use and/or losses from vomiting or diarrhea, with no clinical signs of ascites or edema. Treatment consists of sodium and water replacement and diuretic discontinuation until intravascular volumen is restored.…”