About Hyponatremia
Pathophysiology of
Euvolemic Hyponatremia
Pathophysiology of
Hypervolemic Hyponatremia

Pathophysiology of Euvolemic Hyponatremia

Patients with euvolemic hyponatremia have essentially normal extracellular volume with no signs of pitting edema or ascites. The most common cause of euvolemic hyponatremia is the syndrome of inappropriate antidiuretic hormone secretion (SIADH).1

SIADH is the result of elevated levels of the neurohormone arginine vasopressin (AVP), which plays a critical role in regulating the body's water-sodium balance. AVP binds to V2 receptors in the collecting ducts of the kidneys, causing free water to be reabsorbed into the body rather than being excreted in the urine. Normally, AVP functions to maintain homeostasis; however, in SIADH, inappropriate AVP secretion results in water retention that has a dilutional effect on sodium concentration in the plasma, resulting in hyponatremia.1

As reported in the Hyponatremia Guidelines 2007: Expert Panel Recommendations, examples of euvolemic hyponatremic conditions associated with SIADH may include:

Tumors – Tumors have been found to be ectopic sources of AVP, particularly small-cell pulmonary tumors and head and neck tumors.2 Many of these tumors synthesize and secrete AVP independent of the body's osmotic regulation system.2

Central nervous system (CNS) disorders – Many CNS disorders disrupt signaling pathways between the brain and the hypothalamus, preventing inhibition of AVP even though the patient is hypo-osmolalic.2 Some CNS disorders associated with SIADH include head trauma, subarachnoid hemorrhage, tumors, infections, encephalitis, Guillain-Barré syndrome, and acute psychosis.1,2

Induced by drugs – Certain drugs either stimulate AVP release or potentiate its effect.1 Some of the drugs associated with SIADH include certain antipsychotic agents, antidepressants, anticonvulsants, angiotensin-converting enzyme (ACE) inhibitors, 3,4-Methylenedioxymethamphetamine (MDMA or "ecstasy"), and oxytocin.1,2

Pulmonary diseases – Several pulmonary disorders inappropriately stimulate AVP production, leading to SIADH, including hypoxemia, hypercapnia, and pulmonary infections such as tuberculosis and pneumonia.2 SIADH also occurs in patients on mechanical ventilation and in patients with chronic obstructive pulmonary disease (COPD), due to reduced pulmonary blood volume that activates baroreceptors and stimulates AVP secretion.2

Read a case study of a patient with hyponatremia associated with liver cancer.

Read a case study of a patient with hyponatremia associated with lung cancer.

REFERENCES: 1. Verbalis JG, Goldsmith SR, Greenberg A, Schrier RW, Sterns RH. Hyponatremia treatment guidelines 2007: expert panel recommendations. Am J Med. 2007;120:S1-S21. 2. Siragy H. Hyponatremia, fluid-electrolyte disorders, and the syndrome of inappropriate antidiuretic hormone secretion: diagnosis and treatment options. Endocr Pract. 2006;12:446-457.