Causes of Hyponatremia
Hyponatremia is primarily caused by three major mechanisms: hypovolemic, euvolemic, and hypervolemic states, each with distinct underlying etiologies that affect sodium and water balance. 1
Classification by Volume Status
Hypovolemic Hyponatremia
- Excessive diuretic use - particularly thiazide diuretics 2, 3
- Gastrointestinal losses (vomiting, diarrhea)
- Third-space fluid sequestration (burns, pancreatitis)
- Renal sodium losses (salt-wasting nephropathy, adrenal insufficiency)
- Excessive sweating without adequate electrolyte replacement
Euvolemic Hyponatremia
- Syndrome of Inappropriate Antidiuretic Hormone (SIADH) 1, 4
- Malignancies (lung cancer, brain tumors)
- CNS disorders (stroke, hemorrhage, trauma, infection)
- Pulmonary diseases (pneumonia, tuberculosis, COPD)
- Post-operative state
- Medications (antipsychotics, antidepressants, carbamazepine, oxcarbazepine)
- Hypothyroidism
- Adrenal insufficiency (glucocorticoid deficiency)
- Reset osmostat syndrome
- Primary polydipsia (excessive water intake)
Hypervolemic Hyponatremia
- Liver cirrhosis - due to portal hypertension, systemic vasodilation, and decreased effective plasma volume 2
- Congestive heart failure
- Nephrotic syndrome
- Advanced kidney disease
- Severe protein malnutrition
Pathophysiological Mechanisms
Cirrhosis-Related Hyponatremia
In cirrhosis, hyponatremia develops through specific mechanisms 2:
- Systemic vasodilation from portal hypertension
- Decreased effective plasma volume
- Reduced systemic vascular resistance
- Hyperdynamic circulation
- Excessive activation of renin-angiotensin-aldosterone system
- Inappropriate antidiuretic hormone regulation
- Increased arterial natriuretic peptide
- Decreased prostaglandin E2
- Decreased degradation of antidiuretic hormone
Medication-Induced Hyponatremia
- Diuretics - especially thiazides which impair urinary dilution 3
- Antidepressants (SSRIs, TCAs)
- Antipsychotics
- Anticonvulsants (carbamazepine, oxcarbazepine)
- NSAIDs
- ACE inhibitors
- Chemotherapeutic agents
Pseudohyponatremia
- Hyperlipidemia
- Hyperproteinemia
- Hyperglycemia (translocational hyponatremia)
Clinical Pearls and Pitfalls
- Severity classification: Mild (130-134 mmol/L), moderate (125-129 mmol/L), and severe (<125 mmol/L) 1
- Hyponatremia in cirrhosis significantly increases risk of complications including spontaneous bacterial peritonitis (OR 3.40), hepatorenal syndrome (OR 3.45), and hepatic encephalopathy (OR 2.36) 2
- Even modest hyponatremia (131-135 mmol/L) may increase risk of serious complications 2
- Rapid correction of chronic hyponatremia can lead to osmotic demyelination syndrome 1, 4
- Thiazide diuretics are more commonly associated with severe hyponatremia than loop diuretics 3
- In cirrhotic patients, hyponatremia is often dilutional and associated with increased mortality while awaiting liver transplantation 5
Diagnostic Approach
- Determine volume status (hypovolemic, euvolemic, hypervolemic)
- Measure plasma osmolality
- High osmolality: Consider hyperglycemia
- Normal osmolality: Consider pseudohyponatremia
- Low osmolality: True hyponatremia
- Measure urinary sodium concentration
- High urinary sodium with hypovolemia: Consider renal sodium wasting
- Low urinary sodium with hypovolemia: Consider extrarenal losses
- High urinary sodium with euvolemia: Consider SIADH or endocrine disorders
- Low urinary sodium with hypervolemia: Consider heart failure, cirrhosis
Remember that identifying the underlying cause is essential for appropriate management and prevention of recurrence.