Causes of Hyponatremia
Hyponatremia is caused by multiple conditions that can be categorized based on volume status as hypovolemic, euvolemic, or hypervolemic, with the most common causes being medications, syndrome of inappropriate antidiuretic hormone (SIADH), and advanced liver disease. 1
Classification by Volume Status
Hypovolemic Hyponatremia
- Excessive diuretic use, particularly in patients with liver cirrhosis 2
- Gastrointestinal losses (vomiting, diarrhea) 3
- Severe burns leading to fluid losses 1
- Dehydration from various causes 1
- Third-space fluid sequestration 3
Euvolemic Hyponatremia
- Syndrome of Inappropriate Antidiuretic Hormone (SIADH) secretion 1
- Medications (antidepressants, antipsychotics, anticonvulsants) 3
- Endocrine deficiencies (hypothyroidism, adrenal insufficiency) 1
- Reset osmostat syndrome 1
- Post-operative state, particularly after transsphenoidal surgery 1
Hypervolemic Hyponatremia
- Advanced liver cirrhosis with portal hypertension 2
- Congestive heart failure 1, 3
- Nephrotic syndrome and renal disease 3
- Severe malnutrition 1
Pathophysiological Mechanisms
Liver Cirrhosis-Related Hyponatremia
- Systemic vasodilation due to portal hypertension 2
- Decreased effective plasma volume leading to decreased systemic vascular resistance 2
- Hyperdynamic circulation with increased cardiac output 2
- Accumulation of vasodilatory substances (nitric oxide, glucagon, vasoactive intestinal peptide) 2
- Activation of renin-angiotensin-aldosterone system causing excessive sodium and water reabsorption 2
- Inadequate regulation of antidiuretic hormone (ADH) 2
- Increased arterial natriuretic peptide and decreased prostaglandin E2 2
- Decreased degradation of antidiuretic hormone 2
Other Important Mechanisms
- Primary vasopressin excess (SIADH) 4
- Secondary vasopressin stimulation via baroreceptor mechanisms (cirrhosis, heart failure) 4
- Defective water excretion due to elevated vasopressin levels 5
- Excessive fluid intake overwhelming excretory capacity 5
Laboratory Findings to Identify Causes
- Low plasma osmolality with high urinary sodium: renal disorders, endocrine deficiencies, SIADH, medications 1
- Low plasma osmolality with low urinary sodium: gastrointestinal losses, burns, acute water overload 1
- High plasma osmolality: hyperglycemia (pseudohyponatremia) 3
- Normal plasma osmolality: pseudohyponatremia or post-transurethral prostatic resection syndrome 3
- In SIADH: low plasma concentrations of urate, creatinine, and urea 6
- In cirrhosis/heart failure: slightly elevated plasma urate, creatinine, and urea 6
Clinical Significance and Complications
- Increased risk of complications in cirrhotic patients with sodium <130 mmol/L 2
- Significantly higher risk of spontaneous bacterial peritonitis (OR 3.40) 2
- Increased risk of hepatorenal syndrome (OR 3.45) 2
- Higher incidence of hepatic encephalopathy (OR 2.36) 2
- Neurological symptoms including confusion, seizures, and coma in severe cases 1
- Risk of cerebral edema and hyponatremic encephalopathy in acute severe hyponatremia 3
- Risk of osmotic demyelination syndrome with rapid correction 1
Special Considerations
- Diuretic-induced sodium depletion is the most frequent cause of hyponatremia in cirrhotic patients 7
- Distinguishing between euvolemia and hypovolemia can be clinically challenging 3
- Measurement of plasma osmolality is a useful investigative tool 3
- Urinary sodium concentration helps in diagnosing patients with low plasma osmolality 3
- Hyponatremia in cirrhosis is mostly dilutional and defined at serum sodium <130 mmol/L 2
Understanding the cause of hyponatremia is crucial for appropriate management, as treatment approaches differ significantly based on the underlying etiology and volume status of the patient 1, 3.