Causes of Hyponatremia
Hyponatremia is primarily caused by impaired water excretion or excessive water intake, with specific etiologies classified by volume status as hypovolemic, euvolemic, or hypervolemic. 1, 2
Classification by Volume Status
1. Hypovolemic Hyponatremia
- Gastrointestinal losses: Vomiting, diarrhea, severe burns 2, 3
- Renal losses: Diuretic therapy (especially thiazides), salt-wasting nephropathies 4
- Third-space losses: Burns, pancreatitis, trauma 3
2. Euvolemic Hyponatremia
- Syndrome of Inappropriate Antidiuretic Hormone (SIADH): Most common cause in hospitalized patients 3, 5
- Medications: Antiepileptics (carbamazepine), antidepressants, antipsychotics, chemotherapeutic agents (cyclophosphamide, vincristine) 6, 2
- Endocrine disorders: Adrenal insufficiency, hypothyroidism 1
- Reset osmostat syndrome: Chronic malnutrition, pregnancy 1, 3
- Excessive water intake: Exercise-associated hyponatremia, psychogenic polydipsia 2, 7
3. Hypervolemic Hyponatremia
- Heart failure: Activation of neurohormonal mechanisms including norepinephrine and angiotensin II 6
- Liver cirrhosis: Decreased effective arterial blood volume 1, 3
- Renal failure: Impaired free water excretion 2, 3
Pathophysiological Mechanisms
Impaired Water Excretion
- Neurohormonal activation: In heart failure, norepinephrine and angiotensin II activation decrease sodium delivery to the distal tubule, while arginine vasopressin increases water absorption 6
- Non-osmotic vasopressin release: Major mechanism in most cases of hyponatremia 7
- Renal concentrating defects: Patients with significant renal concentrating defects (e.g., nephrogenic diabetes insipidus) may develop hyponatremia 6
Excessive Water Intake
- Iatrogenic: Inappropriate IV fluid administration, particularly hypotonic fluids 6
- Behavioral: Excessive free water consumption during exercise or psychogenic polydipsia 2, 5
Special Considerations
Medication-Induced Hyponatremia
- Diuretics: Thiazide diuretics are more commonly associated with hyponatremia than loop diuretics 4
- High-risk medications: Desmopressin, carbamazepine, cyclophosphamide, vincristine 6
High-Risk Populations
- Women: More sensitive to hyponatremic injury 7
- Elderly: More susceptible due to age-related changes in water regulation 3
- Postoperative patients: Particularly after transsphenoidal surgery for pituitary macroadenoma 1
- Patients with comorbidities: Heart disease, liver disease, renal dysfunction, adrenal insufficiency 6, 1
Clinical Pearls and Pitfalls
- Hyponatremia can develop rapidly in susceptible patients, especially with thiazide diuretics 4
- Even patients receiving isotonic maintenance IV fluids can develop hyponatremia if they receive IV medications containing free water or consume additional free water enterally 6
- Determining the patient's volume status is crucial for appropriate diagnosis and management 1, 2
- Rapid correction of chronic hyponatremia can lead to osmotic demyelination syndrome, a potentially devastating neurological complication 5
Remember that hyponatremia severity is classified as mild (130-135 mEq/L), moderate (125-129 mEq/L), or severe (<125 mEq/L), with symptoms ranging from mild (nausea, headache) to severe (seizures, altered consciousness) 1, 2.