What are the causes of hyponatremia?

Causes of Hyponatremia

Hyponatremia (serum sodium <135 mEq/L) is primarily caused by disorders of water homeostasis that lead to water retention or sodium loss, with the most common causes being hypovolemic, euvolemic, and hypervolemic states, each with distinct underlying etiologies. 1

Classification by Volume Status

1. Hypovolemic Hyponatremia

Caused by sodium and fluid loss with relatively greater sodium than water loss:

• Gastrointestinal losses:

  • Vomiting
  • Diarrhea
  • Gastrointestinal drainage 2

• Renal losses:

  • Diuretic therapy (especially thiazides)
  • Salt-losing nephropathies
  • Adrenal insufficiency
  • Cerebral salt wasting 3

• Skin losses:

  • Burns
  • Excessive sweating 4

• Third-space losses:

  • Pancreatitis
  • Bowel obstruction
  • Rhabdomyolysis 5

2. Euvolemic Hyponatremia

Caused by water retention with normal total body sodium:

• Syndrome of Inappropriate ADH Secretion (SIADH):

  • Malignancies (especially small cell lung cancer)
  • CNS disorders (stroke, hemorrhage, trauma, infection)
  • Pulmonary disorders (pneumonia, tuberculosis, asthma)
  • Pain, nausea, stress 1

• Medications:

  • Antidepressants (SSRIs, TCAs)
  • Antipsychotics
  • Anticonvulsants (carbamazepine)
  • Antineoplastic agents
  • Opioids 3

• Endocrine disorders:

  • Hypothyroidism
  • Glucocorticoid deficiency 2

• Reset osmostat syndrome 4

• Primary polydipsia (excessive water intake) 1

3. Hypervolemic Hyponatremia

Caused by water retention exceeding sodium retention:

• Heart failure 1
• Liver cirrhosis 4
• Nephrotic syndrome 6
• Renal failure (acute or chronic) 6
• Pregnancy 5

Pseudohyponatremia and Other Special Cases

• Pseudohyponatremia:

  • Hyperlipidemia
  • Hyperproteinemia 3

• Translocational hyponatremia:

  • Hyperglycemia (for every 100 mg/dL increase in glucose above normal, serum sodium decreases by approximately 1.6-2.4 mEq/L) 4

• Post-transurethral prostatic resection syndrome (absorption of hypotonic irrigation fluid) 4

• Exercise-induced hyponatremia (excessive water intake during endurance exercise) 3

Pediatric Considerations

In pediatric patients, additional causes include:

• Inadequate sodium intake in formula/feeding
• Increased insensible losses
• Primary tubular sodium losses 7

Clinical Approach to Diagnosis

1. Confirm true hyponatremia by checking plasma osmolality:

   • High osmolality: Consider hyperglycemia
   • Normal osmolality: Consider pseudohyponatremia
   • Low osmolality: True hyponatremia 4

2. Assess volume status to categorize as hypovolemic, euvolemic, or hypervolemic

3. Measure urinary sodium to differentiate causes:

   • Hypovolemic with low urinary sodium (<20 mmol/L): Extrarenal losses
   • Hypovolemic with high urinary sodium (>20 mmol/L): Renal losses
   • Euvolemic with high urinary sodium: SIADH, adrenal insufficiency
   • Hypervolemic with low urinary sodium: Heart failure, cirrhosis
   • Hypervolemic with high urinary sodium: Renal failure 1, 4

Treatment Considerations

Treatment depends on the underlying cause, severity, and chronicity of hyponatremia:

• Hypovolemic hyponatremia: Isotonic saline to restore volume 2
• Euvolemic hyponatremia: Fluid restriction, treating underlying cause, and in some cases medications like tolvaptan 1
• Hypervolemic hyponatremia: Fluid restriction, diuretics, and treatment of underlying condition 6

Important Cautions

• Avoid rapid correction (>8 mEq/L in 24 hours) to prevent osmotic demyelination syndrome 1
• Severe symptomatic hyponatremia requires careful correction with hypertonic saline and close monitoring 8
• Tolvaptan should be initiated in a hospital setting with close monitoring of serum sodium 8

Understanding the underlying cause of hyponatremia is crucial for appropriate management and prevention of complications.