What causes hyponatremia?

Causes of Hyponatremia

Hyponatremia is primarily caused by systemic vasodilation, decreased effective plasma volume, and dysregulation of antidiuretic hormone, which can be classified based on volume status as hypovolemic, euvolemic, or hypervolemic. 1

Classification by Volume Status

1. Hypovolemic Hyponatremia

• Causes:

  • Excessive diuretic use (especially thiazides) 2, 3
  • Gastrointestinal losses (vomiting, diarrhea) 4
  • Third-space losses (burns, pancreatitis) 5
  • Adrenal insufficiency 1
  • Renal salt wasting 5

• Laboratory findings:

  • Urine sodium <20 mEq/L (with non-renal losses)
  • Urine sodium >20 mEq/L (with renal losses)
  • Variable urine osmolality 1

2. Euvolemic Hyponatremia

• Causes:

  • Syndrome of inappropriate antidiuretic hormone secretion (SIADH) 4, 5
  • Medications (antidepressants, antiepileptics, antipsychotics) 6
  • Reset osmostat syndrome 5
  • Hypothyroidism 1
  • Excessive water intake (psychogenic polydipsia) 4
  • Post-operative state 5

• Laboratory findings:

  • Urine sodium >20-40 mEq/L
  • Urine osmolality >500 mOsm/kg 1

3. Hypervolemic Hyponatremia

• Causes:

  • Liver cirrhosis 2
  • Congestive heart failure 7
  • Nephrotic syndrome 2
  • Renal failure 5

• Laboratory findings:

  • Urine sodium <20 mEq/L
  • Elevated urine osmolality 1

Pathophysiological Mechanisms

In Liver Cirrhosis

Hyponatremia in cirrhosis results from:

• Systemic vasodilation due to portal hypertension
• Decreased effective plasma volume
• Decreased systemic vascular resistance
• Hyperdynamic circulation
• Accumulation of vasodilatory substances (nitric oxide, glucagon, vasoactive intestinal peptide)
• Activation of renin-angiotensin-aldosterone system
• Impaired regulation of antidiuretic hormone
• Increased arterial natriuretic peptide
• Decreased prostaglandin E2
• Decreased degradation of antidiuretic hormone 2

In Heart Failure

• Low cardiac output triggers compensatory neurohormonal activation
• Increased activity of arginine vasopressin (AVP)
• AVP increases free-water reabsorption in renal collecting ducts
• Dilution of plasma sodium concentrations 7

Medication-Induced Hyponatremia

• Thiazide diuretics (more common than loop diuretics) 3
• Antidepressants (especially SSRIs)
• Antiepileptic drugs (carbamazepine)
• Chemotherapeutic agents (cyclophosphamide, vincristine)
• Desmopressin
• Newer antihypertensive agents
• Antibiotics
• Proton pump inhibitors 1, 6

Risk Factors for Developing Hyponatremia

• Advanced liver cirrhosis with ascites 2
• Congestive heart failure 7
• Renal dysfunction 5
• Advanced age
• Female sex
• Low body weight
• Excessive free water intake during exercise 4
• Concurrent use of multiple medications that can cause hyponatremia 6
• Malnutrition
• Alcoholism 1
• Edematous states (CHF, cirrhosis, nephrotic syndrome) 2

Clinical Implications

Hyponatremia severity is classified as:

• Mild (130-134 mmol/L)
• Moderate (125-129 mmol/L)
• Severe (<125 mmol/L) 4

Complications of hyponatremia in cirrhosis with ascites include:

• Spontaneous bacterial peritonitis (OR 3.40)
• Hepatorenal syndrome (OR 3.45)
• Hepatic encephalopathy (OR 2.36) 2

Common Pitfalls in Diagnosis

1. Failing to classify hyponatremia by volume status
2. Not considering medication-induced hyponatremia
3. Overlooking pseudohyponatremia (normal plasma osmolality)
4. Failing to recognize hyperglycemia as a cause of hyponatremia with high plasma osmolality
5. Not distinguishing between acute and chronic hyponatremia, which affects treatment approach 4, 5

Understanding the underlying cause of hyponatremia is essential for appropriate management and prevention of complications, with treatment strategies varying significantly based on volume status and etiology.