What are the causes of hyponatremia?

Causes of Hyponatremia

Hyponatremia (serum sodium <135 mmol/L) should be evaluated based on volume status and serum osmolality to determine the underlying cause. 1

Classification Based on Volume Status

Hypovolemic Hyponatremia

• Excessive diuretic use, particularly in patients with liver cirrhosis 1
• Gastrointestinal losses (vomiting, diarrhea) 2
• Severe burns 1
• Blood loss 3
• Third-space losses 2
• Renal losses (salt-wasting nephropathies) 1

Euvolemic Hyponatremia

• Syndrome of Inappropriate ADH secretion (SIADH) 1
• Cerebral salt wasting (CSW), particularly in neurosurgical patients 1
• Hypothyroidism 1
• Adrenal insufficiency 4
• Medications (antidepressants, antipsychotics, anticonvulsants, antineoplastics) 2
• Reset osmostat syndrome 1
• Acute water overload 1
• Beer potomania (excessive beer intake with low solute intake) 1

Hypervolemic Hyponatremia

• Congestive heart failure 1, 2
• Liver cirrhosis with portal hypertension 1
• Nephrotic syndrome 3
• Renal failure 3
• Advanced liver disease with systemic vasodilation 1

Classification Based on Osmolality

• Hypotonic hyponatremia (low plasma osmolality) - most common form 4
• Isotonic hyponatremia (normal plasma osmolality) - pseudohyponatremia 2
• Hypertonic hyponatremia (high plasma osmolality) - typically due to hyperglycemia 2

Pathophysiological Mechanisms

• Non-osmotic hypersecretion of vasopressin (ADH) - seen in SIADH, heart failure, cirrhosis 1, 5
• Enhanced proximal nephron sodium reabsorption - common in cirrhosis 1
• Impaired free water clearance - occurs in ~60% of cirrhotic patients 1
• Activation of renin-angiotensin-aldosterone system causing excessive sodium and water reabsorption 1

Laboratory Findings in Different Types

• Hypovolemic: Elevated BUN and creatinine, urinary sodium <30 mmol/L 1, 2
• Euvolemic (SIADH): Urine sodium >20 mEq/L, high urine osmolality (>500 mosm/kg), serum uric acid <4 mg/dL 1
• Hypervolemic: Often associated with edema, ascites, distended jugular veins 3

Clinical Significance

• Hyponatremia increases mortality risk, with sodium levels <130 mmol/L linked to a 60-fold increase in fatality (11.2% versus 0.19%) 1
• Cirrhotic patients with sodium <130 mmol/L have increased risk of complications including spontaneous bacterial peritonitis (OR 3.40), hepatorenal syndrome (OR 3.45), and hepatic encephalopathy (OR 2.36) 1
• Even mild hyponatremia is associated with neurocognitive problems, falls, and attention deficits 1

Common Pitfalls in Diagnosis

• Failing to assess volume status accurately - essential for differentiating between causes 1
• Ignoring mild hyponatremia (130-135 mmol/L) as clinically insignificant 1
• Misdiagnosing the volume status in heart failure patients with hyponatremia 1
• Failing to distinguish between SIADH and cerebral salt wasting in neurosurgical patients 1

Remember that initial workup should include serum and urine osmolarity, urine electrolytes, uric acid, and assessment of extracellular fluid volume status to determine the underlying cause of hyponatremia 1.