What are the causes of hyponatremia?

Causes of Hyponatremia

Classification by Volume Status

Hyponatremia develops through three primary mechanisms based on extracellular fluid volume status: hypovolemic, euvolemic, and hypervolemic hyponatremia, each with distinct underlying causes. 1, 2

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Hypovolemic Hyponatremia (True Volume Depletion)

Renal Causes (Urinary Sodium >20-30 mmol/L):

• Excessive diuretic use, particularly thiazide and loop diuretics 1, 2
• Cerebral salt wasting syndrome in neurosurgical patients (especially after subarachnoid hemorrhage) 1, 2
• Salt-wasting nephropathies 1
• Mineralocorticoid deficiency 1

Extrarenal Causes (Urinary Sodium <30 mmol/L):

• Gastrointestinal losses: severe diarrhea, vomiting, nasogastric suction 1, 3
• Third-space fluid sequestration: severe burns, pancreatitis 1, 3
• Significant blood loss 4

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Euvolemic Hyponatremia (Normal Volume Status)

Syndrome of Inappropriate Antidiuretic Hormone (SIADH):

Malignancies:

• Small cell lung cancer (most common) 2
• Pancreatic cancer 2
• Lymphomas 2

Medications (High-Risk):

• Antiepileptics: carbamazepine, oxcarbazepine 1, 2
• Antidepressants: selective serotonin reuptake inhibitors (SSRIs), trazodone 1, 2
• Chemotherapy agents: vincristine, cyclophosphamide 1, 2
• Desmopressin 1, 2

Central Nervous System Disorders:

• Meningitis, encephalitis 1
• Subarachnoid hemorrhage, subdural hematoma 1
• Brain tumors 1

Pulmonary Disorders:

• Pneumonia 1
• Tuberculosis 1

Endocrine Deficiencies:

• Hypothyroidism 1, 2
• Adrenal insufficiency 1, 2

Other Causes:

• Reset osmostat syndrome 3
• Acute water intoxication (psychogenic polydipsia) 4

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Hypervolemic Hyponatremia (Volume Overload with Total Body Sodium Excess)

Cardiac Causes:

• Congestive heart failure with reduced cardiac output triggering neurohormonal activation and increased ADH release 1, 2, 3

Hepatic Causes:

• Cirrhosis with portal hypertension (occurs in approximately 60% of cirrhotic patients) 1, 2
• Non-osmotic hypersecretion of vasopressin 1
• Enhanced proximal nephron sodium reabsorption 1
• Systemic vasodilation with decreased effective plasma volume 1

Renal Causes:

• Chronic kidney disease with impaired free water excretion 2
• Nephrotic syndrome 2
• Acute kidney injury 1

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Special Populations at High Risk

Pediatric Patients:

• Receiving perioperative medications (desmopressin, antiepileptics, chemotherapy) 2
• Congenital or acquired heart disease 2
• Liver disease or renal dysfunction 2

Neurosurgical Patients:

• Cerebral salt wasting is more common than SIADH in this population 1
• Subarachnoid hemorrhage patients (particularly with poor clinical grade, ruptured anterior communicating artery aneurysms, hydrocephalus) 1

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Diagnostic Approach to Determine Etiology

Initial workup should include: 1

• Serum and urine osmolality
• Urine sodium concentration
• Urine electrolytes
• Serum uric acid
• Assessment of extracellular fluid volume status

Key Diagnostic Clues:

• Urinary sodium <30 mmol/L suggests hypovolemic hyponatremia (71-100% positive predictive value for response to saline) 1, 2
• Urinary sodium >20-40 mmol/L with high urine osmolality (>300-500 mOsm/kg) suggests SIADH or renal salt wasting 1, 2
• Serum uric acid <4 mg/dL has 73-100% positive predictive value for SIADH 1, 2

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Common Pitfalls

• Failing to assess volume status accurately leads to inappropriate treatment (fluid restriction in hypovolemia or saline administration in SIADH) 1
• Not distinguishing between SIADH and cerebral salt wasting in neurosurgical patients, as treatments are opposite 1
• Ignoring medication-induced hyponatremia, particularly with high-risk drugs 1, 2
• Overlooking mild hyponatremia (130-135 mmol/L), which increases fall risk and mortality 1