What causes hyponatremia (low sodium levels)?

Causes of Hyponatremia (Low Sodium)

Hyponatremia is primarily caused by three major pathophysiological mechanisms: hypovolemic, euvolemic, and hypervolemic states, each with distinct underlying etiologies that affect sodium balance and water homeostasis.

Classification by Volume Status

1. Hypovolemic Hyponatremia

• Decreased effective circulating volume with sodium loss exceeding water loss
• Common causes:
  • Excessive diuretic use (especially thiazides) 1, 2
  • Gastrointestinal losses (vomiting, diarrhea) 3
  • Third-spacing (burns, pancreatitis) 3
  • Adrenal insufficiency 4
  • Cerebral salt wasting syndrome (particularly in neurosurgical patients) 4
  • Renal salt wasting 3

2. Euvolemic Hyponatremia

• Normal volume status with relative excess of water compared to sodium
• Common causes:
  • Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) 1
    • Malignancies (particularly small cell lung cancer)
    • CNS disorders (stroke, hemorrhage, trauma)
    • Pulmonary diseases (pneumonia, tuberculosis)
    • Medications (antidepressants, antiepileptics, antipsychotics) 2, 5
  • Hypothyroidism 4
  • Primary polydipsia (excessive water intake) 6
  • Post-operative state 1
  • Reset osmostat syndrome 3

3. Hypervolemic Hyponatremia

• Expanded extracellular fluid volume with ascites and edema
• Common causes:
  • Liver cirrhosis 7
  • Congestive heart failure 1, 3
  • Nephrotic syndrome 3
  • Advanced kidney disease 3

Pathophysiology in Specific Conditions

Cirrhosis-Related Hyponatremia

Hyponatremia in cirrhosis is predominantly dilutional, caused by:

• Systemic vasodilation due to portal hypertension 7
• Decreased effective plasma volume 7
• Hyperdynamic circulation 7
• Activation of renin-angiotensin-aldosterone system 7
• Impaired regulation of antidiuretic hormone 7
• Increased arterial natriuretic peptide 7

Drug-Induced Hyponatremia

Multiple medications can cause hyponatremia through various mechanisms:

• Diuretics (especially thiazides) - impair urinary dilution 2
• Antidepressants (SSRIs, TCAs) - enhance ADH effects 2, 5
• Antiepileptics (carbamazepine, oxcarbazepine) - enhance ADH release 2
• Antipsychotics - SIADH-like effect 2
• Proton pump inhibitors - unknown mechanism 2
• Newer antihypertensive agents - various mechanisms 2

Clinical Significance and Complications

Hyponatremia is associated with:

• Increased hospital stay and mortality 1
• Cognitive impairment and gait disturbances in chronic cases 1
• Increased rates of falls and fractures 1
• Secondary osteoporosis 1
• Neurological complications including seizures and coma in severe cases 8, 1

In cirrhotic patients, hyponatremia increases risk of:

• Spontaneous bacterial peritonitis 7
• Hepatorenal syndrome 7
• Hepatic encephalopathy 7

Diagnostic Approach

1. Confirm true hyponatremia by measuring plasma osmolality 3

   • High plasma osmolality: hyperglycemia-induced hyponatremia
   • Normal plasma osmolality: pseudohyponatremia
   • Low plasma osmolality: true hyponatremia

2. Assess volume status to categorize as hypovolemic, euvolemic, or hypervolemic 1

3. Measure urinary sodium concentration 3

   • High urinary sodium (>20 mEq/L) with hypovolemia: renal sodium losses
   • Low urinary sodium (<20 mEq/L) with hypovolemia: extrarenal sodium losses
   • High urinary sodium with euvolemia: SIADH or similar disorders
   • Low urinary sodium with hypervolemia: heart failure, cirrhosis

4. Consider urine osmolality

   • Inappropriately high urine osmolality (>500 mOsm/kg) with euvolemia suggests SIADH 4

Common Pitfalls in Diagnosis

• Misclassification of volume status (especially between euvolemic and hypovolemic states) 4
• Failure to recognize drug-induced hyponatremia 2
• Overlooking hyponatremia in patients with neurological symptoms 1
• Not considering multiple concurrent causes in hospitalized patients 1
• Inadequate monitoring during correction of hyponatremia 4

By understanding these diverse causes and mechanisms, clinicians can better diagnose and manage hyponatremia, which affects approximately 5% of adults and up to 35% of hospitalized patients 1.