Causes of Hyponatremia
Hyponatremia can be classified based on volume status as hypovolemic, euvolemic, or hypervolemic, with each category having distinct etiologies that require different management approaches. 1
Classification by Volume Status
1. Hypovolemic Hyponatremia
- Gastrointestinal losses: Vomiting, diarrhea
- Renal losses:
- Diuretic use (especially thiazides) 2
- Cerebral salt wasting
- Mineralocorticoid deficiency
- Salt-losing nephropathy
- Skin losses: Excessive sweating, burns
- Third-space losses: Pancreatitis, muscle trauma, bowel obstruction
2. Euvolemic Hyponatremia
- Syndrome of Inappropriate Antidiuretic Hormone (SIADH) 3:
- Malignancies (especially small cell lung cancer)
- CNS disorders (stroke, trauma, infection)
- Pulmonary diseases (pneumonia, tuberculosis)
- Medications (antidepressants, antipsychotics, anticonvulsants)
- Endocrine disorders:
- Hypothyroidism
- Adrenal insufficiency
- Reset osmostat syndrome
- Psychogenic polydipsia
- Exercise-associated hyponatremia
3. Hypervolemic Hyponatremia
- Liver cirrhosis 3:
- Due to systemic vasodilation
- Decreased effective plasma volume
- Activation of renin-angiotensin-aldosterone system
- Inadequate regulation of antidiuretic hormone
- Congestive heart failure 4:
- Low cardiac output triggers neurohormonal activation
- Increased AVP activity causes free-water retention
- Nephrotic syndrome
- Renal failure
Pathophysiological Mechanisms
Cirrhosis-Related Hyponatremia
In liver cirrhosis, hyponatremia results from 3:
- Systemic vasodilation due to worsening portal hypertension
- Decreased effective plasma volume
- Decreased systemic vascular resistance
- Decreased mean arterial blood pressure
- Increased cardiac output leading to hyperdynamic circulation
- Accumulation of vasodilatory substances (nitric oxide, glucagon, etc.)
- Excessive sodium and water reabsorption via the renin-angiotensin-aldosterone system
SIADH Criteria
SIADH manifests as euvolemic hypoosmolar hyponatremia with 3:
- Serum sodium < 134 mEq/L
- Plasma osmolality < 275 mosm/kg
- Inappropriately high urine osmolality (> 500 mosm/kg)
- Inappropriately high urinary sodium concentration (> 20 mEq/L)
- Absence of hypothyroidism, adrenal insufficiency, or volume depletion
Diuretic-Induced Hyponatremia
- More commonly caused by thiazide diuretics than loop diuretics 2
- Can develop rapidly in susceptible patients
- Mechanism involves impaired urinary dilution and increased water retention
Severity Classification
Hyponatremia severity is classified as 1, 5:
- Mild: 126-135 mEq/L (often asymptomatic)
- Moderate: 120-125 mEq/L (nausea, headache, confusion)
- Severe: <120 mEq/L (risk of seizures, coma, respiratory arrest)
Diagnostic Approach
The diagnostic approach should include 1:
- Assessment of volume status (hypovolemic, euvolemic, or hypervolemic)
- Measurement of serum osmolality
- Measurement of urine osmolality and sodium concentration
- Evaluation of relevant laboratory parameters (thyroid function, adrenal function)
Laboratory Findings by Etiology
- Hypovolemic: Urine Na <20 mEq/L, variable urine osmolality
- Euvolemic (SIADH): Urine Na >20-40 mEq/L, urine osmolality >500 mOsm/kg
- Hypervolemic: Urine Na <20 mEq/L, elevated urine osmolality
Clinical Implications
Hyponatremia, particularly in cirrhosis, increases the risk of 3:
- Hepatic encephalopathy (odds ratio 3.4)
- Hepatorenal syndrome (odds ratio 3.5)
- Spontaneous bacterial peritonitis (odds ratio 2.4)
- Increased in-hospital waitlist mortality
Early detection and appropriate management are crucial to prevent severe complications such as seizures, coma, and death 3.