What is hyponatremia?

What is Hyponatremia

Hyponatremia is defined as a serum sodium concentration below 135 mmol/L, making it the most common electrolyte disorder encountered in clinical practice, affecting approximately 5% of adults and up to 35% of hospitalized patients. 1, 2

Definition and Classification by Severity

Hyponatremia represents an imbalance where serum sodium falls below the normal threshold, with severity classified as follows:

• Mild hyponatremia: 130-135 mmol/L (or 126-135 mmol/L by some classifications) 1, 3
• Moderate hyponatremia: 120-129 mmol/L (or 120-125 mmol/L) 1, 3
• Severe hyponatremia: <120 mmol/L 1, 3

The condition should be further investigated and treated when serum sodium drops below 131 mmol/L, though even mild hyponatremia warrants attention due to associated morbidity. 1

Pathophysiology and Mechanisms

Hyponatremia most commonly results from water retention rather than true sodium depletion, developing through three primary mechanisms based on volume status: 2

Hypovolemic Hyponatremia (True Volume Depletion)

• Caused by excessive diuretic use, particularly thiazides and loop diuretics 4
• Gastrointestinal losses (vomiting, diarrhea) 1, 5
• Cerebral salt wasting syndrome in neurosurgical patients 4
• Characterized by urinary sodium <30 mmol/L in extrarenal losses 1

Euvolemic Hyponatremia (Normal Volume Status)

• Syndrome of Inappropriate Antidiuretic Hormone (SIADH) is the primary mechanism 4, 3
• Malignancies (small cell lung cancer, pancreatic cancer, lymphomas) 4
• Medications: carbamazepine, oxcarbazepine, SSRIs, vincristine, cyclophosphamide, desmopressin, trazodone 4
• CNS disorders, pulmonary pathology 1
• Characterized by urinary sodium >20-40 mmol/L with urine osmolality >300-500 mOsm/kg 4

Hypervolemic Hyponatremia (Volume Overload)

• Cirrhosis with portal hypertension (occurs in approximately 60% of cirrhotic patients) 4, 6
• Congestive heart failure due to reduced cardiac output triggering neurohormonal activation with increased ADH release 4, 6
• Nephrotic syndrome and chronic kidney disease 4
• Results from non-osmotic hypersecretion of vasopressin and enhanced proximal nephron sodium reabsorption 1

Clinical Significance and Symptoms

Even mild hyponatremia is associated with increased hospital stay, mortality, and significant morbidity. 2

Symptom Severity by Sodium Level

• Mild (130-134 mmol/L): Often few or no symptoms, but associated with cognitive impairment, lack of concentration, forgetfulness, apathy 3
• Moderate (120-129 mmol/L): Nausea, loss of balance, gait disturbances, increased fall risk (21% vs 5% in normonatremic patients) 2, 3
• Severe (<120 mmol/L): Seizures, coma, cardiorespiratory distress, somnolence, obtundation 2, 3

Chronic Complications

• Increased fall risk: 23.8% vs 16.4% in normonatremic patients 2
• Higher fracture rates: 23.3% vs 17.3% over 7.4 years of follow-up 2
• Secondary osteoporosis 2
• 60-fold increase in hospital mortality when sodium <130 mmol/L (11.2% vs 0.19%) 1

Acute vs. Chronic Presentation

• Acute hyponatremia (<48 hours): Causes more severe symptoms due to rapid onset, higher risk of cerebral edema 3
• Chronic hyponatremia (>48 hours): Better tolerated but associated with cognitive impairment and falls 3

Diagnostic Approach

Initial workup should include serum and urine osmolality, urine sodium concentration, urine electrolytes, serum uric acid, and clinical assessment of extracellular fluid volume status. 1, 4

Key Diagnostic Tests

• Urinary sodium <30 mmol/L: Suggests hypovolemic hyponatremia with 71-100% positive predictive value for response to saline 4
• Urinary sodium >20-40 mmol/L with high urine osmolality (>300-500 mOsm/kg): Suggests SIADH or renal salt wasting 4
• Serum uric acid <4 mg/dL: Has 73-100% positive predictive value for SIADH 4
• Plasma osmolality: Differentiates true hypoosmolar hyponatremia from pseudohyponatremia or hyperglycemia-induced hyponatremia 5

Treatment Principles

The approach to managing hyponatremia should consist of treating the underlying cause, with treatment strategy determined by volume status and symptom severity. 2, 5

Critical Safety Consideration

• Maximum correction rate: 8 mmol/L in 24 hours to prevent osmotic demyelination syndrome 1
• High-risk patients (advanced liver disease, alcoholism, malnutrition): 4-6 mmol/L per day 1
• Overly rapid correction can cause osmotic demyelination syndrome, a rare but severe neurological condition resulting in parkinsonism, quadriparesis, or death 2

Treatment by Volume Status

• Hypovolemic: Isotonic saline (0.9% NaCl) for volume repletion 1, 3
• Euvolemic (SIADH): Fluid restriction to 1 L/day; urea and vaptans for resistant cases 2, 3
• Hypervolemic: Fluid restriction to 1-1.5 L/day for sodium <125 mmol/L; vaptans may be considered 1, 3

Severely Symptomatic Hyponatremia

This is a medical emergency requiring immediate treatment with hypertonic saline (3% NaCl) to reverse hyponatremic encephalopathy. 2

• Target correction: 4-6 mmol/L within 1-2 hours or until symptoms resolve 2
• Do not exceed 10 mmol/L correction in first 24 hours 2
• Requires ICU admission with serum sodium monitoring every 2 hours 1