What causes an acute drop in sodium levels, or hyponatremia?

Causes of Acute Hyponatremia

The most common causes of an acute drop in sodium levels include Syndrome of Inappropriate Antidiuretic Hormone (SIADH), excessive free water intake, medication effects, and volume depletion with hypotonic fluid replacement. 1

Classification by Volume Status

Hyponatremia (serum sodium <135 mEq/L) should be categorized based on the patient's volume status:

1. Hypovolemic Hyponatremia

• Renal losses:

  • Diuretic use (especially thiazides)
  • Salt-wasting nephropathies
  • Cerebral salt wasting
  • Mineralocorticoid deficiency

• Extra-renal losses:

  • Vomiting
  • Diarrhea
  • Third-spacing (burns, pancreatitis)
  • Excessive sweating

2. Euvolemic Hyponatremia

• SIADH - occurs in approximately 10-45% of small cell lung cancer cases and 1% of other lung cancers 1
• Medications (SSRIs, carbamazepine, NSAIDs)
• Excessive water intake (psychogenic polydipsia)
• Endocrine disorders (hypothyroidism, adrenal insufficiency)
• Pain, nausea, stress (non-osmotic stimuli for ADH release) 1

3. Hypervolemic Hyponatremia

• Heart failure
• Liver cirrhosis - occurs in patients with advanced cirrhosis due to portal hypertension 1
• Nephrotic syndrome
• Renal failure

Pathophysiology of Acute Hyponatremia

The primary mechanisms causing acute hyponatremia include:

1. Excess ADH (vasopressin) activity - leads to increased water reabsorption in the renal collecting ducts, causing dilutional hyponatremia 1

2. Impaired free water excretion - occurs in conditions with elevated AVP concentrations, which impairs the kidney's ability to excrete free water 1

3. Excessive free water intake - when water intake exceeds the kidney's excretion capacity, especially during exercise (exercise-associated hyponatremia) 1

4. Sodium loss - through renal or extra-renal routes, particularly when replaced with hypotonic fluids 1

Special Considerations

Exercise-Associated Hyponatremia (EAH)

• Occurs in 3-22% of marathon runners 1
• Risk factors: excessive fluid consumption, longer race times (>4 hours), female sex, low BMI
• Primarily caused by dilutional hyponatremia from increased total body water relative to sodium stores 1

Hospital-Acquired Hyponatremia

• Most common in hospitalized patients (15-30% of children and adults) 1
• Often related to administration of hypotonic IV fluids in the setting of elevated AVP concentrations 1
• Particularly dangerous in children, who have a larger brain/skull size ratio 1

Diagnostic Approach

To determine the cause of acute hyponatremia:

1. Assess volume status - physical examination for signs of hypovolemia, euvolemia, or hypervolemia

2. Measure urine sodium and osmolality:

   • Hypovolemic: urine Na+ <20 mmol/L (if extra-renal loss) or >20 mmol/L (if renal loss)
   • SIADH: urine osmolality >500 mOsm/kg, urine Na+ >20 mEq/L 1

3. Check for medications that can cause hyponatremia (diuretics, antidepressants, anticonvulsants)

4. Evaluate for underlying conditions (malignancy, pulmonary disease, CNS disorders)

5. Consider non-osmotic stimuli for ADH release (pain, nausea, stress, postoperative state) 1

Clinical Pearls

• Symptoms depend on the severity and acuity of onset - acute hyponatremia (<48h) is more symptomatic than chronic hyponatremia at the same sodium level 2

• At sodium levels of 125-130 mEq/L, patients typically experience general weakness, confusion, headache, and nausea 1

• When sodium drops below 120 mEq/L, life-threatening manifestations may occur, including seizures, coma, and death due to cerebral edema 1

• Rapid correction of chronic hyponatremia can lead to osmotic demyelination syndrome, a severe neurological condition 3

• In hospitalized patients, always consider the role of hypotonic IV fluids in causing or worsening hyponatremia, especially in the presence of conditions that increase ADH secretion 1