Diagnosis

Hyponatremia

Etiology

Cause [cgu][7zn]

• Comorbidities: kidney failure, pneumonia, heart failure, liver cirrhosis, malignant tumors, stroke, fracture, infections, malignancies, endocrinopathies (hypothyroidism, hypopituitarism, primary adrenal insufficiency (Addison’s disease), diabetes mellitus/hyperglycemia (movement of water out of cells and reduction of serum sodium levels by dilution)

• Drug side-effects: Diuretics, dehydrants, PPI, ACEI/ARB, SSRI, carbamazepine, NSAIDs

• Drugs associated with SIADH: Chlorpropamide, Cyclophosphamide, Vincristine, Vinblastine, Amitriptyline, Haloperidol, SSRI, Monoamine oxidase inhibitor, NSAIDs

• Low-salt diet

Pathophysiology [u2u]

1. Thirst --> ADH --> renal concentration --> serum sodium and osmolality 275 to 290 mOsm/kg

2. Imbalance of water intake and excretion causes hyponatremia or hypernatremia

3. Determine plasma osmolality:

   • Hypertonic hyponatremia: High due to active molecules (hyperglycemia/mannitol)

   • Isotonic hyponatremia: Normal due to elevated lipid profile/hyperproteinemia

   • Hypotonic hyponatremia: Excess of free water --> true hyponatremia

4. Urine Osmolality

   • Urine osmolality < 100 mOsm/kg: primary polydipsia or reset osmostat

   • Urine osmolality > 100 mOsm/kg: ADH state

5. Urine Sodium Concentration

   • Urine sodium < 10 mmol/L: extrarenal loss of fluid (diuretic use and vomiting).

   • Urine sodium > 20 mmol/L: renal loss of urine (diuretics, vomiting, cortisol deficiency, and salt-wasting nephropathies)

6. Asses volume status:

   • Hypervolemia: Increase in sodium with greater increase in total body water

     • Heart failure

     • Liver cirrhosis

     • Renal failure/nephrotic syndrome

   • Euvolemia: Normal body sodium with increase in total body water

     • SIADH: CNS disorder, ectopic ADH, carbamazepine, HIV, pneumonia, tuberculosis

     • Addison's disease

     • Hypothyroidism

     • High fluid intake

     • Drugs: Vasopressin, SSRI, antidepressants, opioids, thiazide diuretics, carbamazepine, vincristine, nicotine, antipsychotics, chlorpropamide, cyclophosphamide, NSAIDs, MDMA, ecstasy

   • Hypovolemia: Decrease in total body water with greater decrease in sodium

     • Gastrointestinal fluid loss: diarrhea or vomiting

     • Renal failure: salt-wasting nephropathies

     • The third spacing: pancreatitis, hypoalbuminemia, ileus, burns

     • Diuretics

     • Osmotic diuresis: glucose, mannitol

     • Cerebral salt-wasting syndrome (urinary salt wasting)

     • Mineralocorticoid deficiency

Complications [u2u]

• Rhabdomyolysis

• Seizures

• Coma

• Osmotic demyelination syndrome (if rapid correction of chronic hyponatremia)

Epidemiology

Prevalence per 100.000 [hn9][cgu][cqa][vpa][a5s][ri6]

Approach

• Blood test: serum osmolality, plasma osmolality, glucose, serum uric acid (reduced in SIADH), hypothalamic–pituitary–adrenal axis, TSH, ACTH, liver function tests

• Urine: stix, urine osmolality, urinary sodium concentration

  • Urine Na: Differentiate between hyponatremia due to hypovolemia and SIADH

    • >20 mEq/L indicates a renal cause

    • <20 mmol/L indicates hypovolemia (or SIADH with low-salt diet)

    • >30 mmol/L suggest SIADH

• CT/MRI caput

• Chest radiography

The diagnostic criteria for SIADH:

1. Normal liver, kidney, and heart function

2. Clinical euvolemia

3. Normal thyroid and adrenal function

4. Hypotonic hyponatremia

5. Urine osmolality greater than 100 mOsm/kg, generally greater than 400-500 mOsm/kg with normal kidney function

Treatment

The treatment of hyponatremia depends on the cause, severity and symptoms. Correct serum sodium levels at the appropriate rate in order to avoid the osmotic demyelination syndrome (elevation of serum sodium concentration by 4–6 mEq/L within the first 4–6 h). Acute hyponatremia (duration < 48 hours) can be safely corrected more quickly than chronic hyponatremia.

1. Acute symptomatic hyponatremia < 24-48 hours: [vpa][fet]

   • Severe symtoms: Bolus 150 mL of 3% NaCl over 20 minutes, 2- 3 times as needed, control Na every 20 minutes

   • Moderate symptoms: Continuous infusion of 3% NaCl at 0.5-2 mL/kg/h

2. Chronic hyponatremia > 48 hours: correction rate 4-6 mmol/L/d

3. Treat underlying cause [vpa][fet]

   • SIADH (chronic euvolemic hyponatremia): Discontinuation of drugs, water restriction, furosemide, careful administration of hypertonic fluids, vasopressin-2 antagonists

   • Hypovolemic hyponatremia: Isotonic saline 0.5-1.0 mL/kg/h

   • Euvolemic and hypervolemic hyponatremia: fluid restriction 500 mL/d, loop diuretics, oral NaCl, vasopressin-2 antagonists

   • Hypotonic hyponatremia: fluid restriction

Differential diagnoses

Acute liver failure, Acute pancreatitis, Adrenal crisis, Adrenal insufficiency, Alcoholism, Cancer origo incerta, Cirrhosis, Clostridium tetani, Cortisol deficiency, Diabetes mellitus, Drug side effects, Gastroenteritis, Heart failure, Hyperkalemia, Hyperphosphatemia, Hyperventilation, Hypocalcemia, Hypocapnia, Hypokalemia, Hypomagnesemia, Hypoparathyroidism, Hypothyroidism, Hypovolemia, Milk-alkali syndrome, Nephrotic syndrome, Primary polydipsia, Pulmonary edema, Renal failure, Syndrome of inappropriate antidiuretic hormone secretion, Trauma