What are the causes of hyponatremia?

Causes of Hyponatremia

Hyponatremia can be classified according to volume status (hypovolemic, euvolemic, hypervolemic) and severity (mild: 126-135 mEq/L, moderate: 120-125 mEq/L, severe: <120 mEq/L), with each classification having distinct etiologies that guide treatment approaches. 1

Classification by Volume Status

1. Hypovolemic Hyponatremia

• Excessive diuretic use - particularly common in cirrhotic patients 2
• Gastrointestinal losses - vomiting, diarrhea, severe burns 3
• Third-space losses - pancreatitis, severe burns
• Adrenal insufficiency - cortisol deficiency leading to impaired free water excretion 1
• Cerebral salt wasting - typically seen with intracranial pathology

2. Euvolemic Hyponatremia

• Syndrome of Inappropriate Antidiuretic Hormone (SIADH) - characterized by hyponatremia, hypoosmolality, inappropriately elevated urine osmolality, and elevated urine sodium 1
  • Causes include:
    • Malignancies (particularly lung cancer)
    • CNS disorders (stroke, hemorrhage, trauma, infection)
    • Pulmonary disorders (pneumonia, tuberculosis, COPD)
    • Medications (see medication list below)
• Hypothyroidism - decreased cardiac output and GFR leading to water retention 1
• Reset osmostat syndrome - abnormal setting of the osmostat controlling ADH release 3
• Primary polydipsia - excessive water intake overwhelming excretory capacity 4
• Post-operative state - often due to inappropriate ADH secretion

3. Hypervolemic Hyponatremia

• Liver cirrhosis - systemic vasodilation due to portal hypertension and decreased effective plasma volume 2
• Congestive heart failure - decreased cardiac output activating neurohormonal systems including AVP 5
• Nephrotic syndrome - hypoalbuminemia leading to decreased effective circulating volume 3
• Renal failure - impaired water excretion 3

Medication-Induced Hyponatremia

• Diuretics - especially thiazides, which impair urinary dilution 3
• Antidepressants - SSRIs, TCAs, MAOIs (increase ADH secretion)
• Antipsychotics - particularly phenothiazines
• Anticonvulsants - carbamazepine, oxcarbazepine, valproate
• Antineoplastic agents - cyclophosphamide, vincristine
• Opioids - stimulate ADH release
• NSAIDs - enhance ADH effects at the renal collecting ducts

Pathophysiological Mechanisms

In Cirrhosis

Hyponatremia in cirrhosis results from:

• Systemic vasodilation due to portal hypertension
• Decreased effective plasma volume
• Decreased systemic vascular resistance
• Hyperdynamic circulation
• Accumulation of vasodilatory substances (nitric oxide, glucagon, vasoactive intestinal peptide)
• Activation of renin-angiotensin-aldosterone system leading to excessive sodium and water reabsorption
• Inadequate regulation of antidiuretic hormone
• Increased arterial natriuretic peptide and decreased prostaglandin E2 2

In Heart Failure

• Low cardiac output triggers compensatory neurohormonal activation
• Increased AVP activity causes free-water reabsorption in renal collecting ducts
• Dilution of plasma sodium concentrations 5

Special Considerations

Pseudohyponatremia

• Normal plasma osmolality with low measured sodium
• Caused by hyperlipidemia or hyperproteinemia 3

Hypertonic Hyponatremia

• High plasma osmolality with low sodium
• Typically caused by hyperglycemia (glucose draws water from intracellular to extracellular space) 3

Post-Transurethral Prostatic Resection Syndrome

• Absorption of hypotonic irrigation fluid during procedure
• Results in acute dilutional hyponatremia 3

Understanding the specific cause of hyponatremia is crucial for appropriate management, as treatment approaches differ significantly based on volume status, severity, and underlying etiology.