What causes reduced serum sodium levels (hyponatremia) in patients?

Causes of Reduced Serum Sodium (Hyponatremia)

Hyponatremia results from an imbalance between water intake and excretion, leading to water retention that dilutes serum sodium concentration below 135 mmol/L. 1

Primary Mechanisms of Hyponatremia

Water Retention (Most Common)

• Non-osmotic vasopressin (ADH) release is the predominant mechanism, where ADH secretion occurs despite low plasma osmolality, impairing free water excretion 1, 2
• This occurs in SIADH, where inappropriate ADH activity leads to water retention and subsequent physiologic natriuresis to maintain fluid balance 3
• In heart failure and cirrhosis, systemic vasodilation and decreased effective plasma volume trigger ADH release despite total body fluid overload 1

Sodium Depletion

• Excessive sodium losses through kidneys (diuretics, salt-wasting nephropathy, cerebral salt wasting) or extrarenal routes (vomiting, diarrhea, burns) 1, 3
• Diuretic use, particularly in cirrhotic patients, commonly causes hypovolemic hyponatremia 1

Classification by Volume Status

Hypovolemic Hyponatremia (True Volume Depletion)

• Renal losses: Diuretics, cerebral salt wasting, adrenal insufficiency, salt-losing nephropathy (urine sodium >20 mmol/L) 1, 3
• Extrarenal losses: Gastrointestinal losses (vomiting, diarrhea), burns, dehydration (urine sodium <30 mmol/L) 1, 3

Euvolemic Hyponatremia (Normal Total Body Sodium)

• SIADH is the classic cause, characterized by inappropriate ADH secretion with urine osmolality >300 mOsm/kg and urine sodium >20-40 mmol/L 3
• Common SIADH triggers include malignancies (especially small cell lung cancer), CNS disorders, pulmonary diseases, medications (SSRIs, carbamazepine, cyclophosphamide), postoperative states, and pain/nausea/stress 1, 3
• Hospital-acquired hyponatremia from hypotonic IV fluids in the setting of elevated ADH affects 15-30% of hospitalized patients and is entirely preventable 3

Hypervolemic Hyponatremia (Excess Total Body Sodium and Water)

• Advanced cirrhosis with portal hypertension causes systemic vasodilation, decreased effective plasma volume, and activation of renin-angiotensin-aldosterone system, leading to excessive sodium and water reabsorption 1
• Heart failure leads to non-osmotic ADH release due to perceived arterial underfilling despite volume overload 1
• Advanced renal failure impairs free water excretion 3

Medication-Induced Hyponatremia

• Diuretics (especially thiazides like HCTZ and indapamide) cause excessive sodium and water loss 1
• Antidepressants (SSRIs, trazodone) place patients at particularly high risk for developing hyponatremia 1
• Vasopressin can cause hyponatremia as an adverse effect 4
• Other medications include carbamazepine, cyclophosphamide, and NSAIDs 3

Special Clinical Scenarios

Neurosurgical Patients

• Cerebral salt wasting (CSW) is more common than SIADH in neurosurgical patients, produced by excessive secretion of natriuretic peptides causing hyponatremia through excessive natriuresis and volume contraction 1
• CSW is more common in patients with poor clinical grade, ruptured anterior communicating artery aneurysms, and hydrocephalus 1

Cirrhotic Patients

• Hyponatremia occurs in approximately 60% of cirrhotic patients, primarily dilutional in nature and defined at serum sodium <130 mmol/L 1
• Systemic vasodilation due to portal hypertension leads to decreased effective plasma volume and decreased systemic vascular resistance 1

Acute Illness States

• Acute pancreatitis is a well-established nonosmotic stimulus for AVP release 3
• Pain, nausea, and stress lead to AVP excess, impairing free-water excretion 3

Clinical Significance

• Even mild hyponatremia (130-135 mmol/L) is associated with increased mortality, with sodium levels <130 mmol/L linked to a 60-fold increase in fatality (11.2% versus 0.19%) 1, 2
• Hyponatremia increases fall risk—21% of hyponatremic patients present with falls compared to 5% of normonatremic patients 1, 2
• In cirrhotic patients with sodium <130 mmol/L, there is increased risk of spontaneous bacterial peritonitis (OR 3.40), hepatorenal syndrome (OR 3.45), and hepatic encephalopathy (OR 2.36) 1

Common Pitfalls

• Pseudohyponatremia from hyperglycemia (add 1.6 mEq/L to sodium for each 100 mg/dL glucose >100 mg/dL) or hypertriglyceridemia must be excluded 1
• Ignoring mild hyponatremia (130-135 mmol/L) as clinically insignificant is a common error, as even mild hyponatremia is associated with cognitive impairment, gait disturbances, and increased fracture risk 1, 2
• Misdiagnosing volume status can lead to inappropriate treatment—physical examination alone has poor accuracy (sensitivity 41.1%, specificity 80%) 1, 3