Causes of Hyponatremia and Hypochloremia
Hyponatremia results from an imbalance between sodium and water in the extracellular compartment, classified by volume status, while hypochloremia typically accompanies hyponatremia and shares similar underlying mechanisms related to sodium handling abnormalities. 1
Classification by Volume Status
The causes of hyponatremia are best understood by assessing the patient's total body volume status, as this directly guides diagnosis and treatment 2:
Hypovolemic Hyponatremia (True Sodium and Volume Depletion)
Extrarenal losses:
- Gastrointestinal fluid losses (vomiting, diarrhea, third-spacing from burns or pancreatitis) typically produce urinary sodium <20 mEq/L 1
- Excessive sweating causing sodium depletion 1
Renal losses:
- Excessive diuretic use, particularly thiazide diuretics and loop diuretics in cirrhotic patients 1, 3
- Salt-wasting nephropathy 4
- Cerebral salt wasting (CSW) in neurosurgical patients, characterized by excessive natriuretic peptide secretion causing hypovolemia with urinary sodium >20 mmol/L despite volume depletion 1
Euvolemic Hyponatremia (Normal Total Body Sodium, Excess Water)
Syndrome of Inappropriate Antidiuretic Hormone (SIADH):
- Malignancies (particularly small cell lung cancer) 4, 5
- CNS disorders (meningitis, encephalitis, stroke, subarachnoid hemorrhage) 4
- Pulmonary diseases (pneumonia, tuberculosis) 4
- Medications including SSRIs, carbamazepine, cyclophosphamide, NSAIDs, and opioids 1, 3
- Postoperative states with pain, nausea, and stress as nonosmotic stimuli for vasopressin release 1
Hospital-acquired hyponatremia:
- Hypotonic IV fluid administration in the setting of elevated antidiuretic hormone, affecting 15-30% of hospitalized patients 1, 4
Endocrine causes:
Other causes:
- Excessive alcohol consumption (beer potomania) with very low-salt diets 3
- Exercise-induced hyponatremia from excessive free water intake 3
Hypervolemic Hyponatremia (Excess Total Body Sodium and Water, with Relatively More Water)
Advanced liver cirrhosis with portal hypertension:
- Systemic vasodilation and decreased effective plasma volume trigger non-osmotic vasopressin hypersecretion 1
- Activation of renin-angiotensin-aldosterone system causes excessive sodium and water reabsorption 1
- Approximately 60% of cirrhotic patients develop dilutional hyponatremia 6
Congestive heart failure:
- Hemodynamic abnormalities trigger neurohormonal pathways including RAAS and arginine vasopressin systems 6
- Inadequate urinary sodium excretion (<50-70 mEq/L) reflects heightened kidney sodium avidity 6
Renal failure:
Hypochloremia Mechanisms
Hypochloremia typically accompanies hyponatremia and shares common pathophysiologic mechanisms 6:
- Abnormalities in sodium handling by the kidneys are associated with abnormalities in chloride handling 6
- Decreased chloride delivery to the macula densa triggers renin release from the juxtaglomerular apparatus, exacerbating maladaptive RAAS stimulation with downstream sodium retention 6
- Hypochloremia confers a strong independent risk for mortality in heart failure patients 6
- Salt- and water-avid states manifest as both hyponatremia and hypochloremia 6
Pseudohyponatremia
Artifactual low sodium measurements occur with:
- Hyperproteinemia 7, 4
- Hyperlipidemia 7, 4
- Hyperglycemia (corrected sodium = measured sodium + 1.6 mEq/L for each 100 mg/dL glucose >100 mg/dL) 1, 7
Common Pitfalls
- Failing to assess volume status accurately leads to incorrect diagnosis and opposite treatments (fluid restriction for SIADH versus volume repletion for CSW) 1
- Ignoring mild hyponatremia (130-135 mmol/L) as clinically insignificant, when it increases fall risk (21% vs 5% in normonatremic patients) and mortality 1
- Misdiagnosing the volume status in heart failure patients with hyponatremia, where physical examination alone has poor sensitivity (41.1%) and specificity (80%) 1
- Not recognizing medication-induced hyponatremia, particularly with diuretics, SSRIs, and carbamazepine 1, 3