What is the pathophysiology of hyponatremia?

Pathophysiology of Hyponatremia

Primary Mechanisms

Hyponatremia develops through three fundamental pathophysiologic mechanisms based on volume status: hypovolemic, euvolemic, and hypervolemic, each driven by distinct underlying processes. 1, 2

Hypovolemic Hyponatremia

• True sodium and volume depletion occurs from gastrointestinal losses (vomiting, diarrhea), excessive diuretic use (particularly thiazides), burns, or cerebral salt wasting syndrome in neurosurgical patients 1, 2, 3
• Despite total body sodium depletion, non-osmotic ADH release is triggered by hypovolemia to preserve intravascular volume, leading to water retention that dilutes remaining sodium 4, 3
• The body prioritizes volume preservation over osmolality regulation, resulting in paradoxical water retention despite hypoosmolality 4

Euvolemic Hyponatremia (SIADH)

• Inappropriate ADH activity causes water retention without corresponding sodium retention, leading to dilutional hyponatremia while maintaining normal total body sodium 2, 5, 3
• Non-osmotic stimuli trigger excessive AVP release, including pain, nausea, stress, malignancies (small cell lung cancer, pancreatic cancer), CNS disorders, pulmonary diseases, and medications (SSRIs, carbamazepine, oxcarbazepine, cyclophosphamide) 2, 4, 3
• Physiologic natriuresis occurs as a compensatory mechanism - the body maintains fluid balance at the expense of plasma sodium by excreting sodium to prevent volume overload 2
• This explains the characteristic finding of urine sodium >20-40 mmol/L despite euvolemia in SIADH 1

Hypervolemic Hyponatremia

• Total body sodium and water are both increased, but water excess exceeds sodium excess, resulting in dilutional hyponatremia 3, 6
• In cirrhosis with portal hypertension (affecting ~60% of cirrhotic patients): systemic vasodilation from portal hypertension decreases effective arterial blood volume, triggering compensatory activation of renin-angiotensin-aldosterone system and non-osmotic ADH release, causing excessive sodium and water reabsorption 1, 2, 7
• In congestive heart failure: reduced cardiac output and blood pressure activate neurohormonal systems (RAAS, sympathetic nervous system, AVP) designed to preserve arterial blood volume, leading to free-water reabsorption in renal collecting ducts that increases blood volume while diluting plasma sodium 6, 7
• Enhanced proximal nephron sodium reabsorption and impaired free water clearance perpetuate the hyponatremic state 1

Common Pathophysiologic Pathway

All three types share a final common pathway: elevated ADH levels combined with continued fluid intake, though the triggers for ADH release differ (hypovolemia, non-osmotic stimuli, or decreased effective arterial volume) 5, 7

Clinical Significance of Pathophysiology

• Acute hyponatremia (<48 hours) causes more severe cerebral edema and neurologic symptoms than chronic hyponatremia because brain cells lack time to adapt through osmolyte extrusion 5, 4
• Chronic hyponatremia (>48 hours) allows brain adaptation through loss of intracellular osmolytes, reducing cerebral edema but creating risk for osmotic demyelination syndrome if corrected too rapidly 1, 4
• Hyponatremia increases mortality 60-fold when sodium <130 mmol/L (11.2% vs 0.19% in normonatremic patients) and increases fall risk (21% vs 5%) 1