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The adverse effects and manifestations of hyponatremia depend on its severity and rapidity of development. Acute hyponatremia (defined as developing within the prior 48 h) leaves the brain hypertonic relative to the hypotonic serum. This osmotic gradient drives water into the brain’s astrocytes, resulting in cerebral edema and CNS symptoms. Acute hyponatremia may cause seizures, brain damage, brainstem herniation, respiratory arrest, rhabdomyolysis and death. Symptoms occur at much more modest degrees of hyponatremia than in patients with chronic hyponatremia. Seizures can occur even at sodium levels above 120 mEq/L. On the other hand, in chronic hyponatremia (most cases), CNS adaptations occur. Astrocytes decrease their intracellular osmolality, decreasing the osmotic flux of water into the brain in turn causing less cerebral edema. Therefore, symptoms tend to develop when hyponatremia is more severe than in patients with acute hyponatremia. Seizures and herniation are much less frequent. Typically, patients with chronic hyponatremia and serum sodium levels > 130 mEq/L are asymptomatic. Symptoms associated with profound hyponatremia (< 125 mEq/L) include nausea (44–49%), vomiting (27–30%), gait disturbance (31%), headache 27%, confusion (14–30%), seizures (5%), and coma.
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Before reviewing the differential diagnosis of hyponatremia, it is useful to briefly review the pathophysiology of normal water handling, antidiuretic hormone (ADH), and then hyponatremia. ADH plays a key role in water handling.
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In health, dehydration increases the serum sodium and osmolality and triggers ADH release. This causes water channels (aquaporins) to be inserted into the luminal membrane of the collecting ducts, promoting water reabsorption. This restores normal osmolality and sodium concentration. Conversely, excessive water ingestion lowers the serum sodium and osmolality suppressing ADH secretion and results in the removal of the aquaporins. This prevents water reabsorption, promotes its excretion and restores the normal osmolality and sodium concentration.
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Hyponatremia occurs when water accumulates in excess of sodium due to an inability to excrete ingested water and in most patients, develops due to an excess of ADH. The excessive ADH release causes persistent, sustained, and inappropriate water reabsorption, diluting the serum sodium (and also simultaneously concentrating the urine). In order to understand the states of increased ADH it is critical to appreciate the triggers of ADH release. ADH is obviously released in response to an increase in osmolality but is also secreted in response to critical hypovolemia (in an attempt to reabsorb water and volume). The hypovolemia can be either real hypovolemia (as in hemorrhagic shock) or perceived hypovolemia, such as when there is an ineffective circulating volume (eg, from severe heart failure [HF]). In addition to these appropriate causes of ADH release, ADH secretion may be inappropriate, causing the syndrome of inappropriate ADH (SIADH). In SIADH, tumors and other diseases cause the release of ADH that is triggered by neither an increase in osmolality nor a decrease in the effective circulating volume. Finally, hyponatremia develops in some patients despite an appropriate suppression of ADH due to the rapid ingestion of such excessive amounts of water that ...