The concentration of sodium reflects the total body store of sodium and its relation to total body water (TBW). In both hypo- and hypernatremia, the total body store of sodium may be high, low, or normal. It is the amount of TBW relative to total body sodium that determines sodium concentration. Sodium is found in highest concentrations in the extracellular compartment and is normally maintained between 135 and 145 mEq/L.

One of the primary regulatory mechanisms is arginine vasopressin (AVP), also known as antidiuretic hormone. AVP is secreted by the posterior pituitary gland in response to the stimulation of osmoreceptors residing in the anterior hypothalamus, baroreceptors in the great vessels, and volume receptors in the left atrium. The release of AVP results in increased water absorption by the renal tubule. Osmoreceptors detect increasing osmolarity, with sodium being the primary ion responsible for extracellular osmolarity. Baroreceptors and volume receptors regulate the intravascular volume. In cases of decreasing intravascular volume and diminishing osmolarity (due to body water in excess of body sodium), the volume receptors will override the osmoreceptors, resulting in AVP secretion and water retention, despite decreasing concentrations of sodium.¹

HYPERNATREMIA

Hypernatremia is defined as serum sodium >150 mEq/L. It may result from intake of sodium in excess of water, or more commonly, from loss of water in excess of sodium (Table 82-1). Primary sodium excess is usually associated with iatrogenic causes, such as inadequately diluted infant formula, excessive sodium bicarbonate administration, or intravenous hypertonic saline administration. More frequently encountered is hypovolemic hypernatremia, in which water loss exceeds sodium loss. The most common cause in pediatrics is gastroenteritis with diarrhea and vomiting. Other causes include increased insensible water loss (i.e., fever, use of radiant warming devices, burns), diabetes mellitus (solute diuresis), or inadequate access to free water.

Diabetes insipidus (DI) is a less common cause of hypovolemic hypernatremia. The essential feature is a functional lack of AVP, resulting in urinary water loss despite increasing osmolarity and hypovolemia. It may be caused by insufficient production and release of AVP (central DI) or end-organ unresponsiveness to AVP (nephrogenic DI). Disruption of the hypothalamic–pituitary axis by tumors, head trauma, hypoxic–ischemic brain injury, or neurosurgical procedures results in central DI. It is frequently seen in children near brain death. Nephrogenic DI is a congenital (x-linked recessive) disorder in which the AVP receptors in the renal tubules are defective and unable to respond to AVP. It is present at birth and can be life-threatening if unrecognized. Inappropriately dilute urine (osmolarity <150 mOsm/L or specific gravity <1.005), serum hyperosmolarity (osmolarity >295 mOsm/L), and hypernatremia characterize both central and nephrogenic DI. In acute situations, they may be differentiated by their responsiveness (central DI) or lack thereof (nephrogenic DI) to vasopressin.