Serum osmolality and hyperosmolar states

Serum osmolality is the sum of the osmolalities of every single dissolved particle in the blood such as sodium and associated anions, potassium, glucose, and urea. Under normal conditions, serum sodium concentration is the major determinant of serum osmolality. Effective blood osmolality, so-called blood tonicity, is created by the endogenous (e.g., sodium and glucose) and exogenous (e.g., mannitol) solutes that are capable of creating an osmotic gradient across the membranes. In case of change in effective blood osmolality, water shifts from the compartment with low osmolality into the compartment with high osmolarity in order to restore serum osmolality. The difference between measured osmolality and calculated osmolarity forms the osmolal gap. An increase in serum osmolal gap can stem from the presence of solutes that are not included in the osmolarity calculation, such as hypertonic treatments or toxic alcoholic ingestions. In clinical practice, determination of serum osmolality and osmolal gap is important in the diagnosis of disorders related to sodium, glucose and water balance, kidney diseases, and small molecule poisonings. As blood hypertonicity exerts its main effects on the brain cells, neurologic symptoms varying from mild neurologic signs and symptoms to life-threatening outcomes such as convulsions or even death may occur. Therefore, hypertonic states should be promptly diagnosed and cautiously managed. In this review, the causes and treatment strategies of hyperosmolar conditions including hypernatremia, diabetic ketoacidosis, hyperglycemic hyperosmolar syndrome, hypertonic treatments, or intoxications are discussed in detail to increase awareness of this important topic with significant clinical consequences.