The latest review in the Disorders of Fluids and Electrolytes series considers the causes and consequences of an abnormal plasma sodium concentration and offers a framework for correcting it.
Human cells dwell in salt water. Their well-being depends on the ability of the body to regulate the salinity of extracellular fluids. By controlling water intake and excretion, the osmoregulatory system normally prevents the plasma sodium concentration from straying outside its normal range (135 to 142 mmol per liter). Failure of the system to regulate within this range exposes cells to hypotonic or hypertonic stress.
• What factors determine plasma sodium concentration, and how does plasma sodium concentration affect cell volume?
Solute concentrations (osmolalities) must be equal inside and outside of cells because water channels (aquaporins) make cell membranes permeable to water. Although sodium is largely extracellular and potassium is intracellular, body fluids can be considered as being in a single “tub” containing sodium, potassium, and water, because osmotic gradients are quickly abolished by water movement across cell membranes. As such, the concentration of sodium in plasma water should equal the concentration of sodium plus potassium in total body water.
Plasma [Na+] = total body (Na+ + K+)/total body H20.
This concentration is altered by net external balances (intake minus output) of sodium, potassium, and water and by internal exchange between sodium that is free in solution and sodium that is bound to polyanionic proteoglycans in bone, cartilage, skin, and connective tissue. The term “tonicity” describes the effect of plasma on cells — hypotonicity makes cells swell and hypertonicity makes them shrink. Hypernatremia always indicates hypertonicity. Hyponatremia usually indicates hypotonicity, but there are exceptions.
Figure 1. Internal and External Solute and Water Balance and the Plasma Sodium Concentration.
• What determines the tonicity of urine, and is urinary sodium excretion linked to plasma sodium concentration?
The electrolyte concentration (sodium plus potassium) of urine, and not its osmolality (which includes electrolytes, urea, and glucose), determines its effect on the plasma sodium concentration. Urine is hypotonic if its electrolyte concentration is lower than that of plasma; because it is partly composed of electrolyte-free water, it will increase plasma sodium concentrations. Conversely, urine is hypertonic if its electrolyte concentration is higher than that of plasma; its excretion will lower plasma sodium concentrations. Urinary excretion of sodium is relatively independent of plasma sodium levels. Excretion of sodium responds to intravascular volume, increasing with volume expansion and decreasing with volume depletion.
Morning Report Questions
Q: What are general guidelines for the management of hyponatremia?
A: Hyponatremia is usually a chronic condition; to reduce symptoms and improve potential outcomes, it should be corrected gradually with the use of fluid restriction, salt tablets, slow infusions of 3% saline, furosemide, urea, or vasopressin antagonists, or by treatment of the underlying cause. Even when symptoms are severe, chronic hyponatremia need not be corrected by increasing the plasma sodium concentration by more than 4 to 6 mmol per liter per day. Regardless of how chronic hyponatremia is treated, inadvertent overcorrection, most commonly caused by excretion of dilute urine, is common and can be very dangerous. If the plasma sodium concentration is less than 120 mmol per liter, or if there are risk factors for osmotic demyelination, correction of the plasma sodium concentration by more than 8 mmol per liter per day should be meticulously avoided through replacement of lost water or prevention of water loss with desmopressin, a synthetic vasopressin.
Table 1. Treatment and Limits of Correction of Severe Hyponatremia.
Table 2. Treatment and Limits of Correction of Severe Hypernatremia.
Q: What are the consequences of rapid changes in plasma sodium concentration?
A: Although osmotic disturbances affect all cells, clinical manifestations of hyponatremia and hypernatremia are primarily neurologic, and rapid changes in plasma sodium concentrations in either direction can cause severe, permanent, and sometimes lethal brain injury. If severe hypernatremia develops over a period of minutes (e.g., after massive ingestion of salt that may occur in a suicide attempt), vascular injury created by a suddenly shrinking brain causes intracranial hemorrhage. Brain swelling from an abrupt onset of hyponatremia results in increased intracranial pressure, impairing cerebral blood flow and sometimes causing herniation. Brain injury after rapid correction of chronic hyponatremia manifests as a biphasic illness called the osmotic demyelination syndrome: an initial reduction in symptoms is followed by a gradual onset of new neurologic findings. The clinical spectrum of the osmotic demyelination syndrome is broad and can include seizures, behavioral abnormalities, and movement disorders. The most severely affected patients become “locked in,” unable to move, speak, or swallow because of demyelination of the central pons. Acute hypernatremia may also cause brain demyelination, without the biphasic clinical course of the osmotic demyelination syndrome.
Figure 3. Consequences of Rapid Changes in the Plasma Sodium Concentration.