Hyponatremia and Hypoosmolar Disorders

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The incidence of hyponatremia depends on the population screened and the criteria used to define the disorder. Hospital incidences of 15% to 22% are common if hyponatremia is defined as any serum sodium concentration ([Na ⁺ ]) of less than 135 mmol/L, but in most studies only 1% to 4% of patients have a serum [Na ⁺ ] lower than 130 mmol/L, and fewer than 1% have a value lower than 120 mmol/L. Multiple studies have confirmed prevalence ranging from 7% in ambulatory populations up to 38% in acutely hospitalized patients. Older individuals are particularly susceptible to hyponatremia, with reported incidence as high as 53% among institutionalized geriatric patients. Although most cases are mild, hyponatremia is important clinically because (1) acute severe hyponatremia can cause substantial morbidity and mortality; (2) mild hyponatremia can progress to more dangerous levels during management of other disorders; (3) general mortality is higher in hyponatremic patients across a wide range of underlying comorbidities; and (4) overly rapid correction of chronic hyponatremia can produce severe neurologic complications and death.

Definitions

Hyponatremia is of clinical significance only when it reflects corresponding plasma hypoosmolality. Plasma osmolality (P _osm ) can be measured directly by osmometry and is expressed as milliosmoles per kilogram of water (mOsm/kg H ₂ O). P _osm can also be calculated from the serum [Na ⁺ ], measured in millimoles per liter (mmol/L), and the glucose and blood urea nitrogen (BUN) levels, both expressed as milligrams per deciliter (mg/dL), as follows:

Because the glucose and BUN concentrations are normally dwarfed by the sodium concentration, osmolality often is estimated simply by doubling the serum [Na ⁺ ]. All three methods produce comparable results under most conditions. However, total osmolality is not always equivalent to effective osmolality , which is sometimes referred to as the tonicity of the plasma. Solutes that are predominantly compartmentalized in the extracellular fluid (ECF) are effective solutes because they create osmotic gradients across cell membranes and lead to osmotic movement of water from the intracellular fluid (ICF) compartment to the ECF compartment. In contrast, solutes that permeate cell membranes (e.g., urea, ethanol, methanol) are not effective solutes, because they do not create osmotic gradients across cell membranes, and therefore they are not associated with secondary water shifts. Only the concentration of effective solutes in plasma should be used to determine whether clinically significant hypoosmolality is present. In most cases, these effective solutes include sodium, its associated anions, and glucose (but only in the presence of insulin deficiency, which allows the development of an ECF/ICF glucose gradient); importantly, urea, a solute that penetrates cells, is not an effective solute.

Hyponatremia and hypoosmolality are usually synonymous, with two important exceptions. First, pseudohyponatremia can be produced by marked elevation of serum lipids or proteins. In such cases, the concentration of Na ⁺ per liter of serum water is unchanged, but the concentration of Na ⁺ per liter of serum is artifactually decreased because of the increased relative proportion occupied by lipid or protein. Although measurement of serum or plasma [Na ⁺ ] by ion-specific electrodes, currently used by most clinical laboratories, is less influenced by high concentrations of lipids or proteins than is measurement of serum [Na ⁺ ] by flame photometry, such errors nonetheless can still occur when serum samples are diluted before measurement in autoanalyzers. However, because direct measurement of P _osm is based on the colligative properties of only the solute particles in solution, increased lipids or proteins will not affect the measured P _osm . Second, high concentrations of effective solutes other than Na ⁺ can cause relative decreases in serum [Na ⁺ ] despite an unchanged P _osm ; this commonly occurs with marked hyperglycemia. Misdiagnosis can be avoided again by direct measurement of P _osm or by correcting the serum [Na ⁺ ] by 1.6 mmol/L for each 100 mg/dL increase in blood glucose concentration greater than 100 mg/dL (although some studies have suggested that 2.4 mmol/L may be a more accurate correction factor, especially when the glucose is very high).

Pathogenesis

The presence of significant hypoosmolality always indicates an excess of water relative to solute in the ECF. Because water moves freely between the ICF and ECF, this also indicates an excess of total body water relative to total body solute. Imbalances between water and solute can be generated initially either by depletion of body solute more than body water or by dilution of body solute because of increases in body water out of proportion to body solute ( Box 7.1 ). However, this distinction represents an oversimplification, because most hypoosmolar states include variable contributions of both solute depletion and water retention. For example, isotonic solute losses occurring during an acute hemorrhage do not produce hypoosmolality until the subsequent retention of water from ingested or infused hypotonic fluids causes a secondary dilution of the remaining ECF solute. Nonetheless, this concept has proved useful because it provides a logical framework for understanding the diagnosis and treatment of hypoosmolar disorders.