How is hyponatremia diagnosed?

Labs measure serum sodium with an ion-selective electrode (ISE) using one of two approaches: the indirect method, which involves diluting the sample prior to measurement, and the direct method, which uses neat, undiluted sample. Although newer technologies require much smaller sample volumes, an estimated 83% of laboratories still measure sodium levels using an indirect methodology.

Overall, serum osmolality and urinary sodium measurements are integral to the diagnosis and management of hyponatremia. Also required are clinical assessment and additional laboratory investigations that may include measuring urine osmolality, serum aldosterone, cortisol, and natriuretic peptide levels.

What methods are used to determine serum osmolality?

Serum osmolality is measured using either freezing point depression or vapor pressure techniques. Sodium is the predominant extracellular solute and major contributor to serum osmolality, while other constituents include glucose and urea. Several formulas are available for calculating serum osmolality, but this one is the most widely used: osmolality = 2 x [Sodium] + [Glucose]/18 + [Urea]/2.8.

What does low serum osmolality indicate?

Potential causes of hyponatremia associated with low osmolality (hypotonicity) and excess extracellular fluid include heart failure, liver cirrhosis, and renal impairment. In patients with heart failure, B-type natriuretic peptides will be increased and urinary sodium will be > 20 mmol/L. Urinary sodium will be low in patients with liver cirrhosis, whereas patients with reduced renal function will also exhibit high urinary sodium because the kidneys aren’t properly reabsorbing it.

Hyponatremia, low osmolality, and normal fluid levels can also indicate renal impairment, as well as the syndrome of inappropriate antidiuretic hormone secretion, adrenal insufficiency, and hypothyroidism. Each of these conditions is characterized by normal or low urea, low creatinine and urea/creatinine ratio, low uric acid, and a urinary sodium ≥ 20–30 mmol/L.

Potential causes of hyponatremia, low osmolality, and fluid loss include gastrointestinal disorders, diuretic therapy, and exercise. Another culprit is cerebral salt loss following a subarachnoid hemorrhage, head injury, or neurological procedures. Typical lab values with these conditions include elevated urea, elevated creatinine and urea/creatinine ratio, elevated uric acid, and a reduced urinary sodium < 20–30 mmol/L.

What does normal serum osmolality indicate?

Hyponatremia in patients with normal osmolality (isotonicity) suggests the presence of pseudohyponatremia, for which corrective action is not required. This can be confirmed by testing for elevated lipids and/or proteins.

When lipids and/or proteins are present in plasma in increased concentrations, this can decrease the percentage of plasma water in the blood. This does not impact direct methods for measuring sodium. However, with indirect methods that apply a dilution step prior to sample analysis, this can lead to falsely low sodium results.

What does high serum osmolality indicate?

Hyperglycemia can cause apparent hyponatremia, and may result in osmotic diuresis leading to high osmolality (hypertonicity). High glucose drives water from the intracellular to the extracellular space, diluting sodium concentration. In such a case, measured sodium levels can be corrected by adding 1.6 to 2.4 mmol of sodium for every 100 mg/dL of glucose above 100 mg/dL. High osmolality can also suggest the presence of other solutes such as mannitol.

What leads to a false hyponatremia result?

In addition to pseudohyponatremia, spurious hyponatremia can occur if a sample is contaminated with intravenous fluid containing sodium at less than half that of serum, such as in dextrose infusion. A simple repeat collection often resolves the issue.

Ibrahim A. Hashim, PhD, DABCC, FACB, is the Arthur J. Gill Professor of Pathology, chief of clinical pathology, and clinical chemistry director at the University of Texas Southwestern Medical Center in Dallas. +Email: Ibrahim.Hashim@utsouthwestern.edu