The osmolality test is a snapshot of the number of solutes present in the plasma, urine, or stool. It is ordered to help evaluate the body’s water balance, its ability to produce and concentrate urine, to help investigate hyponatremia, to detect the presence of toxins such as methanol and ethylene glycol, and to monitor osmotically active drug therapies such as mannitol. It is also ordered to help monitor the effectiveness of treatment for any conditions found.

Plasma osmolality is primarily ordered to investigate hyponatremia. Hyponatremia may be due to sodium loss through the urine or due to increased fluid in the bloodstream. Increased fluid may be due to drinking excessive amounts of water, water retention, decreased ability of the kidneys to produce urine, or the presence of osmotically active agents such as glucose, mannitol, and glycine (a chemical used in surgical irrigation fluids). Marathon runners can experience acute hyponatremia by drinking large quantities of water in a short period of time. In a few cases, this has led to the death of the runner. People who chronically drink excessive amounts of water, by choice or due to a psychological condition, may have chronic hyponatremia. Patients may also appear to have low sodium levels when the percentage of water in their blood decreases due to the presence of increased proteins or lipids.

Mannitol, glycine, and the ingestion of toxins such as methanol and propylene glycol can be detected, evaluated, and monitored by ordering an osmotic gap (also called osmolal gap). This calculation compares measured osmolality with measurements of the major solutes. The osmotic gap is the difference between them and represents the presence of an osmotically active substance in the blood. In order to calculate the osmotic gap, tests for blood sodium, blood urea nitrogen (BUN), and glucose must be performed. Some versions of the osmotic gap calculation also include the measurement of ethanol. An example calculation is:

Plasma Osmotic Gap (Ethanol not always included)

2 x (Na+) + (Glucose/18) + (BUN/2.8) + (Ethanol/3.8)

Note: Glucose, BUN, and Ethanol may be reported in mg/dL (milligrams per deciliter) or mmol/L (millimole per liter). The numbers shown in the equation above are used to convert from mg/dL to mmol/L.

Urine osmolality is frequently ordered along with plasma osmolality. It is used to help evaluate the body’s water balance and to investigate increased and decreased urine output. Increased urine output may be due to increased fluid intake, lack of appropriate amounts of ADH, or diabetes mellitus (increased glucose levels leading to increased urine output). Decreased urine output may be due to a variety of causes including decreased blood flow to the kidneys, an appropriate response to dehydration, or damage to tubular cells in the kidneys. Urine sodium and creatinine are often ordered along with urine osmolality. Sometimes a urine osmotic gap is calculated and used to help evaluate the kidney’s ability to excrete acid and reabsorb bicarbonate, to detect the presence of osmotically active molecules, and to compare with the plasma osmotic gap.

Stool osmolality may sometimes be ordered to help evaluate chronic diarrhea that does not appear to be due to a bacterial or parasitic infection or to another identifiable cause such as intestinal inflammation or damage. Patients with watery chronic diarrhea may have an osmotically active substance (such as a commercial laxative) that is inhibiting the reabsorption of water by the intestines. Sometimes a stool osmotic gap is calculated.

A plasma osmolality test and osmotic gap may be ordered when a patient has symptoms such as thirst, confusion, nausea, headache, lethargy, seizures, or coma that the doctor suspects may be due to hyponatremia or the ingestion of a toxin such as methanol or ethylene glycol. A urine osmolality test may be ordered along with plasma testing when the doctor wants to compare urine results with the plasma osmolality and/or when the patient is producing increased or decreased quantities of urine. Both may be ordered when a doctor suspects that the patient may have diabetes insipidus. Osmolality testing may be ordered on asymptomatic patients with unexplained hyponatremia when a low sodium is discovered during testing for other reasons. Plasma and urine osmolality testing may be ordered frequently to monitor the effectiveness of treatment for these conditions and at regular intervals to monitor patients taking mannitol.

Stool osmolality may be ordered when the doctor suspects that a patient’s chronic diarrhea may be due to an osmotically active substance.

Osmolality is dynamic and will fluctuate as the body responds to and corrects temporary water imbalances. Plasma and urine osmolality tests must be evaluated in the context of the patient’s clinical presentation and along with the findings of other tests, such as sodium, glucose, and BUN. Osmolality results are not diagnostic; they suggest that a patient has an imbalance but they do not pinpoint the cause.

In general, if a patient has an increased plasma osmolality, it is due to either decreased water in the blood or increased solutes. If they have decreased plasma osmolality, it is due to increased fluid levels. When a patient has an increased osmotic gap and is suspected of ingesting a toxin such as methanol, then it is likely that they have, with the size of the gap related to the amount of toxin. During monitoring, if osmolality, the osmotic gap, and findings such as a low sodium level return to normal, then treatment has been effective. With mannitol therapy, the monitoring goal is the maintenance of a stable “therapeutic” osmotic gap and the relief of cerebral edema.

Plasma osmolality may be increased with:

dehydration

diabetes insipidus

hyperglycemia

hypernatremia

ingestion of ethanol, methanol, or ethylene glycol

kidney damage

mannitol therapy

shock

Plasma osmolality may be decreased with:

excess hydration

hyponatremia

inappropriate ADH secretion

When a patient has increased urine output and a low osmolality, then they are either ridding their body of excess fluids or unable to concentrate urine appropriately (which may be due to diabetes insipidus, a lack of ADH). If they have increased urine output and a high osmolality, then it may be due to diabetes mellitus. If a patient has decreased urine output and high osmolality, they may be dehydrated; if they have low or normal osmolality, they may have kidney damage.

Urine osmolality may be increased with:

congestive heart failure

hypernatremia

inappropriate ADH secretion

liver damage

shock

Urine osmolality may be decreased with:

diabetes insipidus

excess fluid intake

hypercalcemia

hypokalemia

kidney tubular damage

If a patient has an increased stool osmolality gap, then it is likely that an osmotically active substance is causing their chronic liquid diarrhea. This can be seen with malabsorption and laxative abuse.

A calculation is sometimes ordered for “free water clearance” to help evaluate the ability of the kidney tubules to appropriately concentrate and dilute urine. When urine osmolality is about the same as plasma osmolality, then free water clearance is zero. When blood volume decreases and urine is concentrated, then free water clearance will be negative. When fluid levels are increased and urine is dilute, then free water clearance will be positive.