Osmolality and Osmolal Gap
When you may have ingested methanol, ethylene glycol, or isopropyl alcohol; when you have a low blood sodium level
No test preparation may be needed; follow any instructions you are given. Some healthcare practitioners may instruct you to fast (nothing to eat or drink except water) for 6 hours before the test, and/or limit fluids for 12-14 hours before the test.
Osmolality is a measure of the number of dissolved particles in a fluid. A test for osmolality measures the amount of dissolved substances such as sodium, potassium, chloride, glucose, and urea in a sample of blood and sometimes in urine. Alternatively, it can be estimated from the major solutes expected to be in the blood or urine.
Water balance in the body is a dynamic process that is regulated by controlling the amount of water eliminated in the urine by the kidneys and by increasing or decreasing water drinking by regulating "thirst." In a healthy person, the body perceives and reacts to changes in the amount of water and particles in the blood.
- When blood osmolality increases with a decrease in the amount of water in the blood or an increase in the number of particles such as sodium, chloride, and glucose, a gland called the hypothalamus releases antidiuretic hormone (ADH). The kidneys respond to ADH by conserving water and producing urine that is more concentrated. The retained water dilutes the blood and lowers blood osmolality back to normal. This also increases blood volume and blood pressure. If this is not sufficient to restore the water balance, then thirst is also stimulated so that the affected person will drink more water.
- When blood osmolality decreases, the release of ADH is suppressed, the kidneys release more dilute urine, the amount of water in the body decreases, thirst is diminished, and blood osmolality increases back toward normal.
A blood (serum) osmolality test is primarily a measure of sodium dissolved in the serum (the liquid portion of blood). Sodium is the major electrolyte in the blood and urine. It works with potassium, chloride, and CO2 (in the form of bicarbonate) to maintain electrical neutrality in the body and acid-base balance. Sodium comes into the body in the diet and is normally conserved or eliminated in the urine by the kidneys to maintain its concentration in the blood within a healthy range.
In addition to electrolytes, glucose and urea contribute to osmolality. Normally their contributions are small, but when someone has high blood glucose (hyperglycemia, as found in untreated diabetes) or high blood urea (seen in diseases such as kidney failure), their influence can be significant.
Serum osmolality is often used in cases of suspected poisoning or overdose. Toxins such as methanol, isopropyl alcohol, ethylene glycol, propylene glycol, and acetone, and drugs such as salicylates (aspirin) can also affect osmolality when ingested in sufficiently large amounts.
A urine osmolality test primarily measures the waste products urea and creatinine. Urea and creatinine are produced and removed by the body at a relatively constant rate.
A serum osmolal gap (osmotic gap) may also be calculated. It is the difference between measured and calculated (estimated) osmolality results. In order to calculate the osmolal gap, tests for blood sodium, blood urea nitrogen (BUN), and glucose must be performed to calculate the expected osmolality. Some versions of the expected osmolality calculation also include the measurement of ethanol. An increase in the osmolal gap (greater than 10) indicates the presence of substances such as toxins, aspirin (salicylates), or mannitol.
How is the test used?
The blood osmolality test is primarily used to help determine whether a person has ingested a toxin such as methanol or ethylene glycol (antifreeze). Sometimes it may be used to investigate low blood sodium and your body’s water balance. Osmolality may be measured directly or estimated using a calculation.
In addition to osmolality, the osmolal gap (osmotic gap) may be calculated and used to detect and/or measure toxins in the blood, such as methanol, ethylene glycol, isopropyl alcohol, and propylene glycol.
Urine osmolality may be used along with serum osmolality to help evaluate the body's water balance and to investigate increased and decreased urination. Urine sodium and creatinine are often ordered along with urine osmolality. Sometimes a urine osmolal gap is calculated and used to help evaluate the kidney's ability to eliminate acid and reabsorb bicarbonate, to detect the presence of osmotically active molecules, and to compare with the serum osmolal gap.
When is it ordered?
This test may be ordered when it is suspected that someone has ingested a toxin such as methanol or ethylene glycol.
Testing may be ordered when a person has an unexplained low blood sodium or signs and symptoms that a healthcare practitioner suspects may be due to low blood sodium such as:
- Excessive thirst
- In severe cases, seizures or coma
A urine osmolality test may be ordered along with blood testing when a health practitioner wants to compare urine results with the serum osmolality and/or when the person being tested is producing increased or decreased amounts of urine.
What does the test result mean?
Osmolality is dynamic and will fluctuate as the body responds to and corrects temporary water imbalances. Serum and urine osmolality tests must be evaluated in the context of the person's signs and symptoms and along with the findings of other tests, such as sodium, glucose, and blood urea nitrogen (BUN). Osmolality results are not diagnostic; they suggest that a person has an imbalance, but they do not pinpoint the cause.
In general, increased serum osmolality may be due to either decreased water in the blood or increased solutes. Examples of conditions in which blood (serum) osmolality may be increased include:
- Toxic ingestion of ethanol, methanol, ethylene glycol, isopropyl alcohol or aspirin (salicylates), for example
- Increase blood glucose
- Increased blood sodium
- Increased nitrogen waste products in the blood (uremia)
- Stroke or head trauma that leads to decreased antidiuretic hormone (ADH)
- Kidney damage and disease
- Mannitol therapy--used in the treatment of brain swelling (cerebral edema)
In general, a decreased serum osmolality may be due to increased fluids. Examples of conditions causing decreased blood osmolality include:
- Excess hydration (drinking excessive amounts of water, water retention or decreased ability of the kidneys to produce urine)
- Decreased blood sodium
- Increased ADH secretion
A serum osmolal gap of greater than 10 is considered abnormal and indicates the presence of an osmotically active substance in the blood. When someone has an increased osmolal gap, a toxic ingestion, such as methanol, is suspected, and the size of the gap is proportional to the amount of toxin. Other common causes of an elevated osmolal gap are alcoholic ketoacidosis, kidney failure, diabetic ketoacidosis, and shock. During monitoring of treatment, the osmolal gap, and findings such as a low sodium level, return to normal.
Urine osmolality is often evaluated in the context of how much urine the person is producing. Increased amounts of urine may be due to increased fluid intake, lack of appropriate amounts of ADH, or diabetes, with increased glucose levels leading to increased urine output. Decreased amounts of urine 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.
- When a person produces increased amounts of urine and urine osmolality is low, then the person either is ridding their body of excess fluids or is unable to concentrate urine appropriately.
- Increased amounts of urine and a high osmolality may be seen when there is a substance being flushed from the body, such as excess glucose with diabetes.
- If a person produces decreased amounts of urine and has high urine osmolality, then the person may be dehydrated
- If someone produces decreased amounts of urine and has low or normal urine osmolality, the person may have kidney damage.
Examples of conditions that can cause increased urine osmolality include:
- Congestive heart failure
- Increased sodium
- Inappropriate ADH secretion
- Adrenal insufficiency/Addison's disease
- Liver damage
- Glucose in the urine (from uncontrolled diabetes)
Examples of conditions that can cause decreased urine osmolality include:
What is the formula for calculating osmolality?
In order to calculate the osmolal gap, tests for blood sodium, blood urea nitrogen (BUN), and glucose must be performed to calculate the expected osmolality. Some versions of the expected osmolality calculation also include the measurement of ethanol. An example calculation is:
Serum Osmolality Calculation (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. For mmol/L, the equation would be:
2 x (Na+) + (Glucose) + (BUN) + (Ethanol)
How is the serum osmolal gap calculated?
Serum osmolal gap = serum osmolality (measured) – serum osmolality (calculated)
My doctor ordered a stool osmolality test. Why?
A stool osmolality test may sometimes be used 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. For the test, a fresh (refrigerated or frozen within about 30 minutes of collection), liquid stool that is not contaminated by urine is collected in a clean container. Bacteria in the stool can change the results of the test within a short period of time.
People 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 osmolal gap is also calculated. An increased stool osmolal gap with chronic diarrhea is likely caused by an osmotically active substance, which can be seen with malabsorption and laxative abuse.
What is the difference between urine osmolality and specific gravity?
Specific gravity is a common part of a urinalysis. It evaluates the weight of solids in water. Osmolality and specific gravity usually change in parallel to each other. When large and heavy molecules (such as glucose and protein) are present in the urine, however, the results will diverge. Specific gravity will be increased more, due to the weight of the molecules, while urine osmolality will be increased less, reflecting the number of molecules. Generally, osmolality is considered a more exact measurement of urine concentration than specific gravity.
What is the difference between osmolality and osmolarity?
Osmolality measures the concentration of solutes in a fluid by looking at the number of particles per weight (kilogram) of fluid. Osmolarity evaluates the number of particles per volume (liter) of fluid. With dilute fluids, they are essentially the same, but differences will be more noticeable at higher concentrations and care must be taken when comparing them as the units for osmolality and osmolarity are not the same.