Osmolality (Osmolarity)
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An osmolality (osmolarity) test measures the concentration of dissolved particles in the blood, urine or sometimes stool using a blood or urine sample. It is used to assess the body’s fluid balance and kidney function, and to help investigate conditions such as dehydration, hyponatraemia or exposure to certain toxins.
Why get tested?
Serum and urine osmolality may be measured together to investigate the cause of a low serum sodium concentration (hyponatraemia), high serum sodium concentration (hypernatraemia), a high or low urine output or excessive thirst. Serum osmolality may also be measured when ingestion of toxic alcohols, such as methanol and ethylene glycol, are suspected. Very rarely stool osmolality is measured to help determine the cause of diarrhoea.
When to get tested?
Serum and urine osmolality may be tested in patients with a low serum sodium concentration, a high serum sodium concentration, an unusually high urine output, an unusually low urine output or excessive thirst.
Serum osmolality should be tested if toxic alcohol poisoning is suspected.
Stool osmolality may rarely be tested in patients with diarrhoea.
Sample required?
A blood sample taken from a vein in your arm; a spot urine sample taken at the same time usually helps the doctor to interpret the results. Local protocols should be followed for fluid deprivation tests when investigating diabetes insipidus. Faecal osmolality requires either a 24-hour collection or freshly passed diarrhoeal stool (faecal osmolal gap).
Test preparation needed?
If required, follow any instructions provided (e.g. paired serum and urine samples before treating low sodium, first morning urine, fluid restriction and timed sampling for a fluid deprivation test). Inform your health care provider of all medications you are taking, for example mannitol.
What is being tested?
Osmolality is a measure of the number of osmotically active solute particles dissolved in a kilogram of solvent (water in biological systems). These osmotically active substances increase osmolality of a fluid and cause solvent (water) to move across membranes. Osmolarity is the number of particles in a litre of fluid. For clinical purposes, osmolality and osmolarity values are approximately the same and used interchangeably. Unlike osmolarity, osmolality is unchanged by temperature.
Serum osmolality is an important stimulus for maintaining water balance by controlling the amount of water excreted in the urine and by regulating water intake through the sensation of thirst. In health, the osmolality of blood is very tightly regulated. Osmotic sensors in the body detect changes in the amount of particles in water in the bloodstream (osmolality). When blood osmolality increases, for example in dehydration, the hypothalamus promotes secretion of the hormone antidiuretic hormone (ADH) from the posterior pituitary. ADH signals for the kidneys to reabsorb and conserve water, resulting in formation of concentrated urine (which has a high osmolality). This retention of water dilutes the blood causing a decrease in osmolality back to normal levels. Increased osmolality also causes a sensation of thirst to promote increased fluid (water) intake which helps to return osmolality to normal levels. If blood osmolality decreases, for example following a large drink of water, then ADH secretion is suppressed and the kidneys excrete increased amounts of dilute urine (with low osmolality). Combined with decreased thirst and therefore decreased fluid (water) intake, this results in a decrease in the amount of water in the body, and so blood osmolality rises to normal. Urine osmolality is a measure of the kidney’s ability to concentrate urine; the more concentrated the urine is, the higher its osmolality. Urine osmolality is largely due to the presence of urea and creatinine. If serum and urine osmolality are not in keeping with each other this may indicate a problem with water balance which may manifest in abnormal sodium results.
Osmolality can be measured directly in the laboratory using an osmometer, often by freezing point depression.
Common questions
Under normal conditions blood and urine osmolality are dependant on each other as urine osmolality changes to maintain a normal blood osmolality. Paired serum and urine osmolality are measured in patients with abnormal sodium or water balance as the relative values can help identify the likely cause of low blood sodium, high blood sodium, high or low urine output and excessive thirst. Differences between measured and calculated blood osmolality are particularly useful in investigating suspected poisoning. Faecal osmolality and osmolal gap have a very minor role in investigating diarrhoea.
Serum and urine osmolality may be tested in patients with a low serum sodium concentration, a high serum sodium concentration, an unusually high urine output, an unusually low urine output or excessive thirst. They help evaluate the body’s sodium and water balance and its ability to appropriately produce and concentrate urine. Serum osmolality can help identify the presence of toxic alcohols when poisoning is suspected. Stool osmolality may very rarely be tested in patients with diarrhoea.
Physiological mechanisms normally maintain plasma osmolality within a tight range.
A high plasma osmolality may be observed in water depletion (dehydration) with reduced urine output, an elevated blood glucose with increased urine output due to uncontrolled Diabetes Mellitus, following ingestion of toxins (including alcohol) and in Diabetes Insipidus (“water diabetes”, a condition in which the urine is always very dilute leading to water loss from the body and possible dehydration).
A decreased plasma osmolality may be seen in water intoxication or any disorder that causes water retention by the kidneys. For example, in a disorder called Syndrome of Inappropriate Antidiuresis (SIAD).
Serum and urine osmolality are often used together to help investigate causes of low serum sodium (hyponatraemia), with the urine osmolality giving information on how concentrated the urine is. Hyponatraemia can occur either due to loss of sodium (e.g. in the urine) or increased fluid volume in the bloodstream. Increased fluid may be due to either increased intake of fluids (e.g. excessive drinking) or retention of fluid by the kidneys (observed as decreased urine output). People who chronically drink excessive amounts of water, either by choice or due to a psychological condition (or associated medication) or brain injury, may have chronic hyponatraemia. The serum osmolality is used to distinguish low sodium with low blood osmolality (hypotonic hyponatraemia) from pseudohyponatraemia (low sodium with normal blood osmolality, for example in patients with high proteins and triglyceride) and low sodium with high blood osmolality (hyperosmolal hyponatraemia, for example in patients with high glucose, ethylene glycol, urea, or mannitol concentrations). This can help direct further investigation and treatment. When blood sodium is low, increased excretion of water in urine can help to return sodium concentration to normal. This results in dilute urine with low osmolality. However, in patients with SIAD there is overproduction of anti-diuretic hormone (ADH) by the hypothalamus resulting in a dilute serum (with low sodium and low osmolality) in the presence of inappropriately concentrated urine (with higher than expected osmolality). This is a diagnosis of exclusion in patients with low sodium.
Serum and urine osmolality also has a role in investigating high blood sodium (hypernatraemia), high urine output and excessive thirst. Increased urine output may be due to a high fluid intake, elevated levels of an osmotically active agent in the urine (e.g. glucose in diabetes mellitus) or inappropriate / absent ADH action (as in Diabetes Insipidus).
Decreased urine output may also be due to a variety of causes, including an appropriate response to dehydration, decreased blood flow to the kidneys or damage to tubular cells in the kidneys. High urine concentrations of osmotically active substances such as glucose or mannitol in the urine can increase urine osmolality and, thus, urine volume and this is termed osmotic diuresis. The accompanying water loss can cause high serum sodium concentration and a sensation of thirst.
Diabetes insipidus (DI) can also cause high urine output (>3 L per day), high sodium and thirst. It results from too little ADH or failure of the kidneys to respond to ADH. People with diabetes insipidus can have a high plasma osmolality in the presence of inappropriately dilute urine. High concentrations of calcium or low concentrations of potassium in the blood can also impair the kidneys response to ADH, causing symptoms of diabetes insipidus. It is diagnosed using a water deprivation test which should be considered in patients with proven high urine volume (polyuria) and a spot urine osmolality which is inappropriately low compared with a high serum osmolality. During the water deprivation test fluid intake is restricted and frequent weight, serum and urine osmolality and electrolyte (sodium) measurements are taken. Decreased fluid intake should result in a lower volume of more concentrated urine with higher osmolality. Failure to concentrate urine in response to fluid deprivation (shown by little change in urine osmolality from a low level) supports a diagnosis of DI. Synthetic ADH (e.g. desmopressin) can be administered part-way through the test to distinguish failure to produce ADH by the pituitary from failure of the kidneys to respond to ADH. This test has risks so should only be performed carefully by specialist medical teams.
Measured and calculated serum osmolality has a role in detecting the presence of ingested toxins such as methanol, ethylene glycol and isopropyl alcohol. Serum osmolality can be measured directly. Particles that contribute to osmolality in serum include sodium, chloride, potassium, bicarbonate, glucose and urea. Several different equations can also be used to calculate (estimate) osmolality, and there is a lack of clear consensus on the best equation to use. Equations (with glucose and urea in mmol/L) include:
Calculated serum osmolality = 1.89 (sodium) + 1.38 (potassium) + 1.08
(glucose) + 1.03 (urea) + 7.45
Calculated serum osmolality = 2 (sodium + potassium) + glucose + urea
Calculated serum osmolality = 2 (sodium) + glucose + urea
Calculated serum osmolality = 1.86 (sodium) + glucose + urea + 9
The difference between measured and calculated serum osmolality (i.e. calculated – measured osmolality) is called the osmolar or osmolal gap. An increase in the osmolar gap (greater than 10 mOsm/kg) indicates the presence of other osmotically active substances, such as toxic alcohols or mannitol, that contribute to osmolality but are not routinely or easily measured.
Faecal (stool) osmolality is rarely requested but can help evaluate diarrhoea for which a cause cannot be found. Watery diarrhoea may be caused by an osmotically active substance e.g. carbohydrate malabsorption that inhibits reabsorption of water by the intestines. Sometimes a stool osmolar gap is calculated. Although not routinely measured, faecal osmolality (in a 24 h specimen) is close to that in plasma (~290 mOsm/kg). A low faecal osmolality suggests factitious diarrhoea as the colon cannot produce stools with osmolality less than that in plasma. Stool sodium, potassium, magnesium, and phosphate may be measured in these people. High faecal osmolality may suggest sample contamination with urine, or bacterial break-down of carbohydrates to produce osmotically active molecules in old samples. The faecal osmolal gap in a freshly passed diarrheal stool is calculated using the formula: Stool osmolal gap = Stool osmolality – 2 x (stool sodium + stool potassium). A gap < 50 mOsmol/kg is compatible with secretory diarrhoea whereas a gap > 125 mOsmol/kg is compatible with osmotic diarrhoea. Laxatives can be either secretory or osmotic.
Calculation of “free water clearance” is sometimes used 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.
Yes. Sometimes people need to be referred to an endocrinologist (a doctor who deals with abnormalities of the hormone producing glands) since abnormal hormone production may be responsible for a low or high plasma osmolality.