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Home , Osmol gap, Plasma osmolality, Urine osmolality

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Osmolality of , and stool

Objectives of this article: 1) What is Osmolality? 2) What are the osmotically active particles of serum, urine and stool? 3) What is the significance of osmolality determination in serum, urine and stool? 4) Determination of osmolality and the normal values – an overview. 5) Case studies and discussion.

What is osmolality?

Osmolality is the determination of the total number of osmotically active particles or ions dissolved in a kilogram of a (serum, urine and stool). It basically measures its solute (particles or ions)/water ratio in the solution.

This reflects the balance between the water and solutes in body fluids and portrays a picture of the overall water balance in the total body.

What are the osmotically active particles in serum, urine and stool?

Sodium, potassium, chloride, , and urea are the osmotically important body fluid solutes.

It is important to note that the size of the particle is not important so that a single ion, e.g. sodium, contributes as much to the serum osmolality as a single large protein molecule, e.g. albumin.

In fact small molecules, like sodium, potassium, chloride, bicarbonate, urea and glucose if present in high concentrations can individually affect the osmolality of a body fluid. Together these make up over 95%of total osmolality of serum.

Large serum components like albumin the most abundant serum protein contribute little to the overall osmolality.

Only a few exogenous compounds such as , , and manitol can be present in the at high enough quantities to significantly affect the osmolality.

If the ration of these osmolar active solutes to water increases the osmolality of the body fluid will increase.

As Sodium is the most abundant extra cellular ion it is the most important osmolary active solute in serum, urine and stool.

Clinical significance Osmolality helps in the evaluation of the body's water balance. 2

Serum osmolality

It is a useful tool in investigating the cause of hyponatraemia.

If a patient with hyponatraemia (serum sodium < 130 mmol/L) has a normal osmolality (280 – 301 mOsm/kg), the patient may have pseudohyponatraemia due to excess lipids or proteins, or the sample may have been collected from a drip arm containing dextrose. This is known as isotonic hyponatraemia.

If the patient has hyponatraemia and an increased osmolality (> 301 mOsm/kg) it is likely the patient has reactive hyponatraemia due to an excess of solute in the extra cellular fluid pulling water out of cells (ICF-inter cellular fluid). Examples of this include increased extra cellular glucose in diabetes mellitus, mannitol treatment or uremia. This is known as hypertonic hyponatraemia.

Movement of water between compartments:

Compartmental exchange of water is regulated by osmotic and hydrostatic pressures. Exchanges between interstitial and intracellular fluids due to the selective permeability of the cellular membranes.www.williamsclass.com/.../Osmosis.gif copied 23/5/11

If ECF becomes hypertonic (increased concentrations of ions) relative to ICF, water moves from ICF to ECF

In patients with a hyponatraemia and a low osmolality (< 280 mOsm/kg) the hydrated state of the patient is critical in determining the cause of the hyponatraemia:

Pt with Edema: Normal hydration : Pt with : Renal failure Hypothyroidism Vomiting Congestive heart failure Hypoadrenalism Diarrhea Nephrotic syndrome Addison’s disease Burns Cirrhosis Metabolic alkalosis

The

The osmolar gap is used to indicate the presence of an exogenous solute affecting the osmolality.

Osmolality can both be measured and calculated (see methods to determine osmolality), the difference between the measured and calculated is known as the osmol gap.

The measured osmolality represents all the osmolar active particles present in the fluid at the time of measurement and includes exogenous solutes like ethanol, mannitol ext. 3

The calculated osmolality only calculates the active particles in the formula of the calculation and does not represent all the active particles.

By calculating the osmol gap we compare measured osmolality with calculated osmolality.

The normal osmolar gap is up to 10 mOsm/kg and values in excess of this usually indicate the presence of an exogenous agent. The most common agent is ethanol, but methanol, mannitol, ethylene glycol, and if present in sufficient quantities can increase the osmolar gap.

In an increased osmolar gap is due to the increased acetone.

Urine osmolality is frequently ordered along with serum osmolality. It is used to help evaluate the kidneys ability to dilute or concentrate the urine. But interpretation of the must be made with the patient’s state of hydration in mind.

It is used to determine the differential diagnosis of hyponatraemia (sodium levels > 150 mmol/L)

With Hyponatraemia it is important to measure the urine osmolality (normal 300 – 900 mOsm/kg- 24h specimen/with average fluid intake) together with the hydration state of the patient. Hyponatraemia is caused either by the excessive water loss (diluted urine) or failure to replace normal water losses (concentrated urine) and the decreased Sodium secretion in the (hormonal abnormalities).

Pt with normal hydration (euvolemia) Dehydrated patient Urine osmolality Urine osmolality Urine osmolality (< 800 mOsm/kg) (> 800 mOsm/kg) (> 800 mOsml/kg)

Diabetes insipidus Concentration of urine due to loss Diarrhea and water loss A deficiency of ADH hormone or a of water but with adequate water without sufficient water intake. insensitivity of the nephron to ADH intake. diluting the urine and increasing the Sodium levels in the blood. 4

Urine sodium and are often ordered along with urine osmolality.

Stool osmolality is used to calculate the faecal osmol gap. This helps evaluate chronic diarrhea (an increase in the amount, liquidity and frequency of stool) that does not appear to be due to a bacterial or parasitic infection or to another identifiable cause such as intestinal inflammation or damage. Normal fecal fluid has an osmolality close to that of plasma ( 290 mOsm/kg), sodium about 30 mmol/L, potassium about 75 mmol/L and magnesium about 50 – 100 mmol/L (depending on diet) but usually < 45 mmol/L.

By using the faecal osmolar gap and the faecal sodium levels we can distinguish between osmotic diarrhea and secretory diarrhea. (See flow diagram)

Faecal osmol gap (for calculation see methods), and sodium levels.

Faecal sodium of < 60 mmol/L and faecal Faecal Na > 90 mmol/L and faecal osmol gap < osmolar gap of > 100mOsm/kg 50 mOsm/kg

Osmotic diarrhea Secretory diarrhea

Osmotic diarrhea:

Conditions that increased osmolality Serum Urine

 Dehydration/sepsis/fever/ sweating/burns  Dehydration  Diabetes mellitus ()  Syndrome Inappropriate ADH secretion (SIADH)  Diabetes insipidus  Adrenal insufficiency  Uremia   Hyponatraemia  Hypernatraemia  Ethanol, methanol, or ethylene glycol ingestion  High protein diet  Mannitol therapy

Conditions that decrease osmolality Serum Urine  Excess hydration  Diabetes insipidus  Hyponatraemia  Excess fluid intake  Syndrome Inappropriate ADH secretion (SIADH)  Acute renal insufficiency  Glomerulonephritis 5

Osmotic diarrhea occurs when too much water is drawn into the bowels. This can be the result of:

Some poorly absorbable carbohydrates - The unabsorbed carbohydrate is metabolized in the gut to short-chain fatty acids, an osmotic active solute, this draws water into the gut leaving a fluid with a low sodium concentration. The diarrhea stops if the patient stops taking the carbohydrate.

Maldigestion - (e.g., pancreatic disease or Coeliac disease), in which the nutrients are left in the lumen to pull in water.

Osmotic laxatives – These laxatives work to alleviate constipation by drawing water into the bowels. In healthy individuals, too much magnesium (Maalox), sulfate salts (Epsom salts) or vitamin C can produce osmotic diarrhea.

Undigested lactose - A person who has lactose intolerance can have difficulty absorbing lactose after an extraordinarily high intake of dairy products.

Fructose malabsorption, excess fructose intake can also cause diarrhea. High-fructose foods that also have high glucose content are more absorbable and less likely to cause diarrhea. Sugar alcohols such as sorbitol (often found in sugar-free foods) are difficult for the body to absorb and, in large amounts, may lead to osmotic diarrhea.

Osmotic diarrhea stops when offending agent (e.g. milk, sorbitol) is stopped.

Secretory diarrhea:

Secretory diarrhea means that there is an increase in the active secretion, or an inhibition of absorption of the ions. There is little to no structural damage.

The most common cause is a cholera toxin that stimulates the secretion of anions, especially chloride ions. Therefore, to maintain a charge balance in the lumen, sodium is carried with it, along with water. In this type of diarrhea intestinal fluid secretion is isotonic with plasma even during fasting. It continues even when there is no oral food intake.

Verner-Morrison syndrome is associated with intestinal tumours secreting vasoactive intestinal peptide (VIP) – VIPoma it is characterised by profuse, watery diarrhoea that results in massive intestinal loss of water, potassium, sodium and bicarbonate, leading to hypovolaemia, hypokalaemia and reduced total body potassium, and achlorhydria ().

Bile salt malabsorption occurs.

Measurements of serum osmolality

Measured osmolality

The osmolality of a solution can be measured using a freezing point depression osmometer. This instrument measures the change in freezing point that occurs in a solution with increasing osmolality. 6

Calculated osmolality

Plasma and urine osmolality can also be calculated from the measured components. While there are many equations, a simple one is as follows: Osmolality (calc) = 1,86 x Na(mmol/L) + Glucose(mmol/L) + urea(mmol/L) + 9.

The sodium x 1,86 accounts for the negative ions associated with sodium and the exclusion of potassium approximately allows for the incomplete dissociation of sodium chloride.

Other formulas can also be used:

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.

Calculated faecal osmolality is calculated from 2 x (Na + K) or 2[Na] + 2[K].

Osmol gap is calculated the same for serum, urine and faecal with the formula: measured osmolality – calculated osmolality = Osmol gap

Case studies:

Case 1:

A 43 year old male with a history of alcohol and depression was found lethargic in his room. He was brought to the emergency room, on examination he was confused and became comatose over the next hours.

Laboratory results:

Glucose = 6,4 mmol/L (3,9 – 6,0 mmol/L) BUN = 6,0 mmol/L (1,7 – 8,3 mmol/L)

Sodium = 145 mmol/L (136 – 145 mmol/L) Potassium = 4, 2 mmol/L (3, 5 – 5, 1 mmol/L)

Chloride = 112 mmol/L (98 – 107 mmol/L) CO2 (bicarbonate) = 7 mmol/L (22 – 29 mmol/L)

Serum Osmolality 383 mOsm/kg = 26 mmol/l

(275 – 295 mOsm/kg)

Blood gas: pH 7, 12 (3, 5-4, 5) CO2 34 mm Hg ()

Blood ethanol was negative and urine toxicology screen was negative

Calculated Osmolality = 1,86 (Na) + urea+ glucose + 9

=1,86 ( 145) + 6,0 + 6.4 + 9 7

= 269,7 + 6,0 + 6.4 + 9

= 291,1 mOsm /kg

Osmol gap = Measured Osmolality - Calculated Osmolality

= 383 mOsm/kg – 291,1 mOsm/kg

= 91,9 mOSm/kg

As the Serum osmolarity and the osmol gap was very increased the doctor suspected an exogenous solute being present. After meeting with the patient’s family the doctor suspected either ethanol, methanol, or ethylene glycol ingestion as the patient regularly ingested an alcoholic drink bought at the local shabeen. He ordered a oxalate crystal test on the patient’s urine.

A moderate amount of these envelope shaped crystals was found in the patient’s urine confirming the ethylene glycol poisoning. He was put on an ethanol drip, treated with bicarbonate for the metabolic acidosis and dialysis. After 4 hours he regained consciousness. The dialysis was continued until his osmol gap was normal.

www.accessemergencymedicine.com/loadBinary.as coppied 26/9/11

Case 2:

An Insulin – dependent patient felt hypoglycaemic and drunk a sugar-rich drink. She had her routine doctor’s appointment and did not inject her usual insulin injection fearing hypoglycaemia while driving. She felt fine on arrival but her showed:

Blood glucose = 28 mmol/L

Sodium = 126 mmol/L

Osmolality = 290 mOsm/kg

Urea, potassium and bicarbonate was normal

The patient is developing a typical dehydration because of the movement of water out of the cells (ICF-intra cellular fluid) into the ECF (extra cellular fluid). This movement is a result of the high glucose levels in the blood changing the isotonic strength of the plasma the sodium is then decreased by dilution.

Case 3:

A 36 year old male fell and hit his head. While the wound was being sutured he became less and less responsive and lapsed into a coma. He was taken to the operating room for treatment, but did not regain consciousness. His urine output averaged 800ml/hour after the surgery.

His Laboratory tests:

Specimen Na K Cl CO2 BUN Creatinine Glucose Osmolality 8

Admission 137 4,2 103 25 15 4,8 Next 155 4,3 116 26 17 97 4,9 morning Next 172 4,6 132 27 19 113 5,5 353 evening Urine 32 9,0 15 105

The increased urine output with the decreased urine osmolality can occur in polydipsia (drinking to much water) or by a decreased secretion of ADH hormone by the pituitary gland. As the patient was comatose the first was eliminated. Decreased secretion of ADH occurs in 30% of head injury patient’s with the resulting Diabetes insipidus. The word diabetes means over production of urine. After the patient was treated with ADH every 2 hours the urine osmolality returned to over 300 mOsm/kg and the urine volume to less than 60ml/hour.

Reference: en.wikipedia.org/wiki/Diarrhea www.gpnotebook.co.uk/simplepage.cfm?ID=1980104756 en.wikipedia.org/wiki/Osmolarity www.encyclo.co.uk/define/osmolality

Tietz textbook of clinical chemistry, 3rd edition – normal ranges