A 40-year-old man is found drowsy at home, 2 days after drinking an unknown liquid from an unlabeled container in his garage. He has no visual symptoms. Results: sodium 140, potassium 5.6, chloride 102 and bicarbonate 6 mmol/L; glucose 6.0 mmol/L (108 mg/dL), urea 9.0 mmol/L (BUN 25 mg/dL), creatinine 410 µmol/L (4.6 mg/dL), lactate 2.8 mmol/L, beta-hydroxybutyrate normal, ethanol not detected and measured osmolality 301 mOsm/kg. His urine contains many colorless envelope- and needle-shaped crystals. Using 2 × Na + glucose + urea, an anion gap reference of 8-16 mmol/L and an osmolal gap reference below 10 mOsm/kg, which conclusion is best supported?

Ethylene glycol, now mostly converted to acids

Methanol, with the parent alcohol still present

No toxic alcohol, because the osmolal gap is normal

Lactic acidosis explaining the whole anion gap

In kidney failure, a urea of 45 mmol/L (BUN 126 mg/dL) raises measured osmolality, yet effective osmolality (tonicity) stays near normal. Why?

Urea moves freely across cell membranes

Urea is mostly bound to plasma albumin

Osmometers do not detect dissolved urea

Sodium falls to offset the urea

With all results in mmol/L, calculated serum osmolality is commonly estimated as:

2 × Na + glucose ÷ 18 + urea ÷ 2.8

Anion gap and osmolality

13 DOH Abu Dhabi (HAAD) lab licensing practice questions on Anion gap and osmolality, part of Clinical Chemistry. The first 13 are below; the first 5 with answers and explanations (tap Show answer after you have chosen), the rest in Learn with a free account.

Question 1 · Hard
A 40-year-old man is found drowsy at home, 2 days after drinking an unknown liquid from an unlabeled container in his garage. He has no visual symptoms. Results: sodium 140, potassium 5.6, chloride 102 and bicarbonate 6 mmol/L; glucose 6.0 mmol/L (108 mg/dL), urea 9.0 mmol/L (BUN 25 mg/dL), creatinine 410 µmol/L (4.6 mg/dL), lactate 2.8 mmol/L, beta-hydroxybutyrate normal, ethanol not detected and measured osmolality 301 mOsm/kg. His urine contains many colorless envelope- and needle-shaped crystals. Using 2 × Na + glucose + urea, an anion gap reference of 8-16 mmol/L and an osmolal gap reference below 10 mOsm/kg, which conclusion is best supported?
1. AMethanol, with the parent alcohol still present
2. BEthylene glycol, now mostly converted to acids
3. CNo toxic alcohol, because the osmolal gap is normal
4. DLactic acidosis explaining the whole anion gap
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Answer: B · Ethylene glycol, now mostly converted to acids
The anion gap is 140 − (102 + 6) = 32 mmol/L, and calculated osmolality is 2 × 140 + 6.0 + 9.0 = 295 mOsm/kg, so the osmolal gap is only 6 mOsm/kg. Two days after ingestion, ethylene glycol has largely been converted to glycolic and oxalic acids, so the osmolal gap falls as the anion gap rises. Calcium oxalate crystals and acute kidney injury support the diagnosis. A normal osmolal gap therefore does not exclude a toxic alcohol in a late presentation; methanol with its parent alcohol still present would raise the gap and typically affects vision. A lactate of 2.8 mmol/L with normal ketones explains only a small part of the raised anion gap.
- A: Unmetabolized methanol would raise the osmolal gap, and methanol affects vision.
- C: Late after ingestion a toxic alcohol is metabolized to acids, and the osmolal gap can be normal.
- D: A lactate of 2.8 mmol/L explains only a small part of an anion gap of 32.
Question 2 · Medium
In kidney failure, a urea of 45 mmol/L (BUN 126 mg/dL) raises measured osmolality, yet effective osmolality (tonicity) stays near normal. Why?
1. AUrea is mostly bound to plasma albumin
2. BUrea moves freely across cell membranes
3. COsmometers do not detect dissolved urea
4. DSodium falls to offset the urea
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Answer: B · Urea moves freely across cell membranes
Urea raises measured osmolality, but it equilibrates across most cell membranes, so it does not draw water out of cells. It is therefore an ineffective osmole, like ethanol. Effective osmolality is estimated as 2 × Na + glucose; with sodium 138 and glucose 5.0 mmol/L it is about 281 mOsm/kg. Sodium and glucose, which stay outside cells, are the solutes that cause water shifts.
- A: Urea is a small free molecule and is not protein-bound.
- C: Osmometers measure all dissolved particles, including urea.
- D: Urea does not lower sodium; it is ineffective because it enters cells.
Question 3 · Easy
In a healthy person, which unmeasured anion accounts for most of the normal anion gap?
1. ASulfate
2. BPhosphate
3. CLactate
4. DAlbumin
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Answer: D · Albumin
The anion gap, sodium minus (chloride plus bicarbonate), reflects anions that are not measured on the routine panel. Albumin carries many negative charges at blood pH and makes up most of the normal gap, with phosphate, sulfate and organic anions adding smaller amounts. This is why a low albumin lowers the gap and can hide an acid such as lactate. Many laboratories adjust the gap for albumin in critically ill patients.
- A: Sulfate contributes only a small amount, rising mainly in kidney failure.
- B: Phosphate contributes only a few mmol/L in health.
- C: Lactate is normally low and adds little until it accumulates in lactic acidosis.
Question 4 · Medium
An unconscious man in the emergency department has an osmolal gap of 30 mOsm/kg (reference below 10), with a normal anion gap and bicarbonate. Which test should be checked first to explain the gap?
1. APlasma lactate
2. BSerum ammonia
3. CSerum salicylate
4. DBlood ethanol level
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Answer: D · Blood ethanol level
Ethanol is the most common cause of a raised osmolal gap, because it is a small molecule present in large molar amounts after drinking. Each 1 mmol/L adds about 1 mOsm/kg, so a level near 30 mmol/L (about 140 mg/dL) would explain a gap of this size. If a gap remains after ethanol is counted, methanol, ethylene glycol or isopropanol must be considered. A normal anion gap fits ethanol, isopropanol, or a toxic alcohol taken so recently that little acid has formed.
- A: Lactic acidosis raises the anion gap, which is normal here, and adds little to the osmolal gap.
- B: Ammonia is present in micromolar amounts and cannot raise osmolality by 30 mOsm/kg.
- C: Salicylate causes a high anion gap acidosis and adds little to measured osmolality.
Question 5 · Easy
With all results in mmol/L, calculated serum osmolality is commonly estimated as:
1. A2 × Na + glucose + urea
2. BNa + glucose + urea
3. C2 × Na + glucose ÷ 18 + urea ÷ 2.8
4. D2 × (Na + glucose) + urea
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Answer: A · 2 × Na + glucose + urea
Sodium is doubled to account for its accompanying anions, mainly chloride and bicarbonate. When glucose and urea are reported in mmol/L they are simply added, because 1 mmol/L of each gives about 1 mOsm/kg. The divisors 18 and 2.8 are needed only to convert glucose and BUN from mg/dL. The result is compared with measured osmolality to give the osmolal gap.
- B: Sodium must be doubled to include its paired anions.
- C: Dividing by 18 and 2.8 converts mg/dL values and would make SI results far too small.
- D: Glucose is a single uncharged particle and is not doubled.
Question 6 · Medium
A laboratory changes its anion gap formula from Na − (Cl + HCO3-) to (Na + K) − (Cl + HCO3-). Its reference interval for the anion gap should:
1. AStay the same
2. BFall by about 4 mmol/L
3. CRoughly double
4. DRise by about 4 mmol/L
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Question 7 · Hard
An ICU patient has received a high-dose intravenous lorazepam infusion for 4 days. She is afebrile with normal blood pressure. Results: pH 7.27, bicarbonate 15 mmol/L, anion gap 22 mmol/L (reference 8-16), lactate 6.5 mmol/L (reference 0.5-2.2), osmolal gap 28 mOsm/kg (reference below 10), ethanol not detected. The most likely cause is:
1. AIsopropanol from skin antiseptic
2. BPropylene glycol in the drug infusion
3. CHidden methanol ingestion
4. DLactic acidosis from septic shock
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Question 8 · Hard
Results: sodium 142 mmol/L, glucose 5.5 mmol/L (99 mg/dL), urea 4.5 mmol/L (BUN 13 mg/dL), ethanol 43 mmol/L (198 mg/dL), measured osmolality 341 mOsm/kg (osmolal gap reference below 10). Counting each mmol/L of ethanol as 1 mOsm/kg, what is the remaining gap and what does it mean?
1. A47 mOsm/kg; a toxic alcohol is likely
2. B146 mOsm/kg; a toxic alcohol is likely
3. C4 mOsm/kg; ethanol explains the gap
4. D38 mOsm/kg; a toxic alcohol is likely
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Question 9 · Hard
A man is admitted 20 hours after drinking an illicitly distilled spirit and reports blurred vision. Results: pH 7.10, bicarbonate 6 mmol/L, anion gap 30 mmol/L (reference 8-16), lactate 2.0 mmol/L, ketones negative, ethanol not detected, osmolal gap 22 mOsm/kg (reference below 10). The most likely cause is:
1. ASalicylate
2. BEthylene glycol
3. CIsopropanol
4. DMethanol
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Question 10 · Medium
After 7 L of 0.9% sodium chloride during trauma resuscitation, a patient has sodium 142, chloride 116 and bicarbonate 17 mmol/L (anion gap reference 8-16), with lactate 1.6 mmol/L (reference 0.5-2.2). The low bicarbonate is best explained by:
1. AKetoacidosis from prolonged fasting
2. BCO2 loss from an underfilled tube
3. CLactic acidosis from hypoperfusion
4. DHyperchloremic acidosis from the saline
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Question 11 · Hard
Ethanol is not detected. Results: sodium 136 mmol/L, glucose 7.0 mmol/L (126 mg/dL), urea 7.0 mmol/L (BUN 20 mg/dL), measured osmolality 318 mOsm/kg. Using 2 × Na + glucose + urea, what is the osmolal gap?
1. A32 mOsm/kg
2. B43 mOsm/kg
3. C39 mOsm/kg
4. D168 mOsm/kg
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Question 12 · Hard
A woman with septic shock and cirrhosis has sodium 136, chloride 104 and bicarbonate 19 mmol/L, and albumin 16 g/L. The anion gap reference is 8-16 mmol/L for albumin 40 g/L; add 0.25 mmol/L for every 1 g/L of albumin below 40. What is the corrected anion gap?
1. A7 mmol/L, low
2. B19 mmol/L, raised
3. C13 mmol/L, normal
4. D17 mmol/L, raised
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Question 13 · Medium
What does a freezing-point osmometer measure?
1. AThe molecular weight of dissolved proteins
2. BThe sodium concentration of the sample, and nothing else
3. CThe pH of the sample at low temperature
4. DFreezing point depression, set by particle number
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Anion gap and osmolality

In kidney failure, a urea of 45 mmol/L (BUN 126 mg/dL) raises measured osmolality, yet effective osmolality (tonicity) stays near normal. Why?

In a healthy person, which unmeasured anion accounts for most of the normal anion gap?

An unconscious man in the emergency department has an osmolal gap of 30 mOsm/kg (reference below 10), with a normal anion gap and bicarbonate. Which test should be checked first to explain the gap?

With all results in mmol/L, calculated serum osmolality is commonly estimated as:

A laboratory changes its anion gap formula from Na − (Cl + HCO3-) to (Na + K) − (Cl + HCO3-). Its reference interval for the anion gap should:

Results: sodium 142 mmol/L, glucose 5.5 mmol/L (99 mg/dL), urea 4.5 mmol/L (BUN 13 mg/dL), ethanol 43 mmol/L (198 mg/dL), measured osmolality 341 mOsm/kg (osmolal gap reference below 10). Counting each mmol/L of ethanol as 1 mOsm/kg, what is the remaining gap and what does it mean?

After 7 L of 0.9% sodium chloride during trauma resuscitation, a patient has sodium 142, chloride 116 and bicarbonate 17 mmol/L (anion gap reference 8-16), with lactate 1.6 mmol/L (reference 0.5-2.2). The low bicarbonate is best explained by:

Ethanol is not detected. Results: sodium 136 mmol/L, glucose 7.0 mmol/L (126 mg/dL), urea 7.0 mmol/L (BUN 20 mg/dL), measured osmolality 318 mOsm/kg. Using 2 × Na + glucose + urea, what is the osmolal gap?

A woman with septic shock and cirrhosis has sodium 136, chloride 104 and bicarbonate 19 mmol/L, and albumin 16 g/L. The anion gap reference is 8-16 mmol/L for albumin 40 g/L; add 0.25 mmol/L for every 1 g/L of albumin below 40. What is the corrected anion gap?

What does a freezing-point osmometer measure?