Question 29.1

A 24-year-old female with a history of depression presents with seizures and decreased consciousness. Her arterial blood gas analysis is shown below, taken on FiO2 0.3.


Patient Value

Adult Normal Range

Barometric pressure      

760 mmHg (100 kPa)



7.35 – 7.45


40 mmHg (5.3 kPa)

35 – 45 (4.6 – 6.0)


110 mmHg (14.6 kPa)       


24 mmol/L

22 – 27

Base Excess

-0.4 mmol/L

-2 – +2


136 mmol/L

135 – 145


4.0 mmol/L

3.5 – 4.5


118 mmol/L*

110 – 110


4.2 mmol/L

3.0 – 7.8


0.8 mmol/L

0.5 – 2.2

a) What is the likely cause of her presentation?

b) State the reasoning for your answer.

(20% marks)

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College answer

Not available.


This question is identical to Question 3.1 from the second paper of 2013. The only difference is that you are asked to "state the reasoning for your answer", whereas in 2013 you merely had to "give your reasoning". One's imagination swims with terrible ideas as to the causes and meanings of these changes.

Let us dissect these results systematically.

  1. The A-a gradient is slightly raised:
    PAO2 = (0.3 × 713) - (40 × 1.25) = 163.9
    Thus, A-a = ( 163.9 - 110) = 53.9mmHg.
  2. There is no acidaemia
  3. The PaCO2 is normal
  4. The SBE is -0.4, suggesting a normal acid-base balance
  5. The respiratory compensation is irrelevant (bicarbonate is ideal)
  6. The anion gap is negative:
    (136) - (118 + 24) = -6, or -2 when calculated with potassium

There are few causes of negative anion gap.

The usual reason for such a result is an abundance of a cation which does not get measured in the normal biochemistry panels. Of these cations, lithium is the most commonly encountered in the clinical setting, followed by Polymyxin B. Halides such as bromide and iodide can cause a negative anion gap in spite of actually being anions themselves; however, by being chemically similar to chloride these ions tend to confuse the chloride-measuring electrode, "posing" as chloride in the laboratory and generating a spuriously elevated chloride value. Magnesium and calcium elevation can also result in a negative anion gap, but this is because they are not routinely included in the calculation of the gap.

Artifactual causes of a low or negative anion gap may include hyperlipidaemia and hypoalbuminaemia (although the "normal" anion gap value will merely trend towards zero with decreasing albumin levels- even without any albumin, the expected "normal" AG is 2.)

In short, the causes of a negative anion gap are as follows:

  • Increase in unmeasured cations
    • Lithium
    • Polymyxin B
    • Magnesium
    • Calcium
  • Interference with the measurement of chloride
    • iodide
    • bromide


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