Question 5.3

A 42-year-old patient is found unconscious after being missing for several days. 

Parameter

Patient Value

Adult Normal Range

pH

7.26*

7.35 – 7.45

pO2

90 mmHg (12 kPa)

pCO2

45 mmHg (6.0 kPa)

35 – 45 (4.7 – 6.0)

Standard bicarbonate

18 mmol/L*

22 – 29

Base excess

-7 mmol/L*

-3 to +3

Sodium

134 mmol/L

135 – 145

Potassium

5.6 mmol/L*

3.5 – 5.2

Calcium (ionized)

0.91 mmol/L*

1.15 – 1.30

Calcium (pH 7.4 adjusted)

0.84 mmol/L*

1.15 – 1.30

Chloride

98 mmol/L

95 – 110

Glucose

8.1 mmol/L

4.0 – 8.0

Lactate

2.2 mmol/L*

0.5 – 1.3

Creatinine

330 µmol/L*

45 – 90

Urea

25 mmol/L*

3 – 8

Serum osmolality (measured)

321 mOsm/kg

280 – 300

a) List the important biochemical abnormalities, showing your calculations where appropriate. (20% marks)
b) List the most likely diagnosis. (5% marks)

c) List two investigations that could help secure the diagnosis. (5% marks)

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College answer

Not available.

Discussion

a)

The biochemical abnormalities:

  • There is acidaemia
  • The PaO2 is relatively normal, though we have no FiO2 for comparison
  • The base excess is low, suggesting a metabolic acidosis
  • The CO2 is making no effort to compensate (the expected CO2 is around 33 using the SBE method, or (1.5×18)+8 = 35 using the classical Bostone calculations). Either way, there is also some mild respiratory acidosis
  • The anion gap is elevated (134 - (98 + 18)) = 18
  • The delta ratio is therefore (18-12)/(24-18) = 1.0, i.e. this is a fairly pure (though mild) HAGMA
  • The calcium is low, and moreover the pH-corrected  calcium is low. It is weird that they might give you both the corrected and the uncorrected variables, as the difference between them is really only the pH, and the trainee cannot be expected to derive much information from this (as the pH was already given to them). However, it may have meaning later, as we shall see. As a reader(Alex Thom) has pointed out, this low calcium may be a clue that calcium oxalate crystals are forming in the urine.
  • The glucose is trivially elevated
  • The urea and creatinine are raised, in a proportion which suggests some dehydration
  • The serum osmolality is given, which is a sign that the college want us to calculate the osmolal gap. The calculated osmolality is (134 ×2) + 25 + 8 = 301, whereas the measured osmolality is 321, i.e the osmolar gap is 20 (whereas the normal is less than 10)

b) The most likely diagnosis - taking into account the fact that the patient "has been missing for several days" and is now unconscious - is intoxication with some kind of toxic alcohol, because there is a combination of a high anion gap and a high osmolar gap.  Methanol or ethylene glycol would each make a valid differential diagnosis, but there are many other possibilities:

  • Toxicological causes
    • Methanol intoxication (the anion is formic acid)
    • Ethylene glycol intoxication (the anions are glycolic acid and oxalic acid)
    • Diethylene glycol intoxication (the anion is 2-hydroxyethoxyacetic acid, HEAA)
    • Propylene glycol intoxication (the anions are pyruvate, lactate and acetate)
    • Salicylate intoxication (the anions are salicylate and lactate)
    • Any toxin causing massive lactic acidosis, eg. isoniazid
  • Endocrine and metabolic disturbances
    • Lactic acidosis
    • Alcoholic or diabetic ketoacidosis
    • Acute kidney injury

Thus,

c)

The two investigations that could "help secure the diagnosis" are

  • Glycolic or oxalic acid levels, or calcium oxalate crystals in the urine
  • Laboratory lactate level (to look for a "lactate gap")

If you had "ketone levels" here, it would not be incorrect per se, but the glucose is fairly normal, making it less likely. You could also consider a salicylate level as a valid alternative answer

References

Erstad, Brian L. "Osmolality and osmolarity: narrowing the terminology gap."Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy23.9 (2003): 1085-1086.

Gennari, F. John. "Current concepts. Serum osmolality. Uses and limitations."The New England journal of medicine 310.2 (1984): 102-105.

Hoffman, Robert S., et al. "Osmol gaps revisited: normal values and limitations."Clinical Toxicology 31.1 (1993): 81-93.

Kraut, Jeffrey A., and Shelly Xiaolei Xing. "Approach to the evaluation of a patient with an increased serum osmolal gap and high-anion-gap metabolic acidosis." American Journal of Kidney Diseases 58.3 (2011): 480-484.