Question 18.3

The following blood results are from a 78-year-old female with Type 2 diabetes and chronic renal failure presenting with breathlessness. Her GP has been treating her with flucloxacillin for cellulitis of her lower limbs.

Parameter	Patient Value	Normal Adult Range
Urea	15.3 mmol/L*	3 – 8
Creatinine	309 μmol/L*	45–90
Sodium	139 mmol/L	134 – 146
Potassium	4.4 mmol/L	3.4 – 5.0
Chloride	115 mmol/L*	100 – 110
Glucose	12.1 mmol/L*	3.0 – 5.4
pH	7.11*	7.35– 7.45
PCO2	13 mmHg (1.7 kPa)*	35– 45 (4.6 – 6.0)
Bicarbonate	4 mmol/L*	22–27
Base Excess	-24 mmol/L*	-2 – +2
Lactate	0.6 mmol/L	< 2.0
Measured osmolality	309 mOsm/L*	280 – 300

a) Describe the acid-base abnormalities in the above results.

b) List three possible causes for this biochemical disturbance.

[Click here to toggle visibility of the answers]

College Answer

a) Severe compensated metabolic acidosis with a raised anion gap (! 20), normal osmolar gap and Δ gap 0.4 (Δ gap suggests mixed AG and NAG MA or renal failure)

b)Possible causes

- DKA
- Renal failure
- Pyroglutamic acidosis

Discussion

Let us dissect these results systematically.

The A-a gradient cannot be calculated.
There is acidaemia
The PaCO₂ is compensatory
The SBE is -24, suggesting a severe metabolic acidosis
The respiratory compensation is adequate.
The expected PaCO₂(4 × 1.5) + 8 = 14mmHg.
The anion gap is raised:
(139) - (115 + 4) = 20, or 24.4 when calculated with potassium
The delta ratio, assuming a normal anion gap is 12 and a normal bicarbonate is 24, would therefore be (20 - 12) / (24 - 4) = 0.4
This suggests that there is a mixed high anion gap and normal anion gap metabolic acidosis here.
The urinary pH and electrolytes are not supplied here.

However, we are supplied with a measured osmolality, which is high - 309 mOsm/L. Is there an osmolar gap? If we calculate the osmolality from the EUCs, we arrive at a value of (139 × 2 + urea + glucose) = 305.4 mOsm/L. So... there is no osmolar gap.

Thus, the only possible explanations must be

Renal failure
DKA
Pyroglutamic acidosis (the college mentioned flucloxacillin, and thus to omit this one from the list of differentials would be amiss)

References

Warnock DG. Uremic acidosis. Kidney Int. 1988 Aug;34(2):278-87.

Relman, Arnold S., Edward J. Lennon, and Jacob Lemann Jr. "Endogenous production of fixed acid and the measurement of the net balance of acid in normal subjects." Journal of Clinical Investigation 40.9 (1961): 1621.

Laffel, Lori. "Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes." Diabetes/metabolism research and reviews 15.6 (1999): 412-426.

Elisaf, Moses S., et al. "Acid-base and electrolyte disturbances in patients with diabetic ketoacidosis." Diabetes research and clinical practice 34.1 (1996): 23-27.

Dempsey GA Lyall HJ, Corke CF, Scheinkestel CD. Pyroglutamic acidemia: a cause of high anion gap metabolic acidosis. Crit Care Med. 2000Jun;28(6):1803-7.

Duewall, Jennifer L., et al. "5-Oxoproline (pyroglutamic) acidosis associated with chronic acetaminophen use." Proceedings (Baylor University. Medical Center) 23.1 (2010): 19.

Akhilesh Kumar and Anand K. Bachhawat Pyroglutamic acid: throwing light on a lightly studied metabolite ,SPECIAL SECTION: CHEMISTRY AND BIOLOGY. CURRENT SCIENCE, VOL. 102, NO. 2, 25 JANUARY 2012. 288

[Submit a comment or correction]