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.

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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.

  1. The A-a gradient cannot be calculated.
  2. There is acidaemia
  3. The PaCO2 is compensatory
  4. The SBE is -24, suggesting a severe metabolic acidosis
  5. The respiratory compensation is adequate. 
    The expected PaCO2(4 × 1.5) + 8 = 14mmHg.
  6. The anion gap is raised:
    (139+ 4.4) - (115 + 4) = 24.4
    The delta ratio suggests that there is a mixed high anion gap and normal anion gap metabolic acidosis here.
    (24.4 - 12) / (24 - 4) = 0.62
  7. 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

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