Quiz

Low Serum Bicarbonate in a Patient With

Diabetes Mellitus: A Quiz
Vladimir Mushailov, Gary Horowitz, and Taimur Dad

Clinical Presentation either by enzymatic reactions to generate products that are

quantified by spectrophotometry or by ion-specific elec-
A 55-year-old woman with a history of insulin-
trode (ISE) techniques that use either indirect or direct
dependent diabetes mellitus was admitted for glucose
measurement. Venous samples are typically analyzed by
optimization prior to bilateral salpingo-oophorectomy
spectrophotometry or indirect ISE methods, while arterial
for ovarian masses. Nephrology was consulted after
blood gas samples use the direct ISE method.
routine morning laboratory measurements revealed a
Turbidity in the blood sample can scatter light and
bicarbonate of 12 mEq/L and an anion gap of 22 mEq/L
produce inaccurate spectrophotometric results. In
(Table 1). Inpatient medications included insulin, and
addition, dilution of the blood samples, as is needed for
acetaminophen as needed. She revealed that a few weeks
enzymatic and indirect ISE techniques, can cause further
prior, she was started on a sodium/glucose cotransporter
inaccuracies owing to incorrect assumptions about the
2 (SGLT2) inhibitor but that she had not taken it in more
distribution of water and solids in the sample (“space-
than 1 week. Her serum glucose was 232 mg/dL and
occupying effect”). This space-occupying effect is
serum creatinine was 1.03 mg/dL (corresponding to an
classically taught as causing pseudo-hyponatremia in
estimated glomerular filtration rate of 61 mL/min/
the setting of either hyperlipidemia or hyper-
1.73 m2). Her examination was unremarkable and she
proteinemia (Fig 1). Hyperlipidemia can affect a broad
was asymptomatic.
number of chemistries, most notably sodium, potas-
sium, and chloride.3 Importantly, use of ISE techniques
• What could be the cause of the high anion gap?
can overcome the light-scattering effect and use of
direct ISE can overcome the space-occupying effect.
• What could be the cause of the low bicarbonate
Most commonly, serum bicarbonate is measured
concentration?
using the enzymatic technique, which assumes a
normal distribution of water and solids in the sample.
• What additional testing is warranted in this
clinical scenario?
What additional testing is warranted in this
clinical scenario?
Discussion In the absence of a clinical reason or other laboratory
evidence for an acidosis other than a low serum bicar-
What could be the cause of the high anion gap? bonate, measurement error should be considered. On
Presence of an elevated anion gap is most often indic- further discussion with our laboratory colleagues, it was
ative of an increase in unmeasured anions in the form of noted that the blood sample from the patient was
organic acids or, less commonly, in the setting of lipemic and that testing had revealed a triglyceride level
hyperalbuminemia or presence of anionic paraprotein.1
Use of the mnemonic “GOLDMARK” (glycols, oxo-
proline, L-lactate, D-lactate, methanol, aspirin, renal
Table 1. Laboratory Values From Venous Blood Sample at 8
failure, and ketoacidosis) can assist in finding the eti- AM
ology of the high anion gap.2 There was no history of
toxic alcohol, aspirin, or long-term acetaminophen Reference
Parameter Value Range
ingestion. Serum osmolar gap was 6 mOsm/kg and
Glucose, mg/dL 232 70-139
toxicology studies did not show presence of ethanol,
SUN, mg/dL 20 6-24
salicylates, or acetaminophen. Serum lactate was normal
Creatinine, mg/dL 1.03 0.57-1.30
and there was no clinical concern for D-lactic acidosis.
Sodium, mEq/L 140 135-145
Serum beta-hydroxybutyrate was not elevated and her
Potassium, mEq/L 4.1 3.6-5.1
urinalysis did not show any ketones (euglycemic
Chloride, mEq/L 106 98-110
QUIZ

ketoacidosis from SGLT2 inhibitors would result in

Bicarbonate, mEq/L 12 20-30
elevated beta-hydroxybutyrate levels). Calculated anion gap, 22
mEq/L
What could be the cause of the low serum Triglycerides, mg/dL 4852 40-250
bicarbonate concentration? Total cholesterol, mg/dL 649 110-199
Serum bicarbonate can be measured using different tech- HDL cholesterol, mg/dL 12 35-75
niques. Analysis of blood chemistries can be performed LDL cholesterol, mg/dL 31 0-129
Quiz

Normal Hypertriglyceridemia
• Sample Na=135 mmol/L • Sample Na=135 mmol/L
• Aqueous phase obtained for • Aqueous phase obtained for
dilution dilution
• Measured Na=126 mmol/L in • Measured Na=115 mmol/L in
diluted sample (since 93% of diluted sample (since 85% of
serum is aqueous) serum is aqueous)
• Reported Na=135 mmol/L • Reported Na=123 mmol/L
(obtained by dividing 126 by (inaccurate since obtained from
0.93) 115 ÷ 0.93, which is based on
the usual assumption of serum
being 93% aqueous instead of
85%)

7% solid phase 15% solid phase

93% aqueous phase 85% aqueous phase

Sample After dilution Sample After dilution

(1:100) (1:100)

Figure 1. Pseudo-hyponatremia resulting from inaccurate dilutional assumption in hypertriglyceridemia (“space-occupying effect”).

of 4852 mg/dL and a total cholesterol level of 649 mg/
dL. In the setting of lipemia, the chemistry analyzers
had been programmed to not report sodium, potas-
sium, and chloride concentrations and to prompt the
technicians to reanalyze those electrolytes using a blood
gas analyzer (using direct ISE). However, there was no
such prompt to reanalyze bicarbonate.
Use of direct ISE was warranted in this scenario, since
this provides a calculated serum bicarbonate concentration
using the Henderson-Hasselbalch equation after directly
measuring pH and pCO2 and avoids errors due to any
space-occupying effect. An arterial blood gas was ob-
tained 5 hours after the patient’s morning laboratory
testing and revealed a pH of 7.43, bicarbonate of 23
mEq/L, and a pCO2 of 36 mm Hg. The arterial blood
sample revealed a normal anion gap of 9 mEq/L. This
arterial blood bicarbonate measurement of 23 meq/L
was confirmed by reanalyzing the patient’s initial venous
blood sample using a blood gas analyzer (direct ISE),
which resulted in a calculated bicarbonate of 24 mEq/L.
Thus, the patient’s venous measured bicarbonate level of 12
mEq/L was inaccurate owing to the light scattering and/
or a space-occupying effect of high triglyceride levels.4,5
Final Diagnosis
Pseudo–anion gap elevation due to pseudo-
Authors’ Affiliation: Tufts Medical Center, Boston,
Massachusetts.
Address for Correspondence: Vladimir Mushailov, MD, 622
West 168th St, PH building 4-124, New York, NY 10034.
Email: Vm2687@cumc.columbia.edu
Support: None.
Financial Disclosure: The authors declare that they have no
relevant financial interests.
Patient Protections: The authors declare that they have
obtained written consent from the patient reported in this
article for publication of the information about her that appears
within this Quiz.
Peer Review: Received April 29, 2022. Direct editorial input from
the Engagement Editor. Accepted in revised form August
12, 2022.
Publication Information: Published by Elsevier Inc. on behalf of
the National Kidney Foundation, Inc. This is a US Government
Work. There are no restrictions on its use. doi: 10.1053/
j.ajkd.2022.08.027
References
1. Kraut JA, Madias NE. Serum anion gap: its uses and limi-
tations in clinical medicine. Clin J Am Soc Nephrol.
2007;2(1):162-174. doi:10.2215/CJN.03020906
2. Mehta AN, Emmett JB, Emmett M. GOLD MARK: an anion
gap mnemonic for the 21st century. Lancet. 2008;372(9642):
892. doi:10.1016/S0140-6736(08)61398-7
3. Dimeski G, Mollee P, Carter A. Effects of hyperlipidemia on
plasma sodium, potassium, and chloride measurements by an
indirect ion-selective electrode measuring system. Clin Chem.
QUIZ

hypobicarbonatemia in the setting of previously 2006;52(1):155-156. doi:10.1373/clinchem.2005.054981

undiagnosed hypertriglyceridemia.
Article Information
Authors’ Full Names and Academic Degrees: Vladimir
Mushailov, MD, Gary Horowitz, MD, and Taimur Dad, MD, MS.
4. Rifkin S, Shaub B. Factitious hypobicarbonatemia associ-
ated with profound hyperlipidemia. Ren Fail. 2014;36(7):
1155-1157. doi:10.3109/0886022X.2014.917945
5. Carag C, Baxi PV, Behara V, Gashti C, Rodby R.
Pseudo-anion gap metabolic acidosis from severe hyper-
triglyceridemia corrected by plasma exchange. Clin Neph-
rol. 2019;92(5):258-262. doi:10.5414/CN109627
 Quiz

FELLOWSHIP PROGRAM HIGHLIGHT

Note from editors: To recognize fellowship programs’ educational mission, AJKD is using its popular Quiz feature to highlight Nephrology
Fellowship programs when an author is a Nephrology Fellow. To participate, Fellowship Program Directors mentor fellows in submitting
prospective Quizzes; those that are selected for publication include a brief description of the fellowship program from the Director. For “Low
Serum Bicarbonate in a Patient With Diabetes Mellitus” the corresponding author is Vladimir Mushailov, who was a Nephrology Fellow at
Tufts Medical Center at the time the Quiz was submitted.
Program: Tufts Medical Center Nephrology Fellowship Training Program (https://www.tuftsmedicalcenter.
org/patient-care-services/departments-and-services/nephrology/training-education)
Program Director: Scott Gilbert, MD
Program Description: The Nephrology Fellowship Training Program at Tufts Medical Center is designed to
provide trainees with the opportunity to achieve the fundamental knowledge, procedural expertise, practical
experience, and professional and ethical skills necessary for the subspecialty of Nephrology. Fellows care for
patients with the full spectrum of kidney disorders at all stages of the disease process. Efforts are made at every
point to emphasize the integration of medical knowledge, compassionate care, and social, psychological, and
economic issues. The program offers 2 distinct fellowship tracks: a 2-year Clinical Track and a 3-year Clinical-
Research Track. In the first year of the Clinical Track, fellows participate in 12 months of clinical rotations along
with twice-weekly half-day continuity clinics and a monthly home dialysis continuity clinic. The second year
comprises advanced clinical rotations, a series of focused study blocks to develop expertise in a specific domain, a
weekly half-day continuity clinic, management of an outpatient hemodialysis shift, and a monthly home dialysis
continuity clinic. The Clinical-Research Track devotes 2 years to research training and 1 year to clinical training
(which is identical to the first year of the Clinical Track). In the first year of research training, fellows are enrolled
in the master’s program in Clinical and Translational Sciences at the Sackler School of Graduate Biomedical
Sciences of Tufts University. They participate in mentored research, attend a weekly half-day continuity clinic,
and manage a hemodialysis shift. The second year involves completion of the master’s thesis and the master’s
degree, and a weekly half-day continuity clinic.
QUIZ