Quiz

Clinical Approach to a Patient With an Acid-Base

Disturbance
Carmen Elena Cervantes, Steven Menez, Jose M. Monroy Trujillo, and Mohamad Hanouneh

Clinical Presentation which is 1.35 in this case. A delta ratio between 1 and 2
suggests that the patient may not have an additional acid-
A 65-year-old woman with a medical history of dia-
base disorder. However, this equation assumes that all
betes mellitus, obesity, compensated cirrhosis, and
buffering is extracellular and by bicarbonate, neither of
nonalcoholic steatohepatitis had right first distal phalanx
which is correct. The calculated PaCO2 by Winter’s for-
osteomyelitis diagnosed 4 weeks before presentation
mula, that is, PaCO2 = (1.5 × [HCO3−] + 8) ± 2, is
and underwent right below-knee amputation. She was
23 mm Hg, which is slightly above the arterial blood
admitted to the hospital with abdominal pain and
gas–measured PaCO2 of 19 mm Hg, indicating that the
hematemesis.
patient also has a respiratory alkalosis. In summary, our
On admission, the patient denied chest pain, short-
patient has a high-AG metabolic acidosis with mild res-
ness of breath, nausea, vomiting, diarrhea, or urinary
piratory alkalosis.
symptoms. She also denied using over-the-counter
medications. Home medications included aspirin,
81 mg, daily; furosemide, 20 mg, daily; insulin glar- What is the differential diagnosis for this
gine, 10 units, daily; levofloxacin, 500 mg, daily; and patient’s acid-base disturbance?
linezolid, 600 mg, twice a day. The causes of high-AG metabolic acidosis are listed in
On physical examination, the patient’s body tem- Box 1.
perature was 36.5  C (97.7  F), heart rate was 86
beats/min, blood pressure was 105/53 mm Hg, Table 1. Patient’s Initial Basic Laboratory Values
respiration rate was 14 breaths/min, and oxygen satu- Reference
ration was 98% while breathing room air. Cardiopul- Test Result Range
monary examination findings were unremarkable. Her Hemoglobin, g/dL 6.9 12-16
abdomen was distended with mild epigastric tenderness White blood cell count, /μL 2,500 3,700-11,000
to palpation. There was no lower extremity edema. Platelet count, ×103/μL 24 150-400
Neurologic examination was positive for asterixis. Sodium, mmol/L 131 132-148
Table 1 outlines the patient’s initial laboratory studies. Potassium, mmol/L 5.5 3.5-5
Urinalysis results were benign and blood cultures were Chloride, mmol/L 94 98-111
negative. Computed tomography of the abdomen Bicarbonate, mmol/L 10 23-32
demonstrated moderate ascites and suggested liver Serum urea nitrogen, mg/dL 29 10-25
cirrhosis. Chest x-ray revealed no acute cardiopulmo- Creatinine, mg/dL 0.69 0.7-1.4
nary process. Calcium, mg/dL 7.9 8.4-10.5
Albumin, g/dL 2.3 3.5-5.0
Glucose, mg/dL 170 65-100
• What is the acid-base disturbance in this case? Alanine aminotransferase, U/L 7 0-45
Aspartate aminotransferase, U/L 16 7-40
• What is the differential diagnosis for this acid- Alkaline phosphatase, U/L 256 40-150
base disturbance? Bilirubin, total, mg/dL 0.3 0-1.5
PTT, s 50 22-32
• What is the most likely cause of this patient’s INR 1.2
acid-base disturbance? LDH, U/L 125 0-249
Lactate, mmol/L 11.5 0.4-1.9
• What is the best treatment for this patient’s β-Hydroxybutyrate, mg/dL 0.3 0-3
QUIZ

metabolic abnormalities? Serum osmolality, mOsm/kg 287 275-295

Serum acetaminophen, μg/mL <5.0
Serum salicylate, mg/dL <0.3 <20
Discussion Serum ethanol, mg/dL 2
What is the acid-base disturbance in this case? Arterial blood gas
pH 7.34 7.35-7.45
Our patient has a high–anion gap (AG) metabolic
PCO2, mm Hg 19 35-45
acidosis; corrected for hypoalbuminemia, the AG equals PO2, mm Hg 116 75-100
31. The increase in AG was essentially matched by a HCO−3, mmol/L 10 18-23
decrease in serum bicarbonate concentration [HCO3−] Abbreviations: INR, international normalized ratio; LDH, lactate dehydroge-
according to the delta ratio, (AG − 12)/(24 − [HCO3−]), nase; PTT, partial thromboplastin time.

What is the most likely cause of this patient’s
acid-base disturbance?
We can further investigate this patient’s acid-base
disturbance through calculation of her osmolar gap
(OG). The calculated osmolality, equivalent to {[2 ×
(sodium in mmol/L)] + [glucose in mg/dL]}/{18 +
[(serum urea nitrogen in mg/dL)/2.8] + [ethanol/
3.7]}, is 282 mOsm/kg in our patient. The OG is
calculated by taking the difference between measured
and calculated serum osmolality, and a normal OG
is ≤10 mOsm/kg. Our patient had an OG of 5 mOsm/
kg so it is unlikely that she had intoxication with glycols
or methanol.
The elevated lactate level (Table 1) in this setting
indicates the presence of lactic acidosis, which can arise
from the causes listed in Box 2. The patient does not
have signs of shock or hypovolemia. We need to ac-
count for our patient’s lactic acidosis in the setting of
normotension. Salicylate toxicity can cause respiratory
alkalosis with high-AG metabolic acidosis. However, it
does not explain the patient’s lactic acidosis. Moreover,
serum salicylate level was undetectable. Ethylene glycol
can lead to a false elevation in L-lactate level due to
cross-reactivity of its metabolites with the oxidase
enzyme that is commonly used to measure ethylene
glycol level.3 However, the normal OG in this patient
makes ethylene glycol and methanol toxicity less likely.
Also, the patient has no history of any other toxic
alcohol exposure. Pyroglutamic acid can be associated
with lactic acidosis; however, this patient did not have a
history of acetaminophen use. The normal β-hydrox-
ybutyrate level and lack of ketonuria exclude
ketoacidosis.
Linezolid is an oxazolidinone antibiotic that inhibits
bacterial protein synthesis. It can also impair mitochon-
drial ribosomal function, leading to severe lactic acidosis,
liver toxicity, and myelosuppression.4 Nucleoside
analogue reverse transcriptase inhibitors, propofol, and
metformin can also lead to mitochondrial dysfunction and
metabolic acidosis. Major risk factors for linezolid toxicity
include prolonged exposure, administration of relatively
higher doses, and baseline chronic liver or kidney dis-
ease.4 Our patient’s high-AG lactic acidosis is most likely
Box 1. Causes of Anion Gap Metabolic Acidosis
QUIZ
• Ketoacidosis
> Diabetic ketoacidosis
> Alcoholic ketoacidosis
> Starvation ketoacidosis
• Lactic acidosis (D-lactate or L-lactate)
• Ingestion
> Intoxication with glycols
> Methanol
> Salicylates
• Kidney failure
Based on information in Gabow.1
Quiz
Box 2. Causes of Lactic Acidosis
Tissue hypoperfusion (type A)
• Hypovolemia
• Septic shock
• Cardiogenic shock
Decreased lactate utilization (type B); usually toxin-
induced impairment of cellular metabolism)
• Usually toxin-induced impairment of cellular metabolism
> Diabetic ketoacidosis
> Metformin
> Ethanol
> Mitochondrial dysfunction (nucleoside analogue
reverse transcriptase inhibitors, propofol, linezolid)
> Malignancy
> HIV infection
> β-Adrenergic agonists (intravenous epinephrine)
D-Lactate acidosis
• Short bowel syndrome
• Propylene glycol
Based on information in Madias.2
explained by linezolid toxicity. The patient’s respiratory
alkalosis was thought to be due to her cirrhosis, which is
associated with an increased level of progesterone, leading
to hyperventilation.
What is the best treatment for this patient’s
metabolic abnormalities?
Lactic acidosis often resolves rapidly following discontin-
uation of linezolid therapy.4,5 The medication was
stopped and repeat laboratory measurements at 72 hours
demonstrated significant improvement and normalization
of the patient’s bicarbonate and lactate values.
Final diagnosis
High–anion gap lactic acidosis caused by line-
zolid toxicity, and respiratory alkalosis caused by
cirrhosis.
Article Information
Authors’ Full Names and Academic Degrees: Carmen Elena
Cervantes, MD, Steven Menez, MD, MHS, Jose M. Monroy
Trujillo, MD, and Mohamad Hanouneh, MD.
Authors’ Affiliations: Division of Nephrology, Department of
Medicine, Johns Hopkins University School of Medicine (CEC,
SM, JMMT, MH); and Nephrology Center of Maryland,
Baltimore, MD (MH).
Address for Correspondence: Carmen Elena Cervantes, MD,
1830 E Monument St, Rm 416, Baltimore, MD 21287. E-mail:
ccervan2@jhmi.edu
Support: None.
Financial Disclosure: The authors declare that they have no
relevant financial interests.
Quiz
Peer Review: Received April 19, 2020. Direct editorial input from 3. Singh R, Arain E, Buth A, Kado J, Soubani A, Imran N.
the Education Editor and a Deputy Editor. Accepted in revised Ethelene glycol poisoning: an unusual cause of altered
form June 27, 2020. mental status and the lessons learned from management of
Publication Information: © 2020 Published by Elsevier Inc. on the disease in the acute setting. Case Rep Crit Care.
behalf of the National Kidney Foundation, Inc. doi: 10.1053/ 2016;2016:9157393.
j.ajkd.2020.06.022 4. LiverTox: Clinical and research information on drug-
induced liver injury. National Institute of Diabetes
and Digestive and Kidney Diseases; 2012. Accessed
References June 27, 2020. https://www.ncbi.nlm.nih.gov/books/
1. Gabow PA. Disorders associated with an altered anion gap. NBK547852/.
Kidney Int. 1985;27(2):472-483. 5. Kraleti S, Soultanova I. Pancytopenia and lactic acidosis
2. Madias NE. Lactic acidosis. Kidney Int. 1986;29(3):752- associated with linezolid use in a patient with empyema.
774. J Ark Med Soc. 2013;110(4):62-63.

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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 “Clinical
Approach to a Patient With an Acid-Base Disturbance,” author Mohamad Hanouneh is a Nephrology Fellow at Johns Hopkins.
Program: Johns Hopkins Nephrology Fellowship Program (www.hopkinsmedicine.org/nephrology/education/)
Program Director: C. John Sperati, MD, MHS
Program Description from Dr Sperati: The Johns Hopkins University School of Medicine has a long history of
discovery in Nephrology, from the earliest demonstration of in vivo dialysis to the development of cutting-edge
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and the Johns Hopkins Bayview Medical Center. The Fellowship has established tracks in Clinical Investigation,
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