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2_ A 44-year-old female presents to the emergency room complaining of acute headache, lethargy and breathlessness. Physical examination reveals tachypnea. Her heart and lung sounds are normal. Past medical history is significant for HIV infection diagnosed 20 years ago. Her medications include a HAART regimen of efivirenz. zidovudine and lamivudine. She has taken these medications consistently for the last nine years, but has been taking zidovudine consistently from the time she was diagnosed with HIV. She denies using any other prescription of over the counter medications. She denies nicotine, alcohol or illicit drug use. On review of systems, she endorses abdominal pain but denies vomiting and diarrhea. Her initial laboratory tests are shown below,
Blood Ph= 7.2, PaO2= 100mmHg, PaCO2= 30mmHg, HCO3= 8mEq/L
WBC count= 9.000/cmm, Hb= 14 mg/dL
Na= 138mEq/L, K= 4mEq/l, Cl-= 104mEqfl-,
ALT= 52U/L, AST= 48U/L
Which of the following is the most likely primary cause of the patient's acid-base disturbance?
A. Increased metabolic rate
B. Decreased oxygen delivery to tissue
C. Reduced oxygen utilization by tissues
D. Impaired excretion of lactic acid
E. Increased gut absorption
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D. Impaired excretion of lactic acid ?
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DD
It is lactic acidosis-steatosis syndrome due to Zidovudine
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_ The correct ans is CCC : Reduced oxygen utilization by tissues
EXplanation:
The patient described most likely is experiencing the lactic acidosis-steatosis syndrome (LASS). LASS is a condition associated with prolonged use of nucleoside reverse transcriptase inhibitors (NRTls). particularly zidovudine. LASS is over twice as common in female patients as it is in male patients. The anion gap metabolic acidosis is evident in the labs given (low pH, primary decrease in HCO3-. compensator/ decrease in PaC02. AG = 26). The associated steatosis is suggested by the modestly elevated transaminases and could be further proven by imaging or fiver biopsy. This condition results from inhibition of mitochondrial DNA synthesis by the NRTi agent. Specifically, NRTls have been shown to inhibit DNA polymerase gamma leading to depletion of mtDNA. Mitochondrial dysfunction ensues causing both steatosis and lactic acidosis. Lactic acidosis in this case results from failure of the tissues to utilize oxygen due to the failure of aerobic metabolism, which takes place in the mitochondria.
(Choice A) An increased metabolic rate may cause lactic acidosis if there is insufficient oxygen present in the tissues and anaerobic metabolism ensues.
(Choice B) Decreased oxygen delivery to tissue may occur in cases of carbon monoxide poisoning, circulatory collapse, occlusive vascular disease and others.
(Choice D) Impaired excretion of lactic acid as well as other serum acids occurs in renal failure resulting in an anion-gap metabolic acidosis.
(Choice E) Increased girt absorption of lactic acid may occur in cases of intestinal blind loop syndrome where excessive production and absorption of D-lactate causes a hypochloremic metabolic acidosis.
Educational objective:
Nucleoside reverse transcriptase inhibitors may cause lactic acidosis and steatosis due to inhibition of DNA polymerase gamma and depletion of mitochondrial DNA.
