From the Guidelines
Refractory lactic acidosis with no identifiable etiology is most likely caused by mitochondrial toxicity, particularly in patients taking Nucleoside Reverse Transcriptase Inhibitors (NRTIs).
Key Points
- The mitochondrial basis of NRTI-induced lactic acidosis and hepatic steatosis is a possible mechanism of cellular injury, as NRTIs inhibit DNA polymerase γ, responsible for mitochondrial DNA synthesis 1.
- Risk factors for experiencing this toxicity include obesity, being female, and prolonged use of NRTIs, although cases have been reported with unknown risk factors 1.
- Clinical signs and symptoms of patients with lactic acidosis syndrome are variable and can include nonspecific gastrointestinal symptoms, abdominal distention, nausea, abdominal pain, vomiting, diarrhea, anorexia, dyspnea, generalized weakness, and hepatomegaly 1.
- Laboratory evaluation may reveal an increased anion gap, elevated aminotransferases, creatine phosphokinase, lactic dehydrogenase, lipase, and amylase, as well as microvesicular steatosis on liver histology 1.
- Discontinuation of NRTIs, bicarbonate infusions, and hemodialysis may be necessary to manage severe lactic acidosis, and thiamine and riboflavin may be administered based on the pathophysiologic hypothesis of sustained cellular dysfunctions of the mitochondrial respiratory chain 1.
From the Research
Causes of Refractory Lactic Acidosis
- Lactic acidosis can be caused by impaired tissue oxygenation (Type A) or disorders in which tissue oxygenation is maintained (Type B) 2
- Type A lactic acidosis occurs when the body must regenerate ATP without oxygen (tissue hypoxia), and can be caused by circulatory, pulmonary, or hemoglobin transfer disorders 3
- Type B lactic acidosis can be caused by malignancies, such as small cell carcinoma of the lung 4, or other abnormal metabolic activities in the absence of hypoxia 5
- Underutilization of lactate can also occur due to liver disease, inhibition of gluconeogenesis, pyruvate dehydrogenase (thiamine) deficiency, and uncoupling of oxidative phosphorylation 3
Identifying the Cause of Refractory Lactic Acidosis with No Identifiable Etiology
- In some cases, refractory lactic acidosis may be caused by an underlying, undiagnosed malignancy, as seen in a case report of a patient with small cell carcinoma of the lung 4
- A systematic approach to diagnosis and management can help identify any underlying pathology and aid in early management 5
- The co-occurrence of both Type A and Type B lactic acidosis can make management difficult, and a thorough evaluation of the patient's condition is necessary to determine the underlying cause 5