1. J. Ryan Altman, MD AM Report 6 October 2009
Lactic Acidosis
J. Ryan Altman, MD
AM Report
6 October 2009

2. Lactic Acidosis
Most common cause of metabolic acidosis in hospitalized patients
Associated with elev anion gap and plasma [lactate] > 4mEq/L
Result of both overproduction and underuse of lacate
Normal plasma [lactate] is 0.5 to 1.5 mEq/L
Causes
Impaired tissue oxygenation (Type A)
Systemic impairment in oxygenation is not apparent (Type B)

3. Lactic Acidosis Type A Type B Impairment of tissue oxygenation
Circulatory or respiratory failure, sepsis, ischemic bowl, carbon monoxide, marked tissue hypoperfusion (shock), hypovolemia
Type B
No impairment of tissue oxygenation (toxin-induced impairment of cellular metabolism or regional areas of ischemia)
Malignancy, alcoholism, NRTIs, salicylates, metformin
Predisposing conditions to metformin toxicity: renal insufficiency (Cr>1.5mg/dl), concurrent HF req pharmacologic therapy, liver disease or EtOH abuse
Malignancy: pathogenesis unclear, but removal of tumor (chemo, irradiation, or surgery) leads to correction of acidosis
Alcoholism: lactate production is nl, but utilization is diminished b/c of impaired hepatic gluconeogenesis.
HIV infection: may be from serious infections leading to sepsis induced lactic acidosis (Type A) or drug induced mitochondrial dysfunction in absence of sepsis or hypoperfusion (Type B)

4. Lactic Acidosis D-lactic acidosis
Seen in pts c jejunoileal bypass, small bowel resection, or other causes of short bowel syndrome
Glc and starch are metabolized in the colon to D-lactic acid, which is then absorbed in to the systemic circulation. Acidemia persists as D-lactate is not recognized by L-lactate dehydrogenase (which normally catalyzes conversion of L-lactate into pyruvate)

5. Lactic Acidosis (Etiologies)
Increased lacate production
Increased pyruvate production
Enzymatic defects in glycogenolysis or gluconeogenesis (type I glycogen storage disease)
Respiratory alkalosis, including salicylate intoxication
Pheochromocytoma
Impaired pyruvate utilization
Decreased activity of pyruvate dehydrogenase or pyruvate carboxylase
Congenital
? Role in DM, Reye’s syndrome

6. Lactic Acidosis (Etiologies)
Increased lactate production
Altered redox state favoring pyruvate conversion to lactate
Enhanced metabolic rate
Grand mal seizure
Severe exercise
Hypothermic shivering
Severe asthma
Decreased O2 delivery
Shock
Cardiac arrest
Acute pulmonary edema
Carbon monoxide poisoning
Severe hypoxemia (PO2 <25-30mmHg)
Pheochromocytoma
Reduced O2 utilization
Cyanide intoxication (decr oxidative metabolism): from cyanide poisoning or during a fire from smoke inhalation of vapors
Drug induced mitochondrial dysfunction due to zidovudine or stavudine
D-lactic acidosis

7. Lactic Acidosis (Etiologies)
Primary decrease in lactate utilization
Hypoperfusion and marked acidemia
Alcoholism
Liver disease
Mechanism uncertain
Malignancy
DM, including metformin in absence of tissue hypoxia
AIDS
Hypoglycemia
Idiopathic

8. Lactic Acidosis
Trizivir (nucleoside reverse transcriptase inhibitor x3)
Abacavir/Lamivudine/Zidovudine
Black Box Warning
Hypersensitivity Rxn (Abacavir)
Pts with HLA-B*5701 allele are at higher risk of hypersensitivity reaction
Hematologic Toxicity (Zidovudine)
Neutropenia and severe anemia
Myopathy (Zidovudine)
Symptomatic myopathy associated with prolonged use
Lactic Acidosis
Both lactic acidosis and severe hepatomegaly c steatosis incl fatal cases, associated with NRTI alone or in combination
Hep B exacerbation
Severe acute Hep B exacerbations in HBV/HIV co-infected pts upon lamivudine d/c. Monitor hepatic function closely for at least several months in HBV/HIV co-infected pts who d/c abacavir/lamivudine; initiate Hep B tx if needed

9. Bibliography
Causes of Lactic Acidosis. 6 Oct 2009.
Sabatine, Marc. Pocket Medicine 3rd Ed.
Epocrates

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