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Lactic Acidosis
J. Ryan Altman, MD
AM Report
6 October 2009
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)
Lactic Acidosis

Type A

Impairment of tissue oxygenation


Type B

Circulatory or respiratory failure, sepsis, ischemic bowl, carbon
monoxide, marked tissue hypoperfusion (shock), hypovolemia
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)
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 Llactate dehydrogenase (which normally
catalyzes conversion of L-lactate into
pyruvate)
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
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






Shock
Cardiac arrest
Acute pulmonary edema
Carbon monoxide poisoning
Severe hypoxemia (PO2 <25-30mmHg)
Pheochromocytoma

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
Decreased O2 delivery
Reduced O2 utilization


D-lactic acidosis
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
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

Symptomatic myopathy associated with prolonged use

Both lactic acidosis and severe hepatomegaly c steatosis incl fatal
cases, associated with NRTI alone or in combination
Myopathy (Zidovudine)
Lactic Acidosis
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
Bibliography
 Causes of Lactic Acidosis.
www.uptodateonline.com 6 Oct 2009.
 Sabatine, Marc. Pocket Medicine 3rd
Ed.
 Epocrates
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