Morning Report: Lactic Acidosis - A Misnomer

Here’s Dr. Nordstrom with today’s Morning Report!

The Case:

69 M with history of HTN and DM presents with 1 day of nausea and vomiting. Pt says he woke up in the morning and after breakfast started feeling dizzy and lightheaded. Vomited 10+ times until he came into ER. Denied travel, no fevers, denied abdominal pain, no diarrhea.

ROS neg

PE:

Vitals: BP 133/76 HR 113 RR 18 Temp 98F

Appears uncomfortable, keeps his eyes closed

Vomiting repeatedly

Cool extremities

Abdomen soft, non-tender, hypoactive BS’s

EKG: sinus tach

Labs:

Trop I: negative

CBC: nml

pH 7.26/15/x/35

Creat: 2.0

Venous lactate: 12

Arterial lactate: 9

Lactic Acidosis: A misnomer

Lactic acid is a normal metabolite that exists as a link between aerobic and anerobic metabolism. During normal (aerobic) metabolism the majority of pyruvate enters the citric acid cycle via the thiamine dependent enzyme pyruvate dehydrogenase. However, when a state of relative oxygen deficiency exists based on cellular demands, increased amounts of pyruvate will be converted to lactate. Lactate can enter the systemic circulation and ultimately be converted back to pyruvate and eventually glucose in the liver via the Cori Cycle (however this is an energy requiring process and will not occur to a significant degree if there is ongoing oxygen deficiency, anerobic metabolism, and relative excess of NADH reducing equivalents).

Lactate itself is actually a weak base and its dissociation into H+ and lactate ion- is not what creates what we typically think of as “Lactic Acidosis.” In fact the production of lactate causes no net gain of H+ ions. Rather the acidosis often associated with lactic acid is the result of the hydrolysis of ATP via the reaction seen below, which does result in a net gain of H+ ions.

ATP + H20 –> ADP + P + H+

When there is ongoing anerobic metabolism, and the krebs cycle is not able to appropriately regenerate ATP, excessive H+ ions accumulate, and can overwhelm physiologic buffers causing an acidosis.

So not all processes that cause an elevated lactate level will produce an acidosis. The differential diagnosis for lactic acidosis is listed below and generally split into types A and B lactic acidosis. (There is often overlap in the pathophysiology)

Type A Lactic Acidosis (poor tissue oxygenation)

– Sepsis / Septic shock / Occult or Cryptic shock

– Cardiogenic, Obstructive, Hemorrhagic shock

– Regional ischemia: mesenteric ischemia, compartment syn, burns, necrotizing fasciitis, trauma

Type B Lactic Acidosis (decreased utilization or increased production)

– Excessive muscle activity: seizure, marathon runners, severe asthma, restrained patients not sedated.

– Toxins: Cyanide, Carbon monoxide, toxic alcohols (glycolate can cause false positive), cocaine

– DKA: (over 40% will have elevated lactate, not associated with worse increased mortality in patients with DKA)

– Thiamine deficiency

– Malignancy (Acute leukemia)

– Liver disease

– Inborn errors of metabolism (mitochondrial disorders)

– Drugs: Metformin, NRTI’s, Linezolid, Tylenol, Propofol

– “Stagnant blood”: RBCs carry out glycolysis but not aerobic metabolism, can be seen if blood sample is not run within 15 mins.

Further history from our patient revealed that he had just started taking Metformin 2 weeks prior to the onset of his symptoms.

Metformin Associated Lactic Acidosis:

– Inhibits cellular aerobic metabolism, decreased hepatic gluconeogenesis.

– Symptoms are nonspecific and include abdominal pain, nausea, vomiting, malaise, myalgia, and dizziness.

– Overall incidence 5/100,000 with metformin use

– Patients who present with toxic ingestion / overdose on metformin tend to have increased lactate levels, but not universally.

– Often associated with co-morbidities: renal insufficiency, CHF.

– Treatment: (generally supportive)

o If patient is in renal failure may need HD

o If HCO3 <5 consider giving bicarb for reduced buffering capacity.

References:

Controversies in Lactic Acidosis, Implications in Critically III Patients. Barry A. Mizock, MD. JAMA 1987. Vol 258. No 4
Etiology and Therapeutic Approach to Elevated Lactate Levels. Lars W. Andersen, MD; Julie Mackenhauer, MD; Jonathan C. Roberts, MD
Katherine M. Berg, MD; Michael N. Cocchi, MD; and Michael W. Donnino, MD. Mayo Clin Proc. 2013;88(10):1127-1140