Lactic Acidosis (Overview)

Lactate is produced from pyruvate in the absence of adequate oxygen in the cells.  Recall from biochemistry the metabolism of glucose in our cells:

• Glucose turns into Pyruvate (via Glycolysis in the cytoplasm) à H2O + CO2 + Lots of ATP (via Krebs cycle and oxidative phosphorylation in the mitochondria, using Oxygen)

In the absence of adequate oxygen, the mitochondrial pathway is not available to create loads of ATP. 

• Instead:  Pyruvate turns into Lactic acid (via lactate dehydrogenase enzyme using NADH as cofactor). 

Lactate is then released into the blood for circulation, and is converted back to pyruvate in the liver (primarily) and kidneys (to a lesser extent). 

Etiologies of Lactic Acidosis - can be thought of under the Cohens-Woods Classification:
1) Type A Lactic Acidosis = Due to Poor Tissue Oxygenation
- Shock (any etiology – cardiogenic, septic, hypovolemic, etc)
- Regional ischemic or infarction – e.g. Ischemic Bowel
- Carbon Monoxide poisoning
- Hypoxic Respiratory Failure

2)  Type B Lactic Acidosis = Occurs in the presence of Normal Tissue Oxygenation
a.   Type B1 = Systemic Diseases
- Liver dysfunction (as lactate is primarily cleared by the liver)
- Renal dysfunction (lactate is cleared to a lesser extent by the kidneys)
- Malignancies – unclear pathophysiology and most malignancies do NOT lead to lactic acidosis.  Proposed mechanisms include: anaerobic metabolism due to dense clusters of tumor cells, Mets to the liver causing hepatic dysfunction, and direct lactate production by tumor cells.
- Alcoholism – due to impaired lactate utilization due to decreased hepatic gluconeogenesis
- Diabetic Ketoacidosis
- Seizures – large production of lactate that is typically rapidly cleared after seizures are controlled

b. Type B2 = Drug/Toxin induced
- Biguanides – classically, Phenformin (the predecessor of Metformin) and to a lesser extent Metformin (controversial)
- HIV meds – NRTIs – cause mitochondrial toxicitiy
- Salicylates
- Isoniazid
- Linezolid
- Cyanide

c.   Type B3 = Inborn errors of metabolism

Must rule out type A lactic acidosis before assuming it is type B!! Also, abdominal pain + lactic acidosis = bowel ischemia until proven otherwise!!

3) D-type Lactic Acidosis - The lactate discussed above is actually L-type lactic acid, which is  what is measured by most assays.  There is also a D-type lactic acid, which is a byproduct of bacterial metabolism in the gut and is absorbed there as well.  It can accumulate in patients with abnormal GI tracts such as short gut syndrome, small bowel resections, jejunoileal bypass, etc.

(Chanu Rhee MD, 1/21/11)