Lactic Acidosis – Types, Causes, and Differential Diagnosis

ACID-BASE DISTURBANCES

Definition: Lactic acidosis is defined as a plasma lactate concentration of 4 mmol/L or higher. Lactate levels > 2 mmol/L defines hyperlactatemia
Cause: Impaired tissue oxygenation → increased anaerobic metabolism → lactate.
Lactic acid levels rise b/c of either increased production or decreased use or both. This happens by 3 mechanisms. 1) Increased pyruvate production. 2) Reduced entry of pyruvate into the mitochondria for oxidation into CO2 and H2O or conversion to glucose precursors. 3) A shift of the reduction-oxidation state inside the cellular cytoplasm that drives the pyruvate/lactate ratio toward lactate.

Type A – Impaired tissue oxygenation (at a systemic level)

Type-A lactic acidosis is 2/2 hypoperfusion and hypoxia, which occurs when an oxygen consumption/delivery mismatch occurs, with resulting anaerobic glycolysis. The hypoperfusion results from hypovolemia, cardiac failure, sepsis, or cardiopulmonary arrest, etc. Examples of type-A lactic acidosis include:

  • Respiratory and circulatory failure
  • All shock states – sepsis/septic shock, cardiogenic shock, hypovolemic shock, obstructive shock.
  • Regional ischemia e.g. limb ischemia, mesenteric ischemia/ischemic bowel,
  • Seizures/convulsions, and
  • Severe cases of shivering.
  • Carbon monoxide
  • Cyanide

Type B – No impairment in tissue oxygenation

“Type-B lactic acidosis is defined as not having to do with tissue hypoxia or hypoperfusion.” “Both type-A and type-B share the fundamental problem of the inability of mitochondria to process the amount of pyruvate with which it is presented.” The lactic acid cycle becomes activated which results in excessive levels of lactate.

Examples of type-B lactic acidosis are:

  • Diabetic ketoacidosis. Pts w/ DKA also often have some degree of lactic acidosis.
  • Metformin can cause lactic acidosis.
  • Epinephrine
  • Liver disease – lactate utilization may fall as a result of liver dysfunction. See Cori cycle or Lactic Acid Cycle.
  • Malignancy e.g. leukemia, lymphoma, and solid malignancies. Could be 2/2 to “anaerobic metabolism due to dense, underperfused clusters of tumor cells and/or metastatic replacement of the hepatic parenchyma has been proposed.” UTD
  • Total parenteral nutrition,
  • HIV – HIV meds (ARTs) can cause some mitochondrial dysfunction → increased lactate.
  • thiamine deficiency,
  • Mitochondrial dysfunction. This can be congenital or drug induced.
  • Congenital lactic acidosis,
  • Trauma,
  • Excessive exercise,
  • Alcoholism / ethanol intoxication. A small amout of lactic acidosis can develop in pts with chronic severe alcoholism. Lactate production is normal, but lactate utilization may fall as a result of liver dysfunction.

D-lactic acidosis 

In nature lactate exists in two isoforms: L-lactate and D-lactate. L-lactate is the most abundant form and is the isoform that is usually measured in point of care lab tests. Blood has about 100 times more  of the L-lactate than the D-lactate stereoisoform. However, D-lactate is the predominant form of lactate produced by some bacterial species. In patients with short bowel syndrome or other forms of gastrointestinal malabsorption, these D-lactate producing bacterial species metabolize (ferment) the abnormally large amounts of glucose and starch are into multiple organic acids, including D-lactic acid. Humans metabolize the D-lactate isoform very slowly and so the levels can rise in plasma leading to metabolic acidosis.

D-lactic acidosis is a rare but occurs with the following:

  • Short bowel syndrome or other forms of G.I. malabsorption
  • Infusion of propylene glycol (a solvent for some IV mes)
  • Diabetic ketoacidosis.

 

Sources / Reference

print