Causes and Classification of Lactic Acidosis.

January 30, 2017

Type A lactic acidosis is by far the commonest group and is usually due to tissue hypoxia caused by systemic or local hypoperfusion, increased glycolysis, reduced oxygen carrying capacity of the blood or reduced tissue oxygen delivery. Apart from excessive muscle activity, other causes of type A lactic acidosis are rare. The inadequate oxygen supply slows mitochondrial metabolism and leads to increased production of lactate from pyruvate. As a byproduct, NAD+ is regenerated so that glycolysis can continue. If hypoxaemia is the only factor, it must be severe to overwhelm the compensatory increase in tissue blood flow triggered by low PO2.

Type B lactic acidosis is rarer and has classically been thought of as hyperlactataemia without evidence of tissue hypoxia; however, many causes of Type B lactic acidosis have occult hypoperfusion. Common drugs and toxins, such as nucleoside reverse-transcriptase inhibitors (NRTIs), toxic alcohols, salicylates, propofol and cyanide, can interfere with oxidative phosphorylation leading to lactic acidosis. Metformin inhibits complex 1 of the mitochondrial respiratory chain and also suppresses hepatic gluconeogenesis, resulting in both accelerated lactate production and reduced lactate metabolism. β2-agonists, including cocaine, epinephrine, inhaled salbutamol and terbutaline, stimulate aerobic glycolysis leading to a build-up of lactic acid levels.