The myth of lactic acidosis

Facts about anaerobic metabolism

• During anaerobic conditions electron transport chain (ETC) i.e. oxidatative phosphorylation cannot function
• Pyruvate generated by the first part of glycolysis cannot enter the Krebs (Citric acid) cycle prior to entering the ETC
• The only available pathway for pyruvate is to be converted to lactate (not lactic acid)
• NAD & FAD that was otherwise generated by the CAC for participation in the ETC is also reduced
• The net effect is a significant reduction in energy yield from one molecule of pyruvate (or glucose)

Facts about lactate

• complementary base
• at physiologic pH is mainly ionised (pKa 4) = trivial amounts of lactic acid
• lactate is measured in clinical labs
• converted from pyruvate in anaerobic metabolism
• can be reconverted to pyruvate in muscle during aerobic conditions or circulated to liver for reconversion to glucose (Cori cycle)
• can be elevated in conditions of v tissue oxygenation, ^ glycolytic activity, v function of ETC, v clearance by liver

Facts about 'lactic acidosis' (correctly renamed lactate associated acidosis)

• Two clinical types - Type A - decreased tissue oxygenation (common) e.g. hypoxia or circulatory shock, Type B - cellular toxins affecting oxidative phosphorylation (uncommon) e.g. cyanide, metformin, salicylate toxicity, thiamine deficiency
• Acidosis is generated by inadequate regeneration of ATP by the reactions of oxidative phosphorylation.
• ATP + H2O <> ADP + Pi + H+
• ATP pool becomes depleted and ADP + Pi + H+ predominate

Hyperlactataemia without acidosis

• Occurs with inadequate clearance of lactate e.g. liver disease or exogenous administration e.g. Ringer's lactate
• In presence of adequate tissue oxygenation and liver function, added lactate can usually be cleared.

Why the confusion?

• During anaerobic metabolism, lactate and H+ appear simultaneously (but produced by separate mechanisms). Both decrease as oxygenation improves.
• In the lab setting, lactic acid can be detected in significant amounts as pH of sample dramatically falls
• In physiologic setting, buffering of plasma pH results in lactate remaining in ionised form

NB physiologic H + measured in nanomolar concentrations (hence use of pH) whilst lactate measured in millimole concentrations. They do not rise in equimolar amonts.

Rising lactate can be used as a marker of anaerobic metabolism, is not the cause of the acidosis and not invariably associated with it.

Elevate lactate can also occur in aerobic conditions due to liver dysfunction.