Lactate has been viewed as a byproduct of anaerobic metabolism and an indicator of tissue hypoperfusion since the 1900s. This theory is still widely believed. Paul busts the myths surrounding lactic acidosis, anaerobic metabolism, tissue hypoxia and the role of lactate in sepsis.
Key take-away facts include:
- The production of lactate actually consumes hydrogen ions. Lactic acidosis is really lactic alkalosis.
- Lactate is produced physiologically and is a precursor for gluconeogenesis.
- During exercise, skeletal muscle exports lactate as the primary fuel for the heart and brain.
- At VO2max, intracellular oxygen stays the same. Anaerobic metabolism in cells only occur as a pre-terminal event. The exception is in complete arterial occlusion.
- Adrenaline promotes lactate production
- Lactate infusion has been shown to increase cardiac output in septic and cardiogenic shock
- Lactate is a survival advantage!
3. Humans drink alcohol
They cannot undergo anaerobic fermentation
and only undergo anaerobic
metabolism as a pre-terminal event
4. The Myths
Lactate causes an acidosis
Increased lactate is due to anaerobic metabolism and decreased
oxygen delivery
Anaerobic production of lactate occurs during exercise
A defining feature of “shock” is anaerobic metabolism
The earth is round
16. Am. J.Physiol 2004;287;R502
Lactic acidosis is a condition that does NOT EXIST
Lactate production retards, not causes, acidosis
The lactic acidosis explanation of metabolic acidosis is not
supported by fundamental biochemistry and has no research
base of support
Acidosis is caused by reactions other than lactate production.
Every time ATP is broken down to ADP and Pi, a proton is
released
17. Normal Lactate Metabolism
Serum Level< 2 mmol/l
Daily production ~ 1400 mmol/day
Metabolized in liver (70%) and
kidney (30%) via Cori cycle
45. Cell-to-cell lactate shuttle
Brain and cardiac oxidation of lactate increase during
exercise and shock
Lactate removal during stress associated with cardiovascular
collapse
Infusion of lactate increases cardiac output in cardiogenic
and septic shock
Infusion of lactate improves energy utilization and cognitive
function afterTBI
50. Clinical Plausibility
Lactate increases in adrenergic states
Lactate increases with epinephrine infusion
Lactate increases with hyperdynamic sepsis
All these states have high cardiac output, high
oxygen delivery and not a trace of “hypoxia”
51. Conclusions
Lactate is not an accurate, reliable or robust marker of “hypoxia”
(whatever that is)
Its link with “hypoxia” is biologically implausible
It is experimentally flawed
It is clinically implausible (except perhaps with complete
regional vessel occlusion)
52. Conclusions
It is now clear that lactate is a major mitochondrial fuel
It is rapidly utilized in cell to cell and intra-cell shuttles
It is taken up by mitochondria to optimize bioenergetics
It acts like a hormone with powerful effects on protein
synthesis
53. Conclusions
Lactate is associated with increased mortality
The association is related to the fact that lactate is a
biomarker of physiological stress
The greater the physiological stress the greater the risk of
death!