Lactate
Why does Lactate Matter?
- Associated with all cause mortality
- Infection related mortality correlates with lactate levels 0-2.4 (4.9% mortality), 2.5-3.9 (9% mortality) and >4 (28.4% mortality) (Shapiro et al)
- But its also associated in Cardiogenic Shock, STEMI, PE, Cardiac arrest and burns
- Lactate clearance is also a good prognostic indicator
So where does lactate come from?
- Normal part of physiology
- In a steady physiological state it is held in equilibrium with pyruvate
- In aerobic states little lactate is produced as most pyruvate enters the krebs cycle
o Really efficient (2 ATS from glycolysis. Another 34 from the Krebs and Oxidative phosphorylation/electron transport chain)
- When the demand for ATP outstrips the oxygenation the krebs cycle cant function and so more lactate is produced to continue the production of ATP
- Remember that lactate and pyruvate are held in equilibrium and so any causes for pyruvate to be increased will also increase lactate.
o Glycolysis is dependent on NAD. Which is produced when pyruvate is converted to lactate. So in anaerobic conditions Glycolysis can continue.
How do we end up with raised lactates?
- I like to think about it in terms of increased production or reduced clearance
- Production
o Split it into physiological and non physiological
§ Physiological
· Tissue Hypoxia
· This can be relative ie exercise or seizure, with increased tissue demand
· Or actual through hypoxia or hypoperfusion
§ Non Physiological
· Impairment of any of the complex metabolic pathways
o Increased pyruvate
§ Either increased glycolysis – stress responses like sepsis, drugs like salbutamol, adrenaline
§ Or impaired PDH (limiting Acetyl Co A production) – thiamine deficiency
o Mitochrondiral disease limiting entry to oxidative pathways
- Reduced Clearance
o most lactate is processed in the liver through gluconeogenesis
§ liver injury
§ metformin (worth noting that metformin by itself will not cause a raised lactate. Only in OD, renal failure or other illness will it contribute to a raised lactate. (only reduces clearance by inhibiting gluconeogeneisis
How do we apply this clinically?
- The trap is that all lactate is hypoxia/shock related
- As we have talked about this is not the case
- Nice acronym for remembering the causes is
L iver
A cclerated glycolysis
C ongential disorders ie mitochrondial
T hiamine deficiency
A nerobic metabolism
T oxic, drug effects
E xtra cellular
S epsis
Liver disease
- Unable to clear lactate
Accelerated glycolysis
- Increased pyruvate
- Increased anaerobic demand
Congential
- Mitochrondrial disease prevents oxaditive pathways
Thiamine
- Deficiency prevents entry to krebs/aerobic pathway
Anaerobic Metabolism
- Regional Tissue Ischaemia
- Ischaemia, limb/bowel (raised lactate 96% Sensitive for bowel ischaemia)
- Compartment syndrome
Toxic/drugs
- Metformin inhibits gluconeogenesis (lactate not converted back to glycose) so increases base levels of lactate in the blood. Tends to only be in unwell patients with renal or heart failure as well. Outside of renal failure, liver failure or OD metformin associated lactates is unlikely
- B2 agonist, adrenaline, CO, alcohol, cocaine increase lactate
- As do linezolid, propofol, theophylline
Extra Cellular
- Alkalosis – lactate shifted into the blood stream
- Ie resp alkalosis
Sepsis
- Shock
- Hypoxia (relative and actual)
- Endogenous catecholamine production
There are a few other causes:
DKA
- Associated with raised Lactates
- High lactate not associated with worse outcomes
- Lactate and glucose levels correlate
- More likely due to altered metabolism rather than hypoperfusion
Malignancy
- Not really understood, most commonly from leukaemia or lymphomas that at rapidly progressive
- ??related to liver involvement causing over expression of glycolytic enzymes
Thoughts on lactate in trauma?
- Initial lactates high In non survivors
- But not always associated with end organ perfusion problems, may reflect high endogenous catelcholamine production, leading to an increase in glycolysis, and so pyruvate and then lactate.
- May indicate underlying tissue hypoperfusion with compensatory vital signs
Any interest in how lactates are measured?
- In POCT blood gas analysers
o From a modified amperometric cell
§ Contains lactate oxidase which produces hydrogen peroxide from lactate
· Hydrogen peroxide is oxidised at a platinum anode which produces a current proportional to the lactate concentration
· (current from a second electrode which functions without the enzyme is subtracted to eliminate inferference)
§ Amperometric cells red 13% higher then lab spectrophotometric analysers (in vitro glycolysis from RBC leads to false elevation of whole blood lactate)
· Correcting for haematocrit reduces this
