ED 3 AM: ambulance rushes in, pt in his 40's unconscious, BP 50/20, HR 140. Reanimation is started and arterial gases are ordered: lactate 10! Two hours later, pt conscious, MAP >65, HR 100, new arterial gases are ordered: lactate 9.

Was reanimation unsuccesful?

Poll & :

First, let's go #BackToBasics w/ lactate:

2 enantiomers: L & D

Formed from pyruvate by LDH (usual ratio 10:1)

PKa 3.8 (lactate predominant over lactic acid)

Can be used for ATP formation or gluconeogenesis (lacpyruvateA-CoA or lacpyruvateoxaloacetate)

We tipically associate w/ O2, but what else can ? Many things!:

Sepsis

Cyanide

CO

: MET, linezolid, paracetamol, NRTI's

thiamine

: Propylene glycol, methanol, ethanol

Malignancy

Cirrhosis

Severe asthma

surgery

So lactate ≠ O2: so far, so good. But it surely does in shock states, right?

Back in 1958, Huckabee observed the relationship between "oxygen debt" and "excess lactate", plotting almost superposable curves from the relationship of them.

Then in 1970, Weil further supported this data w/ a hemorrhagic shock model in which again correlated w/ O2 debt

Furthermore, the classic division of type A and B , assumes the former is always 2/2 a DO2/VO2 mismatch anaerobic glycolysis, and is the cause of in the critically ill pt, whilst the latter represents w/o anaerobic glycolysis.

But... Is it always true?

Not quite. In 1994, Boekstegers et al. measured skeletal muscle pO2 in three groups:
Sepsis
Limited infection
shock

They found pO2 to be in sepsis compared to the other 2 groups, being in more severe sepsis states!

But what about cellular dysoxia, you might ask?

Well, some people asked themselves that same question before! In 1992, Hotchkiss et al. injected fluoromisonidazole (binds covalently to cells in inv proportion to cell O2 tension) in septic and sham operated , finding no diff in it's concentration in various tissues (but )

Furthermore, in 2012 Regueira et al. used 32 w/ peritonitis, tamponade or hypoxemic hypoxia, demonstrating no increase in HIF-1α (hypoxia-inducible factor 1 alpha) in septic animals despite a 2x in lactate levels!

Another theory in sepsis states for is a DO2/VO2 mismatch; this was studied in 9 septic critically ill pts by Ronco et al. back in 1993 and... found sepsis didn't modify critical O2 delivery threshold for anaerobic metabolism compared to controls!

Furthermore, in 1994 Hayes et al. tried to achieve the following goals w/volume :

CI > 4.5 L/min/m²
DO2 >600 mL/min/m²
VO2 > 170 mL/min/m²

If achieved, randomized to dobutamine vs standard care. The results:

= MAP & VO2
in intervention group!

Ok, so where does lactate come from in sepsis?!

Well, here's an alt theory! aerobic glycolisis 2/2 adrenergic state:

CHO metabolism exceeds mitochondria oxidative capacity piruvate produced at rates than PDH can convert to ACoA piruvate lac by mass effect

What supports this theory?:

Septic pts whole mRNA analyisis: GLUT-1, LDH, PKM-2, hexokinase-3, MCT-4
Isotope dilution methods: Lac and glc turnover in
Lac kinetics: normal removal (pb source: production)
Cathecolamines β2 rec Na/K ATPase act

But do all organs produce lactate during sepsis? No! Some production, but some uptake!
The organs that mainly lactate in exp models are the lung and the muscle. And uptakers?:

Gut


Kidney

So, as García-Álvarez et al. fairly put it:

Furthermore, studies using labeled exogenous lactate in septic px have shown that 50-60% goes to oxidation by cells, whilst the remaining 30-40% is used as substrate for glycogen synthesis, acting under stress as both:

Alt fuel to glucose
A source for glucose itself

From all we've reviewed, we can see why the "lactate clearance" approach in sepsis seems to be a goal not to be pursued. We can't know if its "clearance" is 2/2 production, uptake, dilution by or a combination of the three!

Besides, it's levels ≠ or reanimation.

Time to wrap up:

Lactate can be by A LOT of causes

O2 doesn't seem to be lac origin in sepsis

Adrenergic (both endo and exogenous) seems to account for most of lactate in

uptake by organs in seems to be an energy adaptive mechanism

Hope you guys got here and enjoy reading the as much as I enjoyed doing it! Sources (PMID):

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