My friend, Paul Marik, is a mythbuster. He has been vindicated in so many viewpoints that were initially branded as crazy. But… sometimes the weapon he chooses, in his war against perceived pseudo-axioms, is hyperbole. This was the case in a few instances in his talk from SMACC-Chicago on Lactate:
The Paper Paul Cited
- Roberg Article [cite source='pubmed']15308499[/cite]
The Many Retorts Explaining Its Flaws
- If you only read one retort
- [cite source='pubmed']16105825[/cite]
- [cite source='pubmed']16760335[/cite]
- [cite source='pubmed']16105824[/cite]
- [cite source='pubmed']16105823[/cite]
Post-Publication Peer Review
I wanted to be extra sure about this one before sending it to Paul, so I reached out to the brilliant Dr. David Story:
I agree with your thoughts, I’ll try not to be too random in my response as a Stewartite.
From a Stewart perspective Dr Marik’s comments about lactate seem incorrect.
One of the many attractions of the Stewart quantitative approach to acid-base (Stewart 2009) is that one does not have to do hydrogen ion accounting. What determines hydrogen ion concentration (and pH) in body fluids (plasma, interstitial AND intracellular) is the partial pressure of carbon dioxide, the strong-ion-difference, and the total weak acids (Stewart 2009). Water is the hydrogen ion source.
Lactate has a pKa of 3.9 (pH of 50% dissociation), and is therefore almost completely dissociated in plasma at pH 7.40. In plasma, lactate is a strong anion and acts like chloride in quantitative acid-base assessment. This effect can be easily quantified in clinical chemistry (Story 2016).
The same applies to the intracellular environment (Magder 2009) including skeletal muscle at maximal exercise or any lactate producing cell in sepsis. If lactate increases without a change in other ions the strong-ion-difference will decrease and acidity will increase. At extreme exercise the pH in skeletal muscle will be above 6.2. Even if one were to argue that lactate is no longer acting like a strong anion in pockets of extreme acidity such as lysozymes, it would be acting like a weak acid and increases in total lactate will increase acidity. Therefore if lactate goes up, acidity goes up. The paper referred to Dr Marik by Robergs (2004) demonstrates how confusing acid-base can be if trying to account for hydrogen ions, particularly when considering complex metabolism. Ignore the attempts to account for hydrogen ions in assorted cellular events and stick with the strong-ion-difference and total weak acids: increased lactate causes acidosis in any body fluid.
- Stewart PA, Whole-body acid-base balance. IN: Kellum JA, Elbers PWG (Eds) Stewart’s Textbook of Acid-Base. 2nd Ed. www.AcidBase.org, 2009
- Magder S, Intracellular [H+]. IN: Kellum JA, Elbers PWG (Eds) Stewart’s Textbook of Acid-Base. 2nd Ed. www.AcidBase.org, 2009
- Story D. (Open Mind) Stewart Acid-Base: A Simplified Bedside Approach. Anesthesia and Analgesia, 2016 (ePub ahead of print).
- Robergs RA, Ghiasvand F, Parker D. Biochemistry of exercise-induced metabolic acidosis. Am J PhysiolRegulIntegr Comp Physiol. 2004 Sep;287(3):R502-16
Professor David Story, MBBS, MD, BMedSci, FANZCA
Chair of Anaesthesia
The University of Melbourne, Australia