CRIT CLOUD

  • Summaries & Reviews
    • Airway
    • Cardiovascular
    • Controversies
    • Endocrinology
    • Fluids
    • Guidelines
    • Infections
    • Neurology
    • Nutrition
    • Pharmacology
    • Procedures
    • Radiology
    • Renal
    • Resuscitiation
    • Respiratory
    • Sedation
    • Sepsis
    • Transfusion
  • World of Foam
  • FOAM.education
  • Education
    • ACLS Training ICU Lindenhofspital
    • Download Presentations
    • Download CME Galway Clinic 🔒
    • Download CME Lindenhof Hospital 🔒
    • Echo 🔒
    • Presentations🔒
    • Multimedia
  • About Us
    • Contact
  • Summaries & Reviews
    • Airway
    • Cardiovascular
    • Controversies
    • Endocrinology
    • Fluids
    • Guidelines
    • Infections
    • Neurology
    • Nutrition
    • Pharmacology
    • Procedures
    • Radiology
    • Renal
    • Resuscitiation
    • Respiratory
    • Sedation
    • Sepsis
    • Transfusion
  • World of Foam
  • FOAM.education
  • Education
    • ACLS Training ICU Lindenhofspital
    • Download Presentations
    • Download CME Galway Clinic 🔒
    • Download CME Lindenhof Hospital 🔒
    • Echo 🔒
    • Presentations🔒
    • Multimedia
  • About Us
    • Contact

Reviews and Summaries

Lactate - From Bad to Good? An Explanation Trial

14/2/2016

 
Picture
The discussion on the so-called lactic acidosis and its causes have become increasingly attractive over the last couple of years as several biochemical explanations are challenged. A significant confusion persists on the various relationships between lactate, lactic acid and metabolic acidosis. 

Most clinicians continue to refer to the traditional understanding of impaired tissue oxygenation causing increased lactate production, impaired lactate clearance and therefore resultant metabolic acidosis. Just recently we had a discussion on our ward round on this topic when a team member presented the most recent article of UpToDate online on the causes of lactic acidosis. The authors state that 'Lactic acidosis is the most common cause of metabolic acidosis in hospitalised patients' and that 'Lactic acidosis occurs when lactate production exceeds lactate clearance. The increase in lactate production is usually caused by impaired tissue oxygenation...'... finally suggesting that lactate is no good!

These statements support the classical understanding that:
- Hyperlactatemia is caused by tissue hypoxemia, and
- This in turn then leads to a metabolic acidosis called lactic acidosis


This biochemical understanding has persisted for decades, but there are some good reasons to vigorously challenge this traditional aspect on the 'bad' lactate. Lactate turns out to be by far more complex in its characteristics and functions, so I decided to try and make a short but comprehensive overview of this molecule.

What is lactate?

Picture
Lactate is a small organic molecule with the chemical formula CH3CH(OH)CO2H and structurally looks like on the image to the left. It is produced in the cytoplasm of human cells mainly by anaerobic glycolysis by the conversion of pyruvate to lactate by LDH. This chemical reaction results typically in a blood lactate to pyruvate ratio of about 10:1. And while lactate is produced, NAD+ also is incurred, and this actually can accept protons itself, so does not result in acidosis itself.

Lactate arises from the production of energy by consuming glycogen and glucose.

Picture


​Where does it come from?

Picture
Typically most people think of muscles first as an origin of lactate. As a matter of fact lactate originates from many other organs, including our red blood cells. Red blood cells always produce lactate as they lack the mitochondria required to regenerate NAD+ needed for glycolysis.  In general, you can say that tissues with lots of LDH are the primary producers of lactate. Around 20mmol/kg/day of lactate are produced under normal circumstances.

Lactate is not only produced in skeletal muscle.

Muscle: 25%
Skin: 25%
Brain: 20%
RBC: 20%
Intestine: 10%

What happens with it?

Lactate is not just for nothing. After its production by anaerobic glycolysis lactate is reutilised, for instance in the liver and the cortex of the kidneys. As an example: under the influence of cortisol it is used for gluconeogenesis in hepatocytes and restores glucose and glycogen. Also, it is a part of oxidative phosphorylation in the liver, kidney, muscles, the heart and the brain. Like this lactate helps conserve glucose levels in our blood.
​
​Lactate actually serves as a fuel for oxidation and glucose regeneration and therefore is a source for energy itself.
Picture
From The Lancet Endocrinology 2013


​
​How does hyperlactatemia develop?

In general, you can assume that there is a balance between lactate production and its consumption or usage. The classical understanding that tissue hypoxia leads to overproduction and underutilisation by impaired mitochondrial oxidation is correct.

The critical point though is that lactate is also produced via aerobic glycolysis as a response to stress. This happens in septic patients, asthmatic exacerbations, trauma and other critical conditions. In these situations, the trigger for lactate production is adrenergic stimulation and NOT tissue hypoxia. There are also several other reasons for hyperlactatemia other than tissue hypoxia:


Sepsis:      Adrenergic drive
Asthma:    Adrenergic drive
Trauma:    Adrenergic drive
Cardiogenic and haemorrhagic shock: Adrenergic drive
Pheochromocytoma: Adrenergic drive
Inflammation: Cytokine drive
Alkalosis, antiretroviral medication and others


Also, there is good evidence showing that organs like the lungs are an important producer of lactate during stress. And of course in all these conditions hypoxic and non-hypoxic hyperlactatemia might also co-exist.

In critically ill patients often other reasons than tissue hypoxia are responsible for hyperlactatemia (e.g. adrenergic drive).
​

Is lactate harmful?

In contrast to the classical understanding of lactate and lactic acidosis more and more evidence comes up indicating that lactate during stress actually serves as a fuel for energy production. Various tissues, e.g. the myocardium increase their lactate uptake during stress significantly. Also, our brain consumes more lactate during stress which is used for oxidation. Research has shown that lactate infusions improve cardiac output in pigs and even in patients with heart failure. 

Experimental work on isolated muscles suggests that circulating catecholamines and development of acidic conditions during exhaustive exercise may improve muscles' tolerance to elevated K+ levels. This implies that during high-intensity activity with high extracellular K+
 and adrenaline, lactate serves as a performance-enhancing chemical, rather than being the cause of muscle fatigue.

Lactate is not harmful to our organism. On the contrary, recent compelling evidence suggests that lactate might be beneficial, rather than detrimental, during high-intensity activity and to force development in working heart and skeletal muscle.
​

Why do critically ill patients with hyperlactatemia die more often then?

In critical care hyperlactatemia indeed is a marker of illness severity and a strong indicator of mortality. This is especially true for patients with sepsis. However, as described above, hyperlactatemia often doesn't indicate hypoperfusion or tissue hypoxia. Hyperlactatemia rather reflects the severity of illness by representing the degree of our body's activation to stress. A fall in lactate concentration following treatment of critically ill patients is due to an attenuation of the stress response rather than to correction of oxygen debt.

​Hyperlactatemia reflects a severe disease and the patients' response to stress. Patients die due to their illness, not because of high lactate.
​

What about Ringer's lactate?

Picture

Ringer's lactate (RL) is not harmful in patients with hyperlactatemia.

As a matter of fact RL turns out to be superior compared to normal saline in hyperlactatemia, acidotic patients and patients with hyperkalemia.
​

The bottom line

- Lactate is an indicator of stress, a marker of illness severity and a strong predictor of mortality, but not harmful as a molecule itself.

- Lactate is helpful
 as an essential source of energy and an important fuel for oxidation and glucose generation.

- During conditions like septic shock, there is no proof that lactate is produced only due to tissue hypoxia. In fact, well-ventilated lungs provide a large amount of lactate during sepsis. Lactate in sepsis and other critical conditions is mostly not due to hypoxemia or hypoperfusion.

- Ringer's lactate contains sodium lactate, but not lactic acid. Lactate itself, as mentioned above, is beneficial in severe disease. Therefore RL remains the fluid of choice during severe disease like for instance septic shock.

- Ringer's lactate is superior to normal saline in patients with metabolic acidosis, hyperlactatemia and also hyperkalemia.
​

Got interested in some better understanding? START READING HERE:

Emmettt et al. UpToDate online, August 2015, Causes of lactic acidosis

Garcia-Alvarez et al. Critical Care 2014, 18:503


Marik PE, Bellomo R. OA Critical Care 2013 Mar 01;1(1):3

Garcia-Alvarez et al. Lancet Diabetes Endocrinol. 2014 Apr;2(4):339-47.

Andersen JB et al. Journal of Experimental Biology  
2007  210: vii doi: 10.1242/jeb.001107​

Bakker J et al. Intensive Care Med (2016) 42:472–474



Also, have a listen to Bellomo's review on lactate:
Picture
Click in image to listen to podcast

Comments are closed.

    Search


    ​Translate

    Select your language above. Beware: Google Translate is often imprecise and might result in incorrect phrases!

    Picture


    ​Categories

    All
    Airway
    Cardiovascular
    Controversies
    Endocrinology
    Fluids
    For A Smile ; )
    Guidelines
    Infections
    Meducation
    Neurology
    Nutrition
    Pharmacology
    Procedures
    Radiology
    Renal
    Respiratory
    Resuscitation
    SARS CoV 2
    SARS-CoV-2
    Sedation
    Sepsis
    Transfusion

    Archives

    January 2021
    September 2020
    March 2020
    February 2020
    January 2020
    December 2019
    November 2019
    July 2019
    May 2019
    March 2019
    February 2019
    January 2019
    December 2018
    January 2018
    October 2017
    August 2017
    June 2017
    March 2017
    February 2017
    January 2017
    October 2016
    July 2016
    June 2016
    April 2016
    February 2016
    December 2015
    October 2015
    September 2015
    August 2015
    July 2015
    June 2015
    May 2015
    April 2015
    March 2015
    January 2015
    December 2014
    November 2014
    October 2014
    September 2014
    August 2014
    July 2014
    June 2014
    May 2014
    April 2014
    March 2014
    February 2014
    January 2014
    December 2013
    November 2013

    Author

    Timothy Aebi

    RSS Feed

ABOUT US

The Crit ☁​ supports free access medical education. The content of this website can be used and reproduced by stating a reference to our site.
Read our statements here

SEARCH US

CONTACT US

If you have any interesting article or news to be posted on this website, please contact us here
​

FOLLOW US

TRUST US

TWEET US

This website is certified by Health On the Net Foundation. Click to verify. This site complies with the HONcode standard for trustworthy health information:
verify here.

Picture
Follow @BIJCorg

DISCOVER THE WORLD OF #FOAMed HERE
Picture