Talk:Lactic acidosis

Acidosis is not due to lactic acid
As I have mentioned on the talk pages of Anaerobic Respiration and Lactic Acid, relatively recent research has clearly established that lactate production in anaerobic respiration does not cause acidosis. The reference I cited there is http://ajpregu.physiology.org/cgi/reprint/287/3/R502.pdf. Lim Wei Quan (talk) 06:44, 30 October 2008 (UTC) Personally until proven otherwise, I think it warrants staying placed on the wiki to keep a 'warning' as the prevailing ideology behind the article vs leaving it otherwise. —Preceding unsigned comment added by 71.61.125.253 (talk) 07:34, 3 January 2009 (UTC)


 * In humans, perhaps, but lactic acid buildup can cause such extreme acidosis in large reptiles (particularly crocodiles) that it can cause their deaths. See here for a email list posting with direct references to several studies: http://dml.cmnh.org/2001Apr/msg00485.html Since, from this, it's clear that lactic acidosis is real, I'm removing the warning - much of wikipedia is far too human biased anyway. Mokele (talk) 16:00, 31 January 2009 (UTC)


 * I completely agree with the original comment, acidosis during exercise is not due to lactic acid. This is a widespread misconception, pervasive even in the scientific literature and medicine textbooks. Mokele, you are right that exercise (vigorous muscle contraction) does acidify blood; this is what your text on reptiles show, and this is well known in sports medicine. Concomitantly, exercise also produces large amounts of lactate, but this does not mean that lactate itself is the cause of low pH. The acidification is in fact due to slower removal of protons, which happens in anaerobic conditions because mitochondrial respiration is hampered. I am editing the article to better reflect this fact.Rollowicz (talk) 10:02, 27 December 2009 (UTC)


 * I reverted, because there's no reference for this. Can you supply a reference to the claim?  I'm skeptical it has anything to do with mitochondria, simply because it occurs to the greatest degree (lethal blood acidification) in animals with the greatest prevalence of FG muscle muscles (which contain minimal mitochondria). Mokele (talk) 16:19, 27 December 2009 (UTC)


 * Mokele, you reverted my edits before I had the time to insert references. The article by Robergs et al. cited above (http://ajpregu.physiology.org/cgi/reprint/287/3/R502.pdf) is a good review of the literature which clearly shows that lactate formation has nothing to do with acidification. Another good (although quite technical) article is that by Hochachka and Mommsen in Science 1984, http://www.sciencemag.org/cgi/content/abstract/219/4591/1391, which also considers variations on this theme across multiple species and pH ranges. Acidification is due to ATP hydrolysis, which produces one proton per molecule ATP hydrolysed to ADP. In response to your comment, the acidification as such certainly does not require the presence of mitochondria; on the contrary, mitochondrial respiration acts as a proton sink, and prevents acidification. In glycolytic muscle fibers, vigorous contraction produces large quantities of protons from ATP hydrolysis, and glycolysis cannot incorporate these protons back into ATP like oxidative phosphorylation does. Thus, heavy use of glycolytic fibers causes acidification. There is no contradiction in this. Again, lactate production cannot possibly lower pH: lactate is a base, not an acid! Lactic acid, the protonated form, is never produced by lactate dehydrogenase. You can find the correct reaction formula at pH 7 in any biochemistry book, e.g. Stryer. Let me know if you have further questions, so we can reach consensus on this issue. This misconception about lactic acidosis is so prevalent in biomedical literature (even in textbooks and a good number of recent papers) that it would be quite valuable to have a wikipedia page that gives an accurate description. —Preceding unsigned comment added by Rollowicz (talk • contribs) 18:43, 27 December 2009 (UTC)


 * Thanks for the references, they explained things nicely, and I've reverted my revert. (Sorry for my instant skepticism.) However, they do make the entire page name a bit erroneous.  Should we move the page to "exercise-induced metabolic acidosis", and leave a redirect here?  Or, considering how long and how prevalent the concept is, should we maintain the page as-is and retain a clarifying explanation? Mokele (talk) 04:15, 28 December 2009 (UTC)


 * Thanks Mokele. I think we should retain the page name. I agree that the term "lactic acidosis" itself is something of a misnomer, but as you say, this concept has been around for so long that I think terminology is stuck, unfortunately. One could re-interpret the name as "acidosis accompanied by lactate buildup" or some such (it's still true that the pH and lactate are strongly correlated). Also, "exercise-induced metabolic acidosis" is a bit too narrow, as lactic acidosis can be caused by other means, as listed in the article. I'll polish the article some more and fix the references.Rollowicz (talk) 10:27, 28 December 2009 (UTC)


 * So the lactate ends up in the blood and so do the protons eventually. If you have lactate in a solution to which you add protons, won't the protons react with the lactate, making lactic acid? What is the difference between a lactic acid solution and a mix of solutions of lactate anions and free hydrogen kations? The way my untrained eye sees it, lactic acid is eventually produced, not in the cells, but in the blood serum.Misiu mp (talk) 17:00, 19 August 2015 (UTC)

There is no definitive proof that metformin causes lactic acidosis.
There have been no major cases of metformin causing lactic acidosis, and no trials have found metformin to cause lactic acidosis. It is more of a theoretical risk because it is in the biguanide class of drugs, and phenformin notoriously caused lactic acidosis. —Preceding unsigned comment added by 174.0.58.66 (talk) 05:44, 10 February 2009 (UTC)

The statement above is INCORRECT. See http://jmedicalcasereports.com/content/1/1/126 —Preceding unsigned comment added by 174.119.69.25 (talk) 06:51, 6 October 2010 (UTC)

I read the report. Quoting from it "Metformin-associated lactic acidosis is a rare, preventable, but life-threatening adverse event ...". They mentioned that the dosage should not exceed 2.5 grams. Note that it says associated which does not imply causation. So why are doctors yanking people off Metformin with a low dosage of two 500 mg tablets daily when the patient knows that raises their eAG level a good 25 points (almost one level of A1C) and the patient has no gastrointestinal problems in taking Metformin? I know somebody who has that condition. Since the only known bad side effects for Metformin which I have discovered are because of the GI-tract disturbances and lactic-acidosis we are having a problem right now of doctors jumping the gun on getting rid of the Metformin for treatment. It is understandable if they do it if they have conclusive evidence. Quoting again from the same paragraph: ".. high-anion gap metabolic acidosis and high blood lactate concentration ..." The only way you can assess that is with proper tests which includes a blood test. No wonder some type-2 Diabetics just give up on it and say to hell with it and go au-naturale and die from diabetic complications. Enough rest and sleep, dietary changes, and enough exercise only go so far. Insulin for most of these people is just not an option because it is too expensive. Yet the medical people immediately use insulin when it really is not a good option for Type-2 diabetics whose Pancreas secretes enough insulin. hhhobbit (talk) 23:51, 24 June 2016 (UTC)

I guess I should add you not only did not read the jmedicalcasereports carefully enough but did not read one of the reports cited. See http://archinte.jamanetwork.com/article.aspx?articleid=216377 The conclusion states: "There is no evidence to date that metformin therapy is associated with an increased risk of lactic acidosis or with increased levels of lactate compared with other antihyperglycemic treatments if the drugs are prescribed under study conditions, taking into account contraindications." I realize that Metformin was only approved in the US in 1995. But since it has been used for over 40 years in Europe and elsewhere, it seems that SOMETHING else along these lines if it exists would have been shown by now. The JAMA article even shows Metformin has the additional side effects of either weight loss or weight gain prevention. The person I am referring to was losing weight on Metformin. Off of it their weight has now stabilized on 20 pounds too heavy. I repeat, Metformin seems to be getting a bad rap. The only thing negative I have read on Metformin are the gastrointestinal problems and a possible link to lactic acidosis. This person I am referring to took Metformin with only water and at least two hours after and two hours before any meals with no GI problems. They can also take aspirin with no problems. hhhobbit (talk) 00:33, 25 June 2016 (UTC)

Pathphysiology - muscle types
"Also, muscle types that have few mitochondria and preferentially use glycolysis for ATP production (so-called type I fibers) are naturally prone to lactic acidosis." I believe this statement is incorrect. Type 1 (aka slow twitch) are rich in mitochondria; it is the fast twitch types 11x and 11b that have comparatively few mitochondria and preferentially use glycolysis. This is referenced on the Wikipedia entry for muscle: http://en.wikipedia.org/wiki/Muscle#Types —Preceding unsigned comment added by 67.176.94.222 (talk) 19:45, 12 May 2011 (UTC)

Definition of lactic acidosis
Definition stated in this wiki article is: lactate levels >5 mmol/L and serum pH <7.35

Lactic acidosis is in Soyoral at al. 2011 defined as a blood pH less than 7.35 and a serumlactate more than 2mmol/L

I havent checked it up, just wanted to point that out. I wont edit the wiki article since im not an eng. native speaker nor certain.

Soyoral, Y.U., Begenik, H., Emre, H., Aytemiz, E., Ozturk, M., Erkoc, R., 2011. Dialysis therapy for lactic acidosis caused by metformin intoxication: presentation of two cases. Hum Exp Toxicol 30, 1995–1997. — Preceding unsigned comment added by 130.238.244.160 (talk) 13:02, 13 March 2012 (UTC)

Review
The most recent core review is here (2010) but I can't currently access it. JFW &#124; T@lk  10:32, 11 September 2013 (UTC)


 * 10.1186/s13054-014-0503-3 - some big names in critical care medicine seem to imply that C&W type A lactic acidosis is not the actual mechanism behind hyperlactataemia in severe sepsis. JFW &#124; T@lk  14:09, 17 September 2014 (UTC)


 * NEJM Kraut & Madias 10.1056/NEJMra1309483 JFW &#124; T@lk  11:34, 11 December 2014 (UTC)


 * 10.1016/j.mayocp.2013.06.012 Mayo Clin Proc JFW &#124; T@lk  08:17, 1 January 2015 (UTC)


 * In print: mitochondrial lactate metabolism 10.1113/JP278930 JFW &#124; T@lk  12:57, 18 May 2020 (UTC)

Updating and fixing
I had a quick look at the article today while I do a bit of reading myself. I am surprised that the intro said (since October 2010) that lactic acidosis is usually due to D-lactate; in humans that is quite wrong (as Luft demonstrates). The long section about lactic acidosis in ruminants doesn't clarify whether this is D-lactic acidosis (as also discussed briefly by Luft) or whether it is something else altogether. This paper (Owens et al 1998, currently cited) suggests that it's both stereoisomers contributing. JFW &#124; T@lk  14:56, 30 December 2013 (UTC)


 * I also wonder if we need to discuss the fact that in some point-of-care analysers, other substances (such as ethylene glycol) may masquerade as lactate. I will add it if I find a strong source. JFW &#124; T@lk  15:16, 30 December 2013 (UTC)

JAMA
Lactate raised but patient not critically ill? Review: 10.1001/jama.2014.14074 JFW &#124; T@lk  22:30, 1 March 2015 (UTC)


 * And on the other end: what does lactic acidosis mean for haemodynamics? 10.1186/s13054-015-0896-7 (Critical Care, open access). JFW &#124; T@lk  12:09, 23 April 2015 (UTC)

"Nicolas" by Pascal Girard
The title character of the 2009 graphic novella Nicolas is Quebecois cartoonist Pascal Girard's five-year-old brother who died at age 5 in 1990 "of lactic acidosis." Girard's reminiscence includes his childhood fundraising in his neighborhood for lactic acidosis research. This was noted by Maria Popova in her blog, Brainpickings for today's date. I don't know whether this merits inclusion on the Lactic acidosis mainspace page so am recording the information here. -- Deborahjay (talk) 20:20, 23 March 2015 (UTC)

Possibly worth a mention on this page?
Open-label pilot for treatment targeting gut dysbiosis in myalgic encephalomyelitis/chronic fatigue syndromeStudy mentions d-lactate acidosis possibly caused by Streptococcus and other enteric microbiota in ME/CFS patients. — Preceding unsigned comment added by Laterthanyouthink (talk • contribs) 08:25, 14 April 2018 (UTC)


 * That would not be a source that passes the tests listed in WP:MEDRS. Presumably there is no secondary source. JFW &#124; T@lk  08:38, 15 April 2018 (UTC)

Pathophysiology
Moving the previous "pathophysiology" section here, because it was mostly NOR:

Most cells in the body normally metabolize glucose to form water and carbon dioxide in a two-step process. First, glucose is broken down to pyruvate through glycolysis. Then, mitochondria oxidize the pyruvate into water and carbon dioxide by means of the Krebs cycle and oxidative phosphorylation. This second step requires oxygen. The net result is ATP, the energy carrier used by the cell for metabolic activities and to perform work, such as muscle contraction. When the energy in ATP is used during cell work via ATP hydrolysis, hydrogen ions, (positively charged protons) are released. The mitochondria normally incorporate these free hydrogen nuclei back into ATP, thus preventing buildup of unbound hydrogen cations, and maintaining neutral pH.

If oxygen supply is inadequate (hypoxia), the mitochondria are unable to continue creating ATP at a rate sufficient to meet the cell's energy needs. In this situation, glycolysis is increased to provide additional ATP, and the excess pyruvate produced is converted into lactate and released from the cell into the bloodstream, where it accumulates over time. While increased glycolysis helps compensate for less ATP from oxidative phosphorylation, it cannot bind the hydrogen cations that result from ATP hydrolysis. Therefore, hydrogen cation concentration rises and causes acidosis.

The excess hydrogen cations produced during lactic acidosis are widely believed to actually derive from production of lactic acid. This is incorrect, as cells do not produce lactic acid; pyruvate is converted directly into lactate, the anionic form of lactic acid. When excess intracellular lactate is released into the blood, maintenance of electroneutrality of the blood requires that a cation be released into the blood, as well. This can reduce blood pH. Glycolysis coupled with lactate production is neutral in the sense that it does not produce excess hydrogen cations; however, pyruvate production does produce them. Lactate production is buffered intracellularly, e.g. the lactate-producing enzyme, lactate dehydrogenase, binds one hydrogen cation per pyruvate molecule converted. When such buffer systems become saturated, cells will transport lactate into the bloodstream. Hypoxia certainly causes both a buildup of lactate and acidification, and lactate is therefore a good "marker" of hypoxia, but lactate itself is not the cause of low pH. During exercise and some illnesses, lactate production is not generated by lack of oxygen, per se, but by the catecholamine-driven metabolism of glucose (glycolysis) that cells use when they cannot get enough energy from oxygen-based reactions.

Lactate serves as an energy source for other tissues.

Lactic acidosis sometimes occurs without hypoxia, for example, in rare inborn errors of metabolism where mitochondria do not function at full capacity. In such cases, when the body needs more energy than usual, for example during exercise or disease, mitochondria cannot match the cells' demand for ATP, and lactic acidosis results. Also, muscle types that have few mitochondria and preferentially use glycolysis for ATP production (fast-twitch or type II fibers) are naturally prone to lactic acidosis.

Lactic acidosis is also a consequence of the processes causing rigor mortis. In the absence of oxygen, tissue in the muscles of the deceased carry out anaerobic metabolism using muscle glycogen as the energy source, causing acidification. With depletion of muscle glycogen, the loss of ATP causes the muscles to grow stiff, as the actin-myosin bonds cannot be released. (Rigor is later resolved by enzymatic breakdown of the myofibers.)

Might borrow some content once I have found better sources. JFW &#124; T@lk  12:51, 18 May 2020 (UTC)

Source of hydrogen ion
As per the discussions above and the removed "pathophysiology" content, I need a good source because I can write something about the source of protons in lactic acidosis. Anyone got a good one? JFW &#124; T@lk  13:54, 18 May 2020 (UTC)


 * Perhaps the answer will be in here: 10.1007/s00421-017-3795-6 JFW &#124; T@lk  14:51, 18 May 2020 (UTC)