Of rare acid-base disturbances, some are inexplicably favoured by CICM examiners, and other are inexplicably neglected. For some reason pyroglutamic acidosis has been the subject of several SAQs, whereas D-lactic acidosis has never appeared in the exam. It is not even mentioned as one of the worthy differentials. However, this oversight is only a matter of time. The savvy trainee will ensure their own minimal workmanlike understanding of this disorder, so they may make the right kind of sounds at some hypothetical future viva.

In terms of peer-reviewed information on this, one can do no better than the 2020 article by Miroslav Pohanka, or the other one. The content below is a brief summary of these articles. 

D-lactate and L- lactate

Lactic acid comes in two enantiomers: L-lactate and D-lactate. 

D-lactate and L-lactate

As is often the case with isomers, they have very different chemical properties. One isomer might be a completely normal member of the metabolic milieu of the organism, and the other might be a toxic disrupting influence. And they might have completely different pharmacokinetic properties because (for example) they might have very different affinities for the enzyme which is supposed to metabolise them. 

So it is with D-lactate. Whereas L-lactate is the standard form of lactate produced by multicellular organisms, most eukaryotes are unable to produce D-lactate, as our L-lactate dehydrogenase is incapable of it. Howeever, some bacteria produce D-lactate preferentially, and some others have the capability of producing both D and L isoforms (eg. Leuconostoc mesenteroides, an organism also known for its total inborn resistance to vancomycin). The D-lactate producers are usually descriobed as "fermeners", and their names would not be instantly recogniseable to the person who mainly deals with microbiology through reported blood culture results. They are bacteria like Pediococcus and fungi like Sapromyces. Additionally, some old favourites like Pseudomonas and E.coli are also able to express the appropriate enzymes. In humans, D-lactate is mainly synthesised by the Lactobacillus, Bifidobacterium, Eubacterium and Streptococcus bovis in the colon.

Pathophysiology

In summary:

  • Malabsorbed carbohydrate is fermented in the colon, producing an excess of D-lactate.
  • This has been a well-recognised problem in ruminants, where it is associated with
  • "ruminal carbohydrate overload".
  • Normally, humans have a great capacity to metabolise D-lactate (the hepatic metabolism of lactate does not discriminate between isoforms)
  • In specific circumstances, D-lactate can be overproduced in the bowel, leading to toxicity

D-lactate has a direct neurotoxic effect. In 2007, Abeyasekara et al put central lines into eight calves, and infused them with D-lactate. The neurological effect was likened to ethanol intoxication, which relies on the reader's familiarity with what a drunken cow behaves like. Not a problem for the investigators, clearly ("We were impressed with the “drunken” appearance of our calves", they guffawed). In short, clinical features of D-lactic acidosis in humans consist of:

  • Confusion, slurred speech, obtundation and ataxia.
  • Encephalopathy of one sort or another seems to be the most common feature

Implications for the diagnosis of a high anion gap metabolic acidosis

  • D-lactate is not routinely measured (L-lactate levels look normal)
  • Thus, the patients appear to have a high anion gap metabolic acidosis with a normal lactate

Risk factors

  • Short gut patients are particularly at risk
  • Post-pancreatectomy patients who fail to take their enzyme supplements
  • Short gut hippies who ingest Lactobacillus tablets to improve their intestinal microflora
  • Symptoms are exacerbated by increased food intake, and are relieved by fasting

References

Uribarri, Jaime, Man S. Oh, and Hugh J. Carroll. "D-lactic acidosis: a review of clinical presentation, biochemical features, and pathophysiologic mechanisms."MEDICINE-BALTIMORE- 77 (1998): 73-82.

Pohanka, Miroslav. "D-Lactic Acid as a Metabolite: Toxicology, Diagnosis, and Detection." BioMed Research International 2020 (2020).

Kim, Kyung Hyun, et al. "Identification and Characterization of l-Malate Dehydrogenases and the l-Lactate-Biosynthetic Pathway in Leuconostoc mesenteroides ATCC 8293." Journal of agricultural and food chemistry 66.30 (2018): 8086-8093.

Abeysekara, Saman, et al. "D-Lactic acid-induced neurotoxicity in a calf model." American Journal of Physiology-Endocrinology and Metabolism 293.2 (2007): E558-E565.