Metabolic acidosis in calves with neonatal diarrhea was believed to be mainly caused by the loss of bicarbonate via the intestines or the formation of l-lactate during anaerobic glycolysis after tissue hypoperfusion in dehydrated calves. Because d-lactate was not considered to be of interest in human or veterinary medicine, routine diagnostic methods targeted the detection of l-lactate only. The development of stereospecific assays for the measurement of d-lactate facilitated research. This article summarizes the available information on d-lactic metabolic acidosis in neonatal ruminants.

Keywords

d-lactic acidosis

Ruminants

Neonates

Calf diarrhea

Ruminal drinking

Key points

Videos of calves with metabolic acidosis/d-Lactatemia accompany this article at http://www.vetfood.theclinics.com/

Until the 1980s, d-lactic metabolic acidosis was known to occur only in adult ruminants caused by acute ruminal acidosis as a result of carbohydrate overload.1 Metabolic acidosis in calves with neonatal diarrhea was believed to be mainly caused by the loss of bicarbonate via the intestines or the formation of l-lactate during anaerobic glycolysis after tissue hypoperfusion in dehydrated calves. Because d-lactate was not considered to be of interest in human or veterinary medicine, routine diagnostic methods targeted the detection of l-lactate only. The development of stereospecific assays for the measurement of d-lactate2,3 facilitated research in the area, so that our knowledge on the subject has multiplied over the last decade. This article summarizes the available information on d-lactic metabolic acidosis in neonatal ruminants.

Metabolism of d-lactate

In mammals, d-lactatemia is mainly of gastrointestinal origin. The small quantity of d-lactate that is formed in eukaryotic cells through the methylglyoxal pathway seems to be negligible.4

Corresponding to the experience with acute ruminal acidosis in veterinary medicine,1 when in 1979, d-lactic acidosis was first described in humans in a patient affected by short bowel syndrome who presented with neurologic manifestations and severe metabolic acidosis,5 the accumulation of d-lactate was attributed to the absorption of d-lactate abnormally fermented in the colon and not adequately removed because of the lack of specific metabolic pathways. At that time, it was believed that mammals metabolize d-lactate slowly, because of the lack of the specific enzyme d-lactate dehydrogenase. d-α-hydroxy acid dehydrogenase, an intramitochondrial flavoprotein enzyme, was considered the only nonspecific enzyme that initiates the metabolism of d-lactate.6,7

In subsequent decades, evidence was provided by different studies that mammals are able to metabolize d-lactate more efficiently than originally suggested.

Oh and colleagues8 showed that normal humans were able to metabolize d-lactate at a rate of 1.52 mmol/kg/h at a serum level of 5.2 mmol/L, when dl-lactate was infused intravenously (IV) at a rate of 1.92 mmol/kg/h for each stereoisomer. In this study, 75% to 90% of infused d-lactate was metabolized, depending on the infusion rate. The renal threshold of d-lactate is lower than that of l-lactate, and both stereoisomers compete with each other for renal tubular reabsorption, so that a considerable proportion of d-lactate escaped through the kidneys in this experiment. Giesecke and colleagues9 found only an average 1.2% to 2.2% of oral dl-lactic acid loads from 50 to 200 mg/kg body weight (BW) in the urine. de Vrese and colleagues10 established a half-life of 21 minutes for d-lactate in the blood of healthy humans given an oral load of 6.4 mmol/kg BW. When a higher dose of 12.8 mmol/kg BW was used, half-life increased to 40 minutes. Less than 2% of d-lactate was excreted via the kidneys in this study.

As further evidence that d-lactate is readily metabolized by mammals, Flick and Konieczny11 identified d-lactate dehydrogenases in mammalian tissues, capable of converting d-lactate into pyruvate, and providing therefore a glycolysis bypass for pyruvate formation from dihydroxyacetone phosphate. More recently Ling and colleagues12 have shown that d-lactate dehydrogenase activity is high in rat liver cells, whereas it is low in brain and heart tissue.

Both stereoisomers of lactic acid are produced in the gastrointestinal tract of ruminants under physiologic conditions, and considerable amounts of d-lactic and l-lactic acid can be ingested with fermented feeds. In their basic studies on lactic acidosis in cattle after engorgement with highly fermentable carbohydrates, Dunlop and Hammond1 found concentrations of d-lactate of up to 10 mmol/L in the blood of affected animals.

After separate infusion of the sodium salts of the 2 stereoisomers, a slower decline in blood concentration followed the infusion of sodium d-lactate. Later, it was shown that the volume of distribution for d-lactate after a single IV injection of dl-lactate was 23.5% and 24% of BW in a cow and in sheep, respectively, and 31.5% in 4 goats.13 The latter finding was most probably because the goats that were used in this experiment were younger. The half-life of d-lactate increased with increasing concentrations of d-lactate, and goats eliminated d-lactate twice as fast as sheep and the cow in this study.14 The renal threshold concentrations of d-lactate show differences between species, but in general, they are about half as high as the values for l-lactate. In goats, a renal threshold for d-lactate of 1.9 mmol/L was found, whereas the value for sheep and cow was 4.3 mmol/L.15

Induction of high concentrations of d-lactate by injection of 100 mL of a 25% sodium-d-lactate solution (223.07 mmol) in healthy calves led to a higher plasma half-time of d-lactate (183 minutes) than that reported before. Nevertheless, it was shown in this study that young calves are able to eliminate considerable amounts of d-lactate from the blood. The mean value for renal clearance was lower than that given for glomerular filtration rate16 and thus gives strong evidence of tubular reabsorption of d-lactate. The fact that total clearance and the clearance of the 2-compartment model were higher than renal clearance indicated metabolic utilization of d-lactate by the calves.17

Origin of d-lactate in neonatal ruminants

Regardless of the fact that d-lactate can be theoretically introduced through ingestion of fermented feed (spoiled milk or feeding of yogurt instead of milk), the origin of d-lactate in neonatal ruminants is for practical purposes caused by fermentative processes that occur in the reticuloruminal compartment or in the intestinal tract.