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The Veterinary Journal

The Veterinary Journal 179 (2009) 197203 www.elsevier.com/locate/tvjl

Review
D-Lactic

acidosis in calves
*

Ingrid Lorenz

School of Agriculture, Food Science & Veterinary Medicine, University College Dublin, Beleld, Dublin 4, Ireland Accepted 29 August 2007

Abstract Metabolic acidosis has long been known as a frequent and potentially severe complication of neonatal calf diarrhoea. It has also been described in acidosis-without-dehydration syndrome in calves and was suspected to occur during ruminal drinking. Clinical signs of central nervous impairment, particularly changes in behaviour and posture, progressing to coma and recumbency, were originally attributed to this metabolic disturbance. The loss of bicarbonate in the faeces was regarded as the main cause of acidosis in this context. During the past decade, however, evidence has accumulated that D-lactic acidosis is a more common occurrence in calves with neonatal diarrhoea. The most probable source of D-lactataemia is bacterial fermentation of undigested substrate that reaches the large intestine due to damage to small intestinal mucosal epithelium. Recent research has shown that most of the clinical signs that were formerly attributed to acidosis were in fact due to elevated blood levels of D-lactate. The aim of this review is to provide a current overview of D-lactic acidosis. 2007 Elsevier Ltd. All rights reserved.
Keywords:
D-Lactic

acidosis; Calves; Neonatal diarrhoea; Ruminal drinking; Neurological signs

Introduction
D-Lactic acidosis has been recognised in adult ruminants since the middle of the last century. The details of the pathogenesis of acute ruminal acidosis in cattle and the role of D-lactic acid in this context were reported by Dunlop and Hammond (1965). The ingestion of excessive amounts of highly fermentable concentrates is followed by proliferation of Streptococcus bovis in the rumen. This organism metabolises the carbohydrates to produce lactic acid, which decreases the pH of the ruminal uid to ve or below. In this environment, cellulolytic and lactate-using bacteria and protozoa are destroyed, while the growth of lactobacilli is promoted. In the absence of a specic method for the determination of D-lactate, Dunlop and Hammond (1965) used the calculated dierence between total lactate and L-lactate to show that after acute grain engorgement, metabolic acidosis occurs due to accumulation of D-lactic acid in the blood. In humans, D-lactic acidosis was rst described in 1979 (Oh et al., 1979) and a review by Uribarri et al. (1998)

revealed the widespread nature of this condition. D-Lactic acidosis occurs in humans as a rare complication of the short bowel syndrome following surgical removal, or by-passing of, large parts of the small intestine. The main clinical signs reported in humans with D-lactic acidosis are altered mental status, slurred speech, ataxia, disorientation and weakness (Uribarri et al., 1998). In the last two decades, attention has increasingly focussed on the pathophysiological signicance of D-lactic acid in various clinical settings in calves. To facilitate research in this area, assays for the rapid and stereospecic determination of D-lactate in calf serum samples have been developed using high-performance liquid chromatography (Omole et al., 1999) and enzymatic measurement, respectively (Lorenz et al., 2003). The aim of this paper is to provide an overview of the scientic knowledge that has accumulated on this topic during the last twenty years.
D-Lactic

acidosis in ruminal drinkers

Tel.: +353 1 716 6083; fax: +353 1 7166091. E-mail address: Ingrid.Lorenz@ucd.ie.

The rst description of a syndrome in veal calves characterised by unthriftiness, poor appetite, retarded growth,

1090-0233/$ - see front matter 2007 Elsevier Ltd. All rights reserved. doi:10.1016/j.tvjl.2007.08.028

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a dull hair coat and clay-like faeces, which was attributed to a failure of the reticular groove reex in initially healthy calves, was reported by Van Bruinessen-Kapsenberg et al. (1982). Clinical signs appeared after several weeks of ruminal drinking which occurred when the ingested milk enters the reticulo-rumen, where volatile fatty acids and/or lactic acid are produced by bacterial fermentation (Van Weeren-Keverling Buisman, 1989). Dirr (1988) discovered that dysfunction of the reticular groove reex can occur as a complication of various primary diseases, particularly neonatal diarrhoea, in dairy calves. In this study, about 17% of a total of 408 calves, which had been hospitalised with various diseases, showed clinical signs and ruminal uid changes indicating a failure of the reticular groove reex. Dirr (1988) also reported different types of ruminal fermentation depending on the predominant type of acid (lactic acid, butyric acid or both in sequence) recovered in the ruminal uid of 37 ruminal drinkers that could be investigated over a period of several days. Lactic acid fermentation was found in the majority of ruminal drinkers, with the majority of ruminal uid samples from these calves having a concentration of D-lactic acid lower than that of L-lactic acid. On the day of hospitalisation, the values were 10 10 mmol/L and 31 13 mmol/L, respectively, in 20 calves with lactic acid fermentation. Concurrent metabolic disturbances were not described in this study, but it was stated that amelioration of ruminal uid ndings, and thus assumed recovery of the reticular groove reex, depended strongly on recovery from the underlying disease. Baur (1993) reported an attempt to induce ruminal acidosis in young calves by force-feeding whole milk. In all the experimental calves, lactic acid fermentation occurred to various degrees, with concentrations of lactic acid up to 60 mmol/L reported in the ruminal uid. There was no dierentiation between the lactic acid isomers reported in this study. All aected calves showed clinical signs, particularly somnolence and weakness, although metabolic alterations were not examined. In a similar investigation, Gentile (1995) succeeded in producing ruminal acidosis in young calves by intraruminal administration of various oral rehydration solutions. Concentrations of lactic acid in the ruminal uid varied depending on the composition of the uids administered, but in almost all samples D-lactic acid was lower in concentration than L-lactic acid. In that study, only a mild dullness was reported in some of the calves which also had the greater changes in ruminal uid. Although it was assumed that ruminal drinking, like rumen overload in adult cattle, leads to a systemic metabolic acidosis in calves (Dirksen and Baur, 1991), there is no substantial proof of this interrelationship. In a retrospective study of ruminal acidosis in calves without diarrhoea, or a history of diarrhoea under four weeks of age, Gentile et al. (1998) found a high anion gap acidosis in animals with severe ruminal acidosis (pH < 5). As there were no signicant alterations in L-lactate in these calves, D-lac-

tate was suspected as the cause of the elevation of the anion gap, due to the slow metabolism of this isomer. Furthermore, Gentile et al. (2004) also proved that in young calves, as in adult cattle, ruminal acidosis may lead to clinical Dlactic acidosis. Those authors induced ruminal acidosis in young calves by repeated force-feeding with whole milk (1 L; three times daily). All the calves developed D-lactataemia with peak values of 6.7511.1 mmol/L in individual calves and all but one of the calves developed severe systemic acidosis. Due to profound clinical or metabolic alterations (e.g. severe depression, estimated degree of dehydration >10%, absence of sucking reex, lack of appetite for two consecutive feedings, severe metabolic acidosis with calculated actual base excess [ABE] below 15 mmol/ L), force-feeding was discontinued in 7/9 calves. Two calves developed no distinct clinical signs up to day 17 when force-feeding was discontinued.
D-Lactic

acidosis in neonatal calf diarrhoea

Historically, metabolic acidosis in calf diarrhoea was thought to be mainly associated with faecal bicarbonate loss. In the presence of dehydration, reduced renal perfusion, and therefore reduced excretion of hydrogen ions, can exacerbate the situation (Hartmann et al., 1981). The formation of L-lactate during anaerobic glycolysis following tissue hypoperfusion has long been considered the cause of high anion gap acidosis in calves with neonatal diarrhoea. However, L-lactic acidosis has only been found in diarrhoeic calves in their rst week of life (Naylor, 1987), or in older calves immediately prior to death from diarrhoea (Hartmann et al., 1984). Grove-White (1996) also failed to conrm a relationship between L-lactate concentrations and the degree of acidosis, and suggested that exogenous acid production was a major contributor to acidosis in diarrhoeic calves. Kasari and Naylor (1986) were the rst to describe a syndrome of high anion gap acidosis in neonatal calves with no or minimal diarrhoea and without dehydration. The principal clinical signs were unconsciousness or depression, weakness and ataxia. In that study, the variation in clinical signs between calves was highly correlated with their base decit, while intravenous (IV) administration of sodium bicarbonate solution improved the clinical condition of the patients. The increased anion gap indicated an accumulation of organic or inorganic acids which, unfortunately, could not be determined. The concentrations of L-lactate, acetate and acetoacetate were normal, but the concentration of D-lactate was not measured. Schelcher et al. (1998) reported D-lactic acid as the cause of this syndrome of high anion gap acidosis. Mean values of up to approximately 13 mmol/L were reported in aected calves, with values of 1.27 1.14 and 2.31 1.61 mmol/L, respectively, for healthy controls in 2 consecutive years. Calves with uncomplicated diarrhoea showed slightly, but not signicantly, elevated D-lactate concentrations.

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In a study of the metabolic consequences of ruminal drinking, Grude (1999) reported raised serum levels of Dlactate in calves that suered from metabolic acidosis and neonatal diarrhoea, no matter whether ruminal acidosis was present or not. However, in calves with ruminal acidosis, but without systemic metabolic acidosis, serum D-lactate levels were normal, despite high concentrations of Dlactate in the ruminal contents. The results of this study indicated that accumulation of D-lactate in the blood of diarrhoeic calves was not necessarily a consequence of ruminal drinking. Several studies have since revealed that D-lactic acidosis is a common occurrence in hospitalised diarrhoeic calves and that D-lactate levels together with occasionally elevated L-lactate levels largely explain the signicantly elevated anion gaps found in those calves (Omole et al., 2001; Ewaschuk et al., 2003; Lorenz, 2004a). In 300 otherwise unselected calves with neonatal diarrhoea, 55% were found to have D-lactataemia as dened by Uribarri et al. (1998), with blood D-lactate concentration above 3.0 mmol/L (Lorenz, 2004a). Production of D-lactate in diarrhoeic calves High D-lactate concentrations have been found in the faeces of diarrhoeic calves compared with healthy ones (Doll, 1992; Omole et al., 2001; Ewaschuk et al., 2004b). This nding suggested that the gut was the source of D-lactate. The major pathogens involved in calf diarrhoea are known to cause villous atrophy, which may lead to malabsorption of carbohydrates and their subsequent fermentation in the intestine (Youanes and Herdt, 1987). Evidence for this pathogenic mechanism is provided by the fact that D-lactic acidosis has been demonstrated in diarrhoeic calves without elevation of D-lactate concentrations in the rumen (Grude, 1999; Lorenz, 2004a; Ewaschuk et al., 2004b). Ewaschuk et al. (2004b) concluded that colonic D-lactate production contributed more to systemic D-lactic acidosis than ruminal production for the following reasons:  D-lactate concentrations were higher in faeces than in rumen contents in the majority of diarrhoeic calves in their study.  In calves in which D-lactate concentration in ruminal uid exceeded that of faeces, D-lactate in serum was lower than when D-lactate concentrations in the faeces were higher than ruminal D-lactate concentrations.  Faecal D-lactate concentrations, but not ruminal concentrations, were correlated with serum concentrations. Lorenz (2004a) found signicantly higher blood D-lactate concentrations in diarrhoeic calves with ruminal acidosis than in those without, but suggested that the ruminal acidosis might be a complication of the D-lactic acidosis caused by diarrhoea and subsequent malabsorption rather than vice versa. In this case, D-lactic acidosis would lead to general weakness with subsequent failure of the reticular groove reex and ruminal acidosis. In a proportion of

calves euthanased for various medical reasons, with and without diarrhoea, elevated D-lactate levels could be measured throughout the entire intestinal tract. The abomasum, the distal part of the jejunum, the caecum and the colon contained signicantly more Gram-positive rods in cases of D-lactate presence (>3 mmol/L) in these compartments, compared to cases with negligible concentrations of D-lactate at the respective locations (Koenig, 2006). At present, it can only be speculated as to whether D-lactate is actually produced throughout the whole intestinal tract, or only in circumscribed areas and subsequently distributed by means of intestinal motility. Clinical impact of D-lactataemia in calves Clinical assessment of the degree of metabolic acidosis in diarrhoeic calves has been the objective of numerous studies. When Kasari and Naylor (1984) described metabolic acidosis without clinical signs of dehydration in four calves between 9 and 21 days old, they listed coma, or depression with weakness and ataxia, as clinical signs of acidosis. A depression score was established on the basis of the sucking reex, menace response, tactile response, ability to stand, warmth of oral cavity and temperature of extremities. This score was highly correlated (r = 0.87) with base decit in acidotic calves without dehydration (Kasari and Naylor, 1986). In dehydrated calves, the involvement of signs indicative of dehydration or shock (position of the eyeballs, temperature of the oral cavity and extremities) resulted in a decrease in accuracy of the prediction of base excess (Kasari and Naylor, 1985). Naylor (1987, 1989) used age dierence as an aid for the estimation of base decit in diarrhoeic calves. In calves with neonatal diarrhoea, base decit was 11.4 1.7 mmol/L for calves under 8 days of age and 19.5 1.2 mmol/L in older calves. Clinical signs and age of the calf could be used to predict the severity of acidosis. Acidosis was more severe in calves over 8 days of age and also increased in severity with the degree of depression. In calves over 8 days of age presenting in sternal or lateral recumbency, the mean base decit was 16.3 8.3 and 20.3 10.1 mmol/L, respectively. However in calves under 8 days of age, the respective values were 12.1 8.4 and 13.2 9.7 mmol/L. Geishauser and Thunker (1997b) found signicant correla tions between base excess and sucking reex (r = 0.70) as well as ability to stand (r = 0.64). A normal sucking reex was associated with an average base decit of 4.2 mmol/L, weak sucking reex with 11.4 mmol/L and no sucking reex with 21.5 mmol/L. The respective values for normal standing ability, staggering, and recumbency were 5.2 mmol/L, 7.8 mmol/L and 19.1 mmol/L. On the basis of a prospective study of diarrhoeic calves, Wendel et al. (2001) concluded that among several parameters tested, evaluation of behaviour (dened by responsiveness to the environment and assessed using a six point scale from bright and alert to comatose) alone yielded the best estimate for the degree of acidosis

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(r = 0.72). In those calves, posture correlated well with base excess (r = 0.63), but inclusion of this parameter in a logistic regression model did not improve the accuracy of the estimate, as posture and behaviour were closely correlated. Despite the good correlation with behaviour and posture, a wide range of base excess values was detected in calves exhibiting comparable clinical signs. For example, base excess values from +23 to 20 mmol/L were measured in calves categorised as tired and from +21 to 27 mmol/L in calves that stood in a wobbly way. Fig. 1 shows serum D-lactate and base excess values on admission of 300 calves with diarrhoea as primary diagnosis. Although a good overall correlation can be seen between D-lactate concentrations and base excess in those calves, in calves with base excess values of 10 to 25 mmol/L, D-lactate levels were distributed over the entire range of detected values (Lorenz, 2004a). A further study of this subset of diarrhoeic calves with moderate to severe acidosis indicated that D-lactate, rather than metabolic acidosis per se, was associated with impaired posture, behaviour, and especially impairment of the palpebral reex (Table 1), whereas the sucking reex appeared to be inuenced by dehydration and metabolic acidosis (Lorenz, 2004b). In an attempt to prove this hypothesis, D-lactataemia without acidosis was induced in a blinded study involving
30

20 10 0

-10 -20 -30 -40

0 5 10 15 20

D-lactate concentration (mmol/L)

Fig. 1. Blood base excess and serum D-lactate concentration on admission in 300 calves with neonatal diarrhoea as primary diagnosis (Lorenz, 2004a).

ve clinically healthy calves by an injection of 100 mL of a 25% sodium-D-lactate solution (223.07 mmol), while ve control calves were given the same volume of 0.9% sodium chloride. The administration of D-lactate resulted in profound changes in posture and behaviour, although saline did not produce these changes. All experimental calves showed impaired palpebral reex, with three calves somnolent and the remaining two appeared quiet and withdrawn. All calves exhibited a staggering, drunken gait, which was marked in four calves. In four calves, long periods of motionless or slightly wavering/tottering standing with lowered head and drooping ears were recorded. Four calves lay down more often and/or for longer periods than control calves and needed help to rise. All but one calf assumed un-physiological postures while standing (e.g. saw-horse stance) or lying (e.g. one foreleg extended backwards parallel to the body) for prolonged periods. No impairment of the sucking reex could be observed in any of the calves. (Lorenz et al., 2005). This study has been criticised for the high sodium content and the hyperosmolarity of the administered solution, which were suspected to cause or contribute to the observed clinical signs (Stampi, 2005). However, the injection of 100 mL of a 25% sodium L-lactate solution followed by infusion of 300 mL of the same solution over a period of 35 min did not trigger any clinical signs, so hypernatraemia and hyperosmolarity could be ruled out as reasons for the clinical signs in the study of calves with experimentally induced D-lactataemia (Gentile and Lorenz, 2005). Gentile et al. (in press) induced hyperchloremic metabolic acidosis with a mean base decit of up to 22.4 mmol/L with an IV infusion of 4000 mL of a solution containing 400 mmol HCL in 0.9% NaCl over a period of 80 min in healthy calves, although central nervous system (CNS) signs were not observed. In prolonged hydrochloric acid (HCl)-induced acidosis, however, mild depression of neurological function developed (Abeysekara et al., 2007). In this study acidosis was produced by infusion of either an iso-molar DL-lactic acid, L-lactic acid, or HCl, respectively, over a period of 6 h. D-lactate values in cerebrospinal uid correlated to serum concentrations, although cerebrospinal uid concentrations were lower

Table 1 Serum D-lactate concentration and base excess (means sd, and medians) in subsets of diarrhoeic calves diering in posture, behaviour, and palpebral reex (Lorenz, 2004b)
D-Lactate

Base excess (mmol/L)

concentration (mmol/L)

Base excess (mmol/L) 16.1 3.5 (a) Median: 16.8 18.9 3.9 (b) Median: 19.7 16.4 3.4 (a) Median: 16.1 18.8 4.0 (b) Median: 19.5 16.9 3.7 (a) Median: 16.8 18.4 4.0 (a) Median: 18.4

Posture Secure (n = 21) Wobbly or recumbent (n = 59) Behaviour Alert (n = 20) Tired, listless, or comatose (n = 60) Palpebral reex Prompt and complete (n = 13) Delayed, incomplete, or absent (n = 67)

2.4 2.1 (a) Median: 2.2 11.0 3.6 (b) Median:11.1 2.6 3.2 (a) Median: 1.3 10.8 3.6 (b) Median: 10.9 2.3 2.0 (a) Median: 2.2 10.0 4.4 (b) Median: 10.6

Dierent letters indicate signicant dierence between the groups (P < 0.05).

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and also lagged changes in serum concentrations. Only DLlactic acidosis was associated with severe disturbances in neurological functions (i.e. ataxia, and depressed menace, palpebral and tactile reexes), whereas either form of acidosis triggered depression of the sucking reex (Abeysekara et al., 2007). Mechanisms of neurological manifestations of D-lactataemia Historically, two mechanisms have been suggested to explain D-lactate-related encephalopathy: (1) D-lactate has a direct toxic eect on the brain, or (2) other neurotoxic substances are produced under the same conditions. The latter hypothesis has been ruled out, since D-lactate has been shown to induce severe neurological disturbances (Lorenz et al., 2005; Abeysekara et al., 2007). It was hypothesised that D-lactate interfered with pyruvate metabolism due to the similarities between inherited and acquired abnormalities in pyruvate metabolism and D-lactic acidosis. In this context, nutritional deciencies, such as thiamine deciency, would play a major role in the onset and severity of symptoms (Cross and Callaway, 1984). Abeysekara et al. (2007) suggested that D-lactate interferes with energy metabolism in the CNS by competitively blocking L-lactate entry into neurons, where L-lactate has an important role as a source of energy. Treatment of D-lactic acidosis In humans, several approaches have been used to successfully treat D-lactic acidosis (Uribarri et al., 1998): (1) oral antibiotic treatment to decrease the lactate-producing bacterial ora in the intestine; (2) prolonged oral fasting with simultaneous IV alimentation to diminish the quantity of substrate for intestinal fermentation; (3) low carbohydrate diet to diminish substrate available for bacterial fermentation; (4) re-anastomosis of the intestine in cases of intestinal bypass surgery; (5) rehydration and therapy of acidosis with high doses of bicarbonate, and (6) correction of acidosis and simultaneous clearance of D-lactate with haemodialysis. Even without any knowledge of the impact of D-lactate in this context, it was generally agreed that acidosis in diarrhoeic calves should be treated to restore normal body functions and especially to correct neurological disturbances. Sodium bicarbonate is the alkalising agent of choice for the correction of acidosis in the neonatal calf with diarrhoea (Kasari and Naylor, 1985). The amount of bicarbonate required for correction of acidosis is usually calculated using the following formula: HCO mmol body mass kg 3 base deficit mmol=L factor L=kg 1

Sahal et al., 1993), 0.65 (Binding et al., 2000) and 0.8 (Geishauser and Thu nker, 1997a), up to 1.0 or even 1.5 in severe acidosis (Grove-White, 1996). Doll (2002) recommended using the factor of 0.7 for the sake of ongoing losses. An isotonic (1.3%) solution of sodium bicarbonate is normally recommended for IV administration (Geishauser and Thunker, 1997a; Kasari, 1999; Naylor, 2002). Spik ing of isotonic uids with additional sodium bicarbonate (Grove-White, 1996) and administration of hypertonic sodium bicarbonate solutions has also been used successfully (Lorenz and Vogt, 2006). A study on the dynamics of D-lactate after correction of metabolic acidosis conrmed the value of this therapeutic practice. Seventy-three calves up to 3 weeks old with acute diarrhoea and base excess values less than 10 mmol/L were treated for acidosis with an IV administration over 3.5 h of an amount of sodium bicarbonate calculated using a factor of 0.6 in the formula above. Since mean D-lactate levels dropped from 10 mmol/L to 5.4 mmol/L in 24 h, the study showed that calves with elevated D-lactate concentrations do not require additional specic therapy, as D-lactate concentrations regularly decrease after correction of acidosis and restitution of body uid volume (Lorenz and Vogt, 2006). Ewaschuk et al. (2006) reported the same observation and discussed the reduction of D-lactate producing organisms due to antimicrobial treatment combined with enhanced renal excretion as a possible underlying mechanism of this phenomenon. If treated properly, high D-lactate levels have no negative impact on the prognosis of diarrhoeic calves (Lorenz, 2004a). Probiotics and D-lactic acidosis in calves The ecacy of probiotics in the treatment of infectious diarrhoea in humans has recently been reviewed (Allen et al., 2003). Nearly all trials that met the inclusion criteria reported a benecial eect in reducing diarrhoea, which was statistically signicant in many studies. Ewaschuk et al. (2004a) demonstrated the capability of Lactobacillus rhamnosus strain GG (LGG) to maintain viability in the gastrointestinal tract of calves which has possible benecial eects on D-lactate production in diarrhoeic calves. They also conrmed that LGG can be administered in an oral rehydration solution (ORS) without compromising the ecacy of the ORS or the viability of LGG, and that LGG only produces L-lactate, not D-lactate. In a clinical setting, Ewaschuk et al. (2006) tested whether this probiotic reduced gastrointestinal D-lactate production and/or severity of diarrhoea. Forty-eight calves admitted to the clinic for treatment of diarrhoea were randomly assigned to either an experimental group, where L. rhamnosus GG was administered in addition to normal clinical treatment protocols, or a control group. No dierences in serum or faecal D- or L-lactate between the groups were detected at 24 and 48 h after initial administration of L. rhamnosus GG. There was a non-signicant reduction in mortality

The size of the factor used varies considerably and ranges from 0.3 (Glawischnig et al., 1990), 0.5 (Naylor, 1987;

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I. Lorenz / The Veterinary Journal 179 (2009) 197203 Ewaschuk, J.B., Zello, G.A., Naylor, J.M., 2006. Lactobacillus GG does not aect D-lactic acidosis in diarrheic calves, in a clinical setting. Journal of Veterinary Internal Medicine 20, 614619. Geishauser, T., Thunker, B., 1997a. Metabolische Azidose bei neugeborenen Kalbern mit Durchfall Behandlung mit isosmo larer Natriumbikarbonat-Losung. Praktischer Tierarzt 78, 595 600. Geishauser, T., Thunker, B., 1997b. Metabolische Azidose bei neuge borenen Kalbern mit Durchfall Abschatzung an Saugreex oder Stehvermogen. Praktischer Tierarzt 78, 600605. Gentile, A., 1995. Untersuchungen uber die Aziditat der Pansenussigkeit von Kalbern nach intraruminaler Verabreichung von Rehy dratationslosungen. Deutsche tierarztliche Wochenschrift 102, 241 244. Gentile, A., Lorenz, I., 2005. Comparison of the clinical pictures in experimentally induced metabolic acidosis, hyper L-lactataemia and hyper D-lactataemia. In: Proceedings of the Buiatrissima, 1st Swiss Buiatrics Congress 85. Gentile, A., Rademacher, G., Seemann, G., Klee, W., 1998. Systemische Auswirkungen der Pansenazidose im Gefolge von Pansentrinken beim Milchkalb Retrospektive Analyse von 293 Fallen. Tierarztliche Praxis 26, 205209. Gentile, A., Sconza, S., Lorenz, I., Otranto, G., Rademacher, G., Famigli, B.P., Klee, W., 2004. D-lactic acidosis in calves as a consequence of experimentally induced ruminal acidosis. Journal of Veterinary Medicine A 51, 6470. Gentile, A., Lorenz, I., Sconza, S., Klee, W., in press. Experimentallyinduced systemic hyperchloremic acidosis in calves. Journal of Veterinary Internal Medicine. Glawischnig, E., Greber, N., Schlerka, G., 1990. Die Dauertropnfusion bei Kalbern mit hochgradiger Azidose. Tierarztliche Umschau 45, 562569. Grove-White, D.H., 1996. Pathophysiology and treatment of metabolic acidosis in the diarrhoeic calf. In: Proceedings of the XIX World Buiatrics Congress, pp. 102107. Grude, T., 1999. Laktat in Blut, Harn und Pansensaft von Kalbern, insbesondere bei Pansentrinkern, Doctoral Thesis, Munich. Hartmann, H., Meyer, H., Steinbach, G., 1981. Zur Pathogenese des Kalberdurchfalls mit Schlussfolgerungen fur Diatmanahmen. Mon atshefte Veterinarmedizin 36, 371377. Hartmann, H., Meyer, H., Steinbach, G., Schweinitz, P., Lustermann, S., 1984. Zum Sauren-Basen-Haushalt durchfallkranker Kalber. Monats hefte Veterinarmedizin 39, 738742. Kasari, T.R., 1999. Metabolic acidosis in calves. Veterinary Clinics of North America Food Animal Practice 15, 473486. Kasari, T.R., Naylor, J.M., 1984. Metabolic acidosis without clinical signs of dehydration in young calves. Canadian Veterinary Journal 25, 394 399. Kasari, T.R., Naylor, J.M., 1985. Clinical evaluation of sodium bicarbonate, sodium L-lactate, and sodium acetate for the treatment of acidosis in diarrheic calves. Journal of the American Veterinary Medical Association 187, 392397. Kasari, T.R., Naylor, J.M., 1986. Further studies on the clinical features and clinico-pathological ndings of a syndrome of metabolic acidosis with minimal dehydration in neonatal calves. Canadian Journal of Veterinary Research 50, 502508. Koenig, M., 2006. Untersuchungen zur Bildung von D-Laktat im Intestinum des Kalbes, Doctoral Thesis, Munich. Lorenz, I., 2004a. Inuence of D-lactate on metabolic acidosis and on prognosis in neonatal calves with diarrhoea. Journal of Veterinary Medicine A 51, 425428. Lorenz, I., 2004b. Investigations on the inuence of serum D-lactate levels on clinical signs in calves with metabolic acidosis. The Veterinary Journal 168, 323327. Lorenz, I., Vogt, S., 2006. Investigations on the association of D-lactate blood concentrations with the outcome of therapy of acidosis, and with posture and demeanour in young calves with diarrhoea. Journal of Veterinary Medicine A 53, 490494.

and greater faecal dry matter content in L. rhamnosus GGtreated calves. Although these ndings indicated either that the therapeutic use of probiotics may not aect D-lactate production in the intestines, or that more time is required to modify the intestinal ora in a benecial way in calves already aected with diarrhoea, this should not discourage further studies in this area. Conclusions
D-Lactic acidosis is a common occurrence in calves with neonatal diarrhoea, ruminal acidosis, and acidosis without dehydration syndrome. The clinical signs traditionally attributed to metabolic acidosis are mostly due to D-lactataemia which normally resolves after correction of the acidosis and with rehydration therapy. There are limited opportunities to improve therapeutic approaches to D-lactataemia, but there is some potential with therapies targeted on the mechanisms that lead to the decline of Dlactate values after therapy. A better understanding of the metabolism of D-lactate and its excretion in sick calves may also help to nd strategies to prevent accumulation of D-lactate. A further look at the use of probiotics in a prophylactic manner appears to be promising.

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