D-Lactic acidosis in calves

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.     

Influence of D-lactate on metabolic acidosis and on prognosis in neonatal calves with diarrhoea

Three hundred bucket-fed diarrhoeic calves up to the age of 21 days were used to investigate the degree in which D-lactic acid contributes to metabolic acidosis in bucket-fed calves with naturally acquired neonatal diarrhoea. Fifty-five percent of all diarrhoeic calves had serum D-lactate concentrations higher than 3 mmol/l. Mean (+/-SD) D-lactate values were 5.7 mmol/l (+/-5.3, median: 4.1 mmol/l). D-lactate values were distributed over the entire range of detected values from 0 to 17.8 mmol/l in calves with base excess of -10 to -25 mmol/l. Serum D-lactate concentration was higher in patients with ruminal acidosis (6.6 +/- 5.2 mmol/l; median: 5.9 mmol/l) than in those with physiological rumen pH (5.3 +/- 5.4 mmol/l; median: 3.7 mmol/l). There was no evidence of a correlation (r = 0.051) between the serum levels of D-lactate and creatinine (as an indicator of dehydration). D-lactate was correlated significantly with both base excess (r = -0.685) and anion gap (r = 0.647). The proportion of cured patients was not significantly different between the groups with elevated (>3 mmol/l) and normal serum D-lactate concentrations. This study shows that hyper-D-lactataemia occurs frequently in diarrhoeic calves, has no impact on prognosis but may contribute to the clinical picture associated with metabolic acidosis in these animals.     

D-Lactic acidosis in calves as a consequence of experimentally induced ruminal acidosis

In order to test the hypothesis that ruminal drinking in calves can lead to D-lactic metabolic acidosis, ruminal acidosis was induced in nine calves by intraruminal application of untreated whole milk via a stomach tube. The amount of the daily force-fed liquid was 3 x 1 l. The experimental design called for an end of intraruminal applications if two or more of the following signs were observed: severe depression, estimated degree of dehydration >10%, absence of sucking reflex, lack of appetite for two consecutive feedings, severe metabolic acidosis with calculated Actual Base Excess (ABE) <-15 mmol/l. The procedure was scheduled to be discontinued on the 17th day of experiment. The onset of ruminal acidification occurred rapidly, and mean pH value fell from 6.70 (+/-0.48) to 4.90 (+/-0.38) after the first application. The following days the pH values varied between 4 and 5. Rumen acidity was characterized biochemically by a significant increase in both isomers of lactic acid. The effects of the intraruminal administration on the calves were detrimental; eight of nine calves showed an acute disease process. According to the pre-established clinical standard, seven of nine calves were removed from the intraruminal feeding schedule. All but one of the calves developed severe systemic acidosis. The increase in anion gap demonstrated the net acid load. In all the calves D-lactate levels were found to show a significant and rapid increase. On the contrary, L-lactate never deviated from physiological levels. These observations confirm that, in young calves as in adult cattle, ruminal acidosis may lead to a clinically manifested D-lactic metabolic acidosis.     

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

The objective of this prospective study was to elucidate whether amounts of bicarbonate needed for correction of acidosis and normalization of clinical signs are influenced by blood D-lactate concentrations in calves with diarrhoea. In 73 calves up to 3 weeks old with acute diarrhoea and base excess values below -10 mmol/l correction of acidosis was carried out within 3.5-h by intravenous administration of an amount of sodium bicarbonate which was calculated using the formula: HCO (mmol) = body mass (kg) x base deficit (mmol/l) x 0.6 (l/kg). Clinical signs, venous base excess, and plasma D-lactate concentrations were monitored immediately following admission, following correction of acidosis at 4 h and 24 h after admission. The base excess and plasma D-lactate concentrations throughout the study were -17.8 +/- 4.0, -0.4 +/- 0.4, -3.0 +/- 5.5 mmol/l (base excess), and 10.0 +/- 4.9, 9.8 +/- 4.8, 5.4 +/- 3.4 mmol/l (D-lactate) for the three times of examination. Metabolic acidosis was not corrected in more than half of the calves (n = 43) by the calculated amount of bicarbonate, whereas the risk of failure to correct acidosis increases with D-lactate concentrations. The study shows that calves with elevated D-lactate concentrations do not need additional specific therapy, as D-lactate concentrations regularly fall following correction of acidosis and restitution of body fluid volume, for reasons that remain unclear. However, calves with distinct changes in posture and demeanour need higher doses of bicarbonate than calculated with the factor of 0.6 in the formula mentioned above probably because of D-hyperlactataemia.     

Investigations on the influence of serum D-lactate levels on clinical signs in calves with metabolic acidosis

Correlations between the degree of acidosis and clinical signs (changes in posture, behaviour, intensity of suckling reflex) in neonatal diarrhoeic calves have been described in various studies. However, base excess values varied widely in calves exhibiting similar clinical symptoms. The objective of this study was to elucidate whether the clinical picture of acidotic calves with neonatal diarrhoea is influenced more by D-lactate concentration than by degree of acidosis. Eighty calves up to three weeks old that were admitted to the II Medical Animal Clinic with acute diarrhoea and base excess values between -10 and -25 mmol/L were included in the prospective study. Posture, behaviour, suckling and palpebral reflexes, and position of the eyeballs were scored during the initial examination. Base excess and serum D-lactate and urea concentrations were determined in venous blood. In order to quantify the influences of base excess and d-lactate on the clinical parameters, groups of different clinical categories were compared. The results show that variations in behaviour, and in posture can be better explained by elevations of serum D-lactate concentrations than by decreases in base excess. Disturbances of the palpebral reflex appear to be almost completely caused by high levels of D-lactate.     

Anion gap correlates with serum D- and DL-lactate concentration in diarrheic neonatal calves

The objective of this study was to investigate the relationship between serum D- and L-lactate concentrations, and anion gap (AG) in neonatal calves. The association of AG with lactic acidosis in diarrheic calves has only been investigated by measurement of L-lactate in calves with experimentally induced diarrhea. D-lactate has recently been reported to be present in high concentrations in the serum of some diarrheic neonatal calves. The contribution of this acid to AG is not reported. The relationship between AG and L- and D-lactate concentrations was examined in 24 healthy calves and 52 calves with naturally occurring infectious diarrhea with metabolic acidosis. AG was calculated as [Na+ + K+] - [Cl- + HCO3-]. D- and L-lactate were quantified using high-performance liquid chromatography. There was no correlation between L-lactate and AG, contrary to previous reports in the literature. Moderate correlations between D-lactate concentration and AG (r = .74, P < .0001), and between DL-lactate and AG (r = .77), P < .0001) were detected. No differences existed due to the age or sex of the calf. This study indicates that AG provides information on the nature of acidosis in the diarrheic, neonatal calf and reinforces the importance of investigating clinical, in addition to experimental, populations.     

Lactobacillus GG does not affect D-lactic acidosis in diarrheic calves, in a clinical setting

D-lactate, produced by gastrointestinal fermentation, is a major contributor to metabolic acidosis in diarrheic calves. Lactobacillus rhamnosus GG survives gastrointestinal transit in the neonatal calf and does not produce D-lactate. To determine whether this probiotic reduces gastrointestinal D-lactate production or severity of diarrhea or both, 48 calves (mean, 11 days old; range, 2-30 days) admitted to the clinic for treatment of diarrhea were randomly allocated to 2 groups. The experimental group was given Lactobacillus rhamnosus GG (1 x 10(11) cfu/d) PO, dissolved in milk or oral electrolyte solution, in addition to clinic treatment protocols; the other group served as a control. Serum and fecal samples were obtained at admission and at 24 and 48 hours after initial administration of Lactobacillus rhamnosus GG. All samples were analyzed for D- and L-lactate by using high-pressure liquid chromatography. Feces were also analyzed for pathogens, Lactobacillus rhamnosus GG recovery, and dry matter. D-lactic acidemia (>3 mmol/L) was present in 37/48 calves at admission. Lactobacillus rhamnosus GG was recovered in the feces of 13 experimental calves and 0 control calves 24 hours after administration. No difference in serum or fecal D- or L-lactate between the groups was detected at any time point. After therapy, D-lactic acidosis was absent at 48 hours in all but 1 calf. No relation between fecal pathogen (viral, bacterial, or protozoal) and degree of D-lactic acidosis was observed. The reduction in mortality and greater fecal dry matter in Lactobacillus rhamnosus GG-treated calves was not statistically significant.     

Experimentally induced systemic hyperchloremic acidosis in calves

Background: Among the various metabolic disturbances occurring in calves affected by neonatal diarrhea or ruminal acidosis, acidemia constitutes an important condition requiring specific therapy. Although various attempts have been made to estimate the degree of metabolic acidosis on the basis of clinical signs alone, some doubts have been raised regarding the accuracy and predictive value of the clinical variables suggested. HYPOTHESIS: The induction of metabolic acidosis in healthy calves via the infusion of hydrochloric acid (HCl) will lead to a clinical picture similar to that seen in neonatal calves with diarrhea or ruminal acidosis. ANIMALS: The study was carried out on 15 Holstein male calves between 5 and 19 days of age. METHODS: Hyperchloremic metabolic acidosis was induced over a period of 80 minutes by an IV infusion of 4,000 mL of 0.9% NaCl solution containing 400 mM HCl. RESULTS: Acidemia occurred rapidly and increased constantly up to a maximum value, which was reached in all calves by the end of the administration and amounted to a 22.4 mM/L mean base deficit (range from 17.0 to 33.1 mM/L). Despite the relatively severe acute acid-base imbalance during the entire observation period, no calves showed any clinical signs or depressed appetite. CONCLUSIONS AND CLINICAL IMPORTANCE: Factors other than a disturbance of the acid-base balance should be considered to be primarily responsible for the clinical picture in calves affected by diarrhea or ruminal acidosis.     

D-lactate production and excretion in diarrheic calves

The origin of D-lactate, the most important acid contributing to metabolic acidosis in the diarrheic calf, is unknown. We hypothesized that because D-lactate is produced only by microbes, gastrointestinal fermentation is the source. The objective of this study was to determine whether D-lactate production occurs in the rumen, colon, or both, and to measure D- and L-lactate concentrations in urine. Fecal, rumen, blood, and urine samples were obtained from 16 diarrheic and 11 healthy calves. Serum electrolyte concentrations were measured in both groups, and blood gas analyses were performed for diarrheic calves. All samples were analyzed for D- and L-lactate by high performance liquid chromatography (HPLC). Diarrheic calves were generally hyperkalemic with high serum anion gap, depressed serum bicarbonate, and low blood pH. L-lactate was markedly higher in rumen contents (22.7 mmol/ L [median]) and feces (8.6 mmol/L) of diarrheic calves than healthy calves (0.5 mmol/L and 5.1 mmol/L, respectively), but not different in serum or urine. Rumen, fecal, serum, and urine D-lactate concentrations were all significantly higher (P < .05) in diarrheic calves (17.0, 25.4, 13.9, and 19.2 mmol/L, respectively) than in healthy calves (0.5, 9.1, 1.4, and 0.5 mmol/L, respectively). Higher D-lactate concentrations in the rumen and feces of diarrheic calves suggests these sites as the source of D-lactate in blood and urine.     

Clinical and hematological studies in newborn Holstein-Frisian breeding calves with diarrhea in Morocco]

A total of 120 (80 males and 39 females) newborn Holstein-Frisian calves suffering from acute diarrhoea were studied clinically and biochemically, including the following parameters: pH, pCO2, act. HCO3, BE, RBC, PCV, HV, glucose lactate, urea, creatinine, total bilirubin, total protein, AST, Na, K and Cl. The results were interpreted according to their healthy condition, their age as well as their sex. The study had revealed an extreme metabolic acidosis, haemoconcentration, hypoglycaemia and hypofunction in the kidney and liver. Furthermore, the calves with diarrhoea had showed hyponatraemia, hypochloraemia, and hyperkalaemia. Important correlations between clinical and some blood parameters were found. Metabolic acidosis was more severe in male calves than females. These pathophysiological changes should be put in consideration during the therapy of newborn calves suffering from diarrhoea.     

Changes in plasma composition in calves surviving or dying from diarrhoea

With the growing variety of solutions available for oral and parenteral fluid therapy it is increasingly important to define the adverse changes in plasma associated with diarrhoea, particularly those associated with a fatal outcome. The effects of E. coli-induced diarrhoea in week-old Jersey calves were measured, comparing survivors with those that died. The main effects of diarrhoea were dehydration, metabolic acidosis, pre-renal uraemia and hyponatraemia. Hypernatraemia was unusual and mild. Calves which survived tended to be hypokalaemic whereas those which died showed intensifying metabolic acidosis and hyperkalaemia. Hypoglycaemia developed, but it was not generally worse in calves which failed to survive, though there were exceptions.     

Villus atrophy in ruminal drinking calves and mucosal restoration after reconditioning

The effect of reconditioning therapy on 7 chronic ruminal drinking veal calves is described. Two calves that were persistent ruminal drinkers were used as controls. In addition to clinical parameters, the morphological features of proximal jejunum biopsies were used to monitor the effect of therapy. Ruminal drinking calves showed various degrees of hyperplastic villus atrophy. When the reticular groove reflex was restored, clinical recovery was observed within 10 days; the length of villi increased as well as the villus/crypt ratio at the end of the reconditioning period. Crypt depth, however, did not alter, and the mitosis index significantly decreased. Villus atrophy in the controls gradually worsened. While the calves gained weight after recovery, retarded growth from the ruminal drinking period was not compensated.     

Villus atrophy in ruminal drinking calves and mucosal restoration after reconditioning

Summary

The effect of reconditioning therapy on 7 chronic ruminal drinking veal calves is described. Two calves that were persistent ruminal drinkers were used as controls. In addition to clinical parameters, the morphological features of proximal jejunum biopsies were used to monitor the effect of therapy.

Ruminal drinking calves showed various degrees of hyperplastic villus atrophy. When the reticular groove reflex was restored, clinical recovery was observed within 10 days; the length of villi increased as well as the villus/crypt ratio at the end of the reconditioning period. Crypt depth, however, did not alter, and the mitosis index significantly decreased. Villus atrophy in the controls gradually worsened.

While the calves gained weight after recovery, retarded growth from the ruminal drinking period was not compensated.     

Clinical, haematological and biochemical findings in milk-fed calves with chronic indigestion

The principal clinical signs in 59 milk-fed calves with chronic indigestion were general malaise and depression, poor appetite, poor body condition, dehydration, a dull and scaly hair coat, alopecia and clay-like faeces. All the calves had metabolic acidosis, which was associated with an inability to stand up in more than half of them. There were significant differences in the severity of acidosis between the calves that could stand and those that could not. Other signs in some of the calves were dehydration, leucocytosis, and increased activities of liver enzymes.     

Chronic indigestion in milk-fed calves]

Calves with chronic indigestion have disturbed general attitude and condition, decreased appetite, loss of hair, clay-like faeces and ruminal and metabolic acidosis. Possible causes include dysfunction of the oesophageal-groove reflex, reflux of abomasal contents into the rumen and abnormal ruminal motility. The anion gap may be increased or within normal limits. Metabolic acidosis is significantly more severe in calves that are unable to stand than in calves that can stand. Treatment of chronic indigestion consists primarily of intravenous administration of sodium bicarbonate, transfaunation of the rumen and oral administration of electrolyte solutions.     

The role of endotoxins in induced ruminal acidosis in calves.

Experimentally induced ruminal acidosis was carried out in 4 calves to investigate the possibility of resorption of endotoxins from Gram negative bacteria originating from the gastro-intestinal tract. The ruminal acidosis was induced by overfeeding of oats and the effect was evaluated by clinical and blood biochemical changes. Blood samples were collected every 2 h for 60 h before and after experimental feeding. The animals showed signs of ruminal acidosis and also the clinical and blood biochemical changes were similar to those seen after experimental endotoxaemia. However, although being less dramatic the changes in many relevant parameters such as an increase in prostaglandin F metabolite levels, body temperature, endotoxins and a decrease in iron indicate that an endotoxaemic state had occurred. The results of the present study show that ruminal acidosis/stasis is linked to resorption of endotoxins from the gastro-intestinal tract causing endotoxaemia/endotoxicosis.     

The prevalence and clinical relevance of hyperkalaemia in calves with neonatal diarrhoea

One hundred and twenty-four calves with neonatal diarrhoea were investigated in order to assess the prevalence of hyperkalaemia and the associated clinical signs. Hyperkalaemia (potassium concentration >5.8 mmol/L) was recognized in 42 (34%) calves and was more closely associated with dehydration than with decreases in base excess or venous blood pH. In 75 calves with normal blood concentrations of D-lactate (i.e. ?3.96 mmol/L), K concentrations were moderately correlated with base excess values (r = ?0.48, P < 0.001). In contrast, no significant correlation was observed in 49 calves with elevated D-lactate. Only three hyperkalaemic calves had bradycardia and a weak positive correlation was found between heart rate and K concentrations (r = 0.22, P = 0.014). Ten of the 124 calves had cardiac arrhythmia and of these seven had hyperkalaemia indicating that cardiac arrhythmia had a low sensitivity (17%) but a high specificity (96%) as a predictor of hyperkalaemia.In a subset of 34 calves with base excess values ??5 mmol/L and D-lactate concentrations <5 mmol/L (of which 22 had hyperkalaemia), changes in posture/ability to stand could be mainly explained by elevations of K concentrations (P < 0.001) and to a lesser extent by increases in L-lactate concentrations (P = 0.024). Skeletal muscle weakness due to hyperkalaemia alongside hypovolaemia may produce a clinical picture that is similar to that in calves with marked D-lactic acidosis. However, since reductions in the strength of the palpebral reflex are closely correlated with D-lactate concentrations, a prompt palpebral reflex can assist the clinical prediction of hyperkalaemia in calves presenting with a distinct impairment in their ability to stand (specificity 99%, sensitivity 29%).     

Potential protective effects of thiamine supplementation on the ruminal epithelium damage during subacute ruminal acidosis

In ruminants, the ruminal epithelium not only has the function of absorbing nutrients but also is an important tissue to prevent harmful substances in the rumen from entering the blood circulation. Thus, the normal function of ruminal epithelium is critical for ruminants. However, subacute ruminal acidosis induced by high-concentrate diets often damages the barrier function of ruminal epithelium in ruminants. Recently, many studies have shown that dietary supplementation with thiamine is an effective method to alleviate subacute ruminal acidosis. In order to provide theoretical reference for the in-depth study of subacute ruminal acidosis and the application of thiamine in the future, this review introduces the effects of subacute ruminal acidosis on morphological structure, inflammatory response, and tight junction of ruminal epithelium. In addition, this paper summarizes the role of thiamine in maintaining ruminal epithelial function of ruminants during subacute ruminal acidosis challenge.     

Investigations of D-lactate metabolism and the clinical signs of D-lactataemia in calves

Five clinically healthy calves received an intravenous injection of 25 g sodium D-lactate (223 mmol) in 100 ml sterile water and five control calves were given the same volume of 0.9 per cent sodium chloride. Two clinical examiners who were blinded to the status (test or control) of the calves observed that between eight and 40 minutes after the injections the calves that had received sodium-D-lactate could be distinguished with certainty from the control calves on the basis of their clinical signs, for example, an impaired palpebral reflex, somnolence and a staggering gait. One-compartment and two-compartment analyses of the changes in the plasma concentration of D-lactate, and its renal clearance, indicated that the calves metabolised considerable amounts of D-lactate.     

Ultrasonographic examination of the forestomachs and the abomasum in ruminal drinker calves

Background

The study investigated the ultrasonographic appearance of the reticulum, rumen, omasum and abomasum of calves with ruminal drinking syndrome.

Methods

In ten milk-fed calves with ruminal drinking syndrome the reticulum, rumen, omasum and abomasum were examined by ultrasonography using a 5-MHz linear transducer before, during and after the ingestion of milk.

Results

The reticulum could be imaged in eight of ten calves before feeding. The reticular wall appeared as an echoic line, similar to mature cattle, and reticular folds were seen in eight calves. The reticular content appeared as echoic heterogeneous fluid. Reticular contractions were biphasic with 1.0 ± 0.38 contractions per minute. The rumen had a mean wall thickness of 2.1 mm dorsally, 3.5 mm at the level of the longitudinal groove, and 3.2 mm ventrally. The ventral sac of the rumen of all calves contained echoic heterogeneous liquid. During feeding the milk entering the rumen could be seen as hyperechoic liquid in five calves. The omasum was seen on the right side as a crescent-shaped line medial to the liver in seven calves. Only the omasal wall closest to the transducer was seen as an echoic line with a mean thickness of 2.7 mm. The ultrasonographic appearance of the omasum did not change during or after feeding. The abomasum was seen immediately caudal to the xyphoid on both sides of the midline before feeding. The mean length at the ventral midline was 22.2 cm. The ingesta were heterogeneous in all calves and the abomasal folds were distinct in eight. The mean lateral expansion of the abomasum from the ventral midline to the left and right varied from 8.7 to 13.8 cm and from 4.3 to 11.3 cm. The milk entering the abomasum was observed in all calves, and signs of milk clotting were seen in all calves 15 minutes after feeding.

Conclusion

This study showed that ultrasonography is useful for detecting milk in the reticulum and rumen of calves with ruminal drinking syndrome.