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.     

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.     

Floppy kid syndrome caused by D-lactic acidosis in goat kids

BACKGROUND: Goat kids with floppy kid syndrome have metabolic acidosis, muscle weakness, and depression but no dehydration. HYPOTHESIS: D-Lactate is the major component of acidemia in goat kids with floppy kid syndrome. ANIMALS: Fifty-five goat kids with floppy kid syndrome (group F) and 35 clinically healthy goat kids (group C). METHODS: Clinical, biochemical, microbiologic, virologic, parasitologic, and pathologic examinations. RESULTS: The animals in group F had a blood pH of 7.13 +/- 0.11 and a base excess of -17.8 +/- 3.8 mM, which were both lower than the values in the control animals (pH, 7.32 +/- 0.31; base excess, -0.1 +/- 2.7 mM; P < .001). Floppy kids had a significantly larger anion gap than healthy kids (31.2 +/- 3.7 versus 21.5 +/- 8.5 mM; P < .001). The concentration of L-lactate was lower in floppy kids than in healthy kids (0.67 +/- 0.49 versus 1.60 +/- 1.02 mM), but the concentration of D-lactate was higher in floppy kids (7.43 +/- 2.71 versus 0.26 +/- 0.24 mM; P < .001). Intravenous and oral administration of sodium bicarbonate in floppy kids resulted in a significant increase in blood pH and base excess and a decrease in the anion gap (P < .001). In addition, the concentration of L-lactate increased (P = .039). CONCLUSIONS AND CLINICAL IMPORTANCE: Metabolic acidosis in goat kids with floppy kid syndrome is caused by an increase in the plasma concentration of D-lactate.     

Use of a quantitative strong ion approach to determine the mechanism for acid-base abnormalities in sick calves with or without diarrhea

Acid-base abnormalities are frequently present in sick calves. The mechanism for an acid-base disturbance can be characterized using the strong ion approach, which requires accurate values for the total concentration of plasma nonvolatile buffers (A(tot)) and the effective dissociation constant for plasma weak acids (K(a)). The aims of this study were to experimentally determine A(tot), K(a), and net protein charge values for calf plasma and to apply these values quantitatively to data from sick calves to determine underlying mechanisms for the observed acid-base disturbance. Plasma was harvested from 9 healthy Holstein-Friesian calves and concentrations of quantitatively important strong ions (Na+, K+, Ca2+, Mg2+, Cl-, L-lactate) and nonvolatile buffer ions (total protein, albumin, phosphate) were determined. Plasma was tonometered with CO2 at 37 degrees C, and plasma P(CO2) and pH measured over a range of 15-159 mm Hg and 6.93-7.79, respectively. Strong ion difference (SID) was calculated from the measured strong ion concentrations, and nonlinear regression was used to estimate values for A(tot) and K(a) from the measured pH and P(CO2) and calculated SID. The estimated A(tot) and K(a) values were then validated using data from 2 in vivo studies. Mean (+/- SD) values for calf plasma were A(tot) = 0.343 mmol/g of total protein or 0.622 mmol/g of albumin; K(a) = (0.84 +/- 0.41) x 10(-7); pK(a) = 7.08. The net protein charge of calf plasma was 10.5 mEq/L, equivalent to 0.19 mEq/g of total protein or 0.34 mEq/g of albumin. Application of the strong ion approach to acid-base disturbances in 231 sick calves with or without diarrhea indicated that acidemia was due predominantly to a strong ion acidosis in response to hyponatremia accompanied by normochloremia or hyperchloremia and the presence of unidentified strong anions. These results confirm current recommendations that treatment of acidemia in sick calves with or without diarrhea should focus on intravenous or PO administration of a fluid containing sodium and a high effective SID.     

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.     

Effects of intravenous hyperosmotic sodium bicarbonate on arterial and cerebrospinal fluid acid-base status and cardiovascular function in calves with experimentally induced respiratory and strong ion acidosis

The objectives of this study were to determine the effects of hyperosmotic sodium bicarbonate (HSB) administration on arterial and cerebrospinal fluid (CSF) acid-base balance and cardiovascular function in calves with experimentally induced respiratory and strong ion (metabolic) acidosis. Ten healthy male Holstein calves (30-47 kg body weight) were instrumented under halothane anesthesia to permit cardiovascular monitoring and collection of blood samples and CSE Respiratory acidosis was induced by allowing the calves to spontaneously ventilate, and strong ion acidosis was subsequently induced by i.v. administration of L-lactic acid. Calves were then randomly assigned to receive either HSB (8.4% NaHCO3; 5 ml/kg over 5 minutes, i.v.; n=5) or no treatment (controls, n=5) and monitored for 1 hour. Mixed respiratory and strong ion acidosis was accompanied by increased heart rate, cardiac index, mean arterial pressure, cardiac contractility (maximal rate of change of left ventricular pressure), and mean pulmonary artery pressure. Rapid administration of HSB immediately corrected the strong ion acidosis, transiently increased arterial partial pressure of carbon dioxide (P(CO2)), and expanded the plasma volume. The transient increase in arterial P(CO2) did not alter CSF P(CO2) or induce paradoxical CSF acidosis. Compared to untreated control calves, HSB-treated calves had higher cardiac index and contractility and a faster rate of left ventricular relaxation for 1 hour after treatment, indicating that HSB administration improved myocardial systolic function. We conclude that rapid i.v. administration of HSB provided an effective and safe method for treating strong ion acidosis in normovolemic halothane-anesthetized calves with experimentally induced respiratory and strong ion acidosis. Fear of inducing paradoxical CSF acidosis is not a valid reason for withholding HSB administration in calves with mixed respiratory and strong ion acidosis.     

Changes in the profile of liver enzymes in newborn calves induced by experimental,subclinical acidosis in pregnant cows and osmotic diarrhoea

Experimental, subclinical acidosis was induced by oral administration of sacharose during the last 2 months of pregnancy in 15 cows. Seven cows and their newborn calves were used as a control group. The liver enzyme activities in the serum and the blood acid-base status were determined in the 15 calves from the cows in the experimental group. Mannitol was administered orally to 8 calves from the experimental group to induce osmotic diarrhoea. It was concluded that subclinical acidosis in pregnant cows alters the biochemical liver profile of their newborn calves, affecting the aspartate aminotransferase, alanine transaminase, beta glucuronidase, glutamate dehydrogenase and bilirubin activities in the serum, which are associated with oedematous changes to the hepatocytes. Diarrhoea was accompanied by an increase in the alkaline phosphatase and gammaglutamyl transferase activities and a decrease in the total protein concentration in the serum. These changes were apparently related to the numerous necrotic foci in the liver and the proliferation of the Kuppfer cells. It would appear from these results that the liver damage in the newborn calves was associated with the subclinical, metabolic acidosis in their dams and that osmotic diarrhoea occurring in the neonatal period additionally impaired the liver function.Abbreviations ALP alkaline phosphatase - ALT alanine transaminase - AST aspartate aminotransferase - GR betaglucuronidase - bw body weight - ELISA enzyme-linked immunosorbent assay - GD glutamate dehydrogenase - GGT gammaglutamyl transferase - IU international unit     

Effect of quality of colostrum on health,growth and immunoglobulin G concentration in Holstein calves in a hot environment

The aim of this study was to determine the effect of ingestion of pasteurized and subsequently frozen–thawed pooled colostrum (≥50 mg Ig/mL) with different bacterial counts and immunoglobulin concentration (IgC) on the occurrence of diarrhea and pneumonia in 306 neonatal Holstein calves in a hot environment. Calves were assigned to be fed colostrum with total bacterial counts (TBC) lower or greater than 100 000 colony‐forming units (cfu)/mL, total coliform counts (TCC) greater or lower than 10 000 cfu/mL, and IgC lower or higher than 85 mg Ig/mL. Calves fed colostrum with TBC ≥100 000 cfu/mL were more likely (risk ratio 1.34, confidence interval 1.05–1.71; P < 0.05) to present pneumonia than calves receiving colostrum with lower TBC (incidence 53.2 vs. 39.8%). Calves fed colostrum with high TCC had increased chances of suffering pneumonia (51.4 vs. 42.1%; P < 0.05) than calves fed colostrum with lower TCC. Calves fed colostrum with ≥85 mg Ig/mL tended to present higher daily weight gain (505 ± 113 vs. 484 ± 126 g; P = 0.09). TBC and TCC in colostrum did not influence the incidence rate of diarrhea. It was concluded that under the conditions of the present study, heavy contamination of on‐farm pasteurized frozen–thawed colostrum is seemingly unavoidable and this contamination poses a threat for pneumonia, but not for diarrhea.     

Efficacy of two low-dose oral tylosin regimens in controlling the relapse of diarrhea in dogs with tylosin-responsive diarrhea: a prospective,single-blinded,two-arm parallel,clinical field trial

Background

Despite its wide acceptance as a treatment for canine chronic enteropathies, the macrolide antibiotic tylosin lacks official oral dosage recommendations. Not even textbooks share consensus about the dose; daily recommendations vary from 25 to 80 mg/kg and dosing intervals from one to three times daily.The objective of this prospective, single-blinded, two-arm parallel, clinical field trial was to determine whether doses of 5 mg/kg or 15 mg/kg tylosin administered orally once daily for seven days would have a similar effect on fecal consistency in diarrhea relapses to that of a 25 mg/kg dose of tylosin administered once daily for seven days, a dosage that has proved effective in controlling canine tylosin-responsive diarrhea (TRD). A further objective was to compare the efficacy of the 5 mg/kg and 15 mg/kg tylosin dosages. Fifteen client-owned dogs diagnosed with TRD that had responded to a dose of 25 mg/kg tylosin once daily for seven days were enrolled in the study. After a relapse of diarrhea the dogs were allocated into two groups receiving tylosin orally in doses of either 5 mg/kg or 15 mg/kg once daily for seven days. The owners were blinded to the dosage. The elimination of diarrhea was the main criterion in assessing treatment success. The mean fecal consistency score of the last three treatment days for all dosages, including 25 mg/kg, as evaluated by the owners according to a standardized fecal scoring system, served as the primary outcome measures.

Results

All eight dogs responded to the 5 mg/kg dose, and six of seven dogs responded to the 15 mg/kg dose. The mean fecal consistency scores at the 25 mg/kg tylosin dosage were no significantly different from scores at the 5 mg/kg or 15 mg/kg tylosin dosages (P = 0.672, P = 0.345).

Conclusions

Interestingly, 14/15 (93%) of the dogs responding to a dose of 25 mg/kg tylosin once daily for seven days also responded to the lower dosages at diarrhea relapse. The data indicate that a suitable dose of tylosin for treating diarrhea relapse in canine TRD could be as low as 5 mg/kg once daily for seven days.     

Soybean oil supplementation of a high-concentrate diet does not affect site and extent of organic matter, starch, neutral detergent fiber, or nitrogen digestion, but influences both ruminal metabolism and intestinal flow of fatty acids in limit-fed lambs

Our objective was to measure ruminal fermentation characteristics and site and extent of nutrient digestion in sheep limit-fed an 81.6% (DM basis) concentrate diet supplemented with increasing levels of soybean oil. Eight white-faced wether lambs (39.9+/-3.0 kg BW) fitted with ruminal, duodenal, and ileal cannulas were used in a replicated 4 x 4 Latin square experiment. Diets were formulated to contain 15.0% CP (DM basis) and included bromegrass hay (18.4%), cracked corn, soybean oil, corn gluten meal, urea, and limestone. Soybean oil was added to diets at 0, 3.2, 6.3, and 9.4% of dietary DM. The diet was limit-fed at 1.4% of BW. After 14 d of dietary adaptation, Cr2O3 (2.5 g) was dosed at each feeding for 7 d followed by ruminal, duodenal, ileal, and fecal sample collections for 3 d. Digestibilities of OM, starch, NDF, and N were not affected (P = 0.13 to 0.95) by increasing dietary soybean oil level. Means for true ruminal (percentage of intake), lower-tract (percentage entering the duodenum), and total-tract (percentage of intake) digestibility for each nutrient were (mean+/-SEM): OM = 50.7+/-4.66%, 71.6+/-2.58%, and 82.7+/-0.93%; starch = 92.0+/-1.94%, 96.1+/-0.70%, and 99.8+/-0.05%; NDF = 36.7+/-6.75%, 50.9+/-7.58%, and 71.7+/-1.93%; and N = 31.6+/-9.93%, 84.1+/-1.50%, and 81.0+/-1.10%, respectively. Total VFA concentration was greatest in sheep fed 6.3% soybean oil and least in sheep fed 9.4% soybean oil (cubic, P = 0.01). Duodenal flow of fatty acids from the diet and those metabolized within the rumen increased (linear, P < 0.001) with increasing dietary soybean oil level. Ileal flow of 16:0, 17:0, 18:0, 18:1trans, and 18:1cis-9 fatty acids increased (P < or = 0.04) with increasing dietary soybean oil level. Apparent small intestinal disappearance of 18:0 decreased (linear, P = 0.004) as dietary soybean oil increased, and with 9.4% dietary soybean oil, nearly half the duodenal 18:0 was observed at the ileum; thus, the true energy value of the soybean oil decreased with increasing oil supplementation. We conclude that supplementation of a high-concentrate diet with increasing amounts of soybean oil in limit-fed sheep resulted in a trade off between loss of potential dietary energy from the fat and gain of important PUFA and biohydrogenation intermediates, but without a marked influence on digestibility of other important macronutrients.     

Formulating diets based on digestible calcium instead of total calcium does not affect growth performance or carcass characteristics,but microbial phytase ameliorates bone resorption caused by low calcium in diets fed to pigs from 11 to 130 kg

An experiment was conducted to test the hypothesis that the requirement for Ca expressed as a ratio between standardized total tract digestible (STTD) Ca and STTD P obtained in short-term experiments may be applied to pigs fed diets without or with microbial phytase from 11 to 130 kg. In a 5-phase program, 160 pigs (body weight: 11.2 ± 1.8 kg) were randomly allotted to 32 pens and 4 corn–soybean meal-based diets in a 2 × 2 factorial design with 2 diet formulation principles (total Ca or STTD Ca), and 2 phytase inclusion levels (0 or 500 units/kg of feed) assuming phytase released 0.11% STTD P and 0.16% total Ca. The STTD Ca:STTD P ratios were 1.40:1, 1.35:1, 1.25:1, 1.18:1, and 1.10:1 for phases 1 to 5, and STTD P was at the requirement. Weights of pigs and feed left in feeders were recorded at the end of each phase. At the conclusion of phase 1 (day 24), 1 pig per pen was euthanized and a blood sample and the right femur were collected. At the end of phases 2 to 5, a blood sample was collected from the same pig in each pen. At the conclusion of the experiment (day 126), the right femur of 1 pig per pen was collected and carcass characteristics from this pig were measured. No interactions were observed between diet formulation principle and phytase inclusion for growth performance in any phase and no differences among treatments were observed for overall growth performance. Plasma Ca and P and bone ash at the end of phase 1 were also not influenced by dietary treatments. However, on day 126, pigs fed nonphytase diets formulated based on total Ca had greater bone ash than pigs fed STTD Ca-based diets, but if phytase was used, no differences were observed between the 2 formulation principles (interaction P < 0.05). At the end of phases 2 and 3, pigs fed diets without phytase had greater (P < 0.05) plasma P than pigs fed diets with phytase, but no differences were observed at the end of phases 4 and 5. A negative quadratic effect (P < 0.05) of phase (2 to 5) on the concentration of plasma Ca was observed, whereas plasma P increased (quadratic; P < 0.05) from phases 2 to 5. However, there was no interaction or effect of diet formulation principle or phytase inclusion on any carcass characteristics measured. In conclusion, STTD Ca to STTD P ratios can be used in diet formulation for growing-finishing pigs without affecting growth performance or carcass characteristics and phytase inclusion ameliorates bone resorption caused by low dietary Ca and P.     

MRI features can help to confirm a diagnosis of progressive myelomalacia,but may not be accurate in dogs lacking characteristic clinical signs at the time of imaging

Progressive myelomalacia (PMM) is a fatal sequela of acute thoracolumbar intervertebral disc extrusion in dogs, with unpredictable onset in the days after the inciting injury. No single reliable diagnostic test is currently available. Magnetic resonance imaging (MRI) features such as T2-weighted spinal cord hyperintensity and loss of subarachnoid signal in a half-Fourier single-shot turbo spin echo (HASTE) sequence have been associated with PMM, but are sometimes present in other dogs with severe deficits. Magnetic resonance imaging findings in 22 dogs with a clinical or histopathologic diagnosis of PMM and 38 deep pain-negative paraplegic dogs were compared in a retrospective case-control study. Length of T2-weighted hyperintense spinal cord change and HASTE signal loss were significantly associated with clinically evident PMM (P = .0019 and P = .0085), however, there were no significant differences between groups when analysis was restricted to dogs not yet showing clinical signs of PMM. The PMM group also had significantly shorter compressive lesions than the control group (P = 0.026), suggesting a possible role of more severe focal pressure at the extrusion site. A segment of total loss of contrast enhancement in the venous sinuses and meninges, a feature not previously described, was more common in the PMM group and the difference approached significance (P = 0.054). Findings show that MRI features can support the diagnosis in dogs with clinical evidence of PMM, and absence of these features supports absence of PMM at time of imaging. However, their absence does not reliably differentiate dogs with imminent progressive myelomalacia from other dogs with severe deficits following intervertebral disc extrusion.