D-lactic acidosis (DLA) is a disease associated with D-lactatemia, acidosis and neurological signs. However, these associations are ill-defined. Bacterial fermentation in the intestine causes increasing D-lactic acid concentrations in the body. Therefore, DLA is reported secondary to gastrointestinal diseases, such as short bowel syndrome, gastroenteritis or diarrhea. Despite intestinal origin, sudden D-lactatemia is often a result of impaired D-lactate metabolism in the body.<p>
Aims of this work were to determine: 1) Influence of the presence of D-lactate or acidity on neurological disturbances; 2) Effectiveness of parenteral NaHCO3 therapy in correcting cerebrospinal acidity and DLA; 3) Prevalence of DLA in diarrheic lambs and fecal D-lactate thresholds; 4) Effectiveness of malate in preventing DLA.<p>
The methodological tools consisted of animal models (calves and lambs): 1) Advanced surgical procedure in calves for long-lasting atlanto-occipital catheterizations; 2) Intravenous infusions of acids to experimentally induce acidosis; 3) Intravenous NaHCO3 therapies; 4) Sampling of cerebrospinal fluid (CSF), blood, urine and feces from experimental / treated calves or diarrheic lambs for blood gas analysis, and D-lactate separation by chromatography.<p>
D-lactate entered the central nervous system (> 2 mmol/L) from the circulation following experimentally induced D-lactatemia (> 5 mmol/L) and was responsible for neurological disturbances which correlated (r = 0.9, P < 0.05) with both CSF and serum D-lactate concentrations. A zenith of neurological disturbances, ataxia was evident when D-lactate concentration exceeded 12 mmol/L (CSF) and 26 mmol/L (serum), however, a nadir of acidosis (pH 6.9) caused by HCl infusions produced only mild neurological disturbances (P < 0.05). Therapeutic NaHCO3 infusions did not result paradoxical CSF acidosis, but supportive in correcting (P < 0.05) acidosis (ÄpH + 0.11) and D-lactatemia in calves.<p>
In lambs, metabolic acidosis following a range of mild to severe diarrhea was observed with a corresponding range of D-lactate concentrations in both serum (< 0.05−24.0 mmol/L) and feces (< 0.05−31.0 mmol/L). D-lactate was absorbed into the circulation when the fecal D-lactate concentration exceeded 10.2 mmol/L (threshold).
In calves, moderate oral use of malate produced a > 50% (P < 0.05) decrease in fecal and serum D-lactate concentrations suggesting prebiotic properties to prevent DLA. <p>
This dissertation answers the critical questions about the onset of neurological signs in D-lactic acidosis, and advances the current knowledge on the metabolism of D-lactate, the prevention and treatment of acidosis.
| Identifer | oai:union.ndltd.org:USASK/oai:usask.ca:etd-01202009-120329 |
| Date | 21 April 2009 |
| Creators | Abeysekara, Saman |
| Contributors | Paterson, Phyllis G., Naylor, J. M., Hamilton, Donald L., Chilibeck, Philip D., Brocks, D. R., Bandy, Brian, Zello, Gordon A. |
| Publisher | University of Saskatchewan |
| Source Sets | University of Saskatchewan Library |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf, application/octet-stream |
| Source | http://library.usask.ca/theses/available/etd-01202009-120329/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Saskatchewan or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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