Changes

===Pathology===

===Pathology===

Ethylene glycol toxicosis usually results from ingestion although there have been reports of skin contamination resulting in toxicosis in cats <ref name="multiples">  http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 17.11.2010 </ref>. It is absorbed relatively quickly from the gastrointestinal tract <ref name="multiples">  http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 17.11.2010 </ref>, hence the quick manifestation of clinical signs following intoxication. After absorption transformation to its more toxic metabolites takes place in the liver and kidney <ref name="multiples">  http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 17.11.2010 </ref>. It is these substances, rather than ethylene glycol itself that are responsible for the more severe pathological changes in the body <ref name="multiples"> '''BSAVA Manual of Canine and Feline Emergency Care''',(Second Edition), p286-7 </ref> . The enzyme alcohol dehydrogenase, which is inhibited by 4-methylpyrazole <ref name="multiple">'''The 5-Minute Veterinary Consult, Canine and Feline''' (Second Edition),''Lippencott, Williams and Wilkins </ref> , is responsible for the initial conversion of ethylene glycol to glycoaldehyde <ref name="multiples">  http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 17.11.2010 </ref>. Glycoaldehyde in turn is metabolised to glycolic acid. Following this glycolic acid is converted to glyoxylic acid. This reaction, along with the earlier conversion of ethylene glycol to glycoaldehyde, are the rate-limiting steps in the metabolism of ethylene glycol. Finally glycolic acid undergoes metabolic transformation to produce the end product, oxalic acid. Glycolic acid and oxalate are directly nephrotoxic, leading to necrosis of the renal tubules. Glycolic acid is the main metabolite reposponsible for the metabolic acidosis, although oxalate contributes, as does lactic acid, whose formation is increased as an indirect result of the metabolic pathway outlined above <ref name="multiples"> '''http://en.wikipedia.org/wiki/Ethylene_glycol_poisoning#cite_note-Gabow_PA.2C_Clay_K.2C_Sullivan_JB.2C_Lepoff_R_1986_16.E2.80.9320-4''', accessed on 17.10.2010 </ref> . The metabolic acidosis interferes with normal metabolic pathways. In addition to being directly nephrotoxic oxalate binds ionised calcium in the serum forming calcium oxalate crystals which are excreted by the kidney. Some of these crystals accumulate within the kidney tubules resulting in further nephrotoxicity and decreased or complete prevention of urine production. The hypocalcaemia that is present is due not only to calcium oxalate crystal formation but also to the hyperphosphataemia that results from the acute renal failure. The decreased serum calcium level leads tetany <ref name="multiples"> '''Textbook of Veterinary Internal Medicine''', (Seventh Edition), ''Ettinger and Feldman''; p1747 </ref>.

Ethylene glycol toxicosis usually results from ingestion although there have been reports of skin contamination resulting in toxicosis in cats <ref name="multiples">  http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 17.11.2010 </ref>. It is absorbed relatively quickly from the gastrointestinal tract <ref name="multiples">  http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 17.11.2010 </ref>, hence the quick manifestation of clinical signs following intoxication. After absorption transformation to its more toxic metabolites takes place in the liver and kidney <ref name="multiples">  http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 17.11.2010 </ref>. It is these substances, rather than ethylene glycol itself that are responsible for the more severe pathological changes in the body <ref name="multiples"> '''BSAVA Manual of Canine and Feline Emergency Care''',(Second Edition), p286-7 </ref> . The enzyme alcohol dehydrogenase, which is inhibited by 4-methylpyrazole <ref name="multiple">'''The 5-Minute Veterinary Consult, Canine and Feline''' (Second Edition),''Lippencott, Williams and Wilkins </ref> , is responsible for the initial conversion of ethylene glycol to glycoaldehyde <ref name="multiples">  http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/210900.htm, accessed on 17.11.2010 </ref>. Glycoaldehyde in turn is metabolised to glycolic acid. Following this glycolic acid is converted to glyoxylic acid. This reaction, along with the earlier conversion of ethylene glycol to glycoaldehyde, are the rate-limiting steps in the metabolism of ethylene glycol. Finally glycolic acid undergoes metabolic transformation to produce the end product, oxalic acid. Glycolic acid and oxalate are directly nephrotoxic, leading to necrosis of the renal tubules. Glycolic acid is the main metabolite reposponsible for the metabolic acidosis, although oxalate contributes, as does lactic acid, whose formation is increased as an indirect result of the metabolic pathway outlined above <ref name="multiples"> '''http://en.wikipedia.org/wiki/Ethylene_glycol_poisoning#cite_note-Gabow_PA.2C_Clay_K.2C_Sullivan_JB.2C_Lepoff_R_1986_16.E2.80.9320-4''', accessed on 17.10.2010 </ref> . The metabolic acidosis interferes with normal metabolic pathways <ref name="multiples"> '''http://en.wikipedia.org/wiki/Ethylene_glycol_poisoning#cite_note-Gabow_PA.2C_Clay_K.2C_Sullivan_JB.2C_Lepoff_R_1986_16.E2.80.9320-4''', accessed on 17.10.2010 </ref>. In addition to being directly nephrotoxic oxalate binds ionised calcium in the serum forming calcium oxalate crystals which are excreted by the kidney. Some of these crystals accumulate within the kidney tubules resulting in further nephrotoxicity and decreased or complete prevention of urine production. The hypocalcaemia that is present is due not only to calcium oxalate crystal formation but also to the hyperphosphataemia that results from the acute renal failure. The decreased serum calcium level leads tetany <ref name="multiples"> '''Textbook of Veterinary Internal Medicine''', (Seventh Edition), ''Ettinger and Feldman''; p1747 </ref>.