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, hence the quick manifestation of clinical signs following intoxication. Following absorption transformation to its more toxic metabolites takes place in the liver and kidney. It is these substances, rather than ethylene glycol itself that are responsible for the more severe pathological changes in the body. The enzyme alcohol dehydrogenase, which is inhibited by 4-methylpyrazole, is responsible for the initial conversion of ethylene glycol to glycoaldehyde. 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., which interferes with the normal metabolic pathways of the body.  

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, hence the quick manifestation of clinical signs following intoxication. After absorption transformation to its more toxic metabolites takes place in the liver and kidney. It is these substances, rather than ethylene glycol itself that are responsible for the more severe pathological changes in the body. The enzyme alcohol dehydrogenase, which is inhibited by 4-methylpyrazole, is responsible for the initial conversion of ethylene glycol to glycoaldehyde. 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. 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 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>.

Glycolic acid is one such metabolite. It is a direct metabolite of glycoaldehyde which itself is produced following the actions of the enzyme alcohol dehydrogenase on ethylene glycol.

*Tetany results from the binding of Ethylene Glycol meatabolites to calcium ions present in serum <ref name="multiples"> '''Textbook of Veterinary Internal Medicine''', (Seventh Edition), ''Ettinger and Feldman''; p1747 </ref>.