ETHANOL METABOLISM CH 3 CH 3 CH 3 HCHCHC OO O _ O HH + Alcohol DehyAldehyde Dehy EthanolAcetaldehydeAcetate FOMEPIZOLE INHIBITSANTABUSE INHIBITS ALSO METRONIDAZOLE

OTHER ALCOHOLS RR = H METHANOL R=CH 3 ETHANOL HCHR=CH 2 CH 3 PROPANOL OR=CH 2 OHETHYLENE GLYCOL HR=CHOHCH 3 PROPYLENE GLYCOL ETC All react with alcohol dehydrogenase + NAD to give aldehydes, and then with aldehyde dehydrogenase + NAD to give the acids

COMPETITION SHORT CHAIN ALCOHOLS REACT QUICKLY WITH BOTH ENZYMES; LONGER CHAIN ARE SLOWER BUT AFFINITY FOR ALCOHOL DEHY IS GREATER FOR ETHANOL THAN FOR METHANOL OR ETHYLENE GLYCOL SO ETHANOL INHIBITS REACTION WITH THESE OTHER ALCOHOLS

ETHYLENE GLYCOL ANTIFREEZE FAST REACTIONS CH 2 OHCH 2 OHCH 2 OH CH 2 OHCHOCOO - ETHYLENE GLYCOLGLYCOLALDEHYDEGLYCOLATE SLOWER REACTIONS COO - COO - COO - CH 2 OHCHOCOO - GLYCOLATEGLYOXYLATEOXALATE GLYCOLATE CAUSES THE ACIDOSIS OXALATE IS THE MOST LETHAL (BINDS Ca ++ )

HOW TO DIAGNOSE IT HISTORY OF INGESTION HIGH ANION GAP ACIDOSIS NOT KETO OR LACTIC OR RENAL FAILURE (THE COMMON ONES) CALCIUM OXALATE CRYSTALS IN URINE – A BIT LATE! HYPOCALCAEMIA ? WITH TETANY OSMOLAR GAP

ANION GAP Cations (+)Anions (-) Na140Cl105 K 4BIC 26 Ca + Mg 3Albumin 10 Others 1Other proteins 2 TOTAL148Lactate 1 Na + K + 4Ketones 1 Others 3 TOTAL148 Cl + BIC + 17 So Na + K + 4 = Cl + BIC + 17 (Na + K) - (Cl + BIC) = 17 – 4 = 13

OSMOLAR GAP MEASURED P OSM – CALCULATED P OSM CALCULATION OF P OSM 2 X Na + GLUCOSE + UREA THIS GAP IS NORMALLY 0 WITH SD 5 NONIONIC SUBSTANCES SUCH AS ETHANOL, METHANOL, ETHYLENE GLYCOL, PROPYLENE GLYCOL, ISOPROPANOL, ACETONE, MANNITOL

ANOTHER CLUE LABORATORY ASKED “WHY IS OUR LACTATE NORMAL (1) AND BLOOD GAS MACHINE SAYS HIGH (17)?” REPEAT, GET NEW SAMPLE, SAME RESULTS – THEREFORE: CONSULT INTERNET – REPORT THAT SOME BLOOD GAS LACTATE PROBES (OUR TYPE!) REACT TO GLYCOLATE

EXPLANATION OF DISCREPANCY LABORATORY TEST IS DONE WITH AN ENZYME (L-LACTATE DEHYDROGENASE, USES NAD) THAT IS ABSOLUTELY SPECIFIC FOR L-LACTATE AND DOES NOT REACT WITH D- LACTATE OR GLYCOLATE OUR BLOOD GAS MACHINE HAS A LACTATE ELECTRODE THAT USES A MICROBIAL LACTATE OXIDASE THAT REACTS WITH OXYGEN TO GENERATE H 2 O 2 WHICH GIVES THE SIGNAL THIS LACTATE OXIDASE IN OUR MACHINE IS PROMISCUOUS AND REACTS WITH D-LACTATE AND GLYCOLATE AND GIVES A SIGNAL THAT IS REPORTED AS LACTATE OTHER BRANDS OF BLOOD GAS MACHINE HAVE LACTATE OXIDASES FROM DIFFERENT MICROBIAL SOURCES THAT DO NOT REACT THE WAY OUR MACHINE DOES

PROPYLENE GLYCOL THIS IS A “NON-TOXIC” SWEETISH SOLVENT USED TO DISSOLVE OR SUSPEND VARIOUS DRUGS TO MAKE THEIR ORAL ADMINISTRATION EASY IT IS ALSO USED IN REFRIGERATOR COLD BRICKS AS A NONTOXIC WAY TO MAKE A SLUSH OF ICE CRYSTALS (ETHYLENE GLYCOL IS TOXIC, AS WE HAVE SEEN)

PROPYLENE GLYCOL METABOLISM CH 3 CH 3 CH 3 HCOHHCOHHCOH HCHHCOOCO - OH D-L PROPYLENE GLYCOLD-L LACTALDEHYDED-L LACTATE THE L-LACTATE IS METABOLISED BY THE NORMAL PATHWAYS IN THE LIVER TO GLUCOSE ETC THE D-LACTATE IS NOT METABOLISED BUT IS EXCRETED IN URINE NORMALLY THE DOSE IS NOT ENOUGH TO CAUSE SIGNIFICANT D-LACTATE ACIDOSIS