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ETHANOL METABOLISM

ETHANOL METABOLISM. CH 3 CH 3 CH 3 HCH CH C O O O _ O H H + Alcohol Dehy Aldehyde Dehy Ethanol Acetaldehyde Acetate FOMEPIZOLE INHIBITS ANTABUSE INHIBITS ALSO METRONIDAZOLE. OTHER ALCOHOLS. R R = H METHANOL R=CH 3 ETHANOL

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ETHANOL METABOLISM

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  1. ETHANOL METABOLISM CH3 CH3 CH3 HCH CH C O O O _ O H H+ Alcohol Dehy Aldehyde Dehy Ethanol Acetaldehyde Acetate FOMEPIZOLE INHIBITS ANTABUSE INHIBITS ALSO METRONIDAZOLE

  2. OTHER ALCOHOLS R R = H METHANOL R=CH3 ETHANOL HCH R=CH2CH3 PROPANOL O R=CH2OH ETHYLENE GLYCOL H R=CHOHCH3 PROPYLENE GLYCOL ETC All react with alcohol dehydrogenase + NAD to give aldehydes, and then with aldehyde dehydrogenase + NAD to give the acids

  3. 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

  4. ETHYLENE GLYCOLANTIFREEZE FAST REACTIONS • CH2OH CH2OH CH2OH • CH2OH CHO COO- • ETHYLENE GLYCOL GLYCOLALDEHYDE GLYCOLATE SLOWER REACTIONS COO- COO- COO- CH2OH CHO COO- GLYCOLATE GLYOXYLATE OXALATE GLYCOLATE CAUSES THE ACIDOSIS OXALATE IS THE MOST LETHAL (BINDS Ca++)

  5. 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

  6. ANION GAP • Cations (+) Anions (-) • Na 140Cl 105 • K 4BIC 26 Ca + Mg 3 Albumin 10 • Others 1 Other proteins 2 • TOTAL 148 Lactate 1 • Na + K + 4 Ketones 1 • Others 3 • TOTAL 148 • Cl + BIC + 17 • So Na + K + 4 = Cl + BIC + 17 • (Na + K) - (Cl + BIC) = 17 – 4 = 13

  7. OSMOLAR GAP • MEASURED POSM – CALCULATED POSM • CALCULATION OF POSM • 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

  8. 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

  9. 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 H2O2 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

  10. 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)

  11. PROPYLENE GLYCOL METABOLISM CH3 CH3 CH3 HCOH HCOH HCOH HCH HCO OCO- OH D-L PROPYLENE GLYCOL D-L LACTALDEHYDE D-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

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