Transcript Slides - Philippe Le Fevre

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
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
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
• CH2OH
• CH2OH
•
ETHYLENE GLYCOL
COOCH2OH
GLYCOLATE
FAST REACTIONS
CH2OH
CH2OH
CHO
COOGLYCOLALDEHYDE
GLYCOLATE
SLOWER REACTIONS
COOCOOCHO
COOGLYOXYLATE
OXALATE
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 (-)
• Na
140
Cl
105
• K
4
BIC
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
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
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 DLACTATE 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
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
CH3
HCOH
HCH
OH
CH3
HCOH
HCO
CH3
HCOH
OCO-
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