L12 alc metab

Question 1

LO2: expl how metab of alc can dam liv.

Answer 1

-direct- acetald tox norm kept low by ald DH (lowKm for acetald). Long exerc or excess alc can= suffic acetald accum for direct liv dam.
-indirect- excess NADH and aCoA= changes liv metab- fatt liv, alc hep, alc cirr.
-metab resp to chronic alc consump- diag.
Ince aCoA= incr TAG synth= fatt liv. Decr NAD so less avail for conv lactate to Pyruv= Uric ac accum, glycerol metab=hypog, FA oxidat=incr TAG.
-affs of dam liv cells by acetald- leak PM= loss enz eg transamin and gamma GT so present in blood= diag liv cell dam.
Decr func- decr upt and conjug bili= hyperbili jaund.
Decr urea prod so hyperNH3 and incr glutamine.
Decr prot synth so decr alb, CF and lipop. Low serum alb may= odema and incr clott time.
Fatt liv as decr lipop.
-indirect effs alc- cost and CNS effs= poor diet. Vit and min decr, carb and prot decr.
-direc effs alc on GIS- dam cell lining GIT and prod disturbs compound effs of poor diet. Often decr appet, diarr, imp abs eg vitK, folic ac, pyridoxine, thiamine- assoc neurol symps and anaemia (folic ac). Thiamine decr= wernicke korsakoff synd ment confus unsteady gait.
-chronic pancreatitis- asymp sev yr. symp eg const pain red back. Weight loss as malabs as insuff enz. DM if beta cell dam= hyperg and glucosuria.

Question 2

LO3: expl MOA OD disulfiram in tx alc dep.

Answer 2

-PART of tx chronic alc dep. inhib ald DH=acetald accum=hangover. Can impl.

Question 3

LO1: desc ethanol metab.

Answer 3

-zero order kinetics= rate elim Lin/constant 7g/HR eg. Uses for drug, most expon decay 1st order.
Over 90% alc metab liver. Rest excret breath or urine.
Alc oxid by alc DH to acetald (tox) then to acetate by ald DH. Acetate conv back to aCoA to TCA or FA synth.
Smaller amnt alc can also be oxid by cytochrome p450 2E1 enz, or by catalase in brain.
Recom lims- men 21U/wk, wom 14.
Rate metab- 1U=8g alc. Elim 7g/HR.
Can’t synth gluc from alc because producing aCoA.