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Case 13: FASD > Chem Path: Ethanol & toxic alcohols > Flashcards

Chem Path: Ethanol & toxic alcohols Flashcards

1
Q

What is the 3 steps of ethanol metabolism

A

Step 1: ethanol → acetaldehyde
Step 2: acetaldehyde → acetic acid
Step 3: acetic acid → acetyl CoA

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2
Q

Where does the first 2 steps occur

A

Liver

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3
Q

What is the 2 pathways for conversion for step 1

A
  1. ADH
  2. MEOS
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4
Q

When is ADH activate

A

Low ethanol concentration

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5
Q

Why is ADH pathway saturable

A

Dependent on NADH re-oxidation (low capacity)
NADH feeds into electron transport cycle

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6
Q

What is ADH

A

Alcohol dehydrogenase

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7
Q

What is MEOS

A

Microsomal ethanol oxidizing system

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8
Q

When is MEOS activate

A

High ethanol concentration

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9
Q

Part of what system is MEOS

A

CYP P450

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10
Q

What is the effect of MEOS on the liver

A

Increase liver’s capacity to oxidize alcohol & other drugs (barbiturates & paracetamol)

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11
Q

What does MEOS use instead of NAD

A

Oxygen & a wasteful system

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12
Q

What enzyme in step 2 ensure low levels of Acetaldehyde & why

A

Aldehyde dehydrogenase
Highly toxic substance

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13
Q

What type of drug is Flagyl

A

Metronidazole

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14
Q

What is the effect of Flagyl

A

An antimicrobial drug that also inhibits ALD (not drink while on antibiotics)

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15
Q

What genetic predisposition does Oriental population have

A

Lower incidence of alcoholism due to reduced ALD levels

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16
Q

What is the effect of alcohol on Oriental population

A

Alcohol flush syndrome

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17
Q

What is the symptoms of alcohol flushing syndrome

A

Flushes/blotches associated with erythema on face, neck, shoulder or entire body after consuming alcohol

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18
Q

Why does symptoms appear in Oriental population

A

Accumulate of acetaldehyde due to ALD deficiency

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19
Q

For what is the oriental population at greater risk of

A

Oesophageal cancer

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20
Q

What 2 enzymes are required in step 3 of ethanol metabolism

A

Acyl-CoA synthetase & acetyl CoA synthase 2 (mitochondria)

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21
Q

Where does the end product of ethanol metabolism go to

A

Kreb cycle

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22
Q

What is 4 metabolic abnormalities associated with alcohol consumption

A
  1. Hypertriglyceridemia
  2. Ketoacidosis
  3. Fasting hypoglycaemia
  4. Hyperuricemia
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23
Q

Why does hypertriglyceridemia occur in alcohol consumption

A

High NADH/NAD ratio diverts acetyl CoA away from Krebs cycle into fatty acid synthesis
Acetyl CoA is esterified to form TG & exported from liver as VLDL

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24
Q

What is the 2 consequences of hypertriglyceridemia

A

Eruptive xanthomata & acute pancreatitis

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25
Q

Why does ketoacidosis occur in alcohol consumption

A

Acetyl CoA can also form ketone bodies in fasting conditions when insulin is low
High NADH/NAD ratio shifts equilibrium between 2 ketone bodies in favor of ß-hydroxybutyrate

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26
Q

What is the problem with doing a dipstix in a patient with ketoacidosis

A

Detects only acetoacetate that underestimate extent of alcoholic ketoacidosis & ketones on dipstix
Dipstix increase as patient recovers

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27
Q

Why does fasting hypoglycemia occur in alcohol consumption

A

High NADH/NAD ratio due to alcohol metabolism inhibits gluconeogenesis by trapping gluconeogenic intermediates in reduced forms
Once glycogen runs out the liver is no longer able to maintain blood glucose from protein breakdown

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28
Q

What is hypoglycemia accompanied by

A

Ketosis & suppressed insulin

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29
Q

When does fasting hypoglycemia occur

A

Many hours after cessation of drinking

30
Q

Why does hyperuricemia occur in alcohol consumption

A

Activation of acetic acid to acetyl CoA forms AMP from ATP
Fraction of AMP escapes recycling to ATP & degraded to uric acid

31
Q

What is common in alcohol abuser regarding hyperuricemia

A

Gout

32
Q

How to measure osmolality

A

Calculated (2 x Na + urea + glucose) = osmolar gap

33
Q

What is the effect of alcohol on plasma osmolality

A

Measured by osmometry giving a high value but does not cause fluid shift across membranes

34
Q

What is the conclusion than can be made from measured osmolality

A

If measured > calculated it indicated ethanol intoxication/ingestion of another unmeasured osmol (methanol, ethylene glycol or acetone)

35
Q

How to calculate anion gap

A

Na – Cl – HCO3

36
Q

What is a normal anion gap

A

5mmol/L

37
Q

What does an increased anion gap indicate

A

Increased unmeasured anions in plasma & reduce effect of other major anions (Cl & HCO3) to maintain electroneutrality

38
Q

What is the 4 biomarkers of ethanol abuse

A

MCV
CDT
Transaminase
GGT

39
Q

What is GGT

A

Gamma-glutamyl transferase
Hepatic microsomal enzyme induced by ethanol

40
Q

Is GGT sensitive & specific

A

Sensitive but not specific (also induced by chronic drugs use & biliary obstruction)

41
Q

How to ensure that increased GGT indicated drugs abuse

A

Elevated GGT in absence of increased ALP suggest enzyme induction
Biliary obstruction increase in both GGT & ALP

42
Q

What is the criteria for transaminase in ethanol abuse

A

AST/ALT ratio (De Ritis ratio) > 2

43
Q

What does a AST/ALT ratio <2 indicate

A

Alcoholic liver disease

44
Q

Where is carbohydrate deficient transferrin % synthesis & the function

A

Liver
Major circulating iron transporter

45
Q

What is normal appearance of CDT

A

Heavily glycosylated

46
Q

What is the effect of alcohol on CDT

A

Alcohol impairs glycosylation of transferrin by liver but not iron carrying function
Therefor useful marker of excessive alcohol exposure

47
Q

What does MCV indicate

A

Increased size of RBC that can be indicative of alcohol abuse

48
Q

Alongside what should MCV be used for diagnosis

A

Folate/B12 deficiency (other causes of macrocytosis)

49
Q

What is the 2 GIT complication associated with alcohol abuse

A

Pancreatitis
Alcoholic gastritis

50
Q

What 3 vitamin deficiencies does alcohol cause

A

Thiamine deficiency
Nicotinamide deficiency
Vitamin B12 deficiency

51
Q

What is 2 toxic types of alcohol

A

Methanol & ethylene glycol

52
Q

What is the end products of methanol & ethylene glycol metabolism & why is it toxic

A

Methanol to formic acid
Ethylene glycol to glycolic acid
End products are toxic & strong acids (metabolic acidosis)

53
Q

What is the appearance & uses of methanol

A

Volatile liquid with smell/taste like ethanol
Used for racing fuel for cars, antifreeze & window wash solution

54
Q

What is the lethal dose of methanol

A

0.3-1g/kg (80ml in adults)

55
Q

Why is methanol poisoning common

A

Home brewing

56
Q

What is the symptoms associated with methanol ingestion

A

Decreased vision, blindness, pulmonary dysfunction, abdominal pain, coma & rarely Parkinson-like symptoms

57
Q

What is the appearance & uses of ethylene glycol

A

Odor & colorless sweet tasting viscous liquid
Used for antifreeze & brake fluid

58
Q

What is the symptoms associated with ethylene glycol ingestion

A

Oxalate crystals depositing in lungs, heart & kidney (oxalate nephropathy)
Cranial nerve damage followed by organ dysfunction

59
Q

How does oxalate crystal form

A

Final metabolites are oxalate & di-glycolate with high affinity for Ca

60
Q

What is the lethal dose of ethylene glycol

A

1-1.5g/kg (70ml in adults)

61
Q

What is the treatment of alcohol intoxication

A

Antidotes

62
Q

Why is early detection of alcohol intoxication essential

A

Early diagnosis & intervention

63
Q

What is 3 diagnostic criteries for alcohol intoxication

A

Worsening anion gap
Metabolic acidosis
Large but decrease osm gap

64
Q

What treatment for methanol & ethylene glycol intoxication is unhelpful

A

Gastric lavage

65
Q

What is 5 treatment about for methanol & ethylene glycol intoxication

A
  1. IV NaHCO3
  2. Antidotal treatment
  3. Ethanol
  4. Dialysis
  5. Fomepizole
66
Q

What is the effect of IV NaHCO3 in treatment for methanol & ethylene glycol intoxication

A

Correct metabolic acidosis & increase ionization of formate
Facilitate with urinary excretion & reduced penetration into optic nerve

67
Q

What is 3 indication for antidotal treatment

A
  1. Documented history of methanol & ethylene glycol ingestion
  2. Strong suspicion & osmolar gap >10mOsm/kg
  3. Anion gap metabolic acidosis of unknown cause
68
Q

What is a cheap antidote

A

Ethanol because of high affinity for ADH

69
Q

What is 3 indication for dialysis treatment

A
  1. pH<7.3
  2. Methanol >15mmol/L
  3. Ethylene glycol >8mmol/L
70
Q

Why is Fomepizole used

A

Higher affinity of ADH compared to alcohol

71
Q

What is the 3 pros of Fomepizole use

A

Potent
Minimal side effects
No ICU monitoring

72
Q

What is the 3 cons of Fomepizole use

A

Expensive
Low availability (used in children)

Case 13: FASD (9 decks)

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