SYMPOSIUM: Alcohol metabolism

Question 1

Where is alcohol distributed in the body?

Answer 1

Ethanol is water soluble so very little is found in adipose tissue

Question 2

How much alcohol is lost through breath/urine?

Answer 2

10%, the rest is metabolised by the liver

Question 3

What’s meant by the idea that Cytochrome complexes (Cyps) are inducible?

Answer 3

The more you drink, the more cyps will be expressed allowing more metabolism of alcohol

Question 4

CYP2E1 complex is responsible for metabolising what?

Answer 4

Paracetamol into a toxic intermediate that allows paracetamol toxicity

Question 5

What enzyme converts ethanol into acetaldehyde and where is it found?

Answer 5

Alcohol dehydrogenase found in the hepatic cytosol

Question 6

What enzyme converts acetaldehyde into acetate and where is it found?

Answer 6

Aldohehydrogenase found in hepatic mitochondria

Question 7

What are the 2 minor reactions that can convert ethanol into acetyaldehyde?

Answer 7

Catalase in perioxisomes and P4502E1 in microsomes

Question 8

Give an example of a Alcohol dehydrogenase polymorphism?

Answer 8

Asians have B2 ADH isofrom and Europeans have B1 ADH which is 20% slower at metabolising ethanol

Question 9

What is the physiology behind nausea, vomiting and headaches after alcohol drinking?

Answer 9

A build up of acetylaldehyde

Question 10

When alcohol is being metabolised, what is the product that’s released into the blood stream?

Answer 10

Acetate

Question 11

Why does metabolising alcohol increase levels of NADH?

Answer 11

Because both alcohol dehydrogenase and aldehydehydrogenase convert NAH+ into NADH during metabolism

Question 12

What 4 processes does lactic acidosis inhibit?

Answer 12

Glycolysis, citric acid cycle, fatty acid oxidation, and gluconeogenesis

Question 13

What 2 things happen during oxidant stress?

Answer 13

1. Lipid peroxidation associated with acute tissue damage and fibrosis
2. Free-radicals are produced that DNA and cause mutations

Question 14

What alcohol does hand sanitiser contain?

Answer 14

Methanol

Question 15

What 2 alcohols can cause blindness by destroying the optic nerve?

Answer 15

Methanol and formic acid

Question 16

What alcohol does anti-freeze contain?

Answer 16

Ethylene Glycol

Question 17

How does Ethylene Glycol cause toxicity?

Answer 17

Causes acidosis that can affect the heart, CNS, kidney failure, and death

Question 18

What 2 enzymes does all alcohol metabolism use?

Answer 18

Alcohol dehydrogenase and aldehyde dehydrogenase

Question 19

How does the drug Fomepizole act and what is it used to treat?

Answer 19

As a competitive inhibitor to alcohol hydrogenase and is used to treat methanol and ethylene glycol overdose by preventing the formation of toxic intermediates

Question 20

Why can ethanol be used to treat ethylene glycol overdose?

Answer 20

Because alcohol dehydrogenase has a 100x greater affinity for ethanol than ethylene glycol so if they’re co-ingested, the ethanol will be metabolised instead

Question 21

How much pure alcohol is 1 unit?

Answer 21

10ml or 8g of pure alcohol

Question 22

What is the legal driving blood ethanol level in the UK?

Answer 22

80mg/dl

Question 23

What is foetal alcohol syndrome and how does it occur?

Answer 23

Alcohol can cross the placenta and can affect the foetal development

Question 24

What is stupor?

Answer 24

Mental state where people don’t respond to normal conversation only physical stimulation

Question 25

What is alcoholic ketoacidosis?

Answer 25

Metabolic acidosis with an increased anion gap that occurs with chronic alcoholics who binge with little nutritional intake

Question 26

What is the pathophysiology behind alcoholic ketacidosis? (3 points)

Answer 26

1. Glycogen depletion and decreased gluconeogenesis
2. Lipolysis and ketones increased causing supressed insulin
3. Extracellular volume depletion/dehydration

Question 27

In what 3 ways does ethanol cause hypoglycaemia?

Answer 27

1. Decreased intake of glucose
2. Depletion of glycogen
3. Blockade of gluconeogenesis

Question 28

Why are alcoholics given Thiamine?

Answer 28

To prevent CNS damage and in case they have a thiamine deficiency

Question 29

What is pseudo cushings syndrome?

Answer 29

Too much cortisol in the body that goes away when you abstain from alcohol

Question 30

What are 3 endocrine complications of alcohol use?

Answer 30

Decreased testosterone caused by testicular atrophy, pseudo Cushings, metabolic syndrome, and dyslipidaemia

Question 31

What are 3 general nutritional issues with chronic alcoholism and what are the causes?

Answer 31

1. Low Calcium caused by diet and decreased vitamin D
2. Low phosphate caused by diet and increased parathyroid hormone
3. Low Magnesium caused by diet, urinary loss and hyperaldosteronism

Question 32

What are 4 typical liver function results for chronic alcoholism and what causes it?

Answer 32

1. GGT increased by liver enzyme induction
2. ALT and AST increased because of hepatocellular damage
3. Globulin increased by cirrhosis
4. Bilirubin, INR, and albumin decreased by liver failure

Question 33

What is Thiamine (Vitamin B1) important for?

Answer 33

For carbohydrate metabolism and synthesis of nucleotides and amino acids

Question 34

Why does chronic alcohol use cause Thiamine deficiency? (3 points)

Answer 34

Ethanol interference with GI absorbance, Hepatic dysfunction, and malnourishment

Question 35

What is Macrocytosis?

Answer 35

Macrocytic anaemia (raised MCV in a full blood count)

Question 36

What are the 5 relevant blood tests for chronic alcoholism?

Answer 36

Raised MCV, raised [serum ferritin], hyperuricaemia, hypertriglyceridaemia, increased carbohydrate-deficient transferrin

Question 37

What does a carbohydrate-deficient transferrin (CDT) blood test tell you and what is the mechanism behind this?

Answer 37

Someone’s recent alcohol ingestion over the last 7-14 days because alcohol affects the post transitional modifications of the transferrin molecule so if alcohol is ingested, the molecule won’t have as many carbohydrates attached to it

Question 38

What are some possible mechanisms for alcohol causing hypertension?

Answer 38

Impairs baroreceptors, increased sympathetic activity, stimulation of the renin-angiotensin-aldosterone system, an increase in plasma cortisol, an increase in intracellular calcium that causes increased vascular activity, and endothelial inhibition of endothelium-dependent nitric oxide production

Question 39

What 2 enzymes rely on thiamine as a co-factor?

Answer 39

pyruvate dehydrogenase and alpha-ketoglutarate