Metabolism of Alcohol

Question 1

What are the harmful agents in alcohol?

Answer 1

Ethanol
Methanol - from poorly distilled alcohol
Isopropyl alcohol

Question 2

What does the liver oxidise alcohol into?

Answer 2

Oxidises alcohol into water, carbon dioxide, and energy.

Question 3

What is 1 unit of alcohol?

Answer 3

8grams of alcohol

Question 4

What are considered the healthy number of units for men per week?

Answer 4

28 units per week

Question 5

What are considered the healthy number of units for women per week?

Answer 5

21 units per week

Question 6

How does high concentration alcohol affect the stomach?

Answer 6

Inhibits gastric emptying - therefore has a slow absorption.

Question 7

How can alcohol absorption be increased by drug consumption.

Answer 7

Increased by drugs enhancing gastric emptying and

those drugs that inhibit gastric alcohol dehydrogenase

Question 8

Most tissues (e.g. heart, brain and muscles) are
exposed to the same concentration of alcohol as
the blood - why is the exposure to the liver greater?

Answer 8

Exposure of the liver is greater because blood is
received direct from the small bowel via the portal
vein.

Question 9

What physiologic changes accompany alcohol consumption.

Answer 9

Sweating, flushing (dilation of blood vessels) and
bruising.
Body can suffer from heat loss and hypothermia.
Tachycardia and hypertension.
Kidneys secrete more alcohol due to both fluid and alcohol inhibiting ADH.

Question 10

How is absorbed alcohol eliminated?

Answer 10

95% metabolised by the liver.
2-5% is excreted unchanged in urine, sweat,
faeces, milk or breath.

Question 11

What enzymes break down alcohol in the liver?

Answer 11

Alcohol dehydrogenase (ADH) and mitochondrial acetaldehyde dehydrogenase (ALDH) metabolise ethanol consumed.

Question 12

What is the first step in the metabolism of alcohol?

- draw it out.

Answer 12

The first step in the metabolism of alcohol is the oxidation of ethanol to acetaldehyde catalyzed by ADH (in the cytosol) containing the coenzyme NAD+.

Results in the generation of NADH.

Question 13

What is the toxic byproduct produced in the metabolism of alcohol?

Answer 13

Acetaldehyde

Question 14

What is the second step in the metabolism of alcohol?

- draw it out.

Answer 14

Conversion to acetaldehyde into acetate by ALDH (in

mitochondria) also results in the generation of NADH

Question 15

What does the enzyme alcohol dehydrogenase do?

Answer 15

The enzyme alcohol dehydrogenase (ADH) metabolizes the ethanol into toxic acetaldehyde.

Question 16

What is the third step in the metabolism of alcohol?

- draw it out.

Answer 16

The acetate is further oxidized (mitochondrial extrahepatic oxidation) to CO2 and water through the citric acid cycle.

The acetate entering the citric acid cycle generates even more NADH.

Question 17

Explain how alcohol tolerance is built up?

Answer 17

Enzyme induction -
The liver does this by producing larger amounts of the enzymes which break down alcohol.
The brain also has a role in the development of alcohol tolerance. When the neurotransmitter systems in the brain are regularly exposed to large amounts of alcohol they begin to adapt to the presence of alcohol.

Question 18

What are the short term metabolic risks of alcohol?

Answer 18

Block other metabolic pathways in high concentrations.

Converts pyruvic acid to lactic acid - can lead to acidosis.

Inhibits gluconeogenesis which can lead to hypoglycemia.

Inhibits lipolysis and increases lipogenesis.

Question 19

What by byproduct of ethanol is responsible for blocking other metabolic pathways?

Answer 19

Excess NADH

Question 20

What is the significance of inhibited lipolysis and increased lipogenesis?

Answer 20

This leads to the accumulation of fatty acids, which are deposited in the blood (increased risk of MI) and liver.

Excess production of acetyl COA which are converted into ketones leading to ketosis.

Question 21

How does alcohol damage the GI tract?

General effect
Liver
Food
Nurtition 
Bowel
Increases risk of...

Answer 21

▪ Causes inflammation of the tongue, stomach, pancreas, liver and intestines.
▪ Breakdown products lead to fat deposition, fibrosis and scarring of the liver.
▪ Impairs the digestion of food and absorption into blood. Alters food consumption behaviour/selection.
▪ Acetaldehyde (the oxidation product) can interfere with absorption & activation of vitamins.
▪ Motility problems …diarrhoea
▪ Increased risk of cancer…..oesophageal, liver. (hepatocellular carcinoma) and bowel (high calories).

Question 22

What are the effects of alcohol on the pancreas?

Answer 22

• Stimulation of CCK and Secretin release from duodenum.
• Changes in pancreatic blood flow and secretion.
• Toxic metabolites - can lead to necrosis.
• Acute pancreatitis.

Question 23

Why does alcohol cause acute pancreatitis?

Answer 23

Due to increased stimulation of CCK and secretin.

Question 24

What are the stages of alcohol induced liver damage?

Answer 24

Fatty liver > liver fibrosis > liver cirrhosis.

Question 25

Steatosis

Answer 25

Steatosis is abnormal retention of fat (lipids) within a cell or organ.

Question 26

Alcoholic steatohepatitis

Answer 26

Alcoholic Steatohepatitis is a chronic, progressive liver disease characterized by thickening and scarring (fibrosis) of the liver as well as possible death (necrosis) of the liver tissue, brought on by excessive, prolonged alcohol use.
- induced by inflammation.

Question 27

Cirrhosis

Answer 27

Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, is a condition in which the liver does not function properly due to long-term damage. This damage is characterized by the replacement of normal liver tissue by scar tissue.

Question 28

What are the signs of cirrhosis?

Answer 28

Jaundice
Spider naevi
Ascites - fluid in the belly
Haemetemesis
Gynecomastia
Confusion

Question 29

In what way can alcohol affect the oesophagus?

Answer 29

Oesophageal varices

Question 30

Oesophageal varices - what are they and what’s the cause?

Answer 30

Abnormal dilatation of veins due to increase in portal vein pressure.
Can cause life-threatening bleeding

Question 31

How does alcohol affect neurotransmitters in the brain?

Answer 31

Increases dopamine
Inhibits glutamate
Potentiates GABA-A receptor function.
Increase serotonin

Question 32

In relation to alcohol what are ADH and ALDH?

Answer 32

Alcohol dehydrogenase (ADH)
Aldehyde dehydrogenase (ALDH)

Question 33

What does ALDH do?

Answer 33

The liver enzyme aldehyde dehydrogenase (ALDH) metabolizes acetaldehyde into acetate, a less toxic compound that breaks down into water and carbon dioxide.

Question 34

What is the pathology of cirrhosis?

Answer 34

Growth of connective tissue destroys liver cells leading to irreversible damage.

Question 35

What is the difference between alcoholic steatohepatitis and cirrhosis?

Answer 35

Hepatitis may be reversible (curable) whereas cirrhosis refers to permanent scarring of the liver - (often due to chronic hepatitis.

Question 36

What is the pathology of alcoholic steatohepatitis?

Answer 36

Inflammation induces production and accumulation of
extracellular matrix (collagen) from hepatic stellate cells.

This results in liver fibrosis, scar tissue forms; liver can recover but scarring remains.

Question 37

What is the treatment for alcoholic steatohepatitis?

Answer 37

Glucocorticoids

Question 38

What areas of the brain does alcohol affect?

Answer 38

Cerebral impairment - altered judgement, emotions and vision.
Cerebellum - affecting co-ordination.
Medulla - depressing cardiac and respiratory functions.

Question 39

What is the long term affect of alcohol increasing dopamine temporarily?

Answer 39

The absence of alcohol can cause depression and anxiety.

Question 40

What is the effect of alcohol blocking glutmate?

Answer 40

Glutamate is an major excitatory neurotransmitter which when blocked results in cognitive impairment and amnesia and an inability to learn new information.

Question 41

What is the affect of alcohol potentiating GABA receptors?

Answer 41

GABA is major inhibitory neurotransmitter in the brain.
Receptor subtypes:
Alpha5 - memory impairing effects.
Alpha2, alpha3 - relaxation and pleasure mediating effects.
Alpha1 - sedation, anaesthesia and unsteadiness.

Question 42

What subtype of serotonin does alcohol increase the release of?

Answer 42

5-HT

Question 43

What is the effect of alcohol increasing the release of serotonin?

Answer 43

Alcohol increases release of serotonin (5-HT) causing one to become sleepy / even pass out. 5-HT plays a major role in the sleep-wakefulness cycle, mood and emotion.

Question 44

What are some of the long term affects of alcohol on your brain?

Answer 44

Loss of cortical grey matter - particuarly in the prefrontal cortex.

Does boost the growth of some new nerve cells, however these new cells could contribute to
development of alcohol dependence and addiction.

Question 45

What are the benefits of drinking alcohol in middle aged men and women?

Answer 45

Benefits include inhibiting atheroma formation and decreasing rate of blood coagulation.

Question 46

What’s the benefit of drinking red wine?

Answer 46

Red wine – polyphenols (such as procyanidins) reduce incidence of cardiovascular disease.

Anti-atherosclerotic through suppression of excess endothelin-1 (a vasoconstrictor), inducing dilation of blood vessels.

Question 47

What is considered to be 1 unit, regarding, wine, beer, cider, and shots?

Answer 47

Small glass of wine.
Half a pint of cider / beer.
1 single shot.