Paracetamol Overdose

Question 1

What type of cell death is involved in paracetamol poisoning?

Answer 1

necrosis caused by a toxin

Question 2

What % of poisoning cases are caused by paracetamol?

Answer 2

48%

it is the commonest cause of medical admission in under 40s

Question 3

What is significant about acute liver failure?

Answer 3

There has been no history of liver problems before

A liver transplant is required

Question 4

How can you calculate how much alcohol a patient drinks based on what they tell you?

Answer 4

1 litre of 12% wine contains 12 units

1 litre of 40% vodka contains 40 units

Question 5

What are the 2 blood inputs into the liver?

Answer 5

Hepatic portal vein carries deoxygenated blood from the gut

Hepatic artery brings oxygenated blood

Question 6

What is the difference in the volume and pressure of blood flowing into the liver?

Answer 6

the portal vein brings low pressure blood at a higher volume

the hepatic artery brings higher pressure blood but a lower volume

Question 7

Why is the liver less susceptible to ischaemia than other organs?

Answer 7

It can receive a small amount of oxygen from the portal vein if there is a problem with the hepatic artery

Question 8

What are the 5 main functions of the liver?

Answer 8

1. carbohydrate metabolism
2. fat metabolism
3. synthesis and metabolism of amino acids
4. protein synthesis
5. hormone and prohormones

Question 9

What types of proteins are synthesised in the liver?

Answer 9

albumin

C-reactive protein

Complement C1-C9

Procoagulants/anticoagulants

transferrin

Question 10

What are examples of hormones and prohormones synthesised in the liver?

Answer 10

insulin-like growth factor

thrombopoeitin

angiotensinogen

Question 11

What types of things does the liver metabolise and chemically detoxify?

Answer 11

1. alcohol
2. drugs and medications
3. some drugs will be activated by the liver

Question 12

What are 3 further functions of the liver?

Answer 12

1. bilirubin metabolism
2. it is a barrier to sepsis
3. vitamin storage of A, D, B12 and iron

Question 13

Why do liver cells have lots of cytoplasm?

Answer 13

it contains lots of enzymes, endoplasmic reticulum and mitochondria

Question 14

Why does the liver metabolise drugs?

Answer 14

To make toxins in the blood safe and excrete them from the body

Question 15

What are the 2 different types of toxins processed by the liver?

Answer 15

1. idiosyncratic hepatotoxins

2. intrinsic hepatotoxins

Question 16

What is an idiosyncratic reaction?

Answer 16

an unexpected and uncharacteristic reaction to a drug that happens in a rare number of cases

Question 17

What is an intrinsic reaction?

Answer 17

A toxin that would cause damage to everyone’s liver in high doses

Question 18

What are the 2 major pathways?

Answer 18

1. sulphate conjugation

2. glucuronide conjugation

Question 19

What is involved in sulphate conjugation?

Answer 19

Paracetamol is attached to sulfuric acid

This makes it water soluble so that it can be excreted by the kidneys

Question 20

What is the minor pathway for paracetamol metabolism?

Answer 20

The P450 enzyme produces the toxic metabolite NAPQI

This is mopped up by glutathione

Question 21

What happens to NAPQI levels in paracetamol overdose?

Answer 21

There is not enough glutathione to mop up all the NAPQI

NAPQI binds to cellular proteins and leads to hepatic necrosis

Question 22

What is the toxic dose of paracetamol?

Answer 22

4 mg

Question 23

What are the 2 different types of cell death?

Answer 23

Apoptosis - programmed cell death

Necrosis - uncontrolled cell death

Question 24

What enzymes are tested for in liver failure?

Answer 24

AST and ALT

These are raised in liver failure

Question 25

Why does liver cell necrosis cause jaundice?

Answer 25

failure of bilirubin metabolism means there is mostly conjugated hyperbilirubinemia

Question 26

Why does liver cell necrosis lead to hepatic encephalopathy (coma)?

Answer 26

failure to detoxify nitrogenous compounds leads to circulation of excitatory amino acids

Question 27

Why does liver cell necrosis lead to a bleeding tendency?

Answer 27

Failure to synthesise protein means depletion of factors 2. 7. 9. 10.

Question 28

Why does liver cell necrosis lead to renal failure?

What is this called?

Answer 28

shock causes low glomerular filtration

this is hepatorenal syndrome

Question 29

What leads to poorer outcomes in paracetamol poisoning?

Answer 29

1. delayed presentation

2. staggered overdose

Question 30

Why is activated charcoal given to someone who has taken a paracetamol overdose?

Answer 30

It makes the patient vomit to remove the paracetamol from the body

Question 31

What is the main treatment for paracetamol overdose?

How is it given?

Answer 31

N acetyl cysteine

Question 32

How does N acetylcysteine work?

Answer 32

It is converted to L-cysteine and then to glutathione in the body

Glutathione mops up the toxic NAPQI

Question 33

How are doses calculated for treatments of paracetamol overdose?

Answer 33

based on body weight

Question 34

What tool is used to assess whether or not a patient should be given N-acetylcysteine?

Answer 34

The level of paracetamol is tested after 4 hours

On a graph of time against plasma paracetamol concentration, you observe where the patients values lie relative to the treatment line

Question 35

What criteria is used to determine whether someone is suitable for a liver transplant?

Answer 35

King’s College Criteria for Liver Transplantation