Paracetamol Overdose Flashcards

1
Q

What type of cell death is involved in paracetamol poisoning?

A

necrosis caused by a toxin

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2
Q

What % of poisoning cases are caused by paracetamol?

A

48%

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

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3
Q

What is significant about acute liver failure?

A

There has been no history of liver problems before

A liver transplant is required

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4
Q

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

A

1 litre of 12% wine contains 12 units

1 litre of 40% vodka contains 40 units

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5
Q

What are the 2 blood inputs into the liver?

A

Hepatic portal vein carries deoxygenated blood from the gut

Hepatic artery brings oxygenated blood

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6
Q

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

A

the portal vein brings low pressure blood at a higher volume

the hepatic artery brings higher pressure blood but a lower volume

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7
Q

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

A

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

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8
Q

What are the 5 main functions of the liver?

A
  1. carbohydrate metabolism
  2. fat metabolism
  3. synthesis and metabolism of amino acids
  4. protein synthesis
  5. hormone and prohormones
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9
Q

What types of proteins are synthesised in the liver?

A

albumin

C-reactive protein

Complement C1-C9

Procoagulants/anticoagulants

transferrin

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10
Q

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

A

insulin-like growth factor

thrombopoeitin

angiotensinogen

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11
Q

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

A
  1. alcohol
  2. drugs and medications
  3. some drugs will be activated by the liver
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12
Q

What are 3 further functions of the liver?

A
  1. bilirubin metabolism
  2. it is a barrier to sepsis
  3. vitamin storage of A, D, B12 and iron
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13
Q

Why do liver cells have lots of cytoplasm?

A

it contains lots of enzymes, endoplasmic reticulum and mitochondria

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14
Q

Why does the liver metabolise drugs?

A

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

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15
Q

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

A
  1. idiosyncratic hepatotoxins

2. intrinsic hepatotoxins

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16
Q

What is an idiosyncratic reaction?

A

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

17
Q

What is an intrinsic reaction?

A

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

18
Q

What are the 2 major pathways?

A
  1. sulphate conjugation

2. glucuronide conjugation

19
Q

What is involved in sulphate conjugation?

A

Paracetamol is attached to sulfuric acid

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

20
Q

What is the minor pathway for paracetamol metabolism?

A

The P450 enzyme produces the toxic metabolite NAPQI

This is mopped up by glutathione

21
Q

What happens to NAPQI levels in paracetamol overdose?

A

There is not enough glutathione to mop up all the NAPQI

NAPQI binds to cellular proteins and leads to hepatic necrosis

22
Q

What is the toxic dose of paracetamol?

23
Q

What are the 2 different types of cell death?

A

Apoptosis - programmed cell death

Necrosis - uncontrolled cell death

24
Q

What enzymes are tested for in liver failure?

A

AST and ALT

These are raised in liver failure

25
Why does liver cell necrosis cause jaundice?
failure of bilirubin metabolism means there is mostly conjugated hyperbilirubinemia
26
Why does liver cell necrosis lead to hepatic encephalopathy (coma)?
failure to detoxify nitrogenous compounds leads to circulation of excitatory amino acids
27
Why does liver cell necrosis lead to a bleeding tendency?
Failure to synthesise protein means depletion of factors 2. 7. 9. 10.
28
Why does liver cell necrosis lead to renal failure? What is this called?
shock causes low glomerular filtration this is hepatorenal syndrome
29
What leads to poorer outcomes in paracetamol poisoning?
1. delayed presentation | 2. staggered overdose
30
Why is activated charcoal given to someone who has taken a paracetamol overdose?
It makes the patient vomit to remove the paracetamol from the body
31
What is the main treatment for paracetamol overdose? How is it given?
N acetyl cysteine
32
How does N acetylcysteine work?
It is converted to L-cysteine and then to glutathione in the body Glutathione mops up the toxic NAPQI
33
How are doses calculated for treatments of paracetamol overdose?
based on body weight
34
What tool is used to assess whether or not a patient should be given N-acetylcysteine?
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
35
What criteria is used to determine whether someone is suitable for a liver transplant?
King's College Criteria for Liver Transplantation