Paracetamol Overdose Flashcards
What type of cell death is involved in paracetamol poisoning?
necrosis caused by a toxin
What % of poisoning cases are caused by paracetamol?
48%
it is the commonest cause of medical admission in under 40s
What is significant about acute liver failure?
There has been no history of liver problems before
A liver transplant is required
How can you calculate how much alcohol a patient drinks based on what they tell you?
1 litre of 12% wine contains 12 units
1 litre of 40% vodka contains 40 units
What are the 2 blood inputs into the liver?
Hepatic portal vein carries deoxygenated blood from the gut
Hepatic artery brings oxygenated blood
What is the difference in the volume and pressure of blood flowing into the liver?
the portal vein brings low pressure blood at a higher volume
the hepatic artery brings higher pressure blood but a lower volume
Why is the liver less susceptible to ischaemia than other organs?
It can receive a small amount of oxygen from the portal vein if there is a problem with the hepatic artery
What are the 5 main functions of the liver?
- carbohydrate metabolism
- fat metabolism
- synthesis and metabolism of amino acids
- protein synthesis
- hormone and prohormones
What types of proteins are synthesised in the liver?
albumin
C-reactive protein
Complement C1-C9
Procoagulants/anticoagulants
transferrin
What are examples of hormones and prohormones synthesised in the liver?
insulin-like growth factor
thrombopoeitin
angiotensinogen
What types of things does the liver metabolise and chemically detoxify?
- alcohol
- drugs and medications
- some drugs will be activated by the liver
What are 3 further functions of the liver?
- bilirubin metabolism
- it is a barrier to sepsis
- vitamin storage of A, D, B12 and iron
Why do liver cells have lots of cytoplasm?
it contains lots of enzymes, endoplasmic reticulum and mitochondria
Why does the liver metabolise drugs?
To make toxins in the blood safe and excrete them from the body
What are the 2 different types of toxins processed by the liver?
- idiosyncratic hepatotoxins
2. intrinsic hepatotoxins
What is an idiosyncratic reaction?
an unexpected and uncharacteristic reaction to a drug that happens in a rare number of cases
What is an intrinsic reaction?
A toxin that would cause damage to everyone’s liver in high doses
What are the 2 major pathways?
- sulphate conjugation
2. glucuronide conjugation
What is involved in sulphate conjugation?
Paracetamol is attached to sulfuric acid
This makes it water soluble so that it can be excreted by the kidneys
What is the minor pathway for paracetamol metabolism?
The P450 enzyme produces the toxic metabolite NAPQI
This is mopped up by glutathione
What happens to NAPQI levels in paracetamol overdose?
There is not enough glutathione to mop up all the NAPQI
NAPQI binds to cellular proteins and leads to hepatic necrosis
What is the toxic dose of paracetamol?
4 mg
What are the 2 different types of cell death?
Apoptosis - programmed cell death
Necrosis - uncontrolled cell death
What enzymes are tested for in liver failure?
AST and ALT
These are raised in liver failure
Why does liver cell necrosis cause jaundice?
failure of bilirubin metabolism means there is mostly conjugated hyperbilirubinemia
Why does liver cell necrosis lead to hepatic encephalopathy (coma)?
failure to detoxify nitrogenous compounds leads to circulation of excitatory amino acids
Why does liver cell necrosis lead to a bleeding tendency?
Failure to synthesise protein means depletion of factors 2. 7. 9. 10.
Why does liver cell necrosis lead to renal failure?
What is this called?
shock causes low glomerular filtration
this is hepatorenal syndrome
What leads to poorer outcomes in paracetamol poisoning?
- delayed presentation
2. staggered overdose
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
What is the main treatment for paracetamol overdose?
How is it given?
N acetyl cysteine
How does N acetylcysteine work?
It is converted to L-cysteine and then to glutathione in the body
Glutathione mops up the toxic NAPQI
How are doses calculated for treatments of paracetamol overdose?
based on body weight
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
What criteria is used to determine whether someone is suitable for a liver transplant?
King’s College Criteria for Liver Transplantation
