paracetamol overdose Flashcards
what is the cause of death in PO?
cell death caused by necrosis from a toxin - the clinical effects therefore come from the loss of function of cells
why may the effects of PO vary?
it depends on the proportion of cells that are affected and the function remaining to meet the demand of the organ
what is another name for paracetamol?
acetaminophen
what is the prevalence of PO?
48% of all medical admissions and 10000 per year
the commonest cause of medical admissions in under 40s
leading cause for liver failure acutely
what is the affect of PO?
causes severe injury to the liver, abdo pain, very unwell after 40 hours
how would you identify the cause?
the social and medical history
if alcohol then take the amount and the strength to calculate the units
what is the relationship between strength and units?
1 litre of the APV = the number of units
how may PO cases present?
comatosed, acidotic, renal failure, clotting disturbance, ALT far higher than usual such as 1500 when should be <35
what ligaments are in the liver?
the falciform anteriorly separating the left and right loves, the teres posteriorly, the right and left triangular and the coronary ligament posteriorly
what does the gall bladder feed into?
the common bile duct
what is the lobe inferior to the gall bladder?
the quadrate lobe - the caudate is superior to this
what is the exit for the HAP, and PV?
the porta hepatis
what comes off the IVC?
the hepatic veins
what is the structure of the liver?
it is the largest organ in the body weighing around 1.2-1.5kg and is 2.5% of the body mass. There are two blood supplies from the gut and the artery
outline the blood supplies to the liver?
the portal vein comes from the gut and carries 2/3 volume but low pressure blood, the blood from the hepatic artery is oxygenated and higher pressure
why is two supplies beneficial?
it is less susceptible to ischaemia
what are the metabolic functions and some examples of the liver?
carbohydrate (glycogenesis), fat (triglyceride and lipoprotein), amino acid metabolism, protein and amino acid synthesis (albumin, CRP), hormones and prohormones (angiotensin), detoxification (alcohol, medication, drugs, chemicals), activation of drugs and bilirubin metabolism
what other functions does the liver have?
barrier to sepsis and vitamin A, D and B12 and iron storage
what is the histological structure of the liver?
the blood runs along sinusoids into the hepatic vein, the cells are square shaped and the hepatocytes are close to a blood supply, there is lots of mitochondria, ER and cytoplasm for lots of enzymes
how can liver be affected by drugs?
there are two ways:
intrinsic - everyone will react in the same way - will damage all livers in high volumes
idiosyncratic - unexpected and uncharacteristic - most reactions - rare and unpredictable
what are the differences between individuals metabolism?
the liver has evolved to detoxify the blood and make toxins safe, then excrete them. There are many different enzymes and metabolic pathways and people differ in the way that they metabolise things
how does paracetamol metabolism work?
it is attached to sulphuric acid which makes it water soluble and then excretes it by the kidneys or is conjugated with glucuronide. A minor pathway will metabolise paracetamol when a large amount is taken
what causes damage in overdose?
NAPQI
how can NAPQI cause damage?
the ability to detoxify NAPQI is overwhelmed. This means that it cannot be turned into cysteine and mercapturic acid conjugates and that it builds up and attaches to cell proteins to cause damage
what is the reaction for paracetamol metabolism?
paracetamol will be conjugated wither into sulfate or glucuronide. If not it will go through the P450 pathway and make N-acetyl-p-benzoquinoneimine which is toxic. This with glutathione will make cysteine and mercapturic acid conjugates which are non toxic
what is the mechanism of cell death in viral hepatitis and what does it look like?
apoptosis - controlled and programmed - occasional dead cells with dense pink cytoplasm and small nucleus
what is the mechanism of death in PO and what does it look like?
confluent necrosis - uncontrolled - lost all proteins, pink - hepatocytes first as these have the enzymes that metabolise paracetamol
what causes acute liver failure?
over 50% of cells with a loss of function/death
which liver cells die first?
the zone 3 ones as they contain the metabolising enzymes
what are the effects of cell death in the liver?
amino transferase enzymes will peak at around 1000-3000
jaundice - cannot process bilirubin
coma - failure to detoxify nitrogenous compounds
bleeding - failure to synthesis proteins and clotting factors
renal failure - lower glomerular filtration due to shock - hepatorenal syndrome
what is important in PO treatment?
early treatment - delayed presentation and staggered overdose gives poorer outcomes
how do you treat PO?
the dose is calculated based on the body weight - activated charcoal at 150mg/kg makes the patient vomit and remove any paracetamol
N acetyl cysteine IV (or methionine orally if allergic) to give glutathione to mop NAPQI up
test level of paracetamol after 4 hours to identify treatment and risk
how does NAC make glutathione?
N-acetylcysteine - L-cysteine-glutathione
what are the amino transferase enzymes detected by?
ALT and AST through lab tests
what is the major component of jaundice?
conjugated hyperbilirubinaemia
what does failure to detoxify nitrogenous compounds lead to and why?
coma - hepatic encephalopathy due to circulation of excitatory AAs
what factors are depleted in a bleeding tendency in liver failure?
Factors II, VII, IX and X
what is the ITU management for PO?
continue the NAC, intubated, sedated and ventilated with filtration for the kidneys which helps to repair damage and improves prognosis. They will need feeding and ABs/AFs as fungal sepsis is the biggest killer in PO. Only correct clotting if they are bleeding and simultaneously carry out the work up towards the liver transplantation
what needs to be considered for transplantation?
kings college criteria, the elective and urgent lists, the mode (living donor, split, OLT, auxiliary or domino), units and volume of work load and ethical issues
