Clinical symposium 8: Paracetamol overdose and cirrhosis Flashcards
What is the largest solid organ in the body?
Liver
What vessels make up the dual blood supply of the liver?
1) hepatic artery
2) hepatic portal vein
Give 8 functions of the liver:
1) chemical detoxification
2) carbohydrate metabolism
3) coagulation factor synthesis
4) fat metabolism
5) bile production and excretion
6) protein metabolism and synthesis
7) hormone metabolism
8) vitamin storage
How does a healthy liver look? (3)
1) reddish (due to abundance of iron)
2) shiny
3) smooth capsules
How do portal and hepatic vein branches appear under a microscope?
irregular and distended
How do hepatic artery branches appear under a microscope?
thicker and more circular
Define acute liver injury:
an overwhelming assault of the liver causes a significant proportion of hepatocytes to die and once but most eventually regenerate
Define chronic liver injury:
persistent ongoing damage and injury causing a chronic inflammatory response that leads to fibrosis and regeneration and eventually cirrhosis
Give 5 clinical signs for paracetamol overdose:
1) abdominal pain
2) clotting disturbance
3) acidotic blood
4) renal failure
5) liver tests markedly deranged (high transaminases)
True or false: people differ in the way they metabolise drugs
True
What is the term used to describe liver damage caused by a rare, unpredictable reaction of a drug?
idiosyncratic hepatotoxicity
What term is used to describe liver damage caused by high doses of drugs?
intrinsic hepatotoxicity
Give the minor pathway of paracetamol metabolism:
P450 enzymes break paracetamol down, forming NAPQI which glutathione metabolises
What molecule is depleted in paracetamol metabolism following an overdose?
glutathione
How does apoptosis in the liver appear?
holes between cells with presence of acidophil bodies
What are acidophil bodies?
pink, eosinophilic regions
How does acute liver failure affect enzyme release?
aspartate transaminase and alanine transaminase are released into the blood
How does acute liver failure affect bilirubin metabolism?
bilirubin metabolism fails, causing hyperbilirubinaemia and jaundice
How does acute liver failure affect detoxification of nitrogenous compounds?
detoxification of nitrogenous compounds fails resulting in the circulation of excitatory amino acids and possibly hepatic encephalopathy (coma)
How does acute liver failure affect blood clotting
there is failure to synthesis clotting factors II, VII, IX and X causing bleeding tendencies
How does acute liver failure affect the kidneys?
shocks causes low glomerular filtration, leading to renal failure
Give two drugs used to treat paracetamol overdose:
1) activated charcoal
2) N-acetyl cysteine
How does activated charcoal help treat paracetamol overdose?
it prevents absorption in the gut
How does N-acetyl cysteine help treat paracetamol overdose?
it increases glutathione levels
In which zone do toxic metabolites build up in in hepatocytes?
Zone 3
What is the only reliable method of assessing fibrosis of the liver?
liver biopsy
What is cirrhosis?
significant fibrosis with nodularity of parenchyma
What is the only cure for end stage liver disease?
transplantation
How does cirrhosis appear under a microscope?
regenerative nodules of hepatocytes will be surrounded by sheets of fibrous tissue
Give 4 core consequences of cirrhosis of the liver:
1) portal hypertension
2) risk of infection
3) ascites
4) carcinogenesis
How does liver cirrhosis cause portal hypertension?
the stiff, scarred liver puts pressure on the portal venous system
What are the two main effects of increased portal hypertension?
1) oesophageal varices
2) ascites
How does liver cirrhosis increase risk of infection?
alterations in the immune system leads to an increased risk of sepsis
Describe how ascites comes about:
back pressure from portal hypertension increases blood pressure in the kidneys, activating the renin-angiotensin system (causing H2O and Na+ retention) - albumin isn’t synthesised so the osmotic gradient is lost causing fluid to leak into the peritoneum