Flashcards in Liver and gallbladder Deck (118)
Which veins form the portosystemic anastamoses responsible for forming caput medusae in portal hypertension?
Para umbilical veins - portal
Superior and inferior epigastric veins - systemic
What 4 factors can affect the livers ability to metabolise drugs?
Why should the initial dose of a drug prescribed to an elderly person be lower than for a normal adult?
Relative liver mass and hepatic blood flow are reduced so reduced clearance
What should you try to do with polypharmacy?
Rational prescribing - try to minimise the total number of drugs that the patient is taking
Why might children need a higher dose than adults for certain drugs?
Metabolic clearance of the drugs is faster due to mature CYPs and relatively large liver mass and hepatic blood flow
What do phase 1 reactions do to a drug in the liver?
Add a functional group to make it more reactive and therefore provide a site for phase 2 reactions
Which is the most common phase 1 reaction?
Which family of enzymes are largely responsible for oxidation reactions in the liver?
What 3 things do cytochrome P450 enzymes require to function?
Oxygen, NADPH and NADPH cytochrome P450 reductase
What do phase 2 reactions do to a drug in the liver?
Add a large molecule to make it more water soluble and therefore easier to excrete. Also tend to inactivate it. Conjugation
Which drugs are more likely to be excreted via the bile?
Highly ionised or large molecules >500 Da
What are multi drug resistance proteins?
Efflux transporters for removing drug metabolism products from hepatocytes
Give 4 reasons why patients with liver disease are at risk of toxic drug effects at low doses
Reduced functioning of hepatocytes/reduced number to metabolise
Decreased plasma binding proteins so increased bioavailability
If portal hypertension - reduced first pass metabolism and shunting of drug back into systemic circulation
Increased susceptibility to hepatotoxic drugs
What happens in paracetamol induced liver injury?
Overdose of paracetamol causes a saturation of phase 2 enzymes so more phase 1 reactions occur. This causes an accumulation of NAPQBI which is toxic to hepatocytes. At first, glutathione inactivates this toxic product but once it runs out, liver damage occurs.
What would you use acetylcysteine and methionine for?
As antidote to paracetamol overdose as they increase liver synthesis of the cytoprotective glutathione
How can genetics affect people taking codeine?
Some people have low levels of CYP2D6 which is responsible for converting the codeine prodrug into morphine. Codeine itself is a very weak analgesic so patients report little pain relief with many side effects
Why is it important to ask about herbal remedies eg St. John's wort when taking a history?
St. John's wort induces CYP3A and so leads to increased metabolism of drugs such as oral contraceptives, benzodiazepines and warfarin. This reduces their bioavailability
List 5 functions of the liver
Production of plasma proteins
Synthesis, storage and secretion of bile
Excretion of bilirubin
What are Kupffer cells?
Immune cells of liver
Present in sinusoids attached to endothelial cell lining
Ingest bacteria and inflammatory mediators
What 5 types of plasma proteins are made by the liver?
Binding proteins - albumin
Carriage proteins - thyroid binding globulin
Clotting factors - fibrinogen
What are the 6 components of bile?
Which enteric hormone acts to increase bile production of liver?
What do cholangioctyes secrete and where are they?
Lining bile duct, secrete HCO3 and water
What 4 things are bile salts involved in?
Elimination of cholesterol
Emulsification of fats in SI so available to pancreatic lipases
Facilitates absorption of fat soluble vitamins
Prevention of cholesterol precipitation in gallbladder
What are primary bile acids conjugated with to form bile salts?
What are primary bile acids made from?
During recycling of bile salts from terminal ileum, what do bacteria do?
Deconjugate bile salt to bile acid
Which 2 bile components are taken from the blood?
What are bile pigments?
Excretory products being disposed of by liver via gut