GIT Physiology Flashcards
What are the phases of drug metabolism in the liver?
1) Modification 2) Conjugation 3) Excretion
How does the liver modify drugs?
CYP450 enzyme system polarises the drug (makes water soluble) by oxidation, reduction and hydrolysis.
What are 3 ways in which drugs can be conjugated?
Glucuronidation (attached to glucuronic acid, via glucuronosyltransferase)
Acetylation (acetate)
Suplhation (sulphate)
Classify the functions of the liver (6)
Metabolic; exocrine; endocrine; immunologic; drug clearance; synthetic
What is the function of bile?
Essential in the emulsification of dietary lipid
What is the function of bile and how does it achieve this? (5)
Emulsification and absorption of dietary lipid:
- Bile salts surround the lipid, breaking large fat droplets into a suspension of small fat droplets.
- This creates micelles with a hydrophilic shell and hydrophobic centre. Without these micelles, pancreatic lipase cannot act on the lipid centre.
- These micelles come into contact with enterocytes in the gut, which absorbs the lipid contents. (eg. fat-soluble vitamins A, D, E, K are absorbed this way)
- The bile salts remain in the gut and are absorbed in the terminal ileum, return to the liver via the portal vein and are reused.
What are the steps of bilirubin metabolism? (10)
- Hb is broken down in the spleen into it’s constituent amino acids, iron and porphyrin ring.
- Macrophages in the spleen oxidise the porphyrin ring to biliverdin then reduce it to bilirubin.
- Unconjugated bilirubin (water insoluble) is transported to the liver, bound to albumin.
- Bilirubin taken up into hepatocytes and via glucuronosyltransferase, conjugated to glucuronic acid = water soluble CB.
- CB excreted into small intestine in bile.
- Almost all CB is reabsorbed, circles via portal vein to liver and re-secreted into small intestine - ‘enterohepatic circulation’. Some goes to large intestine.
- Large intestine: CB converted to urobilinogen by colonic bacteria.
- Urobilinogen may be oxidised to urobilin and stercobilin and excreted in faeces.
- Alternatively, urobilinogen is reabsorbed by gut and undergoes enterohepatic circulation.
- Urobilinogen uptake in liver is incomplete, thus some circulates to the kidneys and is excreted in urine (yellow colour).
Which enzyme is responsible for the conjugation of bilirubin, making it water soluble?
Glucuronosyltransferase
What is bile made up of?
Water, electrolytes, bile salts (Na & K), bile pigment, cholesterol and phospholipids.
What is bilirubin?
Product of haemoglobin metabolism.
What are the types of jaundice?
Pre-heptic; hepatocellular; post-hepatic.
Which drugs induce hepatic enzymes?
Drugs that induce hepatic enzymes: phenytoin, carbamazepine, barbiturates (notably phenobarbitone), rifampicin, alcohol (chronic abuse), smoking (induces the enzyme CYP1Α2, involved in the metabolism of drugs such as olanzapine and aminophylline).
Mnemonic: PC BRAS.
Which drugs are enzyme inhibitors?
Drugs that inhibit hepatic enzymes:
omeprazole, allopurinol, disulfiram,
erythromycin, valproate, isoniazid,
cimetidine, ethanol (acute alcohol binge), sulphonamides.
Mnemonic: OA DEVICES.
What is stored in the liver?
Glycogen, iron, copper & fat-soluble vitamins
Where is alkaline phosphatase released from and what does an elevation in ALP indicate?
ALP is an enzyme in the biliary canalicular membrane of the hepatocyte.
>3x increase indicates biliary obstruction - intrahepatic or post hepatic.
