7 Liver Failure and Jaundice Flashcards
Q: Why do we produce bile? (3)
A: Cholesterol homeostasis
Dietary lipid / vitamin absorption (particularly fat soluble ones: ADEK)
Removal of xenobiotics (foreign to body)/ drugs/ endogenous waste products (normal from within)
Q: Give 3 examples of endogenous waste products.
A: - cholesterol metabolites
- adrenocortical
- other steroid hormones
Q: What is the main composition of bile? %? 3 other components. What type of solution?
A: water 97%
- bile salts and inorganic salts
- bile pigments bilirubin (BR) and bilivirdin (smaller)
- fatty acids
in an alkaline electrolyte solution
Q: Name 4 other substances excreted into bile.
A: Adrenocortical and other steroid hormones
Drugs/Xenobiotics
Cholesterol
Alkaline Phosphatase (ALP)
Q: How much bile is secreted/produced daily? What colour is it and why? What produces it? (2) Percentages?
A: 500mL
Green/yellow colour because of glucoronides of bile pigments
60% bile secreted by hepatocytes (liver cells)
Up to 40% secreted by cholangiocytes (biliary epithelial cells that line biliary tree)
Q: Where does bile go from the organ of production and how?
A: Bile drains from liver, through bile ducts, into duodenum at duodenal papilla
Q: What is the role of the biliary tree in bile production? (6)
A: (40% bile secreted by cholangiocytes (biliary epithelium))
modifies bile as it flows through
- Alters pH
- alters fluidity
- H20 drawn out of bile (osmosis through paracellular junctions)
- Luminal glucose and some organic acids also reabsorbed
- HCO3- and Cl- actively secreted INTO bile by CFTR mechanism (Cystic Fibrosis Transmembrane Regulator)
- Cholangiocytes contribute IgA by exocytosis into bile
Q: What can a mutation in CFTR affect?
A: 1/3 those with CF have mutation in this
bile does not flow easily through liver and they get cholestasis (slow flow of bile)
Q: Draw a diagram showing a hepatocyte, cholangiocyte and bile flow.
A: REFER
Q: What is bile flow closely related to? Which structures govern the rate of bile flow? Dysruption causes?
A: conc of bile acids and salts in blood
Biliary excretion of bile salts and toxins performed by transporters on apical surface of hepatocytes + cholangiocytes = These biliary transporters also govern rate of bile flow
Dysfunction of the transporters is a cause of cholestasis
Q: What are the main transporters in cells that produce bile? (4-6 names)
A: Bile Salt Excretory Pump (BSEP)
MDR related proteins (MRP1 and MRP3)
products of the familial intrahepatic cholestasis gene (FIC1)
multidrug resistance genes (MDR1 and MDR3)
Q: What’s the role of BSEP? (2) What codes for it?
A: (important for bile acids)
active transport of bile acids across hepatocyte canalicular membranes into bile, and secretion of bile acids is a major determinant of bile flow
ABCB11 gene
Q: What’s the role of MDR1?
A: excretion of xenobiotics, cytotoxins into bile
Q: What’s the role of MDR3?
A: phosphatidylcholine movement
Q: What are bile salts? Synthesised from?
A: Bile acids are conjugated with taurine or glycine (cysteine derivative) in the liver, and the sodium and potassium salts of these conjugated bile acids are called bile salts (conjugated in liver)
Bile acids synthesised from cholesterol
Q: What are the 4 main bile acids in humans?
A: 2 PRIMARY Acids (formed in liver)
-Cholic acid -Chenodeoxycholic acid
converted by colonic bacteria
-Deoxycholic acid -Lithocholic acid
SECONDARY Acids
Q: What are the 2 main roles of bile? How can it do this? What property allows them to do this? Describe (3). Then what happens to them?
A: -Reduce surface tension of fats
-Emulsify fat preparatory to its digestion/ absorption in gut
Bile Salts form Micelles
- Bile salts amphipathic
- One surface has hydrophilic domains, facing OUT (can be carried by water in the bile)
- 2nd has hydrophobic domains, facing IN
- free Fatty Acids and Cholesterol INSIDE
thus transported to GI tract epithelial cells for absorption
Q: What can the action of bile salts be in high concentrations? potentially? How does present? explain.
A: Detergent-like actions make bile salts potentially cytotoxic in high concentrations
condition: ‘bile acid malabsorption’ where bile acid circulation doesn’t work-> too high a bile acid concentration in bile and therefore in the gut which can irritate colon -> gut irritation eg diarrhoea
Q: In terms of bile, what exits the 2 main lobes of the liver and what do they become when they connect? where? What structure connects to them after? followed by? in? ends? Movement is controlled by?
A: right and left hepatic duct (contain bile)
form hepatic duct
join at hilum just outside liver
gall bladder joins to it via its cystic duct to form common bile duct just before it goes to pancreas and joins pancreatic duct
enter duodenum via the ampulla of the bile duct (controlled by sphincter of Oddi)
Q: What happens to bile that enters the bile duct? why?
A: once meets cystic gut of gall bladder, usually the bile is diverted so that it goes to the gall bladder for storage
sphincter of oddi is closed between meals
Q: When does bile enter the duodenum? how?
A: Eating causes sphincter of Oddi to relax
Gastric contents (F.As, A.As > CHOs) enter duodenum causing release of cholecystikinin, CCK (Gut mucosal hormone)
Cholecystikinin causes gall bladder to contract and SoO to relax
Q: What is each hepatocyte apposed to in terms of the biliary system? What happens to the structures they appose?
A: several bile canaliculi
drain-> intralobular bile ducts, coalesce-> interlobular ducts -> R and L hepatic ducts -> join outside liver to form Common Hepatic Duct
Q: What is the structure of enterhepatic circulation? What enters it?
A: blood travelling between small intestine and liver
exit from liver: bile-> enter SI -> reabsorbed into terminal ileum -> transported to enterocytes-> enter portal blood-> taken up by hepatocytes -> excreted into canaliculis -> continue
liver: cells transfer various substances, including drugs, from plasma to bile
bile salts and some drugs
Q: Describe the enterhepatic circulation of drugs. What type? What does it become? allows?
A: Many hydrophilic drug conjugates (esp. glucoronide)
are concentrated in bile -> GUT -> glucoronide hydrolysed -> active drug re released -> reabsorbed -> cycle repeats
“reservoir” of re-circulating drug
can prolong action e.g. morphine
Q: What percentage of bile salts enter enterohepatic circulation? How? What happens to them? (4)
A: -95% bile salts absorbed from small (terminal) ileum - mainly
-by Na+/bile salt co-transport Na+-K+ ATPase system at cell surface
- 5% converted to secondary bile acids in colon:
- deoxycholate absorbed
- lithocholate 99% excreted in stool
-absorbed B.salts –portal vein–> back to liver -> re-excreted in bile
Q: What quantity of bile salt recycles in enterohepatic circulation? How often? (2) What would happen if bile stopped entering the gut? (2)
A: 3g (2x/meal; 6 – 8x/day)
- Up to 50% ingested fat appears in faeces
- malabsorption fat soluble vitamins (A,D,E,K)