Liver Failure and Jaundice Flashcards
State three roles of bile.
(1) Cholesterol homeostasis; (2) Dietary lipid/vitamin absorption; (3) Removal of xenobiotics, drugs and endogenous waste products (e.g. steroid hormones).
List the major components of bile.
Bile salts, cholesterol, bilirubin, phospholipids, bicarbonate, 97% WATER.
How much bile is produced daily?
500 mL The capacity of the gallbladder = 15-60 mL –
Which cell types produce bile? State the relative proportions of bile produced by each cell type.
Hepatocytes - 60% Cholangiocytes (line biliary tube - they are biliary epithelial cells) - 40%
What does bile flow depend on?
The concentration of the bile
What regulates bile concentration?
The transporters in the cholangiocytes.
How is bile modified as it passes through the biliary tree? (x5)
Alters pH and fluidity, water drawn into bile, luminal glucose is reabsorbed, CTFR actively secretes Cl- and HCO3- into bile.
What channel transports bicarbonate and chloride ions into the bile?
CFTR found in cholangiocytes.
What is bile excretion of bile salts and toxins performed by? (x3 main transporters)
Performed by TRANSPORTERS on the apical surface of hepatocytes and cholangiocytes. THREE MAIN TRANSPORTERS: (1) Bile salt excretory pump (BSEP), (2) MRD related proteins (MRP1 & MRP3), (3) FIC1 gene and multidrug resistant genes (MDR1 & MDR3).
What is purpose of BSEP transporter?
Active transport of bile acids across hepatocyte cannalicular membranes into bile, and secretion of bile acids is a major determinant of BILE FLOW.
What is the purpose of the MDR1 transporter?
Mediates canicular excretion of Xenobiotics and cytotoxins.
What is the purpose of the MDR3 transporter?
Transport of phospholipids across canalicular membrane (hepatocyte membrane that forms barrier between hepatocyte cytoplasm and bile canaliculi which drain into the bile duct).
What are bile salts?
Bile acids are conjugated with taurine or glycine in the liver, and the sodium and potassium salts of these are bile salts.
What are bile acids synthesised from?
From cholesterol.
What are the primary bile acids and their respective secondary bile acids? What is the difference between primary and secondary bile acids?
Primary bile acids are produced by the liver.
They are converted to secondary bile acids by the action of COLONIC bacteria.
Deoxycholate is reabsorbed but 99% of lithocholic acid is excreted in the stool. Primary = Cholic Acid + Chenodeoxycholic Acid Secondary = Deoxycholic Acid + Lithocholic Acid respectively.
2 primary and 2 secondary in total.
What is the purpose of the bile acids? (2)
Reduce surface tension of fats, and make fat more easily transportable for digestion/absorption by emulsification.
What percentage of bile is water?
97%
Describe a characteristic of Bile that helps it in its role of transporting fats.
Its amphipathic, a fat and water philic interface.
This means that bile salts form MICELLES which enables transport of fats into body.
WHAT IS A MICELLE?
One surface has hydrophilic domains and faces out, the second surface has hydrophobic domains that face inwards. Free fatty acids and cholesterol inside and thus transported to GIT epithelial cells for absorption.
What is a problem with bile salts? (x2)
(1) Detergent-like actions make bile salths potentially cytotoxic in high concentrations, eg. In pregnancy, a high concentration of bile salt can damage foetus. (2) If not reabsorbed, it can cause duodenal irritation.
Describe the effect of cholecystokinin on bile release. Stimulus?
When food enters the duodenum, cholecystikinin (CCK) is released. —Cholecystokinin causes contraction of the gallbladder and relaxation of the sphincter of Oddi, resulting in large flow of bile into the duodenum.
What percentage of bile salts are reabsorbed in the terminal ileum?
95%.
Describe how terminal ileal disease can cause steatorrhoea.
Terminal ileal disease will mean that less bile salts are reabsorbed so less bile salts are released in the bile into the duodenum so there is less fat emulsification, digestion and absorption so more fat passes through the small intestines and enters the colon and leaves the body.
What is another important consequence of fat digestion and absorption is reduced?
They also absorb fewer fat soluble vitamins - ADEK.
State three important roles of the gallbladder.
Store bile, Acidify bile, Concentrate the bile by H2O diffusion following net absorption of Na+, Cl-, Ca2+… (means that bile pumped from gall bladder is considerably more concentrated than the bile draining directly from the liver).
What is the route that bile follows after production in the liver? (x2 routes)
- Each hepatocyte is apposed to several bile caaliculi.
- Bile drains into bile canaliculi, then intralobular bile ducts, interlobular ducts, right or left hepatic ducts, and finally the hepatic duct which is just outide the liver. Common hepatic duct drainsinto the common bile duct where it drains through the ampulla.
- Common bile duct joined by pancreatic duct prior to entering duodenal papilla.
- The ampulla of the bile duct is controlled by the Sphincter of Oddi.
- If the Ampulla is CLOSED, bile collects in the cystic duct and gall bladder. When the ampulla is open, bile drains into the duodenum.
How does enterohepatic circulation of bile salts work?
95% is reabsorbed in the terminal ileum and circulates in the EH circulation.
Absorbed by Na+/bile salt co-transport, coupled with Na+/K+ ATPase.
