S2: Bile, Gallbladder and Stones Flashcards
Why is the gall bladder important?
- It stores and concentrates bile which is synthesised by the liver
- Modifies fats so they can be digested
- Secretions of gall bladder and pancreas come together and go into the duodenum to neutralise the acidic chyme from the stomach - especially HCO3-
How is bile concentrated in the gallbladder?
How does it get more acidic?
It is concentrated because of active Na+ transport from the gallbladder and H2O follows.
The bile becomes more acidic as Na+ is exchanged for H+, but [Na+] increases as more Cl- and HCO3- are lost. Note that by acidic we are talking about it relative to the bile that would have been in the hepatic duct, the gall bladder bile is around pH 7.
What does pancreatic juice contain?
Bile salts
Bile pigments
Dissolved substances in alkaline electrolytes
List substances that are secreted into bile across the bile canalicular membrane
- Bile acids
- Phosphatidylcholine (phospholipid)
- Conjugated bilirubin
- Cholesterol
- Xenobiotics
There are specific transporters to ferry the above substances into the bile. Substances such as water, glucose, Ca2+, GSH (glutathione), amino acids and urea enter the bile by diffusion.
What can deviation of bile acids: phosphatidylcholine: cholesterol in the canalicular bile ratio lead to?
Cholesterol gallstones (as cholesterol precipitates out)
Describe bile formation
- Bile is formed in the liver from bile acids
- Bile moves through larger ductules and ducts and as they go through their composition is modified by movement of Na+ and H+
- Water may be added at specific tight junctions within ductules lined with cells called cholangiocytes
- Ductules scavenge (remove) glucose, AA and GSH is hydrolysed. This is because too much glucose could result in bacteria.
- Ductules also secrete IgA for mucosal protection and HCO3- in response to secretin in the postprandial period (after a meal).
What are cholangiocytes?
Cells which line tight junctions within ductules that allow water to be added to bile
Flow of bile from hepatocytes to bile duct
Hepatocytes –> Bile canaliculi (merge to form ductules) –> terminal bile ducts –> hepatic ducts (L and R) –> Common bile duct
What two cells secretes components of bile?
- Hepatocytes: secretes cholesterol, lecithin, bile acids, bile pigments (bilirubin, biliverdin, urobilin).
- Epithelial cells of bile ducts: bicarbonate rich salt solution
When is secretion of bile greatest?
Secretion of bile is greatest during and after a meal
This is for a good reason as we want to digest the food, particularly if we have taken a fatty meal
How does increased concentration of bile salt affect bile salt secretion and flow?
Increased [bile salt]blood → ↑ bile salt secretion into bile canaliculi
Increased secretion →↑flow of bile
When does the sphincter of oddi contract and relax?
- Sphincter of Oddi contracts during periods of fasting (interdigestive periods)
- Sphincter of Oddi relaxes during and after meals (digestive periods)
What are the major bile acids found in humans?
- Cholic acid
- Chonedeoxycholic acid
- Deoxycholic acid
- Lithocholic acid
What happens to bile acids in intestine?
Bacteria deconjugate these bile acids. Deconjugated bile acids are excreted or reabsorbed.
This is important because bile acids on their own can be very cytotoxic and conjugating them also enhances their solubility.
Formation of secondary bile acids
How are they bile acids secreted into bile?
- Cholesterol is made into primary bile acids in liver
- Anaerobic bacteria in the colon can modify the primary bile acids
- Bile acids are important in the GIT, they are made from cholesterol and secreted into bile conjugated to glycine or taurine.
How are primary and secondary bile acids removed by intestine into liver?
They travel via portal circulation
List some primary and secondary bile acids
Cholic acid -> Deoxycholic acid
Chenodeoxycholic acid -> Lithocholic acid and ursodeoxycholic acid
Function of bile acids
- Bile acids can be used to eliminate cholesterol
- It also reduces precipitation of cholesterol in the gallbladder, bile acids and phospholipids to help solubilise cholesterol in the bile
- Facilitate the absorption of fat soluble vitamins (A, D, E, K)
- Regulate their own transport and metabolism via enterohepatic circulation
- They regulate lipid and glucose metabolism
How is bile concentrated in the gallbladder?
With NaCl and some H2O loss
Difference in composition of hepatic bile and gallbladder bile
Hepatic bile is roughly 97% water, it also contains cholesterol, lecithin, bile acids, bile pigments etc.
Gallbladder bile is about 87% water, contains HCO3-, Cl-, Ca2+, Mg2+, Na+, cholesterol, bilirubin etc
Is bile essential for life?
We know people have their gall bladders removed. In general cholecystomised patients can have a good quality of life, so long as they don’t take too much fatty foods etc. They also have to lose weight.
Describe the control of gallbladder contraction and bile secretion
The gallbladder contracts when we are feeding which allows bile to be released.
It seems what causes bile acid release is similar to that what causes acid release in the stomach.
In the cephalic phase we have taste, smell and presence of food in the mouth which can lead to initiation of impulses via the vagus nerve.
In the gastric phase, distension of the stomach also initiates impulses via the vagus nerve.
Finally in the intestinal phase we have the period of most gallbladder emptying, there are certain signals that are also important here in emptying the gallbladder (motility) like CCK and secretin.
What causes the release of CCK and secretin?
- CCK is released in response to fat which allows sphincter of oddi to relax, contractions of gallbladder
- Secretin is released in response to acidic chyme (acid needs to be neutralised). This causes duct cells in liver (epithelial) to be stimulated which release bicarbonate
Describe role of sphincter of oddi in bile secretion
Sphincter of Oddi which relaxes as the gallbladder contracts and the pancreatic/gall bladder secretions will occur into the duodenum.
There will be neutralisation of acids and digestion will occur.
Distension of the duodenum will send signals via vagal afferents to the dorsal vagal complex. Signals return via efferents, the relaxation of sphincter of Oddi occurs via NO and VIP (and CCK).
