Bile, Gallbladder and Gallstones Flashcards
What are the physiology and functions of the gallbladder?
Storage and concentration of bile
Concentrated because of active Na+ transport (and H2O) from gallbladder
The pH of bile drops (becomes “acidic”) as Na+ is exchanged for H+
Pancreatic juice- bile salts, bile pigments and dissolved substances in alkaline electrolytes
Where does bile travel through? (How does this influence bile?)
Bile → larger ductules and ducts (composition is modified)
Water is (may be) added via specific tight junctions within ductules (cholangiocytes)
The ductules scavenge glucose, amino acids; GSH is hydrolysed
Ductules secrete IgA (mucosal protection), HCO3- and H2O in response to secretin in the postprandial period
Cholangiocytes secrete bicarbonate and water
Bile flows as follows:
Hepatocytes
↓
Bile canaliculi (merge to form ductules)
↓
Terminal bile ducts
↓
Hepatic ducts (left and right)
↓
Common bile duct
What are the components of bile
These are secreted by 2 different cell types:
Hepatocytes: cholesterol, lecithin, bile acids, bile pigments (bilirubin, biliverdin, urobilin, etc.)
Epithelial cells of bile ducts: bicarbonate-rich salt solution
Secretin & ACh influence the secretion of bicarbonate-rich salt solutions and H2O
Secretion of bile is greatest during and after a meal
Increased [bile salt]blood → ↑ bile salt synthesis & secretion into bile canaliculi …..> gallbladder
Increased secretion →↑flow of bile
Sphincter of Oddi contracts during periods of fasting
Sphincter of Oddi relaxes during and after meals
Is bile essential for life?
Cholecystomised patients can have a good quality of life
What substances are secreted across the bile canalicular membrane?
Substances secreted across the bile canalicular membrane:
Bile acids
Phosphatidylcholine
Conjugated bilirubin
Cholesterol
Xenobiotics (foreign chemicals/substances, e.g. drugs)
Specific transporters ferry the above into bile
Substances such as water, glucose, Ca2+, GSH, amino acids and urea enter the bile by diffusion
What is the composition of hepatic and gallbladder bile?
Hepatic bile = 97% water; cholesterol, lecithin, bile acids, bile pigments, etc.
Gallbladder bile: 89% water; HCO3-, Cl-, Ca2+, Mg2+, Na+, cholesterol, bilirubin, bile salts, etc.
Bile concentrated in gallbladder (NaCl and H2O loss → increased solid content)
Bile goes to the gallbladder between meals when sphincter of Oddi is closed
What are bile acids?
Bile acids are important in GI
Made from cholesterol – helps to reduce cholesterol levels
Secreted into bile and conjugated to glycine or taurine
Conjugation helps to increase the ability of bile acids to be secreted and also decreases their cytotoxicity
Bile acids are also called bile salts
What’s the difference between primary and secondary bile acids?
There are 4 major bile acids found in humans:
*Cholic acid: 50% = quantitatively more important
*Chenodeoxycholic acid: 30%
$Deoxycholic acid: 15% (made from cholic acid)
$Lithocholic acid: 5% (a product of the dissociation of chenodeoxycholic acid)
*Principal primary bile acids formed in the liver
$secondary bile acids are formed in the colon
How do bile/bile acids function as metabolic regulators?
Elimination of cholesterol to bile acids (5% excreted in faeces)
Synthesis and subsequent excretion of bile acids in the faeces represents a significant mechanism for the elimination of excess cholesterol
Reduce the precipitation of cholesterol in gallbladder; bile acids and phospholipids help solubilise cholesterol in the bile
Facilitate the absorption of fat-soluble vitamins (ADEK)
Regulate their own transport and metabolism via enterohepatic circulation
Facilitate the digestion of triglycerides - work in concert with phospholipids (licithin) and monoglycerides to ensure the emulsification of fats
How? Facilitate the digestion of dietary fats by acting as emulsifying agents that render fats accessible to pancreatic lipases
How are bile/bile acids controlled in the gallbladder?
Cephalic phase: taste, smell and presence of food in the mouth → impulses via vagus nerve
Gastric phase: distension of stomach generates impulses in vagus nerve
Intestinal phase: period of most gallbladder emptying; key mediators for the increased release are:
CCK in response to? fats
Secretin in response to? Fats or acidic chyme
Through what mechanism is the secretion of bile into the duodenum controlled?
The presence of food will send those nerves and become innervated, so the vagal afferent will send a message to the dorsal vagal complex in the brain
The efferent vagus nerves will get stimulated and Ach, secretin and CCK will all walk on the gallbladder to cause contraction and the gallbladder will squeeze and allow the secretion of bile, traveling down the cystic duct and into the duodenum
And then the secretions that are coming from the pancreas will join in
The actions of CCK can be felt directly within the gallbladder without the vagal stimulation as it can travel through the blood and contract the gallbladder
Motilin → gallbladder motility and ↑ volume of gall bladder secretions
What controls the contraction of the gallbladder and the release of bile into the duodenum?
Control of gallbladder motility – the basics; as you saw, there are other levels of control
Presence of fatty meal stimulates secretion of cholecystokinin (CCK):
What happens to bile salts after they are used?
Bile salts, lecithin (phospholipids): synthesised in liver
HCO3- and other ions – neutralise acids in duodenum
Bile salts are the most important as far as GI function is concerned
Most of bile salts are reabsorbed (95%) by Na+-bile salt coupled transporters
The bile salts are returned to the liver and secreted again into bile
The recycling pathway from intestine to liver and back to intestine = enterohepatic circulation – recycling of bile salts
The body’s content of bile acid pool (~3.5g) may be recycled ~twice per meal
What happens when enterohepatic circulation is interrupted?
Liver secretes cholesterol in the bile and some of this is excreted in faeces
Interruption of enterohepatic circulation (e.g. after ileal resection) will cause the following:
Excess synthesis of bile salts by the liver
Kidneys will excrete the synthesised bile salts (and some cholesterol)
What are gallstones?
Gallstones (cholelithiasis)
Ratio of incidence of gallstones = 2:1 in women and men, respectively and incidence increases with age
Bile salts (= bile compounded with a cation, e.g. Na+), cholesterol and phospholipids
The higher the cholesterol content of bile, the greater the concentrations of phospholipid and bile acids/salts
What causes the increased cholesterol?
Liver secretes excess
Reabsorption of salt and water which then tends to increase cholesterol levels
The cholesterol crystallises and forms gallstones- precipitation of bile pigments
What are the types of gallstones?
There are 2 types:
Cholesterol stones (85%): obesity cause due to; ↓ bile acids; ↓ phospholipids
Calcium bilirubinate stones – due to ↑ conjugated bilirubin (can cause haemolytic anaemia)
Factors involved in gallstone formation:
1. Bile stasis: stones form in bile that is sequestered in the gallbladder rather than bile that is flowing in the bile ducts into the duodenum
2. Decreased amount of bile acids due to malabsorption (in cystic fibrosis – dehydrated and acidic; 10% higher incidence; Crohn’s disease); problems with bile production – gallbladder and cystic ducts can be blocked by thick mucus
3. Chronic infection – bacteria help in the formation of pigment stones
4. Super-saturation of bile with cholesterol
5. Presence of nucleation factors or glycoprotein??
Ex vivo studies:
Bile from gallstone sufferers: stone forms within 2-3 days
Bile from normal individuals: stone formation takes ~ 2 weeks (is the delay due to presence of anti-nucleation factors?)
