33) Bile, gallbladder and stones Flashcards
What cells synthesise bile?
- The hepatocytes
- It occurs when we are not eating
Describe the movement of bile from the liver to the gall bladder and duodenum
- It flows from the hepatocytes down the bile canaliculi (capillaries) into the (right and left) hepatic ducts that join together to form the common hepatic duct.
- If it needs to be secreted this bile flows down the common bile duct along with the bile in the gall bladder and joins the duodenum at the sphincter of Oddi where the bile is released into the duodenum
- If it needs to be stored it will flow into the cystic duct where it enters the gall bladder to be stored
What is the ampulla of vater?
- The point at which the common bile duct meets the pancreatic duct
- Here the juices from the pancreas and the bile from the liver and gall bladder mmix and are released into the duodenum
- This release is controlled by the sphincter of Oddi
What is the function of the gall bladder?
- It stores and concentrates bile
- It concentrates bile as it has active Na+ transport. In this process water is removed from the gall bladder
- The pH of bile drops as Na+ is exchanged for H+
How does bile salt concentration affect bile salt synthesis?
- As [bile salt] increases it causes the production and secretion of bile salts to also increase
- An increase in bile secretion leads to an increase in bile flow
How does the sphincter of Oddi change its shape to achieve its function?
- The sphincter of Oddi contracts during periods of fasting as there is nothing in the duodenum and so there is no need for the release of pancreatic juices and bile into the small intestines.
- However it relaxes during and after meals as there will be food present in the duodenum so it will need to allow pancreatic juices and bile to flow through and digest the food
What substances are secreted across the bile canalicular membrane?
- Bile acids
- Phosphatidylcholine
- Conjugated bilirubin
- Cholesterol
- Xenobiotics
How are substances secreted by the bile canalicular membrane transported?
- Through specific transporters such as water, glucose, etc
Where do we find the most concentrated bile?
- We find the most concentrated bile in the gall bladder
What are the two pathways in which bile is produced?
- Classical (neutral) pathway: Accounts for majority of the bile produced and most of the intermediates produced by this pathway are neutral
- Alternative (Acidic) pathway: Accounts for the minority of bile produced and most of the intermediates produced by this pathway are acidic
What are bile acids made from?
- They are made from cholesterol (so helps reduce the level of cholesterol in the body)
- Bile acids are secreted into bile and conjugated to glycine or taurine
Why is bile conjugated?
- It helps to increase the ability of bile acids to be secreted and also decreases their cytotoxicity
What are the different types of bile found in humans?
- Cholic acid
- Chenodeoxycholic acid
- Deoxycholic acid
- Lithocholic acid
What are the different subdivisions of the bile found in the body?
- Primary bile acids: Include cholic acid and chenodeoxycholic acid. These are produced in the over
- Secondary bile acids: Include deoxycholic acid (from cholic acid) and lithocholic acid (from chenodeoxycholic acid). These are produced by intestinal bacteria from primary bile acids
What are the main functions of bile?
- Elimination of cholesterol through the synthesis of bile
- Reduce the precipitation of cholesterol in the gall bladder as bile acids and phospholipids help solubilise cholesterol into bile
- Facilitate the absorption of fat-soluble vitamins (ADEK)
- Regulate their own transport and metabolism via enterohepatic circulation
- Facilitate the digestion of triglycerides as they emulsify fats
What controls the release of bile?
- Cephalic phase: Taste, smell and presence of food in the mouth sends impulses via vagus nerve
- Gastric phase: Distension of the stomach generates impulses in the vagus nerve
- Intestinal phase: Period of most gall bladder emptying. Key mediators for the release of bile here is CCK and Secretin
What affects the levels of CCK?
- Presence of a fatty meal in the stomach stimulates secretion of CCK
How does CCK affect the gall bladder and sphincter of Oddi?
- CCK causes the gall bladder to contract and so increasing the flow of bile into the common bile duct
- CCK also causes the sphincter of Oddi to relax which increases blood flow of bile into the duodenum
How is bile released into the duodenum?
- Chyme enters into the duodenum and causes the release of CCK and secretin from the duodenal enteroendocrine cells
- CCK and secretin enter the blood stream
- CCK induces the secretion of enzyme rich pancreatic juices while secretin causes secretion of HCO3- rich pancreatic juices
- Bile salts and secretin are also transported in the blood stream further and stimulate the liver to produce more bile
- CCK in the bloodstream causes the gall bladder to contract and the sphincter of Oddi to relax allowing bile to enter the duodenum
- During cephalic and gastric phases the vagal nerve is stimulated causing weak contractions of the gall bladder
What is the enterohepatic circulation?
- The pathway in which the bile is recycled from the intestine to the liver and back to the intestine
What happens when there is an interruption of the enterohepatic circulation?
- Excess synthesis of bile by the liver
- Kidneys will excrete the synthesised bile salts and some cholesterol
How does age and gender affect incidence of gall stones?
- Gall stones are more common in women
- Incidence of gall stones increases with age
How does concentration of cholesterol affect bile and phospholipids?
- The higher the concentration of cholesterol the higher the concentration of bile and phospholipids
How do gallstones form?
- When cholesterol crystallises it forms gallstones which are precipitates of bile pigments
How does concentration of cholesterol affect incidence of gall stones?
- The higher the concentration of cholesterol the higher the chance of gall stones forming
What causes increased cholesterol?
- Liver secretes excess cholesterol
- Reabsorption of salt and water
What are the two types of gall stones?
- Cholesterol stones: Caused by obesity, decreased levels of bile acids, and decreased levels of phospholipids
- Calcium bilirubinate stones: Due to increased conjugation of bilirubin and can lead to haemolytic anaemia
What are the factors involved in gallstone formation?
- Bile stasis where stones form when bile is sequestered in the gall bladder rathe than flowing in the bile ducts and duodenum
- Decreased amounts of bile acids due to malabsorption . This leads to problems with bile production as the gall bladder and cystic ducts may become blocked by thick mucus
- Chronic infection as bacteria help in the formation of pigment stones
- Super-saturation of bile with cholesterol
- Presence of nucleation factors and glycoproteins
What problems do gallstones cause?
- Sometimes small gall stones have easy passage via the bile duct
- However larger gallstones get lodged in the opening of the gall bladder
- Gall stones can also get lodged in the duct where the pancreas joins the bile duct.
- This stops secretion of bile and pancreatic juices . This leads to nutritional deficiency as digestion of fats is insufficient
- Pressure also beings to build up and causes decreased secretion of bile
- It can cause pain in the upper right quadrant and jaundice
How to diagnose gallstones?
- The colour of urine may be yellow from bilirubin
- Ultrasonography and computer tomography to visualise and detect gallstones within the gall bladder
- Cholescintigraphy where a radioactive tracer is administered to acquire an image of the gall bladder, the ducts and where the gallstone is
- Endoscope retrograde cholangiopancreatography (ERCP) where a contrast media is injected through an endoscope channel to visualise the biliary tree
- Inser devices that can remove gallstone fragments that maybe be obstructing bile flow, pancreatic juice or both
What are the clinical features of gallstones?
- Biliary pain in the upper right quadrant
- Cholestatic jaundice
