Bile, Gall Bladder and Gall Stones Flashcards
What is the ampulla of Vater formed from?
Union of the pancreatic duct and the common bile duct.
Where is the ampulla of Vater found?
Duodenal papilla
What is the general function of the gallbladder?
Stores and concentrates bile.
Why does bile become concentrated within the gall bladder?
Active Na+ transport from the gallbladder.
Why does bile become acidic within the gall bladder?
Na+ is exchanged for H+
Describe bile acid synthesis.
- Occurs in liver cells
- Synthesise primary bile acids (cholic acid and chenodeoxycholic acid) via cytochrome P450-mediated oxidation
Describe the pathway of bile flow
Hepatocytes
⬇
Bile Canaliculi
⬇
Terminal Bile ducts
⬇
Hepatic ducts (left and right)
⬇
Common Bile duct
What two components make up a bile acid?
- bile
- a cation (eg. Na+)
What two cells secrete bile salts?
HEPATOCYTES: secrete cholesterol, bile acids, bile pigments (bilirubin, biliverdin, urobilin)
EPITHELIAL CELLS OF BILE DUCTS: secrete bicarbonate-rich salt solution
What does secretin influence?
Secretion of bicarbonate-rich salt solutions
Can cholecystomised patients have a good quality of life?
Yes, as long as they don’t eat too much fatty food.
What substances are secreted across the canalicular membrane via transporter proteins?
- bile acids
- conjugated bilirubin
- cholesterol
- xenobiotics (foreign chemical/ substance, e.g. drugs)
What substances are secreted into bile by diffusion?
- Water
- Glucose
- GSH (glutathione)
- Amino acids
- Urea
Describe the composition of hepatic bile.
97% water; cholesterol, lecithin, bile acids, bile pigments
Describe the composition of gallbladder bile
89% water; Cl-, Ca2+, Na+, cholesterol, bilirubin, bile salts
When does bile go into the gallbladder between meals?
When Sphincter of Oddi is closed
Describe bile acids.
- Made from cholesterol
- Secreted into bile
- Conjugated to glycine or taurine.
What is the purpose of bile conjugation?
- Increase the ability of bile acids to be secreted
- Decrease cytotoxicity
List and describe the 4 major bile acids found in humans.
PRIMARY BILE ACIDS:
- Cholic Acid
- Chenodeoxycholic Acid
SECONDARY BILE ACIDS:
- Deoxycholic Acid: 15%
- Lithocholic Acid: 5%
What are the differences between primary and secondary bile acids?
- Primary bile acids formed in liver
- Secondary bile acids formed in colon
Outline cholesterol conversion to secondary bile acids.
Cholesterol converted to primary bile acids, then to secondary bile acids.
List the main functions of bile/bile acids as metabolic regulators. PART 1
- elimination of excess cholesterol to bile acids (5% excreted in faeces)
- reduce precipitation of cholesterol in gallbladder (bile acids and phospholipids solubilise cholesterol in bile)
- facilitate the absorption of fat-soluble vitamins (ADEK)
List the main functions of bile/bile acids as metabolic regulators. PART 2
- regulate their own transport and metabolism via enterohepatic circulation
-facilitate the digestion of triglycerides (work in cohort with phospholipids (lecithin) and monoglycerides to ensure the emulsification of fats)
List the main functions of bile/bile acids as metabolic regulators. PART 3
- Act as emulsifying agents that render fats accessible to pancreatic lipase]
Describe the contraction of the gallbladder during the intestinal phase. PART 1
- Vagus nerve conveys information about the state of the body’s organs to the CNS
- Conveys contents of duodenum to the CNS.
Describe the contraction of the gallbladder during the intestinal phase. PART 2
- If duodenum contains lipids, causes the release of CCK
- Stimulates the release of bile which helps in the emulsification of fats and prepares them for digestion by pancreatic lipases.
What is CCK released in response to?
Lipids/fats
What is secretin released in response to?
HCl in the duodenum.
What occurs due to secretin release?
Stimulate duct cells in the liver (to release a bicarbonate-rich solution)
Describe the mechanisms controlling the secretion of bile into the duodenum. PART 1
- When lipids are sensed in the duodenum, trigger the release of CCK
- Directly, contracts the gallbladder.
Describe the mechanisms controlling the secretion of bile into the duodenum. PART 2
- Indirectly, sends a signal to the dorsal vagal complex, which then sends a signal back down to contract the gallbladder (via ACh) and relax the Sphincter of Oddi (via NO/VIP).
What can also control bile secretion?
- Motilin - induces gallbladder emptying
- Antral contractions
What are all of the mechanisms controlling bile secretion, mediated by?
- Distention
- Neuronal and hormonal signals.
On a molecular level, explain how CCK induces bile secretion into the duodenum. PART 1
- Chyme enters the duodenum causing the release of CCK and secretin from the duodenal enteroendocrine cells.
- CCK and secretin enter the bloodstream, absorbed by the intestinal mucosa.
On a molecular level, explain how CCK induces bile secretion into the duodenum. PART 2
- CCK induces the secretion of enzyme-rich pancreatic juice.
- Secretin causes the secretion of bicarbonate-rich pancreatic juice.
On a molecular level, explain how CCK induces bile secretion into the duodenum. PART 3
- Bile salts and secretin are transported via the bloodstream and stimulates the liver to produce bile more rapidly.
- CCK causes the gallbladder to contract and the hepatopancreatic sphincter to relax; bile enters the duodenum.
On a molecular level, explain how CCK induces bile secretion into the duodenum. PART 4
- During the cephalic and gastric phases, vagal nerve stimulation causes weak contractions of the gallbladder.
Describe how bile salts are ‘recycled’. PART 1
- Reabsorbed by Na+-bile salt coupled transporters.
- Returned to the liver and secreted again into the bile.
Describe how bile salts are ‘recycled’. PART 2
- Recycling pathway from the intestine to the liver and back to the intestine is the enterohepatic circulation (via the hepatic portal vein).
Both primary and secondary bile acids are removed by the intestine into the liver via the portal circulation. Explain how. PART 1
- Specific transporters in the terminal ileum that transport bile salts from the lumen of the digestive tract to the intestinal capillaries.
- Bile salts are transported directly to the liver via the hepatic portal vein.
Both primary and secondary bile acids are removed by the intestine into the liver via the portal circulation. Explain how. PART 2
- Hepatocytes take up bile salts from the blood, and increase the secretion of bile salts into the bile canaliculi
- Canaliculi are the passageways that convey bile into the larger bile ducts.
Both primary and secondary bile acids are removed by the intestine into the liver via the portal circulation. Explain how. PART 3
95% of the bile that is released into the small intestine is recycled via the enterohepatic circulation, 5% is lost in the faeces.
What will interruption of the enterohepatic circulation cause?
- excess synthesis of bile salts by the liver (compensate for losing bile salts)
- kidneys will excrete the synthesised bile salts (and some cholesterol)
Describe the formation of gallstones.
Changes in the composition of bile may cause cholesterol to precipitate out to form gallstones.
What causes the increased cholesterol that could cause gallstones?
- excess excretion by liver
- reabsorption of water and salt provides environment for gallstones to form.
What are the two types of gallstones?
- cholesterol stones - due to obesity
- calcium bilirubinate - due to increased conjugated bilirubin
List some factors involved in gallstone formation. PART 1
- Bile Stasis: stones form in bile that is sequestered in the gallbladder rather than flowing in the bile ducts into the duodenum
- Decreased amount of bile acids due to malabsorption (in cystic fibrosis - dehydrated and acidic; 10% incidence)
List some factors involved in gallstone formation. PART 2
- Problems with bile production
- Chronic infection - bacteria help in the formation of pigment stones
- Supersaturation of bile with cholesterol
How would you visualise the gallbladder in a case of gallstones? PART 1
Ultrasonography and computer tomography: explore the upper right quadrant of the gallbladder to detect gallstones
How would you visualise the gallbladder in a case of gallstones? PART 2
Cholescintigraphy: administer technetium-99m-labelled derivative of iminodiacetic acid (radioactive tracer), to show images of the gallbladder and its ducts (inject CCK to see how the gallbladder behaves)
How would you visualise the gallbladder in a case of gallstones? PART 3
Endoscope retrograde cholangiopancreatography (ERCP): can visualise the biliary tree by injecting contrast media from an endoscope channel
What symptoms will you end up with if a gallstone got stuck in each of the three possible places it could form? PART 1 - The Cystic Bile Duct
- painful gallbladder contractions
- inflammation of the gallbladder (acute cholecystitis)
What symptoms will you end up with if a gallstone got stuck in each of the three possible places it could form? PART 2 - The Common Bile Duct
- pain and nausea
- lack of bile release
- failure to excrete bilirubin leads to jaundice
- can cause bacterial infection (cholangitis)
What symptoms will you end up with if a gallstone got stuck in each of the three possible places it could form? PART 3 - The Common Bile Duct
- inappropriate activation of pancreatic enzymes
- acute pancreatitis
What is pancreatic juice made from?
→ bile salts
→bile pigments
→dissolved substances in alkaline electrolytes
Where is water added to bile?
Ductules
What do the ductules do?
→The ductules scavenge glucose, amino acids and hydrolyse GSH
What do ductules secrete and in response to what?
→ IgA (mucosal protection)
→HCO3-
→ H2O
When is secretion of bile the greatest?
→greatest during and after a meal
What does increased bile salt concentration in the blood mean?
→ increased bile salt secretion into bile canaliculi
When does the sphincter of Oddi contract?
→ during periods of fasting
When does the sphincter of Oddi relax?
→ relaxes during and after meals.
What acids are formed from the neutral pathway and in what amounts?
→cholic acid
→ chenodeoxycholic acid
What are the conversions that intestinal bacteria do?
→Chenodeoxycholic acid → Lithocholic acid and Ursodeoxycholic acid
→Cholic acid → Deoxycholic acid
What activates the cephalic phase?
→taste
→ smell
What causes the Sphincter of Oddi to relax?
→NO and VIP
What does a high cholesterol content of bile do?
→The higher the cholesterol content of bile the greater the concentrations of phospholipid and bile salts.
What causes increased cholesterol in gallstone patients?
→Liver secretes excess cholesterol
→Reabsorption of salt and water
→Cholesterol crystallizes and forms gallstones
→Precipitation of bile pigments
How do small gallstones pass?
→ easy passage via bile duct
What does lodging of gallstones cause?
→stoppage of bile and pancreatic secretions
