Bile, Gallbladder and Stones

Question 1

State the physiology and functions of the gallbladder

Answer 1

• Storage and concentration of bile
• Concentrated because of active Na+ transport and H2O from the gallbladder
• pH of bile decreases and becomes acidic when Na+ is exchanged for H+
• Pancreatic juice = bile salts, bile pigments and dissolved substances in alkaline electrolytes

Question 2

State what bile travels through and how it is modified

Answer 2

• Bile travels through ductules and ducts as its composition is modified
• Water may be added via specific tight junctions within ductules (cholangiocytes)
• The ductules scavenge glucose and amino acids and GSH is hydrolysed
• Ductules secrete IgA for mucosal protection as well as HCO3- and H2O in response to secretin in the postprandial period

Bile flows from -

Hepatocytes -> bile canaliculi (with merge to form ductules) -> terminal bile ducts -> hepatic ducts -> common bile ducts

Question 3

State the 2 different cell types that secrete bile and what they secrete

Answer 3

1. Hepatocytes - cholesterol, lecithin, bile acids, bile pigments (bilirubin, biliverdin, urobilin etc)
2. Epithelial cells of bile ducts - bicarbonate rich salt solution - influenced by secretin and acetylcholine

Question 4

When is secretion of bile highest?

Answer 4

During and after a meal

Question 5

What does increased [bile salts] in the blood do?

Answer 5

• Increased [bile salt] in the blood increases bile salt synthesis and secretion into bile canaliculi to the gallbladder
• Increased secretion increases the flow of that bile

Question 6

State when the sphincter of oddi contracts and relaxes

Answer 6

Sphincter of Oddi contracts during periods of fasting

Sphincter of Oddi relaxes during and after meals

Question 7

State the substances secreted across the canalicular membrane and how are they transported

Answer 7

Bile acids
Phosphatidylcholine
Conjugated bilirubin
Cholesterol
Xenobiotics

Specific transporters ferry these substances into bile

Substances like water, glucose, Ca2+, GSH, amino acids and urea enter the bile by diffusion

Question 8

State the composition of hepatic and gallbladder bile composition

Answer 8

• Hepatic bile - 97% water, cholesterol, lecithin, bile acids, bile pigments etc
• Gallbladder bile - 89% water, HCO3-, Cl-, Ca2+, Mg2+, Na+, cholesterol, bilirubin, salts etc
• Bile becomes concentrated in the gallbladder as NaCl and H2O is lost to increase the solid content
• Bile is transferred into the gallbladder between meals when the sphincter of Oddi is closed

Question 9

Which pathways are bile made by?

Answer 9

90% of bile acids are synthesised by the classic/neutral pathway - less is made by the alternative/acidic pathway

Question 10

What are bile acids made from?

Answer 10

Made from cholesterol - helps to reduce cholesterol levels

Question 11

Where are bile acids secreted into and what are they conjugated to?

Answer 11

Secreted into bile and conjugated to glycine or taurine

Question 12

What does conjugation do to bile acids?

Answer 12

• Conjugation helps to increase the ability of bile acids to be secreted and also decreases their cytotoxicity
• Bile acids are also called bile salts

Question 13

State the 4 major bile acids found in humans

Answer 13

• Cholic acid (50%)
• Chenodeoxycholic acid (30%)
• Deoxycholic acid (15%)
• Lithocholic acid (5%)

Question 14

State the differences between the primary and secondary bile acids

Answer 14

• Primary bile acids -
• Made from cholesterol
• Consists of chenodeoxycholic acid and cholic acid
• Formed in the liver
• Secondary bile acids -
• Made from primary bile acids
• Consists of chenodeoxycholic which forms lithocholic acid and ursodeoxycholic acids
• Also consists of cholic acid which forms deoxycholic acid
• Formed in the colon

Question 15

Main functions of bile/bile acids

Answer 15

1. Elimination of cholesterol to bile acids - synthesis and subsequent excretion of bile acids in the faeces represents a significant mechanism for the elimination of excess cholesterol
2. Reduce the precipitation of cholesterol in gallbladder, bile acids and phospholipids to help solubise cholesterol in the bile
3. Facilitate the absorption of fat soluble vitamins (ADEK)
4. Regulate their own transport and metabolism via enterohepatic circulation
5. Facilitate the digestion of triglycerides - work in concert with phospholipids (lecithin) and monoglycerides to ensure the emulsification of fats

Question 16

State the 3 phases and how they link to the gallbladder

Answer 16

Cephalic phase - taste, smell and presence of food in the mouth- impulses via vagus nerve

Gastric phase - distension of the stomach generates impulses in the vagus nerves

Intestinal phase - period of most of the gallbladder emptying, key mediators for an increased release rate are CCK and secretin - promotes gallbladder secretions and epithelial cells of ductules to secrete bicarbonate rich secretions and water

Question 17

Describe the mechanisms controlling secretion of bile into the duodenum

Answer 17

• Presence of food in the duodenum causes signals to be sent by the vagal afferent to the dorsal vagal complex
• This will send signals down the vagal efferents which release acetylcholine at the gallbladder
• CCK secretion from the duodenum also then travels in the bloodstream and acts on the gallbladder to ,alongside acetylcholine, cause smooth muscle of the gallbladder to contract and secrete substances
• Vagal efferents also send signals to the sphincter of Oddi and NO and VIP are released to cause the sphincter to relax to allow bile to pass into the duodenum
• CCK can also have effects on the vagal afferents to stimulate gallbladder secretions

Question 18

Describe the role of CCK in bile secretion

Answer 18

• The presence of a fatty meal stimulates the secretion of cholecystokinin so the plasma [cholecystokinin] increases
• This causes the gallbladder to contract while causes increased flow of bile into the common bile duct
• It also causes the sphincter of Oddi to relax which leads to increased flow of bile into the duodenum

Question 19

Describe the release of bile process overall

Answer 19

1. Chyme entering the duodenum causes the release of cholecystokinin and secretin from duodenal enteroendocrine cells
2. CCK and secretin enter the bloodstream
3. CCK induces secretion of enzyme rich pancreatic juice - secretin causes secretion of HCO3- rich pancreatic juice
4. Bile salts and to a lesser extent secretin transported via the bloodstream stimulate the liver to produce bile more rapidly
5. CCK via the bloodstream causes the gallbladder to contract and hepatopancreatic sphincter to relax - bile enters the duodenum
6. During the cephalic and gastric phases vagal stimulation causes weak contractions of the gallbladder

Question 20

Describe enterohepatic recirculation and what can interrupt it

Answer 20

• Bile salts and lecithin are synthesised in the liver
• HCO3- and other ions neutralise acids in the duodenum
• Bile salts are the most important as far as GI function is concerned
• Most bile salts (95%) are reabsorbed by Na+ bile salt coupled receptors
• The bile salts are returned to the liver and secrete again into bile

Enterohepatic recirculation -
- Enterohepatic recirculation is the recycling pathway of bile salts from the intestine to the liver and back to the intestine
- The liver secretes cholesterol in the bile and some of this is excreted in faeces

Interruption of enterohepatic recirculation -
- Excess synthesis of bile salts by the liver
- Kidneys will excrete the synthesised bile salts and some cholesterol

Question 21

Describe the following about gallstones -
- Incidence rate
- What gallstones are made of
- How they form
- What high cholesterol causes and what high cholesterol is caused by

Answer 21

• Rates of incidence are 2:1 in women and men respectively
• Incidence increases with age
• Bile salts are a bile compounds with a cation like Na+ and along with cholesterol and phospholipids make up gallstones
• The higher the cholesterol content of bile the greater the concentrations of phospholipids and bile acids/salts
• Higher cholesterol can be caused by the liver secreting excess or by the reabsorption of salt and water
• The cholesterol crystallises which forms the gallstones and there is a precipitation of bile pigments

Question 22

State the 2 types of gallstones

Answer 22

Cholesterol stones - 85% due to obesity, less bile acids and/or less phospholipids
Calcium bilirubinate stones - due to increased conjugated bilirubin (haemolytic anaemia)

Question 23

What are they factors involved in gallstone formation

Answer 23

1. Bile stasis - stones that 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 e.g. cystic fibrosis, crohns disease, issues with bile production - the gallbladder and cystic ducts can be blocked with thick mucus
3. Chronic infection - bacteria aid formation of pigment stones
4. Supersaturation of bile with cholesterol
5. Presence of nucleation factors of glycoproteins

Question 24

How do gallstones cause symptoms

Answer 24

• Small gallstones have an easy passage via the bile duct but larger gallstones lodge into the opening of the gallbladder which leads to right upper quadrant pain and jaundice
• Duct from the pancreas joins the bile duct before it joins the duodenum
• Lodging of gallstones at this point stops the bile and pancreatic secretions flowing so pressure builds - causes right upper quadrant pain and jaundice - leads to nutritional deficiency as digestion of fats is inefficient
• Further pressure build up causes decreased secretion of bile and right upper quadrant pain and jaundice

Question 25

How are gallstones diagnosed?

Answer 25

• Ultrasonography and computer tomography - explore the right upper quadrant to detect gallstones
• Cholescintigraphy - administer technetium 99m labelled derivative of iminodiacetic acid (radioactive tracer) - acquire images of gall bladder and ducts
• Endoscope retrograde cholangiopancreotatigraphy- inject contrast media from an endoscope channel and visualise the biliary tree
• Can insert devices to remove gallstone fragments that may be obstructing, bile flow, pancreatic flow or both

Question 26

What are clinical features of gallstones?

Answer 26

• 85% of cases are asymptomatic as the gallstones remain in the gallbladder
• If the neck of the cystic duct is impaired there is right upper pain
• Gallstones that impact the common bile duct cause obstruction of bile flow and jaundice which can cause bacterial infections and right upper pain
• The gallbladder can secrete mucus if inflamed and rupture