Bile, gall bladder and gall stones

Question 1

What forms of the hepatopancreatic duct?

Answer 1

Formed out of the union of pancreatic duct and common bile duct; near the duodenal papillla

Question 2

What is the function of the gallbladder?

Why is the bile concentrated?

Answer 2

• Storage and concentration of bile

* Concentrated because of active Na+ transport (and H2O) from gallbladder

Question 3

What is the percentage of solids in the hepatic duct bile and gallbladder

What is the pH in the hepatic duct bile and gallbladder

Answer 3

2-4 and 10-12

7.8-8.6 and 7.0-7.4

Question 4

Why does the Ph of bile drop?

Answer 4

The pH of bile drops (becomes “acidic”) as Na+ is exchanged for H+

Question 5

What are the contents of the pancreatic juice?

Answer 5

Pancreatic juice: bile salts, bile pigments and dissolved substances in alkaline electrolytes

Question 6

How large are the bile ductules?

Can water be added via specific tight junctions within ductules?

What do the ductules scavenge?

What do the ductules secrete?

Answer 6

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 hydrolyzed

Ductules secrete IgA (mucosal protection), HCO3- and H2O in response to secretin in the postprandial period

Question 7

Where does bile flow to and from?

Answer 7

Bile flows as follows:
Hepatocytes
       ↓
Bile canaliculi (merge to form ductules)
        ↓
Terminal bile ducts
       ↓
Hepatic ducts (left and right)
       ↓
Common bile duct

Question 8

What cells are bile secreted from?

Answer 8

1. Hepatocytes: cholesterol, lecithin, bile acids, bile pigments (bilirubin, biliverdin, urobilin, etc.)
2. Epithelial cells of bile ducts: bicarbonate-rich salt solution
   3. Secretin influences the secretion of bicarbonate-rich salt solutions and H2O

Question 9

What does increased concentration of bile salt in the blood lead to?

Answer 9

• Increased [bile salt]blood → ↑ bile salt secretion into bile canaliculi
Increased secretion →↑flow of bile

Question 10

When does the sphincter of Oddi contract and relax

Answer 10

• Sphincter of Oddi contracts during periods of fasting

* Sphincter of Oddi relaxes during and after meals

Question 11

What substances are secreted across the bile canalicular membrane?

Answer 11

• 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

Question 12

Describe the composition of hepatic and gallbladder bile

Answer 12

• 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

Question 13

What is the purpose of the conjugation of bile acids (remember when we did the liver lecture - the part where bile is made…)

Answer 13

Conjugation helps to increase the ability of bile acids to be secreted and also decreases their cytotoxicity

Question 14

What are the 4 major types of bile acids found in humans ( we already have leant about 2 - remember in the production of bile in the liver lecture)

Answer 14

• *Cholic acid: 50% = quantitatively more important
• *Chenodeoxycholic acid: 30%
• $Deoxycholic acid: 15%
• $Lithocholic acid: 5%

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Question 15

Why do we produce bile acids: the function of bile acids as metabolic regulators

Answer 15

1. Elimination of cholesterol to bile acids (5% excreted in faeces)
   a. 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 help solubilise 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 (licithin) and monoglycerides to ensure the emulsification of fats

Question 16

Describe the mechanisms controlling the secretion of bile into the duodenum

Answer 16

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Motilin → gallbladder motility and ↑ volume of gall bladder secretions

Question 17

What controls the contraction of the gallbladder and the release of bile into the duodenum?

Answer 17

Presence of fatty meal stimulates secretion of cholecystokinin (CCK):

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Question 18

Describe the release of bile into the duodenum

Answer 18

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Question 19

Most bile salts are reabsorbed.

What are they reabsorbed by?

Answer 19

Na+-bile salt coupled transporters

The recycling pathway from intestine to liver and back to intestine = enterohepatic circulation – recycling of bile salts

Question 20

What will interruption of enterohepatic circulation (e.g. after ileal resection) cause?

Answer 20

Excess synthesis of bile salts by the liver

Kidneys will excrete the synthesised bile salts (and some cholesterol)

Question 21

What are gallstones made of?

Answer 21

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 salts

Question 22

What causes increased cholesterol?

How do those 3 ingredients form gallstones?

Answer 22

Liver secretes excess

Reabsorption of salt and water

The cholesterol crystallises and forms gallstones
precipitation of bile pigments

Question 23

What are the two types of gall stones and what are they caused by?

Answer 23

• Cholesterol stones (85%): obesity; ↓ bile acids; ↓ phospholipids
• Calcium bilirubinate stones – due to ↑ conjugated bilirubin (haemolytic anaemia)

Question 24

Describe the factors involved with gallstone formation (Bile stasis, malabsorption, chronic infection, ss, nf and glycol)

Answer 24

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??

Question 25

Where can a gallstone lodge and what can it cause?

Why is bile yellow?

What colours faeces?

Answer 25

• Small gallstones easy passage via bile duct
• Larger gallstones lodge in the opening of gallbladder (right upper quadrant pain; jaundice)
• Duct from pancreas joins the bile duct before it joins the duodenum
• Lodging of gallstones at this point causes the stoppage of bile and pancreatic secretions (pressure builds up; right upper quadrant pain; jaundice)
Consequence → nutritional deficiency as digestion of fats is inefficient
• Further pressure build up causes decreased secretion of bile and right upper quadrant pain Jaundice (increased accumulation of bilirubin in blood)
• Bile is yellow because of bilirubin
• … colour of urine
• Stercobilin colours faeces

Question 26

How can we diagnose the gallstones: visualising the gallbladder

Answer 26

Ultrasonography and computer tomography: explore the right upper quadrant of gallbladder to detect gallstones

Cholescintigraphy: administer tecnetium-99m-labelled derivative of iminodiacetic acid (radioactive tracer)
→ acquire images of gall bladder and ducts

Endoscope retrograde cholangiopancreotography (ERCP): inject contrast media from an endoscope channel and visualise the biliary tree

What else could you do?

Insert device(s) and remove gallstone fragments that may be obstructing the bile flow, pancreatic juice or both

Question 27

Describe the clinical features of a gallstone

Answer 27

• 85% of cases are asymptomatic (gallstones remain in gallbladder)
• If the neck of the cystic duct is impaired → biliary pain of right upper quadrant ensues (acute cholecystitis)
• Gallstones that impact common bile duct → obstruction of bile flow and cholestatic jaundice which can cause bacterial infections (cholangitis) and right upper quadrant pain
• Gallbladder will secrete mucus if inflamed and rupture (mucocele or hydrops)