Bile, Gallbladder and Stones

Question 1

Describe the flow of bile before and during digestion

Answer 1

In the interdigestive period the sphincter of Oddi is contracted to prevent bile flowing into the duodenum. Secretion of bile is greatest during and after a meal due to CCK, which contracts the gallbladder and relaxes sphincter of Oddi

Bile flows from hepatocytes →bile canaliculi (which merge to form ductules) → terminal bile ducts → hepatic ducts (left and right) → common bile duct

Question 2

How does the composition of bile change over time?

Answer 2

Composition of bile is modified in the ductules
Water may be added via specific tight junctions within ductules (cholangiocytes)
The ductules scavenge glucose, aas; GSH is hydrolysed
Ductules secrete IgA (mucosal protection), HCO3- and H2O in response to secretin in the postprandial period

Question 3

How are the components of bile secreted?

Answer 3

The components of bile are secreted by 2 diff cell types:
Hepatocytes: cholesterol, lecithin, bile acids, bile pigments (bilirubin, biliverdin etc)
Epithelial cells of bile ducts: bicarbonate-rich salt solution
Secretin and ACh influences the secretion of bicarbonate-rich salt solutions and H2O

Question 4

What is the Composition of hepatic and gallbladder bile?

Answer 4

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.

Question 5

What are the 2 pathways responsible for bile acid formation?

Answer 5

Classic or neutral pathway: contributes to ~90% of bile salt synthesis
Both cholic acid and chenodeoxycholic acid are formed by the neutral pathway in same amounts.
In the alternative/acidic pathway: only forms chenodeoxycholic acid

Question 6

Describe bile acids

Answer 6

Bile acids are made from cholesterol
Secreted into bile and conjugated to glycine or taurine

Conjugation increases the ability of bile acids to be secreted and also decreases their cytotoxicity
Conjugation occurs in the liver

Question 7

What are the 4 major bile acids?

Answer 7

*Cholic acid: 50% = quantitatively more important
*Chenodeoxycholic acid: 30%
Deoxycholic acid
Lithocholic acid

*Primary bile acids, and these are metabolised into secondary bile acids (other two) by 7-a-dehydroxylase

Question 8

What are the main functions of bile/bile acids?

Answer 8

Bile acid synthesis and excretion in faeces eliminates excess cholesterol
Solubilises cholesterol in the bile, reducing cholesterol precipitation in the gallbladder
Facilitates absorption of fat-soluble vitamins (A,D,E,K)
Work w phospholipids (licithin) and monoglycerides to ensure fat emulsification
Act as emulsifying agents that make fats accessible to pancreatic lipases

Question 9

Describe what happens in the gallbladder during the 3 digestive phases

Answer 9

Cephalic phase: presence of food in the mouth sends impulses via vagus nerve
Gastric phase: stomach distension generates impulses in vagus nerve
Intestinal phase: period of most gallbladder emptying; key mediators for the increased release are:
CCK/Secretin in response to lipids in duodenum and acidic chyme. Stimulates ductal cells to release bicarbonate rich secretions and enhances the effects of Secretin

Question 10

Draw a flow diagram to explain the effects of CCK

Answer 10

CCK also induces secretion of enzyme rich pancreatic juice

Question 11

What is enterohepatic circulation?

Answer 11

Most bile salts are reabsorbed 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

Question 12

What would happen in interruption of the enterohepatic circulation?

Answer 12

Interruption of enterohepatic circulation (e.g. after ileal resection) may cause:

Excess synthesis of bile salts by the liver
Kidneys will excrete the synthesised bile salts (and some cholesterol)

Question 13

What are gallstones?

Answer 13

Gallstones: Precipitation of bile pigments
The higher the cholesterol content of bile, the greater the concs of phospholipid and bile salts
What causes the increased cholesterol?- Liver secretes excess. Reabsorption of salt and water

The cholesterol crystallises and forms gallstones
If the neck of the cystic duct is impaired → biliary pain ensues (acute cholecystitis)

Question 14

What are the types of gallstones?

Answer 14

There are 2 types: 
Cholesterol stones (85%): obesity; ↓ bile acids vs ↓ phospholipids 
Calcium bilirubinate stones – due to ↑ unconjugated bilirubin

Question 15

What are the factors involved in gallstone formation?

Answer 15

Factors involved inc bile stasis: stones form in bile that is sequestered in the gallbladder rather than flowing in the bile ducts and duodenum

Decreased amount of bile acids due to malabsorption (eg in CF), or problems with bile production
Chronic infection – bacteria help in the formation of pigment stones
Super-saturation of bile w cholesterol

Question 16

Give some consequences of gallstones

Answer 16

Lodging of gallstones at the junction of the pancreatic and CB duct blocks bile and pancreatic secretions. Pa builds up, causing nutritional deficiency
Jaundice (increased bilirubin in blood): If a gallstone blocks the flow of bile, jaundice occurs.
Symptoms: yellowing skin and eyes, dark brown urine, pale stools, itching

Blocked bile duct builds up of bile inside the gallbladder, causing infection (acute cholecystitis) or a bile duct infection by bacteria (acute cholangitis)

Question 17

How can you visualise the gallbladder when diagnosing gallstones?

Answer 17

Explore the right upper quadrant of gallbladder to detect gallstones using US and CT
To image the gallbladder and ducts: administer radioactive tracer

Visualise the biliary tree by injecting contrast media from an endoscope channel: (ERCP)

Question 18

What are other clinical presentations/features of gallstones?

Answer 18

Question 19

Why do gallstone patients have right scapula pain?

Answer 19

When your gallbladder is inflamed and swollen, it irritates your phrenic nerve. Your phrenic nerve stretches from the abdomen, through the chest, and into your neck.

Each time you eat a fatty meal, it aggravates the nerve and causes referred pain in your right shoulder blade