Biliary Secretion: liver and Gallbladder function

Question 1

What is bile made up of?

Answer 1

Mixture of salts (50%), pigments (i.g. bilirubin 2%) and cholesterol (4%), phospholipids (ie.g. lecithin 40%); ions; water.

Question 2

True or false: alcohol abuse can lead to accumulation of fat within the hepatocytes (steatohepatitis)

Answer 2

True. Steatohepatitis is fatty liver with inflammation which leads to scarring of liver and cirrhosis.

Question 3

What are some complications of cirrhosis?

Answer 3

1. jaundice
2. ascites,
3. loss of albumin leading to edema
4. problems with blood flow ( lack of clotting factor)
5. Coma
6. Death

Question 4

What are the two primary bile acids?

Answer 4

1. Cholic acid

2. Chenodeoxycholic acid

Question 5

What are the two secondary bile acids?

Answer 5

1. Deoxycholic acid

2. Lithocholic acid

Question 6

Which of the bile acids are the most common and which one is least common?

Answer 6

Cholic acid is most common. Lithocholic acid is least common.

Question 7

What enzyme adds the OH groups to cholesterol to produce primary bile acids?

Answer 7

7a-hydroxylase

Question 8

Where is primary bile acids produced?

Answer 8

Hepatocytes.

Question 9

where are secondary bile acids produced?

Answer 9

lumen of small intestine via bacteria.

Question 10

Which form of bile salts are more effective at solubilizing lipids (primary or secondary)

Answer 10

Primary.

Question 11

What is the primarily cation and anion of bile?

Answer 11

Cation = Na
Anion = Cl and HCO3-

Question 12

What is meant by critical micellar concentration?

Answer 12

It is the concentration of bile at which micelle formation begins.

Question 13

True or False. Only newly formed bile is dumped into the bile canaliculi.

Answer 13

False. Both new and the returning bile are dumped in the canaliculi.

Question 14

What are three components of enterohepatic circulation?

Answer 14

1. bile salts are transported from the ileum to the portal blood
2. bile salts goes back to the liver
3. synthesis of new bile salts to replace amount that was lost.

Question 15

Once bile returns back to the liver, how is it taken up into the hepatocytes?

Answer 15

It’s taken up across the the basolateral membrane of the hepatocytes which is mediated by two types of system:

1. Na-dependent transport protein called sodium taurocholate cotransporting polypeptide (NTCP)
2. Na-independent transport protein, organic anion transport protein (OATPs)

Question 16

In the enterohepatic circulation of bile acids, both active and passive transport processes occur. what’s involved in each.

Answer 16

Active: Ileum
Passive: ileum, jejunum, and colon

Question 17

Via negative feedback, bile salts inhibits what enzyme?

Answer 17

Cholesterol 7a-hyroxylase

Question 18

How is bile synthesis affected after an ileal resection?

Answer 18

Ileal resection interrupts the enterohepatic circulation and so bile synthesis is increased up to 10-fold higher than normal.

Question 19

What cells do secretin stimulate which adds volume to the bile?

Answer 19

Secretin sitmulates ducile cells which adds H20 and HCO3- increasing the volume of bile.

Question 20

The content of the bile in the canaliculi resembles what?

Answer 20

Canalicular bile is primarily ultrafiltrate of plasma. electrolyte and water is added to the in the ducts.

Question 21

In what cell/system is bilirubin formed?

Answer 21

In reticuloendothelial system. RBC is taken up the macrophages and broken down releasing Hg which then is converted to biliverdin and then to bilirubin.

Question 22

Once inside the liver, bilirubin is conjugated to what via what enzyme?

Answer 22

UDP glycoronyl transferase adds glucoronic acid to bilirubin = conjugated.

Question 23

What compounds give feces it’s dark color?

Answer 23

Urobilin and stercobilin

Question 24

Why do infants usualy have increased level of unconjugated bilirubin in the blood during the first week of life.

Answer 24

1. UDP glucoronyl transferase, the enzyme that is needed to conjugate bilirubin, is synthesized slowly after birth. bilirubin remains unconjugated until that enzyme is made.
2. Fetal erythrocytes have shorter life span and so that increased breakdown of feltal erythrocytes elevates bilirubin.

Question 25

What are the diseases associated with hereditary defects in bilirubin metabolism.

Answer 25

Crigler-Najjar, Gilbert’s, Dubin-Johnson, Rotar syndomes.

Question 26

WHat kind of jaundice is seen in hemolytic anemia and what is the cause?

Answer 26

Unconjugated jaundice. It’s due to increased breakdown of RBC, and the increased bilirubin level overswhelms the liver’s capacity to produce conjugated bilirubin resulting in elevated unconjugated bilirubin.

Question 27

In Gilbert’s Syndrome, what kind of jaundice is produced and what is the cause?

Answer 27

Increased in unconjugated bilirubin. It’s due to mutation in gene that code for UDP glucoronyltransferase.

Question 28

In Crigler Najjar syndrome, what kind of jaundice is seen? and what is the cause?

Answer 28

INcreased levels of UNconjugated bilirubin. Also due to mutation in gene that code for UDP glucoronyltrransferase just like in Gilbert’s syndrome.

Question 29

Kernicterus is a condition seen in which kind of Jaundice?

Answer 29

Crigler-Najjar syndrome. where unconjugated bilirubin is elevated and it accumulates in the brain and nerve tissues producing kernicterus. Babies will have neurological problems.

Question 30

Phototherapy is a treatment used in what type of Jaundice?

Answer 30

Used in Gilberts and Crigler-Najjar

Question 31

Phenobarbitol is used in patients with what kind of juandice?

Answer 31

Type Crigler-Najjar syndrome

Question 32

In patients with Dubin-Johnson, would you expect to see elevated liver enzymes?

Answer 32

No.

Question 33

What is the cause of Dubin-Johnson syndrome?

Answer 33

Defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile. The mutation is on multidrug resistance protein 2 (MRP2) which is responsible fro transporting bilirubin out of liver cells into bile.

Question 34

Black pigmentation on liver, and mild jaundice throughout life that which may not present until puberty or adulthood, is what kind of jaundice?

Answer 34

Dubin-johnson

Question 35

THis type of jaundie is common in iranian and moraccan jews

Answer 35

Dubin-Johnson

Question 36

What kind of jaundice is Rotor syndrome?

Answer 36

Build up of both unconjugated and conjugated bilirubin in the blodd but majority is conjugated.

Question 37

In Rotor syndrome, gene mutation affects proteins that normally transports bilirubin and other compounds from the blood into the liver to be cleared from the body. What proteins are these?

Answer 37

OATP1b1 and OATP1b3.

Question 38

would you expect to find a pigmented or unpigmented liver in Rotor syndrome?

Answer 38

Liver cells are NOT pigmented in rotor.

Question 39

Explain how phototherapy works. isomers.

Answer 39

Phototherapy works through a process of isomerization that changes trans-bilirubin into the water-soluble cis bilirubin

Question 40

Gallstones occur when there is excess in either 1 and 2.

Answer 40

1. access pigment of bilirubin breakdown or

2. cholesterol

Question 41

In patients with Mirizzi’s syndrome, the gallstones are located where?

Answer 41

Stones in the cystic duct compressing or fistulizing into the commone hepatic duct.

Question 42

Obstruction of which anatomical position with stones will cause acute cholecystitis and is about 10% of all gallstones cases?

Answer 42

stones imparted in cystic duct.

Question 43

One would not expect to see pancreatitis until gallstones block what structure?

Answer 43

Stones at the entrance at diodnum and obstruct pancreatic duct.