7. Hepatobiliary Function

Question 1

What is the cause of Gilbert’s syndrome?

Answer 1

Mutation in UDP glucuronyl transferase.

Usually results in UDP glucuronyl transferase activity to about 30% of normal.

Question 2

What is usually indicated by elevated serum aminotransferases (ALT/AST)?

Answer 2

Damage to hepatocytes.

Question 3

What is the effect of liver damage on prothrombin time?

Answer 3

Prothrombin time increases due to a lack of hepatic coagulation factors.

Question 4

What five things, discussed in class, can lead to pigment or cholesterol gallstones?

Answer 4

Too much absorption of water from bile.

Too much absorption of bile acids from bile.

Too much cholesterol in bile.

Too much bilirubin in bile (hemolytic anemia).

Inflammation of epithelium.

Question 5

What are the sodium dependent and sodium independent transporters for bile salts on the basolateral side of hepatocytes?

Answer 5

Sodium dependent: sodium taurocholate cotransporting polypeptide (NTCP).

Sodium independent: organic anionic transport proteins (OATPs)

Question 6

Which two transporters of the enterohepatic circulation are sodium dependent, and what spaces do they move bile acids between?

Answer 6

Sodium dependent taurocholate cotransporting polypeptide (NTCP) – from the portal circulation into the hepatocytes.

Apical sodium dependent bile acid transporter (ASBT) – from the intestinal lumen into the enterocytes.

Question 7

What serum aminotransferases are tested as liver function enzymes?

Answer 7

Alanine aminotransferase.

Aspartate aminotransferase.

Question 8

When bilirubin is produced by the reticular endothelial system, it is not water soluble. How does it get to the liver?

Answer 8

Through attachment to albumin.

Question 9

What is the main issue in Dubin-Johnson syndrome?

Answer 9

Increase in serum conjugated bilirubin due to a malfunctioning multidrug-resistant protein 2 (MRP2).

This prevents hepatocytes from being able to secrete bilirubin into the bile canaliculi.

Question 10

What is the primary issue in Rotor syndrome?

Answer 10

Defective OATPs, resulting in an inability to transfer conjugated bilirubin into the hepatocytes from the blood

Question 11

What are the five given treatments for Crigler-Najjar syndrome?

Answer 11

Phototherapy.

Blood transfusions.

Oral calcium phosphate and carbonate.

Liver transplant (some type I patients).

Phenobarbital (type II patients only).

Question 12

How is unconjugated bilirubin neurotoxic?

Answer 12

It upregulates apoptotic events in the neurons, astrocytes, microglia, and oligodendrocytes.

Question 13

How does the amount of bile acid in the portal system regulate the amount of bile acid produced by the liver?

Answer 13

Bile acids inhibit the action of cholesterol 7alpha-hydroxylase – the rate limiting step in bile acid synthesis.

Question 14

What four things, discussed in class, can occur as sequelae to cirrhosis of the liver?

What dysfunction of the liver causes the symptoms?

Answer 14

Ascites – lack of albumin, decreased oncotic pressure.

Hepatic encephalopathy – lack of urea processing.

Bruising – lack of coagulation factors.

Portal hypertension – due to the fibrotic liver.

(Portal hypertension causes caput medusae and esophageal varices)

Question 15

How does conjugated bilirubin get to the small intestine?

Answer 15

Via the common bile duct with the bile.

Question 16

Conjugated bilirubin that passes into the small intestine will undergo a series of steps before it is excreted into the feces. What is responsible for the occurrence of these steps, and what are the intermediates?

Answer 16

The bacteria of the small intestine are responsible for the steps, they unconjugate the bilirubin into urobilinogen.

Conjugated bilirubin -> Urobilinogen -> urobilin + stercobilin -> excretion through the feces.

Question 17

When urobilinogen arrives in the kidneys to be excreted through the urine, what intermediate does it become before it is excreted?

Answer 17

Urobilin.

Question 18

How is phototherapy effective for reducing serum bilirubin in neonates?

Answer 18

Exposure of light with a wavelength of approximately 459 nm causes trans-bilirubin to isomerized into the water-soluble form cis-bilirubin.

Question 19

If urobilinogen does not continue along its path to be excreted into the feces, what other options does it have to leave the small intestine?

Answer 19

Enter the enterohepatic circulation and be returned to the liver.

Question 20

What transporter transports bile acids from the enterocytes into the portal circulation?

Answer 20

Organic solute transporter alpha/beta (OSTalpha/OSTbeta)

Question 21

Where are bile acids reabsorbed in enterohepatic recirculation?

Answer 21

In the distal ileum.

Question 22

What are the two main causes for physiological neonatal jaundice?

Answer 22

Increased bilirubin production, due to the shortened life span of fetal erythrocytes.

Decreased UDP glucuronyl transferase activity as it ramps up slowly after birth.

Question 23

What are the two bile acid transporters that move bile acids from the hepatocytes into the bile canaliculi?

Answer 23

Bile salt excretory pump (BSEP).

Multidrug-resistant protein 2 (MRP2).

Question 24

What are the “bile acid -dependent” portions of bile?

What are the “bile acid-independent” portions of bile?

Answer 24

Bile acid -dependent: bile acids, cations, water from the liver.

Bile acid-independent: bicarbonate from the pancreas, water from the pancreas.

Question 25

Do Gilbert’s syndrome and Crigler-Najjar syndrome cause conjugated or unconjugated jaundice?

Answer 25

Both cause unconjugated jaundice due to dysfunction of UDP glucuronyl transferase.

Question 26

What is the basic issue in Crigler-Najjar syndrome type II?

When do symptoms typically present?

Answer 26

<20% function of UDP glucuronyl transferase.

Much later in life.

Question 27

What diseases discussed can lead to conjugated bilirubinemia?

Answer 27

Dubin-Johnson syndrome.

Rotor syndrome.

Biliary tree obstruction.

Question 28

In which disease discussed does the liver have a black pigmentation?

Answer 28

Dubin-Johnson syndrome.

Question 29

What is the main transporter that moves bile salts from the lumen of the intestine into the enterocytes?

Answer 29

Apical sodium-dependent bile transporter (ASBT)

Question 30

Once bilirubin gets to the liver, it needs to be conjugated. What enzyme performs this function?

Answer 30

UDP glucuronyl transferase.

Question 31

What is the pathological cause of symptoms from Crigler-Najjar syndrome type I?

When do symptoms typically present?

Answer 31

Complete loss of function of UDP glucuronyl transferase.

Immediately after birth.

Question 32

What is usually indicated by elevated alkaline phosphatase?

Answer 32

Bile duct injury.

Question 33

What is the intermediate between hemoglobin and bilirubin?

Answer 33

Biliverdin

Question 34

What are the two types of gallstones?

Answer 34

Pigment gallstones.

Cholesterol gallstones.

Question 35

What is kernicterus?

Answer 35

Kernicterus is a neurologic sequelae of bilirubin-induced neurologic dysfunction.

Clinical features include cerebral palsy, sensorineural hearing loss, and gaze abnormalities.