Hepatobiliary Function

Question 1

Cirrhosis

Answer 1

Scarring of liver tissue.

Can be due to EtOH –> accumulation of fat in hepatocytes –> steatohepatitis –> cirrhosis.

Question 2

How can cirrhosis cause portal HTN?

Answer 2

Increase the resistance to portal blood flow.

Question 3

Esophageal varices

Answer 3

Swollen connection between systemic and portal systems at the inferior part of the esophagus.

Question 4

Caput medusae

Answer 4

Swollen connections between systemic and portal systems around the umbilicus.

Question 5

How can liver dysfunction lead to hepatic encephalopathy?

Answer 5

In cirrhosis there is decreased hepatic urea cycles metabolism. This leads to accumulation of ammonia in systemic circulation and can cross the BBB.

Question 6

2 main functions of bile

Answer 6

Helps eliminate substances from body.

Emulsifies fats.

Question 7

Primary bile salts are produced in:
Secondary bile salts are produced in:
Bile salts are conjugated in:

Answer 7

1 - Liver
2 - SI (intestinal bacteria)
3 - Liver

Question 8

Relative amounts of the 4 bile acids

Answer 8

Cholic acid > chenodeoxycholic acid > deoxycholic acid > lithocholic acid

Question 9

What occurs with bile at the duodenum, jejunum, and ileum?

Answer 9

Bile is release into the 2nd part pf the duodenum.
Micelles are formed and fat is absorbed at the jejunum.
Bile acids are reabsorbed at the ileum.

Question 10

Mechanism of bile secretion and absorption

Answer 10

CCK stimulates secretion of bile from Gb and through sphincter of oddi and into the duodenum.
Bile is transformed to bile salt in the jejunum.
Bile salts enter portal circulation from the ileum and arrive at the liver.

Question 11

What 2 systems control uptake of bile salts across the basolateral membrane of hepatocytes?

Answer 11

NTCP

OATP

Question 12

Which 2 transporters regulate the uptake of bile salts into the bile canaliculus?

Answer 12

bsep
mrp2
*Both require ATP

Question 13

What system regulates uptake of bile acids on the luminal side.

Answer 13

ASBT

Question 14

How much bile is recycled? How much is excreted in feces?

Answer 14

90% recycled and approx 5% excreted in blood

Question 15

Recycling of bile salts is done actively or passively?

Answer 15

Both

Question 16

What happens to the rate of bile synthesis as bile secretion increases?

Answer 16

It decreases.

Question 17

What molecule is inhibited by bile salts?

Answer 17

Cholesterol 7a-hydroxylase

Question 18

What happens when enterohepatic circulation is disrupted?

Answer 18

It can dramatically increase bile synthesis

Question 19

CCK mediates what 2 functional features of the Gb?

Answer 19

Contraction of the Gb

Relaxation of the sphincter of oddi.

Question 20

What enzyme catalyzes bilirubin –> conjugated bilirubin in the liver?
What’s unique about it?

Answer 20

UDP glucuronyl transferase.

It issynthesized slowly after birth, so some newborns can develop jaundice.

Question 21

What 2 molecules give stool a dark color?

Answer 21

Urobilin and stercobilin

Question 22

Jaundice (icterus)

Answer 22

Hyperbilirubinemia.

Yellowed sclera, skin and mucous membranes.

Question 23

Hemolytic anemia

Answer 23

Anemia due to hemolysis, which can lead to increased bilirubin production. The increased bilirubin overwhelms the liver, which cannot conjugate it all. This leads to an increase in unconjugated bilirubin.

Question 24

Physiological jaundice:

What 2 things can cause it?

Answer 24

Increased unconjugated bilirubin during 1st week.
Increased breakdown of RBCs –> increase in bilirubin.
Low activity of UDP glucuronyl transferase.

Question 25

Gilbert syndrome

Answer 25

Increased unconjugated BR.
Usually asymptomatic, but can have episodes when stressed, drinking, etc.
Mutation in gene that codes for UDP glucuronyl transferase (activity is about 30% of normal).

Question 26

Crigler-Najjar syndrome type 1

Answer 26

Starts early in life.
No function of UDP glucuronyl transferase.
Kernicterus (brain damage from increased unconjugated BR)

Question 27

When does kernicterus develop?

What are some clinical features?

Answer 27

During 1 yr postnatally.

Cerebral palsy, hearing loss, gaze abnormalities.

Question 28

Crigler-Najjar syndrome type 2

Answer 28

Starts later in life.
Less than 20% fxn of UDP glucuronyl transferase.
Less likely to cause kernicterus.
Most survive to adulthood.

Question 29

TTMs for Crigler-Najjar (5)

Answer 29

Phototherapy (does not work after 4 y/o)
Blood transfusions
Oral Calcium phosphate and carbonate (form complexes w/ BR in gut)
Liver transplant (type 1)
Phenobarbitol (type 2 only)

Question 30

Dubin-Johnson

Answer 30

Increased BR w/o elevation of liver enzymes.
Defect in hepatocytes’ ability to secrete conjugated BR.
Mutations in MRP2.
Mild jaundice throughout life.
Liver has black pigmenting.

Question 31

Rotor syndrome

Answer 31

Build up of both BRs but mostly conjugated.
Similar to D-J.
Mutations leading to short/nonfxnl OATP1B1 and OATP1B3 proteins.
Liver is not pigmented.

Question 32

What is the primary TTM for a neonate with unconjugated hyperbilirubinemia?
What should the serum level of UBR be?
How does it work?

Answer 32

Phototherapy.
> 21 mg/dL
Changes the trans-BR into water-soluble cis-BR (isomerization).

Question 33

4 mechanisms that Gallstones (Cholelithiasis)

Answer 33

Too much absorption of water from bile.
Too much absorption of bile acids from bile.
Too much cholesterol in bile.
Inflammation of epithelium.

Question 34

3 locations for gallstones and associated pain

Answer 34

Stones that stay in the Gb: usually asymptomatic (75%)
Cystic duct intermittently blocking: intermittent pain (20%)
Cystic duct lodged in cystic duct: acute cholecystitis (10%)
Distal bile duct blockage: jaundice, pain, risk of pancreatitis (5%)

Question 35

Liver function test (LFT)

Answer 35

Not the most precise measure.
Can be abnormal even in pts with a healthy liver.
Include biochemical and functional tests.

Question 36

Liver enzymes commonly measured (3)

Answer 36

ALT
AST
Alkaline phosphatase

Question 37

Elevated aminotransferases (AST/ALT) suggests:

Answer 37

Hepatocyte injury

Question 38

Elevated alkaline phosphatase suggests:

Answer 38

Bile duct injury

Question 39

3 functional tests of the LFTs and what do they suggest if abnormal?

Answer 39

BR: measures liver’s ability to detox metabolites and transport anions into bile.
Albumin: impairment of hepatocyte function.
Prothrombin time (PT): hepatic synthetic dysfunction.

Question 40

Phase I and Phase II of drug metabolism

Answer 40

Phase I: drugs processed via cytochrome P450.

Phase II: conjugation via glucoronide, sulfate, AAs, glutathione.