Hepatobiliary Function

Question 1

What is cirrhosis caused by? (general)

Answer 1

Damage to liver where normal cells are replaced by scar tissue. Causes liver to no longer have that open, easy contact with the blood.

Question 2

What is portal hypertension?

Answer 2

An increase in resistance to portal flow, caused usually by cirrhosis.

Question 3

What two changes do you see from portal HTN?

Answer 3

• caput medusae

- esophageal varices

Question 4

What causes hepatic encephalopathy?

Answer 4

Impairment of urea cycle metabolism leading to increased ammonia, which can easily cross blood-brain-barrier and alter brain function.

Question 5

What is the relative amount of the 4 bile acids?

Answer 5

cholic acid > chenodeoxycholic acid > deoxycholic acid > lithocholic acid

Question 6

What two mechanisms do bile secretion occur via?

Answer 6

• Passive movement of cations into canaliculus

- Stimulated by secretin via secretion of HCO3- and H20 from ductule cells

Question 7

What two systems mediate the uptake of bile salts?

Answer 7

• Na-dependent transport protein (NTCP)

- Na- INDEPENDENT transport protein (OATP)

Question 8

What two transport proteins carry bile salts into the bile canaliculi?

Answer 8

• BSEP (bile salt excretory pump)

- MRP2 (Multidrug resistant protein 2)

Question 9

What condition can hemolytic anemia cause? Why?

Answer 9

• jaundice

- b/c liver is overwhelmed by bilirubin spilling out of destroyed RBCs, get an increase in unconjugated bilirubin

Question 10

What causes neonatal jaundice? (2)

Answer 10

• fetal erythrocytes dying (shorter lifespan)

- less active UDP glucuronyl transferase

Question 11

What does Gilbert syndrome cause? Why? How severe is the illness?

Answer 11

• increased levels of unconjugated bilirubin?
• decreased activity of gene that codes for UDP glucuronyltransferase (UGT1A1)
• it is a mild illness. Don’t usually notice it unless under physiological stress

Question 12

What does Crigler-Najjar syndrome cause? Why? How severe is it?

Answer 12

• increased levels of unconjugated biliruben
• mutation in gene that codes for UDP glucuronyltransferase, leads to less/no function (type 2 vs type 1)
• It can be severe depending on if the enzyme functions not at all (type 1) or has decreased function (type 2)

Question 13

What symptoms can Crigler-Najjar syndrome type 1 cause?

Answer 13

Kernicterus - where unconjugated biliruben concentrates in brain tissues (basal ganglia most specifically)

Question 14

What are the treatments for Crigler-Najjar? (5)

Answer 14

• phototherapy (up to age 4)
• blood transfusions
• oral calcium phosphate and carbonate (complexes w/bilirubin in gut)
• liver transplant (for type 1)
• phenobarbitol (type 2)

Question 15

What does Dubin-Johnson syndrome cause? Why? How severe is it?

Answer 15

• increased levels of conjugated bilirubin
• caused by mutations in gene that code for MRP2, so hepatocytes can’t secrete conjugated bilirubin
• is not very severe

Question 16

What are the symptoms of Dubin-Johnson syndrome?

Answer 16

• mild jaundice through life

- BLACK LIVER

Question 17

What does rotor syndrome cause? Why? How severe is it?

Answer 17

• causes buildup of both conj/unconj bilirubin in blood, though MOST is conjugated
• b/c of gene mutations in gene that codes for OATP1B1/P1B3, leading to absence/nonfunctional proteins
• similar to Dubin-Johnson, but without black liver… not super severe

Question 18

How does phototherapy work?

Answer 18

It converts the trans-bilirubin to cis-bilirubin, making it water-soluble.