7. Hepatobilliary Function

Question 1

How can liver failure lead to edema

Answer 1

• Liver synthesizes almost all plasma proteins

- Liver failure can result in hypoalbuminemia that can lead to edema

Question 2

What is liver Cirrhosis

Answer 2

Chronic liver disease in which normal liver cells are damaged and replaced by scar tissue
-alcohol abuse leads to accumulation of fat within hepatocytes

Question 3

What changes to venous circulation are associated with portal hypertension

Answer 3

Esophageal varices: swollen connection between systemic and portal systems at inferior end of esophagus
Caput Medusae: swollen connections between systemic and portal systems around umbilicus

Question 4

How can liver dysfunction lead to hepatic encephalopathy

Answer 4

Decreased hepatic urea cycle metabolism in the context of liver cirrhosis or portosystemic shunting leads to accumulation of ammonia in the systemic circulation
(ammonia readily crosses the blood-brain barrier)

Question 5

What are the relative amounts of the four bile acids

Answer 5

Most to least

Cholic Acid > Chenodeoxycholic Acid > Deoxycholic Acid > Lithocholic Acid

Question 6

What role does CCK play in bile secretion

Answer 6

CCK-induced gallbladder contraction and sphincter of Oddi relaxation

Question 7

What happens to bile flow between periods of digestion

Answer 7

Gallbladder fills with bile

• Gallbladder is relaxed
• Sphincter of Oddi is closed

Question 8

How are bile salts recirculated

Answer 8

Enterohepatic Circulation

• bile salts are transported from the ileum to the portal blood
• bile salts back to liver
• synthesis of bile salts to replace the amount that was lost

Question 9

Within the enterohepatic circulation what two systems are used to uptake bile salts across the BASOLATERAL membrane of the HEPATOCYTES

Answer 9

• Sodium Dependent (NTCP)

- Sodium Independent (OATPs)

Question 10

What highly efficient system is responsible for more than 90% of the bile acids returning to the portal blood

Answer 10

Ileal transport process

Question 11

What is inhibited by bile salts and helps the negative feedback on bile synthesis

Answer 11

Cholesterol 7alpha-hydroxylase

Question 12

What procedure can reduce bile secretion

Answer 12

Ileal resection

Question 13

What is Icterus

Answer 13

Jaundice- hyperbilirubinemia

Question 14

What known hereditary defects cause UNCONJUGATED Jaundice

Answer 14

Gilbert’s Syndrome

Crigler-Najjar Syndrome (1 and 2)

Question 15

What known hereditary defects cause CONJUGATED Jaundice

Answer 15

Dubin-Johnson

Rotor Syndromes

Question 16

What effect does Hemolytic Anemia have on bilirubin

Answer 16

Increased production of bilirubin overwhelms liver’s capacity to produce conjugated bilirubin which results in INCREASED UNCONJUGATED BILIRUBIN

Question 17

What is physiological neonatal jaundice

Answer 17

Increase in Unconjugated Bilirubin in blood during the first week postnatal age

Caused by

• shortened lifespan of fetal erythrocytes
• low activity of UDP glucuronyl transferase

Question 18

Summarize Gilbert Syndrome

Answer 18

• High levels of UNCONJUGATED Bilirubin in the blood
• Mutation in gene that codes for UDP Glucuronyltransferase
• UGT1A1 activity level is 30% of normal

Question 19

Summarize Crigler-Najjar Syndromes

Answer 19

• High levels of UNCONJUGATED bilirubin in the blood
• Nonhemolytic jaundice
• Mutations in gene related to UDP Glucuronyltransferase
• Type 1 VERY SEVERE

Question 20

What is special about Type 1 Crigler-Najjar

Answer 20

No function in UDP glucuronyltransferase

Kernicterus- brain damage caused by accumulation of unconjugated bilirubin in the brain and nerve tissue

Question 21

What is Kernicterus

Answer 21

Permanent neurologic sequelae of bilirubin-induced neurologic dysfunction

Question 22

Summarize Dubin-Johnson

Answer 22

• Increase in CONJUGATED Bilirubin
• Mutations for gene that encodes the multidrug resistance-associated protein 2 (MRP2)
• Liver has BLACK pigmentation

Question 23

Summarize Rotor Syndrome

Answer 23

• Build up of both unconjugated and conjugated bilirubin but MAJORITY IS CONJUGATED
• Gene mutation causing nonfunctional OATP1B1 and OATP1B3 proteins or an absence of these proteins
• Liver cells are not pigmented

Question 24

What is the primary treatment in neonates with unconjugated hyperbilirubinemia

Answer 24

Phototherapy

Question 25

What are treatments for Crigler-Najjar Syndrome

Answer 25

• Phototherapy
• Blood Transfusions
• Oral calcium phosphate and carbonate
• Liver transplant (type 1)
• Phenobarbitol (type 2 only)

Question 26

What biochemical tests are done to test liver function

Answer 26

Liver enzymes- commonly measured in the serum (ALT, AST and aminotransferases)
Bilirubin
Albumin
PT

Question 27

What do elevated aminotransferases and elevated alkaline phosphatase suggest

Answer 27

Aminotransferase- result of hepatocyte injury

Alkaline phosphatase- result of bile duct injury (cholestasis)

Question 28

What do bilirubin, albumin and PT test tell us

Answer 28

Bilirubin- measure liver’s ability to detoxify metabolites and transport organic ions into bile
Albumin- severe impairment of hepatocyte function decreases albumin in the plasma
PT- reflects the degree of hepatic synthetic dysfunction