GI - Pathology (Jaundice & Hereditary hyperbilirubinemias)

Question 1

What defines and causes jaundice?

Answer 1

Abnormal yellowing of the skin and/or sclera due to bilirubin deposition

Question 2

At what levels of bilirubin does jaundice occur? What are 2 general causes of such levels?

Answer 2

Occurs at high bilirubin levels (> 2.5 mg/dL) in the blood secondary to increased production or defective metabolism

Question 3

What is the urine urobilinogen level like in each of the following disorders involving jaundice: (1) Unconjugated (indirect) hyperbilirubinemia (2) Conjugated (direct) hyperbilirubinemia (3) Mixed (direct and indirect) hyperbilirubinemia?

Answer 3

(1) High (2) Low (3) Normal/High

Question 4

What are 4 diseases with unconjugated (indirect) hyperbilirubinemia?

Answer 4

(1) Hemolytic (2) Physiologic (newborns) (3) Crigler-Najjar (4) Gilbert syndrome

Question 5

What are 3 general conditions with conjugated (direct) hyperbilirubinemia? Give at least 2 examples of specific conditions under each general condition.

Answer 5

(1) Biliary tract obstruction: gallstones, pancreatic liver cancer, liver fluke (2) Biliary tract disease: primary slcerosing cholangitis, primary biliary cirrhosis (3) Excretion defect: Dubin-Johnson syndrome, Rotor syndrome

Question 6

What are 2 diseases with mixed (direct and indirect) hyperbilirubinemia?

Answer 6

(1) Hepatitis (2) Cirrhosis

Question 7

What is the pathophysiology of physiologic neonatal jaundice? What are 2 clinical findings that it can cause?

Answer 7

At birth, immature UDP-glucoronosyltransferase => unconjugated hyperbilirubinemia => jaundice/kernicterus

Question 8

What is the treatment for physiologic neonatal jaundice?

Answer 8

Treatment: Phototherapy (converts unconjugated bilirubin to water-soluble form)

Question 9

What are 4 examples of hereditary hyperbilirubinemias?

Answer 9

(1) Gilbert syndrome (2) Crigler-Najjar syndrome, type I (3) Dubin-Johnson syndrome (4) Rotor syndrome

Question 10

What is the pathophysiology of Gilbert syndrome?

Answer 10

Mildly decreased UDP-glucuronosyltransferase conjugation activity => decreased bilirubin uptake by hepatocytes. Elevated unconjuagted bilirubin without overt hemolysis.

Question 11

How common is Gilbert syndrome? What are its physical/clinical findings?

Answer 11

Very common. Asymptomatic or mild jaundice. No clinical consequences.

Question 12

Under what conditions do bilirubin levels increase in Gilbert syndrome?

Answer 12

Bilirubin increased with fasting and stress

Question 13

What causes Crigler-Najjar syndrome (type I)?

Answer 13

Absent UDP-glucoronosyltransferase

Question 14

When does Crigler-Najjar syndrome (type I) present? When do patients die?

Answer 14

Presents early in life; patients die within a few years

Question 15

What are 3 clinical findings associated with Crigler-Najjar syndrome (type I)?

Answer 15

Findings: (1) jaundice, (2) kernicterus (bilirubin deposition in brain), (3) Increased unconjugated bilirubin

Question 16

What is the treatment for Crigler-Najjar syndrome (type I)?

Answer 16

Treatment: plasmapharesis and phototherapy

Question 17

How does Criger-Najjar syndrome type II compare to type I in terms of severity and treatment?

Answer 17

Type II is less severe and responds to phenobarbital, which increases liver enzyme synthesis

Question 18

What is the defect of Dubin-Johnson syndrome, and what effect does it have?

Answer 18

Conjugated hyperbilirubinemia due to defective liver excretion

Question 19

What is the characteristic finding of Dubin-Johnson syndrome? Is it a benign or malignant syndrome?

Answer 19

Grossly black liver. Benign.

Question 20

How does Rotor syndrome compare to Dubin-Johnson syndrome?

Answer 20

Rotor syndrome is similar but even milder and does not cause black liver

Question 21

What is the defect in Gilbert syndrome, and what effect does it have?

Answer 21

Gilbert = problem with bilirubin uptake => unconjugated bilirubin

Question 22

What is the defect in Crigler-Najjar syndrome, and what effect does it have?

Answer 22

Crigler-Najjar = problem with bilirubin conjugation => unconjugated bilirubin

Question 23

What is the defect in Dubin-Johnson, and what effect does it have?

Answer 23

Dubin-Johnson = problem with excretion of conjugated bilirubin => conjugated bilirubinemia

Question 24

What effect does Rotor syndrome have?

Answer 24

Rotor = mild conjugated hyperbilirubinemia

Question 25

Draw a model demonstrating the major steps in the processing of bilirubin, noting the steps compromised in each of the following hereditary hyperbilirubinemias: (1) Gilbert (2) Crigler-Najjar (3) Dubin-Johnson (4) Rotor.

Answer 25

See p. 364 in First Aid 2014 for visual at bottom left