Jaundice

Question 1

Jaundice?

Answer 1

yellow/green appearance to the skin & eyes (Icterus) produced by increased serum bilirubin
- Usually given in a direct/total relationship

Question 2

Normal bilirubin ranges?

Answer 2

• ranges 0.5 to 1.0 mg/dl.
• Levels >3.0 mg/dl to be clinically jaundiced
  N.B. the Newborn period is the exception

Question 3

Describe bilirubin metabolism?

Answer 3

1. Red cells (Heme) break down forming biliverdin (bile pigment)
   - This is unconjugated (indirect bilirubin).
2. It is transported by albumin & is not soluble - No Bilirubin in the urine
3. The bile pigment is converted to conjugated (Direct bilirubin) by the Kupffer cells of the liver.
4. In the liver, the bilirubin is conjugated
   with UDPglucuronate, making it water-soluble Bilirubin diglucuronide
   i.e. (“direct” conjugated bilirubin).
   - This is soluble & only shows up in blood & urine with obstruction in the system

Question 4

Describe Bilirubin conjugation?

Answer 4

1. In the terminal ileum the bilirubin is converted to stercobilinogen & urobilinogen by natural bacteria
2. Conjugated bilirubin is excreted into the bile and passed into the intestine where it is further metabolised
   - urobilinogen ->urobilin-> stercobilin, which colors the feces brown
   - Some is reabsorbed and returned to the liver
3. Some urobilinogen is found in the urine
4. If excretion of conjugated bilirubin is hindered, it is excreted by the kidney

Question 5

Causes of Pre-hepatic jaundice?

Answer 5

hemolytic disease

Question 6

Causes of Post-hepatic jaundice?

Answer 6

1. Hepatitis
2. Drug induced hepatitis
3. Cirrhosis

Question 7

Causes of Obstructive jaundice?

Answer 7

1. gallstones
2. pancreatic cholangio carcinoma
3. liver fluke - schistosomiasis

Question 8

Consequences of obstructive jaundice?

Answer 8

1. Obstruction of biliary system prevents production of urobiligen & stercobilinogen
2. Stool is light and urine is dark showing bilirubin

Question 9

Classification of hyperbilirubinemia?

Answer 9

1. Increased bilirubin production
2. Decreased bilirubin uptake by the liver
3. Impaired conjugation in the liver
   - unconjugated (indirect) = normal stool and urine color
4. Decreased excretion of bilirubin into the bile (cholestasis)
   - conjugated bilirubin (direct) with dark urine and light stool color

Question 10

Causes of unconjugated (indirect) hyperbilirubinemia?

Answer 10

1. Due to overproduction
2. decreased hepatic uptake
3. decreased conjugation of bilirubin

Question 11

Causes of over production of unconjugated bilirubin?

Answer 11

1. secondary to hemolysis (autoimmune)
2. ineffective erythropoiesis (megablastic anemia)
3. increase RBC fragility/turnover (2,3 DPG deficiency)

Question 12

Causes of impaired hepatic uptake of UB leading to hyperbilirubinemia?

Answer 12

1. Gilbert’s syndrome
2. certain drugs such as rifampin, anesthetics & radiographic dyes

Question 13

Causes of impaired conjugation that lead to UB hyperbilirubunemia?

Answer 13

1. Hepatocellular disease
2. drug inhibition such as chloramphenicol, anabolic steroids
3. genetic disorders such as Gilbert’s syndrome or Crigler- Najjar syndrome (decreased UDP-glucuronyl transferases).

Question 14

What is the most common cause of jaundice?

Answer 14

neonatal jaundice

Question 15

What makes newborns susceptible to having jaundice?

Answer 15

They do not have a significant quantity of glucouronyl transferase (the enzyme used for conjugation), due to enzyme immaturity, but kicks in within a few weeks

Question 16

What is kernicterus?

Answer 16

• is a type of brain damage caused by build up in unconjugated bilirubin in the brain
• that causes athetoid cerebral palsy and hearing loss
• It also causes problems with vision and teeth and sometimes can cause mental retardation

Question 17

How to treat neonatal jaundice?

Answer 17

UV light is used to isomerize the bilirubin, which prevents it from crossing the blood-brain barrier.

Question 18

What causes neonatal jaundice?

Answer 18

1. Rh disease/ABO incompatibility is hemolytic
2. impaired hepatic intake

Question 19

Causes of conjugated (direct) hyperbilirubinemia?

Answer 19

1. Altered biliary drainage
2. impaired hepatic excretion of bile
3. extra hepatic obstructions
4. cholestatic jaundice

Question 20

Causes of altered biliary drainage of bile leading to CB hyperbilirubinemia?

Answer 20

1. TPN, cholestasis, drugs
2. hepatocellular disease
3. cirrhosis
   Note:
   - May occur in setting of cholestasis with impaired formation or excretion of all components of bile or hepatocellular injury independent of cholestasis.
   - May indirectly cause increase in unconjugated also if severe enough

Question 21

Causes of impaired hepatic excretion that leads to CB hyperbilirubenemia?

Answer 21

1. intrahepatic cholestasis
2. Dubin-Johnson syndrome & all disorders in the transport of conjugated bile from the hepatocytes to intrahepatic bile ducts.
3. Drug-induced cholestasis
   - phenothiazines, OCP’s & methyltestosterone

Question 22

Extra hepatic causes of CB hyperbilirubinemia?

Answer 22

1. Gallstones
2. pancreatic/biliary obstructive tumors and strictures
3. biliary atresia

Question 23

Characteristic features of conjugated hyperbilirubinemia?

Answer 23

Dark brown or green urine implies conjugated hyperbilirubinemia

Question 24

What is cholestatic jaundice?

Answer 24

Increased alk phos to 3-4 times normal.

Question 25

Features of cholestatic jaundice?

Answer 25

1. Hypercholesterolemia 2. pruritus 3. malabsorption of fat & fat-soluble vitamins 4. Minimal or marked evidence of liver cell damage.

Question 26

How do you diagnose conugated hyperbilirubinemia?

Answer 26

through history 1. pale stools & pruritus--> cholestasis. 2. nausea--> gallstones = biliary obstruction. 3. Inquire about drugs & alcohol use, risks for viral hepatitis & pre-existing liver disease.

Question 27

Laboratory Diagnosis of conjugated hyperbilirubinemia?

Answer 27

1. biliary obstruction: <5-10 fold increase in transaminases & >2-3x normal alk phos. 2. Hepatocellular disease: >10-15 fold increase in transaminases & < 2-3x normal alk phos.

Question 28

Disorders of the biliary system?

Answer 28

1. sepsis 2. post-op jaundice 3. hepatocellular disease - hepatitis, cirrhosis 4. extrahepatic biliary obstruction

Question 29

Diagnosing sepsis?

Answer 29

1. mainly gram-negative organisms. 2. Mildly elevated serum alk phos

Question 30

Diagnosing post-op jaundice?

Answer 30

1. happens 1-10 days post-op 2. 15% incidence following heart/ 1% elective abdominal surgery 3. Increased alk phos & minimally elevated levels of transaminases 4. Secondary to anesthesia side effects

Question 31

Diagnosing hepatocellular disease?

Answer 31

elevated transaminases, prolonged PT, hypoalbuminemia & clinical features of hepatic dysfunction.

Question 32

Diagnosing extrahepatic biliary obstruction?

Answer 32

1. obstruction of extra hepatic bile ducts--gallstones, neoplasias, bile duct strictures, chronic pancreatitis. 2. Clay-colored stools.

Question 33

Name Special diagnostic procedures in cholestatic jaundice?

Answer 33

1. Extra hepatic obstruction - CT or U/S to determine stone or bile duct dilation. 2. Bile duct dilation - endoscopic retrograde cholangiography (ERCP) for management & treatment. 3. Liver biopsy - for determining cause of intrahepatic cholestasis