JAUNDICE

Question 1

Definition

Answer 1

Elevated total bilirubin, leading to yellow discoloration of the skin and sclera when it exceeds 3mg/dL (50 micromole/L). (unconj>2.5)

Question 2

Bilirubin metabolism and the Enterohepatic circulation (4)

Answer 2

1- Senescent RBCs are destroyed by macrophages in the reticuloendothelial system; the end-product of heme metabolism is unconjugated bilirubin, a lipid soluble product, hence, it is transported in serum bound to albumin
2- Bilirubin is then conjugated in the liver by uridine glucoronosyltransferase, which is water soluble
3- Conjugated bilirubin is secreted into the biliary tree, eventually reaching the common bile duct, which empties into the duodenum. Intestinal bacteria convert conjugated bilirubin into urobilinogen, which is spontaneously oxidized into urobilin and stercobilin giving stool its color
4- In the terminal ileum, where bile is reabsorbed, urobilinogen is reabsorbed; most of it goes back to the liver through the portal circulation, and some of it is excreted in the urine

NOTE: UNconjugated = INdirect = water INsoluble

Question 3

Classification of Jaundice (3)

Answer 3

1- Pre-hepatic/Acholuric: Increased unconjugated bilirubin
- Hemolytic: dark urine, dark stool, high AST
- Congenital: Gilbert syndrome, Crigler-Najjar syndrome
- Neonatal (destruction of fetal hemoglobin)
2- Heaptic/Hepatocellular = HEPATITIS: Increase in BOTH conjugated and unconjugated bilirubin
- High ALT and AST
- Dark urine
3- Post-hepatic/Obstructive/Surgical/Painful: Increased conjugated bilirubin
- High ALP and GGT&raquo_space; AST and ALT
- Dark urine, clay colored stool, pruritis, and nausea
- Decreased intra-hepatic flow:
- Primary biliary cirrhosis, Dubin-Johnson syndrome, Rotor syndrome, drug induced (OCP)
- Decreased extra-hepatic flow:
- Gallstones, tumor of head of pancreas, periampullary tumors

Question 4

Investigations (6)

Answer 4

1- Liver biochemistry:
- AST and ALT indicate hepatocellular damage
- ALT is more specific to the liver
- Usually ALT > AST in liver disease (e.g. viral, fatty, etc)
- If AST > ALT: alcohol-induced hepatitis or cirrhosis
- GGT & ALP: indicate cholestasis
2- Liver ultrasound
3- Liver function
- Albumin: if low, think of liver failure
- Prothrombin time/INR: if prolonged, think of liver failure
4- Virology screen: hepatotropic viruses
5- Antibodies:
- Anti-smooth muscle antibodies = autoimmune hepatitis
- Liver/kidney microsomal antibodies = autoimmune hepatitis
- Anti-mitochondrial antibodies = primary biliary cirrhosis
- Anti-neutrophilic cytoplasmic antibodies = primary sclerosing cholangitis
6- IgGs:
- IgG: autoimmune hepatitis
- IgA: alcohol-induced hepatitis
- IgM: primary biliary cirrhosis

Question 5

Type of Bilirubin elevated

Answer 5

Pre-hepatic: Uncojugated
Hepatic: Both
Post-hepatic: Conjugated

Question 6

Urine (conjugated bilirubin - urobilinogen - bile salts)

Answer 6

Pre-hepatic: Absent / +++ / Absent
Hepatic: ++ / + early, - obstructive / +
Post-hepatic: +++ / Absent / ++

Question 7

Urine color

Answer 7

Pre-hepatic: Dark
Hepatic: Dark
Post-hepatic: Dark

Question 8

Stool color

Answer 8

Pre-hepatic: Dark
Hepatic: Normal
Post-hepatic: Pale

Question 9

AST and ALT

Answer 9

Pre-hepatic: Normal
Hepatic: Very high
Post-hepatic: High

Question 10

ALP and GGT

Answer 10

Pre-hepatic: Normal
Hepatic: High (2-3x normal)
Post-hepatic: High (10-12x normal)