2. Highlights of discussion
Introduction
Basic
chemistry of
bilirubin
Bilirubin
metabolism
•Production
•Uptake
•Conjugation
•Excretion
Etiology
•Bilirubin
metabolism
disorders
•Liver disease
•Bile duct
obstruction
Clinical
approach:
History &
examination
Relevant
investigation
s
3. INTRODUCTION
Jaundice, derived from the French word jaune (in 1300 AD), is the yellowish
discoloration of the skin, conjunctivae, and mucous membranes.
The first description of jaundice is mentioned in EBERS PAPYRUS of Egypt
dating to 3000 BC.
Hippocrates theory of 4 humors: Blood, phlegm, yellow bile & black bile
Ayurveda: Gases, bile & phlegm
4. Clinical jaundice: Jaundice detected by physical examination when serum bilirubin > 3mg/dl
Latent jaundice: ↑ serum bilirubin but not detected by physical examination.
5. Bilirubin chemistry
IUPAC name: 1′,8′-dioxo-1,3,6,7-tetramethyl-2,8-
divinylbiladiene-a,c-dipropionic acid
4 pyrrolinone rings
Internal H bond leads to ridge tiling of molecule
producing Z (trans) confirmation
Hence water insoluble
9. Bilirubin metabolism: Hepatocellular uptake
Mode of uptake: Facilitated diffusion
Via unknown transporter (possibly OATP2/OATP
C/SLC21A6)
Transport cannot occur against a concentration
gradient
Bidirectional
10. Bilirubin metabolism: Intracellular binding
Within the hepatocyte, bilirubin is kept in solution by
binding as a non-substrate ligand to intracellular
protein.
Important of those are glutathione-S-transferases
(GST)/Y protein & fatty acid binding protein/Z protein
formerly called ligandins
11. Bilirubin metabolism: Conjugation
Bilirubin is conjugated with one or two glucuronic acid moieties by a specific UDP-
glucuronosyltransferase to form bilirubin monoglucuronide (BMG) and diglucuronide (BDG),
respectively
Significance
• Glucuronide conjugates are highly soluble in water
• Excretion of bilirubin across the bile canalicular membrane into bile
13. Bilirubin metabolism: Biliary excretion
BMD & BDG are excreted into bile canaliculi by MRP2 (gene
symbol ABCC2) on canalicular membrane (ATP dependent)
Portion of CB is transported into the portal circulation by a
sinusoidal membrane protein MRP3 (gene symbol ABCC3)
The sinusoidal conjugates are reuptaken into the hepatocyte
by reuptake transporters OATP1B1 (gene symbol SLCO1B1)
and OATP1B3 (SLCO1B3)
28. Hemolytic Hepatic Obstructive
HISTORY
• Abdominal pain No Yes/No Yes
• Urine colour Normal (Acholuric) Normal to dark Dark (Choluric)
• Stool colour Normal to dark Normal Pale
• Pruritis No Variable Yes
• Other Recent transfusion Prodrome High grade fever
Anemia Toxin/Drug exposure Mass P/A
h/o CTD, Lymphomas BT/HD/High risk behaviour h/o Past abd surgeries
EXAMINATION
Splenomegaly CLD stigmata Abdominal mass
KF ring Surgical scars
Skin hyperpigmentation
Clinical approach
47. Imaging studies: Abdominal US
First line imaging in suspected hepatobiliary disease
Absence of biliary dilatation suggests intrahepatic cholestasis and r/o extrahepatic
cholestasis
• Inexpensive
• Noninvasive & portable
• GB stone readily detected
Advantages:
• Operator dependent
• Distal CBD obscured by bowel gas
• Difficult in obesity
Limitation:
48. Abdominal CT
Permits accurate measurement of the caliber of biliary tree.
Detects intrahepatic SOL as small as 5mm.
• Noninvasive
• Higher resolution than USG
• Not operator dependent
• Superior images in obese persons
Advantages:
• Potential for contrast induced nephrotoxicity,
anaphylaxis
• Ionizing radiation
Disadvantages:
49. Magnetic Resonance Cholangiopancreaticography (MRCP)
Permits rapid clear-cut delineation of the biliary tree.
Superior to conventional ultrasound or CT for detection of biliary tract obstruction.
• Noninvasive
• Imaging of bile ducts superior to ultrasound and CT
Advantages
• May miss small caliber bile duct disease
Disadvantages
50.
51. It shows the abrupt termination of the dilated pancreatic and bile ducts at the level of
the pancreatic head, the classic sign of the presence of a carcinoma of the head of the
pancreas.
52. Endoscopic Retrograde Cholangiopancreaticography (ERCP)
• Permits direct visualization of biliary tract
• Highly accurate in the diagnosis of biliary obstructions
• Simultaneous therapeutic interventions like sphincterotomy,
stricture dilatation & stent placement can be done
• Acquisition of tissue for biopsy & brushings for cytology
Advantages
• Invasive
• Requires sedation
• Cannot be performed if altered anatomy precludes
endoscopic access to ampulla (e.g., Roux-en-Y loop);
• Has complications (e.g., pancreatitis)
Disadvantages
55. Percutaneous Transhepatic Cholangiography (PTC)
Requires the passage of a needle through the skin and subcutaneous tissues into the hepatic
parenchyma and advancement into a peripheral bile duct
When bile aspirated, a catheter is introduced through the needle, and radiopaque contrast
medium is injected
Applicable for lesions proximal to CHD
• Direct imaging of bile ducts
• Simultaneous therapeutic intervention
Advantages
• Difficult with non dilated intra hepatic bile ducts
Disadvantage
57. Endoscopic Ultrasound (EUS)
Can detect obstruction of the bile duct and major intrahepatic bile ducts
• Imaging of bile ducts superior to ultrasound and CT
• Permits needle aspiration of suspected neoplasms
Advantages
• Requires sedation
Disadvantages
58. S/O biliary tract
obstruction
Abdominal US or CT
Dilated bile ducts
ERCP/THC
Non dilated bile
ducts
Clinical likelihood of
biliary obstruction
Instrinsic liver
disease
Consider
MRCP/EUS
High
Intermediate
Low
Yes No
