Case 6 - Bilirubin workshop

Question 1

elevated bilirubin produces a highly visible symptom, which is?

Answer 1

jaundice - yellowing of the skin and sclera of eyes

Question 2

what is bilirubin?

Answer 2

A yellow pigment resulting from the breakdown of haem (from haemoglobin in red blood cells).
Exists as either conjugated or unconjugated bilirubin

Question 3

conjugated bilirubin is soluble in what, and unconjugated bilirubin is soluble in what?

Answer 3

Unconjugated bilirubin is very lipid soluble but water insoluble
Conjugated bilirubin is water soluble (→ so easy for body get rid of it)

[Unconjugated = indirect, not water-soluble
Conjugated = direct, excreted in urine]

Question 4

bilirubin is normally excreted in what?

Answer 4

Normally excreted in bile and urine.

Question 5

bilirubin in stool and urine?

Answer 5

Gives stool its brown colour and contributes to the yellow tinge of urine.

Question 6

name Key Pre-Analytical Variables for Bilirubin

Answer 6

Exposure to light
Delay in processing
Haemolysed sample
Improper storage temperature
Incorrect tube type
Inadequate mixing or volume

Question 7

name the patterns of Hyperbilirubinaemia

Answer 7

Unconjugated ↑
Conjugated ↑
Mixed

Question 8

likely cause of unconjugated Hyperbilirubinaemia

Answer 8

Pre-hepatic
examples - Haemolysis, Gilbert’s syndrome, Crigler-Najjar

Question 9

likely cause of conjugated Hyperbilirubinaemia

Answer 9

Post-hepatic
examples - gallstones, pancreatic cancer, PBC

Question 10

likely cause of mixed Hyperbilirubinaemia

Answer 10

hepatic
examples - Viral hepatitis, alcoholic liver disease, DILI

Question 11

signs/symptoms of Hyperbilirubinaemia

Answer 11

Jaundice (scleral icterus)
Pale stools
Dark urine
Pruritus

Question 12

Bilirubin Type Likely Involved in jaundice

Answer 12

either

Question 13

Bilirubin Type Likely Involved in pale stools

Answer 13

conjugated

Question 14

Bilirubin Type Likely Involved in dark urine

Answer 14

conjugated

Question 15

Bilirubin Type Likely Involved in pruritis

Answer 15

conjugated

Question 16

Jaundice and Diagnostic Equity - why coloured people have fewer diagnoses for jaundice or have much later diagnoses?

Answer 16

Jaundice is traditionally identified through visible yellowing of the skin and sclerae.
→ Diagnostic delay or misdiagnosis can occur in people with darker skin tones if clinicians rely exclusively on skin colour changes.

The whites of the eyes (sclerae) are the most reliable site for identifying jaundice across all skin tones

Question 17

A 3-day-old term infant presents with yellowing of the skin and sclerae.
Born by uncomplicated vaginal delivery.
Feeding well, no fever.
Bilirubin: Total 240 µmol/L (unconjugated)
Question: What is the likely diagnosis? What further investigations (if any) are needed?

Answer 17

Likely physiological neonatal jaundice.
Cause: immature liver enzymes → delayed conjugation.
Key to rule out:
Haemolytic disease (ABO/Rh incompatibility)
G6PD deficiency
Sepsis
Treatment: phototherapy if levels exceed threshold.

Question 18

26-year-old woman with fatigue, pallor, and mild jaundice.
FBC: anaemia with raised reticulocyte count
LFTs: Total bilirubin 70 µmol/L, unconjugated fraction high
LDH ↑, haptoglobin ↓
Question: What’s causing the hyperbilirubinaemia?

Answer 18

Consistent with haemolytic anaemia (e.g. autoimmune,sickle cell, hereditary spherocytosis etc.), blood film would be very useful.
Excess breakdown of RBCs → elevated unconjugated bilirubin.
No bilirubin in urine.

Question 19

64-year-old man with dark urine, pale stools, and pruritus.
Bilirubin: Total 180 µmol/L, conjugated predominance
ALP ↑↑, GGT ↑, ALT mild ↑
Question: What’s the likely cause?

Answer 19

Likely post-hepatic obstruction (e.g. gallstones, pancreatic head mass, cholangiocarcinoma).
Raised conjugated bilirubin → appears in urine
Pale stools: no bilirubin reaching gut
Confirm with ultrasound or MR Cholangiopancreatography

Question 20

22-year-old man, flu-like symptoms, dark urine, mild RUQ pain.
Has history of engaging in high risk sexual activity.
Total bilirubin 80 µmol/L, mixed conjugated/unconjugated
ALT markedly elevated
Question: What’s the likely cause?

Answer 20

Acute viral hepatitis B
Hepatitis serology: HBsAg +
Hepatocellular damage → impaired conjugation + bile canaliculi blockage
Mixed pattern common
Management: supportive unless fulminant or chronicity develops

Question 21

19-year-old student feels tired during exams, noted scleral icterus.
Bilirubin: 45 µmol/L, unconjugated
All other LFTs normal
Question: Any ideas?

Answer 21

Benign Gilbert’s syndrome – inherited defect in UDP-glucuronyl transferase
Often asymptomatic, mild jaundice in stress/fasting
No treatment needed
Important to avoid unnecessary work-up