IASM Case 4: Bilirubin

Question 1

***Degradation of RBC

Answer 1

RBC
—> cell fragments phagocytised
—> haemoglobin —> Heme / Globin

Globin —> free amino acids (hydrolysis)
***Heme —> Biliverdin + Iron

***Biliverdin —> Bilirubin —> Bile —> faeces
Iron —> storage / reuse / loss by menstruation etc.

Question 2

***Main features of bilirubin metabolism and causes of raised serum

Answer 2

RBC broken down in liver and spleen

• Biliverdin —> Bilirubin (Biliverdin reductase)
• Bilirubin conjugated with glucuronic acids in liver (glucuronyltransferase) —> more water soluble
• Stored in gall bladder and released as bile

Increase in serum bilirubin:

1. Increased destruction of RBC
2. Immature liver metabolism (newborn jaundice)
3. Biliary obstruction (bilirubin backs up into circulation)
4. Liver diseases (hepatitis, cirrhosis)

Question 3

Abnormalities of RBC metabolism lead to shortened RBC survival

Answer 3

Normal: 120 days
Sickle cell: 10-20 days
Neonatal erythrocytes: 60-90 days
Preterm infant: 35-50 days (less antioxidant and prone to oxidative stress damage)

Question 4

***Oxidative stress

Answer 4

Arise from ROS attacking organelles
—> chain reaction to disrupt cellular structure

Antioxidant mainly produced through Pentose phosphate pathway (PPP) —> NADPH
Normal cells produce antioxidant through PPP (Pentose phosphate pathway)

• G6PD (glucose-6-phosphate dehydrogenase) is a crucial enzyme within PPP
  1. make NADPH —> electron donor in thiol cycle —> generate glutathione —> antioxidant
  2. Glutathione drives vitamin C/E cycle to produce other antioxidant

Question 5

Use of phototherapy

Answer 5

Convert unconjugated Bilirubin to Lumirubin (soluble in water)

Question 6

Inheritance of X-linked disorder and reasons for lack of family history in inherited disease

Answer 6

G6PD: X-linked recessive

For carrier mother and normal father (一定無disease allele)
—> only 25% affected son + 25% carrier daughter

Question 7

Examine patient for signs of anaemia and jaundice

Answer 7

Anaemia:

• skin colour (pale)
• central pallor
• peripheral / central cyanosis
• RBC count, haemoglobin
• Normocytic (RBC normal size but low level)
• Normochromic (Haemoglobin normal level but low RBC)

Jaundice:

• yellow pigmentation of skin / sclera
• serum bilirubin

Question 8

Use of laboratory tests in investigation of haemolysis

Answer 8

• Low haemoglobin —> anaemia
• High reticulocyte —> compensated low oxygen carrying capacity of blood
• Irregularly contracted RBC, hemighosts —> RBC under oxidative stress —> G6PD deficiency
• High unconjugated bilirubin —> Increased in RBC decompositions not in liver (not conjugated)

Question 9

Role of breast-feeding in triggering awareness of metabolic abnormality

Answer 9

Breast feeding increase risk of passing chemicals that trigger oxidative damage
—> haemolysis of RBC and rise in unconjugated bilirubin
—> babies often sleepier than normal

Question 10

Role of genetics in antenatal and postnatal period

Answer 10

See lecture

Newborn screening:

• screen infant shortly after birth for conditions treatable in early life
• serious outcomes if untreated / undetected

Prenatal screening:

• better antenatal follow up
• pregnancy decision

Question 11

Understanding of concept of screening for inborn disease

Answer 11

G6PD screening

• umbilical cord blood
• blood count
• reticulocyte count
• liver enzymes
• lactate dehydrogenase
• DNA testing and sequencing of G6PD gene

Parents will be informed by Genetic screening unit / hospital staff for test results

Question 12

Types of anaemia

Answer 12

Normocytic: elevated reticulocyte —> haemolytic anaemia (G6PD)
Normocytic: normal / decreased reticulocyte —> aplastic anaemia

Microcytic: iron-deficiency anaemia, thalassaemia

Macrocytic: megaloplastic —> B12, B9 deficiency
Macrocytic: non-megaloblastic —> Chronic liver disease