IASM Case 4: Bilirubin Flashcards Preview

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Flashcards in IASM Case 4: Bilirubin Deck (12)
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1

***Degradation of RBC

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.

2

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

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)

3

Abnormalities of RBC metabolism lead to shortened RBC survival

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)

4

***Oxidative stress

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

5

Use of phototherapy

Convert unconjugated Bilirubin to Lumirubin (soluble in water)

6

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

G6PD: X-linked recessive

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

7

Examine patient for signs of anaemia and jaundice

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

8

Use of laboratory tests in investigation of haemolysis

- 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)

9

Role of breast-feeding in triggering awareness of metabolic abnormality

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

10

Role of genetics in antenatal and postnatal period

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

11

Understanding of concept of screening for inborn disease

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

12

Types of anaemia

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