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Flashcards in IASM Case 4: Bilirubin Deck (12)
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***Degradation of 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.


***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)


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)


***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


Use of phototherapy

Convert unconjugated Bilirubin to Lumirubin (soluble in water)


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


Examine patient for signs of anaemia and jaundice

- 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)

- yellow pigmentation of skin / sclera
- serum bilirubin


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)


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


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


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


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