Case 2 - Sickle Cell Anaemia

Question 1

What is the structure of adult haemoglobin HbA?

Answer 1

• 2 alpha chain
• 2 beta chain
• 4 haem groups (bind O2)

Question 2

How are the chains in HbA arranged and work?

Answer 2

Tetrahedrally

Allosteric - co-operative binding

Question 3

What genetic pattern does Sickle cell disease show?

Answer 3

Autosomal recessive

Question 4

What is the difference between sickle cell disease and trait?

Answer 4

Disease - 2 HbS gene

Trait - 1 HbS 1 HbA

Question 5

How is the Hb gene mutated to form HbS gene?

Answer 5

Valine (neutral) replaces Glutamate (-ve charge) at the 6th amino acid position of the Beta-chain

Question 6

What sort of mutation is HbA to HbS?

Answer 6

Substitutional mutation

Question 7

When is the HbS structure most harmful?

Answer 7

In a deoxygenated state because the beta-chain changes to sickle shape and polymerise in more acidic (low pH) state - Acidosis [reduced blood flow]
Leads to occlusion of the vessel and infarction

Question 8

Why does HbS polymerise?

Answer 8

Acidosis causes presence of a hydrophobic site - creating a point of contact between two nearby Hb molecules and leads to HbS polymerization

Question 9

How does electrophoresis separate HbA and HbS?

Answer 9

It separates them by charge and mass. HbS is less negative than HbA so it moves less to positive

Question 10

What do we see in the electrophoresis of sickle cell trait?

Answer 10

2 bands because it is heterozygous with both HbA and HbS

Question 11

What are the 4 cell types we see on a blood film for Sickle Cell Anaemia?

Answer 11

• Reticulocyte (young RBC)
• Target cell
• Sickle cell
• Normal RBC

Question 12

Why is there a higher reticulocyte count in Sickle Cell Anaemia?

Answer 12

Bone marrow produce more to compensate for defective sickle cell (which are being turned over rapidly)

Question 13

What is splenomegaly?

Answer 13

Enlarged spleen from micro-infarction due to accumulated sickled cells

Question 14

What is the function of the spleen?

Answer 14

Filters blood

Question 15

What are the symptoms of Sickle cell disease?

Answer 15

Vision loss
Stroke
Bone crises

Question 16

How is vision loss caused?

Answer 16

Sickle cell accumulate in microvessel of retina

• increase in pressure hence damage vessel
• Cause ischaemia leading to chemokine release
• Angiogenesis occurs and collateral is formed
• Collateral is easily damaged and also grows across area of vision

Question 17

What is angiogenesis?

Answer 17

Formation of new blood vessel from spitting of old one

Question 18

What is ischaemia?

Answer 18

Reduction of blood supply from blockage

Question 19

What causes/type of strokes are there?

Answer 19

• Ischaemia (cerebral artery block/ silent stroke)
• Haemorrhagic stroke
• Block of major cerebral arteries

Question 20

What is a silent stroke?

Answer 20

It is asymptomatic and only blocks smaller arteries

Question 21

How does cerebral artery block induce stroke?

Answer 21

O2 deficiency to brain hence tissue death and infarction

Question 22

What is a haemorrhagic stroke?

Answer 22

Due to angiogenesis where more collaterals are produced and gets damaged leading to haemorrhage

Question 23

How does the blockage of a major cerebral arteries lead to stroke in sickle cell disease?

Answer 23

It is major symptomatic stroke where selectins are released and binds to sickle cell invoking inflammatory response hence blocking arteries

Question 24

What happens in a bone crises?

Answer 24

Microvascular occulsion reducing flow to bone marrow

- in a prolonged ischaemia hence promoting sickle formation

Question 25

How can we diagnose sickle cell disease?

Answer 25

• Electrophoresis
• Sickle solubility test
• Genetic screening (Before birth - provide counselling/ After birth - Heel prick test)

Question 26

How does the sickle solubility test determine sickle cell disease?

Answer 26

• Blood is added to sodium dithionite which is haemolytic
• Haemoglobin is released

HbA dissolves easily in blood plasma VS HbS solution turn turbid

Question 27

What are the treatments for Sickle cell disease?

Answer 27

• Blood transfusion
• Painkillers
• Take antibiotic
• Hydroxycarbamide
• Bone marrow transplant
• Gene therapy (avoided - expensive)

Question 28

How do we deal with a bone crises?

Answer 28

• Make sure hydrated
• Keep warm (Promote vasodilation)
• Take painkillers (Do not give morphine firsthand - as highly addictive)
• Take antibiotic

Question 29

Why do sickle cell patients take antibiotic and all vaccinations?

Answer 29

They are susceptible to infection due to lowered immune response (WBC constantly turning over sickle cell)

Question 30

What does hydroxycarbamide do?

Answer 30

It promotes synthesis of HbF which has high affinity for O2

But it suppresses production of reticulocytes and neutrophil –> increase infection

Question 31

How does blood transfusion help sickle cell patients?

Answer 31

Receiving function RBC and have iron chelate therapy to lower iron lv. (High lv. is toxic)

Question 32

What are the preventions of sickle cell disease?

Answer 32

• Keep hydrated
• Keep warm
• Avoid high altitude areas (Lower O2)
• Don’t over exercise (Acidosis)

Question 33

How does sickle cell disease affect daily life?

Answer 33

• Impact on social relationship
• Reduce employability
• Reduce education
• Cost huge

Question 34

What should we look out for in a case of child sickle emergency?

Answer 34

Fever

Vomit

Question 35

What is I.C.E.?

Answer 35

Ideas
Concern
Expectation