Sickle Cell

Question 1

define “electrophoresis”

Answer 1

method of analysing molecules on the basis of charge and weight by measuring their migration in an electric field

Question 2

What changes HbA to HbS

Answer 2

• point mutation in beta-globin gene causes change in amino acid 6 from glutamate (-ve charge hydrophilic) to valine (hydrophobic uncharged) resulting in HbS.
• hydrophobic interactions = clump together + affect b-globin chain

Question 3

does HbA or HbS move closer to the anode?

Answer 3

-HbA is more –vely charged

(as glutamate = hydrophilic and -ve) so migrates further towards anode

Question 4

what shows up on the electrophoresis if the person is a carrier?

Answer 4

some of HbA and some of HbS = carrier as they are heterozygous HbAS

Question 5

results of a full blood count for a sickle cell sufferer?

Answer 5

1. low [Hb] (sign of anaemia)
2. bigger MCV as more reticulocytes (immature red blood cells which are larger than fully mature rbc) as anaemia so bone marrow making more red blood cells
3. high reticulocyte count - due to the premature death of RBCs so bone marrow keeps producing more RBCs

Question 6

why can the MCV sometimes be low?

Answer 6

if you have lost blood / anaemia the iron from the Hb can not be recycled so less rbc can be made

Question 7

what shows anaemia on a blood film?

Answer 7

1. paler rbc = low conc. of Hb (hypochromasia)
2. less cells per unit volume
   (3. microcytic cells)

Question 8

sickle cell characteristics in a blood film

Answer 8

1. sickle cells (poikilocytosis)
2. nucleated RBCs (immature)
3. hypochromic rbcs (paler = low Hb levels)
4. microcytic cells (macrocytic cells arise when there are problems with problems with dna synthesis) - smaller cells indicate slight anaemia
5. Boat cells (poikilocytosis)
6. Howell Jolly bodies (left over nuclear remnants that are usually removed when blood cells are in the spleen) - in sickle cell vessels to spleen can be blocked = less efficient

Question 9

sickle cell carrier on a blood film

Answer 9

you can not see if someone has a sickle cell trait by just looking at their blood film but there may be some early signs of sickling

Question 10

women vs men blood film

Answer 10

women can be menstruating = more likely to have anaemia

Question 11

what happens during a vaso-occlusive crisis (pain crisis)?

Answer 11

sickle cell shape = harder to pass through vessels = vasco-occulusive crisis as a vessel gets blocked = necrosis in healthy tissue

Question 12

impact of sickle cell disease in different areas of the body

Answer 12

• bone marrow ischaemia (in extreme cases avascular necrosis is the death of bone tissue due to a lack of blood supply)
• visual loss (vessels in the eye blocked or e.g. retinal artery or retina can even fall off)
• stroke (blocking arteries to the brain = lack of oxygen to the brain)

Question 13

types of stoke

Answer 13

• ischeamic stroke (most common)

- hemorrhagic stroke (burst of vessels)

Question 14

why is a stroke most common in children with sickle cell

Answer 14

blood vessels are smaller and don’t say their problems, doesn’t know when about to have a crisis as not quite used to it

Question 15

what can trigger a sickle cell crisis

Answer 15

1. cold weather = vasoconstriction = more likely to block off
2. infection = dehydration, lower o2 levels if it is in the lungs = more sickled cells
3. exercise = HR incr. (more o2 needed)
4. dehydration, due to low blood volume
5. stress
6. high altitudes, due to low oxygen
7. alcohol
8. smoking
9. pregnancy
10. other medical conditions, such as diabetes
11. hypoxia

Question 16

how people cope with their disease in their daily lives (self)

Answer 16

1. hot water bottle - vasodilation
2. folic acid = support RBC production
3. hydration (high blood volume = wider lumen)
4. pain killers

main- pain killer, oxygen, fluids

Question 17

doctor intervention to help with sickle cell

Answer 17

1. stronger pain killers i.e. morphine (opioids)
2. antibiotics recommended if there is a chance of infection
3. oxygen is part of the treatment (only sickle cell shape when deoxygenated blood)
4. blood thinners (anticoagulants) -as these patients have an increase rate of DVT and clotting as HbSS more likely to clot)
5. mental support
6. extra fluids (ie IV) to hydrate

Question 18

concept of ICE

Answer 18

Ideas, concerns and expectations - understanding what the patient may be feeling → patient centred care

Question 19

burden of sickle cell on different parts of body

Answer 19

1. CNS (visual loss, pain, stroke, seizures)
2. bones (crisis, avascular necrosis)
3. cardiac (pain, hypertension)
4. spleen (anaemia, Hellman jolly)
5. gastro + urology
6. depression + anxiety

Question 20

ICE

Answer 20

1. Ideas are unemotional thoughts about the nature - health-seeking response; e.g. she has a clear idea + understands what is needed - a person with a severe sore throat may develop the idea that she needs antibiotics.
2. Concerns are the emotional triggers and fears that we all ex- perience to varying degrees. e.g. how it interferes with her life
3. Expectations of the doctor’s likely reaction.
   e. g. expects morphine, folic acid..

Question 21

what amino-acid changes when HbA → HbS

Answer 21

glutamate → valine (replace extra COO- with CH3 therefore no longer -vely charged + hydrophilic)

Question 22

what type of disease is sickle cell anaemia in terms of inheritance?

Answer 22

-Autosomal recessive (if both parents are carriers child has a 25% chance of getting it)

• Homozygous - sickle cell anaemia
• Heterozygous - sickle cell trait (only one mutated allele- most commonly asymptomatic – normal blood count + film)

Question 23

What happens to RBCs during sickle cell anaemia?

Answer 23

• Distorted RBCs, sickled (poikilocytosis)
• Rigid RBCs
• Dehydrated RBCs
• The red blood cells stick together due to the valine instead of glutamic acid due to the hydrophobic interaction which causes polymerisation- which causes blockage of vessels
• Short survival of RBCs- do not survive the normal 120 days
• RBCs have a lower affinity for oxygen- they are hypoxic. But they do release oxygen more easily to tissues.

Question 24

what is the epidemiology of sickle cell?

Answer 24

• Sickle cell trait protects from malaria
• Sickle cell trait is more prevalent in sub-saharan Africa, middle east, Mediterranean and India
• The life expectancy is 42-48 (even lower in LIC) - and patients in their 40s usually have organ damage

Question 25

who is screened for sickle cell disease?

Answer 25

• All pregnant women and newborns are screened

- If both parents are carriers, their child has 25% of having sickle cell anaemia - genetic counselling Is offered

Question 26

why can you perform a solubility test to look for the disease?

Answer 26

• The test works because HbS is insoluble, so separates out,
• The test doesn’t differentiate whether you have trait or anaemia, so gel electrophoresis is then carried out to identify what the patient has

Question 27

what are the chronic complications of sickle cell anaemia?

Answer 27

1. Gall stones - due to haemolysis (= increased excretion of bilirubin into the biliary tract)
2. Priapism - painful, persistent erection
3. Kidney disease - due to ischaemia or haemolysis (free Hb in blood)
4. Avascular necrosis of hips and shoulders - recurrent pain crises and ischaemic damage
5. Leg ulcers
6. Retinopathy (visual loss)
7. Iron overload due to transfusions

Question 28

what are the acute complications of sickle cell anaemia?

Answer 28

1. Dactylitis - pain in the small joints of the hand due to the blood vessel occulosis- which prevents oxygen being delivered to the tissues after blockage. Common in children
2. Sequestration- more common in children- a large volume of blood is pooled into the spleen, resulting in a large spleen. This causes a drop in Hb to the rest of the blood vessels- which causes a drop in blood pressure, profound anaemia. This is common in children + can be precipitated by viral infection
3. Aplastic - sudden drop in bone marrow red cell production
4. Vaso-occlusive - blood vessels are occluded by the sickle cells = pain crises
5. Acute chest syndrome – chest pain, cough, shortness of breath, fever
6. Sepsis: due to a badly damaged spleen

Question 29

What are the issues with giving Murewa morphine?

Answer 29

• Addiction
• She could build up a tolerance to it
• Overdose - sedation

Question 30

Longer term reatment of SCA?

Answer 30

• Hydroxycarbamide- a drug which induces foetal Hb production- which inhibits the sickle RBCS from sticking together.
• Bone marrow transplant- removes all the mutates RBCs from patients- only applicable if very severe and young. Only with a matched sibling donor
• Anti-adhesion agents
• Transfusions
• Gene Therapy as it is caused by a single nucleotide mutation it can be targeted (CRISPR -insertion of a retrovirus which enters the correct gene into the patients stem cells)

Question 31

what are the three main types of normal adult haemoglobin present in the blood and their percentages?

Answer 31

1. HBA (96-98%) 2 alpha 2 beta
2. HBA2 (1.5%-3.2%) 2 alpha 2 delta
3. HBF (0.50.8 %) 2 alpha 2 gamma

Question 32

describe the structure of Haemoglobin?

Answer 32

made of 4 globin chains:

• 2 alpha of 141 amino acids each
• 2 beta chains of 146 amino acids each

Question 33

why does polymerisation occur between sickle cells?

Answer 33

alanine and valine (instead of alanine and glutamate) from two different sickle cells have a hydrophobic interaction so will clump together and block the blood vessels