Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CSIs > CSI 2 - Sickle Cell Disease > Flashcards

CSI 2 - Sickle Cell Disease Flashcards

1
Q

What is normal Hb comprised of?

A

2 alpha, 2 beta chains - tetrameter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Properties of HbA

A

chains arranged tetrahedrally, allosteric protein allows cooperative binding

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Difference between HbS and HbA

A

HbS is created by an autosomal recessive mutation in the beta globin chains (HBB) –> it’s misshapen

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is it called when a person is heterozygous for the sickle cell gene

A

Sickle cell trait

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the mutation described as?

A

Non-conservative missense mutation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Which amino acid is substituted and at what location?

A

Glutamate (negatively charged) for Valine (neutral and therefore hydrophobic)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What consequences does that have for the sickle cell Hb?

A

Same oxygen affinity but when deoxygenated it crystallises out and due to the valine interlocking protrusion, the HbS polymerises

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What increases sickling and why?

A

acidosis –> lower oxygen affinity, so more HbS is deoxygenated
low flow blood vessels –> smaller diameter

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Why is it so dangerous?

A

Can lead to occlusion of the blood vessels –> infarction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What is the definition of electrophoresis?

A

Technique used to separate molecules based on their charge and mass

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Why do sickle cell patients have a higher than normal reticulocyte count?

A

Because bone marrow has to produce more RBCs to compensate for the defective sickling

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the difference between a reticulocyte and an erythrocyte?

A

Polychromatic with a network of reticular rna which is absent in mature cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is splenomegaly and why does it arise in sickle cell patients?

A

enlargement of the spleen due to micro-infarctions as a result of accumulated sickled erythrocytes => needs to compensate for loss of function and it enlarges.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Most common symptoms of sickle cell anaemia

A
  • vision loss
  • bone crises
  • strokes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Explain why vision loss occurs

A
  • sickle cells accumulate within microvessels of the reitna
  • pressure increases
  • vessels are damaged
  • ischaemia causes chemokine release
  • angiogenesis occurs and collaterals form
  • they are easily damaged and can grow across areas of vision
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Explain the types of strokes and why they occur

A

Most common - ischaemic stroke

  • cerebral artery blocked resulting in oxygen deficiency
  • silent strokes occur due to damage to smaller blood vessels and are asymptomatic

Haemmorrhagic stroke:

  • occurs due to angiogenesis
  • collaterals easily broken

Blockage of major cerebral arteries:

  • major symptomatic stroke
  • selectins released which promote clotting of blood
  • susceptibility of sickling increased
17
Q

Explain bone crises?

A
  • reduced flow to the bone marrow - microvascular occlusion
  • prolonged ischaemia leads to infarction
  • ischaemia exacerbates sickling
18
Q

What is the sickle solubility test?

A
  • Blood is taken
  • Sodium dithionide is added which lyses the cells
  • Hb is released
  • HbA dissolves easily in plasma to give a clear solution whilst HbS clumps together (turbid solution with increased optical density) (deoxygenation buffer allows a precipitate to form) –> Test doesn’t distinguish between sickle cell trait and disease
19
Q

List the different treatments for SCA

A
  • Blood transfusions
  • Pain killers and opioids (only for last resort)
  • Keeping warm and hydrated, avoiding high altitudes and low oxygen levels
  • Hydroxycarbamide
  • Bone marrow transplants
  • Gene therapy (viral vectors insert functional gene into haemopoietic stem cell)
  • Antibiotics (penicillin) and routine vaccinations for children (additional flu and hep B vaccines)
20
Q

What measures must be taken during a blood transfusion and why?

A

Iron chelation therapy reduces exccess iron levels which can build up to toxic levels

21
Q

What are the side effects of hydroxycarbamide?

A

Suppresses reticulocyte and neutrophil production => increased risk of infection

22
Q

What is the downside to bone marrow transplant?

A

Only available to young patients, matched donor needs to be found

23
Q

What is the downside to gene therapy?

A

Expensive

24
Q

What is a target cell?

A

Has Hb in area of central pallor where it shouldn’t be

25
Q

What is HbA2 comprised of?

A

two alpha and two delta chains

26
Q

What is HbF comprised of?

A

two alpha chains and two gamma chains

27
Q

Why do sickle cell patients have elevated HbF?

A

It has a greater affinity for oxygen, so ability to capture oxygen increases and it acts as a compensatory mechanism.

28
Q

Describe the bands on the Hb electrophoresis

A

HbA2 is closest to negative side
HbS is in the middle
HbF is next
HbA is the closest to the positive electrode

29
Q

Why are there higher levels of haemopoiesis and what does this result in?

A

There is a high erythrocyte degradation because sickle cells are more susceptible to lysis => compensatory mechanism of releasing reticulocytes

30
Q

What are Howell-Jolly bodies and why are they there?

A

RBCs with nuclear remnants due to impaired function of spleen (where the nuclei are usually removed)

31
Q

What are some other symptoms of sickle cell anaemia

A

Jaundice (due to excess unconjugated bilirubin due to haemolysis)
Splenomegaly

32
Q

What are the acute crises?

A

Dactylitis (pain in hand joints)
Splenic sequestration
Acute chest syndrome, sepsis (bacterial infections, spleen is damaged)

33
Q

What are chronic?

A 
Gall stones due to bilirubin release 
priapism 
kidney damage 
avascular necrosis of hips and shoulders 
leg ulcers 
retinopathy 
iron overload due to transfusions
34
Q

Explain what screening is offered to a newborn baby

A

Screened using a haemoglobin isoelectric focusing (Hb IEF), by taking a heel-prick test

35
Q

Explain what happens in electrophoresis of HbS?

A

AFSC control; intense band in HbS region showing greater concentration; lower normocytic Hb band
HbF band is relatively prevalent due to compensatory mechanism
HbS is further away from anode because valine is uncharged

36
Q

What painkillers can be given for bone crises?

A

Ibuprofen and aspirin

37
Q

What effects does Hydroxycarbamide have?

A

Reduces vaso-occlusion since neutrophils promote vascular adhesion and they are produced less
Stimulates production of foetal Hb

38
Q

What other things are also prescribed?

A

anti-adhesion therapy, folic acid supplements, antibiotics

39
Q

Patient triggers of vaso-occlusive crises

A

cold weather
strenuous exercise - increased deoxygenation of Hb => promotes cell sickling
dehydration

CSIs (1 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions