Topic 4: Sickle Cell Anemia

Question 1

what are hemoglobinopathy?

Answer 1

inherited diseases in which there is a mutation in one of the globin chains genes (either alpha or beta)

usually due to point mutation and usually the B globing gene is effected

Question 2

what’s the lifespan of a sickle cell RBC?

Answer 2

sickle-shaped red blood cells have a much shorter lifespan than normal RBCs

so patients with sickle cell disease may become anemic

Question 3

what is the mutation in sickle cell disease?

Answer 3

point mutation in gene that encodes B globin subunit of Hb

glutamate6valine substitution

Question 4

what’s the inheritance pattern of SCD?

Answer 4

autosomal recessive

carriers have the sickle cell trait so it’s benign but they can have some symptoms

think about the gene as being codominant because the carriers will have some RBCs with the mutated protein containing valine at position number six in circulation

Question 5

what symptoms do sickle cell carriers have?

Answer 5

sickle cell trait

hematuria = blood in urine

renal papillary necrosis

Question 6

What is the probability of passing on either sickle cell disease or sickle cell trait from two parents with sickle cell trait?

Answer 6

There is a 75% chance of passing on either SCD or SCT

25% will be unaffected

Question 7

Is There a Benefit to Having Sickle Cell Trait?

Answer 7

patients with SCT have some protection against malaria

one theory is that the parasite will decrease oxygenation within the RBC it infects. This will cause the cell to sickle and then be cleared by the spleen, limiting the parasite’s ability to infect the host

Question 8

what are the two states of Hb?

Answer 8

taut (T)

relaxed (R)

Question 9

what is the T state of Hb?

Answer 9

T state is when there’s:

• low oxygen
• high CO2
• low pH
• high 2,3-BPG

would you be relaxed or stressed (taut) if you had low oxygen?

Question 10

what is the R state of Hb?

Answer 10

R state is when there’s:

• high oxygen
• low CO2
• high pH
• low 2,3 BPG

would you be relaxed or stressed (taut) if you had low oxygen?

Question 11

why does 2,3-BPG effect what state Hb is in?

Answer 11

2,3-DPG is formed from one of the steps of glycolysis that interacts with hemoglobin to promote release of oxygen molecules

Question 12

what’s a good mnemonic to help remember what shifts the curve to the right?

Answer 12

CADET

high CO2 (hypoventilation)
Acidity
2,3-DGP
Elevation
Temperature

these conditions cause sickling

Question 13

what does the valine substitution in sickle cell do?

Answer 13

in the T state, the valine is exposed which causes problems because its non polar

all the hemoglobin molecules within the RBCs line up with the 6-Valine facing inwards to shield them from the polar environment = polymerization

small amounts of polymerization are reversible but will eventually cause irreversible changes that result in the classic sickling

Question 14

what happens when cells sickle?

Answer 14

they lose their flexibility

sickled cells get trapped in the small vasculature of the reticular-endothelial system of the spleen and capillaries throughout the body

Question 15

what’s the lifespan of a sickled RBC in SCD?

Answer 15

10-30 days

in comparison to 90-120 days

Question 16

Why does HbS stay closer to the cathode in Hb electrophoresis?

Answer 16

cathode = -

normal β globin chain has a glutamate at position 6, but the sickle β globin chain has a valine instead

Glutamate has a negative charge, and valine has a positive charge so HbS migrates closer to the cathode

Question 17

how are the hemoglobin, hematocrit and reticulocyte count altered in the CBC of SCD?

Answer 17

decreased Hb

decreased hematocrit

increased reticulocyte count in an attempt to compensate for early destruction of RBC

Question 18

what are Howell-Jolly bodies?

Answer 18

seen in patients with sickle cell disease – and anyone without a spleen

they consist of small remnants of DNA that are normally removed by the spleen

but in the absence of a spleen, they remain in RBCs and are visible as deeply basophilic, spherical inclusions

they look like blue dots on the RBCs

Question 19

what’s the major complication of sickle cell?

Answer 19

normally, RBCs are flexible enough to bend to get through the narrow lumen of small vessels

when cells sickle, they lose flexibility and will get stuck

when sickle cells get stuck, the lumen becomes further narrowed, causing more cells to join the blockage until the vessel is occluded

repeated vaso-occlusion will damage the spleen, leading to functional asplenia

Question 20

Name the conditions that would make RBCs more likely to sickle.

Answer 20

Hypoventilation (increased CO2)

acidosis

increased elevation

exercise

fever

Question 21

asplenia puts patients at an increased risk for which infections?

Answer 21

increased risk for infections, especially with encapsulated bacteria like:

SHiN:
S. pneumoniae
H. influenzae
N. meningitides

Question 22

what is ischemia?

Answer 22

a restriction in blood supply to tissues, causing a shortage of oxygen that is needed for cellular metabolism

usually caused by problems with blood vessels or blockages

Question 23

what are the two big clinical problems from SCD?

Answer 23

vaso-occlusion will cause ischemia, pain and eventually functional asplenia

Question 24

what are the 4 complications that arise with SCD?

Answer 24

1. avascular necrosis of the hip
2. acute chest syndrome
3. vaso-occlusive pain
4. infection

Question 25

what is avascular necrosis of the hip?

Answer 25

Avascular necrosis happens to the long bones, particularly the head of the femur, which occurs due to vaso-occlusion, leading to infarction of the bony trabeculae

causes pain, often groin pain and pain on weight bearing

often requires surgical intervention

Question 26

what is acute chest syndrome?

Answer 26

includes at least 2 of the following: chest pain, fever, pulmonary infiltrate, respiratory symptoms, or hypoxemia

often caused by infection, which leads to inflammation and oxygen desaturation

this state worsens sickling, causing vaso-occlusion –> this becomes a vicious cycle

Question 27

why are SCD patients more prone to infection?

Answer 27

largely due to asplenia and overall poor tissue perfusion

particularly concerning is bacteremia and sepsis from encapsulated bacteria

there’s also an increased risk for osteomyelitis due to Salmonella

Question 28

how is SCD usually treated?

Answer 28

supplementing with folic acid

folic acid is an important cofactor for DNA synthesis –> in SCD, increased hematopoiesis will consume high levels of folate so folate supplementation will provide adequate folate for this

Question 29

what’s the only drug approved for SCD?

Answer 29

Hydroxyurea

works by increasing the amount of fetal hemoglobin

however, it decreases number of leukocytes and may be carcinogenic, particularly associated with increased risk of leukemia

Question 30

how do you treat acute chest syndrome?

Answer 30

• pain control
• fluids
• supplemental oxygen
• empiric antibiotics