Topic 4: Sickle Cell Anemia Flashcards
what are hemoglobinopathy?
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
what’s the lifespan of a sickle cell RBC?
sickle-shaped red blood cells have a much shorter lifespan than normal RBCs
so patients with sickle cell disease may become anemic
what is the mutation in sickle cell disease?
point mutation in gene that encodes B globin subunit of Hb
glutamate6valine substitution
what’s the inheritance pattern of SCD?
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
what symptoms do sickle cell carriers have?
sickle cell trait
hematuria = blood in urine
renal papillary necrosis
What is the probability of passing on either sickle cell disease or sickle cell trait from two parents with sickle cell trait?
There is a 75% chance of passing on either SCD or SCT
25% will be unaffected
Is There a Benefit to Having Sickle Cell Trait?
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
what are the two states of Hb?
taut (T)
relaxed (R)
what is the T state of Hb?
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?
what is the R state of Hb?
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?
why does 2,3-BPG effect what state Hb is in?
2,3-DPG is formed from one of the steps of glycolysis that interacts with hemoglobin to promote release of oxygen molecules
what’s a good mnemonic to help remember what shifts the curve to the right?
CADET
high CO2 (hypoventilation) Acidity 2,3-DGP Elevation Temperature
these conditions cause sickling
what does the valine substitution in sickle cell do?
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
what happens when cells sickle?
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
what’s the lifespan of a sickled RBC in SCD?
10-30 days
in comparison to 90-120 days
Why does HbS stay closer to the cathode in Hb electrophoresis?
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
how are the hemoglobin, hematocrit and reticulocyte count altered in the CBC of SCD?
decreased Hb
decreased hematocrit
increased reticulocyte count in an attempt to compensate for early destruction of RBC
what are Howell-Jolly bodies?
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
what’s the major complication of sickle cell?
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
Name the conditions that would make RBCs more likely to sickle.
Hypoventilation (increased CO2)
acidosis
increased elevation
exercise
fever
asplenia puts patients at an increased risk for which infections?
increased risk for infections, especially with encapsulated bacteria like:
SHiN:
S. pneumoniae
H. influenzae
N. meningitides
what is ischemia?
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
what are the two big clinical problems from SCD?
vaso-occlusion will cause ischemia, pain and eventually functional asplenia
what are the 4 complications that arise with SCD?
- avascular necrosis of the hip
- acute chest syndrome
- vaso-occlusive pain
- infection
what is avascular necrosis of the hip?
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
what is acute chest syndrome?
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
why are SCD patients more prone to infection?
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
how is SCD usually treated?
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
what’s the only drug approved for SCD?
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
how do you treat acute chest syndrome?
- pain control
- fluids
- supplemental oxygen
- empiric antibiotics
