263b sickle cell Flashcards
hemoglobin - what globin chains are present in adults? what is in each chain?
HbA = a2,b2 (97%)
HbA2=a2d2 (3%)
HbF=a2g2 (increased with hydroxyurea)
heme = Fe + protoporphyrin: can bind O2, CO when reduced (Fe 2+)
where are the two globin gene?
a - chromosome 16
b - chromosome 11
arranged in order of globin production during life
hemoglobin switching
10 weeks: E (embryo) –> gama
birth-6 months: gamma –> B
SCD mutation?
HbS point mutation in B chain
G –> V single amino acid replacement at position 6.
SCD pathogenesis?
Pathogenesis: low O2, dehydration, or acidosis ->
sickling (deoxygenated HbS polymerizes) –>
anemia and vaso-occlusive disease.
SCD - newborn presentation? heterozygote advantage? AA carriers?
Newborns are initially asymptomatic (high HbF and low HbS)
Heterozygotes (sickle cell trait) have resistance to malaria (homozygous will kill you though –> example of balanced polymorphism)
8% of African Americans carry the HbS trait
Sickle cell - skull x-ray appearance?
“Crew cut” on skull x-ray due to marrow expansion from increased erythropoiesis (also in thalassemias).
SCD - treatment?
hydroxyurea (increases HbF)
bone marrow transplantation.
SCD - hydration of RBC?
dehydrated because increased K efflux and KCl- cotransport efflux –> efflux of H2O –> irreversible sickling
SCD - painful crisis presentation?
dactylitis (painful hand swelling) acute chest syndrome (most common cause of death in adults) avascular necrosis stroke (5-10 years old) severe back pain
acute chest syndrome = fever + abnormal CXR + respiratory syndrome
SCD - complications?
aplastic crisis w/ parvovirus B19
autosplenectomy (increased encapsulated bacteria infection risk)
splenic sequestration crisis
salmonella osteomyelitis
painful crisis (vaso-occlusive) - RBC stick, WBC and platelets interact and are activated, NO gets depleted
renal papillary necrosis
