Sickle Cell Disease Ch. 11 Flashcards
What is the genetic cause of Sickle Cell Disease?
point mutation in hemoglobin beta gene (HBB) = substitution of valine for glutamine in B subunit of Hb
What does the point mutation in HBB gene lead to?
new property of Hb alters its solubility in blood especially in deoxygenated state or low pH | ability to bind to O2 unaffected
Define: heterozygote advantage
a mutated allele at same locus as normal allele = advantage of protection against a disease = increases survival
What heterozygote advantage does sickle cell RBCs provide?
sickle shape makes it difficult for malaria parasites to attach onto RBCs
What is the inheritance pattern of Sickle Cell disease?
autosomal recessive
How to sickle cell RBCs take shape?
in hypoxia = Beta-Val-6 of deO2 HbS binds to hydrophobic pocket on adjacent deO2 HbS molecule = join together = form insoluble polymer –> sickle cell shape
What physiological issue does sickle cell RBC shape pose?
aggregate sickle cells –> occlude/block vessels –> pain –> infarct tissues/cells
Sickle cell trait
heterozygous state of the gene for Hb S in sickle cell anemia.
Hemoglobin SC disease
individual has one copy of the gene for sickle cell disease and one copy of the gene for hemoglobin C disease.
Hemoglobin C disease
characterized by episodes of abdominal and joint pain, splenomegaly, mild jaundice; no severe crises | occurs mostly in African Americans, who may show few symptoms
How does a genetic modifier affect an HbS trait individual?
can induce expression of trait in carrier individual
What is compound heterozygosity?
2 different mutations (1 on each allele) for 1 gene = exacerbates issue
What test would you use to determine if a gene has compound heterozygosity?
PCR = to know specifically what the code was
What happens if an HbS carrier has compound heterozygosity?
can make a carrier look affected | “dominant” in presentation but “recessive” in inheritance model
What is apparent heterozygosity in sickle cell carriers?
If locus control for HbA is not working properly but locus control for HbS is working properly = HbS will phenotypically take over
What is novel property mutation?
mutation that gives protein product a new property (ie: shape change in HbS protein)
Compare normal RBC shape with sickle cell RBC shape.
normal = flexible and can squeeze through vessels | sickle cell = rigid and sticky = can aggregate and cause blockage
Compare normal RBC shape with sickle cell RBC shape.
normal = flexible and can squeeze through vessels | sickle cell = rigid and sticky = can aggregate and cause blockage
What is a sickle cell crisis?
acute onset | severe abd pain, stroke, priapism, acute chest syndrome, renal necrosis
What leads to a sickle cell crisis?
multiple occlusions
What is hemolytic anemia?
RBC lysis causing less RBCs circulating = anemia
How does sickle cell disease lead to hemolytic anemia?
sickle cell RBCs get pulled out of circulation for degradation at a faster rate than normal RBCs = less RBCs circulating –> anemia
Compare normal RBC shape with sickle cell RBC shape.
normal = flexible and can squeeze through vessels | sickle cell = rigid and sticky = can aggregate and cause blockage
What is vaso-occlusion?
microcirculation is blocked by sickled RBCs –> ischemic injury to the organ supplied = pain
