Hemoglobin and Hemoglobin S Flashcards
During circulation, where does a RBC spend the most time?
Venous return (~10 seconds)
In most patients with sickle cell disease, HbF ranges from ___ to ___%
5-8%
Some patients with sickle cell disease have up to ___% HbF
20%
Elevated ___ in sickle cell patients often means that they will have a milder case of the disease
HbF
Cells containing HbF survive longer/shorter in the circulation
Longer
HbF reduces sickling and ____-_____ crisis
Vaso-occlusive
Sickle cell disease is characterized by RBCs sickling at low/high O2 pressure
Low
Sickle cell anemia refers to disease that is characterized by an individual who is heterozygous/homozygous for B-globin chain of HbA mutation (Val to Glu at the 6th position)
Homozygous
HbS is comprised of 2 normal a-chains and 2-B chains with what substitution at the 6th position?
Glu to Val (BsBs)
People who are heterozygotes (BaBs) do not typically have symptoms of sickle cell anemia, but they may have some during what type of conditions?
Low O2 –> high altitude, intense exercise
Sickle cell anemia is one of the most common autosomal ______ disorders in the world
recessive
Which state of sickle cell anemia (heterozygous or homozygous) confers resistance to malaria?
Heterozygous
What other amino acid substitution other than Val to Glu at the 6th position can lead to sickle cell anemia?
Lys to Glu at the 6th position
HbC is caused by what mutation?
Lys to Glu substitution at the 6th position
HbCC homozygotes will have mild/severe sickle cell anemia?
Mild
HbAC heterozygotes are asymptomatic/symptomatic
Asymptomatic
HbSC heterozygotes are unique. Why?
They have sickle cell disease; not sure why
Low/high oxygen tension promotes HbS polymerization and RBC sickling
Low oxygen
What does repeated sickling do to the RBC membrane?
Damages it and decreases the cell elasticity
Sickled cells reduce blood flow in the ________ and that leads to _____ and vaso-occlusive episodes
microvasculature; hemolysis
Sicking increases/decreases with time in a low O2 environment
increases
The beta, delta, and gamma subunits of Hb have the same number of amino acids and similar size. What differences create bands in electrophoresis with non-denaturing gel?
Amino acid substitutions
Bs in the B-like globin chain in HbS has the substitution of glu to ___ at the 6th position. This causes a more negative/positive charge in comparison to HbA
valine; more positive
Bc in the B-like globin chain in HbC has the substitution of lys to ___ at the 6th position. This causes a more negative/positive charge in comparison to HbA
glutamic acid; more positive
The double nucleation model applies to which conformation of HbS?
Deoxy (T)
What are the steps in order in the double nucleation model of sickling?
HbS monomers aggregate to form critical nucleus –>Nucleation –> Exponential growth –> Alignment–> Polymer formation–> Sickled RBCs
HbS aggregates together to form what under low O2 conditions in a HbS homozygote?
Critical nucleus
The higher/lower the HbS concentration inside of a RBC means that the critical nucleus concentration will be reached faster, leading to more sickling
higher
Sickle cell patients must be well hydrated. Why?
Dehydration increases Hb concentration
Once the critical nucleus begins to form, the rate of
polymerization is ______ because there are an increasing number of sites for
addition on HbS monomer to the polymer. This leads to what shape curve?
exponential; sigmoidal
In which circulation (venous vs. arterial) will there be more sickling?
Venous
The longer that sickle cell anemia patients’ cells are at a state where they are held at low pO2 for a long period of time, a greater/lesser amount of polymer formation occurs, presumably because this allows longer time for nucleation
Greater
Vasoconstriction or partial occlusion can lead to increased/decreased sickling
Increased bc the RBCs are spending more time in low O2 environment
Unsickling occurs as the pO2 increases and this presents as a _____ function
Linear and not cooperative until the very end when complete disintegration of the polymer occurs at high pO2
Sickling is _____ and unsickling is ______ until the very end at high pO2 when disassociation of complete disintegration of the polymer occurs
Cooperative; not cooperative
T/F: Sickled cells never remain sickled permanently
False
At body temp (37C) a decrease in pH will cause increased/decreased sickling
Increased because there is an increase in H+ and that leads to an acidic environment that is favored by the deoxy form required for sickling
Low pH and high temp = more/less sickling
More
If sickle cell anemia patient has a fever, this will increase/decrease sickling?
Increase
In a sickle cell patient with normal arterial pH and one with acidosis, which scenario will cause the sharpest increase in sickling with increased temp?
Normal arterial pH
