Hemoglobin and Hemoglobin S

Question 1

During circulation, where does a RBC spend the most time?

Answer 1

Venous return (~10 seconds)

Question 2

In most patients with sickle cell disease, HbF ranges from ___ to ___%

Answer 2

5-8%

Question 3

Some patients with sickle cell disease have up to ___% HbF

Answer 3

20%

Question 4

Elevated ___ in sickle cell patients often means that they will have a milder case of the disease

Answer 4

HbF

Question 5

Cells containing HbF survive longer/shorter in the circulation

Answer 5

Longer

Question 6

HbF reduces sickling and ____-_____ crisis

Answer 6

Vaso-occlusive

Question 7

Sickle cell disease is characterized by RBCs sickling at low/high O2 pressure

Answer 7

Low

Question 8

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)

Answer 8

Homozygous

Question 9

HbS is comprised of 2 normal a-chains and 2-B chains with what substitution at the 6th position?

Answer 9

Glu to Val (BsBs)

Question 10

People who are heterozygotes (BaBs) do not typically have symptoms of sickle cell anemia, but they may have some during what type of conditions?

Answer 10

Low O2 –> high altitude, intense exercise

Question 11

Sickle cell anemia is one of the most common autosomal ______ disorders in the world

Answer 11

recessive

Question 12

Which state of sickle cell anemia (heterozygous or homozygous) confers resistance to malaria?

Answer 12

Heterozygous

Question 13

What other amino acid substitution other than Val to Glu at the 6th position can lead to sickle cell anemia?

Answer 13

Lys to Glu at the 6th position

Question 14

HbC is caused by what mutation?

Answer 14

Lys to Glu substitution at the 6th position

Question 15

HbCC homozygotes will have mild/severe sickle cell anemia?

Answer 15

Mild

Question 16

HbAC heterozygotes are asymptomatic/symptomatic

Answer 16

Asymptomatic

Question 17

HbSC heterozygotes are unique. Why?

Answer 17

They have sickle cell disease; not sure why

Question 18

Low/high oxygen tension promotes HbS polymerization and RBC sickling

Answer 18

Low oxygen

Question 19

What does repeated sickling do to the RBC membrane?

Answer 19

Damages it and decreases the cell elasticity

Question 20

Sickled cells reduce blood flow in the ________ and that leads to _____ and vaso-occlusive episodes

Answer 20

microvasculature; hemolysis

Question 21

Sicking increases/decreases with time in a low O2 environment

Answer 21

increases

Question 22

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?

Answer 22

Amino acid substitutions

Question 23

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

Answer 23

valine; more positive

Question 24

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

Answer 24

glutamic acid; more positive

Question 25

The double nucleation model applies to which conformation of HbS?

Answer 25

Deoxy (T)

Question 26

What are the steps in order in the double nucleation model of sickling?

Answer 26

HbS monomers aggregate to form critical nucleus -->Nucleation --> Exponential growth --> Alignment--> Polymer formation--> Sickled RBCs

Question 27

HbS aggregates together to form what under low O2 conditions in a HbS homozygote?

Answer 27

Critical nucleus

Question 28

The higher/lower the HbS concentration inside of a RBC means that the critical nucleus concentration will be reached faster, leading to more sickling

Answer 28

higher

Question 29

Sickle cell patients must be well hydrated. Why?

Answer 29

Dehydration increases Hb concentration

Question 30

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?

Answer 30

exponential; sigmoidal

Question 31

In which circulation (venous vs. arterial) will there be more sickling?

Answer 31

Venous

Question 32

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

Answer 32

Greater

Question 33

Vasoconstriction or partial occlusion can lead to increased/decreased sickling

Answer 33

Increased bc the RBCs are spending more time in low O2 environment

Question 34

Unsickling occurs as the pO2 increases and this presents as a _____ function

Answer 34

Linear and not cooperative until the very end when complete disintegration of the polymer occurs at high pO2

Question 35

Sickling is _____ and unsickling is ______ until the very end at high pO2 when disassociation of complete disintegration of the polymer occurs

Answer 35

Cooperative; not cooperative

Question 36

T/F: Sickled cells never remain sickled permanently

Answer 36

False

Question 37

At body temp (37C) a decrease in pH will cause increased/decreased sickling

Answer 37

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

Question 38

Low pH and high temp = more/less sickling

Answer 38

More

Question 39

If sickle cell anemia patient has a fever, this will increase/decrease sickling?

Answer 39

Increase

Question 40

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?

Answer 40

Normal arterial pH