Hemoglobin Genetics and Abnormalities

Question 1

Shift of hemoglobin curve

Answer 1

If increasing affinity, move left…opposite to right

If remove allosteric, then move to left and remove sigmoid shape

Question 2

Carbon monoxide poisoning…diagnosis, symptoms, how to test

Answer 2

Flu-like viral symptoms with red cherry lips

Test for carboxyhemoglobin

Question 3

CO poison mech

Answer 3

Binds to myglobin and hemoglobin at 200 times oxygen…heme alone will bind 25000 times more strongly

Question 4

How does protein decrease binding affinity of heme for CO

Answer 4

CO prefers to bind linearly, distal histidine (E7) will prevent this…oxygen prefers bent so no effect on that

Question 5

CO half life

Answer 5

320 minutes for air
80 minutes if mask
Lower if hyperbaric oxgyen

Question 6

Alpha like and beta like Hb

Answer 6

Alpha - alpha and zeta

Beta - beta, epsilon, gamma, delta

Question 7

Hemoglobin genetics of alpha like

Answer 7

On chromo 16…2 copies of alpha and one of zeta

Question 8

Hemoglobin genetics of beta like

Answer 8

One copy of each (except gamma) on chromosome 11

Question 9

Sickle cell anemia characteristics

Answer 9

Chonic, genetically transmitted, hemolytic dz

African descent

Question 10

Sickle cell trait vs dz

Answer 10

Trait - AS, heterozygotes (HbA - 50, HbS - 40, some HbA2 and HbF)…asymptomatic

Homozygotes (SS) - HbS>80%, HbF - 1-20%, plus HbA2

Question 11

Sickle cell RBCs

Answer 11

Hemolyze more readily and lead to severe anemia….also trapped in blood vessels

Question 12

Deoxygenated HbS

Answer 12

Forms fibrous precipitate…can be revered with oxygen because HbS does not form fibers

Question 13

Sickle cell mutation and inheritance

Answer 13

In beta chain…Glu to Val
Creates sticky patch on hemoglobin surface

Auto rec

Question 14

Mech of sicle cell sticky

Answer 14

Mutant of B2 subunit attaches to normal hydrophobic subunit of B1 subunit of other deoxy HbS molecules

Question 15

Mech of malaria resistance of heterozygotes

Answer 15

Malaria caused by plasmodium…cells rupture more easily so parasite cannot mature or reporduce

Question 16

HbC and HbE hemoglobinopathy mutations and symptoms

Answer 16

HbC - glutamic to lysine at same site as HbS
HbE - glutamic to lysine at different site than HbS

Homozygotes get mild hemolytic anemia and mild splenomegaly…heterozygotes are asymptomatic

Question 17

Thalassemias result in

Answer 17

Low levels of functional HbA

Anemia, fatigue, pale skin, spleen and liver problems

Question 18

Alpha thalassemia excess and what happens

Answer 18

Excess B chains…form weak tetramers (HbH) that have binding properties more like myoglobin

Question 19

Possibilities of alpha thalssemias

Answer 19

4 deleted - embryonic lethal
3 - intermedia…30% HbH, rest HbA
2 - alpha thalassemia trait…mild anemia
1 - asymptomatic

Question 20

Beta thalassemia what happens

Answer 20

Alpha chains remain monomeric and act like myoglobin…also bind to RBC membranes and cause membrane damage

Question 21

B thalassemia major and minor

Answer 21

Major - both deleted
minor - one

HbF will be upregulated to tyr and compnesate

Question 22

Thalassemia demographics

Answer 22

Mild provide malaria protection

alpha - west africa and thai
beta - mediterranean (also some alpha)