Hemoglobin

Question 1

How much hemoglobin is synthesized before nucleus extrusion?

Answer 1

65%

Question 2

Structure of hemoglobin?

Answer 2

2 a globin chains and 2 B globin chains

Question 3

How many heme are on one subunit?

Answer 3

1 so 4 in total

Question 4

What is the predominant form of hemoglobin in adults?

Answer 4

HbA made of 2 alpha and 2 beta subunits

Question 5

What are the alpha like chains?

Answer 5

Zeta (embryonic)

Alpha

Question 6

What are the beta like chains?

Answer 6

Epsilon (embryonic)
Gamma (fetal)
Delta
Beta

Question 7

Describe embryonic hemoglobin.

Answer 7

Zeta 2 Epsilon 2

It is expressed in yolk sac but not after 8 weeks gestation

Question 8

Describe fetal Hb.

Answer 8

alpha2Gamma2 (Hbf)

Made predominately in the liver and bone marrow. Hb until 34-36 weeks gestation

Question 9

Describe adult Hb.

Answer 9

Alpha2Beta2. In newborn 50-85% is HbF, after one year it reaches 97% HbA.

Question 10

What is fetal to adult Hb switch related to?

Answer 10

Gestational age, premature infants will switch later after birth than full term babies.

Question 11

What amino acid substitution results in HbS?

Answer 11

In the beta globin a switch at amino acid 6 from valine to glutamic acid

Question 12

Significance of F8 Histidine?

Answer 12

Bound to heme group in 6th segment in globin chain.

Question 13

Significance of E7 Histidine?

Answer 13

Called distal histidine and oxygen binds to the iron between the heme and distal histidine.

Question 14

What happens when oxygen binds to Fe?

Answer 14

It pulls on the F8 proximal histidine to move the iron atom into the plane.

Question 15

Difference between myoglobin and hemoglobin?

Answer 15

Myoglobin is a storage molecule

Hemogloin is a transporter

Question 16

What pressure does Hb pick up and drop off O2?

Answer 16

picks up O2 in the lungs at 100mmHg and it drops O2 off at 10 to 20 mm Hg

Question 17

When does myoglobin release O2?

Answer 17

At very low pressures of O2 in the tissues

Question 18

What does 2,3-BPG do?

Answer 18

Shifts the curve to the right, Hb lets go easier of O2

Question 19

Describe the T and R form of Hb?

Answer 19

T has low affinity for Oxygen and R has high affinity for Oxygen.
In non oxygenated Hb beta chains are far apart in T form, in oxygenated Hb beta chains are closer together in R form

Question 20

What stabilizes the T form of Hb?

Answer 20

High 2,3-BPG to release O2

Question 21

What stabilizes R form?

Answer 21

Low 2,3-BPG in lungs leads to the R form, high affinity for O2

Question 22

What is the Bohr Effect?

Answer 22

pH of active tissues is lower which decreases affinity of Hb for O2 as pH decreases. It favors the release of 02.

Question 23

What state is HbF locked in?

Answer 23

R form, it doesn’t bind 2,3-BPG so it has high affinity for oxygen

Question 24

When oxygen is fully bound what state is favored?

Answer 24

R

Question 25

When no oxygen is bound what state is favored?

Answer 25

T

Question 26

What is HbA1c

Answer 26

Glycosylation of the N terminus of Beta globin, it is irreversible. Normally there is 3% in healthy individual in a person with diabetes there is 7-9%.

Question 27

What type of Hemoglobinopathy has a nonfunctioning globin protein and defect in Beta chain?

Answer 27

Sickle Cell

Question 28

What type of Hemoglobinopathy has insufficient amount globin chains produced leading to defective Hb production and damage to RBC's?

Answer 28

Thalassemias

Question 29

What is alpha thalassemia?

Answer 29

defect in both alpha globin chains, deletion of 1,2,3, or 4 apha globin genes. Results in an excess of beta globin. Alpha globin is in fetal and adult so it affects both.

Question 30

How does alpha thalasemia affect fetal life?

Answer 30

excess gamma globin chains tetramers called Hb Bart's.

Question 31

How does alpha thalassemia affect adults?

Answer 31

Excess Beta globin chains form Beta tetramers or HbH

Question 32

Describe alpha+- thalassemia

Answer 32

silent carrier only one alpha gene deleted. Silent hematologic phenotype or moderate thalassemeia

Question 33

Describe alpha-thalassemia train.

Answer 33

Two alpha genes deleted. Results in microcytosis (low Mean cell vol.) and Hypochromia( low mean cell hemoglobin) and normal percentages of HbA2 and HbF

Question 34

HbH disease?

Answer 34

3 alpha genes affected characterized by moderately severe anemia, microcytic, hypochromic hemolytic anemia, hepatosplenomegaly, mild jaundice. Beta tetramers form and slowly precipitate forming inclusion bodies leading to hemolytic anemia

Question 35

Describe Hydrops Fetalis with Hb Bart's.

Answer 35

Both alpha genes are inactivated. --/-- Make Gamma tetramer Hb. Binds 02 delivered by mother but doesn't release it to tissues, severe hypoxia occurs leading to the edema (hydrops) due to congestive heart failure. Massive hepatosplenomegaly. Fatal disease still born or die shortly after birth

Question 36

Beta Thalassemia?

Answer 36

Excess alpha chains precipitate as inclusions and lead to damage of RBC's, Profound anemia, bone changes, occurs early in life, splenomegaly, "Cooley's Anemia"

Question 37

What is the major form of Beta thalassemia?

Answer 37

No beta chain is expressed, severe homozygous condition. Anemia develops around age two progressively severe, failure to thrive, transfusion dependent, expansion of bone marrow.

Question 38

What is Thalassemia Minor?

Answer 38

Partial deficiency in beta chains with milder anemia

Question 39

When is Beta thalassemia seen?

Answer 39

Clinically emerges at 6-12 months of age when HbF switch to HbA occurs. Except switch from gamma to beta doesn't occur and Hb levels progressively drop. Severe anemia occurs and in a smear you see teardrop cells and targer cells.

Question 40

What is typically COD in Beta thalassemia?

Answer 40

The treatment causes death due to iron overloading from the transfusions. Patients die in their 20's or 30's from heart failure

Question 41

Describe the characteristics of hydrops fetalis including the genetic cause and the type of Hb made along with clinical presentation.

Answer 41

In hydrops fetalis both alpha genes are completely inactivated. This results in Bart's Hb, gamma tetramer Hb. This results in a very serious disease in which most babies are born stillborn or die shortly after birth. Hb Bart's has a high affinity for O2 and it binds the delivered oxygen from mother, but doesn't release it to the tissues. This results in severe hypoxia and leads to extreme edema due to CHF. Massive hepatosplenomegaly is also seen due to the body trying to make more RBC's to carry oxygen.