Hemoglobin Flashcards
How much hemoglobin is synthesized before nucleus extrusion?
65%
Structure of hemoglobin?
2 a globin chains and 2 B globin chains
How many heme are on one subunit?
1 so 4 in total
What is the predominant form of hemoglobin in adults?
HbA made of 2 alpha and 2 beta subunits
What are the alpha like chains?
Zeta (embryonic)
Alpha
What are the beta like chains?
Epsilon (embryonic)
Gamma (fetal)
Delta
Beta
Describe embryonic hemoglobin.
Zeta 2 Epsilon 2
It is expressed in yolk sac but not after 8 weeks gestation
Describe fetal Hb.
alpha2Gamma2 (Hbf)
Made predominately in the liver and bone marrow. Hb until 34-36 weeks gestation
Describe adult Hb.
Alpha2Beta2. In newborn 50-85% is HbF, after one year it reaches 97% HbA.
What is fetal to adult Hb switch related to?
Gestational age, premature infants will switch later after birth than full term babies.
What amino acid substitution results in HbS?
In the beta globin a switch at amino acid 6 from valine to glutamic acid
Significance of F8 Histidine?
Bound to heme group in 6th segment in globin chain.
Significance of E7 Histidine?
Called distal histidine and oxygen binds to the iron between the heme and distal histidine.
What happens when oxygen binds to Fe?
It pulls on the F8 proximal histidine to move the iron atom into the plane.
Difference between myoglobin and hemoglobin?
Myoglobin is a storage molecule
Hemogloin is a transporter
What pressure does Hb pick up and drop off O2?
picks up O2 in the lungs at 100mmHg and it drops O2 off at 10 to 20 mm Hg
When does myoglobin release O2?
At very low pressures of O2 in the tissues
What does 2,3-BPG do?
Shifts the curve to the right, Hb lets go easier of O2
Describe the T and R form of Hb?
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
What stabilizes the T form of Hb?
High 2,3-BPG to release O2
What stabilizes R form?
Low 2,3-BPG in lungs leads to the R form, high affinity for O2
What is the Bohr Effect?
pH of active tissues is lower which decreases affinity of Hb for O2 as pH decreases. It favors the release of 02.
What state is HbF locked in?
R form, it doesn’t bind 2,3-BPG so it has high affinity for oxygen
When oxygen is fully bound what state is favored?
R
When no oxygen is bound what state is favored?
T
What is HbA1c
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%.
What type of Hemoglobinopathy has a nonfunctioning globin protein and defect in Beta chain?
Sickle Cell
What type of Hemoglobinopathy has insufficient amount globin chains produced leading to defective Hb production and damage to RBC’s?
Thalassemias
What is alpha thalassemia?
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.
How does alpha thalasemia affect fetal life?
excess gamma globin chains tetramers called Hb Bart’s.
How does alpha thalassemia affect adults?
Excess Beta globin chains form Beta tetramers or HbH
Describe alpha+- thalassemia
silent carrier only one alpha gene deleted. Silent hematologic phenotype or moderate thalassemeia
Describe alpha-thalassemia train.
Two alpha genes deleted. Results in microcytosis (low Mean cell vol.) and Hypochromia( low mean cell hemoglobin) and normal percentages of HbA2 and HbF
HbH disease?
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
Describe Hydrops Fetalis with Hb Bart’s.
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
Beta Thalassemia?
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”
What is the major form of Beta thalassemia?
No beta chain is expressed, severe homozygous condition. Anemia develops around age two progressively severe, failure to thrive, transfusion dependent, expansion of bone marrow.
What is Thalassemia Minor?
Partial deficiency in beta chains with milder anemia
When is Beta thalassemia seen?
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.
What is typically COD in Beta thalassemia?
The treatment causes death due to iron overloading from the transfusions. Patients die in their 20’s or 30’s from heart failure
Describe the characteristics of hydrops fetalis including the genetic cause and the type of Hb made along with clinical presentation.
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.
