Ch. 17 Hemoglobinopathies Flashcards
Destruction of Anemias can be either…
Hereditary
Acquired
Hereditary Destruction Anemias can be classified as
Hemoglobinopathies
Membrane Structural defects
Enzyme defects in RBC defects
Acquired Destruction Anemias can be classified as
Paroxysmal Hemoglobinuria
Immune mediated
Hemoglobinopathies can be due to either
Defective globin synthesis (qualitative defect)
Underproduction of globin chains (quantitative defect)
This is a quantitative defect hemoglobinopathy
Thalassemia
Hemoglobin structure
Heme - 4 Fe atoms surrounded by pyrope ring
Globin - Each ring attached to globin
Hgb A1
alpha 2 beta 2
97% of hemoglobin
Hgb A2
alpha 2 delta 2
<3% of hemoglobin
Hgb F
alpha 2 gamma 2
<2% of hemoglobin
How can gene mutations affect globin chains?
Deletions or substitution of amino acids
Mutations of globin chains can lead to
Dysfunctional hemoglobins that may or may not be clinically silent
What does the efficiency of variant globin chains look like?
Less efficient, see more hgb A1 in heterozygotes than variant hemoglobin
Almost all clinically important globin mutations are where?
Beta chain
If gamma chain abnormalities were present, what would happen?
Fetal death, incompatible with life
Delta chain abnormalities are present, what would happen?
Unimportant because Hgb A2 is <3%
How many copies of defective beta globin chains would one need to have to see disease?
4 copies of alpha chain genes (2 from mom 2 from dad), so more copies are required to see disease
Why is beta chain defect so important?
HgbA1 is the most abundant
Most common lethal mutation in humans
Hemoglobinopathies
Hemoglobinopathies are concentrated in what countries?
Africa
Mediterranean basin
Southeast Asia
Heritages from those countries
How were hemoglobinopathies named initially?
Letters of the alphabet
Hgb A for adult, F for fetal, M for methemoglobin, S for sickle cells.
How are hemoglobinopathies named now?
Which globin chain is affected and what amino acid has changed
(Hgb S = alpha2 beta2 6glu–>val)
Heterozygous
trait
Homozygous
Disease or anemia
Most prevalent hemoglobinopathy world wide
Hgb S
Where is the substitution made on Hgb S?
Valine instead of glutamic acid
6th position of the beta chain
Homozygous notation for Hgb S
Alpha 2 Beta 2 6 glu –> val
Hgb S notation for heterozygous
alpha 2 beta 1 beta 1 6 glu –> val
What is the theory surrounding Hgb S?
Heterozygous state against P. falciparum malaria
Hemoglobin C substitution
Glutamic acid –> Lysine substitution
6th position of the beta chain
Homozygous notation for Hgb C
alpha 2 beta 2 6 glu –> lys
Heterozygous notation for Hgb C
alpha 2 beta 1 beta 1 6 glu –> lys
Geographic Association with Hgb C
same as Hgb S
Why is Hgb C prevalent in the same populations as Hgb S?
thought to assist with malaria resistance
Homozygous Hgb S
Hemoglobin SS
Sickle Cell Anemia
How much hgb A1 is produced in Hgb SS?
None
What percent of African descendants in the US have Hgb SS
0.3-1.3%
Heterogynous Hgb S
Hemoglobin SA
Sickle Cell trait
What percentage of African descendants have Hgb SA
8-10%
How does hemoglobin S function under normal oxygen tension?
Normally
