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27 Cards in this Set
- Front
- Back
what is HbA made of?
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- 2 alpha, 2 beta chains
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what are the characteristics of the alpha & beta globin cluster?
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- alpha: chromosome 16, duplicate genes, homologous
- beta: chromosome 11, one gene |
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what are the Hb genes expressed in gestation & first 6 months of life? what is Hb A2?
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- Hb F sustains fetus (alpha + gamma)
- declines by 6 months - Hb A2 = delta gene + alpha |
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what happens in CO poisoning?
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- Hb curve shifts to the left & cannot unload O2 to tissues --> hypoxia
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what does sickle cell do to the Hb curve?
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- decreased O2 binding & O2 dissociation shifted to the right
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what is the difference between a hemoglobinopathy vs thalassemia?
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- hemoglobinopathy: structural or qualitative changes in Hb
- thalassemia: mutation that leads to decreased production |
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what is beta thalassemia major (coopley's anemia)?
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- very severe anemia, transfusion dependent
- homozygous complete loss of beta globin gene expression |
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what is beta thalassemia intermedia?
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- moderate anemia, not transfusion dependent
- mutations in both alleles but quantity produced of normal HbA is greater than that seen in beta thalassemia major |
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what is beta thalassemia minor?
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- clinically mild or silent
- Mutation of single beta thalassemia allele |
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what is hydrops fetalis (bart's syndrome)?
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- incompatible with life, 4 alpha globin chain mutations
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what is Hb H disease?
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- severe phenotype
- deletion of 3 alpha genes |
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what is alpha thalassemia minor? what is homo vs heterozygous?
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- deletion of 2 alpha genes
- homozygous: on same chromosome (aa/--) - heterozygous: on alternate chromosomes (a-/a-) |
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what is alpha thalassemia trait?
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- individuals have no anemia
- deletion of 1 alpha globin gene (a-/aa) |
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what is the difference b/w a deletion & non-deletion mutation for alpha thalassemia?
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- deletion is more common and actually deletes part of gene
- non-deletion is point mutations that inactivate genes |
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what is Hb Constant Spring?
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- substitution of alpha2 termination codon --> leads to non-functional protein -> elongated unstable chain
- also a variant hemoglobinopathy b/c elongated protein chain produced in addition to decreased synthesis |
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what is the pathophysiology of alpha thalassemia?
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- beta chain excess --> beta tetramers precipitate (Hb H) --> damage & hemolysis
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what is the major difference genetically b/w alpha & beta thalassemias?
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- beta have point mutations rather than deletions
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what do the excess alpha chains bind to in beta thalassemia?
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- can bind to gamma = Hb F increased in adults
- can bind to delta = Hb A2 increased in adults - can bind to itself |
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why do beta thalassemias start having problems early in life?
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- b/c alpha is precipitating in the BM leading to destruction of RBCs & ineffective erythropoiesis
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why do you have to do iron chelation in beta thalassemias?
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- b/c giving them so much blood via transfusion
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what is HbE?
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- a combined hemoglobinopathy & thalassemia
- mutation in mRNA splice site --> reduced synthesis of b-E chain & thalassemia phenotype - abnormal b chain |
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what does the CBC look like in thalassemias?
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- low Hb & Hct
- low MCV or microcytosis = requirement - high red cell count (should be 3x Hb, but way higher than this in thalassemia) |
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what do you see on peripheral blood smear in thalassemias? how do you differentiate it from iron deficiency?
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- see small red cells, hemolytic anemia (polychromasia, basophilic stippling, elevated reticulocyte count)
- poikilocytosis (variable cell shape) - red cell fragments & target cells - iron studies NORMAL! |
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what is basophillic stippling and where do you see it?
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- accumulation of rRNA
- find in hemolytic anemia & Pb poisoning |
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what do you see on electrophoresis for thalassemias? what can you see with alpha thalassemia? HbH? beta thalassemia?
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- NORMAL b/c there is not qualitative disorder only quantitative
- alpha = only see alpha - HbH (3 alpha deleted) = fast migrating beta homotetramer - beta thalassemia = see HbA2 & HbF increased |
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what is HPLC? which thalassemia is it good for?
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- separates Hb based on hydrophobicity
- good for beta thalassemia b/c can separate out Hb A2 & HbF |
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what types of thalassemias do you generally use PCR sequencing for?
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- alpha
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