Flashcard Set Preview
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| 1 |
What is the structure of Fetal Hb?What percentage of Hb is in the adult and fetal form following...
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Fetal Hb consists of two alpha-globin and two gamma-globin chains. Following birth, 99% ...
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| 2 |
Thalassemias are hemoglobinopathies caused by mutations in what genes?
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the globin genes
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| 3 |
What is the genetic composition of a normal individual in terms of the globin genes?
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2 copies of alpha-globin on chromosome 16 and 1 copy of beta-globin on chromosome 11Diploid...
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| 4 |
Deficieny in the production of alpha-globin leads to what?beta-globin?
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alpha-globin: alpha-thalassemiabeta-globin: beta-thalassemia
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| 5 |
What are the genetic defects in alpha and beta-thalassemia?
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alpha-thalassemia = gene deletionBeta-thalassemia = variety of mutations
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| 6 |
What are the variety of mutations associated with Beta-thalassemia?
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promoter region and cap site, exons and introns (nonsense and frame shift), splice-junctions...
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Why are there clinical differences between alpha and beta-thalassemia?
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The duplicity of the alpha chainA singly mutated alpha gene will result in no symptoms even...
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| 8 |
alpha-thalassemiaHb hydrops fetalis (no alpha)
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clinical outcome: severe anemia; death in utero
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alpha-thalaseemiaHbH (one alpha)
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clinical outcome: moderate anemia
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alpha-thalassemiaTrait (two alphas)
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clinical outcome: mild anemia
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beta-thalassemiaBeta Major (no beta)
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clinical outcome: severe anemia, transfusions required
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beta-thalassemiaBeta Minor (one Beta)
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clinical outcome: mild anemia
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| 13 |
Treatments for Beta-thalassemia
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RBC transfusions and iron chelation therapynew: bone marrow transplantation and drug HbFLentivirus...
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| 14 |
What is the single point mutation of sickle cell anemia?
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B-chain of Hb: Glu replaced by Val at 6th position
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| 15 |
Why does HbS offer a selective advantage for resistance to Malaria?
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parasite is injected which decreases blood pH of invaded RBC thereby promoting deoxy-HbS and...
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| 16 |
What are the differences between the oxygen binding properties of HbS and Hb?
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HbS causes sickling of the RBCsdeoxy-HBs is less soluble and precipitates out of solution
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| 17 |
What are the similarities between the oxygen binding properties of HbS and Hb?
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solubility of oxyHbS normaloxygen-dissociation curve and allosteric properties equal
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| 18 |
What is the appearance of the HbS tetrameric molecules in the deoxy form?
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long fibers; Beta-6 Val of HbS makes it sticky by interacting with Phe85 and Val88 of the Beta-chain...
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| 19 |
What are the 5 factors that contribute to the sickling of RBCs?
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cell's degree of deoxygenationintracellular Hb concentration- Hb must be solublelevels of HbFextent...
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| 20 |
What typically maintains the RBC shape?
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erythrocyte membrane skeleton features a protein complex of spectrin, actin and protein 4.1
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| 21 |
Mutation in the B-globin gene leads to the ___ of ____ restriction site.
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loss; MstII restriction site
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| 22 |
What are the biochemical techniques that can be used to detect the products generated by restriction...
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restriction endonuclease digestion and Southern blot
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| 23 |
What causes the change in shape of HbS RBCs?
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aggregated state of the membrane protein complex
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| 24 |
Why are HbS red blood cells so dense?
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low levels of glutathione and oxidation of -SH groups of cysteine residues of spectrin and...
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| 25 |
Why is a consequence of changing to a sickled shape?
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results in membrane damage/leaking of K+, Cl- and water from the cells into the blood- dehydration
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| 26 |
What percentage of RBCs with HbS are irreversibly sickled?
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2-45 %
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| 27 |
What do sickled RBCs make more readily on its altered surface?
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integral erythrocyte membrane glycoproteins like glycophorins- cell adhesion molecules (CAMs)
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| 28 |
What is the function of the protein thrombospondin?
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binds to RBCs and promotes release of adhesion moleculesprovides for activation of adhesion...
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| 29 |
Sickled RBCs use adhesion molecules on the surface of endothelial cells to do what?
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to fix themselves onto blood vessels
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| 30 |
Hypoxia-reoxygenation cycles associated with sickle cell disease induce the release of what...
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Xanthine Oxidase
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| 31 |
What is the role of xanthine oxidase?
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XO binds tightly to cardiovascular walls and impairs vessel functionXO forms oxygen radical...
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| 32 |
What is chronic hemolysis?
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lysis of Hb that leads to cell free Hb in plasma to bind to NO with high affinity- leads to...
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| 33 |
What is the importance of NO to circulation?
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vaso-dilation/relaxation
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| 34 |
What are the clinical features of sickle cell disease (homozygotes for HbS)?
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anemiaperiodic severe attacks of pain and feverAcute Chest Syndrome
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| 35 |
Define the leading cause of death for sickle cell disease.
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ACS; clinically is the presence of new pulmonary infiltrates. It is constantly exposed...
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| 36 |
What is the function of the lung?
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depolymerizing organ that protects the arterial side of circulation
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| 37 |
Sickle cell disease does not appear before three months of age: Why?
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There is still an increased level of HbF in the blood. The clinical effects of HbS are...
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| 38 |
Do HbF blood levels increase, decrease or stay the same in patients with sickle cell disease? ...
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increase to offset the effects of the disease
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| 39 |
Name the 6 treatments for sickle cell disease.
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osmotic swellinghydroxyurea and erythropoietinantibiotics and steroidsstem cell transplantationtransfusionsnitric...
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| 40 |
How does hydroxyurea and erythropoietin diminish the effects of sickle cell disease?
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increase HbF, decreases HbS polymerization and risk of thrombosis
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| 41 |
Hb Hiroshima
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Beta-chain: His 146 replaced by Asp. Poor oxygen delivery in the tissue. Impaired...
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| 42 |
Hb Rahere
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Beta-chain: Lys 82 replaced by Thr. Lowered BPG binding and impaired oxygen delivery.
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Hb Titusville
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Beta-chain: Asp 94 replaced by Asn. Poor oxygen delivery. Impaired Bohr effect.
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