Flashcards in Disorders of Hemoglobin Deck (26):
What is hemoglobin's isoelectric point?
Where does the negative charge in alkaline buffers migrate towards?
Migrates toward the anode (+)
Where does the positive charge in acid buffers migrate towards?
Migrates toward the cathode (-)
What is the genetic abnormality in sickle cell disease?
Homozygous abnormality of beta globin chain
Glu to Val substitution at amino acid 6 of beta chain (beta6Val)
What determines the extent of HbS polymerization?
Time and concentration dependent
What are some factors that affect the concentration of HbS?
Percentage of hemoglobin S of total hemoglobin
Total hemoglobin concentration in the red cells (MCHC) -- increased in states of cellular dehydration, decreased when there is co-existent thalassemia
What are some clinical settings that predispose to sickling??
At what pressure do SS cells being to sickle?
~40 mm Hg
What does the lifespan of an RBC become after it has been sickled?
What are some effects of RBC sickling?
Microvascular occlusion with resultant tissue hypoxia and infarction
Why are newborns with SS clinically fine? When do they begin to show symptoms?
High HbF levels at first
Show signs by about 10-12 weeks
Some clinical manifestations of SS
Acute pain crises
Acute chest syndrome
Aplast crisis (parvovirus B19_
Splenic sequestration crisis
SS laboratory findings
Chronic anemia (about 7)
Sickled cells, target cells and polychromasia
Post-splenectomy changes in adults
What is hemoglobin SC disease??
Hemoglobin C results from glu to lys substitution at the 6th amino acid of the beta globin chain
Generally milder than SS, but highly variable
What is Hb S/Beta thalassemia?
Heterozygous Hb S with trans beta thalassemia allele --> decreased or absent normal beta chains
Hb S > Hb A
How does Hydroxyurea help to treat sickle cell disease?
Inhibits ribonucleotide reductase and causes cell cycle arrest
Increases erythrocyte levels of HbF, ameliorating the sickling manifestations
What is HbC disease? (CC)
Glu to Lys substitution of aa 6 on beta chain
Cells abnormally rigid and dehydrated
RBC life span shorted to 30-35 days
NOT a sickling disorder
What are some lab findings of individuals with HbC?
Numerous target cells
Occasional C crystals
What are thalassemias?
Typically microcytic, hypochromic anemias of varying severity -- d/t decreased Hb production (cytoplastmic maturation defect)
Excess normally produced globin chains accumulate and cause intramedullary cell death and/or decreased RBC survival
Absent or marked decrease in beta chain production
Excess normal alpha chains which precipitate in normoblast and erythrocytes
Intramedullary cell death and decreased RBC lifespan
Severe anemia-- baseline Hb of 2-3
Mild to no anemia
Usually result of gene deletion
1 alpha gene deleted
2 genes deleted
Mild microcytic anemia
Hemoglobin H disease
3 alpha genes deleted
Mild-moderate, chronic hemolytic anemia
Hb H represents beta tetramers
Hb H soluble so does not initially ppt in normoblasts