Disorders of Hemoglobin Flashcards
What is hemoglobin’s isoelectric point?
6.8
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??
Hypoxia Acidosis Dehydration Cold temps Infections
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?
20 days
What are some effects of RBC sickling?
Chronic hemolysis
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
Severe anemia Acute pain crises Auto-splenectomy Acute chest syndrome Strokes Aplast crisis (parvovirus B19_ Infections Liver damage Splenic sequestration crisis Megaloblastic anemia Growth retardation Bony abnormalities Renal dysfunction Leg ulcers Cholelithiasis
SS laboratory findings
Chronic anemia (about 7) Increased bilirubin Sickled cells, target cells and polychromasia Increased reticulocytes Normal MCV 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
Clinically variable
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?
Hemoglobin 8-12 Numerous target cells Mild microcytosis Spherocytes 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
Beta-Thal Major
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
Transfusion dependent
Beta-Thal Minor
Heterozygous form Asymptomatic Mild to no anemia Microcytosis Mild anisopoikilocytosis Basophilic stippling Elevated HbA2
Alpha-Thalassemia
Usually result of gene deletion
Alpha-Thal
Silent carrier
1 alpha gene deleted
Alpha-Thal trait
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
Hydrops fetalis
4 alpha genes deleted
Infants stillborn or die w/i few hours
