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Heme/Lymph > Disorders of Hemoglobin > Flashcards

Flashcards in Disorders of Hemoglobin Deck (26):
1

What is hemoglobin's isoelectric point?

6.8

2

Where does the negative charge in alkaline buffers migrate towards?

Migrates toward the anode (+)

3

Where does the positive charge in acid buffers migrate towards?

Migrates toward the cathode (-)

4

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)

5

What determines the extent of HbS polymerization?

Time and concentration dependent

6

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

7

What are some clinical settings that predispose to sickling??

Hypoxia
Acidosis
Dehydration
Cold temps
Infections

8

At what pressure do SS cells being to sickle?

~40 mm Hg

9

What does the lifespan of an RBC become after it has been sickled?

20 days

10

What are some effects of RBC sickling?

Chronic hemolysis
Microvascular occlusion with resultant tissue hypoxia and infarction

11

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

12

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

13

SS laboratory findings

Chronic anemia (about 7)
Increased bilirubin
Sickled cells, target cells and polychromasia
Increased reticulocytes
Normal MCV
Post-splenectomy changes in adults

14

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

15

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

16

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

17

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

18

What are some lab findings of individuals with HbC?

Hemoglobin 8-12
Numerous target cells
Mild microcytosis
Spherocytes
Occasional C crystals

19

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

20

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

21

Beta-Thal Minor

Heterozygous form
Asymptomatic
Mild to no anemia
Microcytosis
Mild anisopoikilocytosis
Basophilic stippling
Elevated HbA2

22

Alpha-Thalassemia

Usually result of gene deletion

23

Alpha-Thal
Silent carrier

1 alpha gene deleted

24

Alpha-Thal trait

2 genes deleted
Mild microcytic anemia

25

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

26

Hydrops fetalis

4 alpha genes deleted
Infants stillborn or die w/i few hours