01b: Anemia

Question 1

Anemia can be macro/micro/normo-cytic based on:

Answer 1

MCV

Question 2

Megaloblastic anemia: you would expect MCV to be…

Answer 2

over 100 (macrocytic anemia)

Question 3

Megaloblastic anemia: defective (X) is the main mechanism of this disease.

Answer 3

X = DNA synthesis

Question 4

T/F: There’s both defective DNA and RNA synthesis in megaloblastic anemia.

Answer 4

False - just DNA

Question 5

T/F: Megaloblasts are larger and more fragile than their normal bone marrow counterparts.

Answer 5

True - autohemolysis and increased intramedullary cell death

Question 6

T/F: Megaloblasts have high cytoplasmic:nuclear ratio.

Answer 6

False - vice versa

Question 7

Megaloblastic anemia: (pan/reticulo)-cytopenia.

Answer 7

Both

Question 8

List some laboratory findings seen in megaloblastic anemia.

Answer 8

1. High MCV, LDH, BR, serum Fe

2. Low plasma haptoglobin

Question 9

Three main causes of megaloblastic anemia.

Answer 9

1. Folate deficiency
2. B12 deficiency
3. Other rare causes

Question 10

List some drug classes that can cause folate deficiency

Answer 10

Barbiturates and anticonvulsants

Question 11

List some situations/diseases in which increased folate utilization may cause deficiency

Answer 11

1. Pregnancy
2. Hemolytic anemia
3. Inflammatory conditions (RA, Crohn’s, eczema)

Question 12

Folate deficiency can be diagnosed by measuring:

Answer 12

1. serum folate (under 3ug/L)
2. RBC folate (under 100 ug/L)
3. serum homocysteine (elevated)

Question 13

T/F: parenteral folate preparation is seldom needed to correct deficiency.

Answer 13

True

Question 14

T/F: Vitamin B12 deficiency can result in intracellular Folate deficiency

Answer 14

True

Question 15

T/F: Mammals, not plants, synthesize vitamin B12 de novo

Answer 15

False - mammals and higher plants cannot synthesize this (obtained by diet only)

Question 16

T/F: vitamin B12 obtained mainly from animal sources in diet.

Answer 16

True (liver, eggs, cheese, milk,

mollusks)

Question 17

(X) body tissue has large stores (years-worth) of vitamin B12.

Answer 17

X = liver

Question 18

Most common form of vitamin B12 deficiency

Answer 18

Pernicious anemia (acquired/autoimmune or congenital)

Question 19

List some drugs that decrease vitamin B12 absorption

Answer 19

1. Metformin
2. Isoniazid
3. PPIs and H2 blockers
4. Colchicine
5. Neomycin

Question 20

T/F: Nitric oxide is a drug that decreases vitamin B12 absorption.

Answer 20

False - destroys B12

Question 21

T/F: Combined System’s Disease may occur in absence of anemia.

Answer 21

True

Question 22

HbA2 has which chains? How much is in normal adult blood?

Answer 22

2 alpha, 2 delta

3% of Hgb

Question 23

HbS is formed by (X) mutation in (Y) gene.

Answer 23

X = point (GAG to GTG; Glu to Val)
Y = beta-globin codon 6

Question 24

HbC is formed by (X) mutation in (Y) gene.

Answer 24

X = point (GAG to AAG; Glu to Lys)
Y = beta-globin codon 6

Question 25

HbE is formed by (X) mutation in (Y) gene.

Answer 25

``` X = point (GAG to AAG; Glu to Lys) Y = beta-globin codon 26 ```

Question 26

(X) is essentially the only FDA approved drug for SCD. It reduces which Sx/complications?

Answer 26

X = hydroxyurea Pain, hemolysis, acute chest syndrome, and mortality

Question 27

SCD: Transfusions should be used cautiously in which scenarios?

Answer 27

1. Anemia 2. Acute chest syndrome 3. Stroke prevention 4. Pre-op 5. Pregnancy 6. Renal failure

Question 28

Unlike HbS, HbF has a (more/less) hydrophobic patch for lateral interactions with Val on HbS, thus preventing sickling/polymerization.

Answer 28

Less

Question 29

Hb Barts hydrops fetalis is a result of which changes in (X) genes?

Answer 29

Absence of all 4 X = alpha-globin So Hb Bart's (4 gamma chains) are made

Question 30

Hb Bart's causes (anemia/tissue hypoxia) by which mechanism?

Answer 30

Both Anemia: unstable Hgb forms precipitates and shortens RBC life span Hypoxia: unable to deliver O2 to tissues

Question 31

T/F: Patients with identical | β-thalassemia mutations might have different clinical course.

Answer 31

True - depends not only on genotypes, but interactions between other genes/globins

Question 32

Leading cause of death in thalassemias

Answer 32

CV complications

Question 33

T/F: Thalassemia is fatal by age 5 if untreated

Answer 33

True

Question 34

T/F: Sickle cell trait is not a disease

Answer 34

True- normal blood count/film, lifespan, and very few medical problems

Question 35

List some genotypes that comprise the phenotype of SCD

Answer 35

1. HbS homozygote 2. HbSC heterozygotes 3. HbS-beta thal heterozygotes 4. HbSE heterozygotes

Question 36

Aplastic crisis can occur in children with SCD that's complicated by:

Answer 36

Infection (Parvo, salmonella, EBV)

Question 37

Which health maintenance steps are important for kids with SCD?

Answer 37

1. Prophylactic antibiotics 2. Immunization 3. Hydroxyurea 4. Education

Question 38

Most common mutations of beta+ thalassemia are (X) mutations.

Answer 38

X = splicing

Question 39

Most common mutations of beta-0 thalassemia are (X) mutations.

Answer 39

X = nonsense/termination

Question 40

T/F: Individual that's homozygous for HbS also has coexistent α-thalassemia, which leads to milder disease

Answer 40

True- the thalassemia reduces Hb synthesis

Question 41

Sickling of RBC: severe derangement in membrane | structure causes the influx of (X) ions, which then activates an ion channel that permits the efflux of (Y) ions.

Answer 41

``` X = Ca Y = K (and water) ```

Question 42

SCD: The severity of hemolysis correlates with | the percentage of (X) cells.

Answer 42

X = irreversibly sickled cells (even when oxygenated; caused by repetitive sickling/unsickling)

Question 43

T/F: SCD consists of extravascular hemolysis.

Answer 43

True BUT also some intravascular hemolysis

Question 44

T/F: In SCD, microvascular occlusions are related to the number of irreversibly sickled cells in the blood.

Answer 44

False - may be due to other subtle factors, not sure?

Question 45

After vascular injury, platelets bind via (X) receptors to (Y) on exposed extracellular matrix (ECM). This causes them to:

Answer 45

``` X = Glycoprotein Ib (GpIb) Y = vWF ``` Change shape and secrete granules

Question 46

Formation of platelet plug is confined to the area of injury due to action of:

Answer 46

tPA and thrombomodulin

Question 47

Thrombomodulin binds to (X) and converts it from a (pro/anti)-coagulant into a (pro/anti)-coagulant via its ability to (activate/inhibit) (Y).

Answer 47

X = thrombin Pro- to Anti- Activate Y = Protein C (which inhibits FVa and VIIIa)

Question 48

Bernard-Soulier Syndrome is deficiency in:

Answer 48

GpIb receptor on platelet

Question 49

Glanzmann thrombasthenia is deficiency in:

Answer 49

Gp-IIb-IIIa receptor on platelet