Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

HEME > Hemoglobin Disorders (Thalassemia and Sickle Cell) > Flashcards

Hemoglobin Disorders (Thalassemia and Sickle Cell) Flashcards

1
Q

How many Beta globin genes are present on each chromosome?

A

one

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What chromosome is the Beta globin gene located on

A

chromosome 11

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What genotypes are considered to be B-thalassemia major?

A

Bo/Bo or B+/B+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What genotypes are considered to be B-thalassemia minor?

A

B/Bo or B/B+

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Main sign of B-thalassemia minor

A

mild microcytic anemia

Thus, you’ll have decreased hepcidin and increased ferroportin to increase duodenal absorption

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is Fetal Hemoglobin’s structure (HgF)

A

Alpha2/Gamma2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is Hemoglobin A2’s stucture

A

Alpha2/Delta2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is Hemoglobin H’s structure

A

tetramer of betaglobin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Normally, when you’re born what happens to your alpha chain, beta chain, and gamma chain levels

A

alpha chain levels increase slightly but remains relatively constant compared to fetal levels
beta chain levels (initially 0) increase dramatically, and your gamma chain levels decrease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

How many alpha globulin genes are on each chromosome?

A

2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What chromosome is the alpha globulin gene located on?

A

chromosome 16

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Genetic Mechanism causing Alpha Thalassemias

A

gene deletions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Genetic Mechanism causing Beta Thalassemias

A

gene point mutations

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

If one of the 4 alpha genes is deleted, what condition do you have?

A

Alpha Thalassemia silent carrier or Alpha Thalaseemia Trait 1 (-a/aa) but you won’t have anemia because you do have a functional alpha globulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

If two of the 4 alpha genes is deleted, what condition do you have

A

Alpha Thalassemia trait 2 (–/aa) or (-a/-a), in 3% in African Americans

note. you will have some Hb Bart’s in this case

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

If three of the 4 alpha genes are deleted, what condition do you have?

A

Hemoglobin H Disease (a beta tetramer aka HgH)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

If 4 of the 4 alpha genes are deleted, what condition do you have

A

Hydrops Fetalis (from gamma tetramer aka HbBart’s)

18
Q

Microscopic Findings in both Thalassemia’s

A

target cells

microcytic rbc’s

19
Q

Pathogenesis of Beta Thalassemia Major

A

you have massive erythroid hyperplasia (overactive bone marrow pushing out immature cells) that just can’t mature before they die

point mutations on both alleles of beta globulin means decreased beta globulin production.

The subsequent accumulation of unpaired Alpha globulins causes a bunch of bad things. These unpaired globulins–>alpha “hemichromes” or clumps–>inclusion bodies–>mess with cytoskeleton, flip membrane so inner proteins like phosphatidylserine are on the outside. leads to:

Thrombotic tendencies
Membrane damage
Autoimmune hemolysis
Ineffective erythropoesis

20
Q

Why is there Iron Overload in Severe Thalassemia?

A

overactive bone marrow from ineffective erythropoesis reduces hepcidin levels, so you have increased ferroportin, and thus increased serum iron.

you also get excess iron in severe thalassemia when you require chronic blood transfusions (so you should give the blood transfusion with an iron chelator

Iron overload–>cirrhosis–>liver cancer

21
Q

Pathogenesis of Alpha Thalassemia (specfically 3 alpha’s missing)

A

deletion of alpha genes–>unpaired beta’s form tetramers (HgH), but also these beta hemochromes–>heinz bodies and precipitate out, which leads to hemolysis too

note, you see hemolysis and ineffective erythropoesis, but WAY more hemolysis in peripheral blood, red blood cells can actually develop to maturity before lysing.

22
Q

Clinical Findings of Beta Thalassemia Major

A
  1. Expanded facial features, because of expanded bones
  2. Expanded bone marrow–>osteoporosis
  3. Splayed teeth from expanded mandible and maxillary
  4. hepatosplenegomy
  5. skin ulcers (seen in a lot of hemolytic anemias)
23
Q

Clinical Impact of Iron Load in B-Thalassemia Major?

A 
organ damage to...
Liver
Heart
Pancreas
Thyroid
Pituitary gland
Other endocrine organs
24
Q

Why do you not want to do phlebotomy to correct iron overload in Beta Thalassemia Major (you do it in Hemochromatosis)

A

Because in B-Thalassemia, you’re anemic…you DO NOT want to take out MORE blood cells from the body!

25
Q

CBC indicators of thalasemia

A

anemia, microcytic conditions, but normal levels of everything else

26
Q

How do you confirm alpha thalasemia with lab test?

A

you essentially have to first rule out beta thalasemia with a hemoglobin electrophoresis (bc beta thalasemia has elevated HgA2 and HgF) NO iron deficiency

next, you can do PCR for a common mutation (Weir didn’t specify which one)

also in the US you’re more likely to see this condition in African Americans

27
Q

How do you confirm suspicion of beta thalasemia?

A

anemia but no iron deficiency.

hemoglobin electrophoresis checking for elevated HgA2 and HgF

28
Q

Both thalassemia’s are microcytic anemias. What lab value differentiates it from other microcytic anemias?

A

normal (or elevated) iron levels, normal levels of transferrin and ferritin, may have reduced hepcidin IF IRON OVERLOAD, but the MAIN THING:

MCV««70!

29
Q

Treatment option for Beta Thalassemia Major

A

iron chelating (bc of iron overload)
chronic blood transfusions from a young age
treat osteoporosis
treat hypogonadism and other endocrine probz

30
Q

Are allogenic bone marrow transplants successful for thalasemia?

A

In young people yea!

31
Q

Which has a higher affinity for oxygen, HbA or HbH and Hb Bart’s? What’s the implication of this?

A

HbH and Hb Bart’s have a higher affinity for oxygen.
This is bad because they won’t dump the oxygen into tissues like normal hemoglobin
You get hypoxiaaa

32
Q

Do you get iron overload?

A

Not usually…so you don’t get all the endocrine and organ problems as you do in beta thalassemia major

33
Q

Microcytic indication of Alpha Thalasemia that WONT be in Beta Thalassemia?

A

inclusion bodies of HgH (beta globin tetramers) in mature red cells (“golf ball cells” in peripheral blood

34
Q

Genetic cause for Sickle Cell Trait or Disease

A

point mutation on the 6th amino acid for B globulin, causing glutamic acid to change into valine
(to have the disease you need point mutation in both chromosomes)

8% African Americans have the gene

35
Q

Pathogenesis of Sickle Cell Disease

A

mutated betahemoglobin molecules come together to form polymers, altering skeletal shape of the red blood cells. So they plug shit up and cause ischemic damage

Plus, when you have infarctions of bones and other tissues, it is not just due to the clogging of vessels by sickled cells…it is also the resultant inflammatory damage by the white cells and the released nitric oxide (causing vascular spasm)

36
Q

Clinical Findings of Sickle Cells Disease

A

“Hand-foot syndrome” : Dactylitis in children–>epiphyseal infarction, leading to shortened digits

Acute Chest Syndrome: due to fat embolization from the infarcted bone, can clog up pulmonary vessels, causing alveolar edema–>respiratory distress

Skin necrosis and ulceration

37
Q 
On an agar gel, what hemoglobin types would each of the following have a positive result for?
Beta Thal.
Sickle Cell Disease
Sickle Cell Trait
Hemoglobin C
Normal
A 
Beta thalassemia: elevation of A2
Sickle Cell :all S 
Sickle Cell Trait: elevated A and S (more A than S) 
Hb C: A and C
Normal: A
38
Q

Clinical Presentation of S/Beta-thal 0?

A

You would have sickle cell anemia with increased hemoglobin A2 and hemoglobin F levels

39
Q

Sickle Cell Disease Therapy

A

Aggressively Hydrate
Transfuse in certain life threatening situations
(Severe anemia, hepatic crisis, acute chest syndrome, priapism, prophylactic transfusions in children with strokes)
Pain control
Oxygen if hypoxic

40
Q

What do you have to be worried about with chronic transfusions in sickle cell patients

A

They run an increased risk of developing antibodies to minor antigens in donor blood

41
Q

Mechanism of Action of Hydroxyurea treatment for Sickle Cell Anemia

A

Preventative treatment

Inhibits ribonucleotide reductase

It increases fetal hemoglobin and decreases white cells, this is for patients with recurrent crises, so you markedly diminish the crises by decreasing likelihood of flareups

HEME (4 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions