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MLSCI330 Hematology > Hematopoiesis/ Cell Morph > Flashcards

Hematopoiesis/ Cell Morph Flashcards

1
Q

Source of Erythropoietin (EPO)

A

secreted by kidney interstitial cells in hypoxic states

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2
Q

What triggers increased erythropoiesis ?

A
  • Low oxygen (hypoxic)
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3
Q

Function of EPO

A

Promotes RBC production in bone marrow

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4
Q

Why does Erythropoiesis occur in bone marrow ?

A

Microenvironment of :
- STROMAL CELLS secrete cytokines and growth factors
- GROWTH FACTORS (EPO, thrombopoietin, cytokines, estrogen, androgens, thyroid hormones)
- hematopoietic stem cells (HSC)
- regulating HORMONES and mechanisms

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5
Q

What are stromal cells ?

A
  • support cells in bone marrow
    ie. endothelial, adipocytes, lymphocytes, osteoblasts, osteoclasts
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6
Q

How is thrombopoietin a growth factor ?

A
  • secreted by liver and kidneys
  • promotes development of megakaryocytes = PLTs
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7
Q

How are Colony Stimulating Factors a growth factor ?

A

triggers differentiation of myeloblasts into granulocytes

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8
Q

How are thyroid hormones growth factors ?

A

promote Erythropoiesis by increasing Hgb production

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9
Q

How are androgens growth factors ?

A

promotes EPO production

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10
Q

Effect of estrogen on Erythropoiesis

A

promotes Erythropoiesis

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11
Q

HSC cannot be differentiated based off light microscopy. What is the cell marker for leukocytes ?

A

CD45

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12
Q

HSC cannot be differentiated based off light microscopy. What is the cell marker for stem cells/ blasts ?

A

CD34

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13
Q

HSC cannot be differentiated based off light microscopy. What is the cell marker for granulocytes ?

A

CD45/ CD15

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14
Q

How is vit B12 absorbed/ transported ?

A
  • in duodenum (sm int) = vit B12 combines with INTRINSIC FACTOR
  • transport protein carries vit B12 across via endocytosis
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15
Q

Functions of vit B12 and folic acid in Erythropoiesis

A

for DNA synthesis and nuclear maturation

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16
Q

Function of vit B6 (pyridoxine)

A

allow iron incorporation into protoporphyrin ring

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17
Q

Chemical name for vit B6

A

Pyridoxine

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18
Q

How many O2 molecules can hemoglobin carry ?

A

FOUR; 1 for each protoporphyrin IX ring

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19
Q

2 main factors of iron absorption

A
  1. diet
  2. type of intake/ transporter molecules
20
Q

How is iron transported from intestine to storage and hematopoietic sites ?

A
  1. Stomach= ferric converted to ferrous iron by acids
    OR
    Duodenum enterocytes (sm int) = absorbs ferrous iron
  2. Hephaestin= converts ferrous to ferric when iron is released
  3. Blood= transferrin transports ferric iron
  4. Bone marrow= stored as hemosiderin (ferritin in macrophages)
21
Q

Where is iron stored ? Describe difference between 2 storage forms

A
  1. Ferritin= clusters of iron in macrophages of LIVER
  2. Hemosiderin= clusters of ferritin in macrophages of BONE MARROW
22
Q

Importance of vit B6/ pyridoxine & ALA synthase in heme synthesis

A

initiates protoporphyrin formation

23
Q

Importance of Ferrochelatase in heme synthesis

A

catalayzes insertion of ferrous iron into protoporphyrin IX = form heme

24
Q

Describe structure of hemoglobin

A
  • 4 globin chains
  • 4 protoporphyrin IX rings + 4 iron
  • composition of polypeptide chain varies by age
25
Q

Which globin chains make up normal Hgb A1 ?

A

2 alpha & 2 beta

26
Q

Which globin chains make up normal Hgb A2 ?

A

2 alpha & 2 delta (δ)

27
Q

Which globin chains make up normal Hgb F ?

A

2 alpha & 2 gamma (γ)

28
Q

Which chromosome contains genes that code for ALPHA globin chain production ?

A

Chromosome 16 (4 genes)

29
Q

Which chromosome contains genes that code for BETA globin chain production ?

A

Chromosome 11 (2 genes)

30
Q

Common morph changes in maturing leukocytes

A
31
Q

Common morph changes in maturing RBCs

A
32
Q

Common morph changes in maturing PLTs

A
33
Q

3 shunts of Embden-Meyerhof Pathway. What is this pathway for ?

A

RBCs produce net 2 ATP anaerobically:

  1. Hexose monophosphate
  2. Methemoglobin reductase
  3. Rapoport-Leubering Pathway
34
Q

Describe the Hexose monophoshpate shunt

A
  • prevents oxidative damage and maintain ferrous state (transports O2)
  1. G6P dehydrogenase = forms NADPH
  2. NADPH = reduced glutathione (GSH)
  3. GSH breaks down H2O2 to H2O and CO2
35
Q

Describe the Methemoglobin reductase shunt

A
  • slowly returns methemoglobin to ferrous state (transports O2)
  1. G3P dehydrogenase converts G3P to 1-3 bisphosphoglycerate and NADH
  2. Methemoglobin reductase uses NADH = reduced to hemoglobin
36
Q

Describe the Rapoport-Leubering Pathway

A
  • release of O2 into cells = net DEFECIT of 2 ATP in this shunt
  1. Bisphosphoglycerate mutase converts 1,3-BPG = produces 2,3-BPG at the COST OF 4 ATP
  2. 2,3-BPG competes with O2 and binds to heme iron = O2 dissociates into tissues
37
Q

What happens to Hgb in both extravascular vs intravascular hemolysis ?

A

Extravascular= RBCs recycled in spleen; protoporphyrin excreted as bilirubin

Intravascular= Hgb released into blood are recycled in liver; protoporphyrin excreted as bilirubin

38
Q

Metabolic response when [iron] increases ?

A
  • hepcidin (acute phase reactant) binds to ferroportin
  • prevents enterocytes from releasing iron into bloodstream
39
Q

Why is G6PD important for normal red cell survival?

A

It is required to regenerate reduced glutathione

40
Q

What is the function of vitamin B6 (pyridoxine)?

a.
Incorporate iron into the protoporphyrin ring

b.
Activate ALA synthetase to promote iron absorption

c.
Cleave folate from transporters for absorption

d.
Increase iron absorption

A

a.
Incorporate iron into the protoporphyrin ring

41
Q

Absorption of iron is most efficient in the:

a.
Stomach

b.
Ileum

c.
Duodenun

d.
Jejunum

A

c.
Duodenun

42
Q

All of the following are carriers of hemoglobin except:

a.
Albumin

b.
Hemopexin

c.
LDH

d.
Haptoglobin

A

c.
LDH

43
Q
  1. Explain why oxidative stress is detrimental to a RBC.
  2. How do RBCs prevent oxidative damage to itself ?
A

1.
- Oxidative stress damages Hemoglobin by oxidizing iron into the ferric form
- Methemoglobin is ineffective at oxygen transport

  1. Hexose monophosphate shunt:
    - G6P dehydrogenase oxidizes G6P to form NADPH
    - NADPH is used to form reduced glutathione (GSH)
    - GSH breaks down radicals such as hydrogen peroxide = forms water and carbon dioxide
44
Q

What is the sequence of maturity for red blood cells?

a.
basophilic normoblast, pronormoblast, polychromatic normoblast, orthochromic normoblast, reticulocyte, mature RBC

b.
basophilis normoblast, pronormoblast, orthochromic normoblast, polychromatic normoblast, reticulocyte, mature RBC

c.
pronormoblast, basophilic normoblast, polychromatic normoblast, orthochromic normoblast, mature RBC, reticulocyte

d.
pronormoblast, basophilic normoblast, polychromatic normoblast, orthochromic normoblast, reticulocyte, mature RBC

A

d.
pronormoblast, basophilic normoblast, polychromatic normoblast, orthochromic normoblast, reticulocyte, mature RBC

45
Q

Which of the following is not associated with increasing cell maturity in the granulocytic series?

a.
Condensation of chromatin

b.
Segmentation of the nucleus

c.
Increasing cell size

d.
Loss of nucleoli

A

c.
Increasing cell size

46
Q
A

MLSCI330 Hematology (10 decks)

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