HEM Hematopoiesis/ Cell Morph

Question 1

Source of Erythropoietin (EPO)

Answer 1

secreted by kidney interstitial cells in hypoxic states

Question 2

What triggers increased erythropoiesis ?

Answer 2

• Low oxygen (hypoxic)

Question 3

Function of EPO

Answer 3

Promotes RBC production in bone marrow

Question 4

How is thrombopoietin a growth factor ?

Answer 4

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

Question 5

How are Colony Stimulating Factors a growth factor ?

Answer 5

triggers differentiation of myeloblasts into granulocytes

Question 6

How are thyroid hormones growth factors ?

Answer 6

promote Erythropoiesis by increasing Hgb production

Question 7

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

Answer 7

CD45

Question 8

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

Answer 8

CD34

Question 9

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

Answer 9

CD45/ CD15

Question 10

How is vit B12 absorbed/ transported ?

Answer 10

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

Question 11

Functions of vit B12 and folic acid in Erythropoiesis

Answer 11

for DNA synthesis and nuclear maturation

Question 12

Function of vit B6 (pyridoxine)

Answer 12

allow iron incorporation into protoporphyrin ring

Question 13

What state is iron when transported from intestine to storage and hematopoietic sites ?

Answer 13

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

Question 14

Where is iron stored ? Describe difference between 2 storage forms

Answer 14

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

Question 15

Describe structure of hemoglobin

Answer 15

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

Question 16

Which globin chains make up normal Hgb A1 ?

Answer 16

2 alpha & 2 beta

Question 17

Which globin chains make up normal Hgb A2 ?

Answer 17

2 alpha & 2 delta (δ)

Question 18

Which globin chains make up normal Hgb F ?

Answer 18

2 alpha & 2 gamma (γ)

Question 19

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

Answer 19

RBCs produce net 2 ATP anaerobically:

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

Question 20

Describe the Hexose monophoshpate shunt

Answer 20

• 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

Question 21

Describe the Methemoglobin reductase shunt

Answer 21

• 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 back to hemoglobin (ferrous)

NOTE: Methemoglobin cannot bind oxygen = hypoxia

Question 22

Describe the Rapoport-Leubering Pathway

Answer 22

• 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 released into tissues

Question 23

Metabolic response when [iron] increases ?

Answer 23

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

Question 24

Why is G6PD important for normal red cell survival?

Answer 24

It is required to regenerate reduced glutathione and prevent oxidative damage (by H2O2)

Question 25

Absorption of iron is most efficient in the:

a.
Stomach

b.
Ileum

c.
Duodenun

d.
Jejunum

Answer 25

c.
Duodenun

Question 26

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

Answer 26

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

2. 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

Question 27

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

Answer 27

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

Question 28

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

Answer 28

c.
Increasing cell size