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

Why does Erythropoiesis occur in bone marrow ?

Answer 4

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

Question 5

What are stromal cells ?

Answer 5

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

Question 6

How is thrombopoietin a growth factor ?

Answer 6

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

Question 7

How are Colony Stimulating Factors a growth factor ?

Answer 7

triggers differentiation of myeloblasts into granulocytes

Question 8

How are thyroid hormones growth factors ?

Answer 8

promote Erythropoiesis by increasing Hgb production

Question 9

How are androgens growth factors ?

Answer 9

promotes EPO production

Question 10

Effect of estrogen on Erythropoiesis

Answer 10

promotes Erythropoiesis

Question 11

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

Answer 11

CD45

Question 12

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

Answer 12

CD34

Question 13

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

Answer 13

CD45/ CD15

Question 14

How is vit B12 absorbed/ transported ?

Answer 14

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

Question 15

Functions of vit B12 and folic acid in Erythropoiesis

Answer 15

for DNA synthesis and nuclear maturation

Question 16

Function of vit B6 (pyridoxine)

Answer 16

allow iron incorporation into protoporphyrin ring

Question 17

Chemical name for vit B6

Answer 17

Pyridoxine

Question 18

How many O2 molecules can hemoglobin carry ?

Answer 18

FOUR; 1 for each protoporphyrin IX ring

Question 19

2 main factors of iron absorption

Answer 19

1. diet
2. type of intake/ transporter molecules

Question 20

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

Answer 20

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)

Question 21

Where is iron stored ? Describe difference between 2 storage forms

Answer 21

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

Question 22

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

Answer 22

initiates protoporphyrin formation

Question 23

Importance of Ferrochelatase in heme synthesis

Answer 23

catalayzes insertion of ferrous iron into protoporphyrin IX = form heme

Question 24

Describe structure of hemoglobin

Answer 24

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

Question 25

Which globin chains make up normal Hgb A1 ?

Answer 25

2 alpha & 2 beta

Question 26

Which globin chains make up normal Hgb A2 ?

Answer 26

2 alpha & 2 delta (δ)

Question 27

Which globin chains make up normal Hgb F ?

Answer 27

2 alpha & 2 gamma (γ)

Question 28

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

Answer 28

Chromosome 16 (4 genes)

Question 29

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

Answer 29

Chromosome 11 (2 genes)

Question 30

Common morph changes in maturing leukocytes

Question 31

Common morph changes in maturing RBCs

Question 32

Common morph changes in maturing PLTs

Question 33

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

Answer 33

RBCs produce net 2 ATP anaerobically: 1. Hexose monophosphate 2. Methemoglobin reductase 3. Rapoport-Leubering Pathway

Question 34

Describe the Hexose monophoshpate shunt

Answer 34

- 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 35

Describe the Methemoglobin reductase shunt

Answer 35

- 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

Question 36

Describe the Rapoport-Leubering Pathway

Answer 36

- 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

Question 37

What happens to Hgb in both extravascular vs intravascular hemolysis ?

Answer 37

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

Question 38

Metabolic response when [iron] increases ?

Answer 38

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

Question 39

Why is G6PD important for normal red cell survival?

Answer 39

It is required to regenerate reduced glutathione

Question 40

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

Answer 40

a. Incorporate iron into the protoporphyrin ring

Question 41

Absorption of iron is most efficient in the: a. Stomach b. Ileum c. Duodenun d. Jejunum

Answer 41

c. Duodenun

Question 42

All of the following are carriers of hemoglobin except: a. Albumin b. Hemopexin c. LDH d. Haptoglobin

Answer 42

c. LDH

Question 43

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

Answer 43

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 44

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 44

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

Question 45

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 45

c. Increasing cell size