Hematopoiesis/ Cell Morph Flashcards
Source of Erythropoietin (EPO)
secreted by kidney interstitial cells in hypoxic states
What triggers increased erythropoiesis ?
- Low oxygen (hypoxic)
Function of EPO
Promotes RBC production in bone marrow
Why does Erythropoiesis occur in bone marrow ?
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
What are stromal cells ?
- support cells in bone marrow
ie. endothelial, adipocytes, lymphocytes, osteoblasts, osteoclasts
How is thrombopoietin a growth factor ?
- secreted by liver and kidneys
- promotes development of megakaryocytes = PLTs
How are Colony Stimulating Factors a growth factor ?
triggers differentiation of myeloblasts into granulocytes
How are thyroid hormones growth factors ?
promote Erythropoiesis by increasing Hgb production
How are androgens growth factors ?
promotes EPO production
Effect of estrogen on Erythropoiesis
promotes Erythropoiesis
HSC cannot be differentiated based off light microscopy. What is the cell marker for leukocytes ?
CD45
HSC cannot be differentiated based off light microscopy. What is the cell marker for stem cells/ blasts ?
CD34
HSC cannot be differentiated based off light microscopy. What is the cell marker for granulocytes ?
CD45/ CD15
How is vit B12 absorbed/ transported ?
- in duodenum (sm int) = vit B12 combines with INTRINSIC FACTOR
- transport protein carries vit B12 across via endocytosis
Functions of vit B12 and folic acid in Erythropoiesis
for DNA synthesis and nuclear maturation
Function of vit B6 (pyridoxine)
allow iron incorporation into protoporphyrin ring
Chemical name for vit B6
Pyridoxine
How many O2 molecules can hemoglobin carry ?
FOUR; 1 for each protoporphyrin IX ring
2 main factors of iron absorption
- diet
- type of intake/ transporter molecules
How is iron transported from intestine to storage and hematopoietic sites ?
- Stomach= ferric converted to ferrous iron by acids
OR
Duodenum enterocytes (sm int) = absorbs ferrous iron - Hephaestin= converts ferrous to ferric when iron is released
- Blood= transferrin transports ferric iron
- Bone marrow= stored as hemosiderin (ferritin in macrophages)
Where is iron stored ? Describe difference between 2 storage forms
- Ferritin= clusters of iron in macrophages of LIVER
- Hemosiderin= clusters of ferritin in macrophages of BONE MARROW
Importance of vit B6/ pyridoxine & ALA synthase in heme synthesis
initiates protoporphyrin formation
Importance of Ferrochelatase in heme synthesis
catalayzes insertion of ferrous iron into protoporphyrin IX = form heme
Describe structure of hemoglobin
- 4 globin chains
- 4 protoporphyrin IX rings + 4 iron
- composition of polypeptide chain varies by age
Which globin chains make up normal Hgb A1 ?
2 alpha & 2 beta
Which globin chains make up normal Hgb A2 ?
2 alpha & 2 delta (δ)
Which globin chains make up normal Hgb F ?
2 alpha & 2 gamma (γ)
Which chromosome contains genes that code for ALPHA globin chain production ?
Chromosome 16 (4 genes)
Which chromosome contains genes that code for BETA globin chain production ?
Chromosome 11 (2 genes)
Common morph changes in maturing leukocytes
Common morph changes in maturing RBCs
Common morph changes in maturing PLTs
3 shunts of Embden-Meyerhof Pathway. What is this pathway for ?
RBCs produce net 2 ATP anaerobically:
- Hexose monophosphate
- Methemoglobin reductase
- Rapoport-Leubering Pathway
Describe the Hexose monophoshpate shunt
- prevents oxidative damage and maintain ferrous state (transports O2)
- G6P dehydrogenase = forms NADPH
- NADPH = reduced glutathione (GSH)
- GSH breaks down H2O2 to H2O and CO2
Describe the Methemoglobin reductase shunt
- slowly returns methemoglobin to ferrous state (transports O2)
- G3P dehydrogenase converts G3P to 1-3 bisphosphoglycerate and NADH
- Methemoglobin reductase uses NADH = reduced to hemoglobin
Describe the Rapoport-Leubering Pathway
- release of O2 into cells = net DEFECIT of 2 ATP in this shunt
- Bisphosphoglycerate mutase converts 1,3-BPG = produces 2,3-BPG at the COST OF 4 ATP
- 2,3-BPG competes with O2 and binds to heme iron = O2 dissociates into tissues
What happens to Hgb in both extravascular vs intravascular hemolysis ?
Extravascular= RBCs recycled in spleen; protoporphyrin excreted as bilirubin
Intravascular= Hgb released into blood are recycled in liver; protoporphyrin excreted as bilirubin
Metabolic response when [iron] increases ?
- hepcidin (acute phase reactant) binds to ferroportin
- prevents enterocytes from releasing iron into bloodstream
Why is G6PD important for normal red cell survival?
It is required to regenerate reduced glutathione
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.
Incorporate iron into the protoporphyrin ring
Absorption of iron is most efficient in the:
a.
Stomach
b.
Ileum
c.
Duodenun
d.
Jejunum
c.
Duodenun
All of the following are carriers of hemoglobin except:
a.
Albumin
b.
Hemopexin
c.
LDH
d.
Haptoglobin
c.
LDH
- Explain why oxidative stress is detrimental to a RBC.
- How do RBCs prevent oxidative damage to itself ?
1.
- Oxidative stress damages Hemoglobin by oxidizing iron into the ferric form
- Methemoglobin is ineffective at oxygen transport
- 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
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
d.
pronormoblast, basophilic normoblast, polychromatic normoblast, orthochromic normoblast, reticulocyte, mature RBC
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
c.
Increasing cell size
