H&M Chp 2

Question 1

Cell lineage of erythropoiesis

Answer 1

stem cell–>CFUgemm–> BFUe–>CFUe–> erythrocyte precursor

Question 2

What is the first recognizable erythrocyte precursor found in the bone marrow?

Answer 2

pronormoblast

Question 3

What do pronormoblasts look like?

Answer 3

large cell, dark blue cytoplasm, central nucleus with nucleoli, slightly clumped chromatin

Question 4

Pronormoblasts give rise to ___ mature red cells.

Answer 4

16

Question 5

Are nucleated red cells/normoblasts found in peripheral blood?

Answer 5

No- unless erythropoiesis is occuring in extramedullary erythropoiesis or some marrow diseases

Question 6

Of normoblasts, reticulocytes, RBC, which contain nuclear DNA?

Answer 6

normoblast only

Question 7

Of normoblasts, reticulocytes, RBC, which contain RNA in cytoplasm?

Answer 7

normoblast and reticulocyte

Question 8

Of normoblasts, reticulocytes, RBC, which are found in the bone marrow?

Answer 8

all 3

Question 9

Of normoblasts, reticulocytes, RBC, which are found in peripheral blood?

Answer 9

reticulocytes and RBC

Question 10

As normoblasts give rise to progessively smaller cells, they contain progressively more ____ and progessively less _____.

Answer 10

hemoglobin; RNA and protein synthetic apparatus

Question 11

What happens to the nucleus and chromatin as normoblasts are dividing?

Answer 11

becomes more condensed, nucleus is excluded from late normoblasts forming reticulocytes

Question 12

Describe reticulocytes

Answer 12

slightly larger than RBC, 1-2 days in marrow and circulate for 1-2 days before losing all RNA and becoming RBC

Question 13

Describe the structure of erythropoietin.

Answer 13

heavily glycosylated, 165 aa, 34 kDa

Question 14

90% of erythropoietin is produced by ____. 10% is produced by _____.

Answer 14

peritubular interstitial cells of kidney; liver and other places

Question 15

Are there preformed stores of erythropoietin?

Answer 15

no

Question 16

What is the stimulus for production of erythropoietin?

Answer 16

oxygen tension in tissues of the kidney. Hypoxia–> HIFa and b–> erythropoietin production

Question 17

The erythropoietin gene contains a ____ at its 3’ end.

Answer 17

Hif response element

Question 18

Erythropoietin production ____ in anemia. Why?

Answer 18

increases- O2 delivery to kidney is affected

Question 19

What is the function of GATA-1 and FOG-1

Answer 19

These are stimulated by erythropoietin. They enhance expression of erythroid-specific genes and anti-apoptotic genes of the transferring receptor

Question 20

What is the main indication for erythropoietin therapy?

Answer 20

end stage renal disease

Question 21

What metals are required for effective erythropoiesis?

Answer 21

iron and cobalt

Question 22

What vitamins are required for effective erythropoiesis

Answer 22

B12, folate, C, E, B, thiamin, riboflavin

Question 23

What hormones are required for effective erythropoiesis?

Answer 23

androgens, thyroxine

Question 24

Describe Hb A

Answer 24

dominant Hb after 3-6 monthes of age. alpha2beta2 polypeptide chains. Each chain has its own heme group

Question 25

Describe the chains that make up Hb F

Answer 25

alpha2 gamma 2

Question 26

Describe the chains that make up Hb A2

Answer 26

alpha-2-delta-2

Question 27

Heme synthesis occurs largely in the ____.

Answer 27

mitochondria

Question 28

What is the 1st step of heme synthesis?

Answer 28

glycine+ succinyl coA= porphobilinogen. enzyme: rate limiting aminoaevulinic acid (ALA)
coenzyme: B6, which is stim. by erythropoietin

Question 29

What 2 things ultimately come together to form heme?

Answer 29

Fe and protoporphyrin

Question 30

What 2 things come together to form hemoglobin?

Answer 30

heme (from mitochondria) and globin (a2b2 from ribosomes)

Question 31

What do the B chains do when O2 is unloaded?

Answer 31

they are pulled apart, permitting entry of 2,3 DPG resulting in a lower affinity for O2

Question 32

What chain contacts stabilize hemoglobin?

Answer 32

A1B1, A2B2

Question 33

What causes the O2 hemoglobin dissociation curve to shift to the right?

Answer 33

high concentrations of H (lower pH), CO2, DPG, Hb S

Question 34

What causes the O2 hemoglobin dissociation curve to shift to the left?

Answer 34

Hb F,

Question 35

_____ is a clinical state where circulating hemoglobin presents with Fe3 instead of Fe2

Answer 35

methaemoglobinaemia

Question 36

Hemoglobin is broken down by ____.

Answer 36

macrophages

Question 37

When are erythropoietin levels high? Low?

Answer 37

High: tumor secreting erythropoietin causing polycythaemia, low in severe renal disease or polycythaemia vera

Question 38

Side effects of erythropoietin therapy?

Answer 38

rise in blood pressure, thrombosis, local injection reactions

Question 39

What is often needed to maximize erythropoietin therapy?

Answer 39

oral/parenteral iron

Question 40

The P50 of normal blood is ____

Answer 40

26.6 mmHg

Question 41

Inherited defects of RBC membrane proteins can cause _____

Answer 41

spherocytosis and elliptocytosis