Hematopoiesis & Its Impairments

Question 1

What percentage of BM cells are pluripotent stem cells?

Answer 1

1 in 20 million

Question 2

What receptors do pluripotent stem cells have on their surface?

Answer 2

The have growth factor receptors, i.e. GM-CSF.

Question 3

What are Burst Forming Units (BFU) and Colony Forming Units (CFU)?

Answer 3

They are the precursors to Red Blood Cells, from Common myeloid progenitor cells.

Question 4

What can we normally see microscopically in the bone marrow? Percentages?

Answer 4

Erythropoiesis (20-30%)
Myelopoiesis (60-70%)
Thrombopoiesis

Question 5

What is the order of differentiation of granulocyte precursors?

Answer 5

Blasts - Promyelocytes - Myelocytes - Metamyelocytes - Bands and Neutrophils

Question 6

What mnemonic can be used to remember the differentiation order of granulocyte precursors?

Answer 6

Blast and Play My Metal Bands and Nothing (Else)

Question 7

What is a characteristic of blast cells visibly?

Answer 7

They have smudgy chromatin

Question 8

What is a charac of promyelocytes?

Answer 8

Larger than blasts with immature nucleus. Has primary blue granules.

Question 9

What is a charac of myelocytes?

Answer 9

Small, prominent golgi with red granules.

Question 10

What is a characteristic of metamyelocyte?

Answer 10

Nucleus beings to indent

Question 11

At what two stages of granulocyte development can we regulate maturation with G-CSF?

Answer 11

Between Blasts and Promyelocytes

Between Promyelocytes and Myelocytes

Question 12

What are the three end products that can form from blast cells?

Answer 12

Bands and Neutrophils
Megakaryocytes
Normochromic Erythroblasts

Question 13

What do megakaryocytes make?

Answer 13

Platelets

Question 14

What is the prominent characteristic of megakaryocytes?

Answer 14

They are more segmented than neutrophils. Also, they are polyploidy.

Question 15

Explain the regulation of thrombopoeisis.

Answer 15

The liver produces a constant amount of TPO. In normal people, this binds to platelets and megakaryocytes (producing more platelets). In thrombocytopenia, more able to bind to megakaryocytes , leading to increased thrombopoeisis.

Question 16

What are the stages of development to erythroblasts from blasts?

Answer 16

Blast to pronormoblast to basophilic erythroblast to polychromatophilic erythroblast to normochromic erythroblast.

Question 17

What is the mnemonic to remember the development of erythroblasts?

Answer 17

Bored Princes Bump Plenty of Nights

Question 18

What are characteristics of pronormoblasts?

Answer 18

Large with dark blue cytoplasm

Question 19

What are characteristics of basophilic erythroblasts?

Answer 19

Smaller Nucleus with blue nucleus

Question 20

What are characteristics of polychromatophilic erythroblasts?

Answer 20

Grey cytoplasm

Question 21

What must normochromic erythroblasts do before they become mature?

Answer 21

They must extrude their nucleii.

Question 22

Visually compare the BM of someone age 5 and age 35

Answer 22

Age 5 has 80-90% cellularity
Age 35 has 40% cellularity

Has increasing amounts of fatty deposits.

Question 23

What does heme synthesis require?

Answer 23

Iron, B6, Succinyl CoA, Glycine (B12 and Folate)

Question 24

What does globin synthesis require?

Answer 24

Normal Globin Genes, Amino Acids

Question 25

What does DNA synthesis require?

Answer 25

``` Deoxynucleoside Triphosphates Ribonucelotide Reductase (which required Thymidine which requires B12 and Folate) ```

Question 26

What are the three ways to become anemic?

Answer 26

Losing red cells Not making enough red cells Both

Question 27

What ways do we describe cells that are iron deficient?

Answer 27

Microcytosis, Hypochromia, Anisocytosis, Poikilocytosis

Question 28

When giving someone an iron supplement, what is a good co-administration to recommend that they take as well?

Answer 28

Vitamin C, which reduces Dietary Ferric Iron to Ferrous Iron (absorbable).

Question 29

Explain the overall iron uptake process?

Answer 29

Dietary Ferric Iron in the GI tract is reduced to Ferrous Iron by Vitamin C or low pH. Then, it's transported into the plasma. Once here, it's oxidized to Ferric Iron again, where it becomes bound to transferrin. Organs possess transferrin receptors, allowing the iron to brought into cells.

Question 30

Why is the transferrin important in the plasma?

Answer 30

Prevents free iron from making superoxides

Question 31

What is serum ferritin?

Answer 31

Safely stored iron

Question 32

What is serum iron?

Answer 32

The amount of iron that is bound to transferrin in the plasma

Question 33

What levels change during iron deficiency?

Answer 33

Reduced serum iron Reduced iron saturation Increased soluble transferrin receptor (allowing as much iron uptake as possible) Transferrin will be upregulated

Question 34

What is the TIBC?

Answer 34

Total Iron Binding Capacity. The blood's ability to bind iron to transferrin. Functions as an indirect measure of transferrin levels (which is more expensive to directly measure)

Question 35

In iron deficiency how do macrophages in the spleen and liver assist?

Answer 35

They contain ferritin, which they release into the plasma. At this point, the iron is available to be brought into the bone marrow macrophages to be used as red cell precursors.

Question 36

What are characteristics of beta thalassemia?

Answer 36

Microcytic, Hypochromic, frequent target cells, normal or increased numbers of red blood cells.

Question 37

What CBC values change in Beta Thalassemia?

Answer 37

RBC goes up | Hg, Hct, and MCV go down

Question 38

What is the beta gene located?

Answer 38

On chromosome 11, with 6 total copies

Question 39

What is hemoglobin a?

Answer 39

alpha2 beta2

Question 40

What is hemoglobin a2?

Answer 40

alpha2 delta 2

Question 41

What is fetal hemoglobin?

Answer 41

alpha2 gamma2

Question 42

Where the gene locus for alpha globin?

Answer 42

On chrom 16, with 4 fxnal copies (harder to knock out)

Question 43

What area has a high rate of alpha thalassemia with one defective allele

Answer 43

SE asians

Question 44

1 Defective allele in alpha thalassemia leads to what?

Answer 44

Almost nothing

Question 45

2 defective alpha allels leads to what?

Answer 45

mild microcytic anemia, xs hg gamma4 at birth. 3% of african americans

Question 46

3 defective alpha alleles?

Answer 46

hb H disease, variable degree of microcytic anemia

Question 47

Four defective alpha allels?

Answer 47

you're dead, common in SE asia

Question 48

What is the significance of comparing nuclear and cytoplasmic development in impaired dna synthesis of rbcs?

Answer 48

normal/enhanecd maturation of cytoplasm with reduced nuclear maturation

Question 49

What causes megalobastic anemia?

Answer 49

Impaired b12 uptake impaire folate uptake drug effect intrinsic bm dysfunction

Question 50

Is delayed nuclear development common in megaloblastic anemias?

Answer 50

Yes, it's the central feature

Question 51

What comes from the spleen that is essential in causing increased erythropoeisis?

Answer 51

EPO

Question 52

What does hepcidin do?

Answer 52

Impairs the release of Fe2+ to transferrin from storage .

Question 53

How does IL6 regulated hepcidin?

Answer 53

It upregulates it's release because iron is great food for bacteria. So IL6 works to diminish serum iron