Bhl Week 1: Bone Marrow And Hematopoiesis

Front 1

What type of stem cells give rise to all lines of mature blood cells?

Back 1

Pluripotent (totipotent) stem cells

Front 2

T or F

Other than red blood cells, pluripotent stem cells also give rise to some endothelial cells.

Back 2

TRUE

Front 3

What phase are most pluripotent stem cells in?

Back 3

Resting (G0 phase)

Front 4

How many days does it take for a stem cell to mature to a blood cell?

Back 4

10 - 14 days

Front 5

Hematopoietic stem cells initially differentiate into which progenitor cells?

Back 5

1. Common myeloid progenitor (CMP)
2. Common lymphoid progenitor (CLP)

Front 6

CMPs give rise to which cells?

Back 6

1. Erythrocytes
2. Megakaryocytes
3. Granulocytes
4. Monocytes

Front 7

CLPs give rise to which cells?

Back 7

1. B-cells
2. T-cells

Front 8

What does lineage selection probably depend on?

Back 8

1. Mix of growth factors
2. Spatial localization in marrow (specialized niches)

Front 9

Describe where hematopoiesis takes place in the 1st, 2nd, and 3rd trimester.

Back 9

1st trimester --> yolk sac and aorta-gonadal-mesoderm (AGM) area
2nd trimester --> predominantly liver; less so spleen
3rd trimester --> Bone marrow becomes predominant

Front 10

What's the difference between red and yellow bone marrow?

Back 10

Red marrow --> active hematopoiesis; (axial skeleton)

Yellow marrow --> no active hematopoiesis, mainly adipose

Front 11

What type of stromal cells are found in bone marrow?

Back 11

1. Adventitial cells (fibroblast-like)
2. Macrophages
3. Adipocytes
4. Lymphocytes

Front 12

Describe the hematopoietic growth factor receptors and the intracellular signals involved.

Back 12

Many of the receptors are (or activate) protein tyrosine kinases

Signaling pathways involved = JAK, STAT

Front 13

Where are the hematopoietic growth factors mostly produced and which cells produce them?

Back 13

Mostly produced in the bone marrow

*Produced by macrophages, T-cells, adventitial cells

*A few produced outside marrow--> erythropoietin and thrombopoietin

Front 14

Where is Erythropoietin produced?

Back 14

Primarily in kidneys; small amount in liver

Front 15

Where is Thrombopoietin produced?

Back 15

Primarily in liver; some in spleen and bone marrow

Front 16

Where is G-CSF produced, and which cells produce it?

Back 16

Bone marrow

*Produced by macrophages, T-cells, fibroblasts, and/or endothelial cells

Front 17

List 2 therapeutic uses for G-CSF.

Back 17

1. Granulocytopenia due to chemotherapy and other causes
2. Bone marrow transplantation

Front 18

What is the function of G-CSF?

Back 18

1. Stimulates production of granulocytes
2. Stimulates function of mature cells

Front 19

Where is GM-CSF produced, and which cells produce it?

Back 19

Bone marrow

*Produced by macrophages, T-cells, fibroblasts and/or endothelial cells

Front 20

What is the function of GM-CSF?

Back 20

1. Stimulations production of granulocytes AND monocytes
2. Stimulates function of mature cells

Front 21

What are the therapeutic uses of GM-CSF?

Back 21

1. Granulocytopenia due to chemotheraphy and other causes
2. Bone marrow transplantation

Front 22

What conditions stimulate the production of erythropoietin?

Back 22

Renal ischemia or hypoxia

Front 23

List 4 clinical uses of erythropoietin.

Back 23

Anemia caused by:
1. Renal failure
2. Chronic disease (chronic inflammatory states)
3. AIDS
4. Cancer chemotherapy

Front 24

What is the function of thrombopoietin?

Back 24

Stimulates megakaryocyte differentiation and platelet production.

Front 25

What are the possible uses of thrombopoietin?

Back 25

1. Thrombocytopenia
2. Cancer chemotherapy
3. Bone marrow transplantation

Front 26

Name 2 thrombopoietin mimetics that are aprroved for chronic immune thrombocytopenic purpura (ITP).

Back 26

1. Romiplostim (Nplate)
2. Eltrombopag (Promacta)

Front 27

What is the first recognizable granulocyte precursor?

Back 27

Myeloblast

Front 28

What is the key feature of promyelocytes?

Back 28

The presence of primary granules--> large, reddish-purple granules.

(The nucleus remains pretty large and uncondensed, and usually will have a nucleolus)

Front 29

What is the distinguishing feature of the myelocyte stage of granulocyte maturation?

What does the nucleus look like?

Back 29

Presence of secondary granules
(Neutrophilic, eosinophilic, basophilic)

*Nucleus is still round, but may start to become condensed and dark, and the nucleolus is often lost

Front 30

The ability to differentiate different granulocyte precursors begins at what stage of maturation?

Back 30

Myelocyte stage
(depends on which secondary granules the cells have)

Front 31

Describe the shape of the nucleus of a myelocyte, metamyelocyte, band neutrophil, and segmented neutrophil.

Back 31

Myelocyte --> Round
Metamyelocyte --> Indented ("kidney bean")
Band neutrophil --> Horseshoe-shaped
Segmented neutrophil --> Multiple lobes connected by thin strand of chromatin

Front 32

In the early stages of granulocyte maturation, where are the primary changes in the cell occurring?

What about in the late stages of maturation?

Back 32

Early stages --> changes in cytoplasm

Late stages --> changes in nucleus

Front 33

When do granules appear during granulocyte maturation?

Back 33

Promyelocyte stage

(No granules are present in myeloblast stage)

Front 34

Which stage of granulocyte maturation has large, reddish-purple primary granules?

Back 34

Promyelocyte

Front 35

As the granulocyte matures, explain what type of changes occur in the cytoplasm, nucleus, and nucleolus.

Back 35

1. Cytoplasm changes from gray to yellow-tan color
2. Nucleus becomes smaller and more condensed
3. Nucleolus disappears

Front 36

Which stage of granulocyte maturation has an indented, bean-shaped nucleus?

Back 36

Metamyelocyte

Front 37

Which stage of granulocyte maturation has a horse-shoe shaped nucleus?

Back 37

Neutrophilic band

Front 38

What stage of granulocyte should NOT be seen in normal blood smears?

Back 38

Myelocytes and earlier forms (blasts, promyelocytes)

Front 39

Which stage of erythrocyte development has grayish cytoplasm with a condensed nucleus?

Back 39

Polychromatophilic erythroblast

Front 40

Which stage of erythrocyte development has fine chromatin and deep blue cytoplasm?

Back 40

Proerythroblast

Front 41

Which stage of erythrocyte development has red-orange cytoplasm, and a dark, condensed nucleus?

Back 41

Orthochromatophilic eryrthroblast

Front 42

What's the best way to tell a myeloblast and a proerthythroblast apart?

Back 42

Myeloblast has light grey cytoplasm, while a proerythroblast has dark blue cytoplasm

Front 43

When does hemoglobinization begin during erythrocyte maturation?

Back 43

Polychromatophilic erythroblast stage

Front 44

At which stage in erythrocyte maturation is the cell fully hemoglobinized?

Back 44

Orthochromic erythroblast stage

Front 45

Describe the physical appearance of a megakaryocyte.

Back 45

Polylobated nucleus
Abundant pale blue cytoplasm with fine granules

Front 46

What happens between the megakaryoblast stage and the mature megakaryocyte stage?

Back 46

Endomitosis
(multiplication of DNA)

Front 47

A leukoerythroblastic reaction involves the abnormal presence of which cells?

Back 47

Nucleated RBCs and granulocyte precursors in peripheral blood

Front 48

What does a leukoerythroblastic reaction indicate?

Back 48

Abnormality in bone marrow:
1. Fibrosis
2. Metastatic neoplasm
3. Granulomas
4. Osteosclerosis

*Indication for bone biopsy