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IIH > The Bone Marrow and Haematopoiesis > Flashcards

The Bone Marrow and Haematopoiesis Flashcards

1
Q

What cells are contained within normal peripheral blood?

A

1 - Platelets.

2 - RBCs.

3 - WBCs.

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2
Q

List all divisions and subdivisions of leukocytes.

A

• Lymphoid:

1 - T cells.

2 - B cells.

3 - NK cells.

• Myeloid:

  • Monocytes:

4 - Dendritic cells.

5 - Macrophages.

  • Granulocytes:

6 - Eosinophils.

7 - Basophils.

8 - Neutrophils.

9 - Mast cells.

  • Erythrocytes.
  • Megakaryocytes.
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3
Q

What is the function of platelets?

A

To control clot formation and breakdown.

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4
Q

List 2 visual characteristics of platelets.

A

1 - They do not have a nucleus.

2 - They are granulated.

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5
Q

What is the function of the granules contained within platelets?

A

The granules secrete the substances which control clot formation and breakdown.

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6
Q

What is the lifespan of a platelet?

A

8-12 days.

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7
Q

What happens to a platelet at the end of its life?

A

It is removed by macrophages in the spleen and liver.

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8
Q

List 2 symptoms of low levels of platelets.

A

1 - Easy bruising.

2 - Haemorrhages.

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9
Q

What is the lifespan of a neutrophil after it migrates from the blood into tissue?

A

4-5 days.

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10
Q

What is the function of a neutrophil?

A

To engulf and destroy bacteria (phagocytic).

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11
Q

List 3 visual characteristics of neutrophils.

A

1 - They have multilobed nuclei.

2 - They are granulated.

3 - They are the smallest granulocyte.

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12
Q

List 2 functions of eosinophils.

A

1 - To target parasitic infections.

2 - To control allergic reactions.

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13
Q

What is the primary function of basophils?

A

To control allergic reactions.

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14
Q

Which cells are involved in innate immunity?

A

Myeloid cells.

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15
Q

List 2 visual characteristics of lymphoid cells.

A

1 - They are granulated (however have low granularity).

2 - They are relatively small.

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16
Q

Where do T cells originate and develop?

A
  • They originate in bone marrow.

- They migrate and develop in the thymus.

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17
Q

Where do B cells originate and develop?

A

In the bone marrow.

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18
Q

Where do NK cells originate and develop?

A

In the bone marrow.

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19
Q

What is contained within the granules of neutrophils?

A

1 - Lysozyme.

2 - Myeloperoxidase.

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20
Q

What is the function of dendritic cells?

A

They are antigen-presenting cells.

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21
Q

Where do mast cells originate and develop?

A
  • They originate in bone marrow.

- They develop in tissues.

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22
Q

Where do dendritic cells originate and develop?

A
  • They originate in bone marrow.

- They develop in tissues.

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23
Q

List all granulocytes, lymphocytes, RBCs and platelets in order of abundance.

For each, give an approximation of their concentration.

A

1 - RBCs (10^12).

2 - Platelets (10^9).

3 - Neutrophils (10^9).

4 - Eosinophils (10^9).

5 - Basophils (10^9).

6 - Lymphocytes (10^9).

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24
Q

What is the lifespan of a neutrophil in blood?

A

< 48 hours.

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25
Q

What is the lifespan of a red blood cell?

A

120 days.

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26
Q

What is the lifespan of a lymphocyte?

A

Numerous years.

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27
Q

Define haematopoiesis.

A

The production of blood cells.

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28
Q

At which stage in life does haematopoiesis begin?

A

17 days after fertilisation.

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29
Q

What is the rate of production of red blood cells?

A

10^11 per day.

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30
Q

What is the rate of production of neutrophils?

A

10^11 per day.

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31
Q

What is the rate of production of platelets?

A

10^12 per day.

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32
Q

List the sites of haematopoiesis from birth in order from the earliest stage to the latest.

Give an approximation of the number of days / months after conception that these events occur.

A

1 - Yolk sac (17th day).

2 - AGM.

3 - Placenta.

4 - Fetal liver. (2nd - 7th month)

5 - Bone marrow (5 - 9th month).

33
Q

How does the site of haematopoiesis differ between infants and adults?

A
  • In infants, bone marrow in all bones is involved in haematopoiesis.
  • In adults, only the bone marrow in the axial skeleton is involved in haematopoiesis (termed red marrow).
34
Q

Define stem cell.

A

A cell that can divide indefinitely so that it can:

1 - Replenish itself.

2 - Give rise to specialised, differentiated cells.

35
Q

What is the potency of haematopoietic stem cells?

A

Multipotent.

36
Q

What is the potency of the embryonic stem cells that give rise to haematopoietic stem cells?

A

Pluripotent.

37
Q

List the ways in which haematopoietic stem cells / progenitors are identified.

A

1 - Functional assay.

2 - Immunophenotyping.

38
Q

List the ways in which haematopoietic precursors and mature blood cells are identified.

A

1 - Marrow staining.

2 - Immunophenotyping.

39
Q

What are CD markers?

A

A group of antigenic markers, of which each type of haematopoietic cell has a unique profile.

40
Q

List the processes that contribute to a mature cell’s profile of antigenic markers.

A

1 - Lineage and maturation.

2 - Function.

3 - Activation.

41
Q

What is immunophenotyping?

How is it done?

A
  • The use of monoclonal antibodies to identify a cell by matching its antigenic markers to a known profile.
  • Usually done by flow cytometry detecting fluorescent antibodies.
42
Q

Describe the development tree of myeloid cells.

A

Initial steps taken by all mature blood cells:

1 - Long-term haematopoietic stem cell (LT-HSC).

2 - Short-term haematopoietic stem cell (ST-HSC).

3 - Multipotent progenitor cell (MPP).

Subsequent steps for myeloid lineage:

4 - Common myeloid progenitor cell (CMP).

5 - Granulocyte-macrophage progenitor cell (GMP) and megakaryocyte-erythroid progenitor cell (MEP).

43
Q

To which cells do megakaryocyte-erythroid progenitor cells give rise?

A

1 - Erythrocytes.

2 - Megakaryocytes, which give rise to platelets.

44
Q

To which cells do granulocyte-macrophage progenitor cells give rise?

A

Granulocytes:

1 - Eosinophils.

2 - Neutrophils.

3 - Basophils.

Monocytes:

4 - Dendritic cells.

5 - Macrophages.

45
Q

Describe the development tree of lymphoid cells.

A

Initial steps taken by all mature blood cells:

1 - Long-term haematopoietic stem cell (LT-HSC).

2 - Short-term haematopoietic stem cell (ST-HSC).

3 - Multipotent progenitor cell (MPP).

Subsequent steps for lymphoid lineage:

4 - Common lymphoid progenitor cell (CLP).

46
Q

To which cells do common lymphoid progenitor cells give rise?

A

1 - T lymphocytes.

2 - B lymphocytes.

3 - NK cells.

47
Q

What is a distinguishing visual characteristic of megakaryocytes?

A

They are relatively large.

48
Q

List 2 factors that control haematopoiesis.

A

1 - Transcription factors.

2 - Marrow microenvironments.

49
Q

Which molecules of the marrow microenvironment provide extracellular signals for haematopoietic stem cells?

Which cells of the microenvironment express these molecules?

A

1 - Adhesion molecules.

2 - Growth factors.

  • Expressed by macrophages, fibroblasts and adipose tissue.
50
Q

What type of molecules are involved in the control of haematopoiesis?

A

Glycoproteins.

51
Q

List 4 early acting glycoproteins that are involved in the control of haematopoiesis.

A

1 - Stem cell factor.

2 - Flt3 ligand.

3 - IL-3.

4 - TPO.

52
Q

List 4 late acting glycoproteins that are involved in the control of haematopoiesis.

A

1 - G-CSF.

2 - GM-CSF.

3 - EPO.

4 - TPO.

53
Q

List the actions of G-CSF that are involved in the control of haematopoiesis.

A

1 - Proliferation.

2 - Differentiation.

3 - Suppression of apoptosis.

4 - Maturation.

5 - Functional activation.

54
Q

How is a patient’s haematopoiesis status evaluated?

A

By taking a bone marrow biopsy from the ilium using a trephine.

55
Q

List the changes undergone by a granulocyte during maturation from a GMP to a neutrophil.

A

1 - N:C ratio decreases.

2 - Nucleus changes from round to lobulated.

3 - Chromatin becomes more condensed.

4 - Increases in granularity.

56
Q

Describe the maturation stages of a megakaryocyte-erythroid progenitor cell into red blood cells.

A

1 - MEP cell.

2 - Pronormoblast.

3 - Normoblast.

4 - Reticulocyte.

5 - Red blood cell.

57
Q

List one difference between a late normoblast and a reticulocyte.

A

Normoblasts are nucleated whereas reticulytes are enucleated.

58
Q

How are reticulocytes able to produce haemoglobin?

A

They retain the RNA when the nucleus is extruded.

59
Q

Describe the process by which reticulocyte maturation is controlled.

A

1 - Circulating reticulocytes are carried by red blood cells to the kidney.

2 - An O2 sensor in the kidney stimulates peritubular interstitial cells of the outer cortex to secrete erythropoietin.

3 - Erythropoietin triggers the maturation of erythropoietic stem cells in the bone marrow.

60
Q

How many platelets are produced from one megakaryocyte?

A

2000-3000.

61
Q

Describe the process of platelet production.

A

Thrombopoietin (TPO) binds to the TPO receptor on the MEP cell, causing:

1 - Early differentiation,
2 - Proliferation,
3 - Polyploidisation,
4 - Cytoplasmic maturation and
5 - Subsequent platelet release.
62
Q

To what degree does polyploidisation occur in a maturing megakaryocyte?

A

The number of nuclei increases to 64.

63
Q

How long does an erythrocyte transfusion last?

A

1 month.

64
Q

How long does a platelet transfusion last?

A

A few days.

65
Q

How long do stem cell transplants last?

A

For life.

66
Q

List 3 haematopoietic growth factors in clinical use.

A

1 - Erythropoietin.

2 - G-CSF.

3 - TPO receptor agonists.

67
Q

How is erythropoietin administered?

A

Subcutaneously.

68
Q

Where is erythropoietin used clinically?

A

1 - Most often used for patients with end-stage renal disease, where endogenous erythropoietin is low.

2 - For Jehovah’s witnesses that cannot undergo transfusions.

3 - For patients with myelodysplastic syndromes (malignancies that inhibit normal proliferation of myeloid stem cells).

69
Q

What is neutropenia?

A

An abnormally low level of neutrophils.

70
Q

Where is G-CSF used clinically?

A

1 - For primary or secondary prevention of infections in neutropenic patients (e.g. post-chemotherapy).

2 - To mobilise stem cells into the peripheral blood for stem cell harvests (useful for stem cell transplants).

71
Q

List 2 TPO receptor agonists.

How are they administered?

A

1 - Romiplostim (subcutaneous injection).

2 - Eltrombopag (oral)

72
Q

Where are TPO receptor agonists used clinically?

A

1 - For patients with myelodysplastic syndromes (malignancies that inhibit normal proliferation of myeloid stem cells).

2 - Post-chemotherapy.

73
Q

What is thrombocytopenia?

A

An abnormally low level of platelets (platelets are also known as thrombocytes).

74
Q

Define leukaemia.

A

A malignancy of myeloid or lymphoid cells which arise in bone marrow and spread to the blood, lymph nodes and spleen.

75
Q

Define lymphoma.

A

A malignancy of lymphoid cells which arise in lymph nodes and the spleen and spread to involve the blood and bone marrow.

76
Q

What is a myeloma?

A

A malignancy of plasma cells in bone marrow.

77
Q

What is myeloproliferative disease / myelodysplasia?

A

A malignancy that inhibits normal proliferation of myeloid stem cells.

78
Q

What is the difference between acute and chronic leukaemias?

A
  • Acute leukaemias are caused by premature maturation arrest.
  • Chronic leukaemias are caused by an absence of maturation arrest.

IIH (26 decks)

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