The Bone Marrow and Haematopoiesis Flashcards
What cells are contained within normal peripheral blood?
1 - Platelets.
2 - RBCs.
3 - WBCs.
List all divisions and subdivisions of leukocytes.
• 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.
What is the function of platelets?
To control clot formation and breakdown.
List 2 visual characteristics of platelets.
1 - They do not have a nucleus.
2 - They are granulated.
What is the function of the granules contained within platelets?
The granules secrete the substances which control clot formation and breakdown.
What is the lifespan of a platelet?
8-12 days.
What happens to a platelet at the end of its life?
It is removed by macrophages in the spleen and liver.
List 2 symptoms of low levels of platelets.
1 - Easy bruising.
2 - Haemorrhages.
What is the lifespan of a neutrophil after it migrates from the blood into tissue?
4-5 days.
What is the function of a neutrophil?
To engulf and destroy bacteria (phagocytic).
List 3 visual characteristics of neutrophils.
1 - They have multilobed nuclei.
2 - They are granulated.
3 - They are the smallest granulocyte.
List 2 functions of eosinophils.
1 - To target parasitic infections.
2 - To control allergic reactions.
What is the primary function of basophils?
To control allergic reactions.
Which cells are involved in innate immunity?
Myeloid cells.
List 2 visual characteristics of lymphoid cells.
1 - They are granulated (however have low granularity).
2 - They are relatively small.
Where do T cells originate and develop?
- They originate in bone marrow.
- They migrate and develop in the thymus.
Where do B cells originate and develop?
In the bone marrow.
Where do NK cells originate and develop?
In the bone marrow.
What is contained within the granules of neutrophils?
1 - Lysozyme.
2 - Myeloperoxidase.
What is the function of dendritic cells?
They are antigen-presenting cells.
Where do mast cells originate and develop?
- They originate in bone marrow.
- They develop in tissues.
Where do dendritic cells originate and develop?
- They originate in bone marrow.
- They develop in tissues.
List all granulocytes, lymphocytes, RBCs and platelets in order of abundance.
For each, give an approximation of their concentration.
1 - RBCs (10^12).
2 - Platelets (10^9).
3 - Neutrophils (10^9).
4 - Eosinophils (10^9).
5 - Basophils (10^9).
6 - Lymphocytes (10^9).
What is the lifespan of a neutrophil in blood?
< 48 hours.
What is the lifespan of a red blood cell?
120 days.
What is the lifespan of a lymphocyte?
Numerous years.
Define haematopoiesis.
The production of blood cells.
At which stage in life does haematopoiesis begin?
17 days after fertilisation.
What is the rate of production of red blood cells?
10^11 per day.
What is the rate of production of neutrophils?
10^11 per day.
What is the rate of production of platelets?
10^12 per day.
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.
1 - Yolk sac (17th day).
2 - AGM.
3 - Placenta.
4 - Fetal liver. (2nd - 7th month)
5 - Bone marrow (5 - 9th month).
How does the site of haematopoiesis differ between infants and adults?
- 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).
Define stem cell.
A cell that can divide indefinitely so that it can:
1 - Replenish itself.
2 - Give rise to specialised, differentiated cells.
What is the potency of haematopoietic stem cells?
Multipotent.
What is the potency of the embryonic stem cells that give rise to haematopoietic stem cells?
Pluripotent.
List the ways in which haematopoietic stem cells / progenitors are identified.
1 - Functional assay.
2 - Immunophenotyping.
List the ways in which haematopoietic precursors and mature blood cells are identified.
1 - Marrow staining.
2 - Immunophenotyping.
What are CD markers?
A group of antigenic markers, of which each type of haematopoietic cell has a unique profile.
List the processes that contribute to a mature cell’s profile of antigenic markers.
1 - Lineage and maturation.
2 - Function.
3 - Activation.
What is immunophenotyping?
How is it done?
- 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.
Describe the development tree of myeloid cells.
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).
To which cells do megakaryocyte-erythroid progenitor cells give rise?
1 - Erythrocytes.
2 - Megakaryocytes, which give rise to platelets.
To which cells do granulocyte-macrophage progenitor cells give rise?
Granulocytes:
1 - Eosinophils.
2 - Neutrophils.
3 - Basophils.
Monocytes:
4 - Dendritic cells.
5 - Macrophages.
Describe the development tree of lymphoid cells.
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).
To which cells do common lymphoid progenitor cells give rise?
1 - T lymphocytes.
2 - B lymphocytes.
3 - NK cells.
What is a distinguishing visual characteristic of megakaryocytes?
They are relatively large.
List 2 factors that control haematopoiesis.
1 - Transcription factors.
2 - Marrow microenvironments.
Which molecules of the marrow microenvironment provide extracellular signals for haematopoietic stem cells?
Which cells of the microenvironment express these molecules?
1 - Adhesion molecules.
2 - Growth factors.
- Expressed by macrophages, fibroblasts and adipose tissue.
What type of molecules are involved in the control of haematopoiesis?
Glycoproteins.
List 4 early acting glycoproteins that are involved in the control of haematopoiesis.
1 - Stem cell factor.
2 - Flt3 ligand.
3 - IL-3.
4 - TPO.
List 4 late acting glycoproteins that are involved in the control of haematopoiesis.
1 - G-CSF.
2 - GM-CSF.
3 - EPO.
4 - TPO.
List the actions of G-CSF that are involved in the control of haematopoiesis.
1 - Proliferation.
2 - Differentiation.
3 - Suppression of apoptosis.
4 - Maturation.
5 - Functional activation.
How is a patient’s haematopoiesis status evaluated?
By taking a bone marrow biopsy from the ilium using a trephine.
List the changes undergone by a granulocyte during maturation from a GMP to a neutrophil.
1 - N:C ratio decreases.
2 - Nucleus changes from round to lobulated.
3 - Chromatin becomes more condensed.
4 - Increases in granularity.
Describe the maturation stages of a megakaryocyte-erythroid progenitor cell into red blood cells.
1 - MEP cell.
2 - Pronormoblast.
3 - Normoblast.
4 - Reticulocyte.
5 - Red blood cell.
List one difference between a late normoblast and a reticulocyte.
Normoblasts are nucleated whereas reticulytes are enucleated.
How are reticulocytes able to produce haemoglobin?
They retain the RNA when the nucleus is extruded.
Describe the process by which reticulocyte maturation is controlled.
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.
How many platelets are produced from one megakaryocyte?
2000-3000.
Describe the process of platelet production.
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.
To what degree does polyploidisation occur in a maturing megakaryocyte?
The number of nuclei increases to 64.
How long does an erythrocyte transfusion last?
1 month.
How long does a platelet transfusion last?
A few days.
How long do stem cell transplants last?
For life.
List 3 haematopoietic growth factors in clinical use.
1 - Erythropoietin.
2 - G-CSF.
3 - TPO receptor agonists.
How is erythropoietin administered?
Subcutaneously.
Where is erythropoietin used clinically?
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).
What is neutropenia?
An abnormally low level of neutrophils.
Where is G-CSF used clinically?
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).
List 2 TPO receptor agonists.
How are they administered?
1 - Romiplostim (subcutaneous injection).
2 - Eltrombopag (oral)
Where are TPO receptor agonists used clinically?
1 - For patients with myelodysplastic syndromes (malignancies that inhibit normal proliferation of myeloid stem cells).
2 - Post-chemotherapy.
What is thrombocytopenia?
An abnormally low level of platelets (platelets are also known as thrombocytes).
Define leukaemia.
A malignancy of myeloid or lymphoid cells which arise in bone marrow and spread to the blood, lymph nodes and spleen.
Define lymphoma.
A malignancy of lymphoid cells which arise in lymph nodes and the spleen and spread to involve the blood and bone marrow.
What is a myeloma?
A malignancy of plasma cells in bone marrow.
What is myeloproliferative disease / myelodysplasia?
A malignancy that inhibits normal proliferation of myeloid stem cells.
What is the difference between acute and chronic leukaemias?
- Acute leukaemias are caused by premature maturation arrest.
- Chronic leukaemias are caused by an absence of maturation arrest.
