Haematopoeisis Flashcards
Haematopoiesis
formation and development of blood cells
Cellular component of RBC
Erythrocyte
Name the Granulocytes (3)
- Neutrophil
- Eosinophil
- Basophil
Name the Lymphocytes (3)
- B cell
- T cell
- NK cell
Name the 3 types of Leukocytes/WBC (3)
- Lymphocytes
- Granulocytes
- Dendritic cells
What do Megakaryocytes mature into?
Platelets
Where does Haematopoeisis occur?
Bone Marrow
Stages of cell development (4)
- Haematopoietic Stem Cells
- Common Progenitors
- Committed Progenitors
- Mature cells
Describe:
- Haematopoietic Stem Cells
- Common Progenitors
- Committed Progenitors
- Mature cells
(4)
- Multipotent
- Oligopotent
- Unipotent
- released into blood stream
Multipotent (2)
- can self-renew
- can differentiate into any type of HSC
Oligopotent (2)
- can self renew
- can differentiate into a subset of cell types
Unipotent (2)
- can only differentiate into 1 cell type
- with many intermediate stages
Outline the basic stages of Haematopoeisis (5)
- Proliferation
- Differentiation
- Maturation
- Egress from bone marrow
- Survival in tissue
Outline process of Haematopoeisis leading to Platelets (7)
- Long term HSC
- Short term HSC
- Multi Potent Progenitor
- Common Myeloid Progenitor
- Megakaryocyte-Erythroid Progenitor
- Megakaryocyte
- Platelets
Outline process of Haematopoeisis leading to Erythrocytes (6)
- Long term HSC
- Short term HSC
- Multi Potent Progenitor
- Common Myeloid Progenitor
- Megakaryocyte-Erythroid Progenitor
- Erythrocytes
Outline process of Haematopoeisis leading to Granulocytes (6)
- Long term HSC
- Short term HSC
- Multi Potent Progenitor
- Common Myeloid Progenitor
- Granulocyte-Macrophage Prog.
- Granulocytes
Outline process of Haematopoeisis leading to Monocyte (6)
- Long term HSC
- Short term HSC
- Multi Potent Progenitor
- Common Myeloid Progenitor
- Granulocyte-Macrophage Prog.
- Monocyte
Outline process of Haematopoeisis leading to B-cell and T-cell (6)
- Long term HSC
- Short term HSC
- Multi Potent Progenitor
- Common Lymphoid Progenitor
- Pro B and Pro T
- B-cell and T-cell
What needs to maintained to preserve Haematopoeisis?
HSC pool
Stem Cell Factor (1)
What does SCF bind to? (1)
Where is SCF produced? (1)
- Haematopoietic cytokine
- binds to c-kit (the SCF receptor)
- produced by endothelial cells and fibroblasts in bone marrow
What is the differentiation signal for MPP to CMP?
IL-3
What is the differentiation signal for MPP to CLP?
IL-7
BFU (2)
- Burst forming units
- highly proliferative
CFU (2)
- Colony forming units
- limited proliferative capacity
What causes BFU-E to proliferate?
IL-3
What happens when IL-3 causes BFU-E to proliferate? (2)
- rises to multi-clustered colonies of erythroid progenitors (CFU-E)
- which develop to become Erythrocytes (RBC)
Why can’t CFU-E self-proliferate?
When can they proliferate?
- because they only have Erythropoietin receptor
- they can proliferate with Erythropoietin (EPO) binding to its EPO receptor
Stages of Erythrocyte development (6)
- Proerythroblast
- Basophilic Erythroblast
- Polychromatic Erythroblast
- Orthochromatic Erythroblast
- Reticulocyte
- Erythrocyte
How are Erythrocytes removed from circulation? (2)
- Macrophages break them down
- recycle Haemoglobin
What regulates Erythropoiesis? (2)
- Receptors in Kidney tubules
- EPO
Hypoxia (1)
Hypoxia contributing factors (5)
Low O2
- low atmospheric 02
- anaemia
- Hb defect
- reduced renal blood flow
- compromised cardiopulmonary function
What does Kidney produce when Hypoxia is detected?
Erythropoietin (EPO)
What is Erythropoietin? (2)
- cytokine
- stimulates RBC production (erythropoiesis) in bone marrow
How is EPO produced?
by endothelial cells of the peritubular capillaries in renal cortex
How is production of Erythropoietin regulated? (5)
- kidney releases EPO into bloodstream to reach bone marrow
- hence increased Erythropoiesis
- hence more Erythrocytes released into blood
- hence increased O2 capacity
- which inhibits further EPO production
Stages of Thrombopoiesis (4)
- Megakaryoblast
- Pro Megakaryocyte
- Megakaryocyte
- Platelets
What regulates Thrombopoiesis? (2)
- liver and kidney produces
- TPO
What is Thrombopoietin? (3)
- hormone
- stimulates the production and differentiation of megakaryocytes
- signals to increase production of platelets
How is production of Thrombopoietin regulated? (4)
- TPO produced in liver and kidney
- TPO signals to increase platelet production
- mature platelets bind to TPO in bloodstream
- they then internalise TPO and degrade it
Anaemia
deficiency of Erythrocytes or Haemoglobin
Sign of Anaemia
Reticulocytes in peripheral circulation
Transferrin
transports iron through the blood to various tissues and bone marrow
What helps regulate differentiation of monocytes or granulocytes?
The balance of PU.1 and C/EBP-alpha
Monocytes and Granulocytes:
What does CMP (common myeloid progenitor) differentiate into?
GMP (Granulocyte-macrophage progenitor)
PU.1
Transcription factor
1) GM-CSF
2) G-CSF
3) M-CSF
4) What do they bind to?
1) Granulocyte-monocyte Colony Stimulating Factor
2) Granulocyte Colony Stimulating Factor
3) Monocyte Colony Stimulating Factor
4) They’re receptors on GMP (Granulocyte-macrophage progenitor)
What does C/EBP-alpha up regulate?
G-CSFR
Stages of differentiation of Granulocytes (5)
- Myeloblast
- Pro-myelocyte
- Myelocyte
- N.Metamyelocyte
- E.Metamyelocyte
- B-Metamyelocyte
- Neutrophil
- Eosinophil
- Basophil
What promotes differentiation from LT-HSC to ST-HSC?
SCF
What promotes differentiation from MPP to CLP?
IL-7 (MPP to CLP)
1) What promotes differentiation from Pro-B to B-cell?
2) What promotes differentiation from Pro-T to T-cell?
1) IL-6 (Pro-B to B-cell)
2) IL-2 (Pro-T to T-cell)
What promotes differentiation from MPP to CMP? (2)
- IL-3
- GM-CSF
1) What promotes differentiation from CMP to MEP? (2)
2) What promotes differentiation from MEP to Megakaryocyte?
3) What promotes differentiation from MEP to Erythrocyte?
1) IL-3 and GM-CSF
2) TPO
3) EPO
1) What promotes differentiation from GMP to Monocyte?
2) What promotes differentiation from GMP to Neutrophil?
3) What promotes differentiation from GMP to Eosinophil?
4) What promotes differentiation from GMP to Basophil?
1) M-CSF (monocyte)
2) G-CSF (neutrophil)
3) IL-3 and IL-5 (eosinophil)
4) IL-4 (basophil)
Leukaemia (2)
- malignant progressive disease
- bone marrow produces increased number of immature or abnormal leukocytes