Haematopoiesis

Question 1

What is haematopoeisis?

Answer 1

The generation/production of all blood bourne cells e.g. erythrocytes, platlets etc.

Question 2

Why do we need haematopoeisis?

Answer 2

Blood cells have a finite lifespan meaning that we will need to produce more during our lifetime

Question 3

How do we generate all these different types of cells?

Answer 3

Pluripotent stem cells within the blood can differentiate into commited cell lines of the haematopoietic system occuring in the bine marrow except T-cells (thymus)

Question 4

What are the properties of stem cells?

Answer 4

• Self renewal
• Can differentiate into all blood cells

Question 5

What are the sites of haematopoiesis?

Answer 5

• Foetus: 0-2 months = yolk sac 2-7 months = Liver, spleen
• Infants: Bone marrow (practicall all bones)
• Adults: vertebrae, ribs, sternum, skull, sacru, pelvis and proximal ends of the femur

Question 6

What is another major determinant of what a pluripotent stem cell differentiates into?

Answer 6

The microenvironment has a large impact on what cell a stem cell becomes
Such as the extracellular matric (fibronectin, laminin, collagen) - adhesion of cells and soluble factors
Also stromal cells have an impact (macrophages, fibroblasts, endotheilai cells) as they produce soluble factors

Question 7

What soluble factors regulate haematopoiesis?

Answer 7

• Erythropoietin (EPO): Produced in kidneys, induces globin synthesis and promotes differentiation of erythrocytes
• Stem cell factor (SCF): Produced in the marrow stromal cells and stimulates early stem cells to differentiate
• Granulocyte-macrophage colony stimulating factor (GM-CSF) : produced in T-cells, BM stromal cells and stimulates granulocytes and monocytes
• G-CSF
• M-CSF
• Thrombopoietin: Produced in the liver and stimulates platlet production
• Interleukins (IL): IL-1 - stimulates granuolytic cells IL-3 - stimulates growth in all phagocytes IL-6 - stimulates multiple cell types to differentiate

Question 8

Where are red blood cells produced (erythropoiesis)?

Answer 8

Foetus - Liver/spleen
Neonate - Bone marrow
Growing animals - Marrow of all bones
- Red marrow/yellow marrow (femur/humerus) in long bones; flat bones reamin active
- Liver and spleen maintain erythropoietic capacity, especially if increased demaned (extramedullary haematopoiesis), as do long bones (reversion to red marrow)

Question 9

What are the steps of the erythropoietin cycle?

Answer 9

1. EPO stimulates stem cells in the bone marrow
2. Red blood cell precursor goes through stages to become red blood cells
3. Causes negative feedback on EPO as increased oxygen carrying capacity reached
4. If low oxygen tension at proximal tubule EPO is stimulated restarting the cycle

Question 10

How are platlets produced?

Answer 10

Thrombocytopoiesis -
Platelets are derived from the cytoplasm of megakaryocytes in the bone marrow

-Mediated by thrombopoietin produced mainly in the liver
Platlets are small discoid anuclear cells found in the circulation

Question 11

How are neutrophils produced?

Answer 11

Myelopoiesis -
Derived from myeloid precursors

Question 12

What are the different neutrophil pools?

Answer 12

1. Proliferation neutrophil pool: Myeloblast (Mb), Progranulocyte (Pg), Myelocyte (Mc)
2. Maturation neutrophil pool: Metamyelocyte (Mmc), Band neutrophil (B), Segmented neutrophil (S)
3. Storage neutrophil pool: Sub pool of MatNP (ready to be released to marrow sinusoids)
4. Circulating neutrophil pool:
5. Marginated neutrophil pool: ready to exit the circulation and migrate into tissues
6. Tissue neutrophil pool: neutrophils that have migrated into tissues