Lecture 1: Blood and Marrow

Question 1

What is haematopoesis?

Answer 1

Process by which mature blood cells are geerated from stem cells in the bone marrow. Most are short lived so haematopoesis is essential and needs to be regulated constantly.

In adults is is resitricted to long bones in the bone marrow (95%) - mainly rhe sternum, ribs, sacrum, vertebrae, long bones + spleen plays minor role (5%)

Question 2

Peripheral blood cell lineages?

Answer 2

1. Erythroid
2. neutrophil
3. monocyte/macrophage
4. eosinophil
5. Basophil
6. megakaryocyte
7. T lymphocyte
8. B lymphocyte

Question 3

Origin of haematopoetic tissues?

Answer 3

From the mesoderm in blood islands of the yolk sac (to produce transient primitive blood cells) and then into definitive cells from endothelium in the aorta-gonad-mesonephros (AGM) region, (along with some input from the placenta)

Later this shifts to the fetal liver before finally the marrow

In children it is all marrow, however, as we get older this process occurs only in the more proximal axial skeleton as fat replaces heamatopoetic tissue peripherally.

Question 4

Myelofibrosis? what do you know?

Answer 4

Is scarring of the bone marrow. Normal haematopoetic cells get squeezed out and the spleen enlarges in size and reverts back to the fetal pattern of haematopoesis = extramudullary haematopoesis.

Question 5

Bone marrow appearances? Haematopoietic mircoenvironment?

Answer 5

• Includes: trabecular bone, fat cells, haematopoitic tissue in variable quantities.
• Cellularity varies from 30-70% and decreases with age
• Major cellular elements: haematopoetic cells and bone marrow stromal cells (haematopoietic stem cells (HSC) actually only make up 1:10,000-1:100,000 cells)

Microenvironment:

• Stomal cells include fibroblasts, macrophages, fat cells and endothelial cells.
• provides physical support and a microenvironment suitable for blood cell production.
• Endothelial niche and Endosteal niche

Question 6

Lifespan of RBC, Platelets, neutrophils?

Answer 6

RBC : 120 days

Platelets: 5-6 days

Neutrophils: Circulate 5-6 hours then move into tissie

Question 7

Hierarchy of haematopoiesis?

Answer 7

Stem cells to progenitor cell. Then into morphologically identifiable progeny that progressively mature. As cells mature they lose their capacity to proliferate.

Within the circulating blood there is large numbers of mature blood cells and a small number of stem cells and progenitors.

Question 8

HSC features?

Answer 8

Haematopoeitic stem cells constitute a very small fraction (1:10,000 - 1:100,000) of the total bone marrow/blood cell population

1. Self-renewing
2. generation of one or more specialised cell types

They express antigen CD34 and this is used sa a measure of stem cell

Question 9

Collection of HSC?

Answer 9

1. Bone marrow harvest
2. Umbillical cord (good as immunolgically immature)
3. Peripheral blood collection (post haematopoeitic growth factor)

Question 10

Regulation of Haematopoeisis?

Answer 10

Through transcription factors that are switched on and off in the development. Inherent programming within the cells.

Clinically: Growth factors control the development and maturation. These can be modified.

1. EPO (erythropoietin) : for RBC produciton
2. TPO (thrombopoietin) for platelet production
3. G-CSF (granulcyte colony stimulating factor) for neutrophils
4. Others: GM-CSF, multi-CSF (IL3), M_CSF