Lecture 1 - Blood and Bone Marrow

Question 1

Define Haematopoiesis?

Answer 1

The process by which mature blood cells are generated from stem cells in the bone marrow.

Question 2

How often is haematopoiesis required?

Answer 2

Constantly - this is because mature blood cells have relatively short lives. It is even required constantly in an unstressed adult life.

Question 3

What are the eight main lineages of peripheral blood?

Answer 3

1. Erythroid.
2. Neutrophil.
3. Monocyte/Macrophage.
4. Eosinophil.
5. Basophil.
6. Megakaryocyte.
7. T lymphocyte.
8. B lymphocyte.

Question 4

What is haematopoietic tissues?

Answer 4

Tissues that generate non-lymphoid cells of peripheral blood.

Question 5

What are the haematopoietic tissues?

Answer 5

1. Bone marrow (95%) - mainly sternum, ribs, sacrum, vertebrae and long bones.
2. Spleen (5%).

Question 6

Describe the origin of haematopoietic tissues?

Answer 6

Cells of haematopoietic tissues are generated from mesoderm in blood islands of yolk sca (to produce transient ‘primitive’ blood cells) and then ‘definitive’ cells from endothelium in aorta-gonad-mesonephros (AGM) region. The site of haematopoiesis then shifts to fetal liver and subsequently bone marrow.

Question 7

What happens to the bone marrow as we go from infancy to adult life?

Answer 7

In infancy all bone marrow is haematopoietic. During childhood there is progressive fatty replacement of marrow throughout long bones. Haematopoiesis is more proximal as an adult.

Question 8

What happens in disease states?

Answer 8

Haematopoiesis can revert to fetal pattern in disease states. In some blood disorders, there is expansion of haematopoiesis into long bones. Spleen and liver can also resume their fetal haematopoietic roles - ‘extramedullary haematopoiesis’.

Question 9

What is myelofibrosis of splenomegaly?

Answer 9

There is fibrosis of bone marrow and extramedullary haematopoiesis occurs so the spleen takes over and can get bigger.

Question 10

What is adult bone marrow made up of?

Answer 10

Trabecular bone containing: fat and haematopoietic tissue (all in variable quantities).

Question 11

What makes up the major cellular elements of bone marrow?

Answer 11

1. Haematopoietic cells.

2. Bone marrow stromal cells.

Question 12

What are stromal cells made up of?

Answer 12

1. Fibroblasts.
2. Macrophages.
3. Fat cells.
4. Endothelial cells.

Question 13

What do stromal cells do?

Answer 13

Provide physical support and a microenvironment suitable for blood cell production.

Question 14

What makes up the microenvironment?

Answer 14

1. Extracellular matrix.
2. Adhesion molecules.
3. Blood cell growth factors.

Question 15

How many HSC niches are there that support the microenvironment?

Answer 15

Two:
1. Endothelial niche (within blood vessels).
2. Endosteal niche (within bone marrow).
They either expand, differentiate/migrate or apoptosis.

Question 16

What is the lifespan of a RBC?

Answer 16

120 days.

Question 17

What is the lifespan of a platelet?

Answer 17

5-6 days.

Question 18

What is the lifespan of a neutrophil?

Answer 18

5-6 hours.

Question 19

Describe the hierarchy of haematopoiesis?

Answer 19

Stem cells generate progenitor cells. Progenitor cells generate morphologically identifiable progeny that progressively mature. As cells mature they lose their capacity to proliferate.

Question 20

What are the properties of HSC’s?

Answer 20

1. Self-renewal.

2. Generation of one or more specialised cell types.

Question 21

What do human HSC’s express?

Answer 21

Antigen CD34.

Question 22

What is the antigen CD34 used for?

Answer 22

It is used to measure the amount of stem cells our body has left.

Question 23

What are the sources of HSC’s?

Answer 23

1. Bone marrow.
2. Peripheral blood.
3. Umbilical cord.