Haemopoiesis

Question 1

What is the function of platelets?

Answer 1

Primary haemostasis

Question 2

What is the lifespan of red blood cells?

Answer 2

120 days

Question 3

What is the lifespan of neutrophils?

Answer 3

7-8 hours

Question 4

What is the lifespan of platelets?

Answer 4

7-10 days

Question 5

What is the progression of formation of neutrophils?

Answer 5

Myeloblast
Promyelocyte
Myelocyte
Metamyelocyte
Band forms
Neutrophils

Question 6

What are blasts?

Answer 6

Nucleated precursor cells

Question 7

What are megakaryocytes?

Why are they polyploid?

Answer 7

Platelet precursors

They undergo endomitosis, i.e. the nucleus can divide many times without the cytoplasm dividing

Question 8

What is the immediate red cell precursor?

Answer 8

Reticulocytes

Question 9

What is the name for the nucleated precursor between neutrophils and blasts?

Answer 9

Myelocytes

Question 10

Name and describe the 5 events in haemopoiesis?

Answer 10

Self-renewal: a property of stem cells, lost in the descendents.
Proliferation: increase in numbers
Differentiation: Descendents commit to one or more lineages
Maturation: descendents acquire functional properties and may stop proliferating
Apoptosis: descendents undergo cell death

Question 11

What state are stem cells generally in?

Answer 11

A quiescent state

They divide every few weeks

Question 12

What gastrulation layer are haemoopoietic stem cells derived from?

Answer 12

The mesoderm

Question 13

Describe the sites of haemopoiesis in utero

Answer 13

Yolk sac: first site of erythroid activity, stops by week 10
Liver: starts by week 6
Spleen: starts by week 12
Bone marrow: starts by week 16

Question 14

Where are haemopoietic stem cells located in the steady state?
When might this change?

Answer 14

The bone marrow

They can be mobilised into the circulation for harvesting and transplantation

Question 15

What are the compartments of the bone marrow?

Answer 15

Cellular (haemopoietic and non-haemopoietic cells)
Vascular elements
Connective tissue matrix

Question 16

Describe the structure of bone marrow

Answer 16

Haematopoietic and non-haematopoietic cells surrounded by a shell of vascularised and innervated bone
Trabeculae (minute projections of bone) are found throughout the metaphysis so many cells in that region are found close to the bone surface

Question 17

What is the endosteum?

What is it lined by?

Answer 17

The interface between bone and bone marrow

It is covered by bone-lining cells including osteoblasts and osteoclasts

Question 18

Describe the blood supply to the bone

Answer 18

Centrally located nutrient arteries terminate within the bone at the periphery of the marrow space
The marrow cavity has a complex network of blood vessels organised into repeating units
Arteries feed into sinusoids.
There is a rich supply of arterioles and sinusoids near the endosteum.

Question 19

What are sinusoids?

Answer 19

Specialised venules in the marrow that form a reticular network of fenestrated vessels that regulate the passage of cells in and out of the circulation.

Question 20

How do newly formed blood cells pass into the circulation?

Answer 20

They can pass through fenestrations in endothelial cells of the sinusoids to enter the circulation.

Question 21

How do neutrophils get into the circulation?

Answer 21

They actively migrate towards the sinusoid

Question 22

How do platelets get into the circulation?

Answer 22

Megakaryocytes fenestrate the endothelial cell with cytoplasmic processes.
The velocity of flow in the sinusoids fragments the cytoplasmic projections creating platelets which are released into the circulation.

Question 23

What is the difference in red and yellow marrow?

Answer 23

Red marrow is haemopoietically active

Yellow marrow is fatty and inactive

Question 24

Why is there a reduction in marrow cellularity with age?

Answer 24

There is an increase in yellow marrow with age.

Question 25

What is the myeloid: erythroid ratio?
What are its ranges?
How might it change?

Answer 25

The relationship of neutrophils and precursors to the proportion of nucleated red cell precursors.
It ranges from 1.5:1 to 3.3:1
It could be reversed in haemolysis as a compensatory response

Question 26

How is haemopoiesis regulated?

Answer 26

Growth factors (cytokines) including: lineage-specific transcription factors (e.g. CSFs) from the immediate and distant environment. 
The growth factors are generally glycoproteins produced by stroma and differentiated blood cells.
There actions include the promotion of proliferation, differentiation and maturation and changing functional activity. 
The location in the marrow seems to be important.

Question 27

How are different cell lineages compartmentalised in the bone marrow?

Answer 27

The most immature myeloid precursors lie deep in the marrow parenchyma
More mature forms migrate towards the sinus wall
Lymphocytes tend to surround small radial arteries
Erythrocytes form islands around the sinus walls. It occurs around nurse macrophages.

Question 28

What are stromal cells?

Where are they situated in relation to blood precursor cells?

Answer 28

Stromal cells are those which do not mature into the three types of peripheral blood cells (they include macrophages, fat cells, endothelial cells and reticulum cells).
Blood precursors exist in close proximity to the stromal cells. Immature blood cells are attached to the stromal cells by cellular adhesion molecules (e.g. fibronectin and collagen). As blood cells mature the adhesion molecules down regulate and teh cells become less adherent.

Question 29

Can haemopoietic and stromal stem cells produce cells associated with other tissues?

Answer 29

Yes - they exhibit plasticity - this has therapeutic implications as stem cells are used to repair a variety of damaged tissues.

Question 30

What growth factor regulates neutrophil maturation?

Answer 30

G-CSF (granulocyte colony stimulating factor)

Question 31

How is haemopoiesis assessed?

Answer 31

Examination of blood: blood count, cell indices, blood film
Bone marrow examination (less common)
Immunophenotyping

Question 32

What is immunophenotyping?

Answer 32

The study of antigen expression which indicate lineage or stage of development using specific antibodies
It is used to assess precursor cells as they are morphologically indistinguishable.

Question 33

What is CD34?

Answer 33

An antigen present on stem cells (and other cells) that can be used as a stem cell marker.