Haematopoiesis

Question 1

What is Haematopoiesis?

Answer 1

The physiological process of the formation of blood cells

Question 2

Erythropoiesis
Myelopoiesis
Megakaryocytopoiesis

Answer 2

Erythropoiesis - formation of red blood cells
Myelopoiesis - formation of white blood cells ( granulopoiesis - formation of garnulocytes, lymphopoiesis - formation of lymphocytes)
Megakaryocytopoiesis - formation of platelets

Question 3

Review of blood composition
Percentages
Fluid component
Cellular component

Answer 3

Percentages
. plasma 55%
. WBC and platelets <1%
. RBC 45%

Fluid component - plasma containing clotting factors
- serum no clotting factors
- proteins, electrolytes, gases,
hormones, lipids

Cellular Component
- red cells
- platelets
- white cells ( granulocytes-neutrophil, eosinophil,
basophil), (agranulocytes- lymphocytes, B,T< NK cells,
monocytes)

Question 4

The Requirements of normal haemopoiesis

Answer 4

• right genetic makeup
• right environment
• right micronutrients

Question 5

Explain right environment

Answer 5

A. Site
- foetus - yolk sac (0-3 months)
- liver, spleen (2-7 months)
- Adults - Bone marrow
haemopoietic elements, stromal cells

B. Right Microenvironment
- right growth factors
proliferation, maturation, differentiation, regulation of
normal cell growth

Question 6

What are the right micronutrients?

Answer 6

iron
folate
vitamin B12 etc

Question 7

A description of the different environments and timeframe

Answer 7

During embryonic and early foetal life, haematopoiesis occurs in the yolk sac (only erythoblasts) and the liver (all blood cells). Some blood cell formation also occurs in the
spleen (all blood cells) , lymph nodes and thymus (mostly lymphocytes). Bone marrow starts producing
blood cells around 3rd to 4th month and by birth becomes the exclusive site of blood cell formation. In younger age, whole of the skeletal marrow participates in blood cell production. By late
childhood, haematopoiesis becomes restricted to the flat bones such as sternum, ribs, iliac bones and
vertebrae and proximal ends of long bones.

Question 8

The Haemopoietic factory

Answer 8

workers- haemopoietic elements
conditions- growth factors
ingredients - Fe, B12, folate, amino acids
transport dispatch - blood vessels
product - blood cells
destination - organs

Question 9

The Structure of the Bone Marrow

Answer 9

Made up of 2 components
1. Vascular compartment
- nutrient artery -
branches into central longitudinal arteries
» radial branches which eventually open into sinuses
» sinuses converge into central vein that carries blood
into general circulation
2. Extravascular compartment
- haemopoiesis compartment
» stroma of reticular connective tissue
» parenchyma of developing blood cells and fat cells

Question 10

Bone marrow

Answer 10

soft tissue which occupies

1. medullary cavity of long bones
2. trabeculae of spongy bone
3. haversian canals

Question 11

The Red Marrow

Answer 11

• delicate meshwork of reticular tissue
• saturated with cells (haemopoietic elements) at different stages of maturation - mature and immature
• scattered with scanty adipocytes (fat)
• In adults limited to (axial skeleton, pectoral girdle, proximal heads of femur and humerus)
• spongy bone, compact bone

Question 12

The Yellow Marrow

Answer 12

• mostly fatty connective tissue

- during starvation can be used as an energy source

Question 13

The priciples of haemopoiesis

Answer 13

• blood cells originate from the pluripotent haemopoietic stem cells (HSCs)
• for specific cell lineage HSC then goes through - commitment, differentiation, maturation(through several intermediate steps)

NOTE : at each stage - capacity to differentiate is increasing, capacity to divide and self-produce is decreasing(more mature blood cells are not able to divide, usually only mature cells can reach peripheral blood)

hemopoiesis is carefully regulated to hold stable numbers of cells in the blood

Question 14

Stem cells

Answer 14

• totipotent and multipotent
• self renewal - can divide to form another stem cell to maintain a constant pool or reserve of stem cells
• commitment - can form a more committed cell - more restricted fate- to form new tissues (committed cells differentiate and mature)

Question 15

Regulation

Answer 15

1. growth factors - cell lineage, maturation
2. body needs
   - white cells ( acute bacterial infection : increase neutrophils, parasitic infection: increase eosinophils, acute viral infection: increase lymphocytes)

platelets - haemorrhage - increase platelets

red blood cells - hypoxia - (haemorrhage, haemolysis, chronic heart/ lung disease)

3. Normal life span
   apoptosis

Question 16

Haemopoietic growth factors

Answer 16

• most are members of cytokine family eg hormones
• released from haemopoietic , stromal and other cells
  eg T cells, macrophages, stromal cells
  NOTE erythropoietin EPO produced in kidney
  Thrombopoietin TPO produced in liver
• can interact through specific receptors with different types of cells and change their functional activity
  initiate signal transduction pathways, altering transcription factors eg GATA-1 - that in turn activate genes that determine differentiation of blood cells

Question 17

How understanding hematopoiesis has improved treatment of haematological diseases

Answer 17

• eg stem cell transplants in patients with bone marrow failure
• growth factors as treatment- EPO in some anaemia, G-CSF in neutropenic sepsis