Haemopoiesis

Question 1

Haemopoiesis

Answer 1

The formation, development and differentiation of blood cellular components

Question 2

-Erythropoiesis:

Answer 2

formation of red blood cells

Question 3

-Myelopoiesis:

Answer 3

formation of granulocytes and monocytes

Question 4

-Lymphopoiesis:

Answer 4

formation of lymphocytes

Question 5

-Thrombopoiesis :

Answer 5

formation of platelets.

Question 6

THE HAEMOPOIETIC SITES at different stages of development

Answer 6

• Mesoblastic phase
– 2nd week - 3rd month
– Cell clusters in yolk sac
• Hepatic phase
– 2nd – 7th month
– Mainly liver with supplementation from spleen
• Myeloid phase
– 6th month – adult – Red bone marrow

Question 7

Discuss bone marrow sites from infancy to adulthood

Answer 7

In infancy all the bone marrow is haemopoietic.
▪ During childhood, there is progressive fatty replacement of marrow throughout the long bones.
▪ In adult life, haemopoietic marrow is confined to the central skeleton and proximal ends of the femurs and humeri.

Question 8

STAGES IN HAEMOPOIETIC CELL DEVT

Answer 8

Lineage Selection
↓
Physical Maturation
↓
Functional Maturation
↓
Cell Death

Question 9

What is the THE HAEMOPOIETIC STEM CELL

Answer 9

• Starting point of Haemopoiesis.
• Morphologically resembles a small
lymphocyte.
• Exact phenotype unknown,

Question 10

Characteristics of a stem cell

Answer 10

• Has the capacity for self reproduction (self renewal) that is required to maintain cell production for a normal lifetime.
• Pluripotent i.e can generate different types of tissues (Stem Cell Plasticity).
• Humans possess 2 x 10^4 stem cells
▪ One stem cell can produce about 106 mature blood
▪ Daily blood cell formation is 4 x 10^11 cells : 2 x 10^11 RBCS, 1 x 10^11 WBCs and 1 x 10^11 Platelets.
cells after 20 divisions.
▪ When required, the stem cells are able to increase production of any of the cell line

Question 11

Discuss the Bone marrow

Answer 11

• It provides a suitable environment for the stem cells to survive, grow and develop.
• It composed of stromal cells and microvascular network.
• Stem cells are able to move around the body, and are found in small numbers in the periphery.

Question 12

Discuss the stromal cells of bone marrow

Answer 12

Bone marrow: The stromal cells
• Consist of adipocytes, fibroblasts, endothelial cells and macrophages.
• Form extracellular matrix composed of collagen, glycoproteins and glycosaminoglycans.
• Secrete growth factor for stem cell survival

Question 13

Discuss the stromal cells of bone marrow

Answer 13

Bone marrow: The stromal cells
• Consist of adipocytes, fibroblasts, endothelial cells and macrophages.
• Form extracellular matrix composed of collagen, glycoproteins and glycosaminoglycans.
• Secrete growth factor for stem cell survival

Question 14

Discuss PROGENITOR CELLS and what they are characterized by

Answer 14

• Cell differentiation occurs from the stem cells via haemopoietic progenitors.
• They are formed as a result of the loss of one or more developmental potentials of the HSC,
• Characterized by :
- Loss of pluripotency
- Lack of capacity for self renewal
- Higher fraction of cells traversing the cell cycle
. There are 2 types : Multipotential and Committed.

• They are either myeloid or lymphoid progenitors
• Are not visible morphologically
• Their existence can be demonstrated by in-vitro culture techniques
• Very early progenitors: Assayed by culture on bone marrow stroma
• Late progenitors: Assayed on semi-solid media

Question 15

Progenitors develop into

Answer 15

The Precursors
• The morphologically identifiable blood cells • Eventually develop to become mature cells

Question 16

Stages of erythropoiesis

Answer 16

Proerythroblast.
Basophilic normoblast.
Polychromatic Normoblast
Orthochromatic Normoblast.
Reticulocyte.
Erythrocyte (fully mature red blood cell).

Question 17

REGULATION OF HAEMOPOIESIS is controlled by:

Answer 17

Haemopoietic Growth Factors

A balance between cell production and cell death is needed
• When necessary, production of cells may exceed the cell death i.e. haemorrhage.

Question 18

Haemopoietic Growth Factors

Answer 18

• Glycoprotein hormones that regulate the proliferation and differentiation of the progenitor cells.
• May act locally at site of production/ circulate in plasma.
• Can cause cell proliferation, differentiation, maturation, prevent apoptosis and affect function of normal cells.

Question 19

The major sources of growth factors

Answer 19

– T-lymphocytes,
– monocytes (and macrophages)
– stromal cells
• The kidneys produce erythropoietin • The liver produces thrombopoietin

Question 20

Examples of Haemopoietic growth factors

Answer 20

Haemopoietic growth factors
• GM-CSF
• Granulocyte-Macrophage colony stimulating factor
• M-CSF
• Macrophage colony stimulating factor
• Erythropoietin
• Erythropoiesis stimulating hormone
• Thrombopoietin
• Stimulates megakaryopoiesis

Cytokines
•IL(Interleukin) 1, IL 3, IL 4, IL 5, IL 6, IL 9, IL 11
• TGF-β
•SCF (Stem cell factor, also known as kit-ligand)
• Cytokines have no (e.g IL-1) or little (SCF) capacity to stimulate cell proliferation on their own, but are able to synergise with other cytokines to recruit other cells into proliferation

Question 21

General characteristics of Haematopoeitic Growth factors

Answer 21

– Can act at very low concentration
– Affect more 1 lineage
– Show synergistic action
– Act on neoplastic cells equivalent to normal cells
– Act hierarchically
– Produced by many cells
– Usually active on stem/ progenitor cells and on functional end cells
– Multiple actions

Question 22

Growth factors: Clinical applications

Answer 22

• Treatment of anaemia
• Treatment of neutropenia
• Treatment of thrombocytopaenia
• Haemopoietic stem cell transplantation