OVERVIEW OF HAEMATOPOIESIS Flashcards
INTRODUCTION
Haemopoiesis is defined as the formation, development and differentiation of blood cellular components.
Includes: Erythropoiesis, Myelopoiesis(granulocytes and monocytes), Lymphopoiesis and thrombopoiesis
HAEMOPOIETIC SITES
3phases, the mesoblastic, hepatic and myeloid phase
The mesoblastic phase- 2nd week to 3rd month (cells cluster in the yolk sac)
The hepatic phase- the 2nd month to the 7th month ( mainly the liver with the supplementation of the spleen)
The myeloid phase- from the 6th month to adult life, The red bone marrow
In infancy all the bone marrow is haemopoietic
but during childhod there is progressive fatty replacement of the marrow throughout the long bones
Hence in Adults only the central skeleton, and the proximal end of the femurs and humeri have haemopoietic marrows
THE HAEMOPOIETIC STEM CELL AND BONE MARROW
Stages in haemopoietic cell development Lineage selection Physical maturation Functional maturation And Cell death
The haemopoietic stem cell is the starting point of haemopoiesis
Capacity of cell reproduction
Pluripotent i.e it can generate different types of tissues
THE BONE MARROW
It provides suitable environment for the stem cells to survive and grow
Composed of Stromal cells and Microvascular network
BONE MARROW STROMAL CELLS
- Consists of adipocytes, fibroblastss, endothelial cells and macrophages
- they form extracellular matrix composed of collagen, glycoproteins and glycosaminoglycans
- secrete growth factor for stem cell survival
THE PROGENITOR CELLS & PRECURSORS
Cell differentiation occurs from stem cells via haemopoietic progenitors, they are formed as a result of loss of one or more developmental potential of the HSC
Characteristics of Progenitor cells
- loss of pluripotency
- lack of capacity of self renewal
- higher fraction of cells transversing the cell cycle
- 2 types: multipotential and commited
They’re either Myeloid progenitor or Lymphoid progenitor
Not morphologically identifiable but through in vitro techniques
THE PRECURSORS
By the way are morphologically identifiable and they eventually develop to become mature cells
REGULATION OF HAEMOPOIESIS & HAEMOPOIETIC GROWTH FACTORS intro
A balance between cell production and cell death is required
When necessary such as In haemorrhage, cell production will exceed cell death
Haemopoietic growth factors are glycoproteins that regulate the proliferation and differentiation of progenitor cells
They may act locally at site of formation or circulate in plasma. They can cause; cell proliferation, cell differentiation, maturation, prevent apoptosis and affect function of normal cells
Major sources of growth factors; - stromal cells - T-lymphocyte - monocytes ( macrophages) Kidneys produce erythropoietin and Liver produces Thrombopoietin
HAEMOPOIETIC GROWTH FACTORS
Include:
GM-CSF (Granulocyte Macrophage Colony Stimulating factor)
M-CSF (Macrophage Colony Stimulating Factor)
Erythropoietin (Erythropoiesis stimulating hormone)
Thrombopoiesis (Megakaryopoisis stimulating hormone)
Cytokines- InterLeukin, SCF(stem cell factor) or Kit-ligand
GENERAL CHARACTERISTICS OF HAEMOPOIETIC GROWTH FACTORS
Can act in low concentration Can affect more than one lineage Show synergistic action Act on neoplastic and normal cells Act hierachically Produced by many cells Usually active on stem/progenitor cells and on functional end cells
CLINICAL APPLICATION OF GROWTH FACTORS
Treatment of anemia
Treatment of neutropenia
Treatment of thrombocytopenia
Haemopoietic stem cell transplantation