Transcript Normal Haemopoiesis

Normal Haemopoiesis
Dr. Tariq M. Roshan
Department of Hematology
PPSP
Introduction

Life span
 Granulocytes
 Erythrocytes
 Platelets
 Lymphocytes

Derived from Stem cells
 .01% - .05% of the marrow cells
Introduction

Stem cells
 Self renewal
 Plasticity
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Progenitor cells
 Developmentally-restricted cells
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Mature cells
 Mature cell production takes place from the more
developmentally-restricted progenitors
Cell hierarchy (Haemopoiesis
schematic representation)
Sites of Haemopoiesis

Yolk sac

Liver and spleen

Bone marrow
– Gradual replacement
of active (red)
marrow by inactive
(fatty) tissue
– Expansion can occur
during increased
need for cell
production
Stem cells

Self-renewal
 Normally in G0 phase of cell cycle
 The capacity for self-reproduction is vastly in
excess of that required to maintain cell production
for normal lifetime
 As cells increase in number they differentiate as
well

Multipotentiality
 Capacity to generate cells of all the
lymphohaemopoietic lineages
Interaction of stromal cells, growth
factors and haemopoietic cells
Progenitor cells

Encompasses from immediate progeny of
stem cells to cells committed to one
differentiation lineage

Progenitor cells become progressively
more restricted in their differentiation and
proliferation capacity
 Late progenitor cells eventually restricted to one
lineage
Regulation of Haemopoiesis
Controlled cell
death

Controlled cell
production
There should be a balance between cell
production and cell death except at the times of
requirement
Local and Humoral regulation of
Haemopoiesis
Haemopoietic growth factors

GM-CSF
 Granulocyte-Macrophage colony stimulating factor

M-CSF
 Macrophage colony stimulating factor

Erythropoietin
 Erythropoiesis stimulating hormone
(These factors have the capacity to stimulate the proliferation of their
target progenitor cells when used as a sole source of stimulation)

Thrombopoietin
 Stimulates megakaryopoiesis
Haemopoietic growth factors

Cytokines
 IL 1 (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 nine cells into proliferation
Role of growth factors in normal
haemopoiesis
Regulation of Haemopoiesis
Local environmental control
Stromal cell mediated Haemopoiesis
Apoptosis
Haemopoietic
growth factors (Humoral regulation)
Apoptosis

Regulated physiological cell death
 Homeostasis
 Morphological evidence
 Enzymatic digestion of DNA and cell disintegration
 Caspases
 Endonuclease

Two major pathway of activation of
caspases
 Membrane signalling
 Cytochrome c release
Mechanism; apoptosis
Erythropoiesis and erythrocytes

Lifespan – 120 days

Non nucleated

Biconcave disc

Production regulated by Epo

Needs Fe, B12, folate &
other elements for
development
Development of mature red cells
Granulopoiesis

Granulocytes
E
– Neutrophils
– Eosinophils
– Basophils

Only mature cells are
present in peripheral
blood
N
B
Granulopoiesis

Neutrophil
– 2-5 lobe nucleus
– Primary or secondary
granules
 Pink (azurophilic granules)
 Grey-blue granules
– Life 10 hours

Precursors
–
–
–
–
–
Myeloblast <4%
Pro myelocytes
Myelocytes
Metamyelocytes
Band form (stab form)
Neutrophil kinetics
Granulopoiesis

Eosinophils
– Coarser & more deeply red staining granules
– Rarely more than two lobes of nucleus
– Special role in allergy, inflamation & parasite
infection

Basophils
– Occasionally seen
– Dark cytoplasmic granules
– Role in hypersensitivity response
– Give rise to mast cells
Monocytes

Larger than lymphocyte

Oval or indented nucleus

Monocytes >>>>to
macrophage

Specific function depends
on the tissue type
Lymphopoiesis
Immunologically competent cells
 Primary lymphoid organs

 Bone marrow
 Thymus

Secondary lymphoid organs
 Lymph nodes
 Spleen
 Lymphoid tissues

Lymphocytes
 B and T lymphocytes
 NK killer cells
Lymphopoiesis
Thrombopoiesis





Platelet play a major
role in primary
hemostasis
Life span 7-10 days
Production,
fragmentation of
cytoplasm
Megakaryocytes
undergoes
endomitotic division
1/3 in spleen
Summary

Normal haemopoiesis is necessary for the
survival

It is under the control of multiple factors

Normal bone marrow environment is
necessary for normal haemopoiesis

Decreased production results in cytopenias