Transcript Haemopoiesis Clinical application

Haemopoiesis
Clinical application
Dr. Tariq M. Roshan
Department of Hematology
PPSP
Introduction
 Life span




Granulocytes
Erythrocytes
Platelets
Lymphocytes
Introduction
 Stem cells


Self renewal
Plasticity
 Progenitor cells

Developmentally-restricted cells
 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
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
Regulation of Haemopoiesis
Local environmental control
Stromal cell mediated Haemopoiesis
Apoptosis
Haemopoietic
growth factors (Humoral regulation)
Interaction of stromal cells, growth
factors and haemopoietic cells
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
Erythropoiesis and erythrocytes
 Lifespan – 120 days
 Non nucleated
 Biconcave disc
 Production regulated by
Epo
 Needs Fe, B12, folate &
other elements for
development
Functions of erythrocytes
 Transport of respiratory gases

Large surface area : volume ratio

Flexible biconcave disc

Haemoglobin for exchange of gases

Capable of glycolysis for the source of energy for
cell survival
Erythrocyte disorders
 Qualitative

Haemoglobin defect
(Anemia, Thalassaemia, sickle cell anemia etc)

Membrane & enzyme abnormalities
(G6PD, eliptocytosis, stomato-ovalocytosis)
 Quantitative



Increased (polycythemia) inherited / acquired
Decrease (inherited / acquired hypoplasia)
Bleeding
Anaemia
 Reduction in circulation
haemoglobin
 Nutritional deficiency
anaemias




Iron deficiency
anaemia
Iron deficiency
B12 & folate deficiency
anaemia
Protein deficiency
anaemia
Scurvy & other
element deficiency
B12 & folate deficiency
Nutritional deficiency anaemia
clinical application
Angular
Cheilosis
Glossitis
Koilonychia
Marrow iron stores
Plummer-Vinson
syndrome
Anaemia; Globin chain defects
 Thalassaemias

Reduced globin chain
synthesis
 Alpha and Beta
chain synthesis
defects
Thalassaemia
 Haemoglobinopathies

Abnormal globin chain
synthesis
Sickle cell disease
Anaemia; Globin chain defects
Hemoglobin electrophoresis
for the diagnosis of
thalassaemia
X-ray appearance of
Thalassaemic patient
Anaemia; Membrane and enzyme
defects
 Membrane defects
 Elliptocytosis
Elliptocytosis
 Hemolysis

Stomato-ovalocytosis
 Without haemolysis
 Red cell enzymopathies
 G6PD
 Hemolysis after
oxidant stress
 Blood loss
G6PD deficiency
Anaemia; Reduced bone marrow
erythroid
 Marrow failure
 Marrow infiltration
Marrow infiltration
Trephine biopsy (Aplastic
Anemia)
Normal trephine
Leucocytes
 Lymphocytes
Band
E
 Monocytes /
P
Macrophages
 Granulocytes
 Neutrophils
 Eosinophils
 Basophils
N
L
M
B
Lymphocytes
 Count varies with age
1.5 – 3.5 x109/l
 The subset cells are



B-cells
 Antibody mediated
immunity
T-cells
 Cell mediated
immunity
NK cells
Disorders of lymphocytes
Benign disorders
 Lymphocytosis



Viral infections
Bacterial infections
Protozoal infections
 Lymphopenia


Marrow failure (drugs, irradiation)
Infections (viral infections)
 Immune-deficiency syndromes



Antibody deficiency
Cell mediated immune defiency
Combined cell and antibody immune deficiency
Disorders of lymphocytes
Benign disorders
 Infectious
mononucleosis

Epstein-Barr virus
infection
 Autoimmune
lymphoproliferative
syndrome
Disorders of Lymphocytes
Malignant disorders
 Acute lymphoblastic
ALL
leukemia (ALL)
 Chronic lymphocytic
leukemia (CLL)
 Lymphomas
 Non Hodgkin’s
lymphoma
 Hodgkin’s disease
CLL
Monocytes
 Count is 0.2-0.8 x 109/l
 Functions
 Antigen presentation
 Cytokine production
 Phagocytosis
Disorders of Monocytes
 Monocytosis

Benign


Chronic bacterial infection
Malignant

Chronic Myelomonocytic Leukaemia CMML
Neutrophils
 Count 2.5 - 7.5 x 109/l
 Granular cytoplasm
 Transient stay in blood
 Major phagocytic role
 Bacterial killing
 3-5 lobes of nucleus
Disorders of Neutrophil
 Neutrophilia
 Infection (Bacterial)
 Inflammatory conditions
 Neoplasia
 Metabolic conditions
N
 Uraemia



Haemorhage / haemolysis
Corticosteroids
Marrow infiltration
MM
Baso
CML
M
Disorders of Neutrophil
 Neutropenia





Count < 1.5 x 109/l
Drugs
Chemotherapy
Viral infection
Inherited disorders
 Morphological abnormalities



Pelger-Huet anomaly
May-Hegglin anomaly
Chediak-Higashi syndrome
Myeloid malignancies
 Acute Myeloid
Leukaemia
 Chronic Myeloid
Leukaemia
Acute Myeloid Leukaemia
(AML M-3)
 Myeloproliferative
disorder
Chronic Myeloid Leukaemia
Eosinophils
 Count 0.2 – 0.8 x 109/l
 Bilobed nucleus
 Phagocytic activity is low
 Modulation of
hypersensitivity and
allergic reactions
Disorders of Eosinophil
 Eosinophilia
>0.8 x 109/l
 Allergic reactions
 Parasitic infections
 Malignancy




HD, NHL
Inflammatory conditions
Myeloproliferative disorders
Hypereosinophilic syndrome
Basophils
 Count 0.1 – 0.2 x 109/l
 Bilobed nucleus
 Nucleus is hided behind
the granules
 Inflammatory response
 Basophilia is seen in
Myeloproliferative
disorders (CML)
Platelets
 Platelets are fragments
of cytoplasm of bone
marrow
megakaryocytes
 Count 150 – 400 x 109/l
 Major role in
coagulation
Summary
As other rapidly regenerating tissues, the
haemopoietic system is organized in hierarchical
manner
Better understanding of the factors controlling
haemopoiesis is leading a way to better patient
care and reconstitution of different lineages, which
has been refractory to stimulation efforts previously
Understanding of stem cell physiology & pathology
will be essential in the coming years for a
hematopathologist
Thanks.