Haemopoiesis

Clinical application

Prashant Tiwari
B.H.M.S(Ist Year)
NHMC & H
For Department of Physiology
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
Controlled cell production
death

 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

Haemopoietic
Apoptosis growth factors (Humoral regulation)
 Hematopoietic Response

hypoxia RBC

infection granulocyte/monocyte

antigen lymphocyte

hemorrhage platelet
Interaction of stromal cells, growth
factors and haemopoietic cells
Local and Humoral regulation of
Haemopoiesis
WHAT are Hematopoietic Growth
Factors? (SCF, IL-6, GM-CSF, etc.)
 glycoprotein hormones
 secreted by
bone marrow, stromal cells, T-cells and Monocytes.stromal c
 regulate division and differentiation of hematopoietic
cells
 responsible for basal hematopoiesis and maintaining
blood counts in normal ranges
 greatly increased secretion in response to infection
 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 Iron deficiency
haemoglobin anaemia
 Nutritional deficiency
anaemias
 Iron deficiency
 B12 & folate deficiency
anaemia
 Protein deficiency
anaemia
 Scurvy & other
element deficiency

B12 & folate deficiency

 Nutritional deficiency anaemia
clinical application
Angular
Glossitis
Cheilosis
Koilonychia

Marrow iron stores

Plummer-Vinson
syndrome
Anaemia; Globin chain defects

 Thalassaemias

 Reduced globin chain

synthesis
 Alpha and Beta
Thalassaemia
chain synthesis
defects

 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 G6PD deficiency

oxidant stress
 Blood loss
Anaemia; Reduced bone marrow
erythroid
 Marrow failure Trephine biopsy (Aplastic
Anemia)
 Marrow infiltration

Marrow infiltration Normal trephine

Leucocytes
 Lymphocytes Band
E

 Monocytes / P
Macrophages

 Granulocytes N
 Neutrophils L
 Eosinophils M
B
 Basophils
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)

CLL
 Lymphomas
 Non Hodgkin’s

lymphoma
 Hodgkin’s disease
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)
N
 Inflammatory conditions

 Neoplasia

 Metabolic conditions

 Uraemia
MM M
 Haemorhage / haemolysis
 Corticosteroids Baso
 Marrow infiltration

CML
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
Acute Myeloid Leukaemia
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
1. It’s all about the numbers 3 and 4 in haematology:---
 1.34cm2 oxygen carried by 1g of Hb
 Average of 3.4 lobes per neutrophil cell
 3.4mg iron in each g Hb
 34mg bilirubin from each g Hb

2. Some More Haematological Help,As a student or on the ward, it’s handy to

have some values of the white blood cell count (WBC) present. Remember:
“Never Let Mum Eat Beans” and “60, 30, 6, 3, 1”
 N: Neutrophils 60%
 L: Lymphocytes 30%
 M: Monocytes 6%
 E: Eosinophils 3%
 B: Basophils 1%
 Folate deficiency causes (A FOLIC DROP)
 Alcoholism
 Folic acid antagonists
 OCP
 Low dietary intake
 Infection (giardiasis)
 Coeliac disease
 Dilantin (phenytoin)
 Relative folate deficiency
 Old
 Pregnancy

 Causes of thrombocytopenia (PLATELETS)

 Platelet disorders (DIC, TTP, ITP)
 Leukemia
 Anemia
 Trauma
 Enlarged spleen
 Liver disease
 Ethanol
 Toxins e.g. heparin, aspirin, chemotherapy, benzene
 Sepsis
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 in Medical Science.
Bibliography
www.oxfordmedicaleducation.com
Wikipedia
knowmedge.com
www.slideteam.net
medstudents.medicine.umich.edu
Pinterest.com
Google & A.K Jain Physiology Book
Thanks a lot!!!!!!!!!!!!!!!!!!!!!