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
There should be a balance between cell production and cell death except at the times of requirement
Controlled cell death
Controlled cell production
Regulation of Haemopoiesis
Local environmental controlStromal cell mediated Haemopoiesis
Haemopoietic growth factors (Humoral regulation)Apoptosis
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 B12 & folate deficiency
anaemia Protein deficiency
anaemia Scurvy & other
element deficiency
Iron deficiencyanaemia
B12 & folate deficiency
Nutritional deficiency anaemiaclinical application
Angular Cheilosis
Koilonychia
Glossitis
Marrow iron storesPlummer-Vinsonsyndrome
Anaemia; Globin chain defects
Thalassaemias
Reduced globin chain synthesis
Alpha and Beta chain synthesis defects
Haemoglobinopathies
Abnormal globin chain synthesis
Sickle cell disease
Thalassaemia
Anaemia; Globin chain defects
X-ray appearance ofThalassaemic patient
Hemoglobin electrophoresisfor the diagnosis of thalassaemia
Anaemia; Membrane and enzyme defects Membrane defects
Elliptocytosis Hemolysis
Stomato-ovalocytosis Without haemolysis
Red cell enzymopathies G6PD
Hemolysis after oxidant stress
Blood loss
Elliptocytosis
G6PD deficiency
Anaemia; Reduced bone marrow erythroid Marrow failure Marrow infiltration
Trephine biopsy (AplasticAnemia)
Marrow infiltration Normal trephine
Leucocytes
Lymphocytes
Monocytes / Macrophages
Granulocytes Neutrophils Eosinophils Basophils
N
E
B
LM
Band
P
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 lymphocytesBenign 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 lymphocytesBenign disorders Infectious
mononucleosis Epstein-Barr virus
infection
Autoimmune lymphoproliferative syndrome
Disorders of LymphocytesMalignant disorders Acute lymphoblastic
leukemia (ALL)
Chronic lymphocytic leukemia (CLL)
Lymphomas Non Hodgkin’s
lymphoma Hodgkin’s disease
ALL
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
Uraemia Haemorhage / haemolysis Corticosteroids Marrow infiltration
CML
MM M
N
Baso
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
Myeloproliferative disorder
Acute Myeloid Leukaemia(AML M-3)
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.