Haemopoiesis Lecture 1 PDF

Haemopoiesis Dr Amreen Bashir Biomedical Science Lecturer BMS Placement Tutor [email protected] MB438J Aims and Objectives This lecture will outline the processes involved in haemopoiesis – the production of blood cells. Following this lecture you should be able to: – Explain the importance...

Haemopoiesis Dr Amreen Bashir Biomedical Science Lecturer BMS Placement Tutor [email protected] MB438J Aims and Objectives This lecture will outline the processes involved in haemopoiesis – the production of blood cells. Following this lecture you should be able to: – Explain the importance of effective haemopoiesis – Describe the major components of the bone marrow – Describe the mechanism of haemopoiesis and the importance of growth factors – Explain the value of bone marrow analysis  Haemopoiesis Reading : Hoffbrand chapter 1 Moore, Knight and Blann, chapter 1/2/3 A tightly regulated process that forms blood cells 1. Erythropoiesis- red cell production (erythrocytes) Regulated by : Transport 02 from Growth factors Cytokines lungs Environmental factors to tissues Apoptosis 2. Leucopoiesis- white cell production (leucocytes) defend body 3.Thrombopoiesis- against infection platelet production (thrombocytes) prevent blood loss at site of injury Balance Ontogeny of Haemopoiesis Adults Bone marrow of Vertebrae, ribs, sternum, skull, sacrum and pelvis, proximal ends of femur Infants Bone marrow (practically all bones) Foetus 0–2 months (yolk sac of embryo) 2–7 months (liver, spleen) 5–9 months (bone marrow)- at birth sole site Haemopoietic stem & progenitor cells A glance at Bone Marrow Stroma Examples Of Growth Factors Table 3.1 Haemopoietic growth factors page 59 Blann Summary: Role of Growth Factors in Haemopoiesis Apoptosis-programmed Cell Death Morphologically it is characterised by: 1. Cell shrinkage 2. Condensation of nuclear chromatin 3. Fragmentation of the nucleus 4. Cleavage of DNA at internucleosomal sites Specific Haemopoiesis Erythropoiesis- Formation of RBC Reading : Hoffbrand chapter 2 Moore page 60 Normal concentration in the blood 3.9-6.5 X 1012/L  Erythropoiesis Key steps involved in red cell development from a blast cell involve: 1. slow reduction in size 2. loss of the nucleus to become a reticulocyte Process occurs in parallel with development of Haemoglobin Reticulocytes Erythropoiesis is regulated by EPO Stimuli Atmosphere 02 is low Defective cardiac/pulmonary function Damage to the renal circulation EPO levels  Reading : Hoffbrand chapter 24 Thrombopoiesis- platelet production Chapter 3 Moore, knight & Blann Thrombopoiesis  Granulopoiesis Reading : Hoffbrand chapter 8/Moore chapter 3 IL-1, IL3, GM-CSF and M-CSF control proliferation and differentiation. Mature Granulocytes Neutrophil Eosinophil Mature Granulocytes Basophil Monocyte Lymphocyte Production B and T cells – both arise from the Haemopoietic stem cell (IL-7)  B-Cell B cell receptor is membrane bound, after activation secreted as immunoglobulin proteins IgA, IgG,IgM,IgD,IgE  T-Cell Develop from cells that have migrated to thymus express CD4 express CD8 END OF PART 1 Aims and objectives This lecture will outline the processes involved in haemopoiesis – the production of blood cells. Following this lecture you should be able to: – Explain the value of bone marrow analysis  Marrow Analysis Status of and capability for blood cell production. Measure blood cell production, to help diagnose: leukaemia bone marrow disease spread of cancer severe anaemia Cultured for the presence of microorganisms Obtaining Bone Marrow Hip bone (pelvic bone), but it also can be done from the breastbone, lower leg bone or backbone Cleaned with iodine solution or alcohol. Local aesthetic injected Bone marrow needle is then placed through the skin and into the bone. Bone marrow aspiration Bone marrow biopsy Obtaining Bone Marrow Aspiration (skip if your squeamish)  Marrow Aspiration Once aspirated bone marrow is smeared onto a slide and stained for examination: 1.Romanowsky stain 2. Pearls Stain Ferric Iron - Blue Nuclei - Red Bone Marrow Cellularity alters throughout life Normal adult will have 50:50 haemopoetic cells to fat In a healthy individual myeloid WBC precursors exceed number of RBC precursors 3:1- varies with disease- M/E ratio Figure 3.9 Moore, Knight & Blann M/E Ratio Table 3.3 Myeloid/erythroid ratio Moore, Knight & Blann  Fluorescence Flow Cytometry Identifies blood and bone marrow cells according to the presence of CD molecules (glycoprotein's) on the cells surface or in the cytoplasm. Uses: – Panels of markers to confirm diagnosis of malignancies (AML/CLL) – CD34 counts before marrow harvest – Minimal residual disease detection. Familiarise yourself with the appearance & function of cells…  Summary The production of blood cells occurs in a process called haemopoiesis. Haemapoietic tissue consists of stem cells and supportive tissue such as fibroblasts, macrophages and endothelial cells, all of which interact to provide the optimum micro- environment for haemopoiesis. Haemopoiesis is a closely regulated process and is driven by growth factors Each major blood cell lineage has its specific haematopoietic pathway; erythropoeisis thrombopoiesis and Granulopoiesis. Lymphocytes and monocytes also have their own pathway. Bone marrow aspiration is required to confirm diseases (such as myeloma) suspected of having origin in this tissue and to monitor the effect of treatment. Flow cytometry can also be used to evaluate the cell populations in the marrow.  Core textbook/ Additional Reading 1. Haematology Fundamentals of Biomedical Science 2nd edition Gary Moore, Gavin Knight, Andrew Blann- Chapters 1,2 & 3 Essential Haematology, Hoffbrand & Moss Chapter 1 – Haemopoesis Chapter 2 , Pages 16-19 – Erythropoesis Chapter 24, pages 315-317 – Thrombopoesis Chapter 8 – Granulopoiesis Chapter 9 – Lymphocyte production