Haemopoiesis Overview and Mechanisms

Haemopoiesis Overview

• Haemopoiesis is the production of blood cells.
• It's a tightly regulated process.
• The process is driven by growth factors.
• Different blood cell lineages have specific pathways (erythropoiesis, thrombopoiesis, granulopoiesis, and lymphopoiesis).
• The process occurs in the bone marrow.

Aims and Objectives

• The lecture outlines the processes involved in haemopoiesis.
• Students will be able to explain the importance of effective haemopoiesis.
• Students will describe the major components of the bone marrow.
• Students will describe the mechanism of haemopoiesis and the importance of growth factors.
• Students will explain the value of bone marrow analysis.

Types of Haemopoiesis

• Erythropoiesis: Red blood cell production

  • Erythrocytes transport oxygen from lungs to tissues.
  • Regulated by growth factors, cytokines, and environmental factors.
  • Mature red blood cells lose their nuclei.
  • Normal concentration in blood: 3.9-6.5 x 10¹²/L

• Leucopoiesis: White blood cell production

  • Leucocytes defend the body against infection

• Thrombopoiesis: Platelet production

  • Thrombocytes prevent blood loss at injury sites

Ontogeny of Haemopoiesis

• Adult: 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) which becomes the sole site at birth

Haemopoietic Stem & Progenitor Cells

• Specialized cells for blood cell production.
• Originates from common myeloid progenitor which, in turn, originate from pluripotent stem cells; there are common lymphoid progenitor cells too.
• Erythroid, megakaryocyte, granulocyte-monocyte, and eosinophil progenitors come from the common myeloid progenitor.
• Lymphocytes originate from the common lymphoid progenitor.

Bone Marrow Stroma

• The structure of the bone marrow that supports the blood cell development.
• Composed of endothelial cells, fibroblasts, macrophages, and fat cells.
• Crucial in providing the microenvironment for haematopoiesis.

Examples of Growth Factors

• Growth factors are crucial in differentiation of stem cells.
• Interleukins (ILs) stimulate the production of GM-CSF, G-CSF, M-CSF, and IL-6.
• IL-3, IL-4, and IL-6 act on early multipotential cells.
• IL-5 is eosinophil CSF.
• GM-CSF stimulates the function of granulocytes and macrophages.
• Stem cell factor acts on pluripotent stem cells.
• Erythropoietin is primarily produced by the kidney and stimulates red blood cell production.
• Thrombopoietin (primarily from the liver) stimulates megakaryocyte maturation, leading to platelet production.

Apoptosis

• Programmed cell death that is crucial for removing damaged or unnecessary cells.
• Characterized morphologically by cell shrinkage, condensation of chromatin, and nuclear fragmentation.
• Controlled by survival factors (e.g., growth factors), death factors, and inhibitors (e.g., BCL-2).

Specific Haemopoiesis

• Individual pathways for each blood cell type (red blood cells, platelets, and different types of white blood cells).
• Each pathway involves distinct steps and regulatory factors.

Erythropoiesis

• Key steps in red blood cell development include slow reduction in size, and loss of the nucleus to become a reticulocyte
• Process occurs in parallel with development of haemoglobin.

Reticulocytes

• Precursors of mature red blood cells.

Erythropoiesis Regulation

• Erythropoietin (EPO) regulates erythropoiesis.
• Stimulated by low atmospheric oxygen, defective cardiac/pulmonary function, and damage to the renal circulation.
• EPO levels correlate with haemoglobin concentration.

Thrombopoiesis

• Platelet production
• Driven by thrombopoietin (TPO).
• Endomitotic synchronous nuclear replication is involved in platelet production.

Granulopoiesis

• White blood cell production
• Controlled by interleukins (IL-1, IL-3), GM-CSF, and M-CSF.
• Cells develop a characteristic granularity and nuclear condensation, and there is a subsequent reduction of size.

Mature Granulocytes

• Differentiated neutrophils, eosinophils, and basophils.
• Important in the immune response.
• Microscopic images of the different cell types are also provided.

Lymphocyte Production

• B and T cells are produced from haemopoietic stem cells (IL-7)
• B cells make immunoglobulins (IgA, IgG, IgM).
• T cells have different types (helper and cytotoxic).

B-cell

• Features of B-cell activation and differentiation into short-lived or long-lived plasma, with proliferation and mutation being highlighted
• B-cell receptor activation and antibody secretion are described.

T-cell

• T cells originate from cells that have migrated to the thymus.
• Different T-cell types (helper and cytotoxic) with their respective markers (CD4 and CD8).

Marrow Analysis

• Evaluating bone marrow status for blood cell production.
• Used in diagnosing blood disorders (leukaemia, bone marrow diseases).
• Measuring blood cell precursors (M/E ratio).

Obtaining Bone Marrow

• Hip bone (pelvic bone) is a common site for bone marrow aspiration
• Samples are collected using a needle.
• Samples are analyzed to identify microorganisms, cell types, and cell condition (for example, cell size and granularity).

Marrow Aspiration

• Stained using specialized stains for examination (Romanowsky and Perls).

Bone Marrow

• Basic structure and composition.
• Cellularity changes with age.
• Normal M/E ratio - myeloid to erythroid ratio.

M/E ratio

• Myeloid/erythroid ratio in the bone marrow (the proportion of different type blood cells).
• Altered M/E ratios are linked to certain diseases.

Fluorescence Flow Cytometry

• A tool used to identify blood/bone marrow cells by their markers (glycoproteins).
• Important for diagnosis of malignancies and minimal residual disease detection.
• Using panels of markers to identify cells types.

Core Textbook/Additional Reading

• Relevant chapters from specified textbooks provide detailed information on each aspect of haematopoiesis.

This quiz covers the fundamental processes of haemopoiesis, the production of blood cells in the bone marrow. Students will explore different blood cell lineages and the importance of growth factors in regulating this vital process. Key components of bone marrow and their roles in haemopoiesis will also be discussed.