2015 L1 Introduction to Haematology

Haematopoiesis

The process of blood cell formation, involving the differentiation of hematopoietic stem cells into various types of blood cells.

Formed Elements

The cellular components of blood, including red blood cells, white blood cells, and platelets.

Blood Plasma

The liquid component of blood, consisting mostly of water (95%), hormones, plasma proteins, inorganic ions, and waste.

Blood film

Small blood drop spread onto a glass slide (forms a mono-layer). Gives us a cell differencial. Stained using a Romanowksy dye (May Grunwald-Giemsa stain).

Haemopoietic micro-environment

Micro-environment is supported by a connective tissue (extra-cellular matrix) - compartmentalises haemopoietic tissue, provides structural support.

Bone marrow contains a mix of haemopoietic and non-haemopoietic cells.

Vascular supply important for micro-environment.

Red marrow

Excepionally cellular, biopsy needed to view structure.

Haemopoetic tissue described as “cords” - islands of lineage specific differentiation embedded in cords

Sinuses are lined in endothelial cells and are essential in controlling release of mature cells.

How mature cells leave the marrow

Endothelium (lines the sinuses) is tightly packed (size and flexibility exclusion).

Extracellular matrix (ECM) contains adhesion molecules (e.g. P/E selectins) which retain immature cells

• Mature neutrophils can. e induced (by inflammation/ infection to release lactase and MMP to degreed this feature.

Immature cells (Hematopoietic stem cells (HSC)) can return/ “home-in” to the marrow.

Red Blood Cells

Most numerous blood cells. 7um diameter. Erythropoiesis requires the hormone erythropoietin.

Male: 4.5-5.5x1012Cells/L

Female: 3.8-4.8x1012Cells/L

Haemoglobin - 26.7-32.5 pg/cell

Normoblast (Nucleated Red Blood Cell) → Reticulocyte → Mature RBC

Erythropoietin

Required for erythropoiesis.

Produced by peritubular endothelial cells in kidney.

Epo induces differentiation of precursors into RBC.

Haemoglobin

A heterotetramer. Each side chain contain a haem group which minds 1 molecule of oxygen.

Males: 130-180 g/L

Females:115-165 g/L

Reference Range

A range of results expected for 95% of normal individuals (Gaussian distribution), used in lab testing to determine health status. Varies depending on sex and population.

Globin synthesis

Adult haemoglobin (HbA) consists of:

• 2 a-chains

• 2 β-chains

Globin genes are found:

• a-chain chromosome 16

• β-chain chromosome 11

Mixing different globin sub-units gives variants Hb.

Haem biosynthesis

Occurs in: Liver (for inclusion in cytochrome proteins), Muscle (for inclusion in myoglobin) and RBC precursors.

Relies on enzymatic processes - The production of aminolaevulinic acid is a key rate limiting step.

Deficiencies in this process can cause systemic disease.

White blood cells (WBC)

Require GM-CSF to marure into monocytes and neutrophils. Consist of:

• Granulocytes

• Lymphocytes

• Monocytes

Granulocytes

One of two categories of WBC characterized by the presence of granules in their cytoplasm, including neutrophils, eosinophils, and basophils.

Agranulocytes

One of two categories of WBC characterized by the absence of granules in their cytoplasm. Includes Lymphocytes and Monocytes

Monocytes

The largest WBC (0.2 - 0.8x10^9/L), which differentiate into macrophages and dendritic cells in tissues (~50% stored in spleen).

Have a phagocytic role and antigen presenting roles.

Platelets

Second most numerous blood cell type (¤~400x109 cells/litre). Play a crucial role in clotting; normal platelets are discoid and anucleate. Platelets have granulated cytoplasm:

• Alpha granules

• Dense granules

• Lysosome granules

Thrombopoeitin

A hormone produced primarily by the liver and kidneys that regulates the production of platelets from megakaryocytes in the bone marrow. It plays a crucial role in maintaining platelet levels in the bloodstream.

Neutrophils

The most numerous WBC (2-7.5x10^9/L), responsible for non-specific immune responses and contains granules in the cytoplasm:

• Primary granules: Contain lysozyme and other digestive enzymes.

• Secondary granules: Contains lysozyme and collagenase.

Neutrophil maturation

Occurs within bone marrow. Characterised by:

• Increased nuclear segmentation

• Decreased cytoplasmic RNA

• Smaller cell

Lymphocytes

Consisting of B-cells and T-cells. Maturation occurs in Bone marrow & Thymus.

B-lymphocyte terminal differentiation results in plasma cells.

Eosinophils

1% of circulating WBC (0.1-0.4x10^9/L), involved in targeting macroparasites and limiting allergic responses.

Basophils

The least numerous type of WBC (¤0.02-0.10x10^9/L), involved in inflammatory and hypersensitivity responses, secreting heparin.

Macrophages

Terminally differentiated monocytes that are strongly phagocytic and essential for tissue health and immune responses. Localised in tissues, but are not the same across organs. Other roles:

• Iron metabolism

• Wound repair

• Tissue growth