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Histology of the Hematopoietic System Dr Despina Moissidou Histology Lead, QMUL Malta, [email protected] 1 Learning Objectives • Know blood as a special connective tissue type and its cellular constituents • List the different stages of hemopoiesis. • Know the structural characteristics of...

Histology of the Hematopoietic System Dr Despina Moissidou Histology Lead, QMUL Malta, [email protected] 1 Learning Objectives • Know blood as a special connective tissue type and its cellular constituents • List the different stages of hemopoiesis. • Know the structural characteristics of each blood cell type (RBC and WBC) in relation to their function • Describe the histological features of the bone marrow, thymus, lymph node and spleen and understand their role in normal haematopoiesis. • Briefly outline main blood pathologies, such as anaemia 2 Recommended reading material Part 2 “Basic tissue types” Ch.3 Blood, Haemopoiesis and Bone Marrow, and part 3 “Organ Systems”, Ch. 12 Immune system, in Wheater's Functional Histology, 6th Edition (E-Book available from the library) Chapter 10 Blood and chapter 14 Immune System, in: Histology: A Text and Atlas, with Correlated Cell and Molecular Biology, 8th Edition, 2018, W. Pawlina, Michael H. Ross Chapter 12 Blood and chapter 14 Immune system, in: Junqueira's Basic Histology: Text and Atlas, 15th Edition, 2018 Blood • Blood is a fluid connective tissue that circulates through the cardiovascular system. • Consists of cells and extracellular component- protein rich fluid called plasma. • It functions in: – Delivery of nutrient and oxygen to the tissues. – Transport of wastes and carbon dioxide away from the tissues. – Delivery of hormones and regulatory substances to the cell. – Maintenance of homeostasis- acts as buffer. – Transport of immune “players”. 4 Blood • Blood Cells (45% of total volume) • Plasma (55% of total volume) - Liquid extracellular material • The packed volume of RBCs in a sample is called hematocrit. • To prevent clotting, an anticoagulant such as citrate or heparin is added, plasma is called serum. • The preparation method used to display blood cells is called blood smear. – A drop of blood is smeared onto a glass slide, dried and stained (Wright’s stainmethylene blue, basic dye and eosin). 5 Plasma • 91% to 92% of water and 8% to 9% of solids. mainly comprises of: It • Coagulants, mainly fibrinogen, aid in blood clotting • Plasma proteins, such as albumin and globulin, that help maintain the osmotic pressure and transporting other proteins (sugar, fat) • Electrolytes like sodium, potassium, bicarbonate, chloride, and calcium help maintain blood pH • Immunoglobulins help fight infection and various other small amounts of enzymes, hormones, and vitamins 6 Erythrocytes – Red Blood Cells (RBCs) • Function only within the blood stream (erythropoietin main control) • Anucleate, biconcave shape of 7.8μμ (used to estimate the size of other cells). • 120 days lifespan, senescent RBCs are destroyed (hemolysis) in the spleen. • Replaced in the circulation by reticulocytes, which maturate 1 to 2 days after entering the circulation (1% to 2% of circulating RBCs). RBC platelet erythrocytes platelets 7 Platelets • Small fragments derived from the megakaryocyte under the control of thrombopoietin. • Megakaryocytes develop cytoplasmic projections in the periphery that become proplatelets, which fragment into platelets. It takes 7 to 10 days. • Involved in coagulation: platelet plug, coagulation cascade megakaryocytes Platelets and Clotting proteins: Haemostasis • Platelets form an initial plug - primary haemostasis • clotting proteins produce a firm thrombus - secondary haemostasis • Low platelet levels (thrombocytopenia) can cause bleeding and bruising • Low clotting factors e.g. haemophilia- no secondary haemostasis9 Leukocytes – White Blood Cells (WBCs) • Leukocytes are sub-classified into two general groups: – Granulocytes (containing primary, and specific or secondary cytoplasmic granules) : Neutrophils, Eosinophils, Basophils. – Agranulocytes (containing only primary granules): Lymphocytes and Monocytes. 10 Leukocytes 11 Neutrophils • Most common, “lack” of cytoplasmic staining, multi-lobe nucleus polymorphonuclear or polymorphs. • Almost twice the size of RBC, motile cell, very dynamic: - constantly patrol for signs of microbial infections - when found, they trap and kill the invading pathogens - 3 main antimicrobial function: phagocytosis, degranulation, and neutrophil extracellular traps (NETs, release of nuclear material) 12 Neutrophil number changes in disease • Neutrophilia (increase) – – – – Infection Inflammation Tissue damage Haemorrhage • Neutropenia (decrease) – Overwhelming sepsis (blood poisoning) – HIV – Bone marrow failure (no blood cells produced) – aplastic anaemia, leukaemia – Medications – B12/folate deficiency 13 Eosinophils & Basophils EOSINOPHIL BASOPHIL • Same size as neutrophils. •Least numerous of the WBCs. • Eosinophilic granules in their cytoplasm with cytotoxic action (bright orange) • Basophilic granules in their cytoplasm containing histamine: • Associated with allergic reaction, parasitic infections and chronic inflammation. •Variety of causes for increased levels (i.e. chronic myeloid leukemia) Lymphocytes & Monocytes LYMPHOCYTE • About the same size as RBCs. • Three functional distinct types: B cells, T cell and NK cells. • Intensely stained cytoplasm with very thin nucleus. No recognizable cytoplasmic organelles. • Function in adaptive immunity. MONOCYTE • The precursors of the cells of the mononuclear phagocytic system. • They migrate from the bone marrow to the tissues where they differentiate into tissue specific phagocytes such as alveolar macrophages, Kupffer cells etc. • Bent and indented nucleus. 16 Blood examination and diagnosis 17 Cells of immune system- Lymphocytes - B cells, responding to cell-free and cell-bound antigens. - T cells: helper T cells and cytolytic or cytotoxic T cells. T cells respond to cellbound antigens presented by specific molecules. Mature B and T cells circulate in the blood until they reach one of the various secondary lymphoid organs (lymph nodes, spleen, and tonsils). 18 Diffuse Lymphatic Tissues - Lymphatic Nodules • sites of initial immune response, accumulation of lymphocytes in the lamina propria mucosa-associated lymphatic tissue (MALT). • When encounter an antigen they get activated (proliferate and differentiate). 19 Lymph Nodes • Maintain/differentiate B cells (plasma cells and memory cells), and house T cells. • Detect and react to lymph-borne antigens. • Concentrated in certain regions such as the axilla, groin and mesenteries. • Capsule: DCT • Trabeculae: DCT from capsule inside node. • Reticular tissue (meshwork): reticular cells, dendritic cells, macrophages, follicular dendritic cells and reticular fibres and covers the remaining of the organ. Reticular fibres in medulla 20 General Architecture of the Lymph Node Using immunohistochemistry to demonstrate different types of lymphocytes in the lymph node Lymph node cortex Anti-CD3 (T cells) Anti-CD20 (B cells) 21 Thymus • Bilobed organ, site of T-cell differentiation. • After puberty, most of lymphatic tissue is replaced by adipose tissue. • CT surrounds the thymus and subdivides parenchyma into thymic lobules. • Each lobule is composed of a cortical cap on top of an inner medullary tissue. • Parenchyma contains developing T cells (thymocytes) in an extensive meshwork formed by epithelioreticular cells. Thymic cortex 22 Thymus • Epithilioreticular cells are divided into 6 groups, depending on their location • Macrophages: Located in the thymic cortex. • In medulla, reticular cells form Hassal’s corpuscles, concentrically arranged cells with flat nuclei, with keratinized centre. Thymic medulla 23 Spleen • The largest lymphatic organ, filters blood and reacts immunologically. • Enclosed by DCT capsule from which trabeculae extents into parenchyma. • Arteries and veins found in the trabecula. • No cortex, medulla. - White pulp (nodules with B and T cells, APCs, plasma cells). - Red pulp (sinusoids with blood and plates of lymphoid tissue --- splenic cords, old/damaged RBCs, macrophages, lymphocytes). NOTE: Parenchyma is named based on the color of fresh sections 24 ….some clinical correlations 25 Anaemia: a RBC disorder • • • • • Symptoms Tiredness Faint Shortness of breath Worsening of heart related pain (angina) Rapid heart beat (experienced as palpitations) Signs • • • • • • Pale Rapid heart beat (tachycardia) Bounding pulse Systolic flow murmur Cardiac failure Retinal haemorrhages Iron Deficiency anaemia: the most common • • • • • • • Iron key component of Hb Small (microcytic), hypochromic cells Diet is rare cause Menstrual loss (young females) Infection (hookworm) Growth spurt, pregnancy Gastrointestinal loss: Bleeding ulcers, inflammatory bowel disease, CANCER Not the final diagnosis, what is the underlying cause? 26 Types of anaemia: subdivided by Mean Cell Volume (MCV) 27 Types of anaemia: subdivided by production 28 Thank you! 29

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