Chapter-1(M) -Blood component and Hematopoiesis.pptx

Blood components & Hematopoiesis  Introduction  The average person has approximately 70 mL of blood per kilogram body weight (70 mL/kg), or ~5 L total for a 70-kg man. Approximately 50 to 60% of the blood volume is liquid; the remainder is cells.  The liquid component,...

Blood components & Hematopoiesis  Introduction  The average person has approximately 70 mL of blood per kilogram body weight (70 mL/kg), or ~5 L total for a 70-kg man. Approximately 50 to 60% of the blood volume is liquid; the remainder is cells.  The liquid component, called plasma, is nearly 90% water. The remaining 10% includes ions, glucose, amino acids and other metabolites, hormones, and various proteins. The proteins of interest are the coagulation proteins.  Serum is the liquid remaining after blood clots; it is essentially the same as plasma, except that the clotting factors and fibrinogen have been removed. The cells of the blood can be divided into erythrocytes (red blood cells), leukocytes (white blood cells) of various types, and platelets.  Content of the blood  Definition: Blood is a liquid connective tissue  Function of blood: 1. Transports plasma 2. Regulates 55% 3. Protects Cells (formed WBCs and platelets 1%  Component of blood: Cells + plasma elements) RBCs 45%  Red bood cells (Erythrocytes):  Forms about ~ 99% of formed elements in blood  Has no nucleus (no cell division, no organelles.  Biconcave shape (i.e. large surface area, flexible shape permits easy squeeze through small capillaries)  RBC cell life cycle is ~ 120 days (four months).  White blood cells (leukocytes):There are 2 types of leukocytes; 1. Agranular leucocyte: has NO cytoplasmic granules (Monocytes and lymphocytes) 2. Granular leucocyte– has cytoplasmic granules (Neutrophils, Eosinophils and basophils)  Therefore, there are five types of leucocytes in total.  Agranular leucocyte :Monocytes.Nucleus is kidney shaped-.Cytoplasm is blue with a foamy experience- It can develop into macrophage in blood called wandering -.macrophage  LYMPHOCYTES -Nucleus is round, slightly indented and almost fill-up the cytoplasm. It varies in size ; (small) diameter - 6 -9  m (large) diameter 10–14 m -Lymphocytes are primary cells of the immune system and function to produce high degree of specificity. They involved in recognizing what is “not-self”. -There are 2 types of lymphocytes: 1. B-lymphocyte 2. T-lymphocyte.  Granular leucocytes -Cytoplasmic granules are present -There are three kinds of granular leucocytes, eosinphil, basophil and neutrophil.  Eosinophil Cytoplasm is stained red/orange-.with acidic dye Nucleus is 2-lobed and connected-.with a thin or thick strand Granules have regular sizes and -.usually do not block the nucleus  BASOPHIL Cytoplasm is stained blue-purple with basic- dye Nucleus is either bi-lobed or irregular lobed- Granules can be blue and have irregular sizes- NEUTROPHILS Cytoplasm is stained lilac (i.e. takes-up-.acidic and basic dyes) Nucleus is 2 - 5 lobed and connected with-.a thin chromatin Cytoplasmic granules is fine, pale and-.evenly distributed  Different WBC have specific different roles  Therefore changes in normal WBC count can assist in diagnosis  Normal WBC differential count is: - Neutrophils 40 – 80 % - Lymphocytes 20 – 40 % - Monocytes 2 – 10 % - Eosinophils 1–6% - Basophils ½-1%  The references ranges is different from country to another but each country or region should establish its normal ranges.  Lifespan for WBC for a healthy person varies (i.e. days: months; years)  Normal WBC distribution - 2% in blood - 98% (in lymphatic fluid, organs – skin, lungs, spleen and lymph nodes) - Tissues continuously exposed to toxins and microbes have changing levels of WBCs (e.g. skin and mucous membranes) - Normal WBC counts is 4000 – 10, 000 /cmm (cells per mm3) of blood NB: RBC: WBC ratio is ~ 700:1 Some abnormal WBC counts are; i) Leukocytosis (i.e. over 10, 000 per cmm = high number of WBCs) ii) Leukocytopenia (i.e. below 3000 per cmm = Low number of WBCs)  PLATELETS  Cytoplasmic fragments of megakaryocytes  No nucleus, mitochondria is present  Has 2 types of granules; i) Alpha granules – contains fibrinogen, thrombospondin, clotting factors), ii) Dense granules – contains calcium, serotonin, ADP, ATP).  Shape ( 2 forms) i) stimulated form – discoid shape ( 2- 4  m) ii) unstimulated state – spiny spheric shape Function - Helps to stop bleeding in damaged vessels. Haematopoiesis  Hematopoiesis  Hematopoiesis means blood cell formation.  Theterm comes from the Greek haima (blood) and poiein (to make).  For the average adult, the bone marrow produces ~5 x 1011 cells per day. +  Productionof blood cells is highly regulated and balanced.  Hematopoiesis include : * Erythropoiesis: Red blood cells formation. * Leukopoiesis: WBCs formation include: - Myelopoiesis: Granulocytes and monocytes formation. - Lymphopoiesis: Lymphocyetes formation. * Thrombopoiesis: Thrombocytes formation.  HEMATOPOIESIS OF EMBRYOLOGY  Hematopoiesis begins in the yolk sac during the first month of embryogenesis, but gradually shifts to the liver and, to a lesser extent, the spleen.  The liver is the primary site of hematopoiesis during the second trimester; however, the bone marrow becomes the primary site of hematopoiesis after the seventh month.  After birth, the bone marrow is normally the sole site of hematopoiesis (intramedullary hematopoiesis).  Hematopoiesis may resume in the liver and spleen after birth in conditions associated with fibrosis of the bone marrow (extramedullary hematopoiesis).  POSTNATAL HEMATOPOIESIS  During infancy and childhood, there is active hematopoiesis in the medullary cavity of virtually every bone.  With age, the hematopoietically active marrow (red marrow) is gradually replaced by inactive marrow (yellow marrow), which consists predominantly of adipose tissue.  In adults, hematopoiesis is restricted to the proximal long bones and the axial skeleton (skull, vertebral bodies, ribs, sternum, and pelvis).  The yellow marrow can resume active hematopoiesis under conditions of chronic hematologic stress (chronic bleeding or hemolytic anemia). Haemopoietic stem and progenitor cells  Hematopoiesis starts with a pluripotential stem cell that can give rise to the separate cell lineages under the influences of local and humeral factors.  This haemopoietic stem cell is rare, perhaps 1 in every 20 million nucleated cells in bone marrow.  The stem cell has the capability for self-renewal so that marrow cellularity remains constant in a normal healthy steady state.  one stem cell is capable of producing about 1 million mature blood cells after 20 cell divisions Hematopoiesis  Bone marrow stroma  The bone marrow forms a suitable environment for stem cell survival, growth and development.  Bone marrow is composed of: 1-stromal cells 2-microvascular network or Extracellular matrix Bone marrow stroma Bone marrow stroma  The regulation of hemopoiesis  The processes of hematopoiesis are controlled by several growth factors.  Haemopoietic growth factors: They are glycoprotein hormones that regulate the proliferation and differentiation of haemopoietic progenitor cells and the function of mature blood cells Hematopoiesis and growth factors  General Characteristics of growth factors.1.2.3.4.5.6.7.8 Sites of Haemopoiesis Erythropoiesis  Erythropoiesis passes from the stem cell through the progenitor cells colony-forming unit granulocyte, erythroid , monocyte and megakaryocyte (CFUGEMM) Brurst forming unit erythroid (BFUE) the first recognizable erythrocyte precursor in the bone marrow the Pronormoblast Early normoblast Intermediate normoblast Late normoblast Reticulocyte RBCs *Single pronormoblast generate 16 RBCs Erythropoiesis Regulation and Requirements for Erythropoiesis  Circulating erythrocytes – the number remains constant and reflects a balance between RBC production and destruction o Too few red blood cells leads to tissue hypoxia o Too many red blood cells causes undesirable blood viscosity  Erythropoiesis is hormonally controlled and depends on adequate supplies of iron, amino acids, and B vitamins  Hormonal Control of Erythropoiesis 90%  of erythropoietin is produced by the peritubular interstitial cells of the kidney and 10% produced  The erythropoietin secretion is stimulated by : 1. Low oxygen tension. 2. Low hemoglobin concentration. 3. High altitude. 4. Cardiopulmonary diseases. Erythropoietin Mechanism Imb al a nce Start Normal blood oxygen levels Stimulus: Hypoxia due to Im b decreased RBC count, ala decreased availability of O2 nce to blood, or increased Increases tissue demands for O2 O2-carrying ability of blood Reduces O2 levels in blood Erythropoietin Kidney (and liver to a Enhanced stimulates red smaller extent) releases erythropoiesis bone marrow erythropoietin increases RBC count Leukopoiesis  Leukocytes (WBCs)  Leukocytes, the only blood components that are complete cells they classified according to: 1-Cytoplasmic granulation divided to: A- Granulocyte: this include: i- Neutrophil (polymorph) ii- Eosinophil iii- Basophil B-A granulocyte: this include: i- Monocyte ii- Lymphocyte 2-according to their functions to: A- Phagocytes which include the granulocytes and monocyte B- Non-phagocytes or Immunocyte which include the lymphocytes  Granulocytes: Neutrophil (Polymorph nuclear leukocytes) * Account for 40-80% of total WBC’s * Neutrophils have two types of granules that takes up both acidic and basic dyes give the cytoplasm a pink-blue color or gray-blue granules. The granules are divided into primary, which appear at the promyelocyte stage, and secondary (specific) which appear at the myelocyte stage and predominate in the mature neutrophil. * Neutrophils are our body’s bacteria slayers * The lifespan of neutrophils in the blood is only 6- 10 hours.  Granulocytes: Eosinophils  These cells are similar to neutrophils, except that the cytoplasmic granules are coarser and more deeply red staining and have bilobed nuclei ,there are rarely more than three nuclear lobes  Eosinophils account for 1–6% of WBCs  Function: 1. Lead the body’s counterattack against parasitic infections 2. Lessen the severity of allergies by phagocytizing immune complexes (ending allergic reactions) removal of fibrin formed during inflammation.  Granulocytes: Basophil  Account for 0.5-1% of all WBCs  Have U- or S-shaped nuclei with two or three conspicuous constrictions. In the tissues they become mast cells. They have immunoglobulin E (IgE) attachment sites and their degranulation is associated with histamine release.  Have large, purplish-black (basophilic) granules that contain histamine  Histamine – inflammatory chemical that acts as a vasodilator and attracts other WBCs (antihistamines counter this effect)  Monocytes Monocytes spend only a short time in the marrow and, after circulating for 20-40 h, leave the blood to enter the tissues where they mature and carryout their principal functions (differentiate into macrophages). Monocytes account for 2-10% of leukocytes 1. They are the largest leukocytes 2. They have purple-staining, U- or kidney-shaped nuclei  Their extravascular lifespan after their transformation to macrophages may be as long as several months or even years.  Neutrophil and monocyte function 1-Chemotaxis (cell mobilization and migration):  The phagocyte is attracted to bacteria or the site of inflammation by chemotactic substances. 2- Phagocytosis: is process the human body uses to destroy dead or foreign cells 3- Killing and digestion: This occurs by oxygen dependent and oxygen-independent pathways.  Agranulocytes: Lymphocytes Account for 20-40% of WBCs and: Have large, dark-purple, circular nuclei with a thin rim of blue cytoplasm Are found mostly in lymphoid tissue (some circulate in the blood) Most important cells of the immune system There are two types of lymphocytes: T cells and B cells T cells - attack foreign cells directly B cells give rise to plasma cells, which produce antibodies  Lymphoid organs  primary lymphoid organs: These include the bone marrow and thymus in which lymphocytes developed. secondary lymphoid organs: in which specific immune responses are generated are the lymph nodes, spleen and lymphoid tissues of the alimentary and respiratory tracts.  B and T lymphocytes  B cells mature in the bone marrow and circulate in the peripheral blood and in its function mature into memory B cells or plasma cells.  T cells develop from cells that have migrated to the thymus where they differentiate into mature Tcells during passage from the cortex to the medulla. and in its function mature into T helper cells and T cytotoxic cells.  Production of Leukocytes  Leukopoiesis is hormonally stimulated by two families of cytokines (hematopoietic factors) – interleukins and colony-stimulating factors (CSFs)  Interleukins are numbered (e.g., IL-1, IL-2), whereas CSFs are named for the WBCs they stimulate (e.g., granulocyte-CSF stimulates granulocytes)  Macrophages and T cells are the most important sources of cytokines  Many hematopoietic hormones are used clinically to stimulate bone marrow  Control of granulopoiesis:  Many growth factors are involved in this  maturation process including interleukin-1 (IL-1), IL-3, IL-5 (for eosinophils), IL-6, IL-ll, granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G- CSF) and monocyte CSF (MCSF).  The growth factors stimulate proliferation and differentiation and  Platelet production  Platelets are produced in the bone marrow by fragmentation of the cytoplasm of megakaryocytes, one of the largest cells in the body. The precursor of the megakaryocyte-the megakaryoblast arises by a process of differentiation from the haemopoietic stem cell.  The megakaryocyte matures by endomitotic synchronous replication (i.e. DNA replication in the absence of nuclear or cytoplasmic division) enlarging the cytoplasmic volume as the number of nuclear lobes increase in multiples of two.  approximately each megakaryocyte giving rise to 1000- 5000 platelets, The time interval from differentiation of the human stem cell to the production of platelets averages approximately 10 days.  The normal platelet count is (range 150-400 x 109/L) and the normal platelet lifespan is 7-10 days.  Up to one-third of the marrow output of platelets may be trapped at anyone time in the normal spleen but this rises to 90% in cases of massive splenomegaly.  The main platelets function in the clotting mechanism by forming a temporary plug that helps seal breaks in blood vessels Megakaryoblast Promegakaryocyte Platelets Megakaryocyt e  Control of platelets production  Thrombopoietin is the major regulator of platelet production and is constitutively produced by the liver and kidneys.  Thrombopoietin increases the number and rate of maturation of megakaryocytes