Haematopoietic System Student Copy.pdf

Haematopoietic System Dr. Nnamdi Okereke DVM, MSc, PhD Where opportunity creates success Learning outcomes • Describe the components of the haematopoietic system (is it just blood alone?). • Describe blood and its functions (RBC, WBC, Platelet) in the body. • Explain the differences between haemo...

Haematopoietic System Dr. Nnamdi Okereke DVM, MSc, PhD Where opportunity creates success Learning outcomes • Describe the components of the haematopoietic system (is it just blood alone?). • Describe blood and its functions (RBC, WBC, Platelet) in the body. • Explain the differences between haemoglobin and myoglobin. • Explain the differences between granulocytic and agranulocytic leukocytes. • Describe the process of haemostasis. • Differentiate between anticoagulants and procoagulants. • Outline the mechanism of the blood coagulation pathway. • This is the blood-forming system. • It is a complex system within the human body responsible for the production of blood cells (remember immune cells). • The haematopoietic system encompasses the blood, bone marrow, and the lymphoreticular tissues of the thymus, lymph nodes, spleen, and base cells of the reticuloendothelial system. Functions of Blood  Transport  Nutrient storage  Regulation  Immune response  Clotting Origin of Blood cells There are two theories of blood cell origin • Monophyletic theory: This states that all blood cells arise from a single precursor/pleuripotential or myeloid stem cell which proliferates and gives rise to various blood cell types. • Polyphyletic theory: This states that each blood cell type has a separate primitive precursor cell type. Blood colour • The red colour of blood is imparted by the haemoglobin contained within the erythrocytes. • Gradiations of colour from bright red to bluish-purple are seen, depending on the degree of saturation of haemoglobin with oxygen (relate to some disease conditions). • The greater the saturation, the brighter the red colour. • Plasma is yellow to colourless, depending on the quantity and species examined. • Plasma that is ordinarily light yellow when observed in a test tube might be almost colourless in a capillary tube. Not all Blood is red and WHY Blood Potency of Hydrogen (Blood pH) • The normal pH values for arterial and venous blood are slightly different due to differences in gas exchange and metabolic processes that occur in these two types of blood vessels. • Blood has a pH of about 7.4. • Venous blood (7.32-7.42) is slightly more acidic than arterial blood (7.357.45). exception of pulmonary artery and pulmonary vein. • The higher acidity of venous blood is related to the transport of carbon dioxide; higher concentrations of CO2 exist in venous blood. • The hydration of carbon dioxide in venous blood (CO2 +H2O ⇌ H2CO3 ⇌ H+ + HCO3–) forms hydrogen ions, thus resulting in its higher acidity and lower pH. Haematopoiesis • The red blood cells are non-motile cells that in mammals have lost their nucleus (anucleated), Golgi apparatus, ribosomes, mitochondria, and centrioles in the course of maturation. • However, in some anaemia of mammals, nucleated erythrocytes (reticulocytes) are present in the circulating blood. • These reticulocytes also usually constitute 1-3% of the total RBCs in a normal blood picture. • In animals lower than mammals in the phylogenetic scale, notably birds and reptiles, the erythrocytes are elliptical in shape and possess nucleus, but not other organelles like the mitochondria. • Ellipsoid shapes (which species, what differentiates them from others; any different in functions?) The specific shape of Red Blood cells, which is a biconcave disc, provides several important advantages:  Surface Area to Volume Ratio  Flexibility and Deformability  Short Diffusion Path  Increased Oxygen-Carrying Capacity  Durability  Rapid Gas Exchange Benefits of Elliptical shape of RBC in birds  Elliptical Shape  Increased Oxygen-Carrying Capacity  Enhanced Deformability  Adaptations for Altitude  Thermoregulation  Reserve of Oxygen Erythropoiesis from the stem cell to a mature erythrocyte Major Substances required for Erythropoiesis  Erythropoietin  Vitamins 12  Minerals  Nutrients Fate of Erythrocytes • The cells of the reticuloendothelial system (mononuclear phagocytic system) destroy the old, exhausted erythrocytes. • These cells, known also as histiocytes, macrophages vary in size, shape and location, but they possess the common property of ingesting particulate matters like the erythrocytes. • Reticuloendothelial cells include the Stellate or Kupffer cells of the liver, similar cells in the spleen, and certain cells of the bone marrow and lymph nodes. • Macrophages, which are immune cells, play a crucial role in the removal of old and damaged erythrocytes. They engulf the aged RBCs through a process called phagocytosis. • Once inside the macrophage, the erythrocyte is broken down (haemolysis). • Haemoglobin, the protein responsible for carrying oxygen, is broken down into heme and globin. • The iron from heme is recovered and reused in the production of new erythrocytes or stored in the body's iron reserves. • Heme breakdown in macrophages also produces biliverdin, which is then converted into bilirubin (in which species do we not have bilirubin). • Bilirubin is transported to the liver, where it is conjugated and excreted into bile. • Bilirubin is eventually excreted from the body through the faeces and urine. • The yellow colour of bile and faeces is due to the presence of bilirubin Haemoglobin • Haemoglobin is the pigment of erythrocytes that is responsible for the red colour of the blood specifically in the form of oxyhaemoglobin. • Bright red for oxygenated haemoglobin and darker red for a deoxygenated haemoglobin. Differences between Haemoglobin and Myoglobin Structural differences: • Myoglobin consists of a single polypeptide chain with one haeme group, while haemoglobin is a tetramer composed of four polypeptide chains (two alpha chains and two beta chains), each with its haeme group. These structural differences contribute to variations in their oxygen-binding properties. Cooperative binding: • Haemoglobin exhibits cooperative binding, where the binding of one oxygen molecule to one subunit of haemoglobin enhances the binding of subsequent oxygen molecules. This allows haemoglobin to efficiently load up with oxygen in the lungs and release it in the tissues. Myoglobin, being a single subunit protein, does not exhibit cooperative binding to the same extent. Structural differences seen in oxyhaemoglobin, deoxyhaemoglobin and methmoglobin Methaemoglobin • Methaemoglobin is an anaerobically produced form of haemoglobin in which the iron is oxidized from the ferrous (Fe2+) to ferric (Fe3+) state by the superoxides that are normally present in the erythrocytes. • Methaemoglobin is usually found in small amount in circulation because of the action of reducing agents like glutathione and ascorbic acid. • Under some conditions however, for example, administration of drugs like sulphonamides, aminophenols and nitrites, methaemoglobin is found in large quantities in the circulation. Leukocytes Leukocytes/White Blood cells (WBC) • Leukocytes are classified as either granulocytes, containing granules in the cytoplasm, or as agranulocytes, with no granules in the cytoplasm. • There are three types of granulocytes, named according to which component of the haematoxylin and eosin (H&E) stain (haematoxylin: basic and coloured blue; eosin: acidic and coloured red) is taken up by their granules. Neutrophils • Granules are neutral, do not stain • Nuclear lobes increase with age. • Neutrophils are highly phagocytic and this, coupled with their motility (they have ameboid movement and can squeeze through endothelial openings – diapedesis), provides an effective body defence mechanism. • Their numbers increase rapidly during acute bacterial infections, thus, they are the most common first responders to microbial infection. Basophils • Nucleus generally two lobed but difficult to see due to presence of heavy, dense, dark purple granules. • Only accept the basic (haematoxylin) component of the H&E stain. • Basophils seem to lack phagocytic power. • Are responsible for allergen and antigen response (releases histamine causing vasodilation). Eosinophils • Nucleus generally two lobed; bright redorange granules. • They are about the same size as neutrophils. • Only accept the acidic (eosin) component of the H&E stain. • Phagocytic cells; particularly effective with antigen-antibody complexes. • Release antihistamines: increase in allergies and parasitic infections. Monocytes • Monocytes are usually the largest leukocyte seen on a stained blood film. • They have an indented or horseshoe-shaped nucleus. • Circulating monocytes phagocytize bacteria, viruses, and antigen–antibody complexes from the bloodstream. • However, their circulatory phagocytic function is not as pronounced as that which occurs in the tissues. • Monocytes are designed to degrade engulfed tissue debris from chronic inflammatory reactions, thus, their numbers increase in chronic infections. Lymphocytes • Spherical cells with a single, often large nucleus occupying most of the cell’s volume. • Stains purple. • Seen in large (Natural Killer cells) and small (B and T cells) variants. • It is believed that large lymphocytes represent immature forms, whereas small lymphocytes represent more mature forms. Thrombocytes/Platelets Where opportunity creates success • Blood platelets, also called thrombocytes are cytoplasmic fragments from megakaryocytes and are present in circulating blood. • Thrombocytes are produced principally from megakaryocytes. • Platelets (thrombocytes) are small, colourless, round or red-shaped bodies in the circulating blood of animals. • In chicken and other sub-mammalian species, they are nucleated cells and usually oval in shape. *Platelet clumping (which species and clinical significance) Haemostasis • The term haemostasis means the arrest of bleeding (haemorrhage) or prevention of blood loss. • For haemostasis to occur in any ruptured vessel, the following conditions are necessary:  Vascular spasm  Formation of platelet plug  Blood coagulation or clot  Growth of fibrous connective tissues into the blood clot to close the hole in the vessel Anticoagulants There are many anticoagulants used in obtaining blood samples free from clots for the purpose of haemotherapy (import in blood grouping-animal species, blood transfusion) and analytical works. Where opportunity creates success Blood coagulation • Whether the blood will clot or not depends on a balance between these two groups of substances (procoagulants and anticoagulants). • Usually anticoagulants are more in number that is why blood does not often clot in the blood vessels. • However, when a blood vessel is ruptured, the activity of the procoagulants in the damaged area becomes much greater than that of the anticoagulant and this brings about clot formation. Blood clot takes place in 3 ways: • Whether the blood will clot or not depends on a balance between these two groups of substances (procoagulants and anticoagulants). • Usually anticoagulants are more in number that is why blood does not often clot in the blood vessels. • However, when a blood vessel is ruptured, the activity of the procoagulants in the damaged area becomes much greater than that of the anticoagulant and this brings about clot formation. • Prothrombin a plasma protein is an α globulin. • It has a molecular weight of about 68,700. • It is an unstable protein that can easily split into smaller compounds, one of which is thrombin. • The molecular weight of thrombin is about 33,700. Pathways of Blood coagulation