Physiology of Blood PDF

PHYSIOLOGY OF BLOOD Contents Definition of Haematology Brief history of Haematology Functions of Blood Composition of Blood Functions of Plasma Proteins Formed Elements in blood & their functions Stem Cell Theory Haematopoiesis What is Haematology? Hematology is the study of blood, blood components,...

PHYSIOLOGY OF BLOOD Contents Definition of Haematology Brief history of Haematology Functions of Blood Composition of Blood Functions of Plasma Proteins Formed Elements in blood & their functions Stem Cell Theory Haematopoiesis What is Haematology? Hematology is the study of blood, blood components, and blood disorders. – It also includes the study of haematopoiesis, the formation of blood in the bone marrow (the spongy core of bones). The Greek word haimato and the suffix ology are the basis for the medical term hematology meaning "the study of blood." History of Haematology Ancient Egyptians: Blood letting 1628 – English physician, William Harvey discovered that blood travels in a closed circuit with the use of arteries & veins. 1674: Dutch scientist, Antonie van Leeuwenhoek, documented and described red blood cells. 1770-1774: British surgeon, Willam Hewson, discovered white blood cells, fibrinogen (a protein that helps form blood clots), an anticoagulant (substances that prevent blood clots) called Glauber's salt, and the fundamentals of blood coagulation. Hewson is known as the father of hematology. 1818: English physician, James Blundell, performed the first successful human blood transfusion. A blood transfusion takes healthy red blood cells from a donor and gives them to a patient suffering from a blood disorder. 1868: German pathologist, Franz Ernst Christian Neumann, discovered the role of bone marrow in hematopoiesis. 1901: Austrian biologist, Karl Landsteiner, developed the modern classification of blood by group or type (A, B, AB, and O). Characteristics of Blood Approx. 8% total body weight 5-6 liters in males; 4-5 liters in females pH 7.35 - 7.45 (alkaline) Viscosity 4.5 - 5.5 times water Formed elements – RBC, WBC, Platelets FUNCTIONS OF BLOOD Transport of substances Defense against diseases Arrest of bleeding (hemostasis) Maintenance of a stable internal environment (homeostasis) Functions of Blood Transportation Delivering oxygen from the lungs and nutrients from the digestive tract to all body cells. Transporting metabolic waste products from cells to elimination sites (to the lungs to eliminate carbon dioxide, and to the kidneys to dispose of nitrogenous wastes in urine). Transporting hormones from the endocrine organs to their target organs. Functions of Blood Regulation Maintaining appropriate body temperature by absorbing and distributing heat throughout the body and to the skin surface to encourage heat loss. Maintaining normal pH in body tissues. – Many blood proteins and other blood borne solutes act as buffers to prevent excessive or abrupt changes in blood pH that could jeopardize normal cell activities. Additionally, blood acts as the reservoir for the body’s “alkaline reserve” of bicarbonate ions. Maintaining adequate fluid volume in the circulatory system. – Blood proteins prevent excessive fluid loss from the bloodstream into the tissue spaces. As a result, the fluid volume in the blood vessels remains ample to support efficient blood circulation to all parts of the body. Functions of Blood Protection Preventing blood loss. – When a blood vessel is damaged, platelets and plasma proteins initiate clot formation, halting blood loss. Preventing infection. – Drifting along in blood are antibodies, complement proteins, and white blood cells, all of which help defend the body against foreign invaders such as bacteria and viruses. Composition of Blood Composition of Blood Composition of Blood Plasma Liquid part of blood – Pale yellow made up of 91% water, 9% other Colloid: Liquid containing suspended substances that don’t settle out – Albumin: Important in regulation of water movement between tissues and blood – Globulins: Immune system or transport molecules – Fibrinogen: Responsible for formation of blood clots Plasma Proteins Serum differs from plasma by the absence of fibrinogen and other coagulation factors. Serum contains albumin, antibodies & other proteins. The liver synthesizes most of the globulins and coagulation factors. Removal of the albumin and fibrinogen moiety yields the proteins grouped as globulins. Alpha, beta, gamma globulins Gamma globulins – immunoglobulins which are synthesized by plasma cells and lymphocytes – IgA, IgD, IgE, IgG and IgM – Antibodies anti-A, anti-B Major Plasma Proteins Plasma Proteins Constituent Description & Importance Water 90% of plasma volume; dissolving & suspending medium for solutes of blood; absorbs heat Electrolytes Most abundant solutes by number; cations, include sodium, potassium, calcium, magnesium; anions include chloride, phosphate, sulfate and bicarbonate; help to maintain plasma osmotic pressure and normal blood pH Plasma Proteins 8% (by weight) of plasma; all contribute to osmotic pressure & maintain water balance in blood & tissues; all have other functions (transport, enzymatic, etc.) as well Albumin 60% of plasma proteins; produced by the liver; main contributor of osmotic pressure Globulins 36% of plasma proteins Alpha, beta Produced by the liver; most are transport proteins that bind to lipids, metal ions & fat-soluble vitamins Gamma Antibodies released by plasma cells during immune response Plasma Proteins Constituent Description & Importance Gamma globulins Antibodies released by plasma cells during immune response Fibrinogen 4% of plasma proteins; produced by liver; forms fibrin threads of blood clot Non-protein nitrogenous substances By-products of cellular metabolism, such as urea, uric acid, creatinine and ammonium salts Nutrients (organic) Materials absorbed from digestive tract and transported for use throughout body; include glucose and other simple carbohydrates, amino acids (protein digestion products), fatty acids, glycerol and triglycerides (fat digestion products), cholesterol, and vitamins Respiratory gases Oxygen and carbon dioxide; oxygen mostly bound to hemoglobin inside RBCs; carbon dioxide transported dissolved as bicarbonate ion or CO2, or bound to hemoglobin in RBCs Hormones Steroid and thyroid hormones carried by plasma proteins Plasma Proteins Transcobalamin Ceruloplasmin IGF-binding proteins Thyroid-binding globulin Corticosteroid binding globulin Sex hormone binding globulin Vitamin D- binding globulin Erythrocytes, leukocytes and thrombocytes SEM x1,825 Formed Elements Red blood cells (erythrocytes) White blood cells (leukocytes) – Granulocytes Neutrophils Eosinophils Basophils – Agranulocytes Lymphocytes Monocytes Platelets (thrombocytes) Review State 3 important roles of plasma Differentiate between the eosinophil and basophil Differentiate between the neutrophil and monocyte. STEM CELL THEORY All the blood cells are produced by the bone marrow They all come from a single class of primitive mother cell - PLURIPOTENT STEM CELLS These cells give rise to blood cells of: – Myeloid series: Cells arising mainly from the bone marrow – Lymphoid series: Cells arising from bone marrow but maturing in the lymphoid tissues HAEMOPOIESIS Haemo: Referring to blood cells Poiesis: “The development or production of” The word “haemopoiesis” refers to the production & development of all the blood cells: – Erythrocytes: Erythropoiesis – Leucocytes: Leucopoiesis – Thrombocytes: Thrombopoiesis Haematopoiesis Haematopoiesis is the process of generation of all the cell types present in blood. Pluripotent haematopoietic stem cells = adult stem cells Haematopoiesis During Embryonic Life Sites of Haeamatopoiesis at different Stages of Life Haematopoiesis Early foetal life – yolk sac 2nd – 7th month – liver, spleen and lymph nodes 7th – 9th month and after birth – bone marrow During childhood – marrow of all bones After about age 20 – marrow of flat bones Lasts between 4 – 8 days in humans Sites of Blood Production in the Foetus & Postnatal Years Early fetal life - yolk sac 2nd-7th month – liver, spleen and lymph nodes 8th-9th month – bone marrow Childhood – marrow of all bones With increasing age – marrow of flat (membranous) bones e.g. sternum, ribs, pelvis Stages of RBC Differentiation 1. Progenitor Cells – Burst forming units – erythroid (BFU-E): form very large colonies of thousands of nucleated erythroid precursors on culture. – Intermediate forms. – Colony-forming units – erythroid (CFU-E): most differentiated erythroid progenitor cells; form colonies of up to 64 nucleated erythroid progenitor cells. Stages of RBC Differentiation 2. Morphologically recognizable nucleated precursors a. Pronormoblast b. Normoblast: 3 stages of increasing differentiation – (i) Basophilic: the cell has lost its nucleoli and early clumping of nuclear chromatin is seen. The cytoplasm is still deep blue because of its high RNA content. – (ii) Polychromatophilic. The cell and its nucleus are smaller. Large clumps of nuclear chromatin are seen. The colour of the cytoplasm varies from graypurple to purple-pink, reflecting a decreasing RNA content and an increasing Hb content. – (iii) Orthrochromatic. The cell is still smaller, and the nucleus has shrunk into a solid black ball. The cytoplasm is definitively pink. Different Cell Stages During Erythropoiesis Erythropoiesis Requirements for Erythropoiesis Iron Vitamin B12 Folate Androgens Cobalt salt Erythrocytes Structure – Biconcave, anucleate Components – Hemoglobin – Lipids, ATP, carbonic anhydrase Function – Transport oxygen from lungs to tissues and carbon dioxide from tissues to lungs Regulation / Control of Haematopoiesis Is a 2 –tiered process Growth factors prepare early progenitor forms for the effect of the more specific trophic hormones for a particular lineage. Erythropoiesis required the successive participation of a growth factor (or factors) needed to initiate the process and a factor required to sustain the process to its end point. – 1. Burst–promoting activity (BPA) released from the bone marrow – 2. Erythropoietin produced by the kidneys Production of RBCs equals destruction Enough RBCs produced for tissue oxygenation, but not to increase blood viscosity Schematic Diagram of the process of Erythropoiesis Erythropoietin Produced mainly in the kidneys, with small quantities in the liver – Influenced by tissue hypoxia Increases the rate of division of committed stem cells times) (6-8 Could increase the normal reticulocyte count from 1% to about 30% or more Used to treat anemia associated with chronic renal failures, AIDS or cancer chemotherapy Erythropoietin Epo can increase blood viscosity, a major contributor for heart disease Can also lead to sudden death due to drastic reduction in heart rate and development of Epo antibodies which can destroy red blood cells Erythropoiesis Increased erythropoietic activity seen as reticulocyte count greater than 2.5% The blood cells enter the circulation by a process of diapedisis HEMATOPOIETIC GROWTH FACTORS They are heterogeneous group of cytokines that stimulate the progenitor cells and induce proliferation and maturation. They are glycoproteins synthesized by variety of cells in marrow. They bind to specific receptors on the surface of various cells of the hematopoietic system. Characteristics and properties of haematopoietic growth factors 1. 2. 3. 4. Naturally occurring hormones Low molecular weight glycoproteins Variable degrees of species specificity Available in purified form by recombinant DNA technology 5. Responsible for stimulation and release of other growth factors and cytokines Growth Factors Growth and proliferation of pluripotent stem cell. Committed or progenitor cells formed. Process controlled so that production equal destruction. Colony Stimulating Factors GM-CSG A glycoprotein that stimulates proliferation of a common myeloid progenitor and promotes the production of neutrophils, eosinophils, and monocytes-macrophages. G-CSF and M-CSF glycoproteins that guide the ultimate development of granulocytes and monocytes-macrophages/ dendritic cells, respectively IL-3 (multi-CSF) has a broad effect on multiple lineages. The liver and the kidney constitutively produce this glycoprotein. IL-5 sustains the terminal differentiation of eosinophilic precursors. TPO (Thrombopoietin) Binds to a thrombopoietin receptor called c-Mpl. On stimulation by TPO, the Mpl receptor induces an increase in the number and size of megakaryocytes which produce platelets. Erythropoetin Produced by the kidney and to a lesser extent by the liver; supports erythropoiesis or red cell development Regulation of Haematopoiesis Intensity of Haematopoiesis RBCs: 3.5x1011 cells per day Neutrophils: 1011 cells per day Monocytes: 8.4x109 cells per day Platelets: 1011 cells per day Red Blood Cells (Erythrocytes) 70 trillion cells in an average 70 Kg man 25 trillion are red blood cells Human Blood Smear & Erythrocyte Normal Erythrocyte Biconcave disc 7-8 µm in diameter 2.5 µm in thickest part 1.0 µm in thinnest part 90 µm3 in volume 140 µm2 in surface area High surface area to volume ratio Facilitates gas delivery and cell deformability Hierarchy of Haematopoiesis https://connect.springerpub.com/content/book/978-0-82614987-9/chapter/ch01 Selected CDs that belong to different cell types https://connect.springerpub.com/content/book/978-0-8261-49879/chapter/ch01