7 - Haemopoietic System PDF

HAEMOPOIETIC SYSTEM Lecture by: DR. SHAHNAZ MAJEED. PhD  OUTLINE CONTENTS 1 Introduction to haemopoietic system 2 Blood and its functions 2.1 Composition and functions of whole blood 2.2 Haematopoiesis 2.3 Blood coagulation 2.4 Platelet adhesion and ac...

HAEMOPOIETIC SYSTEM Lecture by: DR. SHAHNAZ MAJEED. PhD  OUTLINE CONTENTS 1 Introduction to haemopoietic system 2 Blood and its functions 2.1 Composition and functions of whole blood 2.2 Haematopoiesis 2.3 Blood coagulation 2.4 Platelet adhesion and activation 2.5 Fibrinolysis (thrombolysis) 2.6 ABO Group & Rhesus factor 2.7 Blood transfusion and complication 3 Introduction to haemopoietic diseases  Introduction of Haematopoiesis Haematopoiesis is a Greek word haem means blood" and poiesis to make"; also hematopoiesis in American English; sometimes also haemopoiesis or hemopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells (HSCs). In a healthy adult person, approximately 1011–1012 new blood cells are produced daily in order to maintain steady state levels in the peripheral circulation.  INTRODUCTION Blood is a connective tissue Blood is a body fluid delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cell Blood make up about 7% of body weight (about 5.6 liters in a 70 kg man) Blood in the blood vessels is always in motion – maintains a constant environment for the body cells Blood volume and the concentration of its many constituents are kept within narrow limits by homeostatic mechanisms.  FUNCTIONS OF BLOOD Respiratory: Transport of oxygen from lungs to the tissues and carbon dioxide from the tissue to the lungs. Nutritive: Conveys absorbed food materials, glucose, carbohydrates, aminoacids,fatty acids, vitamins, electrolytes and trace metals from alimentary canal to the tissue for utilization and storage. Homeostatic for water, pH, and electrolyte concentration: Blood forms internal environment of the cell i.e in terms of volume, composition, concentration, pH and temperature which is regulated by normal physiological limits with respect to minor change in body called Homeostasis. Blood has also buffering power helps to maintain blood pH. Regulation of body temperature: Blood preserve very narrow range of body temperature. High conductivity- takes heat from an organ and distribute it through out body. High latent heat of evaporation. High specific heat.  Conti. Chemical for communication and protection: Concentration of hormones and various substances in the blood is regulated through feed back mechanism. With in blood circulates entire complex of humoral antibodies important in defense in against infection, initiate inflammation and regulation of Haemostasis ( Clotting mechanism). Plasma proteins functions: Acts reservoir of proteins Combine with many substances like iron, thyroxine and steroid hormones to form transportable complex from which active components are released at the appropriate sites.  HAEMATOCRIT The cellular element of blood represents 45% of the total blood volume called Packed cell volume (PCV) or Haematocrit. It includes Erythocytes; Normal 5 mllion/ cumm Leucocytes; 4,000 – 11,000/cumm Platelets or Thrombocytes; Normal 1.5 – 4 lacs/cumm. 150,000 – 400,000 lacs/cumm Determined by centrifuging a blood sample à all formed elements will come out of suspension Many factors can alter the hematocrit. E.g.: Increases in cases of dehydration, due to a reduction in plasma volume Decrease due to internal bleeding/problems with RBC formation  PLASMA Plasma = Plasma is a clear straw colored fluid portion of blood which represents 55% of total blood volume Contains 91% of the water 9% solid which comprises of 1% inorganic molecule and 8% organic molecule. Organic molecule contain Albumins Constitute 55% of the plasma proteins Major contributors to the osmotic pressure of the plasma Important in the transport of fatty acids, thyroid hormones, some steroid hormones Globulins Constitute 38% of the plasma proteins. E.g.: Immunoglobulins (antibodies) – attack foreign proteins and pathogens Transport globulin – bind small ions, hormones/compounds that might otherwise be lost at the kidneys Fibrinogen Constitute 7% fibrogen: Function: Blood clotting Constitute 4% of the plasma proteins Prothrombin : 40mg%  ORIGINS OF THE PLASMA PROTEINS In Embryo: Mesenchymal cells through process of secretion of substances forming plasma proteins. First Albumin is formed. In Adults: Albumin mainly liver, Fibrogen from liver Globulin , Liver ( Specially synthesize alpha and beta globulins) spleen and bone marrow. Liver synthesizes & releases > 90% of the plasma proteins Because the liver is the primary source of plasma proteins, liver disorders can alter the composition & functional properties of the blood. E.g.: some forms of liver disease can lead to uncontrolled bleeding due to inadequate synthesis of fibrinogen & other proteins involved in blood clotting. 10 FORMED/CELLULAR ELEMENTS 11  RED BLOOD CELLS (RBC)/ERYTHROCYTES Contain the red pigment hemoglobin (Hb), which binds & transports O2 & CO2 Are the most abundant blood cells – account for 99.9% of the formed elements Structure of RBCs: RBCs is a circular, biconcave disc with a thin central region & a thicker outer margin. Diameter ~ 7.5 µm & thickness ~ 2.5 µm. RBCs has no nucleus, no mitochondria, no ribosome but still can live for 120 days entirely depend on glucose for energy. 12  IMPORTANCE OF RBC SHAPE & SIZE Gives each RBC a relatively large surface area - The larger the surface area, the faster the exchange of O2 & CO2 It enables RBCs to form stacks, like dinner plates, that smooth the flow through narrow blood vessels without affecting the RBCs. It enables RBCs to bend & flex when entering small capillaries and branches. RBCs are very flexible & by changing shape, RBCs can squeeze through small capillaries. 13  HEMOGLOBIN Hemoglobin (Hb) account for over 95% of the intracellular proteins. Hb content of whole blood is reported in terms of grams of Hb per 100ml (g/dl) Normal ranges: Males: 15-18 g/dl Females: 13-16 g/dl Hb is responsible for the cell's ability to transport O2 & CO2 Hb Hb Oxyhemoglobin Carbaminohemoglobin (HbO2) (HbCO2) O2 CO2  HEMOGLOBIN STRUCTURE Each Hb molecule has a complex quaternary shape. Each Hb molecule has:- - two alpha (α) chains - two beta (ß) chains of polypeptides Each of the Hb chains contains a single molecule of heme and contain 146 amino acids.. Heme is a porphyrin (an organic compound generally associated with metal ions). Each heme unit holds an iron à iron can interact with O2 à oxyhemoglobin, HbO2. The iron-oxygen interaction is very weak & can easily be separated without damaging the heme unit/O2 molecules à The binding of O2 + iron is reversible RBCs of an embryo/fetus contain a different form of Hb (fetal Hb) – has higher affinity for O2 than Hb of adults. Oxygenation of 1st haem molecule increase the affinity of 2nd haem for oxygen which 3rd and 4th respectively. Molecular weight of haemoglobin is 68,000. The production of fetal Hb can be stimulated in adults by the administration of drugs (e.g. hydroxyurea/ butyrate) – for treatment of sickle cell anemia/thalassemia 15  HEMOGLOBIN FUNCTION There are approximately 280 million Hb molecules in each RBCs The amount of O2 bound to Hb depends primarily on the O2 contents of the plasma In the peripheral capillaries, plasma CO2 levels are elevated, O2 are low à α and β chains of Hb releases O2 and bind CO2 forming carbaminohemoglobin In the lungs capillaries, plasma O2 levels are high, CO2 are low à RBCs absorb O2 and bind O2 forming oxyhemoglobin Anemia if Hb content of RBCs is reduced Symptoms – weak, lethargic, confused (as the brain is affected) 16  HB LIFE SPAN,CIRCULATION, CONVERSATION & RECYCLING RBCs is exposed to severe mechanical stresses It takes