BMS231 Blood Physiology and Pathophysiology PDF

F A C U L T Y O F P h a r m a c y F A L L 2 0 2 3 aculty of Pharmacy Blood Physiology and Pathophysiology Dr. Ramadan Saad  Objectives At the end of this lecture...

F A C U L T Y O F P h a r m a c y F A L L 2 0 2 3 aculty of Pharmacy Blood Physiology and Pathophysiology Dr. Ramadan Saad  Objectives At the end of this lecture student should be able to: 1. Describe Cellular and non-cellular components of blood 2. Recognize functions of blood 3. Define Erythropoiesis; leucopoiesis, thrombopoiesis. 4. Recognize sites of RBC formation at different developmental age 5. Describe different stages of RBC differenation. 6. Describe features of RBC maturation. 7. Describe regulation of RBC production and erythropoietin hormone secretion in response to hypoxia. 8. Recognize clinical conditions associated with high level of erythropoitein in the blood. 3  Components of Blood Plasma – 55% Blood Cells – 45% – Three types Erythrocytes/RBCs Leukocytes/WBCs Thrombocytes/Platelets  WHAT IS BLOOD? IT IS A LIQUID CONNECTIVE TISSUE IN AN AVERAGE 70 Kg MAN: The average blood volume is 5 – 6 liters. It is roughly 8% of the total body weight. Female: 4-5 L, Male: 5-6 L Hematocrit RBCs as percent of total blood volume BLOOD COMPOSITION 5  HEMATOCRIT (PCV) The volume of erythrocytes in the whole blood expressed in percentage is the Hematocrit. This is also called as Packed Cell Volume or PCV. 7 aculty of PharmacyFunctions of Blood Transport: ◦ Transport of Gases. ◦ Transport of Nutrients ◦ Transport of Hormones. ◦ Transport of waste products. Regulation: ◦ Maintenance of Acid-Base Balance. ◦ Regulation of blood pressure. Defense: ◦ Against infection: White blood cells and Immune system. Hemostasis: stoppage of bleeding by platelets and clotting factors aculty of Pharmacy The Plasma The Plasma constitutes 55% of the blood volume. It is a yellow clear fluid. On standing it clots, the remaining fluid is called serum. The serum is the plasma from which clotting factors are removed. The Plasma is composed of 90% H20, 9% organic constituents, inorganic 9 aculty of Pharmacy Plasma Proteins Type Site of formation Concentration (gm/dL) 1- Albumin Liver 3.5 – 5.0 50% in the liver 2.5 50% in the white blood 2- Globulins cell (lymphocytes) 3- Fibrinogen Liver 0.4 4- Liver 0.01 Prothrombin Albumin /Globulin ratio Decreased in sever advanced liver disease and in infections as a result of increased gamma globulins. 10  Specific Functions of plasma proteins Functions Albumin  Maintains Osmotic Pressure.  Transport smaller molecules such as hormones and ions. Globulins α and ß globulins transport hormones and fat  soluble vitamins.  γ globulins (antibodies) bind to foreign substances. Fibrinogen  Converted into fibrin network that forms blood clots. Prothromb  Blood clotting. 11 aculty of Pharmacy plasma serum clotting proteins (fibrin) Serum; plasma lacking some clotting factors aculty of Pharmacy Leukocytes (White Cells) aculty of Pharmacy Leukocytes are grouped into two major categories: Granulocytes - contain specialized membrane- bound cytoplasmic granules - include neutrophils, eosinophils, and basophils. Agranulocytes - lack obvious granules - include lymphocytes and monocytes aculty of Pharmacy Neutrophils - 40%-70% WBCs - Duration of development: 6-9 days - Life Span: 6 hours to a few days - Function: Phagocytize bacteria  Eosinophils Basophils - 1%-4% WBCs - 0.5% WBCs - Development:6-9 days - Development: 3-7 days - Life Span: 8-12 days - Life Span: a few hours to a few days - Function: - Function: 1) Kill parasitic worms 1) Release histamine and other 2) destroy antigen-antibody mediators of inflammation. complexes 2) Contain heparin, an anticoagulant  Lymphocytes Monocytes - T cells and B cells - 4%-8% WBCs - 20%-45% WBCs - Development: 2-3 days - Development: days to weeks - Life Span: months - Life Span: hours to years - Function: - Function Mount immune response by 1. Phagocytosis direct cell attack (T cells) or 2. develop into macrophages via antibodies (B cells) in tissues  Why Leukopenia during chemotherapy? - Cancerous cells grow fast, which distinguish themselves from most of normal cells. - Chemotherapy is designed to kill fast-growing cells by interrupting mitotic cell division. - Chemotherapy also kills a few normal fast-growing cells including: Leukocytes Hair Intestinal epithelial cells aculty of Pharmacy Blood physiology-2 Dr. Ramadan Saad Erythrocytes (Red Blood Cells, RBCs) Average; 5 million/mm3 Appearance: Biconcave disc shape, which is suited for gas exchange. The shape is flexible so that RBCs can pass though the smallest blood vessels, i.e. capillaries. Structure: -Primary cell content is hemoglobin, the protein that binds oxygen and carbon dioxide. - no nucleus nor mitochondria aculty of Pharmacy Hemoglobin Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Each Hb molecule consists of: Four protein chains—globins Beta Alpha Four heme groups Heme groups Heme groups: (a) Alpha Beta Nonprotein moiety that binds O2 to ferrous ion (Fe2+) at its center CH3 CH CH2 Globins: four protein chains C C HC C C CH Two alpha and two beta chains CH3 C C N N Fe2+ N C C CH3 5% CO2 in blood is bound to globin CH2 CH2 C C N C C CH CH2 HC C C CH moiety COOH C C CH2 CH3 CH2 COOH (b) aculty of Pharmacy Functions of RBCs Functions: Carry Hemoglobin Transport of Oxygen Transport of Carbon Dioxide Buffer (pH regulation) Counts In males 4.8-5.8 million cells/mm3 In females 4.2-5.2 million cells/mm3 Life span 120 days  ERYTHROPOIESIS It is the process of the formation of RBCs. INTRAUTERINE LIFE: Liver & Spleen POST NATAL LIFE: CHILDREN: Predominantly Red Bone Marrow of skeleton: Axial & Appendicular. ADULTS: Red Bone Marrow of Axial Skeleton. 24  Life aculty of Pharmacy Span and Fate of RBCs The life span of RBCs is 120 days. Fate: RBCs cannot reproduce (Why?). They are fragile and rupture easily while passing through tiny vessels especially in the spleen. 25  FACTORS REGULATING ERYTHROPOIESIS 1. Decreased O2 supply to the tissues (Hypoxia): Decreased O supply to the 2 tissues stimulates RBCs production. Hypoxia stimulates erythropoiesis due to the stimulation of the release of erythropoietin hormone. Erythropoietin hormone is produced by the kidney 85% and the liver 15%. Erythropoietin hormone Stimulates RBCs formation. 26  2. Role of nutrients for erythropoesis Cobalamin (Vit B12) has role in RBC maturation found in red meat especially liver. Folic acid has role in RBC maturation in leaves, fish. Vitamin B6 has role in haemoglobin synthesis found in eggs, whole grain and bread, potatoes. Amino acids has role in synthesis of nucleoproteins found in eggs, meat, milk, milk products Vitamin C has role in conversion of folic acid to its active forms aids in absorption. Iron: Essential for the synthesis of Hemoglobin.  Factors Affecting Erythropoiesis (cont.) 3- Hormones: 1- Testosterone hormone stimulates erythropoietin secretion. 2- Thyroid hormones increase cell metabolism. 3- Cortisol hormone increases formation of RBCs. 4- Healthy Liver: Importance of the liver: 1- Forms globin. 2- Stores iron and vitamin B12. 3- Produces 15% of erythropoietin. 5- Healthy Bone Marrow: It is the site of erythropoiesis. It is destroyed by irradiation and tumors. 28  ANEMIAS It is a decrease of red blood cells count, Hb concentration or both It leads to a decrease in O2 supply to the tissues. 29  ANEMIAS Individual Assignment 30 aculty of Pharmacy Erythrocyte Disorders - 2 Polycythemia is an abnormal excess of erythrocytes that increases the viscosity of the blood, causing it to sludge or flow sluggishly. Individual assignment Haemostasis : Vasoconstriction Platelet activation Haemostatic plug Coagulation Stable clot formation Clot dissolution  HEMOSTASIS: Hemostasis is a process which causes bleeding to stop, meaning to keep blood within a damaged blood vessel (the opposite of hemostasis is hemorrhage). It is the first stage of wound healing. 33  Hemostasis BV Injury Tissue Neural Factor Blood Vessel Platelet Coagulation Constriction Activation Activation Primary hemostatic Reduced plug Thromibn, Blood flow Fibrin Stable Hemostatic Plug  1) vascular spasms 3) blood clotting / 2) platelet plug formation coagulation aculty of Pharmacy 1. VASCULAR SPASM Also called Vasoconstriction. Is spontaneous. Immediate but temporary. Lasts for a maximum of 30 minutes. Cause: Myogenic: from the smooth muscles Neurogenic: from the nerves Some chemicals like serotonin 36 2) Form temporary platelet plugs to stop bleeding ◦ Endothelial cells secrete von Willebrand factor to cause platelets to adhere to collagen. ◦ When platelets stick to collagen, they degranulate as platelet secretory granules:  Release ADP, serotonin and thromboxane A2.  Serotonin and thromboxane A2 stimulate vasoconstriction.  ADP and thromboxane A2 make other platelets “sticky.”  Platelets adhere to collagen. aculty of Pharmacy Platelet Plug Formation  Blood coagulation (clot formation) 3. COAGULATION: BASIC THREE STEPS A series of biochemical reactions leading to the formation of a blood clot within few seconds after injury Prothrombin (inactive thrombin) is activated by a long intrinsic or short extrinsic pathways This reaction leads to the activation of thrombin enzyme from inactive form prothrombin Thrombin will change fibrinogen (plasma protein) into fibrin (insoluble protein) 40  Intrinsic pathway The trigger is the activation of factor XII by contact with foreign surface, injured blood vessel, and glass. Activated factor XII will activate factor XI Activated factor Xl will activate IX Activated factor IX + factor VIII + platelet phospholipid factor (PF3)+ Ca activate factor X Following this step the pathway is common for both intrinsic and extrinsic 41  Extrinsic pathway Triggered by material released from damaged tissues (tissue thromboplastin) Tissue thromboplastin + VII + Ca activate X Common pathway Activated factor X + factor V +PF3 + Ca activate prothrombin activator; a proteolytic enzyme which activates prothrombin. Activated prothrombin activates thrombin Thrombin acts on fibrinogen and change it into insoluble thread like fibrin. Factor XIII + Ca strong fibrin (strong clot) 42  Fibrinolysis Formed blood clot can either become fibrous or dissolved. Fibrinolysis (dissolving) = Break down of fibrin by naturally occurring enzyme plasmin therefore prevent intravascular blocking. There is a balance between clotting and fibrinolysis Excess clotting blocking of Blood Vessels Excess fibrinolysis tendency for bleeding 44  Streptokinase Released from Fibrinolys Urokinase Tissue Plasminogen healed tissues Activator (t-PA) is and vascular endothelium Plasminogen Plasmin (Protein in the lys no blood) ri b Fi is Fibrinoge Fibrin n Thrombin FDP * FDP*: Fibrin Degradation Products aculty of Pharmacy Anticoagulants Anticoagulants for clinical use: Heparin - Commercial, extracted from animals  Coumarins - Warfarin, competitive with vitamin K - decrease Factors II, VII, IX, X Prevention of blood coagulation outside the body (decrease calcium ion concentration) Oxalate (precipitation, toxic )  Citrate (deionizer)  EDTA (Chelating agent) Thank you for your attention!