BMS231 (Blood Physio and Patho) - Fall 2023 - Galala University - 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 Faculty of Pharmacy Blood Physiology and Pathophysiology Dr. Ramadan Saad ...

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 Faculty 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 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 Faculty of Pharmacy Functions 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 Faculty 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 constituents and blood gases. 9 Faculty 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 cell 2- Globulins (lymphocytes) 3- Fibrinogen Liver 0.4 4-Prothrombin Liver 0.01 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. Prothrombin Blood clotting. 11 Faculty of Pharmacy plasma serum clotting proteins (fibrin) Serum; plasma lacking some clotting factors Faculty of Pharmacy Leukocytes (White Cells) Faculty 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 Faculty 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) Release histamine and other 1) Kill parasitic worms mediators of inflammation. 2) destroy antigen-antibody 2) Contain heparin, an anticoagulant complexes  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 1. Phagocytosis Mount immune response by direct cell attack (T cells) 2. develop into macrophages or 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 Faculty 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 Faculty 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 C C CH3 N Fe2+ N 5% CO2 in blood is bound to globin moiety CH2 CH2 C C N C C CH CH2 HC C C CH COOH C C CH2 CH3 CH2 COOH (b) Faculty 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 Faculty of Pharmacy Life 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 O2 supply to the 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  Blood Groups These are chemical groups present on the red blood cell membranes. They are antigenic in character, so they are termed agglutinogens. There are two systems for blood group classification (the ABO system & Rh system). According to the ABO system there are two types of agglutinogens called A & B agglutinogen. In the plasma there are antibodies against these agglutinogens , they are termed agglutinins. Agglutinins are of two types alpha (i.e. anti-A antibodies) and beta (ani-B antibodies). According to the presence or absence of A&B agglutinogen, blood groups are classified into 4 types (A,B,AB &O).This is called ABO system for blood group classification.  Blood Groups (ABO) system Blood group Agglutinogen Agglutinins in on red blood the plasma cell membrane A A Beta B B Alpha AB A& B No agglutinins O No Alpha &Beta  Blood Groups According To The Rh System According to the Rh system, Red blood cells are classified according to the presence or absence of antigen (.i.e. agglutingen) D on the red blood cell membrane. If the D agglutinogen is present on the red blood cell membrane, the blood group is considered Rh+ve. If the D agglutinogen is absent on the red blood cell membrane, the blood group is considered Rh-ve. Rh+ve people constitute 85% of the population, while the Rh-ve people constitute the remaining 15%.  Rh Factor Rh Antibodies Second Pregnancy First Pregnancy Another Rh positive fetus Rh negative If this mother did not mom with Rh receive Rhogam (Rh positive fetus antibody) after her first delivery, this baby’s blood cells will be attacked Antibodies develop (erythroblastosis fetalis) which could be fatal for the baby.  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. 37 Steps Of Hemostasis Injury of the blood vessel 1-vasoconstriction of the injured blood vessel 2-Platelet adhesion ( Platelets stick to the cut ends of the vessel wall). 3-Platelet aggregation 4-Formation of blood clot 5- Healing of the vessel  1) vascular spasms 3) blood clotting / 2) platelet plug formation coagulation 1-Vascular Spasm It is initiated by tissue damage through: 1- Nervous: sympathetic over activity & pain. 2- Chemical: release of vasoconstrictor substances from damaged tissues, platelets & arterial wall ( serotonin, thromboxane A2 & endothelin). 3- Myogenic reflex. 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. Faculty of Pharmacy Platelet Plug Formation 3- Coagulation Coagulation follows intrinsic and extrinsic pathways The final three steps of this series of reactions are: Prothrombin activator is formed Prothrombin is converted into thrombin Thrombin catalyzes the joining of fibrinogen into a fibrin mesh.  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 45  Streptokinase Released from Fibrinolysis Urokinase Tissue Plasminogen healed tissues Activator (t-PA) and vascular endothelium Plasminogen Plasmin (Protein in the blood) Fibrinogen Fibrin Thrombin FDP * FDP*: Fibrin Degradation Products Faculty 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 ❖ Citrate ❖ EDTA Thank you for your attention!