Blood Physiology 2021-2022 PDF

Blood Physiology Dr. M. Abdelmohsen Assistant Professor of Physiology MBBCh, MSc, DMSc, DHPE Faculty of Pharmacy 2021-2022  Objectives ❖ At the end of this lecture, the 2nd year student...

Blood Physiology Dr. M. Abdelmohsen Assistant Professor of Physiology MBBCh, MSc, DMSc, DHPE Faculty of Pharmacy 2021-2022  Objectives ❖ At the end of this lecture, the 2nd year student should be able to: Discuss composition of blood. Explain general functions of blood. Discuss erythropoiesis. Explain clotting mechanisms. Explain immunity and compare its types. Discuss pathophysiology of anemia. Explain pathophysiology of immunity. Blood Physiology Dr. Sally Said Donia Assistance Prof. of Physiology  Thicker (more viscous) than water and flows more slowly than water. Physical Temperature of 36.1°C to 37.2°C pH range from 7.35 to 7.45 (slightly characteristics alkaline) of blood Blood volume: 5 to 6 liters in average male and 4 to 5 liters in average female 5  Composition of the blood Plasma: fluid part, 55% of total blood volume, mainly water, organic and inorganic substances. Cellular elements: 45% of total blood volume. RBC or erythrocytes (5x106/mm3) which transport oxygen. WBC or leukocytes (3-10x103/mm3 ) which protect against infection. Platelets or thrombocytes(150-400x103/mm3) they are cell fragments that participate in blood clotting. 6  General functions of blood 1- Transportation: Oxygen from inhaled air in the lung & carbon dioxide from the tissues to the lungs for elimination Blood transports nutrients from the digestive system to the tissue cells. Blood transports waste products from the cells to the kidney and the liver. Blood carries hormones from their glands to the effector organs. 2-Regulation: Buffers in the blood help keep the PH of body fluids at about 7.4 Blood serves to regulate the amount of fluid in the tissues by plasma proteins that maintain the proper osmotic pressure Blood regulates body temperature by redistributing the excess heat. 3- Protection: Blood carries the cells and antibodies (immunity) that defend against pathogens. Blood contains clotting factors that protect against blood loss. Plasma Fluid part of the blood. Mainly water (90%) and others (10%) Others Plasma proteins:7gm/dl which includes: Albumin 3-5gm/dl, Globulin 2.5-3.5gm/dl, fibrinogen 0.3gm/dl and Prothrombin is very small amount 10mg/dl. Other solutes: glu, F.A. vitamines. 9 Plasma proteins: Normal concentration 7 g/dL Albumin: Albumin constitutes about 60% of the total plasma proteins Function: 1- It regulate the colloidal osmotic pressure of blood. 2- It binds many substances to help its transport. Globulins: These are formed of alpha, beta and gamma globulins. Types: α1, α2, β1, β2 and γ globulins Function: 1- alpha and beta globulins are transport proteins. 2- gamma globulins are defensive against foreign proteins (antibodies). Fibrinogen: Function: 1- Is essential for blood clotting. 2- It is important in determination of normal blood viscosity. 10 Plasma proteins: Also include the following: 1) The antibodies combat infection. 2) Blood clotting factors are also manufactured in the liver. 3) Complement: they are enzymes help antibodies against pathogens. others Nutrients: glucose, amino acids, small amount of lipids, mineral salts (chloride, carbonate, or phosphate salts of sodium, potassium, and magnesium) which function as formation of bone, production of hormones, transportation of the gases (O2 and CO2), and maintenance of acid base balance (Buffers) e.g., sodium carbonates. 11 General functions of plasma proteins 12 Buffer action: Help in keeping pH of blood constant. Reservoir functions: carrier proteins for small molecules such as vitamins, hormones, trace elements and drugs. Carry CO2: as carbamino compounds. 13 Nutritive: used by the tissue during prolonged starvation. Osmotic function: plasma proteins (mostly albumin) exert an osmotic pressure across the capillary wall (colloid osmotic pressure or oncotic pressure). Plasma volume regulation tissue fluid formation. Blood clotting: prothrombin and fibrinogen are essential for blood clotting 14 RBCs & Erythropoiesis Blood physiology  RBCs Shape: Biconcave shape. with no nucleus or other organelles and no mitochondrial ATP formation. Size: Mean diameter is 7.8 micrometer. The thickness is about 1 μm in the center 2.5 μm at the periphery. It contains hemoglobin (Hb)1/3 of cell’s weight and gives blood its red color. & Carbonic anhydrase E. 16 Functions of RBC Transport Hb which carries O2 Contain CA enzyme (CO2 transport in the form of bicarbonate ion). RBC are important for normal blood viscosity. 17 Functions of RBCs membrane To maintain the characteristic shape. increases the surface area of RBCs. The main function of RBCs membrane is to keep the hemoglobin inside the red cells. It carries antigen that determines the blood group. 18 Erythropoiesis Definition: Production of mature RBCs (erythrocytes) from erythropoietic stem cell. Sites: During fetal life: in yolk sac. the liver, spleen and lymph node. After birth: RBCs are exclusively in bone marrow of all bones up to the age of 5 years. After the age of 20: membranous bone marrow (vertebrae, sternum, ribs and ilia) is mainly responsible for red cell production in addition to the upper ends of humeri and tibiae. What are the requirements for effective Erythropoiesis? Tissue oxygenation: Hormones: Thyroxine, glucocorticoids and testosterone stimulates RBCs production. Liver: healthy liver is essential for erythropoiesis Bone marrow: It is the site of RBCs production Dietary factors: Protein, iron, all vitamins specially B12 Regulation of erythropoiesis: 1) Erythropoietin hormone: - Site of release: - Mainly the kidney (more than 90 %) and liver (10%) in response to hypoxia (physiological e.g., fetus & high altitudes or pathological e.g., anemia). - In Anemia: Low circulating numbers of RBCs in case of anemia leads to a relatively high level of erythropoietin, which stimulates more production of RBCs in the bone marrow. Regulation of erythropoiesis: 2) Hepcidin: a recent discovered peptide (hormone) produced by the liver may play a role in erythropoiesis. which inhibits iron absorption from the intestinal mucosal cells and inhibits iron release by macrophages and hepatocytes It controls iron absorption in the gastrointestinal tract and iron release from reticuloendothelial tissue. Leukocytes (WBCs) WBCs White blood cells, or leukocytes, are the mobile units of the body’s protective system. They are classified into two main groups: granulocytes and agranulocytes. Immunity: Definition: is the process of defense against invaders and pathogens. Types: 1- Innate (Natural) immunity: direct and rapid 2- Adaptive (acquired) immunity: Mechanisms of Innate (Natural) Skin prevents invasion of pathogens. Macrophages (Monocytes) and microphages (Mainly neutrophils & eosinophils) phagocytose the pathogens (bacteria) and destruct it. Natural killer (NK) cells (type of T cells) is natural cytotoxic to infected cells. Immunity: 2- Adaptive (acquired) immunity: indirect and slower. More effective and produce memory cells for the next same pathogen (as in previous same infection or vaccination). Mechanisms: Humoral: Antibodies produced by B lymphocytes to fix antigens of pathogen directly. Cell-mediated: through T lymphocytes via: 1- Helper T cells (CD4): Identification of antigen presented cells (APC) to help phagocytosis of these infected cells. 2- Cytotoxic T cells (CD8): Destroy the cells contains the antigen. Platelets & Hemostasis Blood Physiology Platelets (thrombocytes) Cell fragments,1-4 m in diameter. Normal count: 150,000- 500,000/mm3. Life span 8-12 days Have many functional characteristics of whole cells although they lack nuclei and cannot reproduce. 28  Hemostasis The term hemostasis means prevention of blood loss. Hemostasis is the process of forming clots in the walls of damaged blood vessels and preventing blood loss, while maintaining blood in a fluid state within the vascular system. 29 Blood Clotting: (by intrinsic or extrinsic pathways): Coagulation: Protective mechanism prevents blood loss from injured blood vessel. Clotting factors are normally inactive in the blood stream. Procoagulants: are compounds promote clotting, Anticoagulants: are compunds prevent clotting. Thrombolytics: are circulating chemicals dissolve clots. All are normally in balance.  II- Platelet plug formation Mechanism: – Vascular spasm – Platelet adherence. – Platelet activation & Release Reaction – Platelet aggregation. – Platelet fusion. – Platelet procoagulant activity. 31 Clotting steps: Injured tissues release → thromboplastin → reacts with proteins (clotting factors) and calcium → prothrombin activator → reacts with calcium → convert prothrombin to thrombin → thrombin converts soluble fibrinogen into insoluble fibrin → forms a network of threads that entraps red blood cells (the clot). Pathophysiology Anemia: Definition: Causal types of anemia: Lack enough healthy RBCs or Hb to 5. Vitamin carry deficiency 1. Aplastic 3. Sickle cell 4.Thalassemia: anemia: e.g., adequate anemia: bone anemia: the genetic 2. Iron vitamin B12 marrow shape of RBC is abnormality of oxygen to insufficiency. deficiency sickle (type of alpha or beta (pernicious anemia. anemia) & folic tissues. All blood cells hemolytic subunit of acid deficiency decrease. anemia). hemoglobin (megaloblastic anemia). Anemia: Definition: Lack enough Analytical (laboratory) types of anemia: healthy RBCs or Hb to carry adequate 2- Normocytic 1- Microcytic 3- Macrocytic oxygen to hypochromic normochromic anemia: vitamin anemia: blood tissues. anemia: iron loss and chronic B12 & folic acid deficiency. deficiency. diseases. Anemia Symptoms & signs of anemia: Fatigue weakness pale or yellowish skin. Irregular heartbeats shortness of breath. Headaches dizziness Chest pain Cold hands and feet. Complications: Extreme fatigue, pregnancy complications, heart problems. Prevention & treatment: Iron: Iron-rich foods (liver beef and meats, beans, lentils & iron-fortified cereals). Folate: fruits and fruit juices, dark green leafy vegetables, bread, cereal, pasta and rice. Vitamin B-12: meat, dairy products, fortified cereal and soy products. Vitamin C (increase iron absorption): citrus fruits and juices, broccoli, melons, and strawberries. Drugs & supplementations: all nutrients can be given as supplementation. ❑ Immunity diseases: Hypersensitivity reactions: exaggerated response of immune system to an antigen that cause tissue damage. Types of hypersensitivity reactions: Type-I (Immediate Hypersensitivity Reaction): over production of IgE e.g., bronchial asthma, allergic rhinitis, and contact dermatitis. Type-II (Cytotoxic Hypersensitivity): IgG type reacts with cell antigen. e.g., Autoimmune hemolytic anemia, erythroblastosis fetalis, and Drug-induced hemolysis. Type-III (Immune complex disease): formation of antigen-antibody complexes. e.g., tissue destruction (vascular injury). Type-IV (Cell-Mediated Hypersensitivity or delayed type): sensitized T-lymphocytes. e.g., contact dermatitis.  Immuno-deficiency diseases: 1. Primary immune-deficiency diseases: early childhood (genetically determined) Deficiencies of antibody (B-cells). Deficiency of cell-mediated (T-cells) Combined T-cells and B-cells Deficiency (Severe disease) Complement factor deficiency. 2. Secondary immuno-deficiency diseases: - Deterioration in previously strong immune status. - Occur secondary to systemic conditions like: - ▪ Diabetes mellitus ▪ Cancer ▪ Human Immuno-deficiency Virus (HIV/AIDS). ▪ Renal failure, Liver failure, Poor nutrition.  Thank You Faculty of Pharmacy 2021-2022