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Physiology for Pharmacy Students Tortora 13th Ebaa M Alzayadneh,PhD Blood • Liquid connective tissue • 3 general functions 1. Transportation – Gases, nutrients, hormones, waste products 2. Regulation – pH, body temperature, osmotic pressure 3. Protection – Clotting, white blood cells, proteins University of Jordan 2 Components of Blood – Blood plasma – water liquid extracellular matrix • 91.5% water, 8.5% solutes (primarily proteins) • Hepatocytes synthesize most plasma proteins – Albumins, fibrinogen, antibodies • Other solutes include electrolytes, nutrients, enzymes, hormones, gases and waste products – Formed elements – cells and cell fragments • Red blood cells (RBCs) • White blood cells (WBCs) • Platelets University of Jordan 3 University of Jordan 4 Formed Elements of Blood University of Jordan 5 Formation of Blood Cells • Negative feedback systems regulate the total number of RBCs and platelets in circulation • Abundance of WBC types based of response to invading pathogens or foreign antigens • Hemopoiesis or hemotopoiesis • Red bone marrow primary site • Pluripotent stem cells have the ability to develop into many different types of cells University of Jordan 6 University of Jordan 7 Formation of Blood Cells • Stem cells in bone marrow – Reproduce themselves – Proliferate and differentiate • Cells enter blood stream through sinusoids • Formed elements do not divide once they leave red bone marrow – Exception is lymphocytes University of Jordan 8 Formation of Blood Cells • Pluripotent stem cells produce – Myeloid stem cells • Give rise to red blood cells, platelets, monocytes, neutrophils, eosinophils and basophils – Lymphoid stem cells give rise to • Lymphocytes • Hemopoietic growth factors regulate differentiation and proliferation – Erythropoietin – RBCs – Thrombopoietin – platelets – Colony-stimulating factors (CSFs) and interleukins – WBCs University of Jordan 9 Red Blood Cells/ Erythrocytes • Contain oxygen-carrying protein hemoglobin • Production = destruction with at least 2 million new RBCs per second • Biconcave disc – increases surface area • Strong, flexible plasma membrane • Glycolipids in plasma membrane responsible for ABO and Rh blood groups • Lack nucleus and other organelles – No mitochondria – doesn’t use oxygen University of Jordan 10 Hemoglobin – Globin – 4 polypeptide chains – Heme in each of 4 chains – Iron ion can combine reversibly with one oxygen molecule – Also transports 23% of total carbon dioxide • Combines with amino acids of globin – Nitric oxide (NO) binds to hemoglobin • Releases NO causing vasodilation to improve blood flow and oxygen delivery University of Jordan 11 Shapes of RBC and Hemoglobin University of Jordan 12 Red Blood Cells • RBC life cycle – Live only about 120 days – Cannot synthesize new components – no nucleus – Ruptured red blood cells removed from circulation and destroyed by fixed phagocytic macrophages in spleen and liver – Breakdown products recycled • Globin’s amino acids reused • Iron reused • Non-iron heme ends as yellow pigment urobilin in urine or brown pigment stercobilin in feces University of Jordan 13 Formation and Destruction of RBC’s Circulation for about 120 days 7 3 Reused for protein synthesis Amino acids Globin 4 6 5 Fe3+ Fe3+ Transferrin 2 Heme Fe3+ Ferritin Transferrin Bilirubin 9 1 Red blood cell Biliverdin Bilirubin 11 10 death and phagocytosis Small intestine Kidney 13 12 Urobilin Macrophage in spleen, liver, or red bone marrow Bilirubin Urobilinogen Stercobilin Urine Liver + Globin + Vitamin B12 + Erythopoietin 8 Erythropoiesis in red bone marrow Bacteria Key: in blood Large 14 intestine in bile Feces University of Jordan 14 Erythropoiesis – Starts in red bone marrow with proerythroblast – Cell near the end of development ejects nucleus and becomes a reticulocyte – Develop into mature RBC within 1-2 days – Negative feedback balances production with destruction – Controlled condition is amount of oxygen delivery to tissues – Hypoxia stimulates release of erythropoietin University of Jordan 15 White Blood Cells/ Leukocytes • Have nuclei • Do not contain hemoglobin • Granular or agranular based on staining highlighting large conspicuous granules • Granular leukocytes – Neutrophils, eosinophils, basophils • Agranular leukocytes – Lymphocytes and monocytes University of Jordan 16 Types of White Blood Cells University of Jordan 17 Functions of WBCs – Usually live a few days – Except for lymphocytes – live for months or years – Far less numerous than RBCs – Leukocytosis is a normal protective response to invaders, strenuous exercise, anesthesia and surgery – Leukopenia is never beneficial – General function to combat invaders by phagocytosis or immune responses University of Jordan 18 Emigration of WBCs • Many WBCs leave the bloodstream • Emigration (formerly diapedesis) • Roll along endothelium • Stick to and then squeeze between endothelial cells • Precise signals vary for different types of WBCs University of Jordan 19 WBCs • Neutrophils and macrophages are active phagocytes – Attracted by chemotaxis • Neutrophils respond most quickly to tissue damage by bacteria – Uses lysozymes, strong oxidants, defensins • Monocytes take longer to arrive but arrive in larger numbers and destroy more microbes – Enlarge and differentiate into macrophages University of Jordan 20 WBCs • Basophils leave capillaries and release granules containing heparin, histamine and serotonin, at sites of inflammation – Intensify inflammatory reaction – Involved in hypersensitivity reactions (allergies) • Eosinophils leave capillaries and enter tissue fluid – Release histaminase, phagocytize antigenantibody complexes and effective against certain parasitic worms University of Jordan 21 Lymphocytes • Lymphocytes are the major soldiers of the immune system – B cells – destroying bacteria and inactivating their toxins – T cells – attack viruses, fungi, transplanted cells, cancer cells and some bacteria – Natural Killer (NK) cells – attack a wide variety of infectious microbes and certain tumor cells University of Jordan 22 Platelets/ Thrombocytes • Myeloid stem cells develop eventually into a megakaryocyte • Splinters into 2000-3000 fragments • Each fragment enclosed in a piece of plasma membrane • Disc-shaped with many vesicles but no nucleus • Help stop blood loss by forming platelet plug • Granules contain blood clot promoting 23 University of Jordan Stem cell transplants • Bone marrow transplant – Recipient's red bone marrow replaced entirely by healthy, noncancerous cells to establish normal blood cell counts – Takes 2-3 weeks to begin producing enough WBCs to fight off infections – Graft-versus-host-disease – transplanted red bone marrow may produce T cells that attack host tissues • Cord-blood transplant University of Jordan – Stem cells obtained from umbilical cord shortly 24