Chapter 19: The Cardiovascular System: The Blood Copyright 2009, John Wiley & Sons, Inc. Blood Liquid connective tissue 3 general functions Transportation 1. Gases, nutrients, hormones, waste products Regulation 2. pH, body temperature, osmotic pressure Protection 3. Clotting, white blood cells, proteins Copyright 2009, John Wiley & Sons, Inc. 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 Copyright 2009, John Wiley & Sons, Inc. Copyright 2009, John Wiley & Sons, Inc. Formed Elements of Blood Copyright 2009, John Wiley & Sons, Inc. 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 Copyright 2009, John Wiley & Sons, Inc. Copyright 2009, John Wiley & Sons, Inc. 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 Copyright 2009, John Wiley & Sons, Inc. Formation of Blood Cells Pluripotent stem cells produce Myeloid stem cells Lymphoid stem cells give rise to Give rise to red blood cells, platelets, monocytes, neutrophils, eosinophils and basophils Lymphocytes Hemopoietic growth factors regulate differentiation and proliferation Erythropoietin – RBCs Thrombopoietin – platelets Colony-stimulating factors (CSFs) and interleukins – WBCs Copyright 2009, John Wiley & Sons, Inc. 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 Copyright 2009, John Wiley & Sons, Inc. 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 Copyright 2009, John Wiley & Sons, Inc. Shapes of RBC and Hemoglobin Copyright 2009, John Wiley & Sons, Inc. 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 Copyright 2009, John Wiley & Sons, Inc. Formation and Destruction of RBC’s Copyright 2009, John Wiley & Sons, Inc. 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 Feces + Globin + Vitamin B12 + Erythopoietin 8 Erythropoiesis in red bone marrow Bacteria Key: in blood Large 14 intestine in bile 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 Copyright 2009, John Wiley & Sons, Inc. 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 Copyright 2009, John Wiley & Sons, Inc. Types of White Blood Cells Copyright 2009, John Wiley & Sons, Inc. 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 Copyright 2009, John Wiley & Sons, Inc. 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 Copyright 2009, John Wiley & Sons, Inc. WBCs Neutrophils and macrophages are active phagocytes Neutrophils respond most quickly to tissue damage by bacteria Attracted by chemotaxis Uses lysozymes, strong oxidants, defensins Monocytes take longer to arrive but arrive in larger numbers and destroy more microbes Enlarge and differentiate into macrophages Copyright 2009, John Wiley & Sons, Inc. WBCs Basophila 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 Copyright 2009, John Wiley & Sons, Inc. 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 Copyright 2009, John Wiley & Sons, Inc. 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 chemicals Short life span – 5-9 days Copyright 2009, John Wiley & Sons, Inc. 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 Stem cells obtained from umbilical cord shortly before birth Easily collected and can be stored indefinitely Less likely to cause graft-versus-host-disease Copyright 2009, John Wiley & Sons, Inc. Hemostasis Sequence of responses that stops bleeding 3 mechanisms reduce blood loss Vascular spasm 1. Platelet plug formation 2. 3. Smooth muscle in artery or arteriole walls contracts Platelets stick to parts of damaged blood vessel, become activated and accumulate large numbers Blood clotting (coagulation) Copyright 2009, John Wiley & Sons, Inc. Platelet Plug Formation Copyright 2009, John Wiley & Sons, Inc. Red blood cell Platelet Collagen fibers and damaged endothelium 11 Platelet adhesion Liberated ADP, serotonin, and thromboxane A2 22 Platelet release reaction Platelet plug 33 Platelet aggregation Blood Clotting 3. Blood clotting Serum is blood plasma minus clotting proteins Clotting – series of chemical reactions culminating in formation of fibrin threads Clotting (coagulation) factors – Ca2+, several inactive enzymes, various molecules associated with platelets or released by damaged tissues Copyright 2009, John Wiley & Sons, Inc. 3 Stages of Clotting 1. 2. 3. Extrinsic or intrinsic pathways lead to formation of prothrombinase Prothrombinase converts prothrombin into thrombin Thrombin converts fibrinogen (soluble) into fibrin (insoluble) forming the threads of the clot Copyright 2009, John Wiley & Sons, Inc. (a) Extrinsic pathway Tissue trauma (b) Intrinsic pathway Blood trauma Damaged endothelial cells expose collagen fibers Tissue factor (TF) Damaged platelets Activated XII Activated platelets Ca2+ Ca2+ + Platelet phospholipids Activated X Activated X V 1 Ca2+ Ca2+ V + PROTHROMBINASE (c) Common pathway Ca2+ Prothrombin (II) THROMBIN Ca2+ 2 XIII Fibrinogen (I) Activated XIII Loose fibrin threads STRENGTHENED FIBRIN THREADS 3 Blood Clotting Extrinsic pathway Fewer steps then intrinsic and occurs rapidly Tissue factor (TF) or thromboplastin leaks into the blood from cells outside (extrinsic to) blood vessels and initiates formation of prothrombinase Intrinsic pathway More complex and slower than extrinsic Activators are either in direct contact with blood or contained within (intrinsic to) the blood Outside tissue damage not needed Also forms prothrombinase Copyright 2009, John Wiley & Sons, Inc. Blood Clotting: Common pathway Marked by formation of prothrombinase Prothrombinase with Ca2+ catalyzes conversion of prothrombin to thrombin Thrombin with Ca2+ converts soluble fibrinogen into insoluble fibrin Thrombin has 2 positive feedback effects Accelerates formation of prothrombinase Thrombin activates platelets Clot formation remains localized because fibrin absorbs thrombin and clotting factor concentrations are low Copyright 2009, John Wiley & Sons, Inc. Blood Groups and Blood Types Agglutinogens – surface of RBCs contain genetically determined assortment of antigens Blood group – based on presence or absence of various antigens At least 24 blood groups and more than 100 antigens ABO and Rh Copyright 2009, John Wiley & Sons, Inc. ABO Blood Group Based on A and B antigens Type A blood has only antigen A Type B blood has only antigen B Type AB blood has antigens A and B Type O blood has neither antigen Universal recipients – neither anti-A or anti-B antibodies Universal donor Reason for antibodies presence not clear Copyright 2009, John Wiley & Sons, Inc. Antigens and Antibodies of ABO Blood Types Copyright 2009, John Wiley & Sons, Inc. Hemolytic Disease Rh blood group People whose RBCs have the Rh antigen are Rh+ People who lack the Rh antigen are RhNormally, blood plasma does not contain anti-RH antibodies Hemolytic disease of the newborn (HDN) – if blood from Rh+ fetus contacts Rhmother during birth, anti-Rh antibodies made Affect is on second Rh+ baby Copyright 2009, John Wiley & Sons, Inc. Typing Blood Single drops of blood are mixed with different antisera Agglutination with an antisera indicates the presence of that antigen on the RBC Copyright 2009, John Wiley & Sons, Inc. End of Chapter 19 Copyright 2009 John Wiley & Sons, Inc. All rights reserved. Reproduction or translation of this work beyond that permitted in section 117 of the 1976 United States Copyright Act without express permission of the copyright owner is unlawful. Request for further information should be addressed to the Permission Department, John Wiley & Sons, Inc. The purchaser may make back-up copies for his/her own use only and not for distribution or resale. The Publishers assumes no responsibility for errors, omissions, or damages caused by the use of theses programs or from the use of the information herein. Copyright 2009, John Wiley & Sons, Inc.