14.1: Introduction Blood: • Is connective tissue • Transports vital substances • Maintains stability of interstitial fluid • Distributes heat Blood cells: • Form in red bone marrow • Red blood cells (RBCs) • White blood cells (WBCs) • Platelets (cell fragments) • The amount of blood varies with body size, changes in fluid concentration, changes in electrolyte concentration, and amount of adipose tissue • Blood is about 8% of body weight • Adult blood volume is about 5 liters 1 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Capillary tube Plasma = 55% Buffy coat Red cells = 45% (hematocrit) Plug 2 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Blood 45% 55% Formed elements Plasma Platelets Red blood cells White blood cells (4.8%) (95.1%) (0.1%) Electrolytes Water (92%) Proteins Wastes Nutrients Gases (7%) Vitamins Hormones Neutrophils Eosinophils Basophils (54–62%) (1–3%) (<1%) Monocytes (3–9%) Lymphocytes Albumins Globulins Fibrinogen N2 O2 CO2 (25–33%) 3 14.2: Blood Cells Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hematopoietic stem cell Hemocytoblast Lymphoid stem cell Myeloid stem cell Myeloblast Proerythroblast Monoblast In red bone marrow Megakaryoblast Lymphoblast T cell precursor Lymphoblast B cell precursor Progranulocyte Erythroblast Neutrophilic myelocyte Basophilic myelocyte Neutrophilic band cell Basophilic band cell Neutrophil Basophil Eosinophilic myelocyte Promonocyte Prolymphocyte Prolymphocyte T lymphocyte B lymphocyte Normoblast Megakaryocyte Eosinophilic band cell Erythrocyte Thrombocytes (platelets) Eosinophil Monocyte Granulocytes Activated in tissues (some cells) In circulating blood Reticulocyte Agranulocytes Macrophage (a) (b) © The McGraw-Hill Companies, Inc./Al Telser, photographer Plasma cell 4 The Origin of Blood Cells • Blood cells originate in red marrow from hemocytoblasts or hematopoietic stem cells • Stem cells can then: • Give rise to more stem cells • Specialize or differentiate when responding to hematopoietic growth factors • Lymphoid stem cells • Myeloid stem cells 5 Characteristics of Red Blood Cells Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Red blood cells are: • Erythrocytes • Biconcave discs • One-third hemoglobin or: • Oxyhemoglobin • Deoxyhemoglobin Top view 7.5 micrometers 2.0 micrometers Sectional view (a) • Able to readily squeeze through capillaries • Lack nuclei and mitochondria 6 (b) b: © Bill Longcore/Photo Researchers, Inc. Red Blood Cell Counts • RBC counts is the number of RBCs in a cubic millimeter or microliter of blood • It may vary depending on age and health • Typical ranges include: • 4,600,000 – 6,200,000 in males • 4,200,000 – 5,400,000 in adult females • 4,500,000 – 5,100,000 in children • RBC counts reflects blood’s oxygen carrying capacity 7 Red Blood Cell Production and Its Control • Erythropoiesis Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • Low blood oxygen causes the kidneys and the liver to release erythropoietin (EPO) which stimulates RBC production Low blood oxygen Liver Kidney Release into bloodstream Stimulation Inhibition – • This is a negative feedback mechanism •Hemocytoblast→erythroblasts→reticulocytes →erythrocytes •Within a few days many new blood cells appear in the circulating blood Erythropoietin Bloodstream + Red bone marrow Increased oxygencarrying capacity Increased number of red blood cells 8 Dietary Factors Affecting Red Blood Cell Production • Vitamin B12 and folic acid are necessary • They are required for DNA synthesis making them necessary for the growth and division of all cells • Iron is also necessary • It is required for hemoglobin synthesis 9 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Red bone marrow Bone 3 Red blood cells produced 4 Red blood cells circulate in bloodstream for about 120 days 5 Macrophage Nutrients from food 2 Blood transports absorbed nutrients Vitamin B12 Folic acid Iron Old red blood cells Absorption 1 6 Hemoglobin Blood Globin + Heme 7 Iron + Biliverdin Liver Small intestine Bile Bilirubin 8 10 Types of White Blood Cells • Leukocytes: White blood cells that Protect against disease •WBC hormones are interleukins and colony-stimulating factors which stimulate development •There are 5 types of WBCs in 2 categories: • Granulocytes 1. Neutrophils 1st to arrive at infections 2. Eosinophils elevated in worm infestation (defends) & allergic reaction 3. Basophils Releases Histamine & Heparin • Agranulocytes 4. Lymphocytes T cells or B cells. B cells produce antibodies 5. Monocytes Phagocytize bacteria, dead cells, and other debris 11 Neutrophils • Light purple granules in acid-base stain with Lobed nucleus •Other names • Segs • Polymorphonuclear leukocyte • Bands (young neutrophils) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • First to arrive at infections • Phagocytic © Ed Reschke • 54% - 62% of leukocytes • Elevated in bacterial infections 12 Eosinophils • Deep red granules in acid stain • Bi-lobed nucleus Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • Moderate allergic reactions • Defend against parasitic worm infestations • 1% - 3% of leukocytes • Elevated in parasitic worm infestations and allergic reactions © Ed Reschke 13 Basophils • Deep blue granules in basic stain • Release histamine • Release heparin • Less than 1% of leukocytes • Similar to eosinophils in size and shape of nuclei Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. © Ed Reschke 14 Monocytes • Largest of all blood cells • Spherical, kidney-shaped, oval or lobed nuclei Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • Leave bloodstream to become macrophages • 3% - 9% of leukocytes • Phagocytize bacteria, dead cells, and other debris © R. Kessel/Visuals Unlimited 15 Lymphocytes • Slightly larger than RBC • Large spherical nucleus surrounded by thin rim of cytoplasm • T cells and B cells • Both important in immunity Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. • B cells produce antibodies • 25% - 33% of leukocytes © Ed Reschke 16 Functions of White Blood Cells • WBCs protect against infection • These leukocytes can squeeze between the cells of a capillary wall and enter the tissue space outside the blood vessel (called diapedesis) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Connective tissue Blood capillary Leukocyte 17 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. 1 Splinter punctures epidermis 2 Bacteria are introduced into the dermis 3 Bacteria multiply 4 Injured cells release histamine, causing blood vessels to dilate Epidermis Dermis Blood vessels 5 Neutrophils move through blood vessel walls and migrate toward bacteria 6 Neutrophils destroy bacteria by phagocytosis 18 White Blood Cell Counts • A procedure used to count number of WBCs per cubic millimeter of blood • Typically 5,000 – 10,000 per cubic millimeter of blood •Leukopenia: • Low WBC count (below 5,000) • Typhoid fever, flu, measles, mumps, chicken pox, AIDS • Leukocytosis: • High WBC count (above 10,000) • Acute infections, vigorous exercise, great loss of body fluids • Differential WBC count • Lists percentages of types of leukocytes • May change in particular diseases 19 20 Blood Platelets •Throytmboces also known as Platelets • They are cell fragments of megakaryocytes • Produced by hemocytoblasts in response to thrombopoietin • hemocytoblast→megakaryocyte→thrombocytes • They lack a nucleus and are roughly half the size of a RBC • There are approximately 150,000 – 450,000 per cubic millimeter of blood • They help repair damaged blood vessels by sticking to broken surfaces 21 • They release seratonin, which causes smooth muscles in walls of blood vessels to contract 22 14.3: Blood Plasma • Blood plasma is: • Straw colored • The liquid portion of blood • 55% of blood volume • 92% water • Includes transporting nutrients, gases, and vitamins • Helps regulate fluid and electrolyte balance and maintain pH 23 Plasma Proteins • These are the most abundant dissolved substances (solutes) in plasma 24 Gases and Nutrients • The most important blood gases: • Oxygen • Carbon dioxide • Plasma nutrients include: • Amino acids • Simple sugars • Nucleotides • Lipids • Fats (triglycerides) • Phospholipids • Cholesterol 25 Nonprotein Nitrogenous Substances • These are molecules containing nitrogen but are not proteins • In plasma they include: • Urea – product of protein catabolism; about 50% of nonprotein nitrogenous substances • Uric acid – product of nucleic acid catabolism • Amino acids – product of protein catabolism • Creatine – stores phosphates • Creatinine – product of creatine metabolism • BUN – blood urea nitrogen; indicates health of kidney’ 26 Plasma Electrolytes • Plasma contains a variety of these ions called electrolytes • They are absorbed from the intestine or released as by-products of cellular metabolism • They include: • Sodium (most abundant with chloride) • Potassium • Calcium • Magnesium • Chloride (most abundant with sodium) • Bicarbonate • Phosphate • Sulfate 27 14.4: Hemostasis • Hemostasis refers to the stoppage of bleeding • Actions that limit or prevent blood loss include: • Blood vessel spasm • Platelet plug formation • Blood coagulation 28 Blood Vessel Spasm • Blood vessel spasm • Triggered by pain receptors, platelet release, or serotonin • Smooth muscle in blood vessel contracts 29 Platelet Plug Formation • Platelet plug formation • Triggered by exposure of platelets to collagen • Platelets adhere to rough surface to form a plug Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Endothelial lining Collagen fiber 1 Break in vessel wall Platelet Red blood cell 2 Blood escaping through break 3 Platelets adhere to each other, to end of broken vessel, and to exposed collagen 4 Platelet plug helps control blood loss 30 Blood Coagulation • Blood coagulation • Triggered by cellular damage and blood contact with foreign surfaces •A blood clot forms as soluble fibrinogen changes to insoluble threads of fibrin, which trap blood cells • Hemostatic mechanism • Causes the formation of a blot clot via a series of reactions which activates the next in a cascade • Occurs extrinsically or intrinsically • Requires clotting factors and vit. K 31 32 Extrinsic Clotting Mechanism • Extrinsic clotting mechanism • Chemical outside of blood vessel triggers blood coagulation •Triggered by tissue thromboplastin (factor III) (not found in blood) • A number of events occur that includes factor VII, factor X, factor V, factor IV, and factor II (prothrombin) • Triggered when blood contacts damaged blood vessel walls or tissues • This is an example of a positive feedback mechanism 33 34 Intrinsic Clotting Mechanism • Intrinsic clotting mechanism • Chemical inside blood triggers blood coagulation •Triggered by Hageman factor XII (found inside blood) • Factor XII activates factor XI which activates IX which joins with factor VIII to activate factor X • Triggered when blood contacts a foreign surface 35 36 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Extrinsic Clotting Mechanism Intrinsic Clotting Mechanism Tissue damage Blood contacts foreign surface Releases Activates Tissue thromboplastin (Factor lll) Activates Hageman Factor Xll (Ca+2) Activates Factor Vll Activates Factor Xl (Ca+2) Activates Factor X Factor lX Activates Factor Vlll platelet phospholipids Factor V (Ca+2) Activates Factor X (Ca+2) Activates Factor V (Ca+2) Prothrombin activator Converts Prothrombin (Factor ll) Thrombin (Factor lla) Converts Fibrinogen (Factor l) Fibrin Factor Xlll Stabilizes Fibrin clot 37 Fate of Blood Clots • After a blood clot forms it retracts and pulls the edges of a broken blood vessel together (to repair) while squeezing the fluid serum from the clot •Platelet-derived growth factor stimulates smooth muscle cells and fibroblasts to repair damaged blood vessel walls • Plasmin (enzyme) digests the blood clots • A thrombus is an abnormal blood clot (very difficult to digest) • An embolus is a blood clot moving through the blood vessels (can cause damage to the heart) 38 Copyright © The McGraw-Hill Companies, Inc. 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Lumen (a) Artery wall Lumen Plaque Artery wall (b) © The McGraw-Hill Companies, Inc./Al Telser, photographer 39 Prevention of Coagulation • The smooth lining of blood vessels discourages the accumulation of platelets and clotting factors (fibrinagin) •As a clot forms fibrin adsorbs thrombin and prevents the clotting reaction from spreading • Anti-thrombin inactivates additional thrombin by binding to it and blocking its action on fibrinogen • Some cells such as basophils and mast cells secrete heparin (an anticoagulant) 40 14.5: Blood Groups and Transfusions • In 1910, identification of the ABO blood antigen gene explained the observed blood type incompatibilities • Today there are 31 different genes known to contribute to the surface features of RBCs determining compatibility between blood types 41 Antigens and Antibodies • Terms to become familiar with: • Agglutination – clumping of red blood cells in response to a reaction between an antibody and an antigen • Antigens – a chemical that stimulates cells to produce antibodies • Antibodies – a protein that reacts against a specific antigen 42 ABO Blood Group • Based on the presence or absence of two major antigens on red blood cell membranes • Antigen A • Antigen B 43 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Red blood cell Anti-B antibody Red blood cell Anti-A antibody Antigen A Antigen B Type A blood Red blood cell Type B blood Anti-A antibody Anti-B antibody Antigen A Antigen B Red blood cell Type AB blood Type O blood 44 ABO Blood Group • When blood cells come in contact with non-compatible antibodies, they will agglutinate (clump together) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Red blood cell Agglutinated red blood cells Antigen A Anti-B antibody Anti-A antibody (a) (c) (b) (d) c: © G.W. Willis/Visuals Unlimited; d: © George W. Wilder/Visuals Unlimited 45 • The Rh blood group was named for the rhesus monkey • The group includes several Rh antigens or factors • Rh positive – presence of antigen D or other Rh antigens on the red blood cell membranes Wilder/Visuals Unlim • Rh negative – lack of these antigens • Anti-Rh antibodies form only in Rh-negative individuals in response to the presence of red blood cells with Rh antigens • The seriousness of the Rh blood group is evident in a fetus that develops the condition erythroblastosis fetalis or hemolytic disease of the newborn ABO Blood Group • Type 0– universal donor • Type AB – universal recipient 47 Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. –– – – – – – – – – –– – – – – – – – – – – – – – –– – – – – – – – – – – – – – – + – – – – + + – – + + + – + – + – + – – – – Rh-negative woman with Rh-positive fetus –– – – – – – – – – –– – – – – – – – – – – – – – –– – – – – – – – – ++ + – ++ – + – + + + – + + + + + + – + – + + – + – – Cells from Rh-positive fetus enter woman’s bloodstream ––– – – –– – – – – – – – – – – –– – – – – – – – –– – – – –– – – –– – – – – – – – – – – – – – – – + – – – – – – – Woman becomes sensitized— antibodies ( + ) form to fight Rh-positive blood cells ––– – – –– – – – – – – – – – – –– – – – – – – – –– – – – –– – – –– – – – – – – – – – – – – – – – – – In the next Rh-positive pregnancy, maternal antibodies attack fetal red blood cells 48