Hole’s Human Anatomy and Physiology Twelfth Edition Shier w Butler w Lewis Chapter 14 Blood Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

14.1: Introduction Blood: Is connective tissue Transports vital substances (Like what?) Maintains stability of interstitial fluid Distributes heat Blood cells: Form mostly in red bone marrow and are: 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 (Why these changes?) Blood is about 8% of body weight Adult blood volume is about 5 liters

Centrifuged Blood Sample Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Centrifuged Blood Sample Liquid (plasma) “Buffy coat” (white blood cells and platelets) Red blood cells Peripheral Blood Smear White blood cells Red blood cells Platelets

Capillary tube Plasma = 55% Buffy coat Red cells = 45% (hematocrit) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Capillary tube Plasma = 55% Buffy coat Red cells = 45% (hematocrit) Plug

Blood 45% 55% Formed elements Plasma Platelets Red blood cells Water 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 Electrolytes Water Proteins Wastes Nutrients Gases (4.8%) (95.1%) (0.1%) (92%) (7%) Vitamins Hormones Neutrophils Eosinophils Basophils Monocytes Lymphocytes Albumins Globulins Fibrinogen N2 O2 CO2 (54–62%) (1–3%) (<1%) (3–9%) (25–33%)

14.2: 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

The Origin of Blood Cells Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Hematopoietic stem cell Myeloid stem cell Lymphoid stem cell Proerythroblast Myeloblast Monoblast Lymphoblast T cell precursor Lymphoblast B cell precursor Megakaryoblast In red bone marrow Progranulocyte Erythroblast Neutrophilic myelocyte Basophilic myelocyte Eosinophilic myelocyte Promonocyte Prolymphocyte Prolymphocyte Normoblast Megakaryocyte Reticulocyte Neutrophilic band cell Basophilic band cell Eosinophilic band cell Erythrocyte In circulating blood Thrombocytes (platelets) T lymphocyte B lymphocyte Neutrophil Basophil Eosinophil Monocyte Granulocytes Agranulocytes Activated in tissues (some cells) Macrophage Plasma cell (a) (b)

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 Able to readily squeeze through capillaries Lack nuclei and mitochondria – (Can they reproduce or metabolize?) Top view 7.5 micrometers 2.0 micrometers Sectional view (a) (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 (Why so high?) 4,200,000 – 5,400,000 in adult females (Why so low?) 4,500,000 – 5,100,000 in children (Why more than women?) RBC counts reflect blood’s oxygen carrying capacity

Red Blood Cell Production and Its Control 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 This is a negative feedback mechanism (What does this mean?) Within a few days many new blood cells appear in the circulating blood Low blood oxygen Release into bloodstream Liver Kidney Stimulation Inhibition – Erythropoietin Increased oxygen- carrying capacity Bloodstream Increased number of red blood cells + Red bone marrow

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

Red bone marrow Bone Nutrients from food 2 Blood transports Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Red bone marrow Bone Nutrients from food 2 Blood transports absorbed nutrients 3 Red blood cells produced Vitamin B12 Folic acid Iron 1 Absorption 4 Red blood cells circulate in bloodstream for about 120 days 5 Macrophage Old red blood cells 6 Hemoglobin Blood Globin + Heme 7 Iron + Biliverdin Bile Liver Small intestine Bilirubin 8

Destruction of Red Blood Cells

Copyright © The McGraw-Hill Companies, Inc Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. (a) (b) a: © The McGraw-Hill Companies, Inc./Al Telser, photographer :b © Ed Reschke

Types of White Blood Cells Are leukocytes Protect against disease WBC hormones are interleukins and colony-stimulating factors which stimulate development There are five types of WBCs in two categories: Granulocytes Neutrophils Eosinophils Basophils Agranulocytes Lymphocytes Monocytes

Neutrophils Light purple granules in acid-base (neutral) stain Lobed nucleus Other names Segs Polymorphonuclear leukocyte Bands (young neutrophils) First to arrive at infections Phagocytic (What is this?) 54% - 62% of leukocytes Elevated in bacterial infections (Why?) Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. © Ed Reschke

Eosinophils Deep red granules in acid stain Bi-lobed nucleus Moderate allergic reactions Defend against parasitic worm infestations 1% - 3% of leukocytes Elevated in parasitic worm infections and allergic reactions Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. © Ed Reschke

Basophils Deep blue granules in basic stain Release histamine (What does this do?) Release heparin (What does this do?) 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

© R. Kessel/Visuals Unlimited Monocytes Largest of all blood cells Spherical, kidney-shaped, oval or lobed nuclei May leave bloodstream to become macrophages 3% - 9% of leukocytes Phagocytize bacteria, dead cells, and other debris Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. © R. Kessel/Visuals Unlimited

Lymphocytes Slightly larger than RBC Large spherical nucleus surrounded by thin rim of cytoplasm T cells and B cells (Why are they named this?) Both important in immunity B cells produce antibodies 25% - 33% of leukocytes Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. © Ed Reschke

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

Bacteria are introduced into the dermis 3 Bacteria multiply 4 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

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 (Why?) Leukocytosis: High WBC count (above 10,000) Acute infections, vigorous exercise, great loss of body fluids (Why?) Differential WBC count Lists percentages of types of leukocytes May change in particular diseases

Blood Platelets Platelets are also known as thrombocytes They are cell fragments of megakaryocytes They lack a nucleus and are roughly half the size of a RBC There are approximately 130,000 – 360,000 per cubic millimeter of blood They help repair damaged blood vessels by sticking to broken surfaces

14.3: Blood Plasma Blood plasma is: Straw colored The liquid portion of blood 55% of blood volume 92% water Function includes transporting nutrients, gases, and vitamins Helps regulate fluid and electrolyte balance and maintain pH (How?)

Plasma Proteins These are the most abundant dissolved substances (solutes) in plasma

Gases and Nutrients The most important blood gases: Oxygen Carbon dioxide Plasma nutrients include: Amino acids Simple sugars Nucleotides Lipids Fats (triglycerides) Phospholipids Cholesterol

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 (What’s catabolism?) Uric acid – product of nucleic acid catabolism (When would this happen?) Amino acids – product of protein catabolism Creatine – stores phosphates (For what purposes?) Creatinine – product of creatine metabolism BUN – blood urea nitrogen; indicates health of kidney (Why is this an indicator of kidney health?)

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 (What are they used for?) They include: Sodium (most abundant with chloride) Potassium Calcium Magnesium Chloride (most abundant with sodium) Bicarbonate Phosphate Sulfate

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

Blood Vessel Spasm Blood vessel spasm Triggered by pain receptors, platelet release, or serotonin Smooth muscle in blood vessel contracts (What does this do?)

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 othe , to end of broken vessel, and to exposed collagen 4 Platelet plug helps control blood loss

Blood Coagulation Blood coagulation Triggered by cellular damage and blood contact with foreign surfaces A blood clot forms This is a: Hemostatic mechanism Causes the formation of a blood clot via a series of reactions which activates the next in a cascade Occurs extrinsically or intrinsically

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 (Why? How does this differ from a negative feedback mechanism?)

© SPL/Photo Researchers, Inc. Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. © SPL/Photo Researchers, Inc.

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 (Can you think of an example?)

Tissue thromboplastin platelet phospholipids 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) Hageman Factor Xll Activates (Ca+2) Activates Factor Vll Factor Xl Activates (Ca+2) Activates Factor X Factor lX Activates Factor Vlll platelet phospholipids Factor V (Ca+2) Factor X Activates (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

Fate of Blood Clots After a blood clot forms it retracts and pulls the edges of a broken blood vessel together 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 digests the blood clots A thrombus is an abnormal blood clot An embolus is a blood clot moving through the blood vessels

Prevention of Coagulation The smooth lining of blood vessels discourages the accumulation of platelets and clotting factors As a clot forms fibrin absorbs 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)

© The McGraw-Hill Companies, Inc./Al Telser, photographer Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Lumen Artery wall Lumen Plaque Artery wall (a) (b) © The McGraw-Hill Companies, Inc./Al Telser, photographer

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

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

ABO Blood Group Based on the presence or absence of two major antigens on red blood cell membranes Antigen A Antigen B

Red blood cell Anti-B antibody Red blood cell Anti-A antibody 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 Type B blood Red blood cell Anti-A antibody Anti-B antibody Antigen A Antigen B Red blood cell Type AB blood Type O blood

Red blood cell Agglutinated red blood cells Antigen A Anti-B antibody 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) (b) (c) (d) c: © G.W. Willis/Visuals Unlimited; figure d: © George W. Wilder/Visuals Unlimited

Rh Blood Group 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 Rh negative – lack of these 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 (How does this happen?)

– – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – – 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

Important Points in Chapter 14: Outcomes to be Assessed 14.1: Introduction Describe the general characteristics of blood and discuss its major functions. Distinguish among the formed elements of blood and the liquid portion of blood. 14.2: Blood Cells Describe the origin of blood cells. Explain the significance of red blood cells counts and how they are used to diagnose disease. Discuss the life cycle of a red blood cell. Summarize the control of red blood cell production.

Important Points in Chapter 14: Outcomes to be Assessed Distinguish among the five types of white blood cells and give the function(s) of each type. Describe a blood platelet and explain its functions. 14.3: Blood Plasma Describe the functions of each of the major components of plasma. 14.4: Hemostasis Define hemostasis and explain the mechanisms that help to achieve it. Review the major steps in coagulation. Explain how to prevent coagulation.

Important Points in Chapter 14: Outcomes to be Assessed 14.5: Blood Groups and Transfusions Explain blood typing and how it is used to avoid adverse reactions following blood transfusions. Describe how blood reactions may occur between fetal and maternal tissues.