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Cardiovascular System Blood The Heart Blood Vessels & Circulation Blood Introduction Functions of Blood Blood Composition Plasma Formed Elements Hemostasis The Blood • To View Video: – Move mouse cursor over slide titlelink – When hand appears, click once • ASX Video plays about 20 min Introduction • Circulatory System Components • Circulatory System Functions • Functions of Blood Learning Objectives • Circulatory System: Explain how the cardiovascular system is related to the circulatory system • Functions of Blood: List & describe five functions of blood Circulatory System • Component Systems: Cardiovascular system Lymphatic system • Functions of Circulatory System: Transport Regulation of body fluids Defense against pathogens Functions of Blood • Transport of dissolved gases, nutrients, hormones, & metabolic wastes • Regulation of pH & electrolyte composition of interstitial fluids • Restriction of fluid losses due to damaged vessels or injury • Defense against toxins & pathogens • Temperature homeostasis Composition of Blood • Plasma & Formed Element • Blood Collection & Analysis Learning Objectives • Blood Composition: Describe the important components of the blood • Blood Collection & Analysis: Describe some of the basic physical features of blood & explain how blood is collected Explain how blood volume can be estimated Blood Tissue • Blood is a fluid connective tissue cellular components: formed elements RBCs, WBCs, platelets matrix: plasma “fibrous” portion – plasma proteins ground substance - serum Blood Composition • Plasma connective tissue matrix: plasma proteins – in solution serum – ground substance (H2O) • Formed elements connective tissue cells: erythrocytes – red blood cells (RBCs) leukocytes – white blood cells (WBCs) platelets – cell fragments Blood Collection • Venipuncture common sampling technique – median cubital vein (ant. surf elbow) superficial veins easy to locate walls of veins are thinner venous blood pressure is relatively low allowing puncture wound to seal quickly most blood analyses Blood Collection • Capillary puncture finger tip is most common blood smear technique • Arterial puncture uncommon sampling technique gas exchange efficiency – radial artery (wrist) or brachial artery (elbow) Whole Blood: Plasma & Formed Elements Plasma Analysis Formed Element Analysis Hematocrit Physical Characteristics • temperature 38 0C (100.4 0 F) slightly higher than normal core B.T. • viscosity 5X that of H20 interaction btw/ proteins, formed elements, & H20 • pH 7.35 – 7.45 slightly alkaline average: 7.4 Blood pH Blood Volume • Male 5 – 6 liters • Female 4 – 5 liters • Relative to body size gender differences reflect differences in ave. body size calculation: 0.07 (7%) of body weight in kg (1kg = 2.2lb) Blood Volume • Blood volume terms hypovolemic – low blood volume normovolemic – normal blood volume hypervolemic – excessive (high) blood volume Plasma • Plasma & Interstitial Fluid • Plasma Proteins • Serum Learning Objectives • Plasma: Discuss the composition & functions of plasma Discuss the origin of plasma proteins Plasma -vInterstitial Fluid • Plasma 46-63 % whole blood: ave. 55 % 92 % H2O 8 % dissolved proteins & ions • Interstitial fluid 96 % H2O similar ion conc. as plasma smaller conc. of proteins & dissolved gasses Plasma Proteins • Albumins 60 % (most abundant) contribute to osmotic pressure function: - transport of fatty acids, thyroid hormones, some steroid hormones, & other subst. Plasma Proteins • Globulins 35 % immunoglobulins – a.k.a., antibodies function: attack foreign proteins & pathogens transport globulins function: bind small ions, hormones, etc to prevent loss at kidneys Plasma Proteins • Fibrinogen 4% function: - blood clotting form fibrin strands serum – blood fluid from which clotting factors have been removed Plasma Protein Origins • Liver 90 % of plasma proteins all albumins fibrinogen most globulins • Lymphocytes – immunoglobulins • Endocrine organs – peptide hormones Ex: α & β cells of pancreas insulin & glucagon Serum • Watery portion of blood containing dissolved substances electrolytes: Na+, K+, Ca2+, Mg+, Cl-, HCO3, etc organic nutrients: fatty acids, amino acids, glucose, etc organic wastes: urea, ammonium ions, etc • W/out clotting factors or clotting proteins Formed Elements • Origin & Production • Erythrocytes (Red Blood Cells) structure & function hemoglobin erythropoiesis blood typing • Leukocytes (White Blood Cells) structure & function leukopoiesis • Platelets structure & function Learning Objectives • Formed Elements: Describe the origin & formation of formed elements in blood • RBCs: List the characteristics & functions of red blood cells Describe the structure of hemoglobin, and indicate its functions Learning Objectives • RBCs: (cont.) Describe the recycling system for aged or damaged RBCs Define erythropoiesis, identify the stages involved in erythrocyte maturation, & describe the homeostatic regulation of RBC production Learning Objectives • RBCs: (cont.) List examples of important tests & cite the normal values for each test Explain the importance of blood typing on the basis of ABO & Rh incompatibilities Hemopoiesis • Production of blood • Stem cells produce daughter cells that remain capable of division throughout life • Hemocytoblasts divide to produce: lymphoid stem cells lymphocyte production myeloid stem cells production of all other: RBCs, platelets, & WBCs Erythrocytes: Red Blood Cells • RBCs = 99% of formed elements • Contain hemoglobin protein binds O2 & CO2 • Imparts deep red color to blood when bound to oxygen: oxyhemoglobin RBC Trivia • # RBCs/μl (mm3): = 4.5-6.0 million for male = 4.2-5.5 million for female • # RBCs in 1 drop of blood = 260 million • total # RBCs in ave adult = 25 trillion • RBCs account for 1/3 of the total # of cells in the human body Red Blood Cells • Hematocrit % of whole blood occupied by cellular components • Adult male – 46% (40-54%) • Adult female – 42% (37-47%) Androgens (♂ hormones) stimulate RBC production; estrogens (♀ hormones) do not Blood Smear RBC WBC platelet RBC Structure & Function • Structure biconcave disk no nucleus in mature, circulating RBCs hemoglobin (Hb) – packs RBC • Effect on function large surface area – rapid absorption & release of O2 formation of stacks – rouleaux allows easy passage through vessels flexibility – ability to squeeze through capillaries Hemoglobin Structure • Structure Quaternary shape – 4 globular polypeptide chains 2 alpha (α) chains 2 beta (β) chains Each subunit has 1 heme group containing Fe • Sickle-cell anemia a.a. sequence error in structure of β chain RBCs “sickle” in low O2 conditions Pleiotropy Normal RBCs Hemoglobin Function • Oxygen transport 280 million Hb molecules/RBC each Hb has 4 heme groups Fe in each heme carries 1 O2 a single RBC carries > 1 billion O2 molecules 98.5% O2 in blood carried by Hb • Oxyhemoglobin HbO2 in↑oxygen environ, Hb binds O2 in↓oxygen environ, Hb releases O2 Hemoglobin Function • Carbon dioxide transport CO2 binds to α & β chains 23% CO2 in blood carried by Hb - remainder carried as HCO3- or dissolved gas • Carbaminohemoglobin HbCO2 in↑carbon dioxide environ, Hb binds CO2 in↓carbon dioxide environ, Hb releases CO2 RBC Life Span & Circulation • route from heart, to peripheral tissues, back to heart takes 1 min – extremely stressful collisions • travels 700 miles in 120 days • worn cells are phagocytized by WBCs • 1% replaced @ day • 3 million new RBCs enter circulation @ sec Erythropoiesis Stimulation of erythropoiesis due to hormone erythropoietin (EPO) produced by kidney in response to hypoxia (↓O2) Blood Typing • Based on surface features of RBCs antigens – surface features (agglutinogens) that trigger immune responses RBCs have 50 different kinds of surface antigens 3 are especially important: A, B, & Rh • Affected by antibodies agglutinins – antibodies that attack RBCs w/ non-self antigens Blood Types • Type A (40% US population) antigen A present on RBC plasma carries anti-B antibodies • Type B (10% US population) antigen B present on RBC plasma carries anti-A antibodies • Type AB (4% US population) antigens A & B present on RBC plasma carries no ant-A or antiB antibodies Blood Types • Type O (46% US population) no A or B antigens present on RBC plasma carries both anti-A & anti-B antibodies universal recipient Blood Groups universal donor Blood Types • Rh factor antigen present – positive Rh factor = Rh+ antigen absent – negative Rh factor = Rh no anti-Rh antibodies are present in Rh- individuals unless due to previous exposure to Rh+ blood “Rh” omitted in blood type terminology Ex: O+ or A- Rh Factors & Pregnancy Erythroblastosis fetalis Blood Group Genetics • Codominance there are 2 dominant traits if inherited, both are expressed in phenotype of offspring type A (IA_), type B (IB_), or type AB (IAIB) • Multiple alleles more than 2 traits (surface features) govern a character (blood type) IA & I B & i Blood Group Genetics • Type A genotypes IAIA – homozygous dominant A IAi – heterozygous A • Type B genotypes IBIB – homozygous dominant B IBi – heterozygous B • Type AB genotype IAIB – homozygous dominant A & B • Type O genotype ii – homozygous recessive Blood Typing Donor Blood Serum Type AB blood has NO A or B antibodies Recipient RBCs Universal Donor Universal Recipient Type B blood carries antibodies against type A Type A blood carries antibodies against type B Type O blood carries antibodies for both type A & type B Genetics Problem 1 • • A woman who is heterozygous for type A blood marries and a man who is heterozygous for type B blood. State the probability that any child they produce will have the following blood types: a) b) c) d) A B AB O ♀ A I i ♂ B X I i IA IB A B I I Type AB i A I i Type A 25% probability for any blood type i B I i Type B ii Type O Genetics Problem 2 • A woman who is heterozygous for Rh+ blood marries and a man with Rhblood. • State the probability that any child they produce will have the following blood types: a) Rh+ b) Rh- ♂ ♀ +/- - X -/+ - +/- -/- Rh-pos Rh-neg +/- -/- Rh-pos Rh-neg Genetics Problem 3 • • A woman who is heterozygous for type A and Rh+ blood marries and a man who is heterozygous for type B- blood. State the probability that any child they produce will have the following blood types: a) b) c) d) A+ AB+ B- e) f) g) h) AB+ ABO+ O- i) Rh+ j) Rh- ♂ A+ BI i X I i ♀ IB- IA+ i A+ BI I BI i Type AB pos i A+ I i Type A pos Type B neg i- iType O neg RBC Problems • Anemia hemoglobin &/or RBC deficiency O2 transport types: Fe-deficiency anemia – affects proper manufacture of hemoglobin pernicious anemia – vitamin B12 deficiency reducing factor necessary for RBC maturation aplastic anemia – reduced manufacture of RBCs sickle-cell anemia – gene mutation resulting in abnormal hemoglobin RBC Problems • Thalassemia inherited disease involving hemoglobin synthesis • Polycythemia production of RBCs types: Primary – natural disorder leading to blood volume & viscosity and to impaired circulation Secondary – develops as compensation for O2 levels: high altitude adaptation Learning Objectives • WBCs: Categorize the various WBCs on the basis of their structures & functions Discuss factors that regulate the production of the various types of WBCs Types of Leukocytes • Granular leukocytes cytoplasm contains many visible granules types: neutrophils eosinophils basophils Types of Leukocytes • Agranular leukocytes cytoplasm contains few or no visible granules types: monocytes lymphocytes Circulation & Movement • amoeboid movement • diapedesis – can squeeze btw adjacent endothelial cells of blood vessels to migrate out of circulatory system • positive chemotaxis – attracted to specific chemical stimuli of damaged cells, invading pathogens, etc • phagocytosis – neutrophils, eosinophils, & monocytes can engulf pathogens, cell debris, etc Circulation & Movement • 6000-9000 leukocytes/μl whole blood • most WBCs are in connective tissue proper or organs of the lymphatic system • circulating leukocytes represent tiny fraction of total WBC count General Functions of Leukocytes • Nonspecific defenses activated by a variety of stimuli do not discriminate btw one type of threat & another types: neutrophils eosinophils basophils monocytes General Functions of Leukocytes • Specific immunity respond to attacks by specific pathogens or toxins types: lymphocytes Neutrophil • Structure polymorphonuclear – segmented nucleus round cell; granules do not stain easily w/ acidic or basic dyes packed w/ lysosomes & bactericidal compounds • Function phagocytize bacteria, fungi, some viruses release chemicals to cause inflammation makes blood vessels permeable attract other WBCs Neutrophil • 50-70% circulating WBCs most numerous WBC in circulation • survive 10 hrs in bloodstream • survive 30 min while destroying bacteria • produced in red bone marrow Eosinophil (a.k.a., acidophil) • Structure bilobed nucleus round cell; granules stain darkly red w/ eosin, an acid-based dye • Function use exocytosis to secrete toxins onto surface of large, multicellular parasites (flukes, tapeworms, etc) phagocytize objects already coated w/ antibodies: bacteria, dead cells, etc respond to allergens reduce inflammation Eosinophil • 2-4 % circulating WBCs • survive minutes to days depending on activity in tissue • produced in red bone marrow Basophil • Structure lobed nucleus – difficult to see due to # of granules round cell; granules stain dark purple or blue w/ basic dyes • Function release heparin to prevent blood clotting release histamine to cause inflammation Basophil • < 1 % circulating WBCs • survival time unknown • produced in red bone marrow Monocyte • Structure kidney bean-shaped nucleus very large cell; abundant, pale cytoplasm • Function in circulation for 24 hrs; enter tissues to become macrophages phagocytic giant cell – fusion of several macrophages to ingest large object Monocyte • 2-8 % of circulating WBCs • survive for months or longer • most produced in red bone marrow Lymphocyte • Structure large, round nucleus generally round cell; little cytoplasm • Function defense against specific pathogens: viruses, bacteria, fungi 3 classes of lymphocytes w/ different functions Lymphocyte • 20-30 % of circulating WBCs • survive months to decades • circulate from blood to tissues & back • produced in red bone marrow & lymphoid tissues Lymphocyte Classes • T cells cellular immunity – defense mechanisms against invading foreign cells and tissues coordination of immune responses Lymphocyte Classes types of T cells: cytotoxic T cells – direct destruction of foreign cells by physical & chemical attack regulatory T cells: • helper T cells – stimulate activity of other T cells & B cells • suppressor T cells – inhibit the activity of other T cells & B cells Lymphocyte Classes • B cells humoral immunity production of antibody defense against antigens on pathogens, foreign cells, etc antibodies produced in one region can destroy pathogens anywhere in the body Lymphocyte Classes • NK cells (a.k.a., “natural killer” or large, granular lymphocytes) immune surveillance detection & destruction of abnormal tissue cells important in destroying cancer cells Blood Cell Origin & Differentiation Regulation of WBC Production • Colony-stimulating factors (CSFs) hormones types of CSFs: M-CSF – stimulates monocyte/macrophage line G-CSF – stimulates production of granulocytes: neutrophils, eosinophils, & basophils Regulation of WBC Production types of CSFs: (cont) GM-CSF – stimulates production of both granulocytes & monocytes Multi-CSF – accelerates production of granulocytes, monocytes, erythrocytes, & platelets Learning Objectives • Platelets: Describe the structure & function of platelets Explain how platelets are formed Platelets • Structure flattened disks or spindle-shaped cell fragments non-nucleate; cytoplasm w/ enzymes & proenzymes • Function transport of clotting chemicals temporary patch formation in walls of damaged blood vessels active contraction following clot formation Platelets • 150,000-500,000 / μl whole blood • survival time 9-12 days • produced in red bone marrow Platelet Production • Thromobocytopoiesis production of platelets contributing factors: thrombopoietin (TPO) – accelerates platelet formation interleukin-6 (Il-6) – stimulates platelet formation Multi-CSF – stimulates production of megakaryocytes Note Structure of Formed Elements: Nuclei Hemostasis • Prevention of blood loss through walls of damaged blood vessels • Establishment of framework for tissue repair Learning Objectives • Hemostasis: Discuss mechanisms that control blood loss after injury Describe the reaction sequences responsible for blood clotting Phases of Hemostasis • Vascular Phase Vascular spasm – automatic contraction of smooth muscle following a cut in the wall of a blood vessel Changes in endothelium: endothelial cells contract & expose underlying basement membrane to blood stream endothelial cell membranes become sticky; in small capillaries, cells from opposite walls may stick together to close off passageway Phases of Hemostasis • Vascular Phase endothelial cells release chemicals & hormones • ADP, tissue factor, prostacyclin • endothelins – peptide hormones (1) stimulate smooth muscle contraction & vascular spasm (2) stimulate production of new endothelial cells, smooth muscle cells, & fibroblasts to accelerate repair Phases of Hemostasis • Platelet Phase Platelet adhesion – platelets begin to stick to endothelial cells Platelet adhesion – platelets begin to stick to each other Platelet plug forms Phases of Hemostasis • Platelet Phase Platelets release chemicals: ADP – promotes aggregation thromboxane A2 – promotes aggregation & secretion; also, smooth muscle contraction & vascular spasm serotonin – assists thromboxane A2 platelet factors – promotes blood coagulation & div. of endothelial cells Ca2+ - promote aggregation & clotting Phases of Hemostasis • Coagulation Phase Blood clotting conversion of circulating fibrinogen to insoluble fibrin forms tangle of fibers that traps blood cells and more platelets Blood Clot Structure Coagulation Phase • Extrinsic pathway begins w/ damaged tissues at injury site outside the blood stream release of tissue factor (TF) activates a series of clotting factors which combine w/ Ca2+ to produce the enzyme prothrombin activator Coagulation Phase • Intrinsic pathway begins w/ damaged tissues at injury site inside the blood stream activates a series of clotting factors which combine w/ Ca2+ to produce the enzyme prothrombin activator Coagulation Phase • Common pathway prothrombin activator from either intrinsic or extrinsic pathway appears in plasma works w/ Ca2+ : prothrombin –prothrombin activator / Ca2+ thrombin circulating globular fibrinogen –thrombin fibrin Blood Clotting Process Clot Retraction & Fibrinolysis • Platelets contract: syneresis pull edges of torn vessel closer together • Fibrinolysis clot dissolves action of plasmin by plasminogen plasminogen –thrombin activator or t-PA plasmin Blood Review • To View Video: – Move mouse cursor over slide titlelink – When hand appears, click once • ASX Video plays about 20 min