Chapter 12 - Cardiovascular PDF

Chapter 12 – Cardiovascular Central Component Peripheral Component Fick Equation VO2= Q x (a-v) O2 difference  Components The fluid (Blood) The pump The tubing (vessels) Figure 12.1 Measurement of the Figure 12.2 Production of Blood...

Chapter 12 – Cardiovascular Central Component Peripheral Component Fick Equation VO2= Q x (a-v) O2 difference  Components The fluid (Blood) The pump The tubing (vessels) Figure 12.1 Measurement of the Figure 12.2 Production of Blood Cells Hematocrit by Centrifugation By the Bone Marrow 3  Figure 12.40 Diagram of a Capillary Cross Section and Electron Micrograph of a Capillary Containing a Single Erythrocyte University of Wisconsin, Michael Noel Hart, M.D., Madison (a) Capillary cross (b) Electron section micrograph 4  Erythrocytes (RBCs) -gas transport-oxygen and carbon dioxide -contain hemoglobin to which oxygen and carbon dioxide reversibly combine. (can carry up to 1.34 ml O2/g) -shape of a biconcave disk -size ~7um in diameter. -a high surface-area-to-volume ratio, which favors diffuse of oxygen and carbon dioxide into and out of the cell. The percentage of the blood made up of red blood cells is called hematocrit (about 45 percent). Anemia - various types Mature erythrocytes: no nucleus or organelles, no Iron mitochondria, no D N A, no R N A, incapable of cell Folic Acid division. Vitamin B12 -last about 120 days. -synthesized in the red bone marrow by erythropoiesis. Carrying proteins -Erythropoietin (a hormone from the kidney) Carbon monoxide Sickle Cell Disease Cobalamin 5 Figure 12.4 Decreased Oxygen Delivery to the Kidneys Increases Erythrocyte Production Via Increased Erythropoietin Secretion 6 Hematocrit Under Various Conditions  ABO Blood Types – Type A blood contains anti-B antibodies. – Type B blood contains anti-A antibodies. – Type AB blood contains neither antibody. – Type O blood contains both anti-A and anti-B antibodies. Antigen on RBCs Antibody in Plasma A Anti-B B Anti-A O Anti-A and anti-B AB Neither anti-A nor anti-B 8 Transfusion Reaction Antibody reactions Abs in the host, not the Abs in the transferred fluid Universal Donor vs Recipient antibody Specific Binding 9 An antibody binds with the specific antigen against which it is produced.  Blood Groups Transfusion reaction occurs when blood of incompatible type is given (donor blood is diluted in recipient) Blood type O is the universal donor Blood type AB is the universal recipient HOST A B AB O Anti-B Anti-A and B nil Anti-A B AB A B O  Other Blood Group Systems. Rh factor – Rh-positive individual has Rh factor – Rh-negative individual lacks Rh factor – Erythroblastosis fetalis (hemolytic disease of the newborn) Occurs when Rh-negative mother develops antibodies against the erythrocytes of an Rh-positive fetus Approximately 12 other minor human erythrocyte antigen systems Figure 12.5 The Systemic Figure 12.6 Distribution of Systemic Blood and Pulmonary Circulations Flow to the Various Organs and Tissues of the Body at Rest Flow at rest Organ (milliliter/minute) Brain 650 (13%) Heart 215 (4%) Skeletal muscle 1030 (20%) Skin 430 (9%) Kidneys 950 (20%) Abdominal 1200 (24%) organs Other 525 (10%) Total 5000 (100%) 12 Figure 12.47 Distribution of the Total Blood Volume in Different Parts of the Circulatory System 13 Figure 12.7 Flow Between Two Points Within a Tube Is Proportional to the Pressure Difference Between the Points 14  Figure 12.8 Effect of Tube Radius (r) on Resistance (R) and Flow 8Lη R= πr 4 (a) Effect of tube diameter on resistance where R = resistance η = fluid viscosity L = length of the tube r = inside radius of the tube 8/π = a mathematical constant (b) Effect of tube diameter on flow 15 Figure 12.11 Path of Blood Flow Through the Entire Circulatory System Volumes Pressures Right side vs Left Side 16 Figure 12.23 Pressures in the Right Ventricle and Pulmonary Artery During the Cardiac Cycle 1 = Ventricular filling 2 = Isovolumetric ventricular contraction 3 = Ventricular ejection 4 = Isovolumetric ventricular relaxation 17  Cardiac Muscle Structure 1. Striated 2. Myosin and actin filaments form sarcomeres. 3. Contraction occurs by means of sliding thin filaments. 4. Unlike skeletal muscle fibers, these fibers are short, branched, and connected via gap junctions called intercalated discs (electrical synapses that permit impulses to be conducted cell to cell). Figure 9.39b Cardiac Muscle Cells and Intercalated Disks (b) Detailed illustration of cardiac muscle and disks 19 Figure 12.13 Conducting System of the Heart (Yellow) 20 Figure 12.14 Sequence of Cardiac Excitation 21 Figure 9.41 Timing of Action Potentials and Twitch Tension in Skeletal and Cardiac Muscles 22 Typical Neuron Figure 12.15 Membrane Potential Recording From a Ventricular Muscle Cell With Simultaneously Measured Permeabilities (P) to K+, Na+, and Ca2+ (- 90 mV) (+66 mV) (+137 mV) (b) Ventricular cell membrane (a) Ventricular cell action potential permeabilities 23 Figure 12.16 Membrane Potential Recording From a Cardiac Nodal Cell With Simultaneously Measured Permeabilities (P) Through Four Different Ion Channels (a) Nodal cell pacemaker potential (b) Nodal cell membrane permeabilities 24 Figure 12.18 Placement of Electrodes in Electrocardiography (a) Standard ECG limb leads (b) Precordial ECG leads 25  Figure 12.17 Idealized Electrocardiogram Recorded From Electrodes Placed on the Wrists Aligned in Time With Action Potentials Recorded From a Single Atrial Muscle Cell and a Single Ventricular Muscle Cell (a) ECG (b) Atrial and ventricular action potentials 26 Figure 12.19 Electrocardiograms From a Healthy Person and From Two People Suffering From Atrioventricular Block Brady- Tachy- (a) Normal ECG (b) Partial AV block (c) Complete AV block 27 Figure 12.20 Relationship Between Membrane Potential Changes and Contraction in a Ventricular Muscle Cell 28 Figure 12.21 Divisions of the Cardiac Cycle: Systole and Diastole 29  Figure 12.22 Summary of Events in the Left Atrium, Left Ventricle, and Aorta During the Cardiac Cycle 30 31 Figure 12.24 Heart Valve Defects Causing Turbulent Blood Flow and Murmurs (a) Normal (open) (c) Stenotic (b) Normal (d) Insufficient (closed) 32 Role of Calcium in Cardiac Muscle Figure 12.12 Autonomic Innervation of the Heart 34 Figure 12.25 Effects of Sympathetic and Parasympathetic Nerve Stimulation on the Slope of the Pacemaker Potential of an SA Nodal Cell 35 Effects of ANS on the SA Node  Regulation of Cardiac Rate Spontaneous depolarization occurs at SA node when HCN channels open, allowing Na+ in. Sympathetic norepinephrine and adrenal epinephrine keep HCN channels open, increasing heart rate. Parasympathetic acetylcholine opens K+ channels, slowing heart rate. Controlled by cardiac center of medulla oblongata that is affected by higher brain centers  Calcium Channels Unlike skeletal muscle, the voltage-gated calcium channels are not directly connected to calcium channels in the SR. Instead, calcium acts as a second messenger to open SR channels. Called calcium-induced calcium release Excitation-contraction coupling is slower. Figure 12.26 Major Factors Influencing Heart Rate 39 Figure 12.29 Mechanisms of Sympathetic Effects on Cardiac Muscle Cell Contractility 40  Figure 12.27 A Ventricular-Function Curve, Which Expresses the Relationship Between End-Diastolic Ventricular Volume and Stroke Volume (the Frank–Starling Mechanism) 41  Figure 12.28 Sympathetic Stimulation Causes Increased Contractility of Ventricular Muscle (a) Stroke volume increased by increased end- (b) Effect of sympathetic stimulation on diastolic volume and sympathetic stimulation ventricular force development 42 Figure 12.30 Major Factors Involved in Increasing Cardiac Output (Q or CO) VO2= Q x (a-v) O2 difference 43  Figure 12.31 Comparative Features of Blood Vessels Lumen SYMP SYMP Endothelial layer Connective Tissue layer BP Smooth Muscle layer Volume Vs Pressure Gas Ex 44 Figure 12.32 Pressures in the Systemic and Pulmonary Vessels 45 Figure 12.34a Typical Arterial Pressure Fluctuations During the Cardiac Cycle for a Young Adult Male - Pressures Average about 10 millimeters Hg Lower in Females (a) Arterial pressure during a cardiac cycle Figure 12.34b Changes in Arterial Pressure with Age in the U.S. (b) Effect of age on arterial pressure 47 Figure 12.35 Sounds Heard Through a Stethoscope as the Cuff Pressure of a Sphygmomanometer Is Gradually Lowered 48  Figure 12.36 Physical Model of the Relationship Between Arterial Pressure, Arteriolar Radius in Different Organs, and Blood-Flow Distribution 49 Figure 12.37 Local Control of Organ Blood Flow in Response to Increases in Metabolic Activity and Decreases in Blood Pressure H+ (a) Active hyperemia (b) Flow autoregulation 50 Figure 12.38 Effects of Sympathetic Nerves and Plasma Epinephrine on the Arterioles in Skeletal Muscle 51 Figure 12.39 Major Factors Affecting Arteriolar Radius 52 Figure 12.41 Diagram of Microcirculation 53  Figure 12.42 Relationship Between Total Cross-Sectional Area and Flow Velocity (a) Cross-sectional area of 1 larger vs. 6 smaller (b) Cross-sectional area and velocity of tubes flow Velocity is slowest in the capillary beds because they have the greatest cross-sectional area. 54  Figure 12.40 Diagram of a Capillary Cross Section and Electron Micrograph of a Capillary Containing a Single Erythrocyte University of Wisconsin, Michael Noel Hart, M.D., Madison (a) Capillary cross (b) Electron section micrograph 55 Figure 12.43 Diffusion Gradients at a Systemic Capillary 56 Figure 12.46 Effects of Arteriolar Vasodilation or Vasoconstriction on Capillary Blood Pressure in a Single Organ 57 Figure 12.49 Major Factors Determining Peripheral Venous Pressure, Venous Return, and Stroke Volume Figure 12.48 The Skeletal Muscle Pump 58 Figure 12.54 Summary of Factors That Determine Systemic Arterial Pressure 59 Table 12.8 Comparison of Hemodynamics in the Systemic and Pulmonary Circuits Systemic Pulmonary Circulation Circulation Cardiac output (Liters/minute)[volume] 5 = 5 Systolic pressure (millimeters Hg) 120 > 25 Diastolic pressure (millimeters Hg) 80 > 10 Mean arterial pressure (millimeters Hg) 93 > 15 60  Figure 12.55 Sequence of Events By Which a Decrease in Blood Volume Leads to a Decrease in Mean Arterial Pressure 61  Arterial Blood Pressure Systolic Pressure (SP): Maximum arterial pressure reached during the peak of ventricular contraction and ejection Diastolic Pressure (DP): Minimum arterial pressure reached just prior to ventricular ejection Arterial Blood Pressure is stated as SP/DP = 120/80 Pulse Pressure (PP): Difference between SP and DP PP = SP − DP = 120 − 80 = 40 mm Hg Mean Arterial Pressure (MAP): Average pressure driving blood to the tissues over cardiac cycle. Approximation formula: MAP = DP + ⅓ PP = 80 + ⅓ (40) = 93 mm Hg 62  Figure 12.56 Location of Arterial Baroreceptors Pressure 63 Figure 12.57a Effect of Changing Mean Arterial Pressure (M AP) on the Firing of Action Potentials by Afferent Neurons From the Carotid Sinus (a) Relationship between MAP and baroreceptor firing 64  Figure 12.57b Baroreceptor Action Potential Firing Frequency Fluctuates With Pressure (b) Effect of arterial and pulse pressure on baroreceptor firing 65 Figure 12.58 Neural Components of the Arterial Baroreceptor Reflex 66 Figure 12.59 Arterial Baroreceptor Reflex Compensation for Hemorrhage 67 Figure 12.60a Causal Relationships Between Arterial Pressure and Blood Volume (a) Effect of an increase in MAP on blood volume 69 Figure 12.60b Causal Relationships Between Arterial Pressure and Blood Volume (b) Effect of an increase in blood volume on MAP 70 Figure 12.61 The Time Course of Cardiovascular Effects of Hemorrhage 71 Figure 12.62 The Autotransfusion Mechanism Compensates for Blood Loss By Causing Interstitial Fluid to Move Into the Capillaries 72 Figure 12.64 Distribution of the Systemic Cardiac Output at Rest and During Strenuous Exercise Source: Adapted from Chapman, C. B., and Mitchell, J. H. “ThePhysiology of Exercise.” Scientific American 212, no. 5 (1965): 88–99. 73 Figure 12.65 Summary of Cardiovascular Changes During Mild Upright Exercise Like Jogging 74 Figure 12.66 Control of the Cardiovascular System During Exercise 75 Figure 12.68 Relationship Between End-Diastolic Ventricular Volume and Stroke Volume in a Normal Heart and One With Heart Failure Due to Systolic Dysfunction 76  Figure 12.69a Anterior View of the Heart Showing the Major Coronary Vessels - Inset Demonstrates Narrowing Due to Atherosclerotic Plaque (a) Atherosclerotic plaque 77  Figure 12.69b-d Dye-Contrast X-Ray Angiography Showing Treatment of Coronary Artery Disease (b) Occlusion of coronary (c) Balloon angioplasty (d) Restoration of blood artery and stent placement flow 78  Atherosclerosis Lipid-filled macrophages and lymphocytes assemble at the site of damage within the tunica interna (fatty streaks). a. Next, layers of smooth muscle are added. b. Finally, a cap of connective tissue covers the layers of smooth muscle, lipids, and cellular debris. c. Progress promoted by inflammation stimulated by cytokines and other paracrine regulators.  Oxidative Stress Fat in aqueous blood LDL Inflammation Lipoproteins -HDLs vs LDLs Antioxidants Ischemia ECG Cholesterol Satins Nitroglycerin Necrosis  Detecting Ischemia 1) Depression of the S-T segment of an electrocardiogram 2) Plasma concentration of blood enzymes a) Creatine phosphokinase (CK) – 3 to 6 hours, return to normal in 3 days b) Lactate dehydrogenase – 48 to 72 hours, elevated about 11 days c) Troponin I –most sensitive test d) Troponin T  SUMMARY Blood elements – RBC info, WBC, Abs, HCT Vessels- flow, pressure, structure, control, local vs systemic, BP, left side vs right side, arteries vs veins, baroreceptors, MAP, PP, rest vs contraction Heart- cellular aspects, Q, control of HR, disease states, F-S law, Diastole, systole  Clinical Case Study A 72-year-old man complained of shortness of breath on exertion. He also experienced a pressure-like chest pain and light-headedness when walking up several flights of stairs. For the past few months he has had to prop his head up using three pillows to keep from feeling short of breath when lying in bed. His feet were swollen, particularly at the end of the day when he had been standing quite a bit. The patient’s heart rate was 86 beats/minute (compared to 78 a year ago), his blood pressure was 115/92 millimeters Hg (compared to 139/75 a year ago), and his respiratory rate was 16 breaths/minutes (compared to 13 a year ago). Examination of the neck revealed that his jugular veins were distended and had very prominent pulses. The strength of his carotid pulse was diminished. Auscultation of his chest revealed a prominent systolic murmur. The diagnosis was heart failure due to stenosis (narrowing) of the aortic valve. How would narrowing of the aortic valve reduce pulse pressure and cardiac output? Explain how compensation for this problem by the baroreceptor reflex would eventually result in hypertrophy of the left ventricle, edema, and shortness of breath. 83  Table 12.9 Fluid Shifts After Hemorrhage Normal Immediately After 18 Hours After Hemorrhage Hemorrhage Total blood volume 5000 4000 4900 (milliliters) Erythrocyte volume 2300 1840 1840 (milliliters) Plasma volume 2700 2160 3060 (milliliters) 84  Composition of the Blood Blood is composed of formed elements (cells and cell fragments) suspended in a liquid called plasma. The formed elements include erythrocytes (red blood cells), leukocytes (white blood cells), and platelets. Plasma carries blood cells, proteins, nutrients, metabolic wastes, and other molecules being transported between organ systems. In a centrifuged blood sample, the hematocrit is the percentage of blood volume that is erythrocytes. 85  Atherosclerosis Most common form of arteriosclerosis (hardening of the arteries) a. Contributes to 50% of the deaths due to heart attack and stroke b. Plaques protrude into the lumen and reduce blood flow. c. Serve as sites for thrombus formation d. Plaques form in response to damage done to the endothelium of a blood vessel. e. Caused by smoking, high blood pressure, diabetes, high cholesterol  Plasma Plasma consists of a large number of inorganic and organic substances dissolved in water. Most (> 90%) of plasma is water. Plasma carries electrolytes, nutrients (glucose, amino acids, vitamins), wastes (urea, bilirubin, creatinine), gases (O2 and CO2), hormones, and plasma proteins such as albumins, globulins, and fibrinogen. Serum is plasma with fibrinogen and other proteins involved in clotting removed. 87  Erythrocytes (Red Blood Cells) – The major function of erythrocytes is gas transport; they carry oxygen taken in by the lungs and carbon dioxide produced by the cells. – Erythrocytes contain large amounts of the protein hemoglobin to which oxygen and carbon dioxide reversibly combine. – They have a shape of a biconcave disk and are small in size (7 micrometers in diameter). Their shape and small size give them a high surface-area-to-volume ratio, which favors diffuse of oxygen and carbon dioxide into and out of the cell. – Mature erythrocytes do not have a nucleus or organelles (no mitochondria, no DNA, no RNA so mature erythrocytes are incapable of cell division). 88  Erythrocytes – Erythrocytes have a short life span and only last about 120 days. – They are synthesized in the red bone marrow by a process called erythropoiesis. – Erythropoietin (a hormone from the kidney) triggers differentiation of stem cells to erythrocytes. 89  Requirements for Normal Erythrocyte Production Iron: Component of hemoglobin (specifically the heme portion to which oxygen binds) Folic acid: Essential for the formation of DNA and normal cell division Vitamin B12: Required for the action of folic acid 90  Filtering and Destruction of Erythrocytes – The spleen filters and removes old erythrocytes, and the liver metabolizes byproducts from breakdown of erythrocytes. – Most of the iron is conserved for the synthesis of new hemoglobin. – Iron is transported in the blood bound to an iron-transport plasma protein called transferrin, which delivers almost all of it to the bone marrow to be incorporated into new erythrocytes. – Iron is stored bound to a protein called ferritin in the liver, spleen, and small intestines. 91  Anemia Anemia is a decrease in the oxygen-carrying capacity of blood due to: a decrease in the total number of erythrocytes, each having a normal quantity of hemoglobin a diminished concentration of hemoglobin per erythrocyte a combination of both Sickle-cell disease (also called sickle-cell anemia) is due to a genetic mutation that alters one amino acid in the hemoglobin chain. At the low oxygen levels existing in many capillaries (the smallest blood vessels), the abnormal hemoglobin molecules interact with each other to form fiber-like polymers that distort the erythrocyte membrane and cause the cell to form sickle shapes or other bizarre forms. This causes both the blockage of capillaries, with consequent tissue damage and pain, and the destruction of the deformed erythrocytes, with consequent anemia. 92  Table 12.1 Major Causes of Anemia Dietary deficiencies of iron (iron-deficiency anemia), vitamin B12 , or folic acid Bone marrow failure due to toxic drugs or cancer Blood loss from the body (hemorrhage) Inadequate secretion of erythropoietin in kidney disease Excessive destruction of erythrocytes (for example, sickle-cell disease) 93  Leukocytes Leukocytes (white blood cells) are involved in immune defenses. They can be divided into granulocytes and agranulocytes. – Granulocytes—contain cytoplasmic granules – Neutrophils – Eosinophils – Basophils – Agranulocytes—do not contain cytoplasmic granules – Monocytes – Lymphocytes – Macrophages 94  Basic Functions of Leukocytes Neutrophils are phagocytes, and their production and release from the bone marrow increase during infections. Eosinophils fight off invasions by eukaryotic parasites; they either release toxic chemicals that kill parasites, or they phagocytize the parasites. Basophils secrete an anticlotting factor called heparin at the site of infection, which helps the circulation flush out the infected site; they also secrete histamine to attract infection-fighting cells and proteins to the site. Monocytes are phagocytes that circulate in the blood for a short time, after which they migrate into tissues and organs and develop into macrophages. Macrophages are large phagocytes capable of engulfing viruses and bacteria. Lymphocytes are comprised of T- and B-lymphocytes that protect against specific pathogens, including viruses, bacteria, toxins, and cancer cells. Some directly attack pathogens, and others secrete antibodies that begin the process of destruction. 95  Platelets – Circulating platelets are colorless, nonnucleated cell fragments that contain numerous granules and are much smaller than erythrocytes. – Platelets are produced when cytoplasmic portions of large bone marrow cells, termed megakaryocytes, pinch off and enter the circulation. – Platelets play a major role in blood clotting. 96  Table 12.2 Reference Table of Major Hematopoietic Growth Factors (HGFs) Name Stimulates Progenitor Cells Leading To: Erythropoietin Erythrocytes Colony-stimulating factors (CSFs) Granulocytes and monocytes (example: granulocyte CSF) Interleukins (example: interleukin 3) Various leukocytes Thrombopoietin Platelets (from megakaryocytes) Stem cell factor Many types of blood cells 97  Circulation The circulatory system forms a closed loop, so that blood pumped out of the heart through one set of vessels returns to the heart by a different set. There are two circuits: systemic and pulmonary. The pulmonary circulation carries oxygen-poor blood from the right ventricle to the lungs, and then returns oxygen-rich blood to the left atrium. The systemic circulation carries oxygen-rich blood from the left ventricle to all the organs and tissues of the body, except the lungs, and then returns oxygen-poor blood to the right atrium. 98  Blood Vessels Blood vessels are classified as arteries, arterioles, capillaries, venules, and veins. All arteries carry blood away from the heart, whereas all veins carry blood to the heart. In general, arteries carry oxygenated blood, and veins carry deoxygenated blood. The exception to this is the pulmonary arteries, which carry deoxygenated blood to the lungs to get oxygenated, and the pulmonary veins, which carry oxygenated blood to the heart to get delivered to the rest of the body. 99  Pressure, Flow, and Resistance Pressure is the force exerted by the blood and is measured in mm Hg (millimeters of mercury). Blood flows from a region of higher pressure to a region of lower pressure. Flow is the volume of blood moved per unit time, and it is measured in milliliters/minute. Resistance describes how difficult it is for blood to flow between two points at any given pressure difference. Resistance is the measure of the friction that impedes flow. The basic equation relating these variables is: F = ∆P/R Flow rate is directly proportional to the pressure difference and inversely proportional to the resistance. 100  Resistance Factors that determine resistance: – Blood viscosity, which is a function of the friction between molecules of a flowing fluid; this is affected by water volume and the number of erythrocytes – Total blood vessel length, which remains constant – Blood vessel radius: Dilated vessels decrease resistance, while constricted vessels increase resistance. The radii of the blood vessels do not remain constant, so this is the most important determinant of changes in resistance. 101  Table 12.3 The Circulatory System Component Function Heart Atria Chambers through which blood flows from veins to ventricles. Atrial contraction adds to ventricular filling but is not essential for it. Ventricles Chambers whose contractions produce the pressures that drive blood through the pulmonary and systemic vascular systems and back to the heart. Vascular system Arteries Low-resistance tubes conducting blood to the various organs with little loss in pressure. They also act as pressure reservoirs for maintaining blood flow during ventricular relaxation. Arterioles Major sites of resistance to flow; responsible for regulating the pattern of blood-flow distribution to the various organs; participate in the regulation of arterial blood pressure. Capillaries Major sites of nutrient, gas, metabolic end product, and fluid exchange between blood and tissues. Venules Capacitance vessels that are sites of migration of leukocytes from the blood into tissues during inflammation and infection. Veins Low-resistance, high capacitance vessels carrying blood back to the heart. Their capacity for blood is adjusted to facilitate this flow. Blood Plasma Liquid portion of blood that contains dissolved nutrients, ions, wastes, gases, and other substances. Its composition equilibrates with that of the interstitial fluid at the capillaries. Cells Includes erythrocytes that function mainly in gas transport, leukocytes that function in immune defenses, and platelets (cell fragments) for blood clotting. 102  Layers of the Wall of the Heart Epicardium: the most superficial (outer) layer; a fibrous layer that is closely affixed to the heart Myocardium: the middle layer of the heart, composed of cardiac muscle; forms the majority of the wall of the heart, and acts as the contractile layer Endothelium: the inner layer of the heart, composed of endothelial cells, or endothelium, which rest on a thin layer of connective tissue; continuous with the lining of the blood vessels entering and leaving the heart 103  Cardiac Muscle The cardiac muscle cells of the myocardium are arranged in layers that are tightly bound together and completely encircle the blood-filled chambers. When the walls of a chamber contract, they come together like a fist squeezing a fluid-filled balloon and exert pressure on the blood they enclose. Every heart cell contracts with every beat of the heart; cardiac muscle cells may contract almost 3 billion times in an average life span without resting. The human heart has a limited ability to replace its muscle cells. It is thought that only about 1% of heart muscle cells are replaced per year. 104  Cardiac Communication Approximately 1% of cardiac cells do not function in contraction but have specialized features that are essential for normal heart excitation. These cells constitute a network known as the conducting system of the heart and are in electrical contact with the cardiac muscle cells via gap junctions. The conducting system initiates the heartbeat and helps spread an action potential rapidly throughout the heart. 105  Innervation of the Heart The heart receives a rich supply of sympathetic and parasympathetic nerve fibers. The sympathetic postganglionic fibers innervate the entire heart and release norepinephrine, whereas the parasympathetic fibers terminate mainly on special cells found in the atria and release primarily acetylcholine. The receptors for norepinephrine on cardiac muscle are mainly beta-adrenergic. The hormone epinephrine, from the adrenal medulla, binds to the same receptors as norepinephrine and exerts the same actions on the heart. The receptors for acetylcholine are of the muscarinic type. 106  Blood Supply to the Heart The blood being pumped through the heart chambers does not exchange nutrients and metabolic end products with the myocardial cells. They receive their blood supply via arteries that branch from the aorta. The arteries supplying the myocardium are the coronary arteries, and the blood flowing through them is the coronary blood flow. The coronary arteries exit from behind the aortic valve cusps in the very first part of the aorta and lead to a branching network of small arteries, arterioles, capillaries, venules, and veins similar to those in other organs. Most of the cardiac veins drain into a single large vein, the coronary sinus, which empties into the right atrium. 107  Excitation of the Heart 1 The sinoatrial (SA) node is normally the pacemaker for the entire heart. The action potential initiated in the SA node spreads throughout the myocardium, passing from cell to cell by way of gap junctions. Depolarization first spreads through the muscle cells of the atria, with conduction rapid enough that the right and left atria contract at essentially the same time. The action potential is conducted relatively rapidly from the SA node to the atrioventricular (AV) node through internodal pathways. The signal then has a 0.1 second delay as it travels through the AV node to allow the atria to contract and totally fill the ventricles before they contract. 108  Excitation of the Heart 2 The wave of depolarization travels down the interventricular septum through conducting-system fibers called the bundle of His. Within the interventricular septum, the bundle of His divides into right and left bundle branches, which separate at the bottom (apex) of the heart and enter the walls of both ventricles. These pathways are composed of Purkinje fibers, which are large diameter, rapidly conducting cells connected by low- resistance gap junctions. The branching network of Purkinje fibers conducts the action potential rapidly to myocytes throughout the ventricles. 109  Nodal Cell Action Potentials The SA node cell does not have a steady resting potential but, instead, undergoes a slow, gradual depolarization called a pacemaker potential; it brings the membrane potential to threshold, at which point an action potential occurs. The pacemaker potential provides the SA node with automaticity, the capacity for spontaneous, rhythmic self- excitation. Because other cells of the conducting system (AV nodal cells, the bundle of His, and the Purkinje fibers) have slower inherent pacemaker rates, they normally are driven to threshold by action potentials from the SA node (which produces 100 depolarizations per minute) and do not manifest their own rhythm. 110  Conduction Disorders Drug- or disease-induced malfunction of the AV node may reduce or completely eliminate the transmission of action potentials from the atria to the ventricles. This is known as an A V conduction disorder. If this occurs, autorhythmic cells in the bundle of His and Purkinje network, no longer driven by the SA node, begin to initiate excitation at their own inherent rate (25 to 40 beats/minute) and become the pacemaker for the ventricles. As a result, the ventricles contract completely out of synchrony with the atria, which continue at the higher rate of the SA node. The current treatment for severe AV conduction disorders, as well as for many other abnormal rhythms, is permanent surgical implantation of an artificial pacemaker that electrically stimulates the ventricular cells at a normal rate. 111  Electrocardiogram 1 The electrocardiogram (ECG) is a tool for evaluating the electrical events within the heart. A typical ECG makes use of multiple combinations of recording locations on the limbs and chest (called ECG leads) to obtain as much information as possible concerning different areas of the heart. The ECG is not a direct record of the changes in membrane potential across individual cardiac muscle cells. It is a measure of the currents generated in the extracellular fluid by the changes occurring simultaneously in many cardiac cells. 112  Electrocardiogram 2 The P wave corresponds to current flow during atrial depolarization. The QRS complex is the result of the ventricular depolarization. The T wave is the result of ventricular repolarization. Atrial repolarization is usually not evident on the ECG because it occurs at the same time as the QRS complex. 113  Table 12.4 Electrocardiography Leads Name of Lead Electrode Placement Electrode Placement Standard Limb Leads Reference Electrode Recording Electrode Lead I Right arm Left arm Lead II Right arm Left leg Lead III Left arm Left leg Augmented Limb Leads aVR Left arm and left leg Right arm aVL Right arm and left leg Left arm aVF Right arm and left arm Left leg Precordial (Chest) Leads V1 Combined limb leads 4th intercostal space, right of sternum V2 Combined limb leads 4th intercostal space, left of sternum V3 Combined limb leads 5th intercostal space, left of sternum V4 Combined limb leads 5th intercostal space, centered on clavicle V5 Combined limb leads 5th intercostal space, left of V4 V6 Combined limb leads 5th intercostal space, under left arm 114  Excitation-Contraction Coupling A small amount of extracellular calcium enters the cell through L-type calcium channels during the plateau of the action potential. This calcium binds to ryanodine receptors on the sarcoplasmic reticulum membrane and triggers the release of a larger quantity of calcium. Calcium activation of thin filaments and cross-bridge cycling then lead to the generation of force. 115  Events of the Cardiac Cycle The orderly process of depolarization triggers a recurring cardiac cycle of atrial and ventricular contractions and relaxations. The cycle is divided into two major phases, both named for events in the ventricles: the period of ventricular contraction and blood ejection called systole, and the alternating period of ventricular relaxation and blood filling, diastole. For a typical heart rate of 72 beats/minute, each cardiac cycle lasts approximately 0.8 seconds, with 0.3 seconds in systole and 0.5 seconds in diastole. 116  Periods During Systole of the Cardiac Cycle Isovolumetric ventricular contraction: First part of systole, in which the ventricles are contracting, but blood cannot leave them, since all of the valves are closed Cardiac muscle is developing tension, but no shortening is possible, since the blood inside the heart cannot be compressed. Ventricular Ejection: Period of ventricular contraction, in which muscle fibers shorten, and blood is forced out of ventricles, into the aorta and pulmonary trunk Aortic and pulmonary valves are forced open by rising pressure in the ventricles Stroke Volume is the volume of blood ejected from each ventricle during systole 117  Periods During Diastole of the Cardiac Cycle Isovolumetric Ventricular Relaxation: First part of diastole, in which the ventricles begin to relax, the aortic and pulmonary valves close, and no blood is entering or leaving the ventricles The AV valves are also closed, and ventricular volume is not changing. Ventricular Filling: The AV valves then open, and blood flows from the atria into the ventricles. The atria contract at end of diastole, but 80% of ventricular filling occurs passively before atrial contraction. 118  Heart Sounds and Valve Function Two heart sounds resulting from cardiac contraction are normally heard through a stethoscope placed on the chest wall. The first sound, a soft, low-pitched lub, is associated with closure of the AV valves; the second sound, a louder dup, is associated with closure of the pulmonary and aortic valves. These sounds, which result from vibrations caused by the closing valves, are normal, but other sounds, known as heart murmurs, can be a sign of heart disease. Normally, blood flow through valves and vessels is laminar flow; it flows in smooth concentric layers. Turbulent flow can be caused by blood flowing rapidly in the usual direction through an abnormally narrowed valve (stenosis)l by blood flowing backward through a damaged, leaky valve (insufficiency), or by blood flowing between the two atria or two ventricles through a small hole in the wall separating them (called a septal defect). 119  Cardiac Output Cardiac output (CO) is the volume of blood pumped out of each ventricle per unit time (Liters/minute). It is the product of heart rate (HR) and stroke volume (SV); CO = HR × SV Normal cardiac output is about 5 liters/minute. In a resting person, SV is fairly constant. If the person experiences blood loss, then SV declines and CO can be maintained by increasing HR. 120  Regulation of Heart Rate Rhythmic heart beats at a rate of about 100 beats/minute will occur in the complete absence of any nervous or hormonal influences on the SA node. This is the inherent autonomous discharge rate of the SA node. The heart rate may be slower or faster than this, however, because the SA node is normally under the constant influence of nerves and hormones. A large number of parasympathetic and sympathetic postganglionic neurons end on the SA node. Activity in the parasympathetic neurons (which travel within the vagus nerves) causes the heart rate to decrease, whereas activity in the sympathetic neurons causes an increase. These are termed chronotropic effects. 121  Control of Stroke Volume Stroke volume (SV) is the volume of blood each ventricle ejects during each contraction. S V is the difference between the end-diastolic volume and the end- systolic volume; SV = EDV − E S V, and the typical S V in a resting individual is 70 milliliters/beat. Three dominant factors regulate SV under most physiological and pathophysiological conditions: – changes in the end-diastolic volume (the volume of blood in the ventricles just before contraction, called the preload) – changes in the magnitude of sympathetic nervous system input to the ventricles – changes in afterload, the arterial pressures against which the ventricles pump 122  The Frank-Starling Mechanism The ventricle contracts more forcefully during systole when it has been filled to a greater degree during diastole. In other words, the stroke volume increases as the end-diastolic volume increases. This relationship is called the Frank–Starling mechanism (or Starling’s law of the heart). Because the end-diastolic volume is a major determinant of how stretched the ventricular sarcomeres are just before contraction, the greater the end-diastolic volume, the greater the stretch and the more forceful the contraction. At any given heart rate, an increase in the venous return—the flow of blood from the veins into the heart—automatically forces an increase in cardiac output by increasing end-diastolic volume and, therefore, stroke volume. 123  Sympathetic Regulation of Stroke Volume The sympathetic neurotransmitter norepinephrine acts on beta-adrenergic receptors to increase ventricular contractility, defined as the strength of contraction at any given end-diastolic volume. Plasma epinephrine acting on these receptors also increases myocardial contractility. Not only does increased sympathetic stimulation of the myocardium cause a more powerful contraction, it also causes both the contraction and relaxation of the ventricles to occur more quickly. 124  Ejection Fraction One way to quantify contractility is through the ejection fraction (EF), defined as the ratio of stroke volume (SV) to end- diastolic volume (EDV); EF = SV/EDV Expressed as a percentage, the ejection fraction averages between 50% and 75% under resting conditions in a healthy heart. Increased contractility causes an increased ejection fraction. 125  Effect of Afterload on Stroke Volume An increased arterial pressure tends to reduce stroke volume. This is because, like a skeletal muscle lifting a weight, the arterial pressure constitutes a “load” that contracting ventricular muscle must work against when it is ejecting blood. A term used to describe how hard the heart must work to eject blood is afterload. The greater the load, the less contracting muscle fibers can shorten at a given contractility. 126  Table 12.5 Effects of Autonomic Nerves on the Heart Area Affected Sympathetic Nerves Parasympathetic Nerves (Norepinephrine on Beta- (Acetylcholine Adrenergic Receptors) on Muscarinic Receptors) SA node Increased heart rate Decreased heart rate AV node Increased conduction rate Decreased conduction rate Atrial muscle Increased contractility Decreased contractility Ventricular Increased contractility No significant effect muscle 127  Measurement of Cardiac Function Human cardiac output and heart function can be measured by a variety of methods. Echocardiography is a noninvasive technique that uses ultrasonic waves. This technique can detect the abnormal functioning of cardiac valves or contractions of the cardiac walls, and can also be used to measure ejection fraction. Cardiac angiography requires the temporary threading of a thin, flexible tube called a catheter through an artery or vein into the heart. A liquid containing radiopaque contrast material is then injected through the catheter during high- speed x-ray videography. This technique is useful for evaluating cardiac function and for identifying narrowed coronary arteries. 128  The Vascular System The vascular system has a major function in regulating blood pressure and distributing blood flow to the various tissues. Elaborate branching and regional specializations of blood vessels enable efficient matching of blood flow to metabolic demand in individual tissues. The entire circulatory system, from the heart to the smallest capillary, has one structural component in common: a smooth, single-celled layer of endothelial cells (endothelium) that is in contact with the flowing blood. The vessels of the circulatory system are the arteries, arterioles, capillaries, venules, and veins. 129  Table 12.6 Functions of Endothelial Cells Serve as a physical lining in heart and blood vessels to which blood cells do not normally adhere Serve as a permeability barrier for the exchange of nutrients, metabolic end products, and fluid between plasma and interstitial fluid; regulate transport of macromolecules and other substances Secrete paracrine agents that act on adjacent vascular smooth muscle cells, including vasodilators such as prostacyclin and nitric oxide (endothelium-derived relaxing factor [EDRF]), and vasoconstrictors such as endothelin-1 Mediate angiogenesis (new capillary growth) Have a central function in vascular remodeling by detecting signals and releasing paracrine agents that act on adjacent cells in the blood vessel wall Contribute to the formation and maintenance of extracellular matrix Produce growth factors in response to damage Secrete substances that regulate platelet clumping, clotting, and anticlotting Synthesize active hormones from inactive precursors (Chapter 14) Extract or degrade hormones and other mediators (Chapters 11, 13) Secrete cytokines during immune responses (Chapter 18) Influence vascular smooth muscle proliferation in the disease atherosclerosis (Chapter 12, Section E) 130  Arteries Arteries can be viewed as elastic tubes due to having thick walls containing large quantities of elastic tissue. They have large radii, which helps them serve as low- resistance tubes conducting blood to the various organs. Arteries, due to their elasticity, also act as “pressure reservoirs” for maintaining blood flow through the tissues during diastole. 131  Arterial Blood Pressure Systolic Pressure (SP): Maximum arterial pressure reached during the peak of ventricular contraction and ejection Diastolic Pressure (DP): Minimum arterial pressure reached just prior to ventricular ejection Arterial Blood Pressure is stated as SP/DP = 120/80 Pulse Pressure (PP): Difference between SP and DP PP = SP − DP = 120 − 80 = 40 mm Hg Mean Arterial Pressure (MAP): Average pressure driving blood to the tissues over cardiac cycle. Approximation formula: MAP = DP + ⅓ PP = 80 + ⅓ (40) = 93 mm Hg 132  Pulse Pressure The difference between systolic pressure and diastolic pressure is called the pulse pressure. It can be felt as a pulsation or throb in the arteries of the wrist or neck with each heartbeat. The most important factors determining the magnitude of the pulse pressure are: stroke volume – speed of ejection of the stroke volume – arterial compliance A decrease in arterial compliance occurs in arteriosclerosis, a stiffening of the arterial walls that progresses with age. 133  Mean Arterial Pressure The mean arterial pressure (MAP) is approximately equal to the diastolic pressure plus one-third of the pulse pressure. The MAP is an important parameter because it is the average pressure driving blood into the tissues averaged over the entire cardiac cycle. 134  Arterioles The arterioles have two major functions: The arterioles in individual organs are responsible for determining the relative blood flows to those organs at any given mean arterial pressure. The arterioles, all together, are the major factor in determining mean arterial pressure itself. Their diameter is controlled by neural, hormonal, and local chemicals; if they contract, blood flow is diverted away from the downstream tissues, and if they dilate, then blood flow to the tissues increases. 135  Flow-Pressure Relationships F = ΔP ∕ R Increasing the resistance through vasoconstriction (decrease in diameter) of arterioles while pressure difference remains constant leads to a decrease in blood flow to a tissue or organ. Decreasing the resistance through vasodilation (increase in diameter) of arterioles, or increasing the pressure difference, leads to an increase in blood flow to a tissue or organ. 136  Regulation of the Diameter of Arterioles 1 Active hyperemia: Increase in blood flow due to increased metabolic activity Example: Blood flow to skeletal muscles increases when actively exercising, due to vasodilation Flow autoregulation: The automatic adjustment of blood flow despite changes in pressures Ensures blood flow to each tissue in proportion to that tissue’s requirement at any instant Example: The kidney reacts to a reduction in blood flow, due to a diseased renal artery, by vasodilating its own arterioles. 137  Regulation of the Diameter of Arterioles 2 Reactive hyperemia: A temporary, significant increase in blood flow to an organ, following release of complete blood flow occlusion. Occurs because arterioles have previously vasodilated in response to decreased blood flow Example: Increase in blood flow to the arm, during a blood pressure reading, after the Brachial Artery has been squeezed shut by the blood pressure cuff Response to injury: Chemicals released by injured cells or found in the blood cause vasodilation of blood vessels in injured area. Example: This occurs during the inflammatory response to injury or infection. 138  Endothelial Cells and Vascular Smooth Muscle Endothelial cells secrete several paracrine agents that diffuse to the adjacent vascular smooth muscle and induce either relaxation or contraction. One of the most important is nitric oxide (NO). NO is released continuously in significant amounts by endothelial cells in the arterioles and contributes to arteriolar vasodilation in the basal state. 139  Table 12.7 Reference Summary of Arteriolar Control in Specific Organs 1 Heart High intrinsic tone; oxygen extraction is very high at rest, so flow must increase when oxygen consumption increases to maintain adequate oxygen delivery. Controlled mainly by local metabolic factors, factors. particularly adenosine, and flow autoregulation; direct sympathetic influences are minor and normally overridden by local During systole, aortic semilunar cusps block the entrances to the coronary arteries, and vessels within the muscle wall are compressed; therefore, coronary flow occurs mainly during diastole. Skeletal Muscle Controlled by local metabolic factors during exercise. Sympathetic activation causes vasoconstriction (mediated by a-adrenergic receptors) in reflex response to decreased arterial pressure. Epinephrine causes vasodilation via b2-adrenergic receptors when present in low concentration, and vasoconstriction via a-adrenergic receptors when present in high concentration. GI Tract, Spleen, Pancreas, and Liver (“Splanchnic Organs”) Actually two capillary beds partially in series with each other; blood from the capillaries of the GI tract, spleen, and pancreas flows via the portal vein to the liver. In addition, the liver receives a separate arterial blood supply. Sympathetic activation causes vasoconstriction, mediated by a-adrenergic receptors, in reflex response to decreased arterial pressure and during stress. In addition, venous constriction causes displacement of a large volume of blood from the liver to the veins of the thorax. Increased blood flow occurs following ingestion of a meal and is mediated by local metabolic factors, neurons, and hormones secreted by the GI tract. 140  Table 12.7 Reference Summary of Arteriolar Control in Specific Organs 2 Kidneys Flow autoregulation is a major factor. Sympathetic stimulation causes vasoconstriction, mediated by a-adrenergic receptors, in reflex response to decreased arterial pressure and during stress. Angiotensin II is also a major vasoconstrictor. These reflexes help conserve sodium and water. Brain Excellent flow autoregulation. Distribution of blood within the brain is controlled by local metabolic factors. Vasodilation occurs in response to increased concentration of carbon dioxide in arterial blood. Influenced relatively little by the autonomic nervous system. Skin Controlled mainly by sympathetic nerves, mediated by a-adrenergic receptors; reflex vasoconstriction occurs in response to decreased arterial pressure and cold, whereas vasodilation occurs in response to heat. Substances released from sweat glands and noncholinergic, nonadrenergic neurons also cause vasodilation. Venous plexus contains large volumes of blood, which contributes to skin color Lungs Very low resistance compared to systemic circulation. Controlled mainly by gravitational forces and passive physical forces within the lung. Constriction mediated by local factors in response to low oxygen concentration—just the opposite of what occurs in the systemic circulation. 141  Capillaries Capillaries are the smallest blood vessels and are comprised of a single layer of endothelial cells. At any moment, they contain 5% of the total circulating blood. They permeate every tissue except the cornea. Gas and nutrient exchange occurs between capillaries and the surrounding interstitial fluid by diffusion. 142  Movement of Substances Between the Interstitial Fluid and the Plasma Three mechanisms allow substances to move between the interstitial fluid and the plasma: Diffusion: Movement of molecules from a region of higher concentration to a region of lower concentration; this is the only significant method of net movement of nutrients and gases across capillary walls Vesicle Transport: Transport of substances across a cell membrane inside a vesicle; small amounts of protein enter (or leave) the cell by endocytosis (exocytosis) Bulk Flow: Transport of protein-free blood plasma across the capillary walls, through water-filled channels. In this case, bulk flow does not transport nutrients or respiratory gases across capillary walls. Instead, its purpose is to distribute extracellular fluid between the blood plasma and the interstitial fluid (ISF). 143  Fluid Movement Across Capillaries The direction fluid moves at the capillaries is dependent on the difference between the net hydrostatic pressure and the net colloid osmotic pressure. Hydrostatic pressure is the force exerted by the fluid pressing against a wall. In the capillaries it is the same as the capillary blood pressure. In capillaries the pressure tends to force fluid out (filtration), especially on the arterial end, where pressure is higher. 144  Venules and Veins Venules have a large capacity for blood, so they are called capacitance vessels. They have some permeability to macromolecules, and they are also the site of migration of leukocytes into tissues during inflammation and infection. The walls of the veins are thinner and much more compliant than those of the arteries. Veins also have less smooth muscle than arteries and arterioles. Because of their high compliance, veins are referred to as capacitance vessels that act as blood reservoirs. 145  Venous Pressure Blood pressure in the veins is approximately 15 millimeters Hg. Several mechanisms exist to aid in venous return: – Respiratory pump: Increased venous pressure caused by downward contraction of the diaphragm during inspiration results in an increase in abdominal pressure. Compressed abdominal veins can only send blood upward toward the thorax, since one-way valves prevent downward backflow. – Muscular pump: When muscles contract, they squeeze the veins. This results in forward movement of blood towards the heart, with backwards flow being prevented by one-way valves. – The smooth muscle in the veins is under sympathetic nervous system control and contracts when stimulated. This causes venous contraction, which also promotes venous return. 146  Regulation of Mean Arterial Pressure Mean Arterial Pressure (MAP): Average pressure that is considered to be the driving force for blood flow to the body (except the lungs) MAP = CO × TPR MAP = Cardiac Output × Total Peripheral Resistance All changes in MAP are the result of changes in CO or TPR. TPR represents the total resistance to flow offered by all systemic blood vessels. The major site of resistance is the arterioles, and changes in TPR are almost entirely the result of changes in arteriolar resistance. Vasodilation causes a decrease in the resistance to flow and decreases the MAP. Vasoconstriction causes an increase in resistance to flow and increases the MAP. Total Peripheral Resistance in the arterioles influences MAP. The distribution of resistance is not important. MAP can remain constant, if one group of arterioles dilates, while an equal-sized group constricts. 147  Baroreceptor Reflexes Baroreceptor Reflexes: A group of homeostatic responses to changes in arterial blood pressure (MAP), which are initiated by arterial stretch/pressure receptors, and carried out by autonomic regulation of the heart and blood vessels. These provide short-term regulation of blood pressure. Arterial Baroreceptors: Stretch/pressure receptors in the Carotid Sinuses (in the Carotid arteries) and the Aortic Arch. These provide sensory input to the medullary cardiovascular control center. 148  Medullary Cardiovascular Center Medullary Cardiovascular Center: Integrating center for baroreceptor reflexes, located in the medulla oblongata of the brainstem The neurons in this center receive input from the various baroreceptors. The input controls action potential frequency from the cardiovascular center to the parasympathetic (Vagus Nerve) output to the heart, and sympathetic output to the heart, arterioles and veins. Hormones: ADH (Vasopressin) & Angiotensin II also increase MAP through vasoconstriction of arterioles. 149  Other Baroreceptors The large systemic veins, the pulmonary vessels, and the walls of the heart also contain baroreceptors. In essence, they contribute a feedforward component of arterial pressure control. For example, a slight decrease in ventricular pressure reflexively increases the activity of the sympathetic nervous system even before the change decreases cardiac output and arterial pressure enough to be detected by the arterial baroreceptors. 150  Other Cardiovascular Reflexes and Responses Blood pressure is also affected by many other factors: Arterial concentrations of oxygen and carbon dioxide Changes in blood flow to the brain Pain Sexual activity Eating Mood Stress 151  Hypotension The term hypotension means a low blood pressure, regardless of the cause. One cause of hypotension is significant loss of blood volume, as in a hemorrhage. This reduces blood flow to the brain and cardiac muscle. Other causes include a decrease in cardiac contractility, strong emotion, and massive release of endogenous substances that relax arteriolar smooth muscle as might occur during an allergic reaction. 152  Hypertension Hypertension is defined as a chronically increased systemic arterial pressure (above 140/90 millimeters Hg). Hypertension is a contributing cause to some of the leading causes of disability and death. One of the organs most affected is the heart. There are two major forms of hypertension. Hypertension of uncertain cause is diagnosed as primary hypertension (formerly called “essential hypertension”). Secondary hypertension is the term used when there are identified causes. Primary hypertension is by far the more common etiology. 153  Shock The term shock denotes any situation in which a decrease in blood flow to the organs and tissues damages them. There are 3 types of shock: – Hypovolemic shock: Due to a decrease in blood volume secondary to hemorrhage or loss of fluid other than blood – Low-resistance shock: Due to a decrease in total peripheral resistance secondary to excessive release of vasodilators, as in allergy and infection. – Cardiogenic shock: Due to an extreme decrease in cardiac output from any of a variety of factors (for example, during a heart attack) 154  Table 12.10 Cardiovascular Changes During Moderate Exercise Variable Change Explanation Cardiac output Increases Heart rate and stroke volume both increase, the former to a much greater extent. Heart rate Increases Sympathetic stimulation of the SA node increases, and parasympathetic stimulation decreases. Stroke volume Increases Contractility increases due to increased sympathetic stimulation of the ventricular myocardium; increased ventricular end-diastolic volume also contributes to increased stroke volume by the Frank– Starling mechanism. Total peripheral resistance Decreases Resistance in heart and skeletal muscles decreases more than resistance in other vascular beds increases. Mean arterial pressure Increases Cardiac output increases more than total peripheral resistance decreases. Pulse pressure Increases Stroke volume and velocity of ejection of the stroke volume increase. End-diastolic volume Increases Filling time is decreased by the high heart rate, but the factors favoring venous return— venoconstriction, skeletal muscle pump, and increased inspiratory movements—more than compensate for it. Blood flow to heart and Increases Active hyperemia occurs in both vascular beds, mediated by local metabolic skeletal muscle factors. Blood flow to skin Increases Sympathetic activation of skin blood vessels is inhibited reflexively by the increase in body temperature. Blood flow to viscera Decreases Sympathetic activation of blood vessels in the abdominal organs and kidneys is increased. Blood flow to brain Increases slightly Autoregulation of brain arterioles maintains constant flow despite the increased mean arterial pressure. 155  Contributing Causes of Primary Hypertension Factors thought to be involved in primary hypertension include: – Genetic problems with the renin-angiotensin-aldosterone system, regulation of endothelial cell function, and arteriolar smooth muscle contraction – Increased total peripheral resistance caused by reduced arteriolar radius – Obesity – Insulin resistance (characteristic of type 2 diabetes) – Chronic high salt intake leading to overstimulation of the sympathetic nervous system – Stress – Smoking – Excess alcohol or caffeine consumption – Poor diet – Low birth weight and not being breast-fed as an infant Primary hypertension can be managed with diet, exercise, and life-style changes, and with medication. 156  Contributing Causes of Secondary Hypertension Factors involved in secondary hypertension include: – Damage to the kidneys or their blood supply can lead to renal hypertension – Excess renal Na + reabsorption – Hypersecretion of cortisol, aldosterone, or thyroid hormone – The abnormal nighttime sleeping pattern, sleep apnea Secondary hypertension can be managed with medication. 157  Table 12.11 Drugs Used to Treat Chronic Hypertension and Their Mechanisms of Action Diuretics; Increase urinary excretion of sodium and water to reduce blood volume and pressure (Chapter 14). Beta-adrenergic receptor antagonists (beta blockers); Decrease cardiac output. Calcium channel antagonists; Decrease entry of Ca2+ into vascular smooth muscle cells leading to vasodilation and decreased total peripheral (systemic vascular) resistance. Renin-angiotensin-aldosterone system inhibitors/antagonists (Chapter 14); Angiotensin-converting enzyme (ACE) inhibitors; Decrease angiotensin II production, leading to vasodilation/decreased total peripheral resistance; also decreases aldosterone allowing more sodium and water excretion. Angiotensin receptor blockers (ARBs); Decrease binding of angiotensin II to its receptors, leading to a decrease in total peripheral resistance; also leads to a decrease in aldosterone allowing more sodium and water excretion. Mineralocorticoid receptor (MR) antagonists; Decrease binding of aldosterone to its receptors in the kidney, allowing more sodium and water excretion. Sympathetic nervous system modulators; Central alpha receptor agonists; Act on targets within the brain to decrease sympathetic outflow. Peripheral alpha receptor antagonists; Relax vascular smooth muscle which leads to a decrease in total peripheral resistance. 158  Congestive Heart Failure Congestive Heart Failure: A condition that occurs when the heart does not pump adequate cardiac output; may be caused by plaque in the arteries, or by damage to the heart because of poor coronary circulation Types of Heart Failure: – Diastolic dysfunction: Involves difficulty with ventricular filling, due to decreased compliance; reduced end diastolic volume leads to reduced stroke volume; often caused by the heart pumping against high arterial pressure (hypertension). – Systolic dysfunction: Involves difficulty with ventricular ejection, due to damage to the myocardium; this can result from a heart attack; decreased contractility leads to a lower stroke volume at any EDV. Reduced cardiac output causes the baroreceptor reflex to occur; this leads to increased heart rate, increased resistance through vasoconstriction, fluid retention. Fluid retention in the interstitial spaces leads to swelling of the legs, and pulmonary edema (which hinders gas exchange in the lungs). 159  Table 12.12 Drugs Used to Treat Chronic Heart Failure and Their Mechanisms of Action Diuretics: Increase urinary excretion of sodium and water to reduce blood volume and pressure (Chapter 14). Reduce excess fluid accumulation contributing to edema and worsening cardiac function. Beta-adrenergic receptor antagonists (beta blockers); Decrease cardiac output lessening strain on the heart. Cardiac inotropic drugs; Enhance beta-adrenergic pathways. Increase ventricular contractility (for example digitalis) by increasing myocardial Ca2+. Renin-angiotensin-aldosterone system inhibitors/blockers (Chapter 14); Angiotensin-converting enzyme (ACE) inhibitors; Decrease angiotensin II production, leading to vasodilation (decreased total peripheral resistance), and decreased aldosterone production (more sodium and water excretion). Angiotensin receptor blockers (ARBs); Decrease binding of angiotensin II to its receptors, leading to decreased total peripheral resistance and decreased aldosterone production (allowing more sodium and water excretion). Mineralocorticoid receptor (MR) antagonists; Decrease binding of aldosterone to its receptors in the kidney, allowing more sodium and water excretion. 160  Clinical Application In coronary artery disease, changes in one or more of the coronary arteries cause insufficient blood flow (ischemia) to the heart. The result may be myocardial damage in the affected region, or even death of that portion of the heart—a myocardial infarction, or heart attack. Approximately 1.1 million Americans have a new or recurrent heart attack each year, and over 40% of them die from it. Sudden cardiac deaths during myocardial infarction are due mainly to ventricular fibrillation, an abnormality in impulse conduction triggered by the damaged myocardial cells. A small fraction of individuals with ventricular fibrillation can be saved if emergency resuscitation procedures are applied immediately after the attack. This includes cardiopulmonary resuscitation (CPR) and defibrillation. 161  Table 12.15 Anticlotting Roles of Endothelial Cells Action Result Normally provide an intact barrier between Platelet aggregation and the formation of tissue the blood and subendothelial connective factor–factor VIIa complexes are not triggered. tissue Synthesize and release PGI2 and nitric oxide These inhibit platelet activation and aggregation. Secrete tissue factor pathway inhibitor This inhibits the ability of tissue factor–factor VIIa complexes to generate factor 10a. Bind thrombin (via thrombomodulin), which Active protein C inactivates clotting factors 8a and then activates protein C 5a. Display heparin molecules on the surfaces Heparin binds antithrombin III, and this molecule of their plasma membranes then inactivates thrombin and several other clotting factors. Secrete tissue plasminogen activator Tissue plasminogen activator catalyzes the formation of plasmin, which dissolves clots. 162  Role of Coagulation Factors in Clot Formation Disorders Hemophilia Genetic disorder caused by deficiency of gene for a specific coagulation factor Von Willebrand’s disease Reduced levels of vWf Decreases platelet plug formation Vitamin K deficiencies Decreased synthesis of clotting factors 163 Figure 12.79 Aortic Stenosis Leading to Heart Failure Access the text alternative for slide images. 164  Circulatory System Overview The three principal components that comprise the circulatory (cardiovascular) system are: – the heart (the pump) – the blood vessels or vascular system (set of interconnected tubes) – the blood (a fluid connective tissue containing water, solutes, and cells that fills the tubes) Cardiovascular system function is impacted by the endocrine, nervous, and urinary systems. 165  Cardiac Muscle Cardiac muscle cells have one to two nuclei that are centrally located. They are striated and use the sliding-filament mechanism to contract. They are branched cells with intercalated disks at their ends, which contain desmosomes and gap junctions. The gap junctions are critical to the heart’s ability to be electrically coupled. The nodal cells have the ability to stimulate their own action potentials. This is called automaticity or autorhythmicity. The absolute refractory period of cardiac muscle cells is about 250 milliseconds. This prevents tetanic contractions, which would interfere with the heart’s ability to function as a pump. 166 Figure 9.40 Excitation-Contraction Coupling in Cardiac Muscle 167