Cardiovascular Physiology Look for these other Mosby Physiology Monograph Series titles: BLAUSTEIN ET AL: Cellular Physiology and Neurophysiology CLOUTIER: Respiratory Physiology HUDNALL: Hematology: A Pathophysiologic Approach JOHNSON: Gastrointestinal Physiology KOEPPEN & STANTON: Renal Physiology PAPPANO & WIER: Cardiovascular Physiology WHITE & PORTERFIELD: Endocrine and Reproduction Physiology Cardiovascular Physiology TENTH EDITION ACHILLES J PAPPANO, PhD Professor Emeritus Department of Cell Biology and Calhoun Cardiology Center University of Connecticut Health Center Farmington, Connecticut WITHROW GIL WIER, PhD Professor Department of Physiology University of Maryland School of Medicine Baltimore, Maryland 1600 John F Kennedy Blvd Ste 1800 Philadelphia, PA 19103-2899 CARDIOVASCULAR PHYSIOLOGY ISBN: 978-0-323-08697-4 Copyright © 2013 by Mosby, an imprint of Elsevier Inc Copyright © 2007, 2001, 1997, 1992, 1986, 1981, 1977, 1972, 1967 by Mosby, Inc., an affiliate of Elsevier Inc All rights reserved No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein) Notice Knowledge and best practice in this field are constantly changing As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility With respect to any drug or pharmaceutical products identified, readers are advised to check the most current information provided (i) on procedures featured or (ii) by the manufacturer of each product to be administered, to verify the recommended dose or formula, the method and duration of administration, and contraindications It is the responsibility of practitioners, relying on their own experience and knowledge of their patients, to make diagnoses, to determine dosages and the best treatment for each individual patient, and to take all appropriate safety precautions To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein Library of Congress Cataloging-in-Publication Data Pappano, Achilles J Cardiovascular physiology / Achilles J Pappano, Withrow Gil Wier 10th ed p ; cm (Mosby physiology monograph series) Rev ed of: Cardiovascular physiology / Matthew N Levy, Achilles J Pappano 9th ed c2007 Includes bibliographical references and index ISBN 978-0-323-08697-4 (pbk.) I Wier, Withrow Gil II Levy, Matthew N., 1922- Cardiovascular physiology III Title IV Series: Mosby physiology monograph series [DNLM: Cardiovascular Physiological Phenomena WG 102] 612.1 dc23 2012032909 Senior Content Strategist: Elyse O’Grady Content Coordinator: Lee Hood Publishing Services Managers: Rajendrababu Hemamalini and Anne Altepeter Senior Project Manager: Douglas Turner Project Manager: Saravanan Thavamani Design Manager: Steven Stave Printed in the United States of America Last digit is the print number: 9 8 7 6 5 4 3 2 To Robert M Berne and Matthew N Levy, whose research and scholarship in cardiovascular physiology have enriched and inspired generations of students and colleagues PREFACE W e believe that physiology is the backbone of clinical medicine In the clinic, the emergency room, the intensive care unit, or the surgical suite, physiological principles are the basis for action But we also find great intellectual satisfaction in the science of physiology as the means to explain the elegant mechanisms of our bodies In the tenth edition of Berne and Levy’s classic monograph on cardiovascular physiology, we have tried to convey both ideas Physiology serves as a foundation that students of medicine must comprehend before they can understand the derangements caused by pathology This text of cardiovascular physiology emphasizes general concepts and regulatory mechanisms To present the various regulatory mechanisms clearly, the component parts of the system are first discussed individually Then, the last chapter describes how various individual components of the cardiovascular system are coordinated The examples describe how the body responds to two important stresses—exercise and hemorrhage Selected pathophysiological examples of abnormal function are included to illustrate and clarify normal physiological processes These examples are distributed throughout the text and are identified by colored boxes with the heading “Clinical Box” The text incorporates the learning objectives for cardiovascular physiology of the American Physiological Society, except for hemostasis and coagulation These last-named topics are found in hematology books The book has been updated and revised extensively The relation between pressure-volume loops and cardiac function curves, newer aspects of vi endothelium function, myocardial metabolism and its relation to oxygen consumption and cardiac energetics, and the regulation of peripheral and coronary blood flows have received particular emphasis Whenever available, physiological data from humans have been included Some old figures have been deleted and many new figures have been added to aid comprehension of the text Selected references appear at the end of each chapter The scientific articles included were chosen for their depth, clarity, and appropriateness Throughout the book, italics are used to emphasize important facts and concepts, and boldface type is used for new terms and definitions Each chapter begins with a list of objectives and ends with a summary to highlight key points Case histories with multiple-choice questions are provided to help in review and to indicate clinical relevance of the material The correct answers and brief explanations for them appear in the appendix We thank our readers for their constructive comments Thanks are also due to the numerous investigators and publishers who have granted permission to use illustrations from their publications In most cases these illustrations have been altered somewhat to increase their didactic utility In some cases, unpublished data from investigations by Robert Berne and Matthew Levy and the current authors have been presented Achilles J Pappano W Gil Wier CONTENTS CHAPTER OVERVIEW OF THE CIRCULATION AND BLOOD The Circulatory System Blood Erythrocytes Leukocytes Lymphocytes Blood Is Divided into Groups by Antigens Located on Erythrocytes Summary Case 1-1 Conduction in Cardiac Fibers Depends on Local Circuit Currents 25 Conduction of the Fast Response 25 Conduction of the Slow Response 27 Cardiac Excitability Depends on the Activation and Inactivation of Specific Currents 27 Fast Response 27 Slow Response 28 Effects of Cycle Length 28 Summary 29 Case 2-1 29 CHAPTER CHAPTER EXCITATION: THE CARDIAC ACTION POTENTIAL 11 Cardiac Action Potentials Consist of Several Phases 11 The Principal Types of Cardiac Action Potentials Are the Slow and Fast Types 12 Ionic Basis of the Resting Potential 13 The Fast Response Depends Mainly on Voltage-Dependent Sodium Channels 15 Ionic Basis of the Slow Response 24 AUTOMATICITY: NATURAL EXCITATION OF THE HEART 31 The Heart Generates Its Own Pacemaking Activity 31 Sinoatrial Node 32 Ionic Basis of Automaticity 34 Overdrive Suppression 35 Atrial Conduction 36 Atrioventricular Conduction 37 Ventricular Conduction 39 An Impulse Can Travel Around a Reentry Loop 41 Afterdepolarizations Lead to Triggered Activity 42 vii viii CONTENTS Early Afterdepolarizations 43 Delayed Afterdepolarizations 43 Electrocardiography Displays the Spread of Cardiac Excitation 44 Scalar Electrocardiography 44 Dysrhythmias Occur Frequently and Constitute Important Clinical Problems 47 Altered Sinoatrial Rhythms 47 Atrioventricular Transmission Blocks 48 Premature Depolarizations 48 Ectopic Tachycardias 49 Fibrillation 49 Summary 51 Case 3-3 52 CHAPTER THE CARDIAC PUMP 55 The Gross and Microscopic Structures of the Heart Are Uniquely Designed for Optimal Function 55 The Myocardial Cell 55 Structure of the Heart: Atria, Ventricles, and Valves 60 The Force of Cardiac Contraction Is Determined by Excitation-Contraction Coupling and the Initial Sarcomere Length of the Myocardial Cells 63 Excitation-Contraction Coupling Is Mediated by Calcium 63 Mechanics of Cardiac Muscle 65 The Sequential Contraction and Relaxation of the Atria and Ventricles Constitute the Cardiac Cycle 69 Ventricular Systole 70 Echocardiography Reveals Movement of the Ventricular Walls and of the Valves 73 The Two Major Heart Sounds Are Produced Mainly by Closure of the Cardiac Valves 74 The Pressure-Volume Relationships in the Intact Heart 75 Passive or Diastolic Pressure-Volume Relationship 75 Active or End-Systolic Pressure-Volume Relationship 77 Pressure and Volume during the Cardiac Cycle: The P-V Loop 77 Preload and Afterload during the Cardiac Cycle 77 Contractility 78 The Fick Principle Is Used to Determine Cardiac Output 79 Summary 89 Case 4-1 90 CHAPTER EGULATION OF THE R HEARTBEAT 91 Heart Rate is Controlled Mainly by the Autonomic Nerves 91 Parasympathetic Pathways 92 Sympathetic Pathways 93 Higher Centers Also Influence Cardiac Performance 97 Heart Rate Can Be Regulated via the Baroreceptor Reflex 97 The Bainbridge Reflex and Atrial Receptors Regulate Heart Rate 98 Respiration Induces a Common Cardiac Dysrhythmia 99 Activation of the Chemoreceptor Reflex Affects Heart Rate 101 Ventricular Receptor Reflexes Play a Minor Role in the Regulation of Heart Rate 102 CONTENTS Myocardial Performance Is Regulated by Intrinsic Mechanisms 102 The Frank-Starling Mechanism Is an Important Regulator of Myocardial Contraction Force 103 Changes in Heart Rate Affect Contractile Force 107 Myocardial Performance Is Regulated by Nervous and Humoral Factors 110 Nervous Control 110 Cardiac Performance Is Also Regulated by Hormonal Substances 113 Summary 116 Case 5-1 117 CHAPTER HEMODYNAMICS 119 Velocity of the Bloodstream Depends on Blood Flow and Vascular Area 119 Blood Flow Depends on the Pressure Gradient 120 Relationship Between Pressure and Flow Depends on the Characteristics of the Conduits 122 Resistance to Flow 125 Resistances in Series and in Parallel 126 Flow May Be Laminar or Turbulent 127 Shear Stress on the Vessel Wall 128 Rheologic Properties of Blood 129 Summary 133 Case 6-6 134 CHAPTER THE ARTERIAL SYSTEM 135 The Hydraulic Filter Converts Pulsatile Flow to Steady Flow 135 ix Arterial Elasticity Compensates for the Intermittent Flow Delivered by the Heart 137 The Arterial Blood Pressure Is Determined by Physical and Physiological Factors 140 Mean Arterial Pressure 140 Cardiac Output 142 Peripheral Resistance 142 Pulse Pressure 144 Stroke Volume 144 Arterial Compliance 145 Total Peripheral Resistance and Arterial Diastolic Pressure 146 The Pressure Curves Change in Arteries at Different Distances from the Heart 147 Blood Pressure Is Measured by a Sphygmomanometer in Human Patients 148 Summary 150 Case 7-1 150 CHAPTER THE MICROCIRCULATION AND LYMPHATICS 153 Functional Anatomy 153 Arterioles Are the Stopcocks of the Circulation 153 Capillaries Permit the Exchange of Water, Solutes, and Gases 154 The Law of Laplace Explains How Capillaries Can Withstand High Intravascular Pressures 155 The Endothelium Plays an Active Role in Regulating the Microcirculation 156 The Endothelium is at the Center of FlowInitiated Mechanotransduction 157 The Endothelium Plays a Passive Role in Transcapillary Exchange 158 278 CARDIOVASCULAR PHYSIOLOGY c the arterial chemoreceptors reflexly induced the parasympathetic nerves to the skin to release neuropeptide Y d the arterial baroreceptors reflexly induced the sympathetic nerves to the skin to release nitric oxide e the arterial baroreceptors reflexly induced the sympathetic nerves to the skin to release norepinephrine The patient’s arterial blood pressure, 85/65 mm Hg, indicates that: a the patient’s left ventricle was pumping an abnormally low cardiac output and low stroke volume b the patient’s left ventricle was pumping more blood than her right ventricle c the patient’s left ventricle was pumping an abnormally low cardiac output but a normal stroke volume d the patient’s left ventricle was pumping a normal cardiac output and an abnormally low stroke volume e the patient’s left ventricle was pumping less blood than her right ventricle If the patient’s bleeding had stopped before she arrived at the hospital, which of the following changes would be expected in the patient’s blood hour after she had arrived at the hospital? a The individual red blood cells would be larger than normal b The hematocrit ratio would be reduced c The lymphocyte count would be abnormally high d The plasma albumin concentration would be increased e The plasma globulin concentration would be increased APPENDIX C A S E S T U D Y A N S W E R S CASE 1-1 b is correct The circulation time will be shortened because some blood passes through the shunt (short circuit) CASE 2-1 c is correct When the extracellular K+ concentration increases, the Nernst equation indicates that the transmembrane potential will become less negative d is correct When the extracellular K+ concentration increases and depolarizes the membrane, the rate of rise of the action potential is diminished because some Na+ channels are inactivated by the persistent depolarization d is correct The Purkinje fibers are automatic fibers, and they generate action potentials at a low frequency whenever they are not depolarized by action potentials that originate in higher- frequency pacemaker sites a is correct When ventricular pacing at 75 beats per minute was discontinued, spontaneous pacemaker activity in the ventricles was suppressed for several seconds because the preceding period of artificial pacing had hyperpolarized the ventricular pacemaker cells (Purkinje fibers) CASE 3-1 c is correct because the PR interval, which indicates the time for conduction from atria through the AV node and ventricular conducting system to the ventricle, is normal 2 e is correct because the QT interval measures the duration of the average ventricular action potential a is correct because heart rate can be taken from either the R-R or the P-P interval when conduction is normal d is correct because there is greater activation of repolarizing K channels when heart rate increases CASE 4-1 d is correct The murmur is characteristic of mitral stenosis c is correct The pulse is totally irregular b is correct A “loop” diuretic like furosemide would relieve the excessive preload and allow the cardiac output to improve and the edema and ascites to subside b is correct The elevated left atrial pressure would be transmitted back to the wedged catheter (wedge pressure) c is correct 300 mL O2/min /[(18 − 8) mL O2/100 mL blood] = 3000 mL/min = L/min CASE 5-1 d is correct A decrease in arterial pressure would reflexly increase sympathetic activity and thereby increase the neuronal release of norepinephrine d is correct The ACh released from vagal fibers acts on muscarinic receptors on SA node automatic cells, and these receptors interact very quickly with specific K+ channels because no second messenger intervenes 279 280 CARDIOVASCULAR PHYSIOLOGY a is correct The cardiac responses to vagal stimulation develop and decay rapidly, but the responses to sympathetic stimulation develop and decay very slowly Hence respiratory dysrhythmia is mediated almost entirely by the vagus nerves, and this dysrhythmia would be abolished by a potent muscarinic antagonist a is correct Heart rate increases during inspiration in this dysrhythmia, and this increase is mediated mainly by a reduction in vagal activity e is correct Acetylcholinesterase is abundant in atrial tissues, and especially in the SA and AV nodes CASE 8-1 d is correct 1[(44 − 8) − 0.7(23 − 3)] = 22 c is correct Portal-caval shunt (portal vein to inferior vena cava) could reduce the high venous pressure in the mesentery by allowing mesenteric blood to bypass the high vascular resistance in the liver This would aid in eliminating the ascites b is correct Albumin is small enough (low molecular weight) to exert the main osmotic force of plasma and large enough to remain within the vascular compartment CASE 8-2 CASE 6-1 b is correct (Pa − Pv)/Q—that is, [(100 − 80) + (80 − 10)]/300—equals 0.30 mm Hg/mL/min d is correct The left ([100 − 10]/500) and right ([100 − 10]/300) vascular resistances were 0.18 and 0.30 mm Hg/mL/min, respectively, and the reciprocals of those resistances were 5.56 and 3.33 mL/min/mm Hg, respectively Hence the reciprocal of the sum (8.89 mL/min/mm Hg) of these reciprocals equals 0.11 mm Hg/mL/min a is correct The pressure difference across the plaque (100 − 80 mm Hg), divided by the flow past the plaque (300 mL/min), equals 0.066 mm Hg/mL/min 1 e is correct The albumin concentration in the patient’s blood is low because of the loss of albumin from the burned tissues This results in a decreased plasma oncotic pressure, and that plus the loss of fluid from the damaged microvessels leads to a decreased blood volume and an increased red blood cell concentration Therefore a plasma transfusion, which supplies albumin plus saline without red blood cells, is the most effective treatment d is correct The small diameter (or radius) of the capillaries is responsible for the low wall tension, according to the law of Laplace, whereby T (wall tension) = P (pressure) × r (radius of capillary) The low wall tension protects against capillary rupture CASE 7-1 a is correct The mean arterial pressure in the systemic and pulmonary vascular beds depends on the outputs of the left and right ventricles and the systemic vascular resistances Over any substantial time interval, the outputs of the two ventricles are equal, but the systemic vascular resistance far exceeds the pulmonary vascular resistance c is correct When the arterial pressure rises, the arteries become less compliant (as does a balloon), and also the arterial compliance decreases with age CASE 9-1 b is correct The arterioles are maximally dilated secondary to the inadequate blood flow that causes the local release of vasodilator metabolites d is correct The ankle-brachial index is taken from the ratio of systolic pressure in the dorsalis pedis artery to that in the brachial artery (112 mm Hg/140 mm Hg = 0.80) a is correct Use of tobacco is believed to be a contributing factor to the cause and exacerbation of thromboangiitis obliterans APPENDIX 281 CASE 10-1 CASE 12-1 c is correct The blood loss would decrease the central venous pressure, and this reduction in cardiac preload would reduce the cardiac output a is correct A drug that improves cardiac contractility would increase cardiac output, a change that would tend to increase the arterial blood volume Hence, if total blood volume remains constant, the venous blood volume would decrease Consequently, the central venous pressure would decline e is correct Gravity acts to pool blood in the compliant, dependent veins, and hence the pressure in the foot veins increases The redistribution of the venous blood volume causes the central venous volume and pressure to diminish The consequent reduction in preload decreases the cardiac output b is correct When the heart rate is abnormally high (250 beats/min), cardiac filling is inadequate, and therefore stroke volume and cardiac output are decreased 1 a is correct The hepatic fibrosis increases the hepatic vascular resistance, and therefore the pressure in the vessels downstream to the liver is elevated Consequently, the balance of Starling forces in the splanchnic capillaries favors the movement of fluid out of the capillaries and into the abdominal cavity CASE 11-1 d is correct Two factors operate in bradycardia At the slower rate, more time is spent in diastole, thereby decreasing coronary resistance (less extravascular compression) However, at the slower rate the heart uses less oxygen and fewer vasodilator metabolites are present, permitting greater expression of basal tone (coronary constriction) The end result is the algebraic sum of these two opposing factors a is correct The coronary vessels are maximally dilated as a result of the accumulation of vasodilator metabolites consequent to an inadequate oxygen supply to the myocardial cells If any vasoconstriction occurred, it would be transient b is correct Endothelin is a powerful vasoconstrictor e is correct With exercise, a denervated heart increases stroke volume more than heart rate to meet the required cardiac output Any increase in heart rate must come from release of epinephrine and norepinephrine from the adrenal medulla CASE 12-2 b is correct The murmur, the high right ventricular systolic pressure with a normal right atrial pressure, the elevated Po2 of the right ventricular blood, and the absence of cyanosis indicated a left-to-right shunt through an interventricular septal defect CASE 12-3 d is correct The ankle-brachial index (ABI) is the ratio of systolic blood pressure in the dorsal pedal artery to that in the brachial artery The ratio (70 mm Hg/140 mm Hg) yields an ABI of 0.5 CASE 13-1 d is correct The patient’s heart became unable to pump enough blood per unit time owing to a decrease in stroke volume and hence in cardiac output a is correct The patient’s body temperature reached an alarmingly high level because of inadequate heat loss via the skin (vasoconstriction secondary to decrease in blood pressure) in the presence of the great heat production in the active muscles CASE 13-2 e is correct The hypotension would act via the arterial baroreceptors to activate the sympathetic nerves to the skin The consequent release of norepinephrine would constrict the cutaneous arterioles, and the skin temperature would drop 282 CARDIOVASCULAR PHYSIOLOGY a is correct The abnormally low mean arterial pressure (about 72 mm Hg) would signify an abnormally small cardiac output The low mean arterial pressure could not have been caused by arterial vasodilation because the baroreceptor reflex response to a low mean arterial pressure would be vasoconstriction, not dilation The low pulse pressure (20 mm Hg) would signify an abnormally small stroke volume 3 b is correct The decrease in capillary hydrostatic pressure draws interstitial fluid into the plasma compartment and thereby dilutes the red cell component of whole blood INDEX A A band, 56f–57f A receptors, 189 a wave, 72 ABI See Ankle-brachial index Accessory atrioventricular pathways, 42b Accumulated vasodilator metabolites, 268–269 Acetylcholine atrioventricular node N region fibers hyperpolarized by, 39 hyperpolarization induced by, 35, 35f muscarinic receptor interactions with, 112 vagal ending release of, 112 Acetylcholinesterase, 280 Acetylstrophanthidin, 43 Acid hydrolases, 275 Acidosis, 115 in hemorrhage, 274 ACTH See Adrenocorticotropic hormone Actin, 55–58 Actin filaments, 172 Action potential amplitude of, 26 contraction and, 12, 57f, 172 cycle length effects on, 28–29 definition of, 11–12 diltiazem effects on, 22f, 23 duration of, 28–29, 28f fast response changes to slow response, 13b conduction of, 25–27 description of, 12, 12f effective refractory period for, 27 excitability affected by, 27–28 voltage-dependent sodium channels and, 15–24 gate concept for, 19 ionic currents, 20f overshoot of, 15–17 phases of, 11–25, 12f plateau phase calcium conductance during, 21–23, 21f, 63–64, 108 definition of, 11–12 early afterdepolarization at end of, 43 genesis of, 20 potassium conductance during, 22–23 propagation of, 25 from Purkinje fibers, 40–41 rate of change of, 26 repolarization definition of, 11–12 Action potential (Continued) early, 20 final, 23 slow response in atrioventricular node N region, 37–38 conduction of, 27 description of, 12, 12f fast responses changed to, 13b ionic basis of, 24–25 relative refractory period during, 27 tetrodotoxin effects on, 13b, 13f, 16 transmembrane See Transmembrane potential types of, 12–13 upstroke of, 11–12, 15–19 Activation of calcium channels, 34, 111 of fast sodium channels, 16 Activation gate, 16 Active hyperemia, 182 Acute coronary artery occlusion, 233b Acute heart failure, 211b Addisonian crisis, 114b Addison’s disease, 114b Adenosine, 245 description of, 182 A1 receptor, 230 A2a receptor, 230, 231f Adenosine triphosphate (ATP), metabolism of, 81–83 sensitive KATP channels, 229, 265 Adenylyl cyclase, 21–22, 112 Adrenal medulla, 185 α-Adrenergic effect, 185 β-Adrenergic drugs, 228 β-Adrenergic effect, 185 β-Adrenergic receptors antagonists, 92 catecholamines and, 21–22, 110–111 β-Adrenoceptor-blocking agent, 228 α1-Adrenoceptors, 254 α-Adrenoceptors, 228 β1-Adrenoceptors, 254 β-Adrenoceptors, 228 Adrenocortical hormones, 113–114 Adrenocorticotropic hormone (ACTH), 275 Adrenomedullary hormones, 113 Afferent arterioles, 250–251 Afterdepolarizations delayed, 43–44 early, 43 triggered activity caused by, 42–44 Afterload cardiac function curve and, 198 definition of, 22b, 103–104 description of, 69 left ventricular, 212 Afterload reducing drugs, 22b A-H interval, 48 Albumin, 163–164, 280 Aldosterone, 189, 273 Alveolus, 245, 246f Ambient temperature, skin blood flow and, 239–240 Amplitude, 26 Anemia blood viscosity in, 130b high altitude and, 7b megaloblastic, 8f microcytic, hypochromic, 5–6, 8f sickle cell, 5–6, 8f, 132b spherocytic, 132b Angina pectoris, 189b, 234b Angioplasty, 233b Angiotensin I, 189, 253, 273 converting enzyme, 253 Angiotensin II, 189, 253, 273 Angiotensin-converting enzyme, 189 Angiotensinogen, 253 Ankle-brachial index (ABI), 148b, 280–281 Anomalous viscosity, 129 ANP See Atrial natriuretic peptide Antegrade impulse, 41–42 Anterior interatrial myocardial band, 36 Antidiuretic hormone, 98, 273 Antigen blood group based on, 7–8 definition of, Aorta aging effects on, 139–140 cardiac cycle changes, 140 characteristics of, 3f static pressure-volume relationship for, 139, 139f wall tension of, 156t Aortic arch, 185–186, 186f, 189 Aortic bodies, 189 Aortic compliance, 139 Aortic insufficiency, 75b Aortic pulse pressure, 139–140, 141f Aortic regurgitation, 145b Aortic stenosis, 75b, 121, 226b Page numbers followed by f indicate figures; t, tables; b, boxes 283 284 INDEX Aortic valve, 61f Apex of heart, 60–62 Apnea, 219–220 Apparent viscosity, 129 Aquaporins, 159 Arachidonic acid, 157f, 275 Arcuate arteries, 250 Arterial baroreceptors, 185–188 Arterial blood pressure, hemorrhage and, 270 Arterial compliance (Ca), 145–146, 200 Arterial diastolic pressure, 146–147 Arterial hypotension, 185 Arterial pulse pressure, 144 Arteries See also specific artery anatomy of, arcuate, 250 celiac, 254 characteristics of, 3f elastic, 135, 136f elasticity of, 137–140 frictional resistance in, functions of, 171 hepatic, 256 inferior mesenteric, 254 renal, 250 superior mesenteric, 254 Arteriogenesis, 233 Arteriolar resistance, 163 Arteriolar vasoconstriction, 270–271 Arterioles afferent, 250–251 anatomy of, 153–156 characteristics of, 3f constriction of, 180f cross-sectional image of, 173f functions of, 135, 171 histology of, 155f, 173f metarterioles, 153–154 nitric oxide effects on, 182 nitroprusside effects on, 179 prostaglandins’ effect on, 182 terminal, 3f, 154 Arterioluminal vessel, 223–224 Arteriosclerosis, 140 Arteriosinusoidal vessel, 223–224 Arteriovenous (AV) anastomoses, 237, 238f Artificial respiration, cardiac output and, 220–221 Ascending aorta, 147 ATP See Adenosine triphosphate Atria anatomy of, 60–62 left See Left atrium right See Right atrium Atrial conduction, 36 Atrial fibrillation, 50, 50f Atrial flutter, 51b Atrial natriuretic peptide (ANP), 98–99 Atrial pacemaker complex, 31 Atrial receptors heart rate regulation by, 98–99 urine volume affected by, 98 Atrial systole, 73 Atrioventricular block bradycardia and, 215b complete, 38–39, 38f, 39b Atrioventricular block (Continued) first-degree, 38, 38f, 39b second-degree, 38, 38f, 39b site of, 48, 48f third-degree, 38–39, 38f, 39b Atrioventricular (AV) node anatomy of, 36f, 37 in atrial fibrillation, 51b automaticity in, 35 cholinesterase in, 92–93 conduction in, 37–39 description in, 12 N region of, 37–38 NH region of, 37–38 AN region of, 37–38 regions of, 37 retrograde conduction through, 38 transmembrane potential from, 39f Atrioventricular pathways, accessory, 42b Atrioventricular valves, 61f, 62 Atropine, 92 Augmentation index, 148 Auricular appendage, 61f Ausculatory method, 149–150 Automaticity in atrioventricular node, 35 ionic basis of, 34–35 properties of, 31 Purkinje fibers, 32, 35 Autonomic nervous system, heart rate regulation by, 91–102 Autoregulation of coronary blood flow, 225 of intestinal circulation, 254 of renal hemodynamics, 252–253 of systemic blood flow, 166, 179–180 Auxiliary pump, 219–220 Auxiliary pumping mechanism, 220b AV node See Atrioventricular node B B lymphocytes, B receptors, 189 Bachmann’s bundle, 36 Bainbridge reflex, 98–99 Balloon angioplasty, 233b Baroreceptor reflex, 269 heart rate regulation by, 97–98 in hemorrhage, 270–272 myocardial performance affected by, 112–113 Baroreceptors arterial, 185–188 cardiopulmonary, 188–189 carotid sinus, 186 definition of, 185–186 sinoaortic, 273 Basal metabolism, 2b Basal tone, 182–183 Basophils, 6f Birth, circulatory system at, 259–260 Blanching, 239 Blood apparent viscosity of, 130 components of, 5–8 erythrocytes See Erythrocytes Blood (Continued) functions of, homeostatic functions of, leukocytes, 6–7 lymphocytes, mobilization of, from capacitance vessels, 185 rheologic properties of, 129–131 viscosity of, 129, 130f Blood clotting aberrations, in hemorrhage, 275 Blood flow arterial, autoregulation of, 179, 225 in capillaries, 3, 4f, 154 cerebral, 243–245 coronary See Coronary blood flow endothelial regulation of, 180–181 equation for, 119 hepatic, 256–257 intestinal, 256 local regulation of, 181–183 nutritional, 154–155 peak velocity of, 121, 121f peripheral See Peripheral blood flow physiological shunting of, 154–155 pressure gradient effects on, 120–121 pulmonary, 247–249 pulsatile arterial, renal, 252 resistance to, 125–127 right ventricle and, 211–214 to skin ambient temperature and, 239–240 body temperature and, 239–240 skin color and, 240 sympathetic nervous system and, 237–239 tissue metabolic activity effects on, 181–183 tissue perfusion alteration effects on, 179 velocity of, 91–102 Blood groups, 7–8 Blood pressure arterial, 140–147 hemorrhage and, 270 baroreceptors’ effect on arterial, 185–188 cardiopulmonary, 188–189 curves, 147–148 determinants of cardiac output See Cardiac output mean arterial pressure, 140–141 overview of, 140 peripheral resistance, 142 pulse pressure, 144 measurement of, 148–150 sphygmomanometer measurement of, 148–150, 149f vascular reflexes’ effect on, 185–189 Blood reservoirs, 206 Blood transfusion, cardiac output affected by, 99f Blood vessels See also specific vessel anatomy of, 1–2, 2f function of, 171 INDEX Blood vessels (Continued) in parallel, 126–127 parasympathetic nervous system, innervation of, 185 resistance, 171 schematic diagram of, 4f in series, 126–127 shear stress on, 128–129 Blood volume decreases in, 189 description of, 5–8, 140 distribution of, 3, 5t vascular function curve affected by, 205–206, 209–210 Blood-brain barrier, 244–245 Blushing, 239 Body temperature, skin blood flow and, 239–240, 281 Bowman capsule, 250–251 Brachial artery, 149–150 Bradycardia, 281 cerebral ischemia and, 272 complete atrioventricular block and, 215b description of, 47–48, 47f sick sinus syndrome and, 215b Bradykinin, 239 Bronchial vasculature, 246–247 Bundle branches anatomy of, 39, 40f block of, 40b left, 39–40, 40f right, 39–40, 40f Bundle of His description of, 17–18 electrogram of, 26f, 48 C c wave, 72 Ca See Arterial compliance Calcium calcium-induced release of, 64–65 delayed afterdepolarizations and, 44 excitation-contraction coupling mediated by, 63–65 intercellular concentration of, 63 from interstitial fluid, 63–64 myoplasmic concentration of, 14t, 172–174 systolic, 63–65 trigger, 63–64 Calcium channel(s) activation of, 34, 111 characteristics of, 21 L-type, 21 stretch effects on, 179 T-type, 21 voltage-gated, 176 Calcium channel antagonists dihydropyridine receptor, 63–64 transmembrane potential affected by, 34f Calmodulin, 172–174 cAMP See Cyclic adenosine monophosphate Capacitance vessels basal tone in, 184b blood mobilization from, 185 constriction of, 184 Capacitance vessels (Continued) description of, 153 sympathetic nerves’ regulation of, 184–185 Capillaries blood flow in, 3, 4f, 154 characteristics of, 3f density of, 154 diameter of, 156, 280 distribution of, 154 endothelial wall, 161f fenestrations in, 158f, 159 flow-limited transfer across, 161–162 hydrostatic pressure in, 163 illustration of, 160f–161f law of Laplace, 155 in myocardium, 58–60 permeability of, 158–159, 158f pinocytotic transfer across, 167 recruitment of, 166 wall tension of, 156t Capillary filtration, 163–165 coefficient, 165 Capillary pressure, 164–165 Capillary recruitment, 166, 265 Carbohydrate metabolism, 84–86 Carbon dioxide central chemoreceptors affected by, 189–190 myocardial performance affected by, 115 Carbon dioxide tension, description of, 189 Cardiac cells effective refractory period, 17–18 excitability of, 27–29 intracellular and extracellular ion concentrations in, 14t potassium concentration in, 13 sodium entry into, 17 sodium equilibrium potential for, 14 Cardiac cycle afterload during, 77–78 aorta changes during, 140 length of, 28–29 norepinephrine release during, 95 preload during, 77–78 pressure-volume graph of, 77 ventricular diastole, 73 ventricular systole, 72 Cardiac excitability, 27–29 Cardiac failure, in hemorrhage, 274 Cardiac fibers conduction in, 25–27 skeletal muscle fibers vs., 58 Cardiac function curve (CFC), 196–197 afterload and, 198 contractility and, 197–198 myocardial compliance and, 198–199 physiological function and, 199–200 Cardiac glycogen levels, 258 Cardiac glycosides, 65 Cardiac muscle characteristics of, 55–58 metabolism of ATP, 81–86 oxygen requirements, 58 skeletal muscle vs., 56f–57f, 58, 59f syncytium, 58 285 Cardiac O2 consumption, 86–88 Cardiac output (CO) artificial respiration and, 220–221 bleeding effects on, 99f blood transfusion effects on, 99f calculation of, 91 central venous pressure and, relationship between, 196–200, 281 description of, 140, 142 elements of, 141 factors controlling, 195–196, 196f Fick principle for measuring, 79–80 Frank-Starling mechanism, 106 gravity and, 216–218, 281 heart rate and, 214–216 indicator dilution technique for measuring, 80–81 mean arterial pressure and, 141f renal circulation and, 250–254 respiratory activity and, 219–220 venous pressure depends on, 205 venous return and, 207 Cardiac valves atrioventricular, 61f, 62 semilunar, 61f, 62 Cardiac work, 86–88 Cardiopulmonary baroreceptors, 188–189 Cardiovascular system, functions of, Cardioversion, 215b Carotid sinus anatomy of, 186f baroreceptors in, 185–186 denervation of, 188 Catecholamines, 272 adrenal medulla secretion of, 185 β-Adrenergic receptors and, 21–22, 110–111 calcium entry into cells affected by, 64–65 cardiac muscle contractility affected by, 21–22 contraction affected by, 65 vascular tone control by, 178 Celiac artery, 254 Cell membranes ionic conductance of, 19 permeability of, 13 Central chemoreceptors, 189–190 Central command, 264 Central nervous system, depression of, in hemorrhage, 274–275 Central terminal, 47 Central venous pressure cardiac output and, relationship between, 196–200, 281 right ventricle and, 211–214 Cerebral circulation, 243–245 Cerebral cortex, 191 Cerebral ischemia, 191b in hemorrhage, 272 CFC See Cardiac function curve cGMP See Cyclic guanosine monophosphate Chemoreceptor(s) central, 189–190 peripheral, 189 stimulation of, 189 286 INDEX Chemoreceptor reflex description of, 101–102 in hemorrhage, 272 Chemotactic substances, Cholecystokinin, 256 Cholinesterase, 92–93 Chord conductance equation, 15 Chordae tendineae, 62 Chronic heart failure, 106b, 211b Circulation, 2f cerebral, 243–245 cutaneous, 237–240 fetal, 257–260 hepatic, 256–257 intestinal, 254–256 pulmonary, 245–250 description of, 1–2 renal, 265 anatomy of, 250–251 cardiac output and, 250–254 hemodynamics of, 252–254 skeletal muscle, 240–243 regulation of, 240–243 splanchnic, 254–257, 265 systemic, 1–2, 245–250 Circulatory system, at birth, 259–260 CO See Cardiac output Compensatory pause, after premature ventricular depolarization, 49 Complete atrioventricular block, 38–39, 38f, 39b bradycardia and, 215b Compliance aortic, 139 arterial, 145–146 Conditioning, 269 Conductance, hydraulic, 127 Conduction and local circuit currents, 25 atrial, 36 atrioventricular node, 37–39 in right bundle branch, 39–40 ventricular, 39–41 Conduction system, 36, 36f Conduction velocity, 26 Congenital cardiac defects, 214b Congestive heart failure, 218b, 256b–257b arterial pulse pressure in, 145b description of, 75b Connexins, 25 Connexons, 58 Conservation of mass, 141 Contractility cardiac function curve and, 197–198 definition of, 78 drugs that affect, 78 heart rate affected by changes in, 107–110 hypoxia effects on, 115 myocardial, 209 norepinephrine effects on, 113, 114f sympathetic nervous system effects on, 110–112 thyroid hormones’ effect on, 114–115 ventricular function curve and, 106–107 Contraction action potential and, 172 atrial, 73 calcium and, 63 catecholamines’ effect on, 65 force of, 63–69 frequency of, 107 isovolumic, 70 skeletal muscle, 182 strength of, 109 velocity of, 69 Coronary artery disease, 27b Coronary artery occlusion, 226b acute, 233b Coronary atherosclerosis, 230b Coronary blood flow cardiac function and, 230–231 coronary collateral vessel development and, 233–234 metabolic factors, 228–230 neural factors of, 225–228 neurohumoral factors of, 225–228 physical factors of, 225–227 Coronary bypass surgery, 233b Coronary collateral vessel, development of, coronary blood flow and, 233–234 Coronary steal, 234b Coronary vessels, 223–224, 224f Corticomedullary junction, 250 Countercurrent exchange, 163, 254 Counterpulsation, 226b Coupled extrasystoles, 48 Coupling interval, 109, 113–114 Creatinine phospholipase (CPIC) equation, 81 Crista dividens, 258 Current calcium diastolic depolarization affected by, 34 inward, 107–108 inward hyperpolarization-induced, 34 transient, 44 potassium, 34 Cushing phenomenon, 245b Cutaneous circulation, 237–240 Cv See Venous compliance Cyclic adenosine monophosphate (cAMP) dependent protein kinase (PKA), 96f description of, 21–22, 95 prostacyclin effects on, 156 Cyclic guanosine monophosphate (cGMP), 34 cGMP-dependent protein kinase, 157 D DADs See Delayed afterdepolarizations Delayed afterdepolarizations (DADs), 43–44 Delayed rectifier potassium channels, 23 Denervation hypersensitivity, 238–239 Dependent variable, 200, 208 Depolarizations description of, 11–12 diastolic, 34 premature atrial, 41, 48, 49f premature ventricular, 48, 49f Depressor area, 183 Depressor effect, 185–186 Diacylglycerol, 178 Diastasis, 73 Diastole calcium removal during, 65 definition of, ventricular, 73 Diastolic depolarization, 34 Diastolic pressure arterial, 146–147 ausculatory method for measuring, 149–150 schematic diagram of, 141f Diffusion of lipid-insoluble molecules, 159–162 water and soluble transfer across endothelium by, 159, 161 Diffusion-limited transport, 162, 162f Digitalis, electrogenic pump affected by, 15 Dihydropyridine receptor, 63–64 Diltiazem, 22f, 23 2,3-Diphosphoglycerate, 7f Dipyridamole, 232 Dissecting aneurysm, 129b Dorsal motor nucleus of vagus, 92 Ductus arteriosus, 258 Ductus venosus, 257–258 Dysrhythmias atrioventricular block See Atrioventricular block definition of, 47 fibrillation, 49–51 premature depolarizations, 48–49 respiratory, 99–100 sinoatrial node rhythm alterations, 47–48 tachycardia See Tachycardia E EADs See Early afterdepolarizations Early afterdepolarizations (EADs), 43 Ectopic foci, 32b Ectopic pacemakers, 32b Edema, 168 pulmonary, 213b–214b EDRF See Endothelium-derived relaxing factor Effective refractory period, 17–18, 27 Einthoven triangle, 45, 46f Ejection rapid, 71 reduced, 71 Ejection fraction, 78, 112 Elastic modulus, 140 Electric shock, for fibrillation, 51 Electrocardiogram configuration of, 37f limb leads for, 45–47 P wave, 37, 45 PR interval, 45 premature atrial depolarization, 48, 49f QRS complex, 37, 45 scalar, 44–47 of supraventricular tachycardia, 50f T wave, 45 of ventricular tachycardia, 50f INDEX Electrocardiography, 44–47 benefits of, 44 scalar, 44–47 Electrogenic pump, 15 Electromechanical coupling, 179 Elephantiasis, 167b Emphysema, 247b End-diastolic pressure, 106 End-diastolic ventricular volume, 106 Endogenous vasoconstrictors, in hemorrhage, 272–273 β-Endorphin, 275 Endothelin, 157, 281 Endothelium blood flow regulation by, 180–181 lipid-soluble molecules across, 162–163 permeability of, 158–159 solute transfer across, 159, 161 water transfer across, 159, 161 Endothelium-derived relaxing factor (EDRF), 157, 157f Energy substrate metabolism, during myocardial ischemia, 231–233 Enkephalins, 275 Eosinophils, 6f Epinephrine, 185–189, 272 Equilibrium point, 208 Equilibrium potentials potassium, 14 sodium, 14 Erythroblast, 8f Erythroblastosis fetalis, 5–6, 8b, 8f Erythrocytes aggregation of, 131 deformability of, 131 description of, 5–6 diameter of, 131 fibrinogen concentration effects on, 131 lifespan of, morphology of, 6f production of, Erythropoiesis, Erythropoietin, Esophageal varices, 256b–257b Essential hypertension, 72b, 130b Excitation-contraction coupling calcium mediation of, 63–69 description of, 21 in vascular smooth muscle, 176 Exercise, 264–269, 281 arterial pressure increase during, 267–268 cardiac output increase in, 266–267 conditioning, 269 mild to moderate, 264–268 performance limits, 269 peripheral resistance declines during, 264–266 physical training, 269 postexercise recovery, 268–269 severe, 268 venous return enhanced in, 267 Extracoronary resistance, 225–226 Extrasystole, 43–44 Extravascular compression, 225–226 F F waves, 50 Fahraeus-Lindqvist phenomenon, 131 Fast response action potential changes to slow response, 13b conduction of, 25–27 description of, 12, 12f effective refractory period for, 27 excitability affected by, 27–28 voltage-dependent sodium channels and, 15–24 Fast sodium channels description of, 16 m gates in, 16 Fatty acid metabolism, 83–86 Febrile infectious diseases, 34b Fenestrations, 158f, 159 Fetal circulation, 257–260 Fetal oxyhemoglobin dissociation curve, 258 Fibrillation, 49–51 atrial, 50, 50f definition of, 49–50 description of, 41 electric shock treatment of, 51 mechanism of, 51 ventricular, 50–51, 50f, 220b Fibrinogen, 131 Fick principle, 79f for oxygen consumption, 80 Fick’s law of diffusion, 159 Filariasis, 167b Filling pressure, of heart, 196 Filtration, 165 Filtration coefficient, 165–167 First heart sound, 74, 74f First-degree atrioventricular block, 38, 38f, 39b Flow equation for, 119 laminar, 122, 123f, 127–128 Poiseuille’s law, 122, 125 pressure and, 122–125 resistance to, 125–127 steady, 122 streamlined, 127–128 turbulent, 128 velocity and, 119, 120f volume, 119 Foot protein, 63–64 Foramen ovale, 258 Force, 66–68 Fourth heart sound, 75 Frank-Starling mechanism cardiac output and, 106 history of, 103–104 in intact preparations, 106–107 premature beats and, 109 representation of, 106–107 Free radicals, Frictional resistance, Functional cardiac murmurs, 128b Functional hyperemia, 256 G Gallop rhythms, 75b Gamma globulins, 287 Gap junctions description of, 25, 58 histology of, 57f in intercalated disks, 57f, 58, 59f Gastrin, 256 GFR See Glomerular filtration rate Gibbs-Donnan effect, 164 Globin definition of, diseases caused by changes in, 5–6 Glomerular filtration rate (GFR), 252–253 Glomeruli, 250–251 Glucagon, 115 Glucose fatty acid cycle, 85 Glucose uptake, regulation of, 84 Glycocalyx, 63–64, 161 Glycolysis, regulation of, 84 G-protein-coupled receptor (GPCR), 96 Graves disease, 2b Gravity, cardiac output and, 216–218, 281 Guanylyl cyclase, 157, 157f H h gate, 16–18 H2 fields of Forel, 97 Heart anatomy of, 1–2 apex of, 60–62 conduction system of, 36, 36f filling pressure of, 196 function of, description of, 171 hypodynamic, 78, 78f mean electrical axis of, 46–47 pericardium of, 63 preload of, 196 sodium requirements of, 63 vasculature and, 207–211 Heart failure, 211b acute, 211b chronic, 106b, 211b congestive, 218b, 256b–257b arterial pulse pressure in, 145b atrial natriuretic peptide levels, 99b description of, 75b left, 247b right, 213, 214b Heart rate bleeding effects on, 99f blood transfusion effects on, 99f cardiac adaptation to alterations in, 105–106 cardiac output and, 214–216 chemoreceptor reflex effects on, 101–102 conditions that affect, 34b contractile force affected by changes in, 107–110 definition of, 91 hypothalamus influences on, 97 intrinsic, 92 lung stretch receptors’ effect on, 100 mean arterial pressure and, 97f normal, 91 peripheral chemoreceptor stimulation effects on, 101–102, 102f regulation of 288 INDEX Heart rate (Continued) autonomic nervous system, 112–113 Bainbridge reflex, 98–99 baroreceptor reflex, 97–98 overview of, 91 parasympathetic pathways, 92–93 sympathetic pathways, 93–97 ventricular receptor reflexes’ role in, 102 during sleep, 91 Heart sounds, 74–75, 74f Hematocrit ratio, 102f, 107, 130f Heme, Hemoglobin description of, iron moiety of, oxygen affinity for, oxygen bound, skin color and, 240 Hemoglobin S, 5–6 Hemorrhage, 269–276 arterial blood pressure and, 270 arterial pressure in, 166b arterial pulse pressure in, 145b compensatory mechanisms, 270–273 baroreceptor reflexes, 270–272 cerebral ischemia, 272 chemoreceptor reflexes, 272 endogenous vasoconstrictors, 272–273 renal conservation of salt and water, 273 tissue fluid reabsorption, 272 decompensatory mechanisms, 273–275 acidosis, 274 blood clotting aberrations, 275 cardiac failure, 274 central nervous system depression, 274–275 reticuloendothelial system depression, 275 positive and negative feedback mechanisms interact, 275–276 Hemorrhagic shock, 270 description of, 185 Heparin, 275 Hepatic acinus, 256 Hepatic arterial system, 256 Hepatic artery, 256 Hepatic circulation, 256–257 anatomy of, 256 blood flow regulation, 256–257 hemodynamics, 256 Hepatic cirrhosis, 256b–257b Homeostasis, Hormones adrenocortical, 113–114 adrenomedullary, 113 myocardial performance affected by, 113–116 thyroid, 114–115 Humoral immunity, H-V interval, 48 Hydraulic conductance, 127 Hydraulic filtering, 135–137 Hydraulic resistance definition of, 125 in parallel, 126–127 in series, 126–127 Hydraulic resistance equation, 125 Hydrogen peroxide, Hydrostatic forces capillary filtration regulated by, 163 disturbances in, 166–167 osmotic forces and, balance between, 163–165 Hydrostatic pressure, 163–165, 218, 282 Hypercapnia, 189 Hyperpolarization, acetylcholine-induced, 35, 35f Hypertension, 218b characteristics of, 147b chronic, 147b description, 129b Hyperthyroidism, 115b Hypervolemia, 205 Hypotension, 226b, 267 orthostatic, 218b postural, 188b Hypothalamus, 190 Hypothyroidism, 115b Hypovolemia, 205 Hypovolemic shock, 248b Hypoxia high altitude and, 7b hypercapnia and, 189 I Idioventricular pacemakers, 32 Immunity, Impulse initiation, 47 Impulse propagation, 47 Inactivation, of fast sodium channels, 16, 18–19 Inactivation gate, 16 Incisura, 147 Independent variable, 200, 208 Indicator dilution technique, for cardiac output measurements, 80–81, 80f Inferior mesenteric artery, 254 Inflow pressure, 123 Inositol 1,4,5-trisphosphate IP3, 175, 177f smooth muscle receptor, 175, 175f Insulin, 115 Insulin levels, effects of, 86 Integrins, 158 Interlobar branches, 250 Interlobular branches, 250–251 Intermittent claudication, 243b Interstitial fluid (ISF) accumulation of, 167b description of, 164–165 Interventricular septum, 61f Intestinal blood flow, 256 Intestinal circulation, 254–256 anatomy of, 254 autoregulation, 254 neural regulation, 254 Intravascular pressure, 179 Intrinsic heart rate, 92 Inwardly rectified potassium current, 23 Inwardly rectifying potassium channels, 13–14 Ion channels, 13 Ischemia, description of, 13b, 230b Isoelectric line, 45 Isometric contraction, 70 Isoproterenol, 21–22, 94 Isovolumetric contraction, 70 Isovolumetric relaxation, 73 J Junctional processes, 63–64 Juxtamedullary glomeruli, 251 K Kidneys, blood flow in See Renal circulation Korotkoff sounds, 149–150 L Lactate oxidation, regulation of, 84–85 Laminar flow, 122, 123f, 127–128 Laplace equation, 155 Laplace relationship, 106 Lateral pressure, 120 Law of conservation of mass, 141 Law of Laplace, 155–156 Left anterior hemiblock, 40b Left atrium, 36f Left auricular appendage, 61f Left bundle branch, 39–40, 40f Left heart failure, 247b Left posterior hemiblock, 40b Left vagus nerve, 92 Left ventricle, 212, 225–226 anatomy of, 36f, 62 description of, 1–2 endocardial surface of, 41 pressure in, 226 ventricular systole effects on, 72 Left ventricular afterload, 212 Left ventricular failure, 213b–214b Left ventricular preload, 213 Less pressure work, 265 Leukocytes, 6–7 Leukotrienes, 275 Limb leads, for electrocardiogram, 45–47 Linear velocity, 119 Lipid-insoluble molecules, 159–162 Lipid-soluble molecules, 162–163 Local anesthetics, 16 Long QT syndrome, 24b Loop diuretic, 279 L-type calcium channels, 21 Lymphatic system, 167–168 Lymphocytes, 5, 6f Lysosomes, M m gate, 16 Macula densa, 253 Maximal dP/dt, 78 Mayer waves, 183–184 Mean arterial pressure, 140–141, 280 definition of, 140 representation of, 97f, 141f Mean circulatory pressure, 202 Mean electrical axis, 46–47 Mechanical restitution curve, 109 INDEX Medulla cardiovascular activity affected by, 183–184 depressor area of, 183 parahypoglossal area of, 97 pressor region of, 183 Megakaryocytes, Megaloblastic anemia, 8f Membrane resting potential, 12f, 13 Membranous septum, 61f Metabolic vasodilators, 264 Metamyelocytes, 6f Metarterioles, 153–154 Microcirculation endothelium’s role in regulation of, 156–157 schematic diagram of, 154f Microcytic, hypochromic anemia, 5–6, 8f Middle cervical ganglia, 93 Mitral insufficiency, 75b Mitral stenosis, 75b murmur and, 279 Mitral valve, 61f, 62 Monocytes, 5, 6f Monokines, 275 Müller maneuver, 219 Murmur, 281 mitral stenosis and, 279 Murmurs, 128b Muscarinic receptors, 228 acetylcholine interactions with, 112 antagonist of, 92 Muscular activity, venous valves and, 218–219 Myocardial cells, 55–60, 110–111 Myocardial compliance, cardiac function curve and, 198–199 Myocardial contractility, 209 Myocardial fibers, Frank-Starling mechanism See Frank-Starling mechanism Myocardial hibernation, 233b Myocardial infarction, 205b Myocardial ischemia, 230b energy substrate metabolism during, 231–233 Myocardial oxygen consumption, 137, 139f Myocardial performance acidosis effects on, 115 blood gases that affect, 115 carbon dioxide effects on, 115 hormones that regulate adrenocortical, 113–114 adrenomedullary, 113 insulin, 115 thyroid, 114–115 intrinsic mechanisms that regulate, 102–110 nervous system control of baroreceptor reflex, 112–113 parasympathetic, 112 sympathetic, 110–112 oxygen effects on, 115–116 Myocardial stunning, 232, 233b Myocardium capillaries in, 58–60 vagus nerve effects on, 112 Myoendothelial junctions, 172 Myofibrils, 56f–57f Myofilaments, 104–105 Myogenic mechanism, 179, 253 Myosin, 55–58 N Na+,K+-ATPase description of, 15, 27b overdrive suppression and, 35–36 Natural pacemaker, 31 Negative feedback mechanism, 270 Negative inotropic agents, 22b Nernst equation, 15–16, 279 Neuropeptide Y, 94f, 95 Neurovascular coupling, 244–245 Neutral proteases, 275 Neutrophils, 6f Newtonian fluids description of, 122, 124 viscosity of, 129 Nitric oxide (NO) arterioles affected by, 182 description of, 157 vasodilation caused by, 181 Nitric oxide synthase, 182 Nitroprusside, 179 NO See Nitric oxide Nonnewtonian fluids, 124 Norepinephrine, 272 cardiac cycle-related release of, 95 contractility affected by, 21–22, 113, 114f description of, 183–184 sympathetic nerve release of, 110–111, 279 Normovolemia, 205 Nucleus ambiguus, 92 Nucleus of the tractus solitarius, 185–186 Nutritional flow, 154–155 O Oncotic pressure, 164–165 Opioids, 275 Opsonic protein, 275 Orthostatic hypotension, 188b, 218b Osmotic forces capillary filtration regulated by, 163 disturbances in, 166–167 hydrostatic forces and, balance between, 163–165 Osmotic pressure, 163 Outflow pressure, 123 Overdrive suppression, 35–36 Overshoot, 15–17 Oxygen cardiac muscle requirements of, 71f hemoglobin binding to, myocardial performance affected by, 115 Oxygen bound hemoglobin, skin color and, 240 Oxygen consumption determination of, 80 Fick principle for, 80 myocardial, 137, 139f Oxygen free radicals, 275 Oxyhemoglobin, Oxyhemoglobin dissociation curve, 7f, 266 P 289 P wave, 37, 45 Pacemaker ectopic, 32b natural, 31 spontaneous activity of, 279 Pacemaker cells automaticity of, 35 discharge frequency of, 33, 33f overdrive suppression, 35–36 Pacemaker fibers, 33 Pacemaker potential, 33 Pacemaker shift, 33 Palpatory method, 149 Papillary muscles, 61f Parasympathetic nervous system blood vessels innervated by, 185 heart rate regulation by, 92–93 myocardial performance affected by, 112 Parasystole, 48 Paroxysmal supraventricular tachycardia, 49, 50f Paroxysmal tachycardia, 31–32 Paroxysmal ventricular tachycardia, 49, 105f Peak velocity, 121, 121f Pericardium definition of, 63 pressure-volume relationship and, 106 Peripheral blood flow description of, 171 endothelial regulation of, 180–181 extrinsic factors involved in description of, 183–191 intrinsic factors and, 191–192 intrinsic factors involved in description of, 179–183 extrinsic factors and, 191–192 myogenic mechanism effects on, 179–180 Peripheral chemoreceptors description of, 189 heart rate affected by, 101–102, 102f Peripheral resistance, 200 aortic baroreceptors’ effect on, 186 carotid sinus effects on, 186–187 description of, 142 total, 4, 146–147 vascular function curve affected by, 206–207, 210–211 Peripheral runoff, 141, 143f, 202 Peritubular capillaries, 251 Permeability of cell membranes, 13 Phagocytosis, Pharmacomechanical coupling, 176 Phasic pressure, 4f Phonocardiogram, 74, 74f Phosphodiesterase, 96f Phospholamban, 65, 110–111 Phospholipase C, 178 Physical training, 269 Physiological shunting, 154–155 Pinocytosis, 158–159, 167 Pitot tubes, 120 Plasma cells, Plasma proteins description of, 164 lymphatic system return of, 168 290 INDEX Plasma substrate, effects of, 86 Plasma transfusion, 280 Plateau phase calcium conductance during, 21–23, 21f, 63–64, 108 definition of, 11–12 early afterdepolarizations at end of, 43 genesis of, 20 potassium conductance during, 22–23 Platelets morphology of, 6f prostacyclin effects on, 156 Pluripotential stem, Poiseuille equation, 216 Poiseuille’s law, 122, 125, 165 Polycythemia, 7b, 130b Portacaval shunt, 256b–257b Portal vein, 256 Portal venous system, 256 Portal-caval shunt, 280 Positive feedback mechanisms, 273 Positive inotropic effect, 77–78 Postcapillary resistance, 256 Postexercise recovery, 268–269 Postextrasystolic potentiation, 109 Postganglionic gray branches, 183 Postganglionic nerves, 95 Postganglionic neurons, 93 Postganglionic sympathetic fibers, 183 Postrepolarization refractoriness, 28 Postsinusoidal, 256 Postural hypotension, 188b Potassium conductance of, during plateau phase, 22–23 extracellular concentration of, 63 Potassium channels, 279 acetylcholine-regulated, 95 delayed rectifier, 23 description of, 13–14 inwardly rectifying, 13–14 Potassium equilibrium potentials, 14 P-P interval, 47–48, 279 PR interval, 45, 279 Precapillary resistance, 165, 256 Precordial leads, 47 Preganglionic neurons, 93 Preganglionic white fibers, 183 Preload description of, 66–69 of heart, 196 left ventricular, 213 Premature atrial depolarizations, 41, 48, 49f Premature beats Frank-Starling mechanism and, 109 weakness of, 109 Premature depolarizations, 31–32 Premature ventricular depolarization, 48, 49f Premature ventricular systole, 109 Presinusoidal, 256 Pressor effect, 185–186 Pressor region, 183 Pressure equation for, 122 flow and, 122–125, 138f inflow, 123 outflow, 123 Pressure drop, 2, 4f Pressure gradient, 120–121 Pressure-volume loop, 77 Pressure-volume relationships, 75–79 active, 77 diastolic, 75–77 end-systolic, 77 passive, 75–77 Principle of “conservation of mass,”, 202 Propranolol, 92, 94 Prostacyclin, 156 Prostaglandins, 182, 275 Pulmonary artery wedge pressure, 247b Pulmonary blood flow, 247–249 Pulmonary circulation, 245–250 description of, 1–2 pressures in, 247 regulation of, 249–250 Pulmonary edema, 213b–214b Pulmonary embolism, 247b Pulmonary hemodynamics, 247–249 Pulmonary reflexes, 191 Pulmonary veins, 61f, 247 Pulmonic valve, 61f Pulsatile arterial blood flow, Pulse, 149–150, 279 Pulse pressure aortic, 139–140, 141f arterial, 144 arterial compliance effects on, 145 blood pressure and, 144 schematic diagram of, 141f stroke volume and, 141f Pump, 200 auxiliary, 219–220 Purkinje fibers action potentials from, 40–41, 44f anatomy of, 39–40, 40f automaticity properties of, 32, 35, 279 definition of, 39–40 description of, 12 Pyruvate oxidative, regulation of, 84–85 Q QRS complex, 37, 45 QT interval, 45, 279 long QT syndrome, 24b R Radial pulse, 149 Rapid ejection, 71 Rapid filling phase, 71f, 73 Rate of change of potential, 26 Rate-pressure product, 87 Raynaud’s disease, 240b Reactive hyperemia, 182f, 183, 239 Reentry bidirectional block, 41 conditions necessary for, 41 definition of, 41 unidirectional block, 41–42, 42f Reflection coefficient, 161–163 Refractory period effective, 17–18, 27 relative, 27 Relative hematocrit, 131 Relative refractory period, 27 Renal artery, 250 Renal circulation, 265 anatomy of, 250–251 cardiac output and, 250–254 Renal conservation, of salt and water, 273 Renal hemodynamics, 252 blood flow, 252 circulation, 252–254 autoregulation, 252–253 neural regulation, 253–254 segmental resistance, 252 Renin, 189, 273 Renin-angiotensin system, 253 Repolarization definition of, 11–12 early, 20 final, 23 Residual volume, 72 Resistance arteriolar, 163 blood flow, 125 definition of, 125 to flow, 125–127 hydraulic, 125 peripheral aortic baroreceptors’ effect on, 188 carotid sinus effect on, 188 description of, 142 total, 146–147 precapillary, 165 total peripheral, 146–147 Resistance vessels, 171 constriction, 184 description of, 153, 171 epinephrine effects on, 185 hemorrhage shock effects on, 185 sympathetic nerves’ regulation f, 184–185 Respiratory activity, cardiac output and, 219–220 Respiratory cardiac dysrhythmia, 99–100 Resting cell membrane, 13 Resting membrane potential, level of, 26 Resultant cardiac vector, 45 Reticulocytes, 8f Reticuloendothelial system, depression of, in hemorrhage, 275 Retrograde impulse, 41–42 Reynolds’s number, 128 Rh-negative, 7–8 Rh-positive, 7–8 Rhythmicity, 31 Right atrial pressure, description of, 104 Right atrium, 36f Right auricular appendage, 61f Right bundle branch, 39–40, 40f Right heart failure, 213, 214b Right vagus nerve, 92 Right ventricle anatomy of, 36f, 62 blood flow in, 1–2 blood flow regulation and, 211–214 central venous pressure and, 211–214 endocardial surface of, 41 INDEX Right ventricular ejection, 71–72 Ryanodine receptors, 63–64, 175f S SA See Sinoatrial node Sarcolemma, 56f Sarcomeres, definition of, 55–58 Sarcoplasmic reticulum adenosine triphosphate hydrolysis by, 114 anatomy of, 56f, 59f, 60 systolic calcium uptake by, 78 Scalar electrocardiography, 44–47 Scalar quantities, 44–45 Second heart sound, 74, 74f Second-degree atrioventricular block, 38, 38f, 39b Semilunar valves anatomy of, 61f, 62 ejection phase, 74 Severe exercise, 268 Shear rate, 124–125 Shear stress on blood vessel wall, 128–129 definition of, 124–125 Shear thinning, 131 Shock electric, for fibrillation, 51 hemorrhagic, 270 Shunting, physiological, 154–155 Sick sinus syndrome, 36b bradycardia and, 215b Sickle cell anemia, 5–6, 8f, 132b Sinoaortic baroreceptors, 273 Sinoatrial (SA) node, 32–34 anatomy of, 32, 32f cardiac ganglion cells in, 92 cells of, 32 cholinesterase in, 92–93 description of, 11–12 rhythm alterations, 47–48 slow response in, 27 tonic influence of, 91–92 transmembrane potential from, 32, 34f Sinus bradycardia, 47–48, 47f Sinus rhythm, 47f Sinus tachycardia, 47f Sinuses of Valsalva, 62 Skeletal muscle circulation, 240–243 regulation of, 240–243 fast, 58 Skin blood flow to ambient temperature and, 239–240 body temperature and, 239–240, 281 skin color and, 240 sympathetic nervous system and, 237–239 color of O2 bound hemoglobin, 240 skin blood flow and, 240 description of, 191 temperature of, 281 Slow diastolic depolarization, 35 Slow response, excitability affected by, 28 Slow response action potential in atrioventricular node N region, 37–38 conduction of, 27 description of, 12, 12f fast responses changed to, 13b ionic basis of, 24–25 relative refractory period during, 28 Smooth muscle skeletal muscle vs., 172–174 vascular cells of, 172 contractile state of, 181–182 cross-sectional image of, 173f description of, 172 Smooth muscle pump, 175f Sodium cardiac glycosides’ effect on, 65 heart requirements for, 63 transmembrane movement of, 16 Sodium-calcium exchange (NCX) cardiac muscle, 64f vascular smooth muscle, 175f, 176 Sodium channels, 279 current flow through, 20f fast, 16, 25–27 gating of, 16, 18f structure of, 17f Sodium equilibrium potentials, 14 Solutes endothelial transfer of, 159, 161 movement of, 161 Spherocytic anemia, 132b Sphygmomanometer, 148–150, 149f Splanchnic circulation, 254–257, 265 Split sound, 75 Staircase phenomenon, 107 Starling hypothesis, 165 Static pressure, 120, 202 Static pressure-volume relationship, 139 Steady flow, 122 Stem cells, erythrocytes from, Stokes-Adams attacks, 39b Streamlined flow, 127–128 Stretch receptors, 273 Stroke volume arterial compliance and, 145–146 changes in, 144f definition of, 104 pulse pressure and, 144–145 Superior mesenteric artery, 254 Supraventricular tachycardia, 215b description of, 42b paroxysmal, 49, 50f Sympathetic nerves, section of, 184–185 Sympathetic nervous system heart rate regulation, 93–97 myocardial performance affected by, 110–112 skin blood flow and, 237–239 vasoconstrictor fibers of, 184 Systemic circulation, 1–2, 245–250 Systole atrial, 73 calcium, 63–65 definition of, ventricular 291 Systole (Continued) description of, 69–73 premature, 109 Systolic pressure ausculatory method for measuring, 149–150 description of, 141f, 144 T T lymphocytes, T wave, 45 Tachycardia diastasis during, 73 ectopic, 49 paroxysmal, 31–32, 49 sinus, 47f supraventricular, 215b description, 42b paroxysmal, 49, 50f ventricular, 215b paroxysmal, 49, 50f Temperature ambient, skin blood flow and, 239–240 body, skin blood flow and, 239–240 of skin, 281 Terminal arterioles, 3f, 154 Tetrodotoxin action potential affected by, 13b, 13f, 16 sinoatrial node and, 32–33 Thalassemia, 5–6 Thebesian vessel, 223–224 Thermodilution, 81 Third heart sound, 75 Third-degree atrioventricular block, 38–39, 38f, 39b Thoracic duct, 168 Threshold, 15–16 Threshold potential, 16–17 Thrombi, 128b, 275 Thromboangitis obliterans, tobacco and, 280 Thromboxanes, 275 Thyroid hormones, 114–115 Tissue fluid, reabsorption of, in hemorrhage, 272 Tissue pressure, 163 Titin, 68–69 Tobacco, thromboangitis obliterans and, 280 Tone, definition of, 171 Total peripheral resistance, 146–147 Total pressure, 120 Transient inward current, 44 Transient outward current, 20 Transmembrane potential from atrioventricular node, 39f potassium effects on, 14 from sinoatrial node, 32, 34f sodium effects on, 14 vagal stimulus effect on, 35f Transmural pressure, 154, 249 Transverse tubules, 56f–57f, 58–60, 59f–60f Traube-Hering waves, 183–184 Treppe phenomenon, 107 Tricuspid valve, 61f, 62 292 INDEX Trigger calcium, 63–64 Triggered activity, 65–69 T-type calcium channel, 21 Tubuloglomerular feedback, 253 Turbulent flow, 128 U U tube, 216 Universal donors, 7–8 Universal recipients, 7–8 Upstroke of action potential, 11–12, 15–19 V v wave, 72 Vagus nerve, myocardial performance affected by, 112, 280 Valsalva maneuver, 220 Varicose veins, 219b, 242b Vasa recta, 251 Vascular endothelial growth factors (VEGFs), 167, 234 Vascular function curve (VFC), 196 blood volume and, 205–206, 209–210 central venous pressure and cardiac output, 200–207 mechanical analysis of, 203–205 peripheral resistance and, 206–207, 210–211 Vascular reflexes, blood pressure affected by, 185–189 Vascular resistance, epinephrine effects on, 185 Vascular smooth muscle cells of, 172 contractile state of, 181–182 cross-sectional image of, 173f description of, 172 Vascular system, bronchial, 246–247 Vasoconstriction, epinephrine-induced, 185 Vasoconstrictor tone, 191 Vasodilation interstitial fluid osmolarity as cause of, 182 mediators of, 182 Vasodilation (Continued) metabolites produced by, 181, 280 vascular resistance controlled by, 182–183 Vasomotion, 154 Vasopressin, 98, 273 Vasovagal syncope, 102b VEGFs See Vascular endothelial growth factors (VEGFs) Veins See also specific vein characteristics of, 3f Velocity flow and, 119, 120f linear, 119 peak, 121, 121f Venae cavae characteristics of, 3f cross-sectional area of, Venoconstriction, 270 Venomotor tone, 206 Venous compliance (Cv), 200 Venous pooling, 217 Venous pressure, cardiac output and, 205 Venous return, cardiac output and, 207 Venous valves, muscular activity and, 218–219 Ventricles anatomy of, 60–62 left See Left ventricle right See Right ventricle volume changes in, 104–105 Ventricular conduction, 39–41 Ventricular diastole, 73 Ventricular ejection, 62 Ventricular fibrillation, 50–51, 50f, 220b Ventricular filling, rapid phase, 71f, 73 Ventricular function curves, 106–107 Ventricular hypertrophy, 47b Ventricular receptors, 102b Ventricular systole description, 70–73 premature, 109 Ventricular tachycardia, 215b paroxysmal, 49, 105f Venules, 3f Vessels See also Blood vessels arterioluminal, 223–224 arteriosinusoidal, 223–224 coronary, 223–224, 224f coronary collateral, 233–234 thebesian, 223–224 VFC See Vascular function curve Viscosity anomalous, 129 apparent, 129 of blood, 129, 130f definition of, 124 dimensions of, 125 for newtonian fluid, 129 of plasma, 129–130 Viscous drag, 129 Voltage clamping, 14 Voltage-dependent phenomenon, 16–17 Voltage-dependent sodium channels description of, 16 fast response action potential affected by, 15–24 schematic diagram of, 17f Voltage-gated calcium channels, 21f, 176 Volume flow, 119 Vulnerable period, 51 W Wall thickness, 155 Waterfall effect, 248–249 Wedge pressure, 279 Windkessel, 135 Wolff-Parkinson-White syndrome, 42b Z Z line anatomy of, 55–58, 56f electrical stimulation, 63–64 Zero cardiac output, 205 ... Physiology KOEPPEN & STANTON: Renal Physiology PAPPANO & WIER: Cardiovascular Physiology WHITE & PORTERFIELD: Endocrine and Reproduction Physiology Cardiovascular Physiology TENTH EDITION ACHILLES J PAPPANO,... Cataloging-in-Publication Data Pappano, Achilles J Cardiovascular physiology / Achilles J Pappano, Withrow Gil Wier 10th ed p ; cm (Mosby physiology monograph series) Rev ed of: Cardiovascular physiology / Matthew... (pbk.) I Wier, Withrow Gil II Levy, Matthew N., 1922- Cardiovascular physiology III Title IV Series: Mosby physiology monograph series [DNLM: Cardiovascular Physiological Phenomena WG 102] 612.1