(BQ) Part 1 book Cardiovascular physiology presents the following contents: Overview of the circulation and blood, excitation - The cardiac action potential, automaticity - Natural excitation of the heart, the cardiac pump, regulation of the heartbeat, hemodynamics.
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 158 132 CARDIOVASCULAR PHYSIOLOGY Hmicro/Hsys Arterial Venous 1.0 0.8 FIGURE 6-16 n The hematocrit ratio (Hmicro) of the blood in various-sized arterial and venous microvessels in the cat mesentery, relative to the hematocrit ratio (Hsys) in the large systemic vessels The hematocrit ratio is least in the capillaries and tiny venules. (Modified from Lipowsky HH, Usami S, Chien S: In vivo measurements of “apparent viscosity” and microvessel hematocrit in the mesentery of the cat Microvasc Res 19:297, 1980.) 0.6 70 60 50 40 30 20 10 10 20 30 40 50 60 70 Vessel diameter (µm) CLINICAL BOX Viscosity (cp) If the red blood cells become hardened, as they are in certain spherocytic anemias, shear thinning may become much less prominent When erythrocytes are extremely deformed, especially in sickle cell anemia, they tend to aggregate and completely block flow in small vessels; the tissues supplied by those vessels frequently become infarcted 60 120 180 240 Shear rate/s FIGURE 6-17 n Decrease in the viscosity of blood (in centipoise) at increasing rates of shear The shear rate refers to the velocity of one layer of fluid relative to that of the adjacent layers and is directionally related to the rate of flow. (Redrawn from Amin TM, Sirs JA: The blood rheology of man and various animal species Q J Exp Physiol 70:37, 1985.) HEMODYNAMICS 133 Erythrocyte flexibility (% min−1) 0 Fibrinogen concentration (mg/mL) FIGURE 6-18 n The effect of the plasma fibrinogen concen- tration on the flexibility of human erythrocytes. (Redrawn from Amin TM, Sirs JA: The blood rheology of man and various animal species Q J Exp Physiol 70:37, 1985.) S U M M A R Y n n n n n he vascular system is composed of two major subT divisions in series with each other—the systemic circulation and the pulmonary circulation Each subdivision consists of several types of vessels (e.g., arteries, arterioles, capillaries) aligned in series with one another In general, the vessels of a given type are arranged in parallel with each other The mean velocity ( v ) of blood flow in a given type of vessel is directly proportional to the total blood flow (Qt) being pumped by the heart, and it is inversely proportional to the cross-sectional area (A) of all the parallel vessels of that type; i.e., v = Qt / A The laterally directed pressure in the bloodstream decreases as the flow velocity increases; the decrement in lateral pressure is proportional to the square of the velocity When blood flow is steady and laminar in vessels larger than arterioles, the flow (Q) is proportional to the pressure drop down the vessel (Pi − Po) and to the fourth power of the radius (r), and it is inversely proportional to the length (l) of the vessel and to the n n n n viscosity (η) of the fluid; i.e., Q = π(Pi − Po)r4/8ηl (Poiseuille’s law) For resistances aligned in series, the total resistance equals the sum of the individual resistances For resistances aligned in parallel, the reciprocal of the total resistance equals the sum of the reciprocals of the individual resistances Flow tends to become turbulent when flow velocity is high, when fluid viscosity is low, when tube diameter is large, or when the wall of the vessel is very irregular Blood flow is nonnewtonian in very small vessels; i.e., Poiseuille’s law is not applicable The apparent viscosity of blood diminishes as shear rate (flow) increases and as the tube dimensions decrease ADDITIONAL READING Baskurt OK, Meiselman HJ: Blood rheology and hemodynamics, Semin Thromb Hemost 29:435, 2003 Cecchi E, Gigioli C, Valente S, et al: Role of hemodynamic shear stress in cardiovascular disease, Atheroclerosis 214:249, 2011 Chiu J-J, Chien S: Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives, Physiol Rev 91:327, 2011 134 CARDIOVASCULAR PHYSIOLOGY Helmke BP: Molecular control of cytoskeletal mechanics by hemodynamic forces, Physiology 20:43, 2005 Hoeks APG, Samijo SK, Brands PJ, et al: Noninvasive determination of shear-rate distribution across the arterial wall, Hypertension 26:26, 1995 Kwaan HC, Wang J: Hyperviscosity in polycythemia vera and other red cell abnormalities, Semin Thromb Hemost 29:451, 2003 Long DS, Smith ML, Pries A, et al: Microviscometry reveals reduced blood viscosity and altered shear rate and shear stress profiles in microvessels after hemodilution, Proc Natl Acad Sci U S A 101:10060, 2004 McCue S, Noria S, Langille BL: Shear-induced reorganization of endothelial cell cytoskeleton and adhesion complexes, Trends Cardiovasc Med 14:143, 2004 Pries AR, Secomb TW: Microvascular blood viscosity in vivo and the endothelial surface layer, Am J Physiol 289:H2657, 2005 Pries AR, Secomb TW, Gaetgens P: Design principles of vascular beds, Circ Res 77:1017, 1995 Resnick N, Yahav H, Shay-Salit A, et al: Fluid shear stress and the vascular endothelium: for better and for worse, Prog Biophys Mol Biol 81:177, 2003 Tyml K, Anderson D, Lidington D, Ladak HM: A new method for assessing arteriolar diameter and hemodynamic resistance using image analysis of vessel lumen, Am J Physiol 284:H1721, 2003 CASE 6-6 HISTORY A 70-year-old man complained of severe pain in his right leg whenever he walked briskly; the pain disappeared soon after he stopped walking His doctor referred him to a vascular surgeon, who carried out several hemodynamic tests Angiography showed partial obstruction by large arteriosclerotic plaques about cm distal to the origin of the right femoral artery The left femoral artery appeared to be normal The mean arterial pressure in the left femoral artery with the patient at rest was 100 mm Hg, and the blood flow in this artery was 500 mL/min The mean arterial pressure in the right femoral artery proximal to the obstruction was 100 mm Hg, and just distal to the obstruction, it was 80 mm Hg The blood flow in this artery was 300 mL/min The mean venous pressure was 10 mm Hg in the left and right femoral veins QUESTIONS The resistance to blood flow in the vascular bed perfused by the right femoral artery was: a 0.03 mm Hg/mL/min b 0.30 mm Hg/mL/min c 3.00 mm Hg/mL/min d 3.33 mm Hg/mL/min e 33.3 mm Hg/mL/min The resistance to blood flow (Rt) in the combined vascular beds perfused by both femoral arteries was: a 0.48 mm Hg/mL/min b 0.84 mm Hg/mL/min c 1.10 mm Hg/mL/min d 0.11 mm Hg/mL/min e 11.1 mm Hg/mL/min The resistance to flow imposed by the arteriosclerotic obstruction in the right femoral artery amounted to: a 0.066 mm Hg/mL/min b 0.660 mm Hg/mL/min c 0.15 mm Hg/mL/min d 1.50 mm Hg/mL/min e 15.0 mm Hg/mL/min ... Substances 11 3 Summary 11 6 Case 5 -1 11 7 CHAPTER HEMODYNAMICS 11 9 Velocity of the Bloodstream Depends on Blood Flow and Vascular Area 11 9 Blood Flow Depends on the Pressure Gradient 12 0... and Cardiac Output 216 Gravity 216 Muscular Activity and Venous Valves 218 Respiratory Activity 219 Artificial Respiration 220 Summary 2 21 Case 10 -1 2 21 CHAPTER 11 CORONARY CIRCULATION... imprint of Elsevier Inc Copyright © 2007, 20 01, 19 97, 19 92, 19 86, 19 81, 19 77, 19 72, 19 67 by Mosby, Inc., an affiliate of Elsevier Inc All rights reserved No part of this publication may be reproduced