28,99 €
Mehr erfahren.
- Herausgeber: John Wiley & Sons
- Kategorie: Fachliteratur
- Serie: At a Glance
- Sprache: Englisch
This concise and accessible text provides an integrated overview of the cardiovascular system - considering the basic sciences which underpin the system and applying this knowledge to clinical practice and therapeutics. A general introduction to the cardiovascular system is followed by chapters on key topics such as anatomy and histology, blood and body fluids, biochemistry, excitation-contraction coupling, form and function, integration and regulation, pathology and therapeutics, clinical examination and investigation - all supported by clinical cases for self-assessment. Highly visual colour illustrations complement the text and consolidate learning.
The Cardiovascular System at a Glance is the perfect introduction and revision aid to understanding the heart and circulation and now also features:
- An additional chapter on pulmonary hypertension
- Even more simplified illustrations to aid easier understanding
- Reorganized and revised chapters for greater clarity
- Brand new and updated clinical case studies illustrating clinical relevance and for self-assessment
The fourth edition of The Cardiovascular System at a Glance is an ideal resource for medical students, whilst students of other health professions and specialist cardiology nurses will also find it invaluable. Examination candidates who need an authoritative, concise, and clinically relevant guide to the cardiovascular system will find it extremely useful.
A companion website featuring cases from this and previous editions, along with additional summary revision aids, is available at www.ataglanceseries.com/cardiovascular.
Sie lesen das E-Book in den Legimi-Apps auf:
Seitenzahl: 403
Veröffentlichungsjahr: 2012
Ähnliche
Table of Contents
Cover
Companion website
Title page
Copyright page
Preface
Recommended reading
Acknowledgements
List of abbreviations
Introduction
1 Overview of the cardiovascular system
Blood vessel functions
Anatomy and histology
2 Gross anatomy and histology of the heart
Gross anatomy of the heart
Structure of the myocardium
Coronary circulation
3 Vascular anatomy
The systemic circulation
The pulmonary circulation
The splanchnic circulation
The lymphatic system
4 Vascular histology and smooth muscle cell ultrastructure
Exchange vessel structure
Smooth muscle cell ultrastructure
Blood and body fluids
5 Constituents of blood
Plasma
Blood cells
6 Erythropoiesis, haemoglobin and anaemia
Erythropoiesis
Haemoglobin
Anaemia
7 Haemostasis
Primary haemostasis
Formation of the blood clot
Inhibitors of haemostasis and fibrinolysis
Defects in haemostasis
8 Thrombosis and anticoagulants
Thrombosis
Antiplatelet drugs
Anticoagulant drugs
Some laboratory investigations
9 Blood groups and transfusions
Blood groups
Complications of blood transfusions
Blood storage
Cellular physiology
10 Membrane potential, ion channels and pumps
Resting membrane potential
Ion channels and gating
Ion pumps and exchangers
Ion pumps and membrane potential
11 Electrophysiology of cardiac muscle and origin of the heart beat
Ventricular muscle action potential
Role of Na+–Ca2+ exchange
Sinoatrial node
Other regions of the heart
12 Cardiac muscle excitation–contraction coupling
Initiation of contraction
Generation of tension
Relaxation mechanisms
Regulation of contractility
Influence of heart rate
13 Electrical conduction system in the heart
Electrical conduction in cardiac muscle
Conduction pathways in the heart
Abnormalities of impulse generation or conduction
14 The electrocardiogram
Recording the ECG
General features of the ECG
Basic interpretation of the ECG
15 Vascular smooth muscle excitation–contraction coupling
Regulation of contraction by Ca2+ and myosin phosphorylation
Vasoconstricting mechanisms
Ca2+ removal and vasodilator mechanisms
Form and function
16 Cardiac cycle
17 Control of cardiac output
Ventricular function curves
Role of Starling’s law
The autonomic nervous system
Vascular function curves and Guyton’s analysis
18 Haemodynamics
Relationships between pressure, resistance and flow
Blood viscosity
Laminar flow
Wall tension
19 Blood pressure and flow in the arteries and arterioles
Factors controlling arterial blood pressure
Blood pressure and flow in the arteries
Arterioles and vascular resistance
20 The microcirculation and lymphatic system, and diapedesis
Organization of the microcirculation
Movement of solutes across the capillary wall
The blood–brain barrier
Diapedesis
The lymphatic system
21 Fluid filtration in the microcirculation
Movement of water across the capillary wall
Water filtration and absorption
Pulmonary and systemic oedema
22 The venous system
Venous arterial compliance
The veins as capacitance vessels
Effects of posture
23 Local control of blood flow
Autoregulation
Metabolic and reactive hyperaemia
Metabolic factors
Other local mechanisms
24 Regulation of the vasculature by the endothelium
Nitric oxide
Other endothelium-derived relaxing mechanisms
Endothelium-derived constricting factors
Endothelium in cardiovascular disease
25 The coronary, cutaneous and cerebral circulations
Coronary circulation
Cutaneous circulation
Cerebral circulation
26 The pulmonary, skeletal muscle and fetal circulations
The pulmonary circulation
The skeletal muscle circulation
The fetal circulation
Circulatory changes at birth
Integration and regulation
27 Cardiovascular reflexes
Intrinsic cardiovascular reflexes
Extrinsic reflexes
Central regulation of cardiovascular reflexes
28 Autonomic control of the cardiovascular system
The sympathetic system
The parasympathetic system
29 The control of blood volume
Role of sodium and osmoregulation
Control of Na+ and blood volume by the kidneys
Antidiuretic hormone in volume regulation
30 Cardiovascular effects of exercise
Effects of exercise on plasma volume
Regulation and coordination of the cardiovascular adaptation to exercise
Effects of training
31 Shock and haemorrhage
Haemorrhagic shock
Other types of hypovolaemic shock
Low-resistance shock
History, examination and investigations
32 History and examination of the cardiovascular system
History
Examination
33 Cardiovascular investigations
X-rays (chest radiography)
Echocardiography and Doppler ultrasound
Catheterization and angiography
Imaging
Pathology and therapeutics
34 Risk factors for cardiovascular disease
Modifiable risk factors
Fixed risk factors
35 β-Blockers, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and Ca2+ channel blockers
β-Adrenoceptor antagonists (β-blockers)
Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers
Ca2+ channel blockers
36 Hyperlipidaemias
Lipoproteins and lipid transport
Hyperlipidaemias: types and treatments
37 Atherosclerosis
Pathogenesis of atherosclerosis
Oxidized low-density lipoprotein, macrophages and atherogenesis
Clinical consequences of advanced atherosclerosis
38 Treatment of hypertension
39 Mechanisms of primary hypertension
The kidney and sodium in hypertension
Neurogenic and humoral theories of hypertension
Vascular remodelling
Secondary hypertension
Consequences of hypertension
40 Stable and variant angina
Pathophysiology
Diagnosis
Prognosis
Management
41 Pharmacological management of stable and variant angina
Anti-anginals
β-Adrenergic receptor blockers
Ca2+-channel blockers (also Ca2+ antagonists)
Nitrovasodilators
Other anti-anginals
Management of variant angina
Drugs for secondary prevention of cardiovascular disease
42 Acute coronary syndromes: Unstable angina and non-ST segment elevation myocardial infarction
Pathophysiology of UA/NSTEMI
Risk stratification
Management
43 Revascularization
Revascularization vs medical management: which patients benefit?
PCI vs CABG
Benefits of revascularization
44 Pathophysiology of acute myocardial infarction
Role of thrombosis in MI
Mechanisms and consequences of plaque rupture
Evolution of the infarct
45 Acute coronary syndromes: ST segment elevation myocardial infarction
Symptoms and signs
Investigations
Management
Complications of acute myocardial infarction
46 Heart failure
Causes of heart failure
Pathophysiology
47 Treatment of chronic heart failure
ACEI and other vasodilators
β-Receptor blockers
Aldosterone antagonists
Diuretics
Cardiac glycosides
48 Mechanisms of arrhythmia
Disorders of impulse generation: latent pacemakers and triggered automaticity
Abnormal impulse conduction: re-entry
The sympathetic nervous system and arrhythmias
49 Supraventricular tachyarrhythmias
50 Ventricular tachyarrhythmias and non-pharmacological treatment of arrhythmias
Specific ventricular tachyarrhythmias
Non-pharmacological treatment for arrhythmias
51 Pharmacological treatment of arrhythmias
Class I drugs
Class II drugs
Class III drugs
Class IV drugs, adenosine and digoxin
52 Pulmonary hypertension
Types of pulmonary hypertension
Pulmonary arterial hypertension
53 Diseases of the aortic valve
Aortic stenosis
Aortic regurgitation
54 Diseases of the mitral valve
Mitral stenosis
Mitral regurgitation
55 Genetic and congenital heart disease
Hypertrophic obstructive cardiomyopathy
Channelopathies
Congenital heart disease
Self-assessment
Case studies and questions
Case studies answers
Index
This new edition is also available as an e-book.
For more details, please see www.wiley.com/buy/9780470655948 or scan this QR code:
Companion website
A companion website is available at:
www.ataglanceseries.com/cardiovascular
featuring:
• Case Studies from this and previous editions
• Key points for revision
This edition first published 2013 © 2013 by John Wiley & Sons, Ltd
Previous editions 1999, 2004, 2007
Blackwell Publishing was acquired by John Wiley & Sons in February 2007. Blackwell’s publishing program has been merged with Wiley’s global Scientific, Technical and Medical business to form Wiley-Blackwell.
Registered office: John Wiley & Sons, Ltd, The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK
Editorial offices: 9600 Garsington Road, Oxford, OX4 2DQ, UK
The Atrium, Southern Gate, Chichester, West Sussex, PO19 8SQ, UK
350 Main Street, Malden, MA 02148-5020, USA
For details of our global editorial offices, for customer services and for information about how to apply for permission to reuse the copyright material in this book please see our website at www.wiley.com/wiley-blackwell.
The right of the authors to be identified as the authors of this work has been asserted in accordance with the UK Copyright, Designs and Patents Act 1988.
All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by the UK Copyright, Designs and Patents Act 1988, without the prior permission of the publisher.
Designations used by companies to distinguish their products are often claimed as trademarks. All brand names and product names used in this book are trade names, service marks, trademarks or registered trademarks of their respective owners. The publisher is not associated with any product or vendor mentioned in this book. This publication is designed to provide accurate and authoritative information in regard to the subject matter covered. It is sold on the understanding that the publisher is not engaged in rendering professional services. If professional advice or other expert assistance is required, the services of a competent professional should be sought.
Library of Congress Cataloging-in-Publication Data
Aaronson, Philip I. (Philip Irving), 1953–
The cardiovascular system at a glance / Philip I. Aaronson, Jeremy P.T. Ward, Michelle J. Connolly. – 4th ed.
p. cm.
Includes bibliographical references and index.
ISBN 978-0-470-65594-8 (pbk. : alk. paper) 1. Cardiovascular system–Physiology. 2. Cardiovascular system–Pathophysiology. I. Ward, Jeremy P. T. II. Connolly, Michelle J. III. Title.
QP101.C293 2013
612.1–dc23
2012024674
A catalogue record for this book is available from the British Library.
Cover image: Getty images
Cover design by Meaden Creative
Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic books.
Preface
This book is designed to present a concise description of the cardiovascular system which integrates normal structure and function with pathophysiology, pharmacology and therapeutics. We therefore cover in an accessible yet comprehensive manner all of the topics that preclinical medical students and biomedical science students are likely to encounter when they are learning about the cardiovascular system. However, our aims in writing and revising this book have always been more ambitious – we have also sought to provide to our readers a straightforward description of many fascinating and important topics that are neglected or covered only superficially by many other textbooks and most university and medical courses. We hope that this book will not only inform you about the cardiovascular system, but enthuse you to look more deeply into at least some of its many remarkable aspects.
In addition to making substantial revisions designed to update the topics, address reviewers’ criticisms and simplify some of the diagrams, we have added a new chapter on pulmonary hypertension for this fourth edition and written eight entirely new self-assessment case studies, each drawing on encounters with real patients.
Philip I. AaronsonJeremy P.T. WardMichelle J. Connolly
Recommended reading
Bonow R.O., Mann D.L., Zipes D.P. & Libby P. (Eds) (2011) Braunwald’s Heart Disease: A Textbook of Cardiovascular Medicine, 9th edition. Elsevier Health Sciences.
Levick J.R. (2010) An Introduction to Cardiovascular Physiology, 5th edition. Hodder Arnold.
Lilly L.S. (Ed). (2010) Pathophysiology of Heart Disease: A Collaborative Project of Medical Students and Faculty, 5th edition. Lippincott Williams and Wilkins.
Acknowledgements
We are most grateful to Dr Daniela Sergi, consultant in acute medicine at North Middlesex University Hospital NHS Trust, and Dr Paul E. Pfeffer, specialist registrar and clinical research fellow at Guy’s and St Thomas’ NHS Foundation Trust for reviewing the clinical chapters and case studies.
We would also like to thank Professor Horst Olschewski and Dr Gabor Kovacs, internationally renowned experts on pulmonary hypertension at the Ludwig Boltzmann Institute for Lung Vascular Research at the Medical University of Graz, Austria, for writing the new case study on pulmonary arterial hypertension.
We are grateful to Karen Moore for her assistance in keeping track of our progress, putting up so gracefully with our missed deadlines, and generally making sure that this book and its companion website not only became a reality, but did so on schedule. Finally, as always, we thank our readers, particularly our students at King’s College London, whose support over the years has encouraged us to keep trying to make this book better.
List of abbreviations
5-HT
5-hydroxytryptamine (serotonin)
AAA
abdominal aortic aneurysm
ABP
arterial blood pressure
AC
adenylate cyclase
ACE
angiotensin-converting enzyme
ACEI
angiotensin-converting enzyme inhibitor/s
ACS
acute coronary syndromes
ADH
antidiuretic hormone
ADMA
asymmetrical dimethyl arginine
ADP
adenosine diphosphate
AF
atrial fibrillation
AMP
adenosine monophosphate
ANP
atrial natriuretic peptide
ANS
autonomic nervous system
AP
action potential
APAH
pulmonary hypertension associated with other conditions
APC
active protein C
APD
action potential duration
aPTT
activated partial thromboplastin time
AR
aortic regurgitation
ARB
angiotensin II receptor blocker
ARDS
acute respiratory distress syndrome
AS
aortic stenosis
ASD
atrial septal defect
ATP
adenosine triphosphate
AV
atrioventricular
AVA
arteriovenous anastomosis
AVN
atrioventricular node
AVNRT
atrioventricular nodal re-entrant tachycardia
AVRT
atrioventricular re-entrant tachycardia
BBB
blood–brain barrier
BP
blood pressure
CABG
coronary artery bypass grafting
CAD
coronary artery disease
CaM
calmodulin
cAMP
cyclic adenosine monophosphate
CCB
calcium-channel blocker
CE
cholesteryl ester
CETP
cholesteryl ester transfer protein
CFU-E
colony-forming unit erythroid cell
cGMP
cyclic guanosine monophosphate
CHD
congenital heart disease
CHD
coronary heart disease
CHF
chronic heart failure
CICR
calcium-induced calcium release
CK-MB
creatine kinase MB
CNS
central nervous system
CO
cardiac output
COPD
chronic obstructive pulmonary disease
COX
cyclooxygenase
CPVT
catecholaminergic polymorphic ventricular tachycardia
CRP
C-reactive protein
CSF
cerebrospinal fluid
CT
computed tomography
CTPA
computed tomography pulmonary angiogram
CVD
cardiovascular disease
CVP
central venous pressure
CXR
chest X-ray
DAD
delayed afterdepolarization
DAG
diacylglycerol
DBP
diastolic blood pressure
DC
direct current
DHP
dihydropyridine
DIC
disseminated intravascular coagulation
DM2
type 2 diabetes mellitus
DVT
deep venous/vein thrombosis
EAD
early afterdepolarization
ECF
extracellular fluid
ECG
electrocardiogram/electrocardiograph (EKG)
ECM
extracellular matrix
EDHF
endothelium-derived hyperpolarizing factor
EDP
end-diastolic pressure
EDRF
endothelium-derived relaxing factor
EDTA
ethylenediaminetetraacetic acid
EDV
end-diastolic volume
EET
epoxyeicosatrienoic acid
EnaC
epithelial sodium channel
eNOS
endothelial NOS
ERP
effective refractory period
ESR
erythrocyte sedimentation rate
FDP
fibrin degradation product
GP
glycoprotein
GPI
glycoprotein inhibitor
GTN
glyceryl trinitrate
Hb
haemoglobin
HCM
hypertrophic cardiomyopathy
HDL
high-density lipoprotein
HEET
hydroxyeicosatetraenoic acid
HMG-CoA
hydroxy-methylglutanyl coenzyme A
hPAH
heritable pulmonary arterial hypertension
HPV
hypoxic pulmonary vasoconstriction
HR
heart rate
ICD
implantable cardioverter defibrillator
IDL
intermediate-density lipoprotein
Ig
immunoglobulin
IML
intermediolateral
iNOS
inducible NOS
INR
international normalized ratio
IP
3
inisotol 1,4,5-triphosphate
iPAH
idiopathic pulmonary arterial hypertension
ISH
isolated systolic hypertension
JVP
jugular venous pressure
LA
left atrium
LDL
low-density lipoprotein
LITA
left internal thoracic artery
LMWH
low molecular weight heparin
L-NAME
L-nitro arginine methyl ester
LPL
lipoprotein lipase
LQT
long QT
LV
left ventricle/left ventricular
LVH
left ventricular hypertrophy
MABP
mean arterial blood pressure
MCH
mean cell haemoglobin
MCHC
mean cell haemoglobin concentration
MCV
mean cell volume
MI
myocardial infarction
MLCK
myosin light-chain kinase
mPAP
mean pressure in the pulmonary artery
MR
mitral regurgitation
MRI
magnetic resonance imaging
MS
mitral stenosis
MW
molecular weight
NCX
Na
+
–Ca
2+
exchanger
NK
natural killer
NO
nitric oxide
NOS
nitric oxide synthase
nNOS
neuronal nitric oxide synthase
NSAID
non-steroidal anti-inflammatory drug
NSCC
non-selective cation channel
NSTEMI
non-ST segment elevation myocardial infarction
NTS
nucleus tractus solitarius
NYHA
New York Heart Association
PA
postero-anterior
PA
pulmonary artery
PAH
pulmonary arterial hypertension
PAI-1
plasminogen activator inhibitor-1
PCI
percutaneous coronary intervention
PCV
packed cell volume
PD
potential difference
PDA
patent ductus arteriosus
PDE
phosphodiesterase
PE
pulmonary embolism
PGE
2
prostaglandin E
2
PGl
2
prostacyclin
PH
pulmonary hypertension
PI3K
phosphatidylinositol 3-kinase
PKA
protein kinase A
PKC
protein kinase C
PKG
cyclic GMP-dependent protein kinase
PLD
phospholipid
PMCA
plasma membrane Ca
2+
-ATPase
PMN
polymorphonuclear leucocyte
PND
paroxysmal nocturnal dyspnoea
PPAR
proliferator-activated receptor
PRU
peripheral resistance unit
PT
prothrombin time
PTCA
percutaneous transcoronary angioplasty
PVC
premature ventricular contraction
PVR
pulmonary vascular resistance
RAA
renin–angiotensin–aldosterone
RCA
radiofrequency catheter ablation
RCC
red cell count
RGC
receptor-gated channel
RMP
resting membrane potential
RV
right ventricle/right ventricular
RVLM
rostral ventrolateral medulla
RVOT
right ventricular outflow tract tachycardia
RyR
ryanodine receptor
SAN
sinoatrial node
SERCA
smooth endoplasmic reticulum Ca
2+
-ATPase
SHO
senior house officer
SK
streptokinase
SMTC
S-methyl-L-thiocitrulline
SOC
store-operated Ca
2+
channel
SPECT
single photon emission computed tomography
SR
sarcoplasmic reticulum
STEMI
ST elevation myocardial infarction
SV
stroke volume
SVR
systemic vascular resistance
SVT
supraventricular tachycardia
TAFI
thrombin activated fibrinolysis inhibitor
TAVI
transcatheter aortic valve implantation
TB
tuberculosis
TEE
transthoracic echocardiogram
TF
tissue factor thromboplastin
TFPI
tissue factor pathway inhibitor
TGF
transforming growth factor
TOE
transoesophageal echocardiography/echocardiogram
tPA
tissue plasminogen activator
TPR
total peripheral resistance
TRP
transient receptor potential
TXA
2
thromboxane A
2
UA
unstable angina
uPA
urokinase
VF
ventricular fibrillation
VGC
voltage-gated channel
VLDL
very low density lipoprotein
VSD
ventricular septal defect
VSM
vascular smooth muscle
VT
ventricular tachycardia
VTE
venous thromboembolism
vWF
von Willebrand factor
WBCC
white blood cell count
WPW
Wolff–Parkinson–White
1
Overview of the Cardiovascular System
The cardiovascular system is composed of the heart, blood vessels and blood. In simple terms, its main functions are:
Blood is composed of plasma, an aqueous solution containing electrolytes, proteins and other molecules, in which cells are suspended. The cells comprise 40–45% of blood volume and are mainly erythrocytes, but also white blood cells and platelets. Blood volume is about 5.5 L in an ‘average’ 70-kg man.
Figure 1 illustrates the ‘plumbing’ of the cardiovascular system.
Blood is driven through the cardiovascular system by the heart, a muscular pump divided into left and right sides. Each side contains two chambers, an atrium and a ventricle, composed mainly of cardiac muscle cells. The thin-walled atria serve to fill or ‘prime’ the thick-walled ventricles, which when full constrict forcefully, creating a pressure head that drives the blood out into the body. Blood enters and leaves each chamber of the heart through separate one-way valves, which open and close reciprocally (i.e. one closes before the other opens) to ensure that flow is unidirectional.
Consider the flow of blood, starting with its exit from the left ventricle.
When the ventricles contract, the left ventricular internal pressure rises from 0 to 120 mmHg (atmospheric pressure = 0). As the pressure rises, the aortic valve opens and blood is expelled into the aorta, the first and largest artery of the systemic circulation. This period of ventricular contraction is termed systole. The maximal pressure during systole is called the systolic pressure, and it serves both to drive blood through the aorta and to distend the aorta, which is quite elastic. The aortic valve then closes, and the left ventricle relaxes so that it can be refilled with blood from the left atrium via the mitral valve. The period of relaxation is called diastole. During diastole aortic blood flow and pressure diminish but do not fall to zero, because elastic recoil of the aorta continues to exert a diastolic pressure on the blood, which gradually falls to a minimum level of about 80 mmHg. The difference between systolic and diastolic pressures is termed the pulse pressure. Mean arterial blood pressure (MABP) is pressure averaged over the entire cardiac cycle. Because the heart spends approximately 60% of the cardiac cycle in diastole, the MABP is approximately equal to the diastolic pressure + one-third of the pulse pressure, rather than to the arithmetic average of the systolic and diastolic pressures.
The blood flows from the aorta into the major arteries, each of which supplies blood to an organ or body region. These arteries divide and subdivide into smaller muscular arteries, which eventually give rise to the arterioles – arteries with diameters of <100 µm. Blood enters the arterioles at a mean pressure of about 60–70 mmHg.
The walls of the arteries and arterioles have circumferentially arranged layers of smooth muscle cells. The lumen of the entire vascular system is lined by a monolayer of endothelial cells. These cells secrete vasoactive substances and serve as a barrier, restricting and controlling the movement of fluid, molecules and cells into and out of the vasculature.
The arterioles lead to the smallest vessels, the capillaries, which form a dense network within all body tissues. The capillary wall is a layer of overlapping endothelial cells, with no smooth muscle cells. The pressure in the capillaries ranges from about 25 mmHg on the arterial side to 15 mmHg at the venous end. The capillaries converge into small venules, which also have thin walls of mainly endothelial cells. The venules merge into larger venules, with an increasing content of smooth muscle cells as they widen. These then converge to become veins, which progressively join to give rise to the superior and inferior venae cavae, through which blood returns to the right side of the heart. Veins have a larger diameter than arteries, and thus offer relatively little resistance to flow. The small pressure gradient between venules (15 mmHg) and the venae cavae (0 mmHg) is therefore sufficient to drive blood back to the heart.
Blood from the venae cavae enters the right atrium, and then the right ventricle through the tricuspid valve. Contraction of the right ventricle, simultaneous with that of the left ventricle, forces blood through the pulmonary valve into the pulmonary artery, which progressively subdivides to form the arteries, arterioles and capillaries of the pulmonary circulation. The pulmonary circulation is shorter and has a much lower pressure than the systemic circulation, with systolic and diastolic pressures of about 25 and 10 mmHg, respectively. The pulmonary capillary network within the lungs surrounds the alveoli of the lungs, allowing exchange of CO2 for O2. Oxygenated blood enters pulmonary venules and veins, and then the left atrium, which pumps it into the left ventricle for the next systemic cycle.
The output of the right ventricle is slightly lower than that of the left ventricle. This is because 1–2% of the systemic blood flow never reaches the right atrium, but is shunted to the left side of the heart via the bronchial circulation (Figure 1) and a small fraction of coronary blood flow drains into the thebesian veins (see Chapter 2).
Blood Vessel Functions
Each vessel type has important functions in addition to being a conduit for blood.
The branching system of elastic and muscular arteries progressively reduces the pulsations in blood pressure and flow imposed by the intermittent ventricular contractions.
The smallest arteries and arterioles have a crucial role in regulating the amount of blood flowing to the tissues by dilating or constricting. This function is regulated by the sympathetic nervous system, and factors generated locally in tissues. These vessels are referred to as resistance arteries, because their constriction resists the flow of blood.
Capillaries and small venules are the exchange vessels. Through their walls, gases, fluids and molecules are transferred between blood and tissues. White blood cells can also pass through the venule walls to fight infection in the tissues.
Venules can constrict to offer resistance to the blood flow, and the ratio of arteriolar and venular resistance exerts an important influence on the movement of fluid between capillaries and tissues, thereby affecting blood volume.
The veins are thin walled and very distensible, and therefore contain about 70% of all blood in the cardiovascular system. The arteries contain just 17% of total blood volume. Veins and venules thus serve as volume reservoirs, which can shift blood from the peripheral circulation into the heart and arteries by constricting. In doing so, they can help to increase the cardiac output (volume of blood pumped by the heart per unit time), and they are also able to maintain the blood pressure and tissue perfusion in essential organs if haemorrhage (blood loss) occurs.
2
Gross Anatomy and Histology of the Heart
Gross Anatomy of the Heart (Figure 2a)
The heart consists of four chambers. Blood flows into the right atrium via the superior and inferior venae cavae. The left and right atria connect to the ventricles via the mitral (two cusps) and tricuspid (three cusps) atrioventricular (AV) valves, respectively. The AV valves are passive and close when the ventricular pressure exceeds that in the atrium. They are prevented from being everted into the atria during systole by fine cords (chordae tendineae) attached between the free margins of the cusps and the papillary muscles, which contract during systole. The outflow from the right ventricle passes through the pulmonary semilunar valve to the pulmonary artery, and that from the left ventricle enters the aorta via the aortic semilunar valve. These valves close passively at the end of systole, when ventricular pressure falls below that of the arteries. Both semilunar valves have three cusps.
The cusps or leaflets of the cardiac valves are formed of fibrous connective tissue, covered in a thin layer of cells similar to and contiguous with the endocardium (AV valves and ventricular surface of semilunar valves) and endothelium (vascular side of semilunar valves). When closed, the cusps form a tight seal (come to apposition) at the commissures (line at which the edges of the leaflets meet).
The atria and ventricles are separated by a band of fibrous connective tissue called the annulus fibrosus, which provides a skeleton for attachment of the muscle and insertion of the valves. It also prevents electrical conduction between the atria and ventricles except at the atrioventricular node (AVN). This is situated near the interatrial septum and the mouth of the coronary sinus and is an important element of the cardiac electrical conduction system (see Chapter 13).
The ventricles fill during diastole; at the initiation of the heart beat the atria contract and complete ventricular filling. As the ventricles contract the pressure rises sharply, closing the AV valves. When ventricular pressure exceeds the pulmonary artery or aortic pressure, the semilunar valves open and ejection occurs (see Chapter 16). As systole ends and ventricular pressure falls, the semilunar valves are closed by backflow of blood from the arteries.
The force of contraction is generated by the muscle of the heart, the myocardium. The atrial walls are thin. The greater pressure generated by the left ventricle compared with the right is reflected by its greater wall thickness. The inside of the heart is covered in a thin layer of cells called the endocardium, which is similar to the endothelium of blood vessels. The outer surface of the myocardium is covered by the epicardium, a layer of mesothelial cells. The whole heart is enclosed in the pericardium, a thin fibrous sheath or sac, which prevents excessive enlargement. The pericardial space contains interstitial fluid as a lubricant.
Structure of the Myocardium
The myocardium consists of cardiac myocytes (muscle cells) that show a striated subcellular structure, although they are less organized than skeletal muscle. The cells are relatively small (100 × 20 µm) and branched, with a single nucleus, and are rich in mitochondria. They are connected together as a network by intercalated discs (Figure 2b), where the cell membranes are closely opposed. The intercalated discs provide both a structural attachment by ‘glueing’ the cells together at desmosomes, and an electrical connection through gap junctions formed of pores made up of proteins called connexons. As a result, the myocardium acts as a functional syncytium, in other words as a single functional unit, even though the individual cells are still separate. The gap junctions play a vital part in conduction of the electrical impulse through the myocardium (see Chapter 13).
The myocytes contain actin and myosin filaments which form the contractile apparatus, and exhibit the classic M and Z lines and A, H and I bands (Figure 2c). The intercalated discs always coincide with a Z line, as it is here that the actin filaments are anchored to the cytoskeleton. At the Z lines the sarcolemma (cell membrane) forms tubular invaginations into the cells known as the transverse (T) tubular system. The sarcoplasmic reticulum (SR) is less extensive than in skeletal muscle, and runs generally in parallel with the length of the cell (Figure 2d). Close to the T tubules the SR forms terminal cisternae that with the T tubule make up diads (Figure 2e), an important component of excitation–contraction coupling (see Chapter 12). The typical triad seen in skeletal muscle is less often present. The T tubules and SR never physically join, but are separated by a narrow gap. The myocardium has an extensive system of capillaries.
Coronary Circulation (Figure 2f)
The heart has a rich blood supply, derived from the left and right coronary arteries. These arise separately from the aortic sinus at the base of the aorta, behind the cusps of the aortic valve. They are not blocked by the cusps during systole because of eddy currents, and remain patent throughout the cardiac cycle. The right coronary artery runs forward between the pulmonary trunk and right atrium, to the AV sulcus. As it descends to the lower margin of the heart, it divides to posterior descending and right marginal branches. The left coronary artery runs behind the pulmonary trunk and forward between it and the left atrium. It divides into the circumflex, left marginal and anterior descending branches. There are anastomoses between the left and right marginal branches, and the anterior and posterior descending arteries, although these are not sufficient to maintain perfusion if one side of the coronary circulation is occluded.
Most of the blood returns to the right atrium via the coronary sinus, and anterior cardiac veins. The large and small coronary veins run parallel to the left and right coronary arteries, respectively, and empty into the sinus. Numerous other small vessels empty into the cardiac chambers directly, including thebesian veins and arteriosinusoidal vessels.
The coronary circulation is capable of developing a good collateral system in ischaemic heart disease, when a branch or branches are occluded by, for example, atheromatous plaques. Most of the left ventricle is supplied by the left coronary artery, and occlusion can therefore be very dangerous. The AVN and sinus node are supplied by the right coronary artery in the majority of people; disease in this artery can cause a slow heart rate and AV block (see Chapters 13 and 14).
3
Vascular Anatomy
The blood vessels of the cardiovascular system are for convenience of description classified into arteries (elastic and muscular), resistance vessels (small arteries and arterioles), capillaries, venules and veins. Typical dimensions for the different types of vessel are illustrated.
The Systemic Circulation
Arteries
The systemic (or greater) circulation begins with the pumping of blood by the left ventricle into the largest artery, the aorta. This ascends from the top of the heart, bends downward at the aortic arch and descends just anterior to the spinal column. The aorta bifurcates into the left and right iliac arteries, which supply the pelvis and legs. The major arteries supplying the head, the arms and the heart arise from the aortic arch, and the main arteries supplying the visceral organs branch from the descending aorta. All of the major organs except the liver (see below) are therefore supplied with blood by arteries that arise from the aorta. The fundamentally parallel organization of the systemic vasculature has a number of advantages over the alternative series arrangement, in which blood would flow sequentially through one organ after another. The parallel arrangement of the vascular system ensures that the supply of blood to each organ is relatively independent, is driven by a large pressure head, and also that each organ receives highly oxygenated blood.
The aorta and its major branches (brachiocephalic, common carotid, subclavian and common iliac arteries) are termed elastic arteries. In addition to conducting blood away from the heart, these arteries distend during systole and recoil during diastole, damping the pulse wave and evening out the discontinuous flow of blood created by the heart’s intermittent pumping action.
Elastic arteries branch to give rise to muscular arteries with relatively thicker walls; this prevents their collapse when joints bend. The muscular arteries give rise to resistance vessels, so named because they present the greatest part of the resistance of the vasculature to the flow of blood. These are sometimes subclassified into small arteries, which have multiple layers of smooth muscle cells in their walls, and arterioles, which have one or two layers of smooth muscle cells. Resistance vessels have the highest wall to lumen ratio in the vasculature. The degree of constriction or tone of these vessels regulates the amount of blood flowing to each small area of tissue. All but the smallest resistance vessels tend to be heavily innervated (especially in the splanchnic, renal and cutaneous vasculatures) by the sympathetic nervous system, the activity of which usually causes them to constrict (see Chapter 28).
Arterial Anastomoses
In addition to branching to give rise to smaller vessels, arteries and arterioles may also merge to form anastomoses. These are found in many circulations (e.g. the brain, mesentery, uterus, around joints) and provide an alternative supply of blood if one artery is blocked. If this occurs, the anastamosing artery gradually enlarges, providing a collateral circulation.
The smallest arterioles, capillaries and postcapillary venules comprise the microcirculation, the structure and function of which is described in Chapters 20 and 21.
Veins
The venous system can be divided into the venules, which contain one or two layers of smooth muscle cells, and the veins. The veins of the limbs, particularly the legs, contain paired semilunar valves which ensure that the blood cannot move backwards. These are orientated so that they are pressed against the venous wall when the blood is flowing forward, but are forced out to occlude the lumen when the blood flow reverses.
The veins from the head, neck and arms come together to form the superior vena cava, and those from the lower part of the body merge into the inferior vena cava. These deliver blood to the right atrium, which pumps it into the right ventricle.
The one or two veins draining a body region typically run next to the artery supplying that region. This promotes heat conservation, because at low temperatures the warmer arterial blood gives up its heat to the cooler venous blood, rather than to the external environment. The pulsations of the artery caused by the heart beat also aid the venous flow of blood.
The Pulmonary Circulation
The pulmonary (or lesser) circulation begins when blood is pumped by the right ventricle into the main pulmonary artery, which immediately bifurcates into the right and left pulmonary arteries supplying each lung. This ‘venous’ blood is oxygenated during its passage through the pulmonary capillaries. It then returns to the heart via the pulmonary veins to the left atrium, which pumps it into the left ventricle. The metabolic demands of the lungs are not met by the pulmonary circulation, but by the bronchial circulation. This arises from the intercostal arteries, which branch from the aorta. Most of the veins of the bronchial circulation terminate in the right atrium, but some drain into the pulmonary veins (see Chapter 26).
The Splanchnic Circulation
The arrangement of the splanchnic circulation (liver and digestive organs) is a partial exception to the parallel organization of the systemic vasculature (see Figure 1). Although a fraction of the blood supply to the liver is provided by the hepatic artery, the liver receives most (approximately 70%) of its blood via the portal vein. This vessel carries venous blood that has passed through the capillary beds of the stomach, spleen, pancreas and intestine. Most of the liver’s circulation is therefore in series with that of the digestive organs. This arrangement facilitates hepatic uptake of nutrients and detoxification of foreign substances that have been absorbed during digestion. This type of sequential perfusion of two capillary beds is referred to as a portal circulation. A somewhat different type of portal circulation is also found within the kidney.
The Lymphatic System
The body contains a parallel circulatory system of lymphatic vessels and nodes (see Chapter 20). The lymphatic system functions to return to the cardiovascular system the approximately 8 L/day of interstitial fluid that leaves the exchange vessels to enter body tissues. The larger lymphatic vessels pass through nodes containing lymphocytes, which act to mount an immune response to microbes, bacterial toxins and other foreign material carried into the lymphatic system with the interstitial fluid.
4
Vascular Histology and Smooth Muscle Cell Ultrastructure
Larger blood vessels share a common three-layered structure. Figure 4a illustrates the arrangement of these layers, or tunics, in a muscular artery.
A thin inner layer, the tunica intima, comprises an endothelial cell monolayer (endothelium) supported by connective tissue. The endothelial cells lining the vascular lumen are sealed to each other by tight junctions, which restrict the diffusion of large molecules across the endothelium. The endothelial cells have a crucial role in controlling vascular permeability, vasoconstriction, angiogenesis (growth of new blood vessels) and regulation of haemostasis. The intima is relatively thicker in larger arteries, and contains some smooth muscle cells in large and medium-sized arteries and veins.
The thick middle layer, the tunica media, is separated from the intima by a fenestrated (perforated) sheath, the internal elastic lamina, mostly composed of elastin. The media contains smooth muscle cells embedded in an extracellular matrix (ECM) composed mainly of collagen, elastin and proteoglycans. The cells are shaped like elongated and irregular spindles or cylinders with tapering ends, and are 15–100 µm long. In the arterial system, they are orientated circularly or in a low-pitch spiral, so that the vascular lumen narrows when they contract. Individual cells are long enough to wrap around small arterioles several times.
Adjacent smooth muscle cells form gap junctions. These are areas of close cellular contact in which arrays of large channels called connexons span both cell membranes, allowing ions to flow from one cell to another. The smooth muscle cells therefore form a syncytium, in which depolarization spreads from each cell to its neighbours.
An external elastic lamina separates the tunica media from the outer layer, the tunica adventitia. This contains collagenous tissue supporting fibroblasts and nerves. In large arteries and veins, the adventitia contains vasa vasorum, small blood vessels that also penetrate into the outer portion of the media and supply the vascular wall with oxygen and nutrients.
These three layers are also present in the venous system, but are less distinct. Compared with arteries, veins have a thinner tunica media containing a smaller amount of smooth muscle cells, which also tend to have a more random orientation.
The protein elastin is found mainly in the arteries. Molecules of elastin are arranged into a network of randomly coiled fibres. These molecular ‘springs’ allow arteries to expand during systole and then rebound during diastole to keep the blood flowing forward. This is particularly important in the aorta and other large elastic arteries, in which the media contains fenestrated sheets of elastin separating the smooth muscle cells into multiple concentric layers (lamellae).
The fibrous protein collagen is present in all three layers of the vascular wall, and functions as a framework that anchors the smooth muscle cells in place. At high internal pressures, the collagen network becomes very rigid, limiting vascular distensibility. This is particularly important in veins, which have a higher collagen content than arteries.
Exchange Vessel Structure
Capillaries and postcapillary venules are tubes formed of a single layer of overlapping endothelial cells. This is supported and surrounded on the external side by the basal lamina, a 50–100 nm layer of fibrous proteins including collagen, and glycoproteins. Pericytes, isolated cells that can give rise to smooth muscle cells during angiogenesis, adhere to the outside of the basal lamina, especially in postcapillary venules. The luminal side of the endothelium is coated by glycocalyx, a dense glycoprotein network attached to the cell membrane.
There are three types of capillaries, and these differ in their locations and permeabilities. Their structures are illustrated in Chapter 20.
Continuous capillaries occur in skin, muscles, lungs and the central nervous system. They have a low permeability to molecules that cannot pass readily through cell membranes, owing to the presence of tight junctions which bring the overlapping membranes of adjacent endothelial cells into close contact. The tight junctions run around the perimeter of each cell, forming a seal restricting the paracellular flow of molecules of molecular weight (MW) >10 000. These junctions are especially tight in most capillaries of the central nervous system, and form an integral part of the blood–brain barrier (see Chapter 20).
Fenestrated capillaries are much more permeable than continuous capillaries. These are found in endocrine glands, renal glomeruli, intestinal villi and other tissues in which large amounts of fluid or metabolites enter or leave capillaries. In addition to having leakier intercellular junctions, the endothelial cells of these capillaries contain fenestrae, circular pores of diameter 50–100 nm spanning areas of the cells where the cytoplasm is thinned. Except in the renal glomeruli, fenestrae are usually covered by a thin perforated diaphragm.
Discontinuous capillaries or sinusoids are found in liver, spleen and bone marrow. These are large, irregularly shaped capillaries with gaps between the endothelial cells wide enough to allow large proteins and even erythrocytes to cross the capillary wall.
Smooth Muscle Cell Ultrastructure
The cytoplasm of vascular smooth muscle cells contains thin actin and thick myosin filaments (Figure 4b). Instead of being aligned into sarcomeres as in cardiac myocytes, groups of actin filaments running roughly parallel to the long axis of the cell are anchored at one end into elongated dense bodies in the cytoplasm and dense bands along the inner face of the cell membrane. Dense bodies and bands are linked by bundles of intermediate filaments composed mainly of the proteins desmin and vimentin to form the cytoskeleton, an internal scaffold giving the cell its shape. The free ends of the actin filaments interdigitate with myosin filaments. The myosin crossbridges are structured so that the actin filaments on either side of a myosin filament are pulled in opposite directions during crossbridge cycling. This draws the dense bodies towards each other, causing the cytoskeleton, and therefore the cell, to shorten. The dense bands are attached to the ECM by membrane-spanning proteins called integrins, allowing force development to be distributed throughout the vascular wall. The interaction between the ECM and integrins is a dynamic process which is affected by forces exerted on the matrix by the pressure inside the vessel. This allows the integrins, which are signalling molecules capable of influencing both cytoskeletal structure and signal transduction, to orchestrate cellular responses to changes in pressure.
The sarcoplasmic reticulum (SR, also termed smooth endoplasmic reticulum) occupies 2–6% of cell volume. This network of tubes and flattened sacs permeates the cell and contains a high concentration (∼0.5 mmol/L) of free Ca2+. Elements of the SR closely approach the cell membrane. Several types of Ca2+-regulated ion channels and transporters are concentrated in these areas of the plasmalemma, which may have an important role in cellular excitation.
The nucleus is located in the central part of the cell. Organelles including rough endoplasmic reticulum, Golgi complex and mitochondria are mainly found in the perinuclear region.
5
Constituents of Blood
The primary function of blood is to deliver O2 and energy sources to the tissues, and to remove CO2 and waste products. It contains elements of the defence and immune systems, is important for regulation of temperature and transports hormones and other signalling molecules between tissues. In a 70-kg man blood volume is ∼5500 mL, or 8% of body weight. Blood consists of plasma and blood cells. If blood is centrifuged, the cells sediment as the packed cell volume (PCV, haematocrit), normally ∼45% of total volume (i.e. PCV = 0.45) in men, less in women (Figure 5).
Plasma
The plasma volume is ∼5% of body weight. It consists of ions in solution and a variety of plasma proteins. Normal ranges for key constituents are shown in Figure 5. After clotting, a straw-coloured fluid called serum remains, from which fibrinogen and other clotting factors have been removed. The relative osmotic pressures of plasma, interstitial and intracellular fluid are critical for maintenance of tissue cell volume, and are related to the amount of osmotically active particles (molecules) per litre, or osmolarity (mosmol/L); as plasma is not an ideal fluid (it contains slow diffusing proteins), the term osmolality (mosmol/kg H2O) is often used instead. Plasma osmolality is ∼290 mosmol/kg H2O, mostly due to dissolved ions and small diffusible molecules (e.g. glucose and urea). These diffuse easily across capillaries, and the crystalloid osmotic pressure they exert is therefore the same either side of the capillary wall. Proteins do not easily pass through capillary walls, and are responsible for the oncotic (or colloidal osmotic) pressure of the plasma. This is much smaller than crystalloid osmotic pressure, but is critical for fluid transfer across capillary walls because it differs between plasma and interstitial fluid (see Chapter 21). Oncotic pressure is expressed in terms of pressure, and in plasma is normally ∼25 mmHg. Maintenance of plasma osmolality is vital for regulation of blood volume (see Chapter 29).
Ionic Composition
Na+ is the most prevalent ion in plasma, and the main determinant of plasma osmolality. The figure shows concentrations of the major ions; others are present in smaller amounts. Changes in ionic concentration can have major consequences for excitable tissues (e.g. K+, Ca2+). Whereas Na+, K+ and Cl− completely dissociate in plasma, Ca2+ and Mg2+ are partly bound to plasma proteins, so that free concentration is ∼50% of the total.
Proteins
Normal total plasma protein concentration is 65–83 g/L. Most plasma proteins other than γ-globulins (see below) are synthesized in the liver. Proteins can ionize as either acids or bases because they have both NH2 and COOH groups. At pH 7.4 they are mostly in the anionic (acidic) form. Their ability to accept or donate H+ means they can act as buffers, and account for ∼15% of the buffering capacity of blood. Plasma proteins have important transport functions. They bind with many hormones (e.g. cortisol, thyroxine), metals (e.g. iron) and drugs, and therefore modulate their free concentration and thus biological activity. Plasma proteins encompass albumin, fibrinogen and globulins (Figure 5). Globulins are further classified as α-, β- and γ-globulins. β-Globulins include transferrin (iron transport), components of complement (immune system), and prothrombin and plasminogen, which with fibrinogen are involved in blood clotting (Chapter 7). The most important γ-globulins are the immunoglobulins (e.g. IgG, IgE, IgM).
Blood Cells
In the adult, all blood cells are produced in the red bone marrow, although in the fetus, and following bone marrow damage in the adult, they are also produced in the liver and spleen. The marrow contains a small number of uncommitted stem cells, which differentiate into specific committed stem cells for each blood cell type. Platelets are not true cells, but small (∼3 µm) vesicle-like structures formed from megakaryocytes in the bone marrow, containing clearly visible dense granules. Platelets play a key role in haemostasis (Chapter 7), and have a lifespan of ∼4 days.
Erythrocytes
Erythrocytes (red cells) are by far the most numerous cells in the blood (Figure 5), with ∼5.5 × 1012/L in males (red cell count, RCC). Erythrocytes are biconcave discs with no nucleus, and a mean cell volume (MCV) of ∼85 fL. Each contains ∼30 pg haemoglobin (mean cell haemoglobin, MCH), which is responsible for carriage of O2 and plays an important part in acid–base buffering. Blood contains ∼160 g/L (male) and ∼140 g/L (female) haemoglobin. The shape and flexibility of erythrocytes allows them to deform easily and pass through the capillaries. When blood is allowed to stand in the presence of anticoagulant, the cells slowly sediment (erythrocyte sedimentation rate, ESR). The ESR is increased when cells stack together (form rouleaux), and in pregnancy and inflammatory disease, and decreased by low plasma fibrinogen. Erythrocytes have an average lifespan of 120 days. Their formation (erythropoiesis) and related diseases are discussed in Chapter 6.
