An Introduction to Cardiovascular Physiology

281 Pages·1991·20.045 MB·English

by  J. R. Levick (Auth.)

An Introduction to
Cardiovascular Physiology
J R Levick,
MA, DPWI, BM, BCh
Reader in Physiology, St George's Hospital Medical School, London
Butterworths
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First published, 1991
© Butterworth & Co (Publishers) Ltd, 1991
British Library Cataloguing in Publication Data
Levick, J. R.
An introduction to cardiovascular physiology.
1. Man. Cardiovascular system. Physiology
I. Title
612.1
ISBN 0-750-61028-X
Library of Congress Cataloging-in-Publication Data
Levick, J. R. (J. Rodney)
An introduction to cardiovascular physiology/J.R. Levick.
p. cm.
Includes bibliographical references.
Includes index.
ISBN 0-750-61028-X :
1. Cardiovascular system-Physiology. I. Title.
[DNLM: 1. Cardiovascular System-physiology. WG 102 L664i]
QP101.L47 1990
612.1-dc20
DNLM/DLC
for Library of Congress 90-1811
CIP
Composition by Genesis Typesetting, Laser Quay, Rochester, Kent
Printed and bound in Great Britain by Alden Press (London & Northampton) Ltd,
London, England
Preface
This is an introductory text designed pri- plasma to the tissue - merits more than the
marily for students of medicine and physiol- few lines usually accorded to it in introduc-
ogy. The teaching style is necessarily didac- tory texts. Major advances continue apace
tic in many places (The way it works is like in other fields too, for example the elucida-
this, . . /) but also, where space permits, I tion of the biochemical events underlying
have tried to show how our knowledge of Starling's law of the heart, the discovery of
the circulation is derived from experimental new vasoactive substances produced by
observations. The latter not only puts flesh endothelium, the exploration of non-
on the didactic bones, but ultimately keep adrenergic, non-cholinergic neurotransmis-
the student (and the writer) in contact with sion, rapid advances in vascular smooth
reality. Human data are presented where muscle physiology, and new concepts on
possible, and their relevance to human how the central nervous control of the
disease is emphasized. The occasional anec- circulation is organized.
dotes and doggerel betray a deplorable I would like to thank many friends and
levity on my part, but will have earned their colleagues - Tom Bolton, John Gamble, Max
place if they interest the reader, and doubly Lab, William Large, Janice Marshall,
so if they help to make a point memorable. Charles Michel, Mark Noble, Peter Simkin,
The undergraduate will find a useful guide Laurence Smaje, Mike Spyer and John
to learning objectives in the coloured box at Widdicombe - for helpful comments on
the beginning of each chapter. sections of the text. Any mistakes or
The traditional weighting of subject mat- muddles that remain are, of course, entirely
ter has been re-thought, resulting in a fuller my own; please do not hesitate to point
account of microvascular physiology than is them out to me. Perhaps I should thank the
usual. This reflects the explosion of micro- cardiovascular system too, for proving to be
vascular research over the past two decad- even more fascinating than I had realized
des. Even setting aside these advances, it before writing this book!
seems self-evident that the culminating,
fundamental function of the cardiovascular Rodney Levick
system - the transfer of nutrients from St. George's Hospital Medical School
v
Chapter 1
Overview of the cardiovascular
system
1.1 Diffusion: its virtues and 1.5 Introducing some hydraulic
limitations considerations: pressure and
flow
1 • 2 Functions of the
1 • 6 Structure and functional
cardiovascular system
classification of blood vessels
1.7 Plumbing of the vascular
1.3 Circulation of blood
circuits
1.4 Cardiac output and its 1 • 8 Central control of the
distribution cardiovascular system
1.1 Diffusion: its virtues and
The heart and blood vessels form a system
for the rapid transport of oxygen, nutrients, limitations
waste products and heat around the body.
Small primitive organisms lack such a The 'drunkard's walk' theory. Diffusion is a
system because their needs can be met by passive process in that it is not driven by
direct diffusion from the environment, and metabolic energy but arises from the innate
even in man diffusion remains the fun- random thermal motion of molecules in a
damental transport process between blood solution or gas. Although each individual
and cells. In order to appreciate fully the movement of a solute molecule occurs in a
need for a cardiovascular system we must random direction (the 'drunkard's walk')
begin by considering some properties of the this nevertheless produces a net movement
diffusion process. of solute in the presence of a concentration
1
Overview of the cardiovascular system
(A) (B) direction increases with the square of
distance:
t^x (1.1)
2
f = 1 AC= 6 (see footnote to Table 1.1); and as a result
diffusional transport is extremely slow over
large distances. While diffusion across a
short distance-such as the neuromuscular
C=8 C=2
Table 1.1 Time taken for a glucose molecule to
diffuse a specified distance in one direction
Distance Time Comparable distance
t=2 AC=2 (x) (tr in vivo
0.1 [Am 0.000005 s Neuromuscular gap
1.0 \im 0.0005 s Capillary wall
10.0 um 0.05 s Cell to capillary
C=6 C=4 1 mm 9.26 min Skin, artery wall
1 cm 15.4 h Ventricle wall
Figure 1.1 Sketch illustrating how random
molecular steps result in a net movement of * Times are calculated by Einstein's equation t = xtflD. 'D* is
solute down a concentration gradient. At time 1 the solute diffusion coefficient. For glucose in water at 37°C, D
(upper sketch) there are 8 molecules per unit is 0.9 x 10"5 cm2/s (Einstein, A. (1905) Theory of Broumkn
Movement (trans, and ed. by R. Fiirth and A. D. Cowper, 1956),
volume in (A) and 2 in (B). At time 2 (lower
Dover Publications, New York)
sketch) each molecule has moved a unit step in a
random direction. Because there was a greater
density of molecules in A there was a greater
probability of random movement from A to B, gap (0.1 urn) takes only 5 millionths of a
resulting in a net 'downhill flux second, diffusion across the heart wall
7
(approximately 1 cm) is hopelessly slow,
taking over half a day (Table 1.1). Sadly,
Nature often proves the validity of Ein-
gradient. Figure 1.1 illustrates how this stein's equation and Figure 1.2 is an
happens. Notice that although the net example of this: it shows the heart of a
transfer of solute is from compartment A patient who suffered a coronary thrombosis
into compartment B there is also a smaller (obstruction of the blood supply to the heart
backflux into compartment A. This can be wall). The pale area in the wall is muscle
proved by adding a trace of radiolabeled which has died from lack of oxygen even
solute to compartment B; some labelled though the adjacent cavity (the left ventri-
molecules appear in compartment A even cle) was fully of richly oxygenated blood;
though the net diffusion is from A to B. the patient died simply because a distance
of a few millimetres reduced diffusional
The importance of diffusion distance The transport to an inadequate rate.
rate at which diffusional transport occurs is
critically important because the supply of Convection for fast long-distance transport
nutrients must keep up with cellular de- Clearly then, for distances greater than
mand. However, as Albert Einstein showed approximately 0.1mm a faster transport
the time (t) that it takes a randomly jumping system is needed and this is provided by the
particle to move a distance x in one specific cardiovascular system (Figure 1.3). The
2
1.3 Circulation of blood
cardiovascular system still relies on diffu-
sion for the uptake of molecules at points of
close proximity to the environment (e.g.
oxygen uptake into lung capillaries) but it
then transports them rapidly over large
distances by sweeping them along in a
stream of pumped fluid. This form of
transport is called bulk flow or convective
transport. Convective transport requires an
energy input and this is provided by a
pump, the heart. In man convection takes
only 30 s to carry oxygen over a metre or
more from the lungs to the smallest blood
vessels of the limbs (capillaries). Over the
final 10-20 microns separating the capillary
Figure 1.2 Section through the left ventricle of a from the cells, diffusion is again the main
human heart after a coronary thrombosis. The transport process.
section is stained to show intracellular enzyme
content. The pale area marked by asterisks is an
infarct, an area of muscle severely damaged or
killed by oxygen lack; the pallor is due to the 1.2 Functions of the
intracellular enzyme having leaked out of the
dying cells. The infarct was caused by a cardiovascular system
thrombus in a coronary artery, blocking the
convectional delivery of oxygen. Diffusion of The first and foremost function is the rapid
oxygen from the blood in the adjacent cavity of convection of oxygen, glucose, amino acids,
the left ventricle is unaffected yet only a thin rim fatty acids, vitamins, drugs and water to the
of tissue (approximately 1 mm) can survive on tissues and the rapid washout of metabolic
this diffusional flux. (Courtesy of Professor M.
waste products like carbon dioxide, urea
Davies, St. George's Hospital Medical School,
and creatinine. The cardiovascular system is
London)
also part of a control system in that it
distributes hormones to the tissues and
even secretes some hormones itself (e.g.
Lung Heart Cell atrial natriuretic peptide; see Chapter 11). In
addition, the circulation plays a vital role in
temperature regulation, for it regulates the
delivery of heat from the core of the body to
^C^~ the skin, and a vital role in reproduction, as it
Metabolic provides the mechanism for penile erection.
energy
R
1.3 Circulation of blood
The heart is an intermittent muscular
Diffusion Convection Diffusion
pump, or rather two adjacent pumps, the
0.5 |im 1m 10 |im
right and left ventricles (see Figure 1.4).
Figure 1.3 Schematic diagram of the mammalian
cardiovascular system to illustrate the roles of Each pump is filled from a reservoir, the
diffusion and convection in oxygen transport. L, right or left atrium. The right ventricle
left side of heart. R, right side of heart. The pumps blood through the lungs to the left
pulmonary and systemic circulations lie in series side (the pulmonary circulation) and the left
3
Overview of the cardiovascular system
Brain
svc |
Aorta
ivc \
ISplanchnic
| circulation
I Renal portal
[system
^^^^^^^^^1
Trunk
^ and legs ^ • • ^ ^ • • ^ •^
1-1
Figure 1.4 General arrangement of the circulation showing right and left
sides of the heart in series. Circulations to individual organs are mostly in
parallel (e.g. cerebral and coronary circulations) but a few are in series
(liver, renal tubules). Note that the bronchial venous blood drains
anomolously into the left rather than right atrium. PA, PV, pulmonary
artery and vein; RA, LA, right and left atrium (an 'atrium' was a Roman
hall); RV, LV, right and left ventricle; SVC, IVC, superior and inferior vena
cava
ventricle simultaneously pumps blood heart and veins, as was first established by
through the rest of the body and back to the the London physician, William Harvey, in a
right side (the systemic circulation). The celebrated book entitled De Motu Cordis
blood is compelled to follow a circular (Concerning the Movement of the Heart) in
pathway by one-way valves located in the 1628.
4
1.5 Introducing some hydraulic considerations: pressure and flow
Pulmonary circulation Venous blood en- adapts rapidly to changing internal or
ters the right atrium from the two major external circumstances. In severe exercise
veins, the superior and inferior venae for example, when oxygen demand can
cavae, then flows through a valve into the increase tenfold, the heart responds with a
right ventricle. The ventricle, which is fourfold increase in output, or even more in
composed mainly of cardiac muscle, re- athletes. These changes imply that special
ceives the blood while it is in a state of control systems must exist for regulating the
relaxation called diastole (pronounced die- heart beat, and these controls are the
a-stole-ea). Contraction, or 'systole' (pro- subject of Chapters 3 and 6.
nounced sis-tole-ea), then forces part of the
blood out through the pulmonary artery Distribution of cardiac output The output
and into the lungs at a low pressure. Gases of the right ventricle passes to the lungs
exchange by diffusion in the lung air sacs alone. The output of the left ventricle is in
(alveoli) raising the blood oxygen content general distributed to the peripheral tissues
from approximately 150 ml/1 (venous blood) in proportion to their metabolic rate; resting
to 195 ml/1. The oxygenated blood returns skeletal muscle for example accounts for
through the pulmonary veins to the left around 20% of human oxygen consumption
atrium and left ventricle. and the muscle receives roughly 20% of the
cardiac output (Figure 1.5). This egalitarian
Systemic circulation The left ventricle principle is over-ridden, however, where
contracts virtually simultaneously with the the particular function of an organ requires
right and ejects the same volume of blood a higher blood flow; the kidneys consume
but at a much higher presure. The blood only 6% of the body's oxygen yet receive
flows through the aorta and the branching 20% of the cardiac output since this is
arterial system into fine thin-walled tubes necessary for their excretory function. As a
called capillaries. Here the ultimate function result some other tissues are relatively
of the cardiovascular system is fulfilled as ill-supplied and, rather surprisingly, cardiac
dissolved gases and nutrients diffuse be- muscle is one of them. Consequently, it is
tween the capillary blood and the tissue compelled to extract an unusually high
cells. The circulation of the blood is com- proportion of the oxygen content of the
pleted by the venous system which con- blood, namely 65-75%. The distribution of
ducts blood back to the venae cavae. the cardiac output is not fixed, however, but
is actively adjusted to meet varying con-
ditions. A good example of this is provided
by heavy exercise, where the proportion of
the cardiac output going to skeletal muscle
1.4 Cardiac output and its
increases to 80% or more, owing to wide-
distribution ning of the vessels supplying blood to the
muscle (vasodilatation).
The cardiac output is the volume of blood
ejected by one ventricle during one minute,
and this depends on both the volume
ejected per contraction (the stroke volume) 1.5 Introducing some
and the number of contractions per minute
hydraulic considerations:
(heart rate). In a resting 70kg adult, the
stroke volume is 70-80 ml and the heart rate pressure and flow
is approximately 65-75 beats/min, so the
resting cardiac output is approximately Blood pressure What drives blood along
75 ml x 70 per min or roughly 51 per min. the blood vessels after it has left the heart?
The output is not fixed, however, and The main factor is the gradient of pressure
5
Overview of the cardiovascular system
Cardiac output
g)
H
m
m
(
e
ur
s
s
e
Pr
ean ocity m/s)
Mel c
v (
(a) al ctional cm2) ->
Totoss-searea(
Oxygen consumption cr
Figure 1.6 The profile of blood pressure and
velocity in the systemic circulation of a resting
man. The abscissa represents distance along the
vessels. Velocity at any level is the cardiac output
divided by total cross-sectional area of the
vascular bed at that point. Pressure in the
pulmonary artery is shown as a dotted line. Ao,
human aorta. VC, human vena cava. (From
several sources)
(b) to atmospheric pressure, and the pressure
difference drives blood from artery to vein.
Figure 1.5 The distribution of left ventricular Arterial pressure is pulsatile, however, not
output in a resting man (top) compared with the steady, because the heart ejects blood
oxygen consumption (bottom) of the various intermittently: between successive ejection
tissues. GIT = gastrointestinal tract. (From phases the systemic arterial pressure decays
Wade, O. L. and Bishop, J. M. (1962) Cardiac from 120mmHg to approximately
Output and Regional Blood Flow, Blackwell,
80mmHg, while pulmonary pressure de-
Oxford, by permission)
cays from 25 mmHg to lOmmHg (Figure
1.6). The conventional way of writing this is
along the vessel. Ventricular ejection raises 120/80 mmHg and 25/10 mmHg. The con-
aortic blood pressure to approximately ventional units are mmHg above atmos-
120mmHg above atmospheric pressure pheric pressure because human blood
while the pressure in the great veins is close pressure is measured clinically with a
6
1.6 Structure and functional classification of blood vessels
mercury column, taking atmospheric press- regulated. Equation 1.3 shows that there are
ure as the reference of zero level (see essentially only two ways of altering flow:
Appendix, 'Pressure'). either the driving pressure must be changed
or else the vascular resistance. In normal
Simple 'law of flow' The relation between subjects blood pressure is in fact kept
a pulsatile flow and pulsatile driving press- roughly constant, and it is changes in
ure is quite complex (Chapter 7), but it is vascular resistance that regulate local blood
useful at this stage to consider a simpler flow. During salivation, for example, blood
situation, such as water flowing along a flow to the salivary glands can increase 10
rigid tube under a steady pressure gradient. times due to a fall in vascular resistance to
Under these conditions, flow (Q) is directly one-tenth its former value, while the driv-
proportional to the pressure difference ing pressure (arterial pressure) does not
between the inlet (Pi) and outlet (P ) of the increase at all. Changes in vascular resist-
2
tube: ance are brought about by contraction or
relaxation of the vessels, so we should next
Q^Pi-Pi (1.2)
consider their structure.
Flow is often represented by Q because Q
stands for quantity of fluid and the dot
denotes rate of passage, this being New- 1.6 Structure and functional
ton's original calculus notation. It should be
classification of blood
noted that flow is by definition a rate (the
passage of a volume or mass per unit time) vessels
and the common expression 'rate of flow' is
really rather muddling and best avoided. By The aorta and pulmonary artery divide into
inserting a proportionality factor (K) into the smaller arteries, which branch progressively
above expression we can change it into an to form narrow high-resistance vessels
equation describing flow: called arterioles (see Figure 1.8). Arterioles
branch into innumerable capillaries which
Q = K.(P-P) (1.3)
l 2 then converge to form venules and veins.
where K is called the hydraulic conductance of The characteristic dimensions of these
the tube. Conductance is the reciprocal of various vessels are set out in Table 1.2.
resistance (R), so we can also write:
Structure of the blood vessel wall
(1.4)
With the exception of capillaries all blood
vessels have the same basic three-layered
This expression is a form of Darcy's law of plan (see Figure 1.7) consisting of a tunica
flow and is analogous to Ohm's law for an intima (innermost layer), tunica media
electrical current (/ = AV7R). It states that (middle layer) and tunica adventitia (outer
flow is proportional to driving pressure (Pi layer). The intima consists of flat endothelial
— P ) and is inversely proportional to the cells resting on a thin layer of connective
2
hydraulic resistance. The total resistance of tissue. The endothelial layer is the main
the systemic circulation in man is around barrier to plasma proteins and also secretes
0.02 mmHg per ml/min while that of the many vasoactive products, but it is mech-
pulmonary circulation is only 0.003 mmHg anically weak. The media supplies mechanic-
per ml/min, and the latter low value al strength and contractile power. It consists
explains why a very low pressure suffices to of spindle-shaped smooth muscle cells
drive the cardiac output through the lungs. arranged circularly and embedded in a
The law of flow also helps us to under- matrix of elastin and collagen fibres. Inter-
stand how the blood flow to an organ is nal and external elastic laminae (sheets)
7