Human

For medical students

 HUMAN

PHYSIOLOGY
FOR MEDICAL STUDENTS

CARDIOVASCULAR SYSTEM

MAGDI SABRY, MD
professor of physiology
Faculty of Medicine
AI-Azhar University
CAIRO

2011
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DEDICATED TO

MY TEACHERS THROUGHOUT MY LIFE. partic:ular~r the

.fint 2 teachers. my lute parents.

MY FAITHFUL LATE WIFE. the ligltl tltat disappeared

.from l[le but i.\ t!l'erlu.\ling inside me.

MY SONS, SHERIF, AMR AND ESSAM, AND THEIR WIVES,

tht•ir lm·e gil'e.\ me hope and intere.\ t in 1[/t' ami make.\· their
happiness my chitigoal.

MY GRANDCHILDREN, AHMED, NOURHAN and SAMA

SHERIF, YASMIN and MOHAMMED AMR, AND AYA and AL Y ESSAM.
the beautijit! young angel.' that hal'£' added a new kind f~l
lwppinl'.\ .\ lo my ![f"e.
 PREFAC~
With recent advances in the jield of human physioloxy , it has
become urgelllto provide a11 up to date re view 011 the subject.

This hook is provided to h elp m edic:al students in understanding

modem cardio va scular p hysiology. It presents th e 11•lwle s ubject
i 11 a b ri eJ: c:omprehensi 11e, and up to date for m.

Great eff ort 1vas don e to p e1ject su ch a 1•ast subject in an e asi~1·

understandable expression and in a such reasonable bulk. It includes
as much simplified ami c:lear illustrations as possihle, and to maintain
simplici~J', they have been presented in a diag Nwllmttic: for m , photo-
g raphs were great~J' excluded.

The major part of my g ratitude sh ould he g iven to all wlto taug ht

m e as well as to my firmi~J' 1vlto, patiently, supported m e during
preparation oft/tis book.

A ny suggestions, remarks or criticism will be xrelllly ll'elcomed,

h eartily appreciated and veJJI much considered.

I hop e this book will be a real h elp to underg raduate m edical students
as 1vell as to p ostg raduates and candidates of hig h er degrees, in the
field of human physiology.
MAGDI SABRY, 1993

Second edition 1998

Third edition 2003
Preface to the fourth edition
Tlti.\ new edition i.\ or~r_:inal both in \/tape wul co11tent\. l 1nprm•t•d
data am/ mataia/ that i.'i no longer re/ei'(IJI/ ll't'rL' t!liminatt•d am/ all
dwptt!n lull't' been e.\·temil·e~r l'l'l'i,ed am/ updated. llort• fi~urt'\ am/
iffu,trutimt' ll't'rc> imrotlucetl. ami rece111 data ll'«'rt' fUitfl'tl d\t'll'ltere
.\pecial~r ahoul thl' cardim•a.\CIIIar regulatory mt'dumin am/ tl~t• l'ircu-
futirm through spedal rl'giom, and mtJ\1 .'uhj£'t't\ lun•t• ht't'll t•mnplt'tl'(l'
reH•rill£'11.
 CONTENTS Page

Chapter 1 :Mechanism of heart beating ........................ 1

Chapter 2 ·The properties of the cardiac muscle ............... 9

Chapter 3 ·The cardiac cycle .................................................. 27

Chapter 4 :The electrocardiogram and arrhythmias .... 44

Chapter 5 ·T he heart rate .. .................. .. .......................... 68

Chapter 6 ·T he cardiac output and venous return ...... 77

Chapter 7 The cardiac energetics ........................................... 89

Chapter 8 The vascular system biophysics .................. 94

Chapter 9 : The arterial blood pressure ........................ 99

Chapter 10 ·Regulation of the arteriolar diameter ...... 111

Chapter 11 :The capillary (micro) circulation and

lymph circulation and edema ..................116

Chapter 12 :The venous circulation ........................................ 124

Chapter 13 :The coronary circulation ...................... ... 128

Chapter 14 : The cerebral circulation ............... .. ......... 133

Chapter 15: The pulmonary circulation ..... .. ............... 137

Chapter 16: Effects of exercise on the circulation ........ 141

Chapter 17: Hemorrhage, shock and heart failure ........ 143

CHAPTER 1

MECHANISM OF HEART BEATING

The cardiovascular .\ )'Stem (CJIS) in a closed system in wh ich blood

circulates, and it consists of the hea r t and blood vessels (figure I).
Pulmon11y corculat•on

Ao ra

Superlo <
vena cav~
- - - Heart

lnleno<
vena uv1

Ve•n•. vtnuhn. and venou1 ••nu~

Fi gure 1 The cardiovascular ystem

Functional anatomy of the heart
The human heart is a muscular organ enclosed in a thin fibrous
connective tissue sac called the per icardium. This sac contains a few ml of a
clear watery nu id whi ch serves as a lubrican t to heart movement. It is also
relati vely inelastic ·(which limits excess ive enlargement of the heart). The
wall of the heart is formed of a special kind of muscle fibres ca lled the
cardiac: muscle fibres, and they are collecti\ ely 1-..no'm as the myocardi um.
The arteries that supply the myocardium arc branchc. from the aorta and nrc
ca ll ed the coronary arter ies. The inner surface or the myocardium is lined
by a thin layer of endotheli al ce ll s ca lled the end oca rdium . This endotheli al
ce ll layer does not onl y line the hea rt caviti es but also th e entire vascul ar
system. The heart is divided into riglrt an d left h alves each of which consists
of one atrium and one ventricle, and the 2 atria are separoted by an inter-
atritil H'plwn II'!Jile the 2 \'C!IIIricle.\ are sepamtl'd hy an intl!I'I'C' IIIricular
 2
Chapter I The !teart (cardiac) valves

septum. The atrial myocardium is much thinner than that of the

ventric les, and the left ventricular wall is about 3 times as thick as the
right l'entricular 'vall (about 15 and 5 mm respectively).

THE HEART (CARDIAC) VALVES : Each ventricle has an inlet

(= atrioventricular) valve which separates it from the atrium), and an outlet
valve which sepa rates it from the vessel that originates from it (figure 2 left).
.·

vems

IVC

Figure 2: Direction ot"blood now in the heart (Jell) and the papi ll ary
musc les (right). T and M = Tricuspid and Mitral valves. A and P = Aort ic
and Pulmonary valv~s . PA = Pulmonary Artery. SVC = Superior vena cava
·and rvc = l'nferior vena cava.

The !low or blood through both the heart and the vascular system is uni-
directional (i.e. it nows in one direction only)ji·omthe atria to the ventricles
to the arteries then to the veins and finally to the atria again. Such unidirec-
tional blood flow is produced by the action of 4 valves in the heart that
open and close passively i. e. only as a result of pressure differences across
them (sec the cardiac cycle. chapter 3). These valves include the following :
(A) The atrioventricular valves(= A-V valves) : These const itute
the inlet va lves to the ventricles (see above), and they include (I) T he tri-
cuspid valve in the right side : Th is cons ists of 3 cusps (or leaflets) and it
allows blood t1ow only from the right atrium to the right ventricle (2) The
bicuspid (or mitral) va lve in the left side : This consists of 2 cusps, and it
allows blood flow on ly from the left atrium to the left ventricle.
 3
Chapter 1 Divisions o{ the circulatorv spstem

** Certain musc les ca lled the papillary muscles project from the
ventri cu lar wa lls into the ventricu lar cavities. The tendons of th ese muscles
are firm fibrou s cords ca ll ed the chordae lendineae and they arc
attached to the margins o.lthe cusps(~( the A-V valves (figure 2 right). These
muscles contract at the same time of ventricu lar contraction , lead ing to pu ll
of the cordae tendineac downwards. This prevents eversion (~t the cusps of
the A- V valves into the corresponding atria during velllricular contraction.
(B) The semilunar valves : These constitute the outlet va lves from the
ventricles (sec above), and they include (1) The pulmonary va lve in the
right side : This all ows blood flow only from the right ventricle to the
pulmonCIIy arte1y (figure 2 left) (2) The aortic va lve in the left side : This
allows blood flow on(v from the left ventricle to the aorta (figure 2 left).
Each of these va lves is formed of 3 cusps, which arc hal/moon shaped
pockets (so they are frequen tly also ca lled the semilunar valves).
::._ The atrial and ventricu lar musculatures are sepa rated by fibrous tissue
that surrounds the atrioventricular va lvu lar openings(= A-V ring or fibrous
skeleton of the heart). This ring is an electrical insulator, so action poten-
tials cannot normally be conductedfrom the atria to the ventricles via this
tissue and they arc conducted only via the AV nod e & A V bundle(page 6)
DIVISIONS OF THE CIRCULATORY SYSTEM
(1) The systemic (or greater) circulation
This circulation starts from the left ventricle -7 aorta -7 large arteries
-7 small arteries -7 arterio les -7 capillaries -7 venu les -7 veins -7
SVC and IVC (super ior and inferior venae cavae) -7 right atri um.
(2) The pulmonary (or lesser) circulation
This circulation lies in series with the systemic circu lation, and it starts from
the right ventricle -7 pulmonary trunk (= pulmonary artery) -7 lungs -7
pulmonary capillaries -7 4 pulmonary veins -7 left atrium.
(3) The special circulations
These include the ci rcu lations at specific sites e.g. the cap illary ( = micro),
lymph, coronary and cerebral circulations.

CHARACTERISTICS OF VARIOUS BLOOD VESSELS

(1) The aorta and pulmonary artery arc elastic vessels. The aortic elasti -
city is essential to maimain the arterial blood pressure (page I 0 I).
(2) The medium-s ize and sma ll arteries arc muscular low resistan ce
vessels that deliver blood to the tissues at a considerable pressure.
(3) The arterioles are muscular high resistance vessels that regulate the
blood flow to ti ssues and maintain the arterial blood pressure (page I 0 I).
 4
Chapter 1 The low and high pressure svstems

(4) The capillaries are exchange vessels through whi ch nuid s and various
substances are exchanged between the blood and the ti ssues.
(5) Th e vein s and pulmonary vessels arc capacitance vessels that acco-
mmodate large volumes of blood under low pressure (volume reservoir) .
::..::. During rest, more than ha(f of the blood volume (about 54 %) is
present in the systemic veins, in contrast to 12 % in the heart, 1 I % in the
arterial .~yslem , 5 % in the capillaries. and 18 % in the pulmonw y vessels.

THE LOW AND HIGH PRESSURE SYSTEMS

The left ventricle and the systemic arterial system (aort a, arteries
and arterioles) constitute a high pressure .\ )JStem because it normally
contains a small percentage of the blood volume but under a high pressure.
On the other hand, the systemic veins, pulmonary vessels and heart
chambers other t han t he left ventricle constitute a low pressure system
that norm all y contain s a mu ch greater amount of the blood vo lume (see
above) but under a low pressure.

FUNCTIONS OF THE ATRIA AND VENTRICLES

The pumping action of the ventricles is the main force that propels
blood to the peripheral circul atory system, so loss of such functi on is fatal. On
the other hand, the atria perform the followin g functions (1) Blood
storage : They receive and store the venous return during ventricular
systole then deli ver it to the ventricles during ventricular diastole
(2) The atrial walls contain stretch receptors that monitor changes in the
intra-atrial pressure and initi ate several regulatOJJI cardiovascular reflexes
(3) Certain atrial cells secrete the atrial natriuretic peptide (ANP) which
favours excretion ofN a... and water by .the kidney (refer to endocrine glands).

Figure 3 : The contractile cardiac muscle fibres

 5
Chapter 1 Mechanism o(h eart benting

TYPES OF CARDIAC MUSCLE FIBRES

(A) Contractile cardiac muscle fibres (99 %)

These are the libres that constitute the atrial and l'entricular 111alls.
They are characterized by the following :
( 1) They branch and interdigitate (ligure 3). hut eachjibre is a separate
cell surrounded by a cell membrane (the sarcolemma).
(2) They arc stiated like skeletal muscles and also contra<.:t by a similar
mechanism. They contain actin. myosin, troponin and tropomyosin, but the
Tsystem is located at the Z lines (not at the A-1 junctions). They also <.:o ntain
an additional protein called dystrophin (the congenital deficiency or which
leads to one type of a serious heart disease known as cardiomyopathy).
(3) There are in tercalated disks (or discs) along the muscle libres
(figure 3) which arc nlways present at the Z lines. These disks arc actual ly
cell membranes that separate indi vidunl fibres f'rom one another. At each
disk. the cell membranes fuse and fonn gap junctions that allow free
diffusion of ions. Therefore, the disks provide low-resistance br idges that
all ow rapid spread of excitation waves from one fibre to other lib res.
Accordingly.ji·omthejimctional point <ll'ieiV, the cardia<.: muscle con-
stitutes a syncytium that obeys the all or mme law, and leads to its con trac -
tion as one unit (resulting in a more efficient pumping force). The heart con-
tains 2 functional syncytia (the walls of the 2 atria .form one .\)1/l()'lium and
the walls of t!te 2 ventricles form t!te ot!ter), and these syncytia arc comp-
letely separa ted from each other by the fibrous A-V ring (page 3).
(B) Autorhythmic cardiac muscle fibres (1 %)
These arc modi)led almost non-contractile cardi ac muscle fib cs (bec-
ause they contain few contractile myofibrils) that arc specinli;l.!d for
generation (initiation), co nduction a nd distributio n of cardiac impulses
(action potentials) that stimu late the contractile muscle fibres. They constit-
ute a network known as the condu cting system of the heart (sec next). and
they contact the contractile muscle fibres via gap junctions.

MECHANISM OF HEART BEATING

llcart beating (i.e. l'elltricular contraction) is produced by the ef'fe<.:t or

action potentials that arc initiated & propagated to the ventricles by ll spec:ia-
li-;,ed muscular co mlu ctin~ system in the heart. This consists or 3 paris:
 6
Chapter I Th e conducting .w stem o[the heart

(A) The nodal system

This includes 2 nodes that arc loca ted in the right atrium (figure 4) :
( I ) T he sinoat rial node (SAN), which is located in the wall of the right
atrium ncar the open ing of the superior vena cava.
(2) The atrioventricular node (A VX ), which is located at the base of the
right atrium near the interventricular septum.

(B) The internodal system

Thi!:l system consists of 3 muscular tracts that connect the SAl\ to the A V
( 1) The anterior internodal tract : This ex tends directly from the SAN to
the 1\ VN and also gives a branch to the le n atrium (through the interatri al
::;cptum) ca lled Bacltma11n's bundle, whi ch exc ites the krt atrium at ncn rly
the same time of right atrial excitation, so both atria would contract simul-
tall eous~) '.
(2) The middle intemodaltract (= Wenckebaclt 's tract ).
(3) 'l11e posterior intemodaltract (= Thorel's tract).

(C) Tile His-Purkinje system

This system transm its the excitation waves to the right and lef't ventricul ar
musc le, and it includes the foll owing 3 structures :
(1 ) T he A-V (or atrioventricular) bundle (= bundl e of His) : This consists
of a strand of specialized cardiac muscle cells that ari c from the A-V node
and pass through the A- V fibrous ring to the upper part of the inter-
ventricular septum. It is the Oil~\' 1/0rma/muscu/ur colll/ecticm helll'ee/1 tlw
atria ollllthe l'entrides, a~Uithe A V 11ode a11d A I' hundle IIOI'IIwl~l' constitute
the on~r eleclrical com1ection that links the atria and the 1·emricles.
Sometimes, the hcan may contain other muscular connections e.g. the
bundle of Kent (page 65).
(2) T he right and left branches of the bund le of II is : These start at the
top or the interventricul ar septum and run down 0 11 either side of' this septum
under the endocardium to the apex of the heart then they arc reflected up-
\\ards along the inner sides of the lateral wall::; of the ventricles to the base
of the heart.
(3) The Pu rki njc fibres : These arc fi ne fib res that arise from the right and
len bundle branches and transmit excitation waves to the ventricu lar muscle.
 7
Cltaeter I Initiation am/ spread o{cardiac excitation

Actoon polenoal
SAnodt
Supenor vena cava

Sonoatrtal noda Common bundle .....

lntarnodal pathways ---~"""-'*~le~
Bundle branchu
-- -t---...J
Amovenmcular node p~,~~!'~!'! - .,...,____ ,J

_vent":~'~'-multle... I

Right bundlt branch

ECG

02 04 06
Lelt poatertOr tue~cle Tune (s)

Figure 4: The conducting system of the heart (left) and the action potent ials
recorded from va rious regions or the heart (right) ..

INITIATION AND SPREAD OF CARDIAC EXCITATION

-Cardiac excitat ion is initiated by an action potential (= cardiac impulse)

that is spontaneously genera ted by self-excitab le card ia<.: cel ls present in the
nodal and 1/is-Purkinje systems <.:a iled autnrhythmic cells (sec nhovc). The
cells in the va rious sites of these systems differ in their inherent rates or
generating action potentials. but normally tlte site that has the fastest rate
of autorhytlunicity drives the rest of the heart at its rate and is knmv11 as
the pacemaker(= speed maker) oftlte /t eart.
- Norma lly.the SAN has I he fastest inherent rate of disc harge (I 00-110
/minute) and is thus the IIOrmal (or primlii:J') pacemaker of the /teart . In thi s
case. the 11011-SA nodal outorlrytlrmic cells ore unahle to ossu11U! their sloll'er
rates c~/ discharge because they are depolarized by the impulses that or-
iginate in the SA node before they reach the threshold of their ow n rhythms.
However. these cells arc lat ent pacemakers that can be brought into action
hut o11~1· c!fierfailure oftlw SA node autorhythmicity due to disease.
- In the nodal tissues (p<H1icula rl y the S/\N). there arc special round cells
that contain few organelks. These cells arc probably the actual pacemaker
cells (so they are frequently ca lled the P cells).
 8
Chapter I Overdrive suppression

- Atrial exc itation : The cardiac impul se spreads from the SAN to the
atria leading to their exc itation. It then reaches the A VN via both tire atrial
111/IScu/ature am/ t!te 3 internodal tracts (sec above). These tracts constitute
more rFtpidly-conducting pathways but they seem to be jimctiona/ rather
than anatomical (because the most accurate histologica l studies did not yet
demonstrate clearly the presence of speciali zed bundles of cel ls in the atria).
- AV nodal conduction : The cardiac impulse is delayed in tlte AVN
about 0.1 second (page 20). Such A V delay is important because it allo111s
complete atrial depolari';.ation am/ contraction (as JVe!l as emptying of
tlteir blood content into tlte 11entricles) before ventricular depo/ari-:;ation
and contraction occur (refer to the cardiac cycle, chapter 3).
-Ventricular excitation : After leaving the A V node. the cardiac
impul se travels rapidly down the A V bundle and is then transmitted by the
Purkinje system to the ventricles. The muscle fibres in the His-Purkinjc
system arc specialized fo r rapid propagation or action potentials. and this
results in excitation of every part of both ventricles at nearly the same time.
Exc ita-tion sta rts in the in terventricular septum from left to right (because
the septum receives a Mig .from the !e.fl bundle branch) then the Purkinjc
fibres transmit the impulse outwards through the ventricu lar walls (i.e. from
the endocardium to the ep icardium).
:.:_ T he conducti ng system is more organized, mo•·e dcvchlJ>ed and
more complex in the ventricles than in the atria. This is because the
ventricular muscle mass is much larger and requires such hi ghly organized
conducting system to convey excitation to both ventricles at nearly the same
time (so that a single strong contraction that ejects blood e ffi cientl y is prod-
uced). If ventricu lar excitati on depends only on the syncytial structure of the
myocardium (i.c.on cell to cell spread of the cardiac impul se via the gap jun-
ctions), the ventricular muscle ncar the A V node wi ll contract before excita-
tion reaches the heart apex, which would result in an inefficient pumping.
OVERDRIVE SUPPRESSION
Thi s is depression of a pacemaker automaticity after its excitati on for a
period at a greater frequency than its inherent rhythmicity. Thi s phenomenon
explains why automaticity in the latent pacemakers of the heart is depressed
by the stronger SAN automaticity. It also explains the depression of SAN
automaticit_v (/an atrial ectopicfocus.fires a! a higherji·equenc.y than that of
the SAN e.g. in cases of atrial .flutter and fibrillation (in which case, the
ectopic focus becomes the pacemaker of the heart). In the later condition, if
the ectopic focus stops firin g suddenly, the SAN wil l resume its activity but
not immediately, because it requires an interval to recover from depress ion
(= sinu s node recovery time). During thi s interva l, the heart stops beating
and ir it is prolonged, syncope(= loss of consciousness) may occur.
 9
CHAPTER2

I PROPERTIES OF THE CARDIAC MUSCLE I

fn add ition to the syncytium property of the cardiac muscle (= [j'onejibre
is stimulated, the entire myocardial unit contract), it also has the properties
of (a) Excitability (b) Automaticity a nd rhythm icity or auto-rhythmici ty
(page 16) (c) Conductivity (page 19) (d) Contr actili ty (page 2 1) .

(A) EX CITABILITY
( ELECTRICAL ACTIVITY OF THE HEART)

This is the ability of the cardiac musc le fibres to respond to adequate stimuli,
and the response is their depo larizati on and generation of action poten tials.

Myocardial excitation contraction coupling

Depolarization of the ca rdiac muscle fibres markedly increases their

cytosolic (in tracellular) Ca2 ' content, which combines to troponin C lead-
ing to their contract ion exactly as occurs in skeletal mu.w:les, and their
relaxat ion also occurs as in skeletal musc les (refer to nerve and musc le).
During cardiac excitation . the cytosol ic Ca2- is derived !"rom 2 sources
(1) The sarcoplasmic reticulum (the main source) (2) The ext racel lu lar fluid
(the depo larization wave causes opening of the slow (= long-lasting) Ca 2;
chann els in th e sarcolemma, lead ing to Ca 2 influx from the ECF into the
cardiac muscle fibres mai11~y during the plateau phase t~l rite action
pote11tial (page I I ).
Although the amount of Ca 2 ~ diffusing from the ECF is normally very
small, yet it is very important because it acts as a signal for release ofmuclt
more Ca 2+ from tlte sarcoplasmic reticulum.
The force of contractiou is directly proportioual to rite amount of
cytosolic er/~ (therefore, the dmgs rhat h!ock rhe Cc/~ channels decrease
1
Ca ' influx, leading to disappearance of the plateau phase of the cardiac
action potential and weakening r?f"theforce r?l cardiac muscle contraclion).
Relaxation of the cardiac muscle occurs as a result of decreasing the
intrace llu lar Ca 2• content to its pre-contraction level (so that its content
remains constant). Th is occurs by (a) Act ive reuptake or Ca 2 ' into the
sa rcop lasm ic reticulum (b) Active pumpin& of excess Ca 2 ' outside the
ca rdiac muscle fib res by an antiporr Na +_ Ca· ~ exc/umger carrier.
 10
Chapter 2 Characteristics o(lh e cardiac action potentials

THE CARDIAC ACTION POTENTIALS

Normally, slow and fast response ca rdiac action pote ntials arc recorded
(figure 5). The former is recorded from the S-A n ode ami A-JI node because
they arc poor in gap junctions (so the ca rdiac fibres in these nod<.:s arc ca lled
slo1v-response fibres ) while the latter is recorded from the atria and
l'entric:les as well as tile His - Purkinje system wh ich arc rich in gap junc-
ti ons (so the cardiac fibres in these regions arc ca ll ed j(1st-responsejibres) .
..50 A
-<'G
''"'
·.;:.
+50

c> 0
~ E 0
a..-
Q)
c -so -50
~
..0
E -100
CD -100
~

Figure 5 : A fast response action potential (A) and a slow response action
potentia l (B) reco rded from a ventricular musc le and the SAN respecti vel y.

Characteristics of the cardiac action potentials

Figu re 5 A shows a fast-response action potential recorded from a

,·entricu/or 1111/Scle .fibre (those recorded ji-om the atrial am/ Purkil1ie jihres
1w:t· in the duration l~( their components. and are sholl'n in .figure 4). The
resting potential in th c::.e fibres is about -90 mV, and the action pot<.:ntial is
characteri;ed by ( I) A steep upstroke (2) A large amp litude (up to I 20 to t
30 mV) (3) Presence of a plateau .
On the other hand, figure 5 B illustrates a slow response action potential
recorded from the SA node. The resting potential in the fibres of this n.:gion
is less negative than in the fast response fibres (-55 to -60 rnV ), and the
action potential is characterized by (t) Presence ofa pr cpotc ntinl (page 17)
(2) i\ less steep (i.e. slo'') upstroke (3) A sma ll amp litude (up to r- I to t I 0
mV) (4) o (or a brief) platea u.

Ionic basis of the cardiac action potential

(1) The fast response action potential consists of 5 phases ( ligurc

6). These phases and the associated ionic changes inc lude the fo llowing :
(a) Phase 0 (upstroke) : Thi s is caused by rupid depo larization of the ce ll
membrane (whi ch overs hoots to + 20 to + 30 mV). It is due to rapid Na+
innux secondary to ac tivati on (opening) of voltage-gated l11st 'a channels.
 II
Chapter 2 Ionic bm;is o{the cardiac actio11 pote11tials

(b) Phase 1 (early or partial repolarizatinn) : Th is is ca used by (1 ) ln-

activ<Hion (closure) or a channels (2) Liule K+ cfnux (as a result or a small
increase inK permeability secondary to opening or some K channeL).

(c) Phase 2 (pl ateau) : This is a unique phase in the fast response action
24
potential and is caused by increased Ca influx seconda ry to opening of
21
slow L (= lo11g-lasting) Ca chan11els (this is the Co 2 ' that stimulates Ct/'
releaseJi·om the .wrcop/asmic reticulum during excitation contraction coup-
ling, page 9). Ca 2 ' influx ba lances the increas ing K ' c nlu x. so the memb-
rane potentia l is kept constant as a plateau close to 0 mV (figure 6).

(d) Phase 3 (rapid r cpolarization) :This is caused by a marked increase in

K efflux in addition to inacti' ation (= closure) or theCa~ channels.

(e) Phase 4 (restora tion of the resting me mbran e potential) : This is

achieved by the Na+-lr pump which pumps outwards the a that had
entered the ca rdiac muscle fibre during phase 0, and pumps inwards the K '
that had left the cardiac muscle fibre during phases I. 2 and 3 (see above).

(2) The slow response action potential can also be divided into
5 phases (figure 6). However, the upstroke is slmr and is preceded by a
prepoteutial (page 17), reaches only to + l to+ I 0 mV and is caused mainly
by a11 increase i11 Ca 1+ influx ''ia slow L Ca 2+ clumuels. There is almost 110
plateau. and phases l. 2 and 3 merge together constituting a descending
repolarization phase which is more gradual than in the 1:1st response action
potential (figure 9). but is abo caused by an increase in K cfflux.
The following table summarizes the dirfercnces bctween the fast and slow
response action potentials (in a ventricu lar and SAN fibres respectively).

Fast response action potential Slow response action potential

The resting potential is about -90 mV
and remains constan t till excitation
The upstroke is rapid. It is due to Na ,.
influx. and reaches up to ~ 20 to - 30
mV
There is a prominent plat~au
The litllin g phase is rapid
The resting potential is -55 to - 60 mV
and is unstable (show ing prepotcntial)
The upstroke is slow. lt is due to Ca -
.
inllux. and reaches only to .J.. I to + I 0
mV
There is no {or a brief) plateau
The l~tlling phase is gradual
 12
Chapter 2 E:n:itabilitt• changes during cardiac action potentials

0 -

m~

Figu re 6 : Excitability changes during the fast and slow response cardiac
act ion potentia Is.

Excitability changes during cardiac action potentials

Dunng the fast and slo" action potentials. the com!sponding cardiac
mu-;clc fibre pas~ in the folio\\ tng 2 stage.\ of refrac:torine.,s (= unrespon-
sil'en ess) 111hich occur 11Wi11~11 as a result of inactil'tttion l~l the Na '
clullmef., in the cardiac lltttscle fibres ( figun: 6) :

( I) Absolute refractory period (ARP) : This is a period during which the

excitabi lity level is :ero (i.e. no stimulus whatever its st rength can initiate a
propagall:d action potential). In ca~c of the ra~t response. it extends from the
'tart olplwve 0 to the midcl/e o/ phose 3. '' hilc in the siO\\ respon~e. it cont-
tmtcs fill n'J)' !ale 111 plmw 3. Dunng the ARP. strong stimuli were found to
produce a local response which ha~ a low amplitude and conducts slowly. so
this period is also called the effi.•ctil·e refraclmy period ( E R P).

(2) Relati ve refractor y period (RRP) : This is a period during which the
cxc it ability is improved but still hclow normal, and on ly stimuli that exceed
the normal threshold can produce propagated action potentials (which arc
~low-ri~ing and of IO\\ amplitudes). In case of the fast response. it occupies
the remainder of phase 3. while in the slo\\' re ponsc. it extends in phase .J
after repolarization of the muscle fibre is completed. The later property or
the slow response fibres is called post-repolari:ation refractoriness.
 13
Chapter 2 Th e cardiac ARP

~ A third phase of excitability call ed the supernorma l phase occurs

only in thejast resp o11se.fihres. This phase occupies p/ws'e .J of the acti on
potcnti:ll, and during it the excitability is more than nonnal (so wea k stimuli
can produce propagated acti on potentials). Ea rly in thi s phase. an excitation
wave from an ectopic focus (or any other ex ternal source) is dangerous
because it may lead to ventricular fibrillation under certain conditi ons. so
thi s peri od has been ca lled the vu lnerable period {page 62).

0 100 200 300

ms

Figure 7 : Time relationship between the mechanical response. the acti on

potential and the various phases or exc itability in a vcntriculnr muscle !ibrc.

Time re lationship between electrical and mechanical responses

In the contractile fast response fibres, the mechanical response starts just
alter thc depolariza tion phase (phase 0) of the action potenti al. It continues
for a longer time than the action potential (figure 7) .. and the systole reaches
mn ximum at the end of the plateau phase (phase 2) whil e the first halr orthc
diastole coincides with the rapid phase of repolarization (phase 3) and the
second hal r of diastole coincides with phase 4.

Characteristics and importance of the ARPin cardiac muscle

Compared with skeleta l muscles, the duration of the ARP in th e

contractile(= fast response) ca rdiac muscle fibres is mu ch longer. This is
due to presence of the p lareau phase of the ac:rio11 poremial (during which
the membrane potential is zero i.e. the ce ll membranes arc depolari zed). It
occupies phases 0. I. 2 and the first half of phase 3, and is a!most as long as
the period of contraction . Accordingly. the cardiac muscle c wJIIO f he re-
srimulored during contractio11. This is an imporumt protection m echanism
 14
Cha[J(er 2 Factors that a{tect cardiac e.x:citabilit!l

that prevents summation of contractions and tetanus ( susta ined contrac-

tion) of the card iac muscle, which is fata l because the pumping function or
the heart will be lost (such function requires alternate periods of contraction
and re laxation, to eject blood then fill again respectively).
T he duratio n of the cardiac ARP is deter min ed mainly by the dura-
tion of th e platea u phase of the action potential. The following factors
affect the duration of the ARP through ajf"ecting the duration lithe plateau :
( I ) Regional fa cto rs : The ARP is longer in the ventricles than in the atria
because the the plateau is longer in the ventricular muscle (figure -l ).
(2) Autonom ic innervation : Sympathetic stimulation increases the memb-
rane conducwnce to Ca 2~, leading to prolongation of both the plateau phase
of the action potential as well as the ARP. By an opposite mechanism. para-
sympathetic (vagal) stimulation shortens the atrial ARP.
(3) C hemica l fa cto rs : ll ypoca lccmia, 0 2 lack c- hypoxia) and certain
drugs (e.g. procainamidc and quinidine) prolong the ARP.

FACTORS THAT AFFECT CARDIAC EXCITABILITY

( I ) Nervous fnctors : Sympathetic stimulati on increases the exc itability and

may activate ectopic 1<.1c i lending to tachycardia or extrasystolcs (sec below)

(2) Physical fa ctors : An increase in the body temperature increases the

cardiac excitability and vice versa.

(3) Chemical fact ors :

(a) Inorganic ions :
- Calcium : ll ypen.:a lcemia decreases the myocardia l excitability and
shortens the ARP while hypocalcemia exerts opposi te effects.
- Potassium : ll yperka lemia decreases the myocardial excitability and may
cause cardiac nrrcst in diastole wh ile hypokalemia increases it and may
activate ectopic loci.
- Soc/hun : Change~ in the serum a level do not significantly nffcct the
myocardial excitability but they affect the amplitude of the action potential.
(b) Hypoxia and ischemia: These decrease the myocardial excitabi lity.
(c~ Hormones : Catecholamines and thyroxine increase the myocardial
excitability and may activate ectopic foci (like sympathetic stimulation).
(d) Dm~s : Xnn thines (e.g. cn iTeine and theophylline) increase the myo-
cardial excitabi lit y whi le cholinergic drugs. quinidine and procai namidc dec-
rease it (the faller 2 dmgs ar e used to depress active ectopicfoci).
 15
Chapter 2 Extrasvstoles (premature beats)

EXTRASYSTOLES (= PREMATURE BEATS)

These are abnorma l systoles (contract ions) that arc produced by
impulses discharged from a hyperexcitable ectopic fo cus (= a focus other
than the S-A node). These fo ci may arise in the ventricle (producing
ventricular e:K:trasystoles) or in the atria or the /\-V node (producing
supraventricular extrasystole.\·), and they may develop normally (e.g. as a
result of excessive smoking) or pathologica lly (e.g. in myocardial ischemia).
Mechanism of extra systoles & the compensatory pause
Extrasystolcs arc produced only when an ectopic rocus discharges
during diasto le i.e. during the RRP (impul ses discharged during systole
fall in the ARP and arc not effective). They arc ca lled premature beats
because they do not increase the heart rate, and they lead to irregulariO' of
the !teart mte am/ are fr equently associated with pulse deficit (page 41)
because they arc usually weak and cause ejecti on or sma ll amounts of blood.
Ventricular cx trasystoles arc followed by long interva ls called compen-
satory pauses (CPs) which replace some missed normal beats . so the
duration of an exrra.~:\ 'Slo le and rhe following comJH!nsalOI~ ' pause + the
preceding com raction = durarion of 2 normal heats (figure 8).
The cause of the CP is that the normal impulse disc:lwrged .fi"om rhe S-A
node ajier w1 exrrasystole reaches the l'entricle ll'hile it is in the contmcrion
phase (i.e. rhe A RP) of the exrra.~:\'srole, so ir 11·ill he inejfective and acc-
ordingly 110 conrraction occurs and a CP ll'i/1 he recorded insread. However,
the next SA node impulse will be effecti ve (because the ventricle will be no
longer in the refractory state) and will produce a contraction which is usually
stronger them normal (= post-cxtrasystolic po tentiation. page 24). Such
strong contraction + increased ven tricul ar filling with blood du ring the CP
increase the stroke I'Oiume and the amplitude (?/!he arterial pulse.
A trial extrasystoles are often followed by sltorl or incomplete (or no)
CPs because the impulses that produce them also srimulare the S-A node,
which causes rapid shift to the nom1al si nus rhythm.

( ver~ ~ r ~ •'lll'\r)

Figure 8: Ex trasystolcs (premature beats). CP - Compensatory Pause.

P.P. = Post-cxtrasystolic Potentiati on.
 16
Chapter 2 A utomaticit11 am/ rh vtltmicitp

Physiological differences between cardiac and skeletal muscles

( 1) Skeletal musck contraction is initialed by impulses reaching the motor

end plates via the motor nerves whi le cardiac muscle comraction depends on
impulses initiated in a pacemaker and transmitted directly from cell to cell.
(2) The resting membrane potential of the slow response cardiac muscle
fibres (in the nodal tissue) on ly is unstable leading to prepotentials and
spontaneous discharge (sec nex t page).
(3) The action potential in the contractile (fast response)cardiac musc le fibr-
es onl y shows a plateau so the A RP is much longer than in ske letal muscle.
(4) Skeletal muscle on~1· can be tetanized due to summation of contractions.
(5) In the cardiac musc:le only. the excitarion-contraction coup ling depends
on the ex tracell ula r Ca 2• .
(6) The cardiac muscle only obeys the all or mme law.

(B) AUTOMATICITY & RHYTHMICITY(AUTORHYTHMICITY}

Automaticity is the property of self-excitation (i.e. abil ity of spontaneous

genera tion of action potentials independent or ex trinsic stimu li ). On the
other hand. rhythmicity is the regular gen eration of these action potentials.
The contractile cardiac muscle fibres do not n ormal~}' gen erate action pot-
entials. ln contrast, all pans or the conducting system arc normally capable
of autorhythmicity. but the llomwl (primar.1~ pacemaker is the S -A node.
while the A - V node is a secondar.l' pacemaker and the Purkinje system is a
tertiary pacemaker. The latter 2 act as latent pacemakers i.e. ihc A- V node
acts on ly if the S-A node is damaged, while the tertiary pacemaker takes
over only if impulse conduction via the A-V node is comp letely blocked.
The normal inherent rate or autorhythmicity or the S-A node (= sin us
rhythm) is 100- 11 0 I minute, while that of the A-V node(= noda l rhythm)
is 45-60 I minute and that or the Purkinje system (- idiovcntricu la r
rhythm) is 25-40 I minute.The unequal autorhythmi c activ ity in various reg-
ions is due to dil'fcrcnccs in th ei r rates of developing pn.:potentials (sec next)
Autorhythmicity is n myogeni c property (i.e. independent or the cardiac
nerve supply). This is evidenced by the foll owing :
(1) Completely denervated hearts continue beating rhyt hmi cally.
(2) Hea rts removed from the body and placed in su itable solu tions continue
beating for relat ive ly long periods.
(3) The transplanted hearts ha ve no nerve suppl y but they beat regularly.
:.:::._The cl'lcct of' various ractors on autorhythmici ty is ca lled chrono-
t ropism. Factors that increase autorhythmici ty arc ca lled + vc chronotropic
11H.:tors wh ile factors that decrease it arc called - ve chronotropi c factors.
 17
Chapter 2 ft-1ec/umism o[ a utorhJ•tlwticitl'

Prepotonbal

Time
Figure 9 : SA n od~ potentials (prepotential and action potential).

MECHANISM OF AUTORHYTHMICITY
The prepotential (or pacemaker "JO entiat)
The pacemaker cells in the nodal ti sue {SA node and A\ ' node) ha\e a
rc-.ting membrane potential of -55 to - 60 mV. l iO\\C\Cr. it i~ not stable. ~o
that after each impulse. gradual dcpolarintion occur-. -.pontancously till a
thn.:~hold {the firing lcn:l) b reached (- 40 to- 45 mV) at \\ hich an action
pot~ntial (i.e. an impulse) is initiated (figu re 9). Thi s gradual depolarization
i~ ca lled pacemaker pot ential , prcpotcntia l or diasto lic depolarization.
Mechanism of the pacemaker potential
The pacemaker potential (or prepotential) occur:, mainly secondary to a
progressive spontaneous reduction of the cell membrane permeability to
K (\\ hich decreases K ~11lu\. thus the membran~ ''ill be depolarized). Ca~
Influx\ ia T (tramient) fa.\1 er/~ d umnels also contribute.
~ A drug that op~n~ the K channels decreases both the rate offiring of
the SA node and the heart rate because (1) It increa-;e~ the cell membrane
pl.!mleabiliry to K , and this oppose. the spontancou~ reduction of the cell
membrane pem1eahility to K that produces the paccmnk~r potential (sec
above) (2) lt promotes K crn ux and hyperpolariza ti on or the S-A node
m~mbrane, and thi s prolongs the time required to reach the tiring threshold.
(\ 1\ 1\ 1\ (\ 0

2IJ'Q_\Jj}_~_ Symp~mctc A
60 mV

''""uJ1tton A

Figure I 0 : Effects of sympathetic and parasympatheti<.: (vaga l) stimulation

on the ~lop~ of prcpotential in the SA node ..
 18
Chapter 2 Factors that a[[ec:t autor/t)'t/uuic:itp

FACTORS THAT AFFECT AUTORHYTHMICITY

(1) NERVOUS FACTORS

(a) Parasympathetic stimulation decreases (slows) the slope of the pre-
potentials (figure I0). and accordingly the autorhythmicity of the pacemaker
ce lls is n::duced resulting in bra£~rcordia. Such -1•e chronotropic £:/Tee!
occu r~ secondary to ope11ing of the K c/wnnels (by the action of the
released acetylcholine on M~ muscarinic receptors) which leads to the same
effects produced by the drugs that open the K. channels (see above).

(b) Sympathetic stimulation increases (accelerates) the slope of the pre-

poten tia ls (ligurc I0). and accord ingly the autorhythm icity of the pm:emakcr
cells is increased resulting in tachycardio. Such I 1'<:' chroi/OfroJJic t:JJ'ect
occurs second<HY to closure ofthe K' clwnnels (by the action of the rdeascd
norepinephrine on beta 2 receptors) which leads to more rapid development
of the prcpotcntials.

(2) PHYSICAL FACTORS

1\ utorhythm ici ty is affected by temperature. 1\ rise ofth c body tem perature
(e.g. in muscul ar exercise and feve rs) increases the heart rate by about I0-20
beats I mi nute lor eac h I°C rise. On the other hand, in cases of hypothermia
the autorhythmici ty and heart .rate arc decreased. These effects occur secon-
dary to changes in the metabolic activity of the pacemaker ce lls in the SAN.

(3) MECHANICAL FACTORS

Distention of the right atrium increases the autorhyrhmicity of the pace-
maker S/\N probably secondary to st retch( - Bain bridge effect. page 73).
This response is important in transplanted hearts (which arc denervated) to
increase their ru tcs of beat ing when the venous return incrcnscs.

(4) CHEMICAL FACTORS

(a) Hormones : Catccholamines and thyroxine increase the autorhythmieity

by a mechani sm simi lar to that of sympathetic stimulation (sec above).
(h) Blood gases : Mild hypoxia increases the autorhythmicity (by stimu lat-
ing the pacemaker cel ls both directl y and by increasing sympathe tic ac ti vi ty)
whi le severe hypoxia & hypercapnia inhibit it and may cause cu rdiae arrest.
 19
Chapter 2 Conduc:th•itr in tlte cardiac muscle

(c) lnor~a nic ion s : l lyperkalcmia and hypercal cem ia dccn.:asc the slope or
thl! pacemaker potential and inhibit the autorhythmicity. whik hypokalemia
and hypocalcemia incn. :a~e it (by afTccting K nuxes). On the other hand.
both hypcrnatrcmia and hyponatremia tend to inhibit autorhythmicity.
(d) II + ion concentration (pH ) : Acidosis decrcasacs while alkalosis
incn.:ases the autorhythmicity (but in se,ere alkalosi-.. it is also inhibited).
(c) Dru~!l : ) 1npathomimetic drugs increase the autorh) thmicit) while
cholinergic drugs inhibit 11. Digitalis. although increasing the cardiac contra-
ctility. depresses the nodal ti ssue activity and exerts vagal-like cf"IC<.:ts
spe<.:iall) on the A-V node (reducing its rhythmicit) and conducti\ ity).
(f) Tox ins : Certain to\ in-. inhibit the aurorh) thmicity e.g. the toxin releas-
ed by the bacteria hat cause diphtheria (in this disease, a high fi.:n;r
associated with brady<.:ardia indicates ca rdiac dcprl!ssion).

(C) CONDUCT! VITY

This is the ability or the cardiac muscle to transmit action potentials from
one fibre to the adjacent libre. The impulses originating in the. -A node arc
conducted to the atria then through the conducting system to the ventricles
(page 8), nnd the last actil'ated parts are tlte postembawt! portion oftlw left
l'entride am/tlte pulmonm:JI conus t~f"tlt e rigltt l't!lllride.

The conduction velocity 'aries in di ITerent regions or the heart as folio"'" :

(I) It is /owe.\1 in the 1/()(/a/ tissues because they arc poor in gap junction"
(about 0.()5 meter I secmul in the A-V node am/ e1•en le.u in tile S-A node).
(2) It is moclemte in atrial and \'Cntricular muscle (a\erage I meler second)
(3) It 1s lughe.\t in the Purkinje netll"ork because 11 IS rich 111 gap junctions
(about./ meters I second). This allows complete and simultaneous excitation
or both ventricles.

A
f ·
v

Figure II : The A- V nodal region. I = AN region. 2 = N region. 3 = NII

region. A - atrium. V = ventric le. F = fibrous tissue septum.
 20
Chapter 2 Conduction in the A-V nodtil region

CONDUCTION IN THE A-V NODAL REGION

The 1\-V node can be functionally divided into 3 regions (fi gure 11)
(a) T he AN ( = Atrio-Noda l ) region : This is the upper part. It constitutes a
transitional zone between the atrial muscle and the next region of the node.
(b) T heN (=l'iodal) region : This is the middle and main part of the node.
(c) Th e NH (=Nodal-His) region : This is the lower part. Its libres merge
with the fibres that constitute the bundle of I lis.
1\- V nodal conduct ion is cllaracteri:ed by a delay of about 0.1 second
for impulse transmission to the ventricles due to 2 main factors :
( 1) The nodal muscle fibres are slowly-conduct ing (slow-response fibres)
that arc small in size and poor in gap junctions.
(2) The specia l cha racteristics (properties) of theN region of th e A-V
node, which include the following :
(a) The conducrion 1·eloc:iry is slo11·est in theN region (but however. the
greatest A-V nodal delay occurs in the AN region of the node because its
path length is greater than that of theN region) ..
(b) The conduction of impu lses through both the AN nnd Nil region s is
all or none wh ile it is dccrcment al in t heN region (i.e. the amplitude or the
:H.:lion potential tkcreascs gradually as it traverses theN region).
(c) The fibres in the N region show post-rcpolarization refractoriness
i.e. they remain relatively refractory (= incxcitablc or unresponsive) for a
significant time (phase 4) after their complete repolarization (page 12).

Importance of A-V nodal delay

( I) It allows the atria to depolari:e, contract ami emp~l' their blood
content into the 1•entricles before ventricular excitation occurs.
(2) It limits conduction ofirnpul es through the A-V node (wh ich ca nnot
no rm a ll ~ conduct more tha n 220 or 230 impulses I minu te) in en es of
high atrial rhythms e.g. atrial fibrillmion and lluttcr (page 61 ). This function
is important because excessive ventricular tachycardia is associntcd wi th
marked short en ing or the diastolic periods (during which ventricular fillin g
occurs) which results in pumping less amounts ofblood than normal.

FACTORS THAT AFFECT CARDIAC CONDUCTIVITY

(1) NERVOUS FACTORS

Sympathetic stimulation accelerates conducti vity (so it reduces the A- V
noda l delay) while vagal stimulation delays it and may cause heart block.
 21
Chapter 2 Mrm:ardial colltrac:tilit!'

(2) PHYSICAL FACTORS

Ri. e of the body temperature increases the rat~: of cardiac conductivity
while it is decreased in cases of hypothermia.
(3) CHEMICAL FACTORS
(a) Hormones : Conductivity is increased by catcc holamines & thyroxine.
(b) Blood gases: Conducti vi ty is decreased in cases of0 2 lack (ischemia).
(c) In orga ni c ions : Conductiv ity is decreased in most cases of electrolyte
disturbance (specially K ).
(d) H • ion concentration (pll ) : Conducti\ it) i" dccrca..,cd in acidosi'> and
slight!) increased in alkalosis.
(c) Drugs :Condueti\ ity is decreased by digitalis & cholinergic dmg:> (spec-
ially at the A-V node). whi le it is increased by sympathomimetic drugs.
~T h e conducti vity is also increased in the Wolff Parkinson-White syn-
drome (page 65) and decn:ascd in cases of hea rt blot:k (page 65).

(D) CONTRACT! LITY (CARDIAC MECHANICS)

The property of contracti lity doc not simply mean the ability of the
cardiac muscle fibres to contract but it refers to the force ge11erated by
myocardial c:rmtrac:tion.
The mechanism of myocardial muscle contraction is the same as tltat occ-
urring i11 skeletal muscles. It also depends on availabi lity of Ca~ and the
proccs of excitation-contraction coupling was explained before (page 9)

FACTORS THAT AFFECT CARDIAC CONTRACTILITY

These include the card iac preload and aftcrload, in addition to
intrinsic (cardiac) factors and ex trinsic (ext racardia c) fa ctors.

(A) CARDIAC PRELOAD (length-tension relationship)

What is meant by the preload '? : The preload is the load that detenn-
ines the resting length cl a muscle before con/metion.
Ca use of ca rdiac preload : The amount (or mte) of' ''enous hlood retum
is the main determinant of' the cardiac preload. and since the venous return
also detem1ines the end diastolic 'olume (EDV) and pressure (EDP). estima-
tion of either can be used to indicate the magniwdc or the cardiac preload .
Effects of ca rdiac preloa d : An increase in the cardiac preload increases
the tension de1·eloped hy rlw ''entricular mu.w:le ll.\ ll'e/1 as its l'elocif.l' (~f'
shortening (sec below), result ing in a more forcefu l ventricular contraction
 22
Chapter 2 Starling law and its significance

and an increase in the stroke vo lume. However, thi s occurs on ly up to a

certain limi t (at a sarcomere length of 2.2 microns) after which the peak
vcntricu lar perfo rmancc is dccrcascd (figure 12).
Such effects arc duc to an increase in (a) The exten t of overlap between
actin and myosin (which increases the number of interacting cross bridges)
(b) The affinity of the contracti le protein troponin C to Ca 1 ,.

Stmling (or Frank-Starling) law

This law describes the above length-tension relationship in muscles. It
states that " Within limits, the force of myocardial contraction is directly
proportional to the initial length of the cardiac muscle fibres ".

Vnnlt~Cular EOV

Figure 12: The Frank-Starling curves.

The Frank- Starltng curves

These curves illustrate the Starling law in \arious conditions of myo-
card ial contractility (figure 12). The middle curve shows the relation bet-
ween the EDV and the level of ventricular performance in normal resting
conditions, while the upper curve shows the effect of positive inotropic
l'a<.: tors and the lower curve shows the effect of negative inotropic l~1 ct ors .

Significance of Starling law

Starling law autoregulates the cardiac function according to changes in
the initial length of the cardiac muscle fibres as follows :
( I) In normal hearts : It allows changes in the right ventricular output to
match changes in the venous return (VR), and it also maintains equal outputs
from both ventricles e.g. if" the system ic (V R) increases, the right vent ricular
I ~ DV and output also increase, which matches the increased (V R). At the
same time, the pulmonary (VR) will also increase leadi ng to increase of the
len ventricu lar EDV and output, which balances the right ventricul ar output.
 23
Chapter 2 Factors a(fectim: contractifill' (a(terload)

(2) In failing hea rts : Ln this condition. the ventricular pumping power
is decreased. This leads to rise of the EDV. which increases the myocardial
contract ility (thus preventing much decrease in the cardiac output).
(3) In d enen ·a ted hea r ts (e.g. tra nspla nted hearts) : In these hearts.
autoregulation of myocardial contractility through Starling law becomes the
main mechanism that adjusts the pumping capacity of the heart.
(4) In cases of hyperte nsion : In these cases, the stroke volume of the
left ventricle would decrease. l lowcver, the remaining blood volume in the
left ventricle + blood returning fi·om the le n at rium during diastole wi ll
increase its EDV. Thi s leads to a powerful len ventricular contraction acco-
rding to Starling law, th us the accumu lated blood in the left ventricle will be
pumped inspire of the increased arterial blood pressure.

(B) CARDIAC AFTERLOAD (force-velocity relationship)

What is m eant by aftcrload ? : The aftcrload is the load that the muscle
faces when it begins to c:omract .
Ca use of cardiac a fte rl oad : The cardiac uftcrload is determined by the
magnitude of aortic impedance (resistance agai11st ll'hic:h the lefl1·entricle
or
ejects blood). The latter is determined by the leve l the aortic pressure and
other l~1ctors (e.g. it increases in aortic valve stenosis and in polycythemia).
Effects of ca rdiac after load : Changes in the aftcrload affect the extent
and velocity of shortening of 1he cardiac muscle as shown in the for c.c-
vclocity curve (figure 13). The l'elocity of shortening is inl'erse(v pro-
portioned 10 the magnitude (~/afterload. At Lero aftcrload. maximal ve locity
is achieved (Vmax) wh ile at a certain alkrload (Lo in the lower curve in
ligure 13), the velocity becomes zero and the muscle contracts isometrically.
/"'v,....
E~11ne
lnctta.l~ P<•~

--- - - - - · ~ol

5 10 IS
All.oo.d (O)

F igure 13 : The fo rce-veloc ity curve in the cardiac muscle.

 24
Chapter 2 Intrinsic (cardiac) (actors afl'ecting contractilitr

_:: The velocity of shortening is also affected by changes in the preload ami
tlte contractility stflle. An increase in the preload increases the initial veloc-
ity of shortening at any given aftcrload but not the Vmax (midd le curve in
figure 13). On the other hand. +vc inotropic agents (as epinephrine) increase
both the initial & maximal ve locity of shortening (upper curve in figure 13).

(C) INTRINSIC (CARDIAC) FACTORS

A significant loss of the ventricular muscle mass (e.g. due to infarction)

decreases the myocardial contractility proportionately. ll owever, apart from
this factor, 2 other cardiac factors affect myocardial contractility. These arc :

(1) The heart rate (Force-frequency relationship)

An increase in the fi·equency of cardiac stimulati on (e.g. in cases of tachy-

cardia) increases the contractility (a staircase phenomenon), and vice versa.
This is due to the increase in the number of depolarizations (which increases
the intracellular Ca 2 ~ content and its availability to the contractile proteins).
Also, the beats that fo llow the compensatory pauses of premature beats
( ex t~·asystole~) ~rc usually :trongcr. than normal. This is called e_o~ tcxtra ­
systohc potentiatiOn (page I:::>), and IS due to 11/0re release<?! ca- .from the
sarcoplasmic reticulum (S R) which occurs as follows : The premature impu-
lse increases the intracellular Ca2+ content as a result of Ca 2 ' influx from the
ECF. so the amount of Ca2- reuptake by the (SR) is im;reased during the
compensatory pause. and accordingly the next impulse leads to release of
excess Ca 2- from the (SR) which increases the force of contraction.

(2) The cardiac inotropic state (cardiac inotropy)

Cardiac inotropy is a peculiar intrinsic property of the cardiac

muscle. It signifies that the myocardial contracti lity can be increased or
decreased independent (?( clwnges in the preload or <.{/ierload. It is
determined primarily by the amount of (or sensitivi ty to) the delivered Ca 2 '
to the contractile proteins (actin and myosin), and the factors that increase
the myocardial colltractility are called +ve inotropic factors while the
factors that decrease it are called -ve inotropic factors.
The cardiac inotropic state is increased in cases of tachycardia (sec
above) and is also il!fluem:ed hy many e.rtracardiac (actors {see he/ow).
~ Th e major factors that determine cardiac: performance include(/)
The preload (2) Tlt e ajterload (3) The frequency of/wart contraction (4)
Tlte cardiac inotropic state.
 25
Chapter 2 Extrinsic (extracanliac) {actors a{[ecting contractilitp

(D) EXTRINSIC (EXTRACARDIAC) FACTORS

These factors affect the cardiac inotropic state, and they include :

{1) NERVOUS FACTORS

Sympathetic stimulation exerts a +ve inotropic effect by increasing (a)

The heart rate (b) C{,clic-AMP in the cardiac musc le fibres (which leads to
activation of the Ca-' channels resulting in more Ca21 influx from the ECF
2
and more Ca ' release from the sarcop lasmic reticu lum) .Converse ly,
parasympathetic (vagal) stimulation exet.1S a -ve inotropic effect by opposite
mechanisms, but on the atria l muscle only because the vagi nerves do not
supply the ventricles (refer to autonomic N.S.).

{2) PHYSICAL FACTORS

A moderate rise of the body temperature increases cardiac contractil ity

21
(by increasing the Ca influx and ATP formation in the cardiac muscl e)
while an excessive rise of the body temperature (e. g. in fevers) ex hausts the
metabolic substrates in the ca rdiac muscle and decreases its contractility.
Hypothermia also decreases cn rdiac contractility.

(3) CHEMICAL FACTORS

(A) Hormones : Cnteclto/amines (= epinephrine. norepinephrine and

dopamine) and the pancreatic hom1one glucagon exert a 1 ve inotropic effect
by increasing the cyclic-AMP content. Insulin ami thyroxine also excn a
+ve inotropic effect (the former by enhancing glucose transport into the cel ls
and the latler by enhancing the response to catecholamines and formation or
enzymes that have a high ATPase activity).

(B) Blood gases : Moderate hypoxia (= 0~ lack) and hypercapnia (= CO~

excess) increase the cardiac contractility through stimulating tht! peripheral
chemoreceptors (which increases the sympathetic discharge to the heart). On
the other hand, severe hypox ia and hypercapnia directly depress the cardiac
muscle and decrease its contractiliry.

(C) H+ io n concentration (pH) : An increase of the blood fl-1 '] i.e. drop
of the blood pH (acidosis) produces a-ve inotrop ic effect by inhibiting Ca~
release from the (SR) and its binding to troponin C,and may stop the heart in
 26
Chapter2 Extrinsic (extracardiac) factors affecting contractilitr

diastole (like excess K+). On the other hand, a decrease of the blood [H+] i.e.
rise of the blood pH (alkalosis) produces a + vc inotropic effect by an
opposite mechanism, and may stop the heart in systole (like excess Ca2+).

(D) Inorganic ions :

- Sodium : Hypematremia favours Na+ influx & Ca2+ efflux (by the antiport
Na+- Ca2+ exchanger carrier), so it exerts a - ve inotropic effect. On the other
hand, hyponatremia exerts a +ve inotropic effect by an opposite mechanism.
- Potassium : Hyperkalemia exerts a - ve inotropic effect and may stop the
heart in diastole because the excess K+ in the ECF causes partial depolariza-
tion of the cardiac muscle cells, so the amplitude of the action potential is
decreased leading to less Ca2+ influx. On the other hand, hypokalemia
produces a + ve inotropic effect by an opposite mechanism.
- Calcium : Hypercalcemia exerts a + ve inotropic effect as a result of more
Ca2+ influx. It prolongs the systole on the expense of the diastole and the
heart may stop in systole (Cal+ rigor), so i. v. Ca 2+ injections should be
given very' slowly. On the other hand, hypocalcemia usually has a little (or
no) -ve inotropic effect, since lowering of the serum Ca2 + level causes fatal
tetany before affecting the heart (refer to endocrine glands).

(E) Toxins : Certain snake venoms and the toxin released by the bacteria
that cause diphtheria produce a - ve inotropic effect (mostly by a direct
action on the contractile mechanism of the cardiac muscle)

(F) Drugs:

- Cardiac glycosides (e.g. digitalis) : These drugs inhibit the Na+-K-+

ATPase in the cell membranes, so the intracellular Na+ concentration
increases. However, the Na+- Ca2+ anti port carrier promotes Na+ efflux in
exchange with Ca 2+ influx from the ECF. Accordingly, the intracellular Ca2+
concentration increases, producing a + ve inotropic effect.
- Xantltines (e.g. caffeine and tlteophylline) : These drugs exert a +ve
inotropic effect through increasing the intracellular cyclic-AMP (by inhibit-
ing the phosphodiesterase enzyme which breaks down cyclic-AMP).
- Quinidine, barbiturates, procainamide (and other anesthetic drugs) as
well as the Ca1+ channel blocker drugs all exert a - ve inotropic effect by
decreasing the Ca2+ influx into the cardiac muscle fibres.
 27
CHAPTER3

THE CARDIAC CYCLE

Acting as n hydrauli c pump, the human heart has periods of contraction
(du ring which blood is pumped into the large arteries) that alternate with
peri ods of relaxation (during which blood fills the heart). These cont raction
and relaxation periods occur in cycles known as the cardiac cycles. each of
which COII'iists ofa period of contraclion called ,\ ystole /ol!mi'C!d hy a period
of' relaxalion called diastole. and they nonnally occur at a rate of about 75
t.:~•cles p er minute during rest (i.c.cach cycle lasts about 0.8 second ).

lsovolumlc relaxation
Ejoctlonl
lsovolumrc
con1rac11on \
[
/
I
r
nopid intlow
Oraslasis
/AtriAl systole

120 Aortrc Aortrcvalvc

valve closes
100
c;;
:I:
E
§. 60
80
....
-----
opens

---r---
........ ___ Aonrc pressure

Q)
5
"'"' 40
Q) A·V volvo
a: 20 opens
c v
,...::_ _ Atnal pressure
0
Ventncular pressure

~·~j
e 9o
Ventncular volume

::>

~ 50

Systole Orastolo

Figure 14 : Phases and events that occur in the left side of the heart and
aorta during the cardiac cycle.
 2g
Chapter 3 Phases o[lhe cardiac C}lc/e

The mechan ica l events (i. e. changes in pressure and volume) that occu r
in the left side of the heur t during one cardiac cycle as well as the aortic
pressure changes and the associated valvular el'ents. heart .\'0111/d\· and ECG
tracing are all shown in ligure I4.
The mechanical events that occur in the right side of the hea11 and the
pulmonary artery arc similar to t hose occurr ing in the left side and aorta
(figure 15), except that the right ventricular pressure during .\:l'Stole and the
pressures i11 the pulmonw:r arte1y are much /0\l'(!r than those in the leji
l'entride and aorta (so constituting part of the low pressu r e system , page 4)

Aight~::r
p-e:uTC

Figure 15 : Changes that occur in the righ t ventricul ar and pulmonary

arteri al pressures during the cardiac cycle.
PHASES OF THE CARDIAC CYCLE

The cardiac cyc le starts by atriai .\JIStole (about 0. 1 second) that is foll owed
by ventricular systole then ventricular diastole. The atrial diastole starts
early in vemricular systole then conlinues for about 0. 7 second.
VENTRICULAR SYSTOLE

This lasts about 0.3 second and it includes 3 p hases (a) Isometric (=
isovolumetric or iso ,·olumic) contraCiion phase (0.05 second) (b) Maximum
(rapid) ejection phase (0. 15 second) (c) Reduced ejectio11 phase (0.1 second).
(a) THE ISOMETRIC CONTRACTION PHASE
The events that occur during this phase include the following :
( 1) Ventricu lar pressure and volum e : The ventricles contract isometric-
ally (i.e. without shortening of the cardiac musc le fibres) thus the ventric-
ular pressure rises sharply while the ventricular volume remains constant.
(2) Valves : Both A-V \'(/ll'es are closed because the ventricular pressures
exceed the atria l pressures, and both semilunar valves also remain closed.
(3) Soun ds : The first/teart sou11d is produced in this phase as a result or
closure of the A- V va lves (see below).
 29
Chapter 3 Phases o[ventriculnr srstole

(4) At rial pressu re : This increases . lightly on closure of the A- V valve!'i

due to ballooning (bulging) of their cusps into the atrial ca\ itics.
(5) Ao rti c and pulmonary artery pressures : These gradua lly decrease
due to now or blood from the aorta and pulmonary artery to the peripheral
sma ller vessels. They decrease to minimum values at the end of this phase(=
diastolic blood pressure) just before ventricular ejection (to about 80
mmllg in the aorta and 9 mm l lg in the pulmonary artery).
(6) ECC : The Q wave stans about 0.02 second before thi phase. whi le
the Rand S waves arc recorded during it.

(b) THE MAXIMUM EJECTION PHASE

The evems that occur during this phase include the following :
( 1) Vcn tl'i cular vo lum e and pressu re : The ventricles contract isotonically
(i.e. the cardiac muscle fibrc5 arc . hortencd). thus the 'cntricular 'olumcs
rapidly decrease while the ventricular pressures increase graduall y to a max-
imum of 120 mmHg in the left ventricle and 25 mmHg in the right ventricle.
(2) Valves : Both AV valves remain closed while both semilunar l'ah·es
open when the 'entricular prc5sures exceed the diastolic pressur~~ in the
great arteries (about 80 mmllg in the aortu and 9 mmll g in. the pulmonary
artery) which results in blood eje<.:tion in these vessels.
(3) Ao rti c a nd pulm onar y art ery pressu res : These increase gradual ly
(due to blood ejection from the 'cmriclcs) to a maximum that nearly equals
the maximum pressures in the t:orresponding ventric les i.e. 120 mm llg in
the aorta and 25 mmllg in the pulmonary artery(= systolic bl ood press ure).
(4) Atri ul pressure: This is initially decreased due to widening of' the atrial
ca' itics which occurs as a result of{a) Atnal dia5tolc (h) Pulling of' the 1\-V
fibrous ring downwards during ventricular contraction (c) Des<.:cn t or the
cusps of the A V valves after blood ejection from the vcntridcs. 71!e atrial
pressure then gradual~v increases due to the continuous ve11ous retum.
(5) Sounds : The first heart sound continues for a brief period in this phase
(6) ECG: The S-T segment is recorded and the T wuve starts in this phase.

(c) THE REDUCED EJECTION PHASE

The events in this phase arc just cominuation of those occurring in the
preceding phase, and they include the following :
(1) Ventricular volume : Thi s is further decreased.
(2) Ventricular press ure : This starts Lo decrease due to pumping of most
of the ventricular blood into the great aneries during ma:-.imum ejection.
(3) Aortic and pulmonary artery pressures : These decrease bct:ausc the
ejected amounts of blood from the ventricles into the aorta and pu lmonary
artery become smaller than the amount of blood leaving them lo the
 30
Chapter 3 Phases of' ventricular diastole

peripheral sma ller vessels. ll owcver. they gradually become slightly more
than the ventricular pressures (although both arc decreasing), but in pile of
that the blood flow from the ventricles to the aorta and pulmonary aticry
continues by the momentum of the fonvard blood fl ow.
(4) Va lves : The semilunar valves arc open and the A V valves remain closed
(5) Atri al press ure : Thi s is still increasing due to continuous venous return
(6) Sounds : There arc no sounds in this phase.
(7) ECC:Thc ascending limb & top of the T wave arc recorded in this phase

PROTO DIASTOLE

This is a very shot1 period that ll'as descrihed between the end of
ventricular systole and start of ventricular diastole. However, this period is
general ly considered a part or the isovolumetric relaxation phase.

VENTRICULAR DIASTOLE

This lasts about 0.5 seco nd and it includes 4 phases :

(I) lsometr·ic (= isovolum ctric or isovolumic) relaxation phase (0.05 sec.)
(2) Rapid (maxim al) tilling phase ( Ea rly ventricular d iastole) (0.15 sec.).
(3) Slow (reduced) tilling phase (M id-ventricular d iastole) (0.20 sec.).
(4) Late ventricular diastole (coincident with atri al systole).(O.I 0 sec.).

(a) ISOMETRIC (ISO VOLUMETRIC) RELAXA T/ON PHASE

The events thai occur during thi s phase inc lude the fol lowing:
( I ) Ventricular pressure and volume : The ventric les relax isoml!trica lly
(without lengthening of the cardiac fibres) so the ventricular pressure falls
sharply to about 0 mmHg while the ventricular volume remains constant.
(2) Atrial pressure : This is still increasing due to continuou. venous return
(3) Va lves : Both semil111wr mlves are closed because the arterial pressures
exceed the ventricular pressures, and both .tl-1' \'{/h•es also remain closed.
(4) Sounds : The second heart sowul is produced in this phnse as a result of
closure of the semi lunar va lves (see below).
(5) ECG : The descending limb of the T wave is recorded in this phase.
(6) Aortic and pulmonary artery pressures : These gradually decrease
(due to flow of blood from the aorta and pulmonary arlety to the peripheral
smaller vesse ls) with appearance of a dicrotic notch and a dicnHic wave
(sec next).
 31
Chapter 3 Phases o[ 1•entricu/ar diastole

THE DICROTIC NOTCH and WAVE (WINDKESSEL EFFECT)

1\t the start or isomctril! relaxation, the blood in the aorta and pulmonary
artery flows back towa rds the corresponding ventricles (because of thL:
higher pressures in these vessels as described above). This results in (a)
Closure or the semilunar valves and production or the second hea r t sound
(b) 1\ small o ·cillation (disturbance) on the downslope or the aortic and pul -
monary arterial pressure curves called the dicrotic notch or in cisura (due to
vihrations in the hlooJ ll'helllhe semilunar I'O!I·e.\ are sudden~! ' closed).
Following the dicrotic notch, a wave called the dicrotic wave is record-
ed due to a slight increase in the aortic and pulmonary arterial pressures
(whi ch then decrease gradual ly due to flow of blood to the peripheral
sma ll er vessels). This wave ocl!up ies the diastolil! period and is produced as
a result of clastic reco il of t he ao r tic a nd pulmonary arteri al wa lls. The
latter e!Tect is produced by a mechanism called the wi nd kcssel effect, which
occurs as follows : Stretching or the aorta and pulmonary artery during the
ejection phases creates potential energy in their walls, and during isometric
relaxation, this energy is converted into kinetic energy which causes these
vessels to rebound (leading to their recoil). The windkessel effect maintains
forward movement or blood during ventri cular diastoles. which renders the
blood flow to the tiss ues to be continuous (during both systoles and
diastoles) and not pul satile (i.e. not interm ittent during systo les only).

(b) RAPID (MAXIMAL) FILLING PHASE

In this phase, the atrial pressure exceeds the vcntril!tllar pressure, so the
1\ V valves open and the accumulated blood into the atria rushes into the
ventricles. The events that occur include the following :
(1) Valves : The A V valves open while the semilunar valves remain closed
(2) At ria l pressure : This initially decreases due to rush of blood from the
atria into the ventricles then it increases due to the continuous venous return.
(3) Ventricula r pressure: This initially decreases due to ventricu lar relaxa-
tion by the rushing blood from the atria, then it increitSes gradually with the
increased amount of blood pumped from the atria.
(4) Ventricula r volume : This increases markedly as a result of filling or
the ventricles by the blood coming from the atria.
(5) Ao rtic and pulmonary artery pressu res : These decrease gradually due
to the continuous blood now.from the aorta and pulmonay arteries to th~..:
peripheral small artcrie. .
(6) Sounds : The 3rtl lteart .wnmd is produced in this phase (see below).
(7) ECG : The early part or the T-P segment and the U wave (if present) arc
n.:co rded in this phase.
 32
Chapter 3 Diastasis and atrial spstole

(c) SLOW (REDUCED) FILLING PHASE (DIASTASIS)

This pha se is a continuation of the rapid lilling phase and is associated

with the followin g even ts :
( 1) Valves: The A V valves arc open while the semilunar va lves arc closed.
(2) Atrial pressure : This is till increasing due to the venous retum.
(3) Ven tricu lar pressure and volume : These gradually increase but at a
slower rate (due to reduction of the amount of blood coming from the atria).
(4) Aortic and pulmonary artery pressures : These arc still decrca!)ing
due to continuous blood ilo\\ from the aorta and pulmonary artc1y to the
peripheral small arteries.
(5) Sound s: There arc 110 sot11uls in thi s phase.
(6) l~C G : The late part of the T-P segment and the start of" the P wuve arc
n.:corded in this phase.

DIASTASIS and ATRIAL SYSTOLE

The sloll' .filling phase is .fl"equent~~- called diastasis because of the very
slow lil ling to the ex tent that the blood almost stagnates in the heart till the
next cyt:lc starts. llowevcr, ve1:r lote in ventricular diastole, the ntria t:on-
tract Hnd s11ch atrial systole usually causes an additiona l 20 %1 Iii ling or the
ventri cles. The events that occur during atrial systole include tlte./(JIImving
(I) Atrial pressure : This initiall y increases due to decrease of the atrial
volume. then it decreases due to rush of blood into the ventricl es ..
(2) \ 'cntriculnr volume and press ure : These also sli gh tly increase by cfT-
cct of the blood pumped from the atria.
(3) \'a i\'CS : The AV va h es nrc open while the sem ilunar vahes arc closed.
(4) Ao rti c and pulmonary a rtery pressures : These arc grad ually decreas-
ing due to continuous blood flow from the aorta and pulmonary artery to the
peripheral small arteries.
(5) Sounds: The fourth heart sound is produced in this phase (sec below)
(6) ECC : The P wave starts about 0.02 second before this phase, whi le the
main part or the P wave. the P-R segment and the Q wave occu r during it.

REMEMBER

~ The systo lic pressure in each ve11tricle is nearly equal to that in its
corresponding artery i.e. about 120 mmll g in the le ft ventricle (as in the
aorta) and 25 mmH g in the right ve ntricle (as in the pulmonary artery). Con -
verse ly, the diastolic pressure in each ventricles is equa l (about 0 mmllg).
 33
Cllapler3 Tile velllriclllar press11re - vo/11111e loop

~The elasticity (compliance) of the aorta is important because (1)

It prevents excessive increase in the systolic pressure during ventricular
systole (2) It allows continuous blood flow to the tissues (windkessel effect).
Thus, in arteriosclerosis, the systolic pressure rises markedly (figure 19) and
the blood flow to the tissues becomes almost only during systoles.
~ The AV valves open during atrial systole and the filling phases,
and close in the other phases. On the other hand, the semilunar valves
open during the ejection phases and close in the other phases.
~ During the isovolumetric phases (I) All valves are closed and the
ventricles become closed chambers (2) The muscle te11.<iio11 o11ly is dru11ged
(not the muscle length). The tension increases during isovolumetric con-
traction ( = interval between the start of ventricular systole and opening l?l
the semilunar valves), and decreases during isovolumetric relaxation(= int-
ten•al between closure of the semilunar valves and opening (?l the A V valves)
~ The amount of blood present in the ventricles just before the start
of systole is called the end diastolic volume (about 130 ml during rest)
while the amount of blood that remains in the ventricles after ejection is
called the end systolic volume (about 50 ml during rest). The ejected
amount of blood per beat is therefore about 80 ml and is called the stroke
volume. It constitutes about 65 % of the end diastolic volume, and this is
called the ejection fraction (page 77).
~ The incisura (= dicrotic notch) that is recorded on the downslope
of the arterial pressure curve (figure 14) indicates the end of ventricular
systole, closure of the semilunar valves and start of ventricular diastole.

m
T
I
l.
.. 0
~
.:
;; l
:' •o~ I
I .l_,
o --------~==~~-----Lt~!
L·
__j i
~0 lOC I.SO
left ventricular volume (mil

Figure 16 : The left ventricular pressure-volume loop during a cardiac cycle.

 3-t
Chapter 3 The heart souml.\

The ventricular pressure volume loop during the cardiac cycle

fhc \ cntriculm pressure.: and 'olurne changes dunng the cardiac cycle
can be demonstrated in the form or a loop. A normal/e.fi ''entricular loop is
shown in figure 16. and is intcrprcted as follows :
( I) The mitral valve opens at A. and ventricular filling occurs between
A and C. The initial decrea:-.c in pressure (from A to 13) is due to ventricular
rd,l\ation b) the rushmg blood from the lefl atnum.
(2) The mitral 'ah c elm,!!!'> at C and isometnc 'entncular contracuon
occurs between C and D.
(3) The aonic ,·ah c opens at D. and rapid ejection occurs bel\\ een D
ami I ~ while reduced ejecti on oecttrs between E and F.
(..t) The aortic valve closes nt F. and isometric ventricular re laxation
m.:curs between F and A. At A the mitral valve opens starting a new cycle.

EVALUATION OF LEFT VENTRICULAR PERFORMANCE

This can be carried out by determination of the loiiO\\ ing periods :

( I) The total electromechanical systole (QS2) : This is the period from
tlH.: onset of the QRS complex of the ECG to the closure or the aortic valve
as determined by the onset of the second bean sound ( s , ).
(2) T he lcrt ventricul ar ej ection tim e (LVET) : This is the period from
the beginning of rise of the arterial pressure to the dicrotic notch.
(3) The pre-ejection period (PEP) : This is the difTercnce between QS~
and LVET. It represents the time for the electrical and mechanical events
that precede '>)'Stolle ejection. The ratio (PEP I LV ET' ) is nom1ally about
<>.35. and it incrca:-.es without changes in OS:! if the ldi 'entricular pcrfoml-
ance is decreased.
THE HEART SOUNDS

The heart sounds can bc recorded through a sensi ti ve microphone placed on

the chest wall (a proccss called phonoc••rdiogra phy). Thc recorded trat:ing

STSIOlf OIAllOlf
~r-------~'-----~

..... 1 - - . . --..: 2
I
..
I
. ·-- ... .: . . I
'
I

,- ---·-- - ·'-
1
1 I

Fi1!ure 17 : A nonnal phonocardiogram.

 35
Chapter 3 The first heart sotmd

is called the phonocard iogram, and it shows that 4 sounds occur normally
during each cardiac cycle (figure 17). The first and second sounds arc
always heard through au scu ltution (= listening by a stethoscope). On the
other hand, the third sound is sometimes heard in children while the fourth
sound is normally inaudible in all ages.
The first sound occurs at the start of ventricular systole and is heard
as "lub" whi le the second sound occurs at the start of ventricula r diastole
and is heard as "dup". Since the duration of systole is shorter than that of the
diastole (about 0.3 and 0.5 second respective ly), heart beating has the
rhythm of lub d11p -pause- l11h dup -pause- l11b d11p- pause, and so on. ln
tachycardia, the diastolic periods are reduced, so the pauses are shortened
and the identification of the 2 sounds becomes di rficult. However, they can
sti ll be differentiated by simultaneous palpation of the carotid pulse (the
sound that occurs about the same time of that pulse is the first hea rt sou nd).

THE FIRST HEART SOUND

Timing in the cardiac cycle: This sound coincides with the onset of vent-
ricular systole, so it falls mainly during the isometric c:o11tractio11 phase and
also extends in the ea rly part or the max imum ejec:tio11 phase (figure 14).
Cause: Closure of the AV va lves
Mechanism : The sound is produced by the vibrations set up in the blood,
chordae tendineac and ventricular wall after closure of the A V valves. Tt is
not the result of snapping shut of the valves (because blood greatly damps
the effect of slapping ofthe valve leafl ets together).
Characters: lt is a soft low pitched sound.
Duration : About 0.15 second.
Site of bearing : Closure of the mitral va lve is best heard over the apex of
the heart at the 5th left intercostal space I 0 em from the midline just internal
to the midclavicular li ne. On the other hand, closure of the tricuspid valve is
best heard at the lower end of the sternum ( ligure 18).

Splitting of the first heart sound

Normal ly, the mitral valve closes before the tricuspid valve. and this would
produce splilling of the first sound. However, this is difficult to detect by 1

auscultation (and even by phonocardiography) because the sounds produced

by closue ofboth va lves are low pitched and merge into each other.
 36
Chapter 3 Til e .\econd heart .w nmd

Fi~:.urc
18 : Sites of hearing the heart sounds by the stethoscope.
M. T. 1\ and r = Mitral. rnt:u'>ptd. Aorti~.: and Pulmon:11y areas. 1 and 5
L.J.S. 2nd and 5th le n int e r~.:os tal spaces. nu: . line midclavicular line.

THE SECOND HEART SOUND

Timing in the cardiac cycle : This sound coinctdes '' ith the onset or' ent-
ricular dia-.tolc. so it fa! 1-. dunng the isometric re/axMion pfla,e (figure I -1 ).
Ca use : Closure or thl! -.emtlunar valves.
'Jcchanism : The sound is prodm:t.:d by the vibration" set up in tlw blood.
'l!ntricular ''alb and \\'alb or the aorta and pulmonar) artel) after closure of
the semi lunar valves. It is also not the result ofsnapping shut of tile vah•es
C haracters : It is sharp and has a higher pitch than that of th~: first sound .
Dura tion : /\bout 0.12 se<.:ond.
S it e of hearing: Closu rl! or the aortic va lve i!-. h~:ard over the sewnd costal
t:art ilage at the right Slt.:rnal border, while closure of tht.: pulmonary va lve is
heard at the second left intercostal space close to the !-> ternum (figure 18).

Physiological splitting of the second heart sound

Normally. the pu lm onary va lve closes after the aortic valve (because
the right ventri cle is weaker than thl! left ventricle. so its systole is longer)
 37
Chapter 3 Gallop rhvtltm

leading to sp litting of the second sound. Such splitting is more ap parent

durin g deep inspiration bt.:causc this increases the venous return which
further delays closure of the pulmonary valve (= physiological sp littin g). In
addition, splitting ofthc second sound is characterized by the following :
(1) Jt is easier to hear titan splitting of tlte first sound (because closure of
the semi lunar valves produces higb pitched sounds).
(2) lL is heard almost only at tlte pulmolllll)' area (because closure of the
aortic va lve is audible in all areas of the precordium wh ile c losure of the pul-
monary va lve is heard only close to the pulmonary area).
(3) ll is more easily heard in children nnd it may be inaudible in older
individuals spec ially males (due to muscle noise and the thick chest wall).

Paradoxical splitting of the second heart sound

This is a condition in which the pulmonary va lve closes before the

aortic va lve. It is characteristic of left ventricular failure (due to the slower
ejection from the left ventricle than normal which delays closure of the
aortic valve). Tn this case, deep inspiration does not increase splitting oftlte
second sou11d but rather decreases it (= paradoxica l splitting).

THE THIRD HEART SOUND

This is a so ft low pitched sound that occurs during the rapid fillin g
phase of the cardiac cycle (ligure 14). Tt is produced as a result of oscilla-
tion of the rush ing blood from the atria into the ventricules. Its duration is
about 0. I scco nd .and is best heard during expira ti on at the apex of the heart.

THE FOURTH HEART SOUND

This is a fa int very low pitched sound that occurs during atrial systole
and its mec hanism is simil ar to that producing the third sound. Its duration is
0.03- 0.05 second and is normally inaudible (see above).

GALLOP RHYTHM

In some heart diseases (specially lefi veutricularfailure) and certain

other conditions (e.g. severe anemia and thyrotoxicosis). the 3rd or 4h heart
sound is augmented and becomes audible. On auscu ltating the heart in these
condi ti ons, more than 2 sounds wil l be heard during each cardiac cycle, and
these sounds follow each ot her in a rhyt hm similar to that produced by a
g~lllopin g horse (so it is rclc rrcd to as a gallop rhythm ).
 3R
Chapter 3 lfeartmm·11wrs

HEART MURMURS

A heart murmur is an abnormal sound i.e. a sound that is not normally

present (in contrast to g allop). They arc produced when the nonm1l si len t
(- laminar) blood now is replaced by a turbulent (noisy) blood now, which
occurs when the blood velocity exceeds a certa in limit (page 95). The blood
velocity incrcascs after an urea of partial obstruction in a blood vessel anti
also as it passes through stenotic or insufficient heart valves. A stcnotic
valve is a stiff nmTOII'I!d t•ah·e that does not open complete~\ ' while:; an
insurfit:icnt (or incompetent) va lve is a valve that does not close co mplete~\' .

TYPES OF HEART MURMURS

(1) Systolic murmurs : Thesc occur during the ventri cu lar systolic peri od
(i.e. between the first and second sounds). Thcy may occur '''ithout heart
disease (e.g. in anemia. fevers and exercise) or as a result or va lvu lar dis-
orders produced by diseases (specially rheumatic fever) or congenital abnor-
mali ties. The va lvular disorders that produce systolic murmurs arc either :
(a) Stenosis of one of the semilunar valves
(h) In competence of one of th e AV valves: This may occur clue to sca-
rring or the valve cusps or a disorder in the papillary musc le-chordae tend in-
enc system. In these leaky valves. blood regurgitation occurs toward the atria
during ventricul ar systole resulting in the abnormal sound.
(c) Ventricular Septal Defect (VSD) (a congenital abnormality).

(2) Diastolic murmu rs : These occur during the ventricul ar diastoli c per-
iod (i.e. betwcen the second sound and th e next first sound) as a result or
either or the follow ing valvu lar disorders :
(a) Stenosis of one of the A V valves (e.g. due 10 rheumatic rever).
(b) Inco mpetence of one of the semiluna r valves : In aot1ic incompe-
tence (which is com monl y due to sypltilis ), blood regurgitates f'rom the aorta
ino the len ventricle during vcntricular diastole resulting in a murmur as
well as reduction 1~/ the diastolic preS.\'111'<!. Tht.! systolic pressure abo
increases (bccau~e the left vemricle will eject a larger \Oiumc of blood than
nonnal) so the pulse pressure also increases (sec below).

(3) Continuous murmurs (during systole & diastolc)c.g. in patent ductus

arteriosus (since the aortic B.P.is always higher than the pulm. arterial 13.P.).
 39
Chapter 3 Th e arterial pulse

Pat""t ClUCl\J•
0

f<'ig urc 19 : The arterial pulse waves in vnrious conditi ons.

THE ARTERIAL PULSE

This is the expansion of the arteries that occurs during left ventricular
systole as a resu lt of blood ejection. The ejected blood expands the proximal
part or the aorta producing a cent ral pulse which then sets up a press ure
wa ve that trave ls along the arteries lead ing to their expansion wh ich is called
the periph eral pulse.
The rate of pulse wave transmission is inverse~J' proportional to the
arteria/ wall compliance (so it is about .f meters I second in Fhe aorfa and 16
meters I second in the small arteries). It is also mucltfnster titan the velocity
t~( b/oot!.flmv (the velocity of the latter is on~l' about 0. 5 m eter I second ).

The arterial pulse wave

The nonnal arterial pulse wave (figure 19) is similar to the aortic press-
ure curve recorded during the cardiac cycle (figure 14 ). and it consists of :
( I) An ascending limb (or anacrotic) limb : This occurs during left
ventricu lar systole as a resu lt or rise or the arteria l blood pressure produced
by blood ejection into the aorta. The arteria l blood pressure nonnal ly
increases to a maximum of about 120 mm l lg (= systolic blood pressure)
(2) A descending (or catacrotic) limb : This occurs during left vent -
ricular din. tole as a result of fall of the artcrinl blood pressure produced b)
~ . . l:ape or blood from the aorta to the peripheral arteries. The arterial blood
pr~~!iurc normally decrease~ to a minimum or about HO mmHg (- diastolic
 -tO
Clwmer 3 The pul.\e pressure

h/ootl pre.\sure). As in thl! aort1t: pressure t:un c. thl! <kSt:l!IHiing limb also
t:ontain~ a tlic:rtltic: 11otc:lt tmd a dicrotic wm•e ( t sl!vcra l minor o~cillations).

Changes in the pulse wave in peripheral arteries

The peripheral pulse is twmwi~J' delay ed than the central pulsl! by periods
that \ ar) according to the site of the artery (e.g. the pulse in tht: radial artery
at the" nst ,., nonnall) felt about 0.1 second artcr the peak of aortit: pulse).
In .tddition. its shape i~ altered and it!> amplitude become:- progrc~si\cl)
less as it tnt\ cis into the pcnphcral vessels (so capillw:r pul.wrion\ occur
on~r [/the aortic pulsations ore exrreme~r large or rhe arrerioles are greor~r
diloted). This is ca llt:d dampin g of the press ure pulses, and is prod uced by
the comhined ef/ect <?l the resistance to hloud 1110\'elllent in the 1•essels <Is
ll'e!l w r/1(' compliml<'£' o/rhe l'e.,sels.
:: In the femoral artcr). the amplitude of the pulses ruther increases
probabl) b) effect of rejlectet! H•m•es from diMal poi11ts i11 the arteria/tree.
ln addllion. the incisura bewmcs less sharp but the diastolic ll'al'es becom e
m ore appare11t particularly the dicrotic H•m •e.

The pulse pressure

Thi~ equals the differcnt:c bl.!twccn the systolic and diastolic pressures.
so it is normally about .tO mm ll g. It increase\· !!'rlu.:' \ysrolic pressure rises
or rhe clwsrolic preuure fall\ (or hoth change' rogether) e.g. in ca\e,· of'
anerio.\cll'ro\i \. parenr duu II\ orreriosus and cwrr ic reg111~!!, IWI ion (figure
19). ' '' ma/{11i111de i., determined by 3 main factors\\ hid1 are the folltm ing:
( I ) T he stroke volu me.
(2) T he speed by " hich the stroke volu me is ej ected.
(3 ) T he co mplia nce (d istensibili ty) of the arter ies.
The magnirude (~/the pulse pressure is direct~\' proportional to rhe
.lint 2jclctors and ill\'ersC'~\ ' proporrional ro the thil'(/faclor.
:: /\hscnce oft hl.! pube is not ah1•ay.\ indimril·e l?/stuppoge (J(h/ood
/loll' (tf the mean arterial pressure is main tained normal at about 95 mm ll g,
there" ill he an adequate blood flow although the pulse is not detected).
:: hamination or the arterial pul e gi\ es information about the heart
role one/ r/11·rhm as \l·e/1 as the h•,·e/.\ of the .\_n/0/h am/ pulse pre\.\1/res.

Abnormal patterns of the arterial pulse

( I) Pulsus a lt crnans (a ltcmating large and small pulsations) : Thi s is a sign

of advanced left ventricu lar failure (specially if due to hypcrtl.!nsion). It is
 -ll
Cltapter 3 Tlt e jugular l'enous pulse

probably due to prolongation of the ARP in some myocardial fibres as a

resu lt or 0:! lack (page 14) whi ch causes these fibres to respond on ly to
every other i111pul se (so there will be alternating increase and decrease in the
number of the contracting muscle fibres. which results in this type of pu lse).
(2) Pulse deficit (the pulse rate is Jess than the heart rate) : This
commonly occurs in case· of extrasystoles (page 15) and atrial fibrillation
(page 61 ). In the !alter condition. 2 heart beat~ frequently come so close to
each other that the left ventricle "ill have too little time to fill beween the
beats. Accordi ngly. the 2nd beat pumps no (or very liLtlc) blood. which fails
to produce an arterial pulse (although it produces heart sounds). Therefore,
the pul se becomes irregular <!nd its rate during a certa in time wi ll be lcs.
than the heart rate during the same time (normally both arc equul).
(3) Pulsus pa radoxus : Normall y. the venous return increases during
inspiration (due to the increased intrathoracic negativity) and this would
increase the left ventricular stroke volume and the arterial pube amp litude.
ll owever. this docs not occur because the pulmonary vesse ls arc also dilated
due to the same cause, and wil l accommodate much of the right ven tricular
outpu t, so the left ventricular stroke volume and the arterial pulse amp litude
arc IIOI'IIIlil~l' kept constant or they 11/C~I' be slight~v decrea,·ed
Pulsus paradoxus m eans marked decrease r~f'tlte arterial pulse
amplitude durin~-: inspimtion. It occurs in cardiac diseases that detJ"ease the
ve11ous retum e.g. c:onstricth'e pericarditis and cardiac: tfiiiiJWnade (=
cardiac compression) 'vvhich is often due to a massi,•e pericardia/ c:flitsion.
(4) Flat (platea u) pul se : This is characteristic of aortic sten osis (figure
19). The pulse wave rises slowly to a lower amplitude than normal. and is
also delayed than normal (so it is also ca lled pulsus tardus).
(5) Water hammer pulse (= Collapsing or Cor rigan's pul se) : This
occurs in all cases of increased pulse pressure (page 40) special ly aortic
va lve insurticicncy (or incompetence). In the Iauer case. the pu lse waves rise
sharply to a high vo lume then rapidly co llapse (i.e. fal l abruptly) as n result
of sudden drop from a high systolic pressure to a very low dinstolit: pressure
(due to blood regurgitation into the left ventricle) and the dicrotic notch and
dicrotic \\'U\'C disappear (figure 19). The systolic ejection or blood may also
be strong enough to cause head nodding with each heart beat.
(6) Thready pulse (i.c.very rapid - low amplitude pulse waves) : This
specially occurs alier a severe hemo1Thagc as wel l as in heart f:1i lu rc.

THE JUGULAR VENOUS PULSE (J .V.P.)

The J. V.P. is the pressure changes that occur in the jugular veins during
the cardiac cycle. It can be seen by the naked eye and can also be recorded
(the record is call ed the pltfebogram ). It consists or 3 positi,·e waves (called
 -11
Chapter 3 Walles o[llte j ugular l•en ou!> p u i.\C!

the a, c and v waves) and 2 depress ions (called the:\ a nd y descents). Suc..:h
changes arc transmitt ed from th e right atrium because there nrc no va lve~
at th e entry or the venae c:wac into the right ntriuni, so they arc simi lar to the
atrial pressure changes (figure 14) but they arc slightly delayed (ligurc 20).

.....__ _ _ _ Algt\1 "lllal

pros:.ut\3

Jugular
- - -- vonous
pro:.sure
'i

Time-

Fi gure 20 : Record ol"thc J.V. P, carotid pressure and ri ght atrial press ure

THE (a) WAVE

Thi!-. wave occurs during atrial systo le. Its ascending limb i!-> due to ( 1)
Increase of the right atrial pressure (\\ hich is transmitted to the jugular
'ctns) (2) Damming (or accumulation) of blood in the jugular' cins (due to
constnc..:tton of the orifices of the \Cnac ca,ac during atrial s)stolc). On the
other hand. Its descending limb i:. due to decrease of the right atrial pressure
as blood lea\'es the right atrium and emers the right 'entriclc.

THE (c) WAVE

The a~<.:cnding limb of this wa\c occurs during isovolum ct ric ventric-
ul ar co ntraction due to ( 1) Bulging of the tricuspid valve into the right
atrium (which incrca~es the right atrial pressure). (2) The carotid artery
pul.\ ation.\ (\\ hich arc transmitted to the jugular \Cins). On the other hand.
lis clescemling limh ami tlte x clescem occur during car l ~ ejectio n due to
111creow 111 tlte rigltt atrial capadtr (\\ hich decn.:ases the right atnal
prc-.sure) as a result l>f ( l ) i\trial relaxation (diustole) (2) Pulling of the J\ - V
ring downward during ventricular systole (3) Descent or the tricuspid ,alvc
to its normal position as blood is pumped out from the ri ght ventricle ..
 -B
Chapter 3 Clinical signific:rmce o(t!Je jugular venous pulse

THE (v) WAVE

The ascending limb or thi s wave occu rs during most of the ej ection
phases of the ca rdia c cycle as well as t he isovolum ctric relaxation phase
due to increase of the right atrial pressure as a result of accumulati on of the
venous blood returned to the right atrium while the tricuspid valve is closed.
On the other hand. its desc:e11ding limb and they desce11t occur during the
rapid fillin g phase due to drop of the right atrial pressure as a result or
openi ng of the tricuspid vah e and rush of blood into the right vent rick.

CLINICAL SIGNIFICANCE OF THE JVP

(A) The a-c interval (from the sta rt of the "a" wHve to the start of the "c"
wave) is an index (~/co /lducril •ity through the A- V node. It corresponds to the
P-R interval of The ECG. and its nonnal dural ion is 0.12 - 0. 2 1 second.
(B) The .1. V.P. waves arc Hltered in many cardiac di seases, so its recording
is helpful in the diagnosis of these diseases. For examp le :
( J ) Large "c" and '\" wa,·cs are recorded in cases of tr icuspid
in co mpetence due to blood regurgitation from the right ventricle .into the
right atrium during ventricular systole.
(2) The "a" wave amplitude is much increased in cnses or tricuspid ste no-
sis , pulm ona ry stenosis and pulm ona ry hypertens ion.
(3) Giant "a" waves ca lled ca nnon waves are recorded if the right atrium
and right ven tricle contract at the same time (so the tricuspid va lve is closed
leading to much rise of the right atri al pressure). This occurs in cases of A-V
dissociation (e.g. in complete heart block a/1(11·entricular tach.1·cardia).
(4) The "a" waves disappear in atrial fibrillation due to ineffic ient atrial
contraction. However. in this case the number or the "c" and """ waves is
greater than normal but arc quite irregular (page 6 1).
(5) Inspection of the J. V. P. can di fferetiale atrial from ventricular extra-
systoles (atrial extrasystoles produce a J.V .P. that contains the "a" waves
whil e ventri cular cx trasystolcs produce a J.V. P. that lacks the "a" waves).
CHAPTER4

THE ELECTROCARDIOGRAM (ECG)

AND THE ARRHYTHMIAS
The electrical currents generated a. a result of myocardial electrical
acti\ it) (depolari7<lllon and repolarintion) nrc conducted through the body
fluid" to the hod) -.urface "here the) can be detected and recorded. 'I he
n.:cord is called the I·C<i. and it evaluates the cardiac ch.:ctric events (which
greatl y helps in the diagnos1" of many cardiac diseases). I hc apparatus used
is called the electromrdiogroph. and it consists basically of a sensitil·e
gall'lmometer and 2 <!lectrodes (which are applied to the skin}.

RECORDING OF THE ECG (THE ECG LEADS)

The 2 electrodes that record the ECG can be applied at many areas of
the skin. and any particular arrangement of these electrodes is called a lead.
12 of such leads (sometime!'> more} are usually used to record the electric
cardiac cvcnts from dil'li.:rcnt situations. These EC'(i leads arc 2 mai n types :

(A) Bipolar limb leads (standard limb leads of Einthoven)

These leads record the differences between the potentials in 2 limbs.

3 of ~ u c h leads arc record ed (figure 21 ). which include :
( I} Lead I : This records the difference bet\\ een the potential in the left am1
(It\) and that in the nght ann (RA) i.e. LA - RA or \ ' L - \ R (\' \Oltagc).
(2} Lead II : This records the difference between the potential in the left leg
(LL) and that in the right ann (RA} i.e. LL- RA or \' F- \ 'n (F foot).
(3) Lead 111 : This records the difference between the potentia l in the len
leg (LL) and that in the len : ~n n (LA) i.e. LL- LA or VF- VL.

Einthoven's triangle

'I his is an imaginar) equilateral triangle. thl! -.1tb. of'' l11ch represent the
3 bipolar limb leads (figure-. 21 and 30) and the heart lies at its centre.

Einthoven's law

'I his law states that the sum or 'oltages in leads I and Ill equab the
volt age in lead II (li gure 30 h), and it can be used to ca lc t~lat c the vol tage or
a certain lead i r the voltages or the other 2 leads are known.
 45
Chapter 4 R ecording o(llte electrocardiogram

Connec tt'd to ECG

- I

COMO<Iod '" l C(j

Figure 21 : The bipolar leads (standard limb leads).

(B) Unipolar leads

Thesl! measure the abso lute (i.e. actual) potent ia l at a certain poi nt. Thi s is
carried out by appl ying one electrode from the elec troca rdiograph to the des-
ired point (= l l'e or exploring electrode) while the other electrode is made
ind[f!'erent or -ve (i .e. at 0 potential). Therefore. a unipolar lead measures the
diffe rence between the potential recorded by the exploring electrode and
7ero potcmial.

f'igurc 22: Recording of the unipolar chest leads (T= central terminal)..
 46
Cllapter4 The unipolar leads

How can an ECG electrode be made indifferent (at 0 potential) ?

The potentials in o closed circuit neutmli::e each other, so their
algehmic sum = ::ero. Electrodes rrom the 3 li mbs that arc con nected to a
common tenninal constitllle o closed circuit. so the potential at such
common (or central) tem1inal will be zero. Therefore. when the central
terminal is connected to the -vc pole of the electrocardiograph. it will
consti tute an indif'f'erent electrode having zero potential (= Wilson'!->
electrode). and in such case app~ring the exploring electmde (i.e. the
electrode connected tv the 1 I'C! pole of The electrocardiograph) at a cerwin
poiw (11·hether at the limbs themseh·es or on the chest ll'ct!l as sholl'n in
.figure 22) will record the ahsolllle potential at that point.

Types of unipolar leads

( I) Unipolar limb leads : These record the absolute potential at the right
arm, left arm and left leg (by applying the +ve electrode at these limbs) and
the potentials obtained arc called VR, VL and VF respectively (figure 23).
(2) Unipolar chest leads (Wilson's precordial or V leads) : These
record the absolute potential at 6 standard points on the anterior chest wa ll
designated as V1 to Jl6 • the locations of which arc as follows (figure 23) :
V1 : ;\t the right margin of the sternum in the 4th right intercostal space.
V2 : ;\t the left margin of the sternum in the 4th lcll intercostal space.
V3 :Midway between V ~ and V-1.
V4 : At the left midclavicular line in the 5th intercostal space.
V!' : At the left anterior axillary line and at the same level or V ,.
V(, :At the left midaxillary line and at the same level of V., and Ys.

...
/-'!\
. •...
~~ v ··:. .. · .
-· 3. .
. ' v4 ·. vs Vs

• VF

figu rc 23 : Local ion or the ~o:\ploring electrode in various unipolar lead:-.

 47
Cltapter 4 Calibration o[ tlte electrocardior:raplt

The augmented unipolar limb leads (Goldberger's leads)

These arc magni ficd unipolar limb leads (by 50 %) without change in
configuration, so they arc ca lled aVR, aVL and avr (a = augm~ntcd).Thcy
arc easier to interpret and arc routi nely recorded by modern ECG machines.
The augmentation of a unipolar limb lead is achieved by disconnecting its
electrode from the central terminal. rn this case. the augmented lead
measures the difference between the potential in one limb and the sum of
potentials in the other 2 limbs e.g. to record aVR. the electrode or the central
terminal at the right arm is unattached (figure 24).

Figu r e 24: Recording or augmented VR (aVR).

Calibration of the electrocardiograph

The electrocardiograph records 011 upward (+1•e) deflection wlten a
depolarization wa ve moves to ward lite explori11g elect-rode or a
rep olari:ation wave moves a way from it, a11d vice versa (figure 25). It is
al o arranged in a way that a change f~( JmV produces a dejlection of /0 mm
amplitude. so each mm in the l'ertical lines c~( the tracing paper (side ol o
small square) equals 0. 1 m V. On the other hand, the recording speed is u~­
ually 25 111111 per second, so the duration of each 111111 in rite lwri;ontol line.,
of the tmcing paper (side of a small square) equals 0. 0-1 seco11d, and the
durati on or each 5 111111 (side ofa hig square) equals 0.2 second (ligurc 27).

Calculation of the heart rate from the ECG

The duration of a single cardiac cycle is first detennincd (by mu lt ip lyi ng
the distance in mm between 2 success ive R waves x 0.04). The hea rt rate is
then ca lculated by linding the number of cycles per minu te (60 seconds) c.~.
if the measured distance was 15 mm. the duration of a sing le cardiac ~ycle:
15 x 0.04 0.6 second and the hcati rate = 60 I 0.6 = I 00 beats I minute.
 48
Chapter 4 S pread o( cardiac excitation

:::The hean rate can also be dctennined by counting the number of small
or big squares in the ECCi paper as follows : When the recording speed is 15
mm per .\ecoml. one minute on the ECG paper" ill he represented by 25 x 60
1500 mm (i.e. 1500 small squnres or 300 big squares). In this case. if tht!
duration of one cardiac cyc.:le was 15 mm (i.e. 15 small squares or 3 big
squnrcs), then the heart rate 1500 I 15 or 300 I J I00 beats I minute.

~i~Jl
(n.lu .• • · i·• ~• 'I' • • .1, ~

c. i-~·l
. . + •

sI ' s/
o . ,M.JI•uuiiU4'' f, orn l•tt 10 fl\tf\1
Ot~PQI .u., .. t•on hom lt:h to H ~tl •t

(
+
-.J -/lA G -rl JL + I

Rt:9QII41ft U I•on •-... ''"'"" "'hom u .-, t to a.h

ih•""'"•'-1 1~ !- .,of.nWlQ l1w.tn J. tt ' '' n;J11

c= ±++ { k
( p:-Av ± ~t -r

Htpot.t~ U l>Un (ompltltd

A c.5J()I.WIUI•....n (QI'tl . . . . t.d

Figu re 25 : Denections produced by depolarinllion and repolarization in

skeletal m (le ft ) and cardiac m (right).£ = exp loring electrode. S = stimul us.

Spread of cardiac excitation

Depolarization in itiated in the S-A node spn.:ads through the atria fro m
right to left, then in the interventricular septu m from left to right (by a twig
from the left bundle branch). In the ventricular wall. it spreads from the
endocardial to tlte epicardial surface. and the last pans to be depolarized
arc the posterobasal ponion of the left 'cntricle. the pulmonal') conus and
thl.! uppennost part of the inten entricular septum (figure 26 ).
 49
Chapter4 Spread of cardiac excitation

Figure 26 : Normal spread of electrical activity in the heart. The direction of

the depolarization wave in each part is represented by an arrow(= vector).
 50
Chapter 4 The normal electmcardiogram

THE NORMAL ELECTROCARDIOGRAM (ECG)

The ECG consists of 5 main waves cal led P, Q, R, S and T waves, and
sometimes, there is an additional wave following the T wave ca lled U wave
(figure 27). Such waves arc separated by segments, and each starts and ends
at the isoelcctric line. The Q, R & S waves form a complex ca lled the QRS
complex. and fi·cqucntl y the Q and S waves arc nonnally not clear in some
leads. The terminat ion of the QRS complex at the isoc lcctric line is ca lled
the J point. and its determination is clinica lly important.
A
1.0
I I I I l
._
~~dELE~~A 1c
LINE-
0.5

PA SEGMENT ~MENTT !"-..

--tTi4 1 iJ.
++~u~
0
~~
PA INTERVAL O
~ ~~
I
I I
- 0.5 I 1
O~ I~TEAVAL~OASOUAATION 1_ r-h
0 0.2 0.4 0.6
Time hi

Figure 27 : A classic ECG tracing recorded from a left precordial lead (V6 ) .

PWAVE
Thi s wave is produced as a result of atrial depolari':;ation , and normally it s
amplitude is about 0.1 mY while its duration docs not exceed 0. 1 second. It
is normally positive in all leads except aVR (page 53) Its ) irs/ part is due to
right aTrial activation while its terminal part is due to leji arrial activation.
Abnorma lities of the P wave : In left atrial hyp ertrophy (e.g. due to
mitral stenosis), the P waves enlarge and become notched (= P mitrale) and
their dural ion increases because depolarization of the hypertrophied muscle
Lakes more time than norm al. In right atrial hypertroph y (e.g. due to tri -
cuspid stenos is), the amp!itude and durati on or the right part or the P waves
increase and overlap the !crt part, resulting in tall peaked P 1raves with
almost normal duration (= P pulmonale). The P waves are also inverted in
A V nodal rhy thm and disappear in atrial./ibrillation (page 6 1).
:_: Normally , there is no "'ove representing depolari::ation r?(llie SA node
beca use exci tati on of this node docs not generate suffic ient electrica l activ ity
to reach the body surface. Also there is no ll'ave representing atrial repolar-
i::arion because it is normally small and is masked by the waves of ventri c-
ular depolarization (i.e. the QRS comp lex) which occur at the same time.
 51
Chapter 4 Th e n ormal electrocardiogram

QRS COMPLEX
This wave is produced as a resu lt of ventricular depolarization and its
duration is 0. 06-0.1 second. Depolari::ation of the interventricular septum
produces rhe small Q wave. which is nomwlly negative in the leads facing
the le:fi ventricle because the depolarization vector of the septum is directed
.fi'om le.fi to right (figure 26).
The R wave is a large wave having an amp litude about I0 mm (I mV)
that is caused by Jepolari::ation ofrhe apex and l'enrricular ll'a/1. It is+ vc in
the leads facing the left ventricle because ventricular depo larization proceeds
from the endocardiu m towards the epicardium and the depolarization vector
of the left ventricle predominates over that of the right ventricle (figure 26).
On the other hand, the S wave is due to depolari::ation of the postero-
het.wl part o,j'the leji ventricle and the pul11wnw:v conus, and it is normal ly
negati ve in the leads fac ing the left ventri cle because the depolarization
vector of these areas is directed from left to right (figure 26) .
.:=.The QRS amplitude is much larger than that of the P waves because
the ventricular muscle //lass is greater than that of the atria (so generating
more electric activity). ll owever, the duration of the QRS complex is almost
equal or even sho1ier than that of the P waves because the Purkil?ie .\ystem
rapid~1· propagates excitation in the l'entricles.
Abn ormalities of t he QRS complex occur in cases of vent ricu lar hyper-
trophy, in fa rcti on and cxtrasystoles, as well as in bundle branch block and
most cases of electrolyte disturbance (see below).

Twave
Th is wave is prod uced ns t, resu lt of ventricular repolarization. It s amp-
litude is 0. 2- 0.4 m V, \vhi le its duration is 0. 2 - 0. 25 second (longer than the
QRS complex because repolari::ation is slower than depolari:ation).
Why the T wave is positive ? As a repolarization wave , the T wave should
be negati ve (opposite to the depolari zation wave,QRS complex).Hovvever it
is n ormally +ve (figure 27) because the last part of the ventricular muscle to
depolarize is the first part to repolarize, and thus ventricular repolari:.ation
proceeds from the myocardial epicardial surface towards the endocardial
smface, which results in an upright (+ ve) deflection (figure 25).
Repolarization fa ils to start at the myocardi al endocardial surface probably
as a result of ischemia (which may occur at this site due to the high ventric-
ular pressure during ventricu lar systo le that compresses the blood vessels).
Abnormalities of the T wave : The T wave bcomes inverted (or iso-
clectr ic) in cases of myocard ial ischem ia, ventricu lar hypert rophy and extra-
systoles, bundle branch block and digitalis overdosage. On the other hand .
its amplitude increases in cases of sympathetic overactivity. muscular exer-
cise and. hyperkalem ia (page 57).
 52
Cltapter .J P-R and 0- T intervals and S- T segment

U WAVE
This is a small positive wave that fo ll ows the T wave. It is probably
produced by slmv repolari:.ation oftlte Purk inje network. ll owever, it is not
a constant finding and its physiological signi fica nee remains unseuled.

P-R INTERVAL
This is the interval from the start of the P wave to the start of the R wa,·e
(i.e. from the onset or atrial excitation to the onset of ventricular excitation).
It normally ranges from 0.12 to 0.21 second. This time involves conduction
of the cardiac impulse through the A V nodal region. so it is an index f()r the
duration of A V nodal delay. It is prolonged in (a) First degree heart block
(b) Increased vagal tone. \\'hile it is shorten ed in (a) A-V nodal rhythm (b)
Sympathet ic overactivity (c) Wolff-Parkinson-White syndrome (page ()5).
The P- R segment :This is a segment between the end of the P wave and
start of ventricular depolarization. During this segment,dcpolarization occurs
in the conducting system (starting hy the .A/' node at the tOp (~/the P II 'C/1'£:') .
ll owever,it is si lent (contains no waves) because the depolarized ti ssue is too
smal l to generate elect ri c changes great enough to reach the body surfitce.

Q-T INTERVAL
This is the interva l from the onset of' the Q wave to the end or the Twave.
It is normally 0.3- 0.4 s~cond (varying inverse ly wit h the hcurt rate), and it
provides an index or the duration or the ventricular act ion potl!ntial

S-T SEGMENT
This is the segment from the end of the S wave (J point) to the start of
the T wave. and its duration nom1ally average~ 0.12 second. During thi~ seg-
ment. alll•entricular fibres are depolari:ed. so it is nom1ally isockctric and
its del•iation indicates myocardial injtl1)' or damage (page 56).

Time relation between the ECG and ventricular action potential

The QRS complex corresponds to the depolarization phase i.e. tht.:
upstroke or the action potential (phase 0). the S-T segment to the p l ut~au
phase (phase 2), the T wave to the repolarization phase (phase 3), and the T-
p segment to phase 4 of the action potential. (figurl! 4 right).
Relation between ECG and the events of the cardiac cycle
The P wave precede:-, th..: atrial systole and the QRS com plex precedes the
isometric vcntricu lar con tracti on (each by about 0.02 second ). Also. tl1<: jirst
heart .\'OIIIId coincides \l'ith the swnmit of the R ll'ave ,,·hile the second hellrf
sot111d coincides ll'ith the end o,/the T wave (figure 14).
 53
Chapter 4 Normal ECG variations
II III aVR aVL aVF

Figm·c 28: An ECG of a normal adu lt man showing the records of the
bipolar and unipolar limb leads (notice inversion of all wave. in lead aVR).

Normal ECG variations in different leads

{1) Lead aVR : The P wave. QRS complex and T wave arc all normally
negative (in verted) deflections in lead aVR (figure 28) because the vectors
of atrial and ventricular depolarization (figure 26) and that or ventri cular
rcpolarization move away li·om the exp loring elect rode at the right arm.
{2) The precordial leads : The electri c forces of the heart act in the
frontal, sagitta l and horizontal directions, and the precordial leads look at the
heast in a horizontal plane from the front and left sides. In the right
precordial leads e.g. V 1 and V2 (whi ch look at the right ventricle). there arc
small R waves followed by deepS waves (figure 29). whi le in left precordial
leads e.g. V5 and V6 (which look at the len ven tricle), there arc small Q
waves lollo'vvccl by large R waves (figure 29). Th is is because :
(a) The excitation wave at the interventricular septum moves from len to
right (figure 26). producing small + ve (R) waves in right precordial leads
and small -ve (Q) waves in left precordial leads.
(h) Exc itation then proceeds from the endocardia l to the epicardial surf'acc
in hoth ventricles sim ultaneous~" (figure 26) As the left vent ri (;ul ar mass is
greater than that of the right ventric le. the electrical chang~s occurring in
the left ventricle predominate, so rhe ventricular depolari::ation \'ecwr is
directed towards· the left, producing large R waves in the left precordial
leads and deepS waves in the ri ght precordial lends.

VI V2
/ I
t +
Figure 29 : Configurati on of the QRS complex in the precordial leads (a, b.
c. d & e show the order in which excitation spreads through the venrriclcs).
 54
Owpter .J Mean electric axis o(llre ventricles

Mean electric axis of the ventricles

The depolarization wave in each cardiac muscle fibre is represented by

an an·ow pointing to the + ve direction (figure 25) called a vector, the
magnitude and direction of which vary in different fibres. The vectors of all
ventricu lar muscle fib res are represented by a single vector that can be
determined from Einthoven's triangle (figure 30 a) and is ca lled the mean
electric tL\·is of tire ventricles. It represents an electromotive force that is
normally directed down\\'ards and to the left bcl\,een -30° nnd t 110° (figure
30 c) at an average or 1 60°
The projection or the electric axis is toward the + ve pole in the 3 bipolar
limb leads, w - re dejlec1ions are normal~r recorded in 1hese leadr;. This is
shown in figure 30 b (which also illustrates Eimhoven's loll', page 44).

:~e:
mm 5
0
•5
-0
-S :Smm

b I

~L
r:::
• 16
II

<II
- 1 - I
• 15mm + IOmm

Figure 30 : The mean clccrric axis of the vent ride~.

-v- '_A_
- +

._A_-\:W-
~w~ + +
Aogh l • •I• deviation
VT + +
Left ads devilll ion

Figure 31 :Right and left ax is deviat ion.

 55
Chapter 4 ECG manifestations o[ axis deviation

AXIS DEVIATION
Tht.: mean electric ax is may he sh[jied to the l'i~ht or to the leji.
Right axis deviation normally occurs in vertica l ht.:arts (t.:.g. in lul l
subjects) but pathologically it occurs in many conditions particularly rig ht
11entricular hypertrophy ami right bundle branch block (sec below) In this
case, the projection of the electric ax is is toward the -ve pole in lead T and
toward the -1 vc pole in lead Ill. so in ECG there arc deep S \I'Cll'es in l ead I
and high R 11'(/I'L'S in lead III (figure 31 ).
Left axis deviation nonnally occurs in horizontal hearts (e.g. in short
stout subjects and pregnant women) but pathologically it occurs in man)
conditions particu larly left ventricular hypertrophy amllefi humlle branclt
block (sec below). ln thi. case. the projection of the electric axis is toward
the +vc pole in lead I and toward the -ve pole in lead Ill , so in ECG there nrc
hi gh R waves in lead I and deepS waves in lead Ill (figure 31 ).

I.- ~

I!
I I
I I
l

I
I
""" ~~
I
v1 v2 v3 V4 v5 v6
f igure 32 : ECG manifestations of right and len ventricu lar hypt.:rtrophy
(the P waves may be normally inverted in lead V1). Notice axis dev iation.
 56
Cltapter .J ECG IIUmi[estations o[veutricu/ar hvpertropltJ'

ECG MANIFESTATIONS OF VENTRICULAR HYPERTROPHY

Left ventricular hypertrophy (fi gure 32) leads to (I) Appearance ol'
high R waves in Je ll r record ial leads (V5 and V1,) and ut:cp S waves in ri ght
precordial leads (VI anu V ~ ) (2) Inversion ofT waves in the len rrel:ordial
leads (due to relative ischemia of the increased muscle mass) (3) Le ft a xis
deviation bemuse the greal muscle mass (l the lej; l'entricle a/loll's (a)
Generation of excess electrical currents i11 the left side of the heart (b)Comp-
lctc dcpolari;ntion of the right ventricle before the left ventricle. which crea-
tes a strong potential from the right side tOward the left side of the heart.
Right ventri cu la r hypertrophy (figure 32) leads to ( I ) Appearance
of high R \\'aves in right precordial leads (V 1 and V 2) which exceed the
depth of the S waves. together with deepS wa\es in left prel:ordialleads (V,
and V f>) (2) Inversion or T waves in the right precordial leads (due to rela-
tive ischemia or the increased muscle mass) (4) R ight a xis deviation (uue to
the samt.: c.:aust.:s of lcl1 a\is ueviation in left ventricular hypertrophy).

ECG MANIFESTATIONS OF CORONARY INSUFFICIENCY

As a result of coronary insuffic iency, the myocardium may suffe r onl y
ische mia but injury or necr osis (= death of musc le) occur in severe cases.
Ma nifestation of isc hemia : The resulting hypoxia re t ard~ rcpo lari;ation
in the !.!pit:ardial side of tht.: a!Tcctcd p<u1, so rcpo larization sta rt s from the
t.:ndot:a rdium towa rd the epicardium producing inverted T wm•es.
Manifestation of injury (current of injury) : Th is l:auses S-T sexment
slr((t (elevation or depression depending on the site of the exp loring elect-
rod\!) as follows : lnjw:r o( the cardiac muscle causes persistent clepolari:a-
lion in the t{//ected part, and this results in flow of a current between the
pathologically depo larized and the normal po lari;cd parts ca ll ed the current
of inj ury. This current leads lO incomplete rcpolarization or the cardiac mus-
cle, ~o the T-P segmenl pOientialfe,·el becomes d(fferelll fi·mn that l?/ the S- T
segment (normally both are isoelcctric) and this causes the S-T segment to
appear as if it 1vas shifted. alllwugh !he slt!f; 11·as ac:tuol~r in the T-P
sel!.ment. Tht.: Jailer is shifted downward in the leads facing the injury. so the
I ~ CG finding in these leads is S-T segm elll e!el'flfion (ligurc 34).

figure 33 : Production or pathological Q wave due to myocardial infarcti on.

 57
Chapter 4 ECG mani(estations o( mvocardial in(arction

Manifestation of necrosis (= infarction) : This occurs almost always

in the le./i ventricular wall or imervenlricular septum or both (right ventri cu-
lar infitrction is rare). The necrosed myocardium becomes electrically- inert
and cannot be depo larized. 1r the whole free thickness of the left ventricular
wall is nccrosed. it creates a !tole or a window through wh ich an exploring
electrode reflects th e electrical acti vity of the distant bealthy muscl e in the
interventricular septum and right ventricle. This result s in recording ol' a
deep (= patlwlogiwl) Q •va11e (more than 0.2 mY) because the electric
acti vity is direc ted away from the recording electrode (figure 33). If the
necrosis \vas partial (e.g. subendocard ial on ly). R waves will be recordcd,the
amplitude ofwhich varies inversely with the extent of nec rosis (figure 34).
An infarcted area due to coronmy heart disease (= occ lusion or the
coronary arteries commonl y as a result of thrombosis) consists of dead ti ssue
(necrosis) surrounded by a 1.0ne of tissue injury, around whi ch there is a
zone of isc hemic tissue (figure 34), so an elec trode facing this area will
record the ECG changes produced by these ciTects. In the acute stage, ihe
first sign to appear (within a few minutes) is S-T segment elevation
(injury). This is fo llwcd a few hours later by appearance or deep Q waves
(necrosis) then by T wave inversion. After 1-2 weeks, the S-T segments be-
come isoelectric again, and after a few months the T waves become upright.
However, the deep (pathologica l) Q waves persist and become perman-
ent for life (ind icating presence of an old myocard ial infarction).

Figure 34 : ECG manifestations ofcorona ty artery occlusion.

EFFECTS OF CHANGES IN SERUM Na+ and K+ LEVELS ON ECG

(1) Na+ : Hyponatremia causes low-voltage QRS complexes while hyper-
natrcm ia causes almost no e ffects.
(2) K+ : The first ECG sign in hyperka lemia is appearance of ta ll-peaked
T waves (disturbed repolarization). This is fo llowed by absence of P waves
(atrial an·est), S-T segment depression, prolongation of the QRS complexes
and A-V block then by ventri cular arrhythmia ending by its standstill. Hypo-
kalemia is a less serious conditi on and is associated with pro longation of the
P-R and Q-T intervals, prominent U waves and in version of the T waves.
 58
Chapter4 The arrhJJt/unias (or d)Jsrhythmias)

THE ARRHYTHMIAS (or DYSRHYTHMIAS)

These arc abnormalities in the number or regularity of heart beating.

Depending on the cause, cardiac anhythmi as can be classified into 2 types:

(1) Arrhythmias due to disturbances in impulse

formation
These arc produced as a result of' either :
(a) Alteration of S-A nod e rhythmicity : These lead to the various sinu s
rhythms (which include sinus tachycardia, sinu::; hradycardia. respirat01:1·
sinus arrhythmia and A- V nodal rhythm)
(b) Presence of ectopic foci : In this case, impulses originate ou tside the
S-1\ node and lead to the various ectopic rhythms (which include e.xtm-
systoles, paro.\y .w wl tachycardia. a frio/ and ventricular fibrillation, as ll'ell
as atrial flutter).

(2) Arrhythmias due to disturbances in impulse

conduction
These arc produced as a result of either S-A hlock, A- V hlock or the
Wo(fFParl(inson-White syndrome (sec below).

Sinus tachycardia and sinus bradycardia

In sinus tachycardia, the pacemaker (S-A node) rhythmicity is stimulated

e.g in muscular exercise (due to increased sympathetic activity), and the
hca t1 rate increases to 100-120 I minute. On the other hand, in sinus brady-
cardia, the S-/\ node rhythmicity is inhibited e.g. in athletes (due to incr-
eased vagal tone) and the heart rate is decreased below 60 I minute. in
both conditions the ECG shows normal complexes hut their rate is faster or
slower 1han normal depending on the com/ilion (figure 35) ..

Figure 35 : (a) Sinus bradycardia ( heart rate 50 /minute) an<..l (b) Sinus
tachycardia (heart rate 120 /minute).
 59
Cltapter4 Tlte arrltrthmias (or dvsrltvthmia.\)

Respiratory sinus arrhythmia

The heart rate is increased during inspiration and decreased during exp-
iration. The ECG sholl's normal complexes but their rate is faster or slo11·er
!lum normal depending 011 the respimtOJ)' phase. II is a normal findin g that
commonly occurs in children and young adults, and it is due to fluctuations
in the strength oftlte vagal tone that affects the the rate or S-A node rhyth-
micity (the causes or these nuctuations arc discussed in detail on page 72).

A - V nodal rhythm

This condition occurs when the A-V node hecomes the pacemaker
following damage or the S-A node. The ECG shows (a) Bradycardia
(because the A- V node rhythmicity is less than that or the S-A node) (b)
Short P-R intervals (because the impulses reach tht: vt:n triclcs more rapidly
than nonnal) (c) In verted P waves (because the direction or atrial depolariz-
ation waves is reversed). The P waves are .frequelll~r buried in the QRS
complexes or they mayfollow the QRS complexes (producing negative P-R
intervals) if the ventricles are excited before the atria (figure 36).

Figure 36: A-V nodal rhythm . Notice bradycardia (hea rt rate about 60/min)
and inverted P waves following the QRS complexes ( -vc P-R intervals).

Extrasystoles (or premature beats)

These are produced by impulses discharged during IIOrmal SA rhythm from

el:topic foci that act as pacemakers for only one heat. In the ECG, they
produce l:Omplcxes early in tlte T-P interval (when the heart is totall y
repolarizcd). There arc 2 main types of premature beats :
(1) Supraventricular premature beats( figure 37a): These arc produced
by impulses discharged from ectopic foci in the atria or A- V node. The ECG
shows (a) Abnormal P wave (commonly inverted) because the impulse
spreads in the atria in an abnormal way (2) Normal QRST wm,es (the
impulse spreads via the normal conducting system) (3) Almost normal T-Q
interval because thl:rc is 110 or short compensafOIJ' pause (page 15). Th ~ P-
I? interval is shortened if the ectopic focus was in or near to the A- V node.
 60
Chapter .J Th e a rrlt rtlt mias (or d!'s rh )'llunias)

(2) Ventricular premature beats (figure 37 b) : These arc product:d by

1111pu l st:~ discharged from ventricular ectopic foci. The ECG shows (a)
\\'ide high abnorma ll y-shaped QRS complex ( M:::.are QRS) dut: to the
rdativcly slow conduction oftlu! impulse through the l'ellfricular muscle ( h)
.\'o P ll'ave because the abnorma l impulse is incapab le of exci ting the
Purkinje-11 is system. so upward conduction to the atria does not occur (c)
Prolongati on of the foll owi ng T-Q in terval dut: to presence of' a complete
compen.wttm:r pause (d) lm•erted T ll'al'e (c) Axis del'illliou.

Figure 37: Supravcnt.(atriul ) c.x trasystolcs (a) and vt:nl. extrasysto lcs (b).

Paroxysmal tachycardia
This is a pathological condition characterized by paroxysms (auacks) of
tachycardia. ft is due to activation of ectopic foci that discharge at a n11e of
150-220 I minute (average 200 I minute): Like cxtrasysto lcs, they may dev-
elop in the atrin, A-V nod e or the ventricles (but unlike ex trasystoles, they
suppress the SA node during the attack and become the pacemaker instead)
and accordingly. there arc 2 main types of this arrhythmia :
(1) Paroxysmal supraventricular tachycardi a : In ECG (figure 38 a).
all compkxcs show abnormal P ll·a1·es (like !>Upraventrieular ex trasystolcs).
The atrial type may also occu r in the IVoljj:Parkinson- IVhite jyndrome (page
65) and is usually associated with some degree or/\- V block (so the vent-
ricular rate is only 170 - 180 I min ute in most cases).
(2) Paroxysmal ventricu lar tachycard ia : In ECG (figu re 38 b), all
complexes show wide hig h hi::::are-shaped QRS complexes and im ·erted T
II'OI'e s withollf preceding P \l'lll'es (l ike ventricular cxtrasystoles). The vent-
ricular mtc is 150-220 I minute and this is more dangerous than the at rial
type bccaust: (a) It leads 10 nwrked reduction c?l the cardiac output (b) It
predisposes to ventricularjihrillation. Because the impulses cannot be con-
ducted retrograde via the lli s-purkinje system, the atria l rhythm is normal
i.e. it fo llows the S-A node rhythm(= atrioventricu lar dissociation).
 61
Chapter .J Tlte arrltrtltmias (or drsrltrtltmias)

- . . -~ __. . . - ; - . =: ;:

-
Figure 38 : Paroxysmal at ri nltat:hyca rdia (a) and vent. tachycardia (b).

Atrial flutter
This is a pathologicnl condi tion in which the atria beat regul11r~1' at a rate
or 250-350 I minute by impulses discharged from :1 hyperexcitable ec topic
focus. /\s the /\- V node cannot conduct more than 230 impulses minute.
physiotoxical incomplete /t eart block de\ clops, and the ventricles respond
once for every 1 or 3 atrial beats. So in ECG. each 2 or 3 P waves are follo-
wed by one QRST. and the P Hm'es are ohnumwl while the QRS and T
waves arc norma l in shape and occur regularly but at a rapid rate (figure J9).

ATRIAL RATE 270/MIN. VENTRICULAR RATE 90/MIN.

Figure 39 : An ECG showing atrial flutt er (not icc regular 3: I A- V bl ock).

Atrial fibrillation
Thi s is a patho logical condition in which the atria bear irregular~r at a rate
or 350-500/minute in response to impulses discharged from llllllliple ectopic
foci or generated by circus mol'l!m ent (sec below). Physiological heart block
develops but irregularly (however. it is important since it pre1•e11ts del•elop-
m ent of 11entricular fibrilllllion ). So the ven tricles bea t irregularly at a rate
of I00- 150 I minute and pulse deficit may occ.:ur (page 41 ). The auial fibres
contract a.\)'llchronous~r. so the atria appenr as a quil·ering bag of ,,·orms.
This leads to inefficient atrial contraction and blood stagnation in the atria
which predisposes to intra-atrial 1/trombosis (this is dangerous because
blood clots rrcqucntly detach and oc.:c luuc important arteries). In ECCi. there
arc no P waves (which arc replaced by line osc illati ons called F waves ), and
the QRS and T waves arc normnl in shape but irregular in rate (figure 40).
 62
Chapter .J The arrh vthmias (or drsrh)'tlunias)

Figure ..JO : An ECG showing atrial fibrillation (notice F waves and irregular
QRS complexes).

Ventricular fibrillation

This occurs as a result of either (I) Impulses discharged from multiple

ec topic loci (specially nlkr an allack of paroxysmal ventricular tachycardia)
(2) Re-ellfi:J' ami circus movements of impulses initiated by an electric
!)hock or a premature impulse during the vulnerable period (sec belo\\)
specia lly after myocardial inlim:tion. It is fatal because it results in loss or
the ventricu lar pumping power (which leads to stoppage of the ci rcu lation).
In I:CCi, the QRS complexes arc quite irregular in shape. rhythm and
amplitude nnd all waves are not clear and cannot be identified (figure -ll ).

Figure 4 1 : An ECG showing ven t. fibr ill ation ending by cardiac standstill.

The vu lnerable period

This is a short period at the end of cardiac rcpolarization (during the early
pa11 of phase ..f of the action potential. page 13) that coincides with the
doH•nslope of the T ll'ave (figure 4). It i. a da ngerous period because
during it some fibres ure complete ly repolari zed and some arc incompletel y
repolarizcd while f'ew others arc stil l depolarized. and this condition favours
reentry and circus movements or impulses (see below) that may lead to
ventricular librillation.

MECHANISMS THAT INITIATE ALTERATIONS IN CARDIAC RHYTHM

Alterntions in the cardiac rhythm arc produced by 2 main mechanisms :

( I) Abnorma l automaticity of the S-A node produced by changes in the
slope of the prepotential (page 17) (2) The reemry phenomenon.
 63
Chapter 4 The arrltt•tltmias (or dvsrltt'lluuias)

Figu rc 42 : Circus movement through a cardiac muscle strip. The ::.haded

area in (b) is an area of block.

RE- ENTRY (C IRCUS MOVEMENT)

A circus movement develops when an impulse spreads in a circular path-
way from a certain area of ca rdiac muscle then re-cntcrs and rc-cxcites the
initial area, and this process is repented resul ting in continuous excitatation.
It is more liabl e to occu r during the 111ilnerab/e period (sec above) and by
application of a weak electric: sltoc:k to the !teart (sec below). The mecha-
nisms or establ ishment of such circus movcmems arc the following :
( 1) In a circular cardiac muscle strip (figure ..Q). if tlll:rc is a tran:>icnt block
at one side (e.g. due to ARP),an impulse will spread along the other side and
on reaching the blocked area, the cause or block would have disappeared, so
the impul se wi ll re-enter the initial area and start a circus movement.
(2) In a circular cardi ac muscle strip (figure -B), if the initiall y-stimulated
area was recovered (i.e. becomes no longer in the ARP) on arrival or the im-
pulse. the impulse wil l re-enter the initial area and start a circus movement.
This is favoure d when :
(a) The length of the impulse pathway is prolonged (e.g. in dilated hearts).
(b) The velocity of conduction of the impu lse is decreased (e.g in ischemia).
(c) The ARPin the original area is shonencd (e.g. b) norepinephrine).

Normal pathway

0000 Absolut41Y
refrxt orv

Absolut el y
refrxtorv
Relattvtlv
rt frJctorv

Long palh·N~Y

Figu re 43 : Circus movement through a cardiac musc le strip.

 (>4
Cltapter 4 Tlte arrh)ltlunias (or dr.,rll l'tlullitl.\ )

The right atrial muscle that surrounds the openings or the 2 venae
'~ 1'
cavae is a comm on site for ini tiati on of circus move ments. and thi s may be
responsible fo r prod uction or atria l fi bril lation and may also contri bu te in the
production of atria l flull er and paroxysmal atrial tachycardia as we ll.

Physiologic basis of treatment of atrial f lutter and fibrillation

( l ) Q uinidin e (pro longs the ARP. so it suppresses circus movements).
(2) B-rcceptor blocke rs e.g. atenolol (decrease cardiac exc itabi li ty).
(3) Digitalis (decreases cardiac conduc ti vity special!) at the A- V node).
(..t) In creasing the ca rdi ac ' aga l discharge e.g. by applying pres-;un.: on
the eyeba ll (page 75 ) or massaging the carotid sinus (page 73).
(5) Ca rdiac dc fihrill ation (app~l'ing strong electric curre111s to the heart) :
Thi s maneuver can treat atrial flun cr and fibr illation as well as ventricular
tachyca rdia and fib rill ati on as foll ows : The strong cu tTc nt dcpolarii'cs all
cardiac lihrc!-> !-> imu llancously causing them to become re!hH.:tory . As a
result. all impulses fro m ectopic foc i or in itiated by reentry stop !'or a few
seconds. a fter which the hea rt starts beating again by the S-A nodal rhythm.

.:_: While strong currents can treat ventricular fi brill ation , weal< alt ernnting
currents may cau se ve ntricular tihrillation. This is because the dcpolariz-
ali on wave produced by the current spreads in all directi ons leavin g the
muscle under the stimul ating cleetrock in a re fi·actory state. ll owevcr. thi s
muscle starts to recO\ cr after about 0.25 second. and some fi bres recover
earl ier than others. This is an appropri ate condi tion for reeutry ami circus
m ovem ents to de11e/op (see above) wh ich lead to ventricular fibril lation.

ARRHYTHMIAS DUE TO CONDUCTIVITY DISTURBANCES

Sinoatrial block
This is often due 10 increased vaga l tone. Some impulses .formed in the
S-A node foil to he conducted to the atria. result ing in dropped beats and
absence or whole cyc les (PQRST) in ECG (figure 44). Dropped beats arc
abo encountered in cases or sinoatrial arrest (o disorder in the S-. 1 node
a.nodated ll'ith failure offomwtion of impulses in the node 11·hi/e the ahilif.l'
o(tlreir comluction to the atria is normal) ..

Figure 44: ECG in case of sinoatrial block or arrest. Arrow = absent cycle.
 65
Chapter .J The arrhrtlunia' (or drsrhrthmias)

:.::. Another disorder or the S-A node i~ the \ ick \ inuo; o;y ndrom c. in
which the node is artccted by certain disease processes that lead to marked
bradycardia. The main symptoms or this disorder arc di::::::i11ess owi .\I'IJCopc·
(j'ointi11p,). and it can be treated by implanting an electro11ic pan'llwka.

Wolff-Parkinson-White syndrome (accelerated A-V conduction)

In the he<ll1s of some indi\ iduals. there is n conducting muscular bundle
bel\\ een the atria and \ entricles in addition fO the II ' hum /Ie. This bundle ,..,
called the bundle of 1\:cnt and it conduct.., impube:-. /mter tlum lht 1-1
humlle The cardiac 1111pube-. arc conducted b) both bundl e\. but since the
bundle of Kent has a !:1-.ter conducti\'il). one 'entnclc ,.., e\Citcd l.!arlicr than
the other. so the I C(j shows wide slurred QRS complc\c.., and short PR
in ten ab '' ith normal P w;n es ( ligurc ..f5).
I . : ' ' . : I : :
1R · · · ·
I I •

· ~ · i ·-~ 1

h-+rll lr r1- ~~t~mr

t · · · • · • :.t

Fil,!urc ..fS: An I ('(i in a case of\Volff-Parkin-.on -\Vhite syndrome.

rhis syndrome predisposes to paroxysmal atrial tach) cardia i/wl utriol

pre11wt11re heat occtii'S. This is because the impulse tha t produces the atrial
premature bcm is conducted to the ventricles via the /\- V node and \\'hen
ventricular acti,·ation reaches the ventricular end of' tht.: bund le of Kent. this
bundle \\ill transmit the impulse retrograde to tht.: atria and a c1rcu..,
mO\ emcnt ''ill thus be established leading to atrial tm:hycardia. less
commonly. the premature beat is conducted to the \ entricle" 'ia the bundle
of kent then transmitted retrograde ro the atria 'ia the A\' node.

PA • 038 t Second-degree heart block

(2: 1 hun block)
Font dt9ree ht.n block

Ficurc 46: First tkgrc~.: heart block(lcft) and 2ru1degree lwart block (right).

Atrioventricular (A-V or heart) block

Thi s ortcn resu lts secondary to ischemia oftlte A-I ' nodal or infranodal
regions and according to severit y, there arc 3 degrees :
 66
Cllapter4 Tile arrhl'lhmia.<t (or dvsrlrvtlrmias)

(1) First degree heart block : This is the mildest degree. All impulses
are conducted to the velllricles, but much slower than normal. It can be
diagnosed on(v.fiYHn ECG, in which it is indicated by prolongation of the P-
R intervals more than 0.21 second (figure 46 left).
(2) Second degree heart block : In this type, the conduction through
the A-V node fails intermittently, so in ECG some P waves arc not followed
by QRS complexes. This may occur irregularly leading to dropped ventricu-
lar contractions (partial heart block) or regularly (im:omplete heart block).
The latter may be 2:1 or 3: I block i.e. a ventricular beat follows every
second or third atrial beat, and in ECG there is one QRS complex for every 2
or 3 P waves (figure 46 right). However, in some cases, there is gradual
prolongation of the P-R intervals in successive complexes till a P wave is
not followed by a QRS complex and this process is repeated. Such case is
known as Wcnckebach's phenomenon or block (figure 47).

o. s. o. s. s. s. o. za s. o n s.
Figure 47: Wenckebach's block. Arrows= P waves not followed by QRS.

(3) Third degree (or complete) heart block: This is the most severe
degree in which impulse conduction through the A-V node is completely
blocked. The atria beat regularly at a rate of about 70 I minute (the sinus
rhythm) producing nonnal P waves in ECG. On the other hand, the vent-
ricles also beat regularly but at a much slower rate (25-40 /minute) known as
the idioventricular rhythm (which also often produces normal QRS compl-
exes in ECG because it is initiated by impulses discharged from a latent
pacemaker that develops in the bundle of His below the site of the lesion).
However, the P waves and QRS complexes arc not related, a condition
called A-V dissociation (figure 48) as occurs in paroxysmal ventricular
tachycardia (page 60). Complete heart block is often incompatible with life,
and it can be treated by implanting an electric stimulator in the ventricles.

f" ··'··' , .., ·... .~r-,.. -·: r:

'--trf.-il-=:b+-:i-:J-+:l=t'--H=-1--+:d~-- - - :-:-1- - -1-P
'IJ "[-'! ··[D· 1 D lil• ··~~:; -~-----
,A, A lA i ·. ,:.J. ~·~•t·A Ia..
-~. • ":"" lr' ..
"''lii"P""" "' ' IJI" .• -1'!11~ I"""' !fir...
aVF'~- . _ ... i::l •. :. .; ''':i;;il:'CitJIIIJ',iii;ifj;. 4:;~1J
Complete heart block. Atrial rata, 107; ventricular rate. 43

Figure 48: An ECG showing 3rd degree heart block(notc A-Y dissociation).
 67
Cltapter .J Tlt e arrlt)'tl1111ias (or dt•srll t•flllnias)

Stokes - Adams syndrome

This is a condition in" hich there arc periods of' vent ricular asystole that
laM a minute or more. It occurs tn cases of prolonged S-t\ block as well as
during transition from incomplete to complete ht:mt hlm.:k (due to delayed
initiation of the idioventricular rhythm). It leads to marked decrease of the
cardiac output. and the resulting c(!rebral ischemia causes diuiness then un-
consciousness within 2 minut<.:s. and death occurs if it lasts lorn longer tim<.: .

Bundle branch block (BBB)

Injury of the right or left bundle branches is a serious condition that is
commonly due to ischt.:tnia. It causes activation of' om.: ventricle before th<.:
ot her because th<.: dcpolari;ation wave reaches tlu: af'l't.:cted side via th<.:
siO\\ ly-conducting ventrtcular muscle. It does not lead to atTh) thmia but tt
cnn be diagnosed from ECG. in which the nHtntfcstations arc due to the
abnormal paUl\\ays of the depolarization and repolaritation \\a\cs. and they
include the folio'' ing (figure -t9) :
(a) Prolonged slurred QRS complexes in various kads (more than 0.12 s<.:c).
(h) T wave invt.:rsion in tht.: leads fltcing the affected side.
(c) Right or le n axis dt.:viat ion (lkpcnding on the af'lect<.:d sidt.:).

~ I :-~~ r •. 1
• ·! 1 II 1 '---:

/··-'-'"" .
_ ~-1. J i j • JJI
~-0...1~\
I •\\.
::. JJ I • : aVR a\'F

r 1 ]~· t,l.r, hf
·,i'~tr~ WY~
·-l _! I, . I . ~ : . _.' i .-
I .• - ,.. . ·' t'
·-=-t·- I'
l/ ... 11
t
I ' I
.,
1
_j

f.
r
I
.. ·- '· j·...
·1
t -,·
.,, ! '-
·-·--

\'1 '"2 , , v~ i . v• • LL vj •• • i~ I.:~

Figure 49: ECG manif'cstations in le ft BBB (note lcf'l axis deviation).

 6X
CHAPTERS

THE HEART RATE

FUNCTIONS OF NERVES THAT SUPPLY THE HEART

(A) Functions of the cardiac sympathetic nerves

Th~: ~~ mpathl:tic n~n e~ ::.uppl) all pans or th~ heart (atria. 'emricles.
conduction syst~m and the coronary \'esse!.). \\'hen activated. they lead to :
( I ) Increase or cardiac properties including (a) Rhythmicity i.e. the heart rate
( \·e'clmmotroptc eflect) (b) Contracrilit) (- 1·e inotropic eflect) (c) Excita-
bility (cm1sing cxtrasysto lcs) (d) Conductivity (dc<.:rcasing /\- V noda l delay).
(2) /\n incn.:as~.: or the cardiac output. heart work and 0 2 i:onsumption.
{3) \ ' .D. or the coromuy vessels (by the effect(~/ metabolite.,).

(B) Functions of the cardiac parasympathetic (vagal) nerves

Th ~..:se nerves supply the atri a, the S-1\ and /\ - V nodes and the coronary
vcssds but not th e ventricl es. When activated, they lead to :
( I ) Dcpre~sion or cardiac properties includ ing (n) Rhythmicity i.e. the heart
rate (- 1·e chronotropic (:fleet) (b) Atrial contractility (c) /\ tria l exc itab ilit y
(so it can stop atrial tac:ltycardia am/ extrasystoles) (d) Conductivity (it
prolongs A V nodal de lay and may produce bean block).
(2) !\ clel:rcasc or the cardiac output. heart work and 0 2 consumption.
(3) V. D. or the coronary \'esse Is .
.:..:. The right sympathetic and vagus nern~s influence the SA node while
the !crt sympathetic and \'agus nerves influence the A V node.
~ 13oth types of nerves also contain afferent ncn e fibr·cs. The symp-
athetic a rrcrent fibres transmit pain signals from the heart \\hi lc the \a gal
afferent fibres carry signa ls rrom atrial and ventricular receptors (sec below).

THE CARDIOVASCULAR CENTRES

These are located in the reticular fom1ation or the medulla ohlongata

and lower part of the pons and arc also ca lled the vasomotor centre. They
regulate (control) both the heart rate all(/ contmctility as wel l as the
diameter <~/the arterioles and \'C'IIItles through af'kc ting the discharge in the
o111rmom ic 1/eJ'\'es tha t supp~v these stm<·t11res. They i ncludc a se/ISOIJ'
region in the 1111cleus <~/the tractus solitarius (which receives the inrut
signals to the centre) as well as the followi ng centres (figure 50) :
 69
ChapterS Tile cardiovascular ce11tre."i

Figure SO : Nerves that supply the heart and their central control.

(1) Vasoconstrictor centre (VCC) : Stimulation of this centre increases

the sympathetic discharge to (a) All blood vessels (leading to generalized
V.e.) (b) The adrenal medullae (leading to secretion of catecholamines) (c)
The heart (leading to increase ofthe heart rate and cardiac contractility). The
part of the vee which produces these cardiac eflccts is sometimes called
the cardiac accelerator centre (CAC).
(2) Vasodilator centre (VDC) : Stimulation of this centre leads to
generalized V.D. tllro11glt i11hibiti11g tire activity of the VCC.
(3) The cardiac centre : This consists mai11/y of a cardiac Inhibitory
centre (CIC) which, when excited, stimulates the ac!iacent nuclei l~( the
vagi nerves, and these in turn transmit signals that decrease the heart rate
and atrial contractility. The CAC is related to the vee as described above.
 70
Chapter 5 Srmpathetic amll'lrga/tones on the h eart

tntt>rnal carotul
nrtery

uinUB
/. external
·u;;:-tr....-,- carotid
I L.---1i:::IIG( artery

figure 51 : The mechanism (pathway) or vagal tone on the heart..

THE SYMPATHETIC TONE ON THE HEART

This i ~ posiril·e~\' inmropic (increasing the \'cntricular pumping power 20-
25 %) and positil·e~\ ' chronotropic (tending to increase the heart rate to about
I 50 I minute). Ho'vvever, the latter effect is antagonized by the more strong-
er vaga l tone (sec below). Thus. block ing the sympathetic act ivity decreases
the ve ntri cular pumping power 20-25 % but has 110 £:/!'ec:t on the heart rate.

THEVAGALTONEONTHEHEART
This is a continuous inhibitory effect exerted by the vagi nerves on the
heart dur·ing rest. It dominates over the sympathetic tone at the S-A node,
reducing its rhythmi city from about I 00 to about 75 impulses I minute (but it
cloe-; not t!f.Tect the \'C!IItricular p11111ping poll'er because the vagi do not
suppl y the ventricles). Thus, \'agotomy leads· to marked increase <~f'rlw heal'/
mte (to about 150 beats I minute l~v e.flect <~f' th e .\:\'lltpathetic tone) as well as
to a slight increase of the ventricular pumping power (/~r ejj'ect t~l the
i11creased heart mle) .
 71
Chapter 5 Mechanism o{l'agallone amltlte l'ftt:al escape

Mechanism (nervous pathway) of the vagal tone

The cardiac vagal tone is a reflex which occurs as follows (figure 5 1) :
The initiating stimulus of the vagal tone on the heart is the arterial blood
pressure. It stimulates certain stretch receptors located main ly in the walls of
the aortic arch ami carotid sinus called the a rterial baroreceptors o r
prcssor cccptors (page I 02).
Impulses di charged from these receptors arc conducted to the medulla
ob longata via afferent nerve fibres in the aortic am/ carotid siuus uetw!s
(which arc branches of the 1·agus and glossophm:rngeolneiTf!.\ respt!ctivcly).
Such impubcs stimulate the CIC. which in tum. discharge. tonic impulses
via efferent vaga l nerve fibres that depress the inherent high autorhythmicity
ofthe SA node (figure 51).
~ Complete denetTation of the heart increases the heart rate on~r to the
inherent SA autorhythmicity i.e. to about I 00 beats I minute (and not to
150 beats minute.:) due to Joss ofthc sympathetic 10ne (which also decreases
the vcmriculnr pumping power by 20-25 %).

THE VAGAL ESCAPE

This rclcrs to the escape t~lt!t e ventricles Fom tlte inhibitmJ' effect
t~l th e l'a,~ i
nerl'es. Thus, after heart beating stops by a strong bi latera l vagal
stim tll ation, the ventricles start beating niter a short time hy their own
idi ovcntric ular rhythm (25-40 /minute). This property is bcndicia l in cases
of complete hea11 block in which rbe idioventricular rhythm cannot be
decreased by vaga l st imul ation (but it can be increased by sympathetic stim-
ulation bceauo;c the 'entriclcs arc innervated by sympathetic ncn cs ).
~The aortic and carotid sinus nCf\.C5 also transmit impulses f'rom the
peripheral dtemoreceptors in the aortic am/ carotid bodies ( lig.urc 51).

REGULATION (CONTROL) OF THE HEART RATE

Thl! heart rate can be determined by counting the arterial pulse. tlte /t eart
sounds (usin,r: tlte stet/I(Jscope) or the ECG wm•es and it normally avcrng.cs
75 beats minute (rnngi 60-90 1 minute) in young adult males during rest. It
is basica ll y determined by the strength oftlte vagal tone, and is subjected to
m a ny physiolog ica l variations such as (J) ft is about I]() I mimue i11neu·~1·
hom il!(wus (due to absence of the vagal tone) (2) It is more in females than
in mn lcs (due to less vagal tone in lcmalcs) and is slowest in at!t/etes (due to
a stronger vagal tone than in sedentary persons) (3) It shows diumal
variations (bein g lowest in the early morning) (4) It increases on chan gi ng
from the recumbent to the up right posture (page I03).
 T2
ClwtJ/er 5 Nen •ou.\ regulation o(tlle heart rille

The fn:qucnc) of di...,chargt.: of the S-A node (whtch determine~ the

heart rate) is atTcctt.:d (or regulated) hy ncn ou!l and chemica l factor!~. ""
well as by certain other n1ctors that direct I) affect the S-1\ node activit).

NERVOUS REGULATION OF THE HEART RATE

l'he heart rate i-. ncn uu"l) regulated through the carclwnt\Cttlar celt II'<' '
(.,ct.: abon:) \\ htch control the \\'11/f'CIIhetic anclJ>tlra,rmpcllheth clisc:lwrge to
the heart. The acti' ity of these centres is affected by (A) Impulses discharg-
ed from certain supraspinal centn:s (B) Man) reflexes 1nitiated from the
CVS itself as'' ell as from several extravascular structures (sec next).

(A) SUPRASPINAL CENTRES THAT AFFECT THE HEART RATE

(1) The cerebral cortex

The conical intlut.:ncc on the heart rate is e\ ident by alteration of the heart
rate a... a response in man) C'fmditioned rejlexe\. Also. through such cortical
Influence, some indi\ iduals can 'oluntarily control their heart rates.

(2) The hypothalamus and limbic system

These struttures arc concerned with emotional reaction.\ . Most emotions

arc associated with tachycardia (e.g. before starting a rate). ll owcver, severe
emotions are li·equently associated with bradyc.;ardia

(3) The respiratory centre

Respiratory sinus arrhythmia

This tt.:nn rcfers to the im:rcasc of the heart rate during inspiration and it-,
decrease dunng expiration that commonly m:curs normally in young individ-
uab and children (page 59). I his phenomenon is primaril) due to flu ctua-
tions in tbe st rength of th e Htga ltonc to th e heart during th e respiratory
cycle which occur as follows : During inspiruti on. impubes discharged from
the impirat or~ centre and .tl ...o in afferent 'agal ncn c fibres from certain
-,t rctch rcccptot·s in th e lungs. in!tihittftc CIC so the cardtac 'agal tone 1s
decreased resultmg 111 heart acceleration. Dunng expiration. the"e impul...c-,
.tre no longer disdwrgcd. resulting in decrease of the heart rate.
 73
Chapter 5 Nerwms regulation o[tlte !teart rate

(B) REFLEXES INITIATED FROM THE CVS

(1) Marey's reflex (Marey's law)

"A rise or the arteria l blood pressure (ABP) leads to a decrease of' the
heart rate and \'ice \'ersa, provided other t~lctor affec ting the heart rate
remain constant". It is initiated hy stimulation of the w·teria/ hororecepton-
olld its patlnt ·t~r is the same patlnray o/the \'Ogol !VIle (page 7 1).

Eff cts- of stimulation of rile arterial !Jaroreceptors

( I) Stimulation or both the CIC (resulting in rcllcx bradycardia) as \\'ell
as the VDC (resulting in generali zed V.D . and hypotcn ion).
(2) Inhibiti on of' the respiratory centre (resulting in temporary apnea).
(J) Inhi bition ofsecrction of the antid iuretic hormone (A DII).

The carotid sinus syndrome

In some individuals. tlte carotid sinus is abnormal()' ltypersensitive
so that mild pressure on the carotid sinus behind the angk of the mandible
(e.g. duri11g slwl'ing or b.'' a tig ht collar) leads to bradycardia and general iz-
ed V. D. that may be severe enough to decrease the ca rdiac output and AB P
to the extent or producing brain ischemia (Ill(/ syn cope ( f~lintin g).
~On the same basis, an attack or paroxysmal atrinl tachycard ia can be
terminated through initiating o carotid sinus re.flex (by light massaging ol'
the carotid sinus. page 64).

(2) Bainbridge reflex

" : Ill increase in the right atrial pressure lead\· to !teart acceleration".
Impulses arc discharged from spec ial ttl(:llycardia-produciu,~ atrial recep-
tors (sec below) via afferent vagal nerve fibres to tht.: medull a \\here they
stimulate the CAC leading to heart acceleration. However. such response is
not constant and its physio logica l role is not settl ed, and !>Ome authors
believe that the resulting increase in the heart rate is due to direct
.\timulathm o(. tile S-..1 node as a result of
. stretch. and !> llt:h dTect i!>
so metimes ca lled the "Bainbridge effect".

Effects of rise of the r ight atrial pressure

( I) Tachycan.lia (Bainbridge reflex ) (2) Tachypnea i.e. accch:ration or
breathing (previously called /Iarrison's reflex) (3) Genera lized V.D. and
decrease or the artcrla l blood pressure (4) Coronary V.D. (prev iou sly cal led
A llrep's reflex) (5) lnhihitirm <~{secretion <?l the w1tidiuretic hormone (6)
Stimulation <~(secretion <~{ the atrial natriuretic peptide (AN P).
 74
Chapter 5 Ner11ous regulation olt!te !teart rate

The atrial stretch receptors (baroreceptors)

(I ) Type A : These arc barorcccptors that are stimulated when the wriaf
pressure increases.
(2) Type B: These are volume receptors that arc sti mulated as a result of
distemion (l the atrial \\'ails.
As in case or the arterial baroreccptors. stimulation or both types
or receptors leads to gem:rali:i'cd V.D. and .hypotension but somet imes with
tachy cardia (Ba in bridge reflex) and tachypnea (Harrison's rcncx)., and type
A atrial receptors are prohah~l' respons ihlefor the faller effects.

(3) Reflexes from the left ventricle

(A) Distention or the le/1 ventricle leads to bradycarJia, temporary

apnea. V.D. and hypotension. Such response is in it iated by sti mu lation or
barorcceptors in th e ventri cular wa ll (page I 0 I) and its signiticance ts
unknown (however. it may have a role in maintenance ofthe vaga l tone).

(B) The Bezold- Jarisch reflex (coronary chemoreflex)

Injection c?f" certain suhstances (e.g. serotonin. \'eratridine or capsaicin)
into the comnw:1· arteries that supp~1· the /eli \lentride leads 10 hrot~\'Cardia,
1'. D. and hypotension I hrough stimulation of certain ventricular chemo-
receptors. Its significance is unknown, but it IIWJ' he the cause of' the severe
hypotensionthatJi·equent~l·/'olfoii'S lllyocardial il?f'arction (in which case it is
probably in itiated by certain substances re leased rrom the infarcted tissue).
:.:_ The cardiovascu lar centres arc also re nex ly contro lled by impulses
discharged from the periplieml c!Jemureceptors lucalcd in the aortic and
carotid bodies (figure 51). These receptors are sensi ti ve to changes in the
blood levels of co~' 02 and H' (part icularly 0 :! lack) and will be discussed
in detai l with chemical regulation oflhc hea rt rate (page 75).

(C) REFLEXES INITIATED FROM EXTRA-VASCULAR

STRUCTURES

(1) FROM THE LUNGS

(A) Stimulation of the barorcccptors in th e pu lm on ary vessels (page

I 0 I) leads to temporary apnc:~ , bradycard ia, V.D. and hypotens ion. On the
other ha nd, lung il!flotion leads to the su111e eJj'ects but is assoc iated with
tacltycardia which is produced as a result of stimul ation of certain stretch
receptors in the lungs (refer to respiratc>1y sinus arrhyth111ia. page 72).
 75
Chapter 5 Chemical regulation o(lhe !teart rate

(B) The pulmonary chemoreflex

IJ!jection (~( certain substances (e.g. serotoni11 or capsaicin) il1fo the
pulmonmy vessels leads to bradycardia, V. D. and hypotension through
stimulation of certain pulmonarv chemoreceptor.\·. lt is simil ar to the
corona ry chemorefl ex (see above) and its significance is also unknovvn.

(2) FROM SKELETAL MUSCLES (ALAM-SMIRK REFLEX)

" Volun/C/Iy contraction of skeletal 11111.W:Ies leads to m1 increase of the
heart rate" . lmpulses arc generated from receptors in the musc les and joints
during contracti on and arc transmitted to the medulla oblongata where they
stimulate the vee and inhibit the ete, resulting in acceleration of the heart.

(3) FROM THE SKIN AND VISCERA

Exposure to cold and moderate painrul stimuli rrom the skin or viscera
usuall y result in renex increase or the heart rate. llowevcr, severe ptun
(special ly from the viscera) is eo11unon ly assoc iated with bradycardia.

(4) FROM THE EYES ( OCULO-CARDIAC REFLEX)

" App~ving pressure to the eyeball results i11 re.flex decrease (i the heart
mte ". I mpu lscs rrom the eye are transmitted to the nervous system where
they stimul ate the etC. Such response can he used to terminate a11 a/lack (?f
paroxysmal alrial (bU1110t ventriculc11 ) ICichycardia (page 64) ..
*->' Signals from certain sensitive areas in the body known as the t rigger
a reas (e.g. the larynx, testes and epigastri c region) also result in ca rdiac
slow ing, and IJe(/\~Jl hlows to these areas may lead to cardiac arrest.

CHEMICAL REGULATION OF THE HEART RATE

(A) EFFECT OF CHANGES IN BLOOD GASES

(1) 0 2 lack (hypoxia)
A moder(l{e 02 lack increases the heart rate by (a) A direct meclwnism
(stimulation or the S-A node activity) (b) A Cel/trai/Jiechanism (in hi bi ti on or
the eie) (c) A reJlex mechanism (stimulati on of the vee through exciting
the periph eral chcmorcceptors in the carotid and aortic bod ies).
On the other hand , severe hypox ia clccreascs the heart rate due to
inhibi tion ofboth the vee as well as the S-A node activity.
(2) C02 excess (hypercapnia) and H+ increase
A moderate hypercapnia and~ increase (acido!> is) increase the heart nne
by the followin g mechanisms (a) Inhibition of the e1e (after an initial short
period or stimulation) (b) Stimulation of the vee through exc iting the peri-
 76
Clta{Jter 5 Chemical regulation o(tlte !teart rate

pheral chcmoreccptors (specially by II ' increase) (c) Stimulation ol' the vee
through excit ing the cen tral chcrnorccept ors (on ly by co:! excess).
On the other hand. severe livpercapnia or acidosis decrease the hea rt
rate due to inhibition of the S-A node activity and paralysis of the VCC.

Effects of asphyxia on the heart rate : Asphyxia is associated wit h

horh hypoxia am/ hypercapnio, and it affects the heart rate as follows :
( I) Initial slowing: This is due lo the initial stimulation ol"thc CI C and inh-
ibition of the S-A node that arc produced by hypercapnia (sec above).
(2) Acceleratio n : This is produced by the effects or mild hypox ia and also
as a result of inhibition or the Cle induced by hypercapni a (see above).
(3) Premortal slowing : This is due to inhibition or the S-A node and para-
lysis of the vee induced by persistent hypoxia and hypercapnia.

(B) EFFECTS OF HORMONES, DRUGS AND CHEMICALS

(1) ADRENALINE : Sma ll doses increase the heart rate wh ile large doses
eleva te the ABP which decreases the heart rate through the Marcy's reflex.
(2) NORADRENALINE : Thi s is a potelll V.C. honnone that markedly elev-
ates the ABP, whi ch decreases the heart rate through the Marcy's rencx.
(3) THYROXINE : This increases the heart rate by stimulat ion of the S-A
node and increasing the metabolic rate (the formed metabolites cause V.D .
which increases the venous return, resulting in the Bainbridge retlex)
(4) ATROPINE: Th is accelerates the heart by blocking parasymp. activity.
(5) HISTAMINE : Th is is a potent V.D. substance which leads to marked
drop of the ABP, resu lting in heart acce lerat ion through the Marcy's rencx.
(6) BILE SALTS : These inhibit the S-A node acti vi ty and stimulate the C IC
leading to bradycardia (refer to digestion).
(7) A UTONOMIC DRUGS: Sympathomimetic drugs cause tachycardia while
parasympathomimetic drugs cause bradycardia (refer to autonomic N.S.) ..

FACTORS THAT DIRECTLY AFFECT THE S- A NODE ACTIVITY

(1) PHYSICAL FACTORS : An increase of the body temperature by

one °C increases the heart rate by 10-20 beats I minute and vice versa.
(2) MECHANICAL FACTORS : Right au·ial distention may directly
excite the S-A node leading to tachycard ia( = Baihbridgc effect. page 73).
(3) CHEM ICA L FACTORS : The S-A node is direct ly exci ted by mild
hypoxia. catccholamines, thyrox ine. certain electrol ytes & in alka lemia,
wh ile it is directly inhibited by severe hypoxia & hypercapnia, bile salts. cer-
tain electrolytes, cholinergic drugs & in acidemia (see rhythmicity . page 18).
 77
CHAPTER 6

THC CARDIAC OUTPUT AND VENOUS

RETURN
Definition : The cardiac output (CO) is the amount of blood pumped by
each ventricle per minut e (so it is also called the cardiac minute l'olume).

Normal values : Th~ normal CO at rest is 5- 5.5 litres per minute. and it
is equa l for both ventricles (page 86). The CO per square meter of body
surfi1ce area is ca lled the cardiac index. and its normal value in adults is
about 3.2 litre.\· I square meter I minute
The CO eq ual s the product of the heart rate x strol<c volu me. The
stroke 1•olume (SJI) is t!te volume of blood pumped by eac:!t 11entricle I beat
and it equals the d[fli.•rC'IIce be11ree11 the 1'£'1/triculor e11d diastolic and e11d
.\:1·stolic 1'0l11mes (/:.J)V and ESV respectil·e~\'). The EDV is the amount of
blood in the ve ntricles at the end of diastole while the ESV is the
amount of blood in the ventricles at the end of systole (i.e. the amount ol·
blood thnt rema ins in the ventricle after eject ion ). The normnl EDV and ESV
during n..:sl average 130 ml and 50 ml respectively. Thus, the average
rest ing SV = EOV- ESV = 130 -50 = about ~0 ml .

The ejection fraction (EF) : This is the percentage of the end diastoli <.:
blood volume that is ejected per beat. It equals the SV I EDV x I 00 and
normal ly at rest. it averages 80 I 130 x I00 - 65 'Yo (range 60 75 %) i.e.
on~r ahout 213 r~/the £1)1' is nomwl~r c:jeCied during each ')'\'tole.

FACTORS THAT AFFECT THE END SYSTOLIC VOLUME (ESV)

These arc the same factors that affect myocardial comractility (page
11 ). ll owcver. +vc inotropic factors decrease th eE V, and vice versa.

DIASTOLIC (RELAXATION) PROPERTIES OF ... HE VENTRICLE!)

/ 'enlricular relaxation is importantji>r normal cardiac flmction (like'
l'elllriculor contmction) since deficient relaxation also dc<.:rcascs the S\' and
CO (due to impaim1cnt of ventricular fillin g). The process of ven tri cula r
relaxation is determined by both ac:til·e and passi1·e properties :
( I) Ac ti ve rela xation property of the ventricles : This refers to the re-
laxa tion th at O<.:t:urs as a result of Ca 2+ reuptakc by the sart:op lasmi<.:
reti t:ulum nnd is known as lu sitropy. It is rcsponsihlc for most of ventricu lar
fillin g during ea rly diastole, so positive lusi tropic li1ctors (e.g. most positive
inotropic f(lctors) increase ventricular filling.
 78
Chapter 6 Booster pump {imction o[the atria

(2) Passive reJax<ltion property of the ventricles : This refers to the

various mechanical fitctors that passively affect ventricu lar relaxation. These
factors c?ffecr the extent of ventricular Jill ing and include specia lly ventric-
ula r complia nce (= distensibility) and sti ffn ess. The extent of ventricular
rela.wtion is decreased (/the ventricular complia11ce is decreased e.g. as a
resu lt of cardiac tamponade (see below) or increased vent ricular sti ffncss (as
occurs in cases of infarction and hypertrophy).

FACTORS THAT AFFECT THE END DIASTOLIC VOLUME (EDV)

(1) Atria l pressure : This is thefl//ing pressure of the ventricles. lts incr-
ease (e.g. as a resu lt of atrial systole) increases the EDV and vice versa.
(2) Blood volume : Hypovolemia decreases the mean circulatory pressure
(MCP, sec below) resu lting in reduction of the venous ret urn (VR), atri al
pressure and EDV. l lypcrvolcmia produces opposite effects.
(3) Venous tone : Venoconstriction (by sympathetic stimu lation) increa-
ses the MCP resulting in increase of the VR, atrial pressure and EDV
(4) lntrapericardial pressure : Its increase e.g. as a result of flu id or
blood accum ulation(= cardiac tamponade) decreases the EDV (sec above).
(5) Atria l fibr illation : This weakens atrial contraction, thus the booster
pump runction of the atria and the EDV arc decreased (sec below).
(6) Intrathoracic pressure : An increase of its negati vity (e.g. in deep
inspi ration) increases the VR and promotes ventricular relaxation, and both
e ffects increase the EDV. Opposite effects occur if its negativity is lost or
becomes posi ti ve (e.g. in case of pneumot horax).
(7) Mu s c le c ontra ction : This increases the VR, atrial pressure and EDV.
(8) Posture : In the upright position, blood pools in the lower limbs by the
effect of gravity, thus the VR, atrial pressure and EDV tend to decrease
(however. this is normally prevented by cena in mechanisms, page 83).
(9) Ventricular complia nce and stiffness : The EDV is directly pro-
porti ona l to the former and inversely proportional to the latter.

The booster pump function of the atria

Atrial systole enhances (adds to) the pump function of the ventricles
because it favours ventricular fi lling. This is ca ll ed the booster pump
.fimction of the atria (boost = increase the value), and is normally insig-
nificant since it contributes for only 20-30% of ventricular filling. l lowcvcr,
such atria l booster etTect increases and becomes important in 2 conditions :
( I) When the veno11s return increases : In this case. stretching or the right
atrium increases its pumping power according to Starl ing Jaw, which increa-
ses ventricular fi lling and consequent ly the SV and CO ..
 79
Chapter 6 Measurement o[llte cardiac output

(2) Wilen the /t eart rate increases : In this case, the SV would decrease
because the diastolic periods (during which v~.:n tri cu lar filling occurs) arc
shortened. However, the atrial contractions become stronger(= atr ial kicks)
probably due to the force-frequency relationsh ip (page 24). which favours
ventricular fil ling. so the SV and CO are not decreased and may increase.
Consequent ly, loss of effective atria l contraction (e.g. in atrial fibrillation)
reduces the heart's ability to increase the CO during st resses assot:iatcd with
increased VR and heart rate (e.g. muscular exercise and emotions).

METHODS OF MEASUREMENT OF CARDIAC OUTPUT

(1) ECHOCARDIOGRAPHY: This method is non-in vasive (i.e. it doesn't

involve insertion of a cardiac catheter or injection or chemica ls). It records
both the EDV and ESV, so the SV can be ca lculated, and the CO can then be
obtained by multiplying the SV x heart rate (sec above).
(2) APPLICATION OF FICK'S PRINCIPLE : The Fick's princip le states
that " the amount of a substance taken by an organ /minute = arterial level
of this substance- its \'enous level x hlood.flo11· in that organ /minute ". This
principle can be used to calcu late the CO oftlw rigiit••entricle (which norm-
ally equa ls the CO of the left ventricle) by determination or the following :
(a) The total 0 2 consumption I minute (norma ll y 250 ml /minute):
(b) 0 2 content in venous blood (known by analysis of blood obtained from
the pulmonary trunk by a cardiac catheter and is nom1ally 140 ml I litre).
(c) 0 2 content in arterial blood (known by analysis of blood obtained from
an artery by puncture under local Wlestilesia and is normally 190 ml I litre).
By app lying the Fick's principle, the amount or 0 2 taken by the lungs per
minute = arterio-venous 0:! difference X blood !low in the lungS per minute
(the CO of the right ventric le) i.e. 250 = 190-140 x rightllentricular CO. So
the right ventricular CO = 250 I 190-140 = 250 /50 = 5 litres I minute
(3) INDICATOR DILUTION METHOD: A known amount of a dye (or a
radioactive isotope) is injected into an arm vein (say 5 mg), and its conc-
entration is determined every 2 seconds in seria l samp les of arterial blood
and plotted against time (ligure 52). The concentration or the dye increa. cs
graduall y to a maximum after which it declines then ri ses again (indicating
its rccirculation).Thc time of a single circulation of the dye through the heart
(the end of which is indi cated by re-risc of its concent ration in the arterial
blood) is determined by extrapolation of the curve as shown in figure 52.
The average concentration or the dye in the arterial blood is deter-
mined. Suppose it was 1.6 mg per litre, and ir the time or a single circulation
of the dye through the heart was 39 seconds during rest. then the blood
flow from the left ventricle (i.e. its output) in 39 seconds = 5 I 1.6 = 3.1
litres, and its output per minute = 3. 1 x 60 I 39 = 4.7 litrcs.
 HO
Chapter 6 Factors that a/feet the cardiac output

.:_: During exercise, the time of a single circulation of the dye through the
heart is shorter (9 seconds). In this casl.!, if the avt:rage concentration of the
dye in the arterial blood was 1.51 mg /litre, then the left vent. output in 9
seconds =- 5 I 1.51 = 3.3 litres and its output I minute = 3.3 x 60/9 = 22 litres
=Another method that depends on dilution is the thermodilution method
which involves injection of cold sal ine into the right atrium and detection of
the change in the temperature of the pulmonary arterial blood.

5.0

A-~'·,
4.0
3.0
2.0

,.., 1.0 l 0,

!~
l-0.8
0.6
04
0. 3
- Rest
0.2 a..--o Exercise

0. 1
0 4 8 12 16 20 24 28 32 36
Tome (I)

Figu re 52 : Determination of the cardiac output by the dye dilution method.

FACTORS THAT AFFECT THE CARDIAC OUTPUT

The cardiac output (CO) is a!Tected by changes in either the heart rate
(IIR) or the str oke volume (SV), and such changes arc regulated by both
extracardiac (extrinJic) and intmcardiac (intrinsic) meclumisms (page 84 ).

(A) EFFECTS OF CHANGES IN THE (HR) ON THE (CO)

( I) As the 1IR decreas<.:s b<.:low 70 beats I minute, the SV is increased
(because the ventricles have enough time for maximum tilling) and the CO
remains almost constant.
(2) ll' the HR decreases below 50 beats I minute, the increase in the SV
cannot compensate for the slowing of the heart. and the CO is decreased.
 81
Chapter 6 Factors that affect th e cardiac output

(3) /\s the HR increases from 70 to 180-200 beats I minute. the SV is

decreased as a result of shortening of the dinstolic periods (during '' hich
ventricular filling occurs). ll owcvcr. the CO remains constan t or increases
slightly due to heart acceleration.
(4) If the liR increases above 180-200 beats I minute, the diastolic
periods become much shortened. so the SV is markedly decreased and the
CO wi ll also be decreased because the decrease in SV is not compensated by
heart accclerntion.
~ 711C!rej(>re. both ercessh·e acceleration and sloll'ing l~/ tllf.! heart are
associated 11·ith decrease o{the CO.

(B) FACTORS THAT AFFECT THE STROKE VOLUME

(1) THE CARDIAC PUMPING POWER

This is affected by the cardiac inotropic stale. preload and al"tcrload

and the myocardial blood supp ly as well as by other factors e.g. it increases
in cases of sympathetic overactivity and ventricular hypertrophy. and
decreases in cases of severe loss of the function ing myocardium (e.g. as a
result of' mass ive in farc tion).

(2) THE VENOUS RETURN (VR) ( =CARDIAC INPUT)

The VR is a hasic determinant of the Sl' and CO. It acts by affecting

the EDV through the Starling law. and its volume is affected by the
following fltetors :
(a) The mcw1 circulotm:\' pressure (MC.: P) or 111ean syste111ic .fillinp, pre-
ssure (MSFP) : This is the mean pressure in the systemic circulation. It reJ:
lects the degree offilling l?/the circulation and its magni tude is directly pro-
portional to the blood volume and inversel y proportional to the ,·cnous capa-
city. Normally. it is 7- 10 mm Hg and the VR is directly proponionalto it.
(b) The right atrial pressure (RAP) : This is norma lly abo11t 2 mm ll g
during recumbency and 0 mm llg in the standing posi tion. nnd the VR is
in versely proporti onal to it.
(c) The resistance to the I'R (R\') : Nonnally. this is about 1.4 mmllg I
litre ofblood flow, and the VR is inversely proportional to it.
The n:lation between these lhctors is as fo llo\\'s :

VR = MCP- RAP (i.e. the V R is directly proporti ona l to the difTcrcncc

Rv between the MCP and RAP. and inversely propor-
tional to the Rv) .
 82
Chapter 6 Factors tlwt a fleet the 11enous rerum

Permissive function of the heart

The term "permissi' e function" refers to the ability of the heart to act as
a hydraulic pump that permils pumping c~l t·ariuhle wnounls of I'R, and
under n ormal conditions, the CO is determined by the rate of VR am/ botlt
are kept equal.
Duri ng rest, the VR is 5- 5.5 li tres I mi nu te and an equa l CO is eje<.:ted by
the ventri<.:les through their illlrinsic: auwregula1m:' ' IIU.!clwnism., (page !-15).
These rnc<.:hanisms aided by the sympathetic tone on the heart (page 70) cnn
in<.:rease the CO up to 15-25 litres I minute e.g. during muscu lar exercise( -
cardiac permissive level). Greater outputs more than the permissive level
<.:an sti ll be cje<.:ted by (a) Neuro-hormonal meclwni\111.\' (increasing the
S) mpathetic acti\ ity and secretion or catccholamines from the adrenal medu-
llae) (b) Cardiac hypertrOJJI!y (whic h can increase the CO up to 35 lit res I
minute in well-trained athletes).

FACTORS THAT AFFECT THE VENOUS RETURN (VR)

( I) Vcnou s pressure grad ient : This is the dijference beM een rite M CP
am/rite right atrial pre.,·sure and it is the primttl:t' determinant of lite VR (=
cardiac input) . The greater this pressure gmdienl. the more becomes the
I X and l'ice t·ersa.
(2) Skeletal muscle pump : Skeletal muscle <.:ont ract ion compresses the
'cins inside them. This propels blood towards the heart, and retrograde no,,
(i.e. backflow or blood) is prevented by the l'e /1 0 11.\' 1'11/ lleS. Such errect is
also exerted. but to a liuk extent, by the arterial pulsations.
(3) Respiratory pump : During inspiration, the negativity of the intra-
thoracic pressure increases. so the thorac ic veins diIale and their resistance
to blood Oow is decreased. At the same time, the intra-abdominal pressure
in<.: rcascs (due to dcs<.:ent o r the diaphragm) whi ch compres.scs nncl increases
the pressure in the abdominal veins. The resu lt ing incn.:asc in pressure grad-
ient between the thoracic and abdominal veins help::. VR towa rds the heart.
(-t) Venou s (venomotor) tone : This is a state of' partial constriction or
the venules during rc. t caused by continuous sympathetic discharge to these
vessels. It crea tes an upstream pressure that ma inta ins theVR against gravity.
(5) Cardiac suction for ces : During \Cntricular systole. the downward
movement of the A- V ri ng acts as a suction force that draws blood from the
veins into the atria. Also du ring early ventricular diastole, the rapid ' cntricu-
lar expansion is associated with increased infl ow from the li ll ed atria, which
de<.:reascs the atrial pressure resulting in sucti on o r blood from the veins.
(6) Blood volume: A decrease ofthc blood volume (e.g. due to hemo-
rrhage) decreases the MCP resulting in reduct ion of' thc VR. and vice versa.
 X3
Chapter 6 The ceutral••euous pressure (CJIP)

(7) G ravity : This antagoni;es the VR from the lower limbs. l lowever,
thb effect is norma/lr unto~oni=ed hy the thoracic allll 11111\CIIIor ptmtps. the
''<'IWIJWtor tmte and the cardiac s11ction forces (figure 53) ..
(R) Arter iolar and cap illary dia meters : Arteriolar dilatation ckcrcnses
the resistance to blood now and increases the VR, and vice versa. On the
other hand. severe capi llary dilatation leads to pooling of blood in the capill-
aries. which decreases the MCP resulting in marked reduction of the VR.
(9) Sy mpath etic stimu lation : This increases thl! VR b) incrcas111g the
'l!nous tone and the cardiac suction forces (sec abo\ e) as "d I as b) prod-
ucing arteriolar \'.D. in skdetal muscles.

VENOMOTOR TONE

Figure 53 : ~lechanisms that help the ,·enous return from the lower limbs.

THE CENTRAL VENOUS PRESSURE (CVP)

This is the pressure in the g reat thoracic ••eius at their entmnce into
the right atrium . It is closely related to the right atria l pressu re and both
affect the CO directly and the VR inversely. It norllla ll y ra nges from about 2
mm ll g during standing to 4.6 mm l lg in the recumbl.!nt position.
 !:)4
Chapter 6 Regulation (control) o(tlte cardiac: output

The cardiac-vascular coupling function of the CVP

The CVP acts as a coupler between the blood inflow rrom the
vessels (VR) and the blood outllow from the heart (CO) wh ich allows
intrinsic interaction between tlte cardiac am/ vm;cular functions.
/\ccordingly, its leve l is determined by the equi li brium bet'vveen the VR and
CO (e.g. it increases ir the VR is increased with a constant or decreased CO,
and decreases if the CO is increased with a constant or decreased VR). and
at the same timc. changes in the CV P causes alterations in the VR and CO.

DIFFERENCES BETWEEN the CVP and MCP

(1) The CVP is a (~\'IIOIIlic pressure (recorded during the physiologica l stale
or the circulat ion). while the MCP is a static pres.wre (recorded on ly expcr-
imemally al'tcr stopping thc cardiac input and output).
(2) The CYP couples cardiac and ''ascular jimctions while the MCP
reflects the degree r?f:JIIIing of the systemic circularion.
(3) The CV P level is determined by the ventricular fJlllllfJing fJ<J\\'er. the VR
and the blood \'Oiume. whi le the MCP is determined by the h/ood \'OIIIIIW
and \'enous cupucity.
(~)The CYP is increased in cases of heart failure>. increased intrathoracic
or imrapericurdial pressures. hypen •olemia a11d {/the I'R increases (e.g. by
increased sympathetic activity), while the MCP is increased in cases of
lzvpervolemio and decreased ''enous capacity (e.g. by sympathetic activity).
(5) The CYP is decreased in cases of hypovolemia and venocl ilatati on as
we ll as on stnnding (by the crrect or grav ity) and during deep inspiration
while the MCP is decreased on ly in cases of hypovolemia and venod ilatation

REGULATION (CONTROL) OF THE CARDIAC OUTPUT

This occurs through regulation or t he stroke volum e and heart ra te,

and such regulation is produced by the !'allowing 1 mechanisms:

(1) EXTRINSIC REGULATION

This regulates both tlte stroke volume an d heart rate by effect or :
(a) T he auto nomic nerves : Activation or the sympathetic system
increases tht.: CO as a result or increasing both the heart rate and SV, whil e
parasympathetic activa tion decreases the co by opposite crrects.
(b) Hormones: Catecholam int.:s and thyroxine increase the CO by exerting
bo th+ ve inotropic and+ ve chronotropic effects (like sympathetic ac ti vity).
Glucagon and insulin also exert a t- \'C inotropic crrcct (page 25).
 X5
C!tapter 6 fletemmetric amlltom eometric autoret:ulatioll o[llte CO

(2) INTRINSIC REGULATION

This regulates the stroke vo lum e only, and it im:ludes heteromctri c
and homco mctric regu la tion (or autoregul ati on).

(a) Heterometric autoregulation (Starling law)

This is regu lat ion or the SV through changing the initial length of the
muscle fibres. Filling or the ventricle lends to its expans ion. thus the F.D\'
and length of the muscle fibres increase, and according to Starling Ia\\'. the
force of contraction increases lending to an increase of' the SV. This type or
regu lation occurs on increas ing the preload and is th e lirst mec hani sm for
adjusting the CO according to changes in the venous return.

(b) Homeometric autoregutatlon

This is regulation of the SV without a cha nge in the length of musd c
fi hrcs. A prolonged incrca~c in EDV is folio'' cd by its tkcrcnsc to its
nom1al level while the ESV decreases less thnn its nonnal le' d by more
forceful ,·cntricular contraction. thus the SV remains elevated. Thi effect
occurs on development of nn a fterloa d e.g. as a rc!-ult or an increase in the
aortic impedance secondary to rise or the ar1crial blood pressure. It may be
due to either ( I) lncreose of 1/ie coroJw1:r blood .flo II' ns a resu lt of the
increased arterial blood pressure (2) Lop/ace law (which statl!s that the' cnt-
ricular wa ll tension i~ directly prop011ional to the intrmcntricular pressure).
The follo\\'ing table summarizes the main diiTcrences between hctero-
mcrric and homeomctric autoregulation of the cardiac output.

Heterometric Homeometric
autoregulation autoregulation
Initiating
Increased EDY Increased aortic impedance
stimulus
1\ chan ge in cardiac inotropic
Basis Starling law
state
Sta r1s berorc homeometric Start:. after heteromctric
Timing
auton;gulation autorel!u lat ion
Duration Transient (short term) ProlonQed (long term).
Loading state Preload phenomenon A rterload phenomenon
Avai lable Ca - in the
Limit The leve l of EDY
myocardium
MomenL to moment
Steady increase in the cardiac
adjustment or the YR and
Significance contracti lity with the increased
CO, and ba lance of the
aortic impedance
outputs or both ventricles.
 86
Chapter 6 Plt!'siologica!l'ariations o[llte CO

Physiological coordination of right and left ventri cular pumps

Momentarily changes in thc ou tput or one vent ricle arc norma lly
fo ll owed by sim ilar changes in the output of the other so that the blood.flow
ra/e in !he syslemic: 0/1(1 pulmonw:l' circula!ions is mainlained equal. This is
carried out by cardiac and vascular mechanisms :
( I ) Ca rdiac mecha nism : This involves the Frunf..-Starling mechanism.
Since the 2 ventricles arc connecled in series. a change in the ejected blood
'olumc from the right 'entricle leads to a corresponding change in the EDV
or the lcti ventricle, resulting in a balanced out now fi·om the 2 ventricles.
(2) Vascular mechanisms : These include the following :
(a) The transmission of the right ventricular output via the pulmonary
vessels to the left atrium is norma ll y rapid enough to be synchronized with
the krt ventricular rapid lilting phase (thus the EDV of' the left ventricle is
directly alfcctcd by the right ventricular out now).
(b) The bronchial circulation (which is a pan of the ten ventricular our-
put) serves to equalize the outputs of the 2 'entricles because it communic-
ates with the pulmonary circulation via a physiologic.: shunt.
(c) The pulmonary cin.:ulation stores a variable amount of blood which
can balance tcmponuy di ITeren<.:es in the outputs or the 2 ventricles after a
lew beats.

PHYSIOLOGICAL VARIATIONS OF THE CO

( I) Sleep : The CO remains almost cons/ant during mlm sleep.

(2) Posture : Changing from the recumbent to the upright posture tends h
decrease the CO by about 30 °" due to decrease lllhe I' R as a result of pool-
ing or blood in the lower limbs by effect of gravity . l lowcver. certain
compe!TSalol:r meclwni.\·ms prevent the decrease t~/lhe VR (page 83) and
help maintenance or the CO and arteria l blood press ure constant (page 126) ..
(3) Meals : During the fi rst ICw hours after rncnl s, the CO is increased due
to increase td'hloodJlo ll' i11the spla11chnic c:irculatio11.
(4) Temperat ure : At high environmental temp. (above 30 11C), the CO is
increased due to increase or blood now in the skin. It also increases at very
low temp.due to increase t?{lhe m uscle lone & shivering (see in metabolism)
(5) Pregnancy : The CO is marked ly increased during pregnancy {specially
in the later months) secondary to !he i11creased u1eri11e blood jloll'.
(6) Emotions : The CO irH.:n;ascs up to 100 %1 in most emotions due to
stimulalio11 o_ftlle S)'lllpa!IIC!tic-adrellal.\ystem.
(7) Muscul ar exercise : This prod uces the highest physiologica l increase in
the CO. II i11creases up to 7Ji;/c/.,· or more in ll'ell-trained athletes.
 H7
Chapter 6 Relation between the flAP, CO and VR

Relation between the right atrial pressure (RAP) and CO

The RAP is lhe tillin g p•·cssu•·c of lh c right ventri cle. II" the R/\P
increases. the right ventricular I ~ DV. SV and CO will also im;rcase. and this
consequently Ieath to an incrcasl! of the len ventricular SV and CO. On the
other hand. if the RAP is decreased. opposite effects o<.:eur. Such relation is
shown in the c~lrd i ac function (or cardiac output) cu rves {figure 54).
The middle curve shows the cardiac function in the normal restin g
condition in the upright position {in which the RAP is about 0 mmllg and
the CO about 5.5 litrcs minute). The cune is shi fted up\\a rds in h ~ per-
effecti ve hea rts (where at any given RAP. a greater CO is pumped) and
down\\ards in hypoeffectivc hearts (where at any given RAP. a smaller
CO is pumped). The main causes ofhypereiTecti ve and hypocffcctivc hearts
arc shown in the following table :

HYPEREFFECTJVE HEART HYPOEFFECTIVE HEART

- Parasympathetic stimula tion or
Sympathetic stimulation
Positive inotropic factors
--
Physio logical card iac hypertrophy (as
occurs in well -trained athletes)
Decreased vascu lar resistance (e.g. due
to a Jarl!.e arteriovenous fistula)
Increased heart rate
Moderate change in blood temperature
-
svmoatheti<.: dcnervat ion
egativc inotropi c factors
-
I !cart weakening (e.g.due to is<.:hcmia.
diphtheria toxi n or myocarditis} _
Increased vascular resistance (<tort ic
im1Jedance) e.g. due to hvpertcnsion
Heart block (and some arrhythmia:-)
Extreme change ~-
in blood temperature
-

Relation between the right atrial pressure (RAP) and VR

The volume of VR is directly proportional to the difTcrencc bel\\ ecn
the MCP and the RAP. Thus. a rise of the RAP is associated with a decrease
of the VR and vice versa. Such relation is shown in the veno us return (or
vascul a r fun ction) curves (ligure 55a). The middle curve ~hows the normal
resting conditions in the upright position, in which the MCP is 7 mm llg and
the RAP 0 mml lg. and the VR about 5.5 litrcs ' minute. It also shows that a:.
the RAP increases, the VR is decreased till it stops when the RAP becomes
7 mmHg, at which the pressure gradient becomes zero. On the other hand.
when the RAP decreases. the VR increases till it reaches a maximum then
plalcau at about -2 mmHg (because at such negative pressure. the intra-
thoracic veins nrc collapsed. preventing further increase in the VR).
E ffects of cluln gcs in the MC P : An increase of the MCJ> (e.g. by infusion
of2 litres of sali ne) shifts the curve upwards and to the ri ght (upper curve in
figure 55 a) indi cating a greater VR than normal at any given R/\P . On the
other hand. a decrease of the MCP (e.g. after loss or 20 % of the blood
vo lume) produces an opposite effect (lower curve in ligurc 55 a).
 88
C/rapter6 Re/atimr hetwee11 tire RAP. CO a11d VR

Figure 54: The cardiac function (or cardiac output) curves.

Effects of changes in the resistance to venous return (Rv) : The

VR varies inversely with the Rv (page 81 ). Thus a decrease of the Rv (e.g.
due to presence of a large arteriovenous fistula) increases the slope of the
venous return curve and rotates it upward and to the right (upper curve in
figure 55 b), indicating a greater VR than normal at any given RAP without
a change in the MCP. On the other hand, an increase of the Rv (e.g. due to
compression of the inferior vena cava by a tumour) produces opposite
effects (lower curve in figure 55 b).

0 4 8
1\.Af lmtnH;:

Figure 55: The venous return (or vascular function) curves.

CHAPTER 7

THE CARDIAC ENERGETICS I

CHARACTERISTICS OF CARDIAC MUSCLE METABOLISM

(I) A high rare qlO! consumption both at rest and during exercise.
(2) No 0 ! debt because energy production in the heart is almost completely
dependent on aerobic (oxidative) metabolism.
(3) A high 0_, exlracticm ratio (the cardiac muscle extract~ 70-80 % or th..:
arterial 0~ content at rest and greater amounts during exercise).
(4) A loll' l'enou.'> 0 1 resen ·e (due to high 0 ~ extraction from arterial blood)
so extra 01 can he suppled onfl' hy increasing the coronOJ:I' hlood.flow.
(5) Special metaholic .whstmte.\' : At rest, jilfZI' acid,· arc the main subs-
tances that supply energy. During exercise. laclic acid and glucose become
also important energy producing substrates.

THE WORK OF THE HEART

The cardiac worh. is divided into 2 types :

(1) Internal work :This is the work done to generate tension in the ventri-
cular wa ll s. it is a useless work since it is not eiTecti ve in blood movement.
(2) External work :This is used for ejection or a certa in blood vo lume at a
given pressure and with a certain ve locity. It is the ejfectil'e (or usejitl)
work for the pump function of the heart. and is classi ficd into 2 divisions :
(A) Pressu re-volume work (= potential or pumping work) : This is the
work done for ejection of the cardiac output against the arterial blood press-
ure. It constin1tes 99 1% of the external cardiac work and it consists of2 parts
(a) Volume work i.e. the work used to eject the stroke volume
(b) Pressure work i.e. the work used to create pressure in the ejected
blood vo lume. It is much greater !l/(/1/ tire \'OIIIIIU! \I'Ork, thus a pressure
overload (e.g. in aortic stenosis) is more exhaustive for ventri cular function
than a vo lume overload (e.g. in aortic regurgitation) .
.:_:The stroke work (SW) is the work done during a beat. It is calculated
by multiplying the SVx m ean arterial blood pressure. and is normally 0.93
and 0.14 Newton meter for the left and right ventricles respectively (the S\V
is lower in the right ventricle because the pulmonary arterial blood pressure
is much lower than the systemic arterial blood pressure) .
.:_:The minut e work of a ventricle (i.e. the work done per minute)
heart rate x (SW) of the ventricle cardiac output x mean blood pressure
in the corresponding artery (aorta or puluwmn:J' arte1y) ..
 90
Chapter 7 Tlte cardiac reser11e

(B) Kinetic (acce leration) work : This is the work done to give velocity
to the ejected blood in th~ vascular system. It constitutes aminor.frac:tion of
tlte extemal cardiac work at rest (only about I %,) . and it i~ normally l'<flllll
in hoth ''entricles (about 0.009 Newton meter each). ll owevcr, it is markedly
increased during exercise.
::_ The exte rnal cardiac work I beat during rest == 0.93 + 0.14 + (0.009 x 2)
= I .ORR Newton meter = 0.1 I Kg. meter = about one joule.

THE CARDIAC RESERVE

DEFINITION : ll is the ability of the hea.rt to increase its work and output.
IMPORTANCE : The cur·diac reser"e is important for ( I ) Performance or
~everc muscular effort~ (the cardiac output can be increased up to 35 litres in
ath letes) (2) Maintenance or efficient cardiac pumping in tlw early stages of
some diseases e.g. hypertension. heart fai lure and most valvulu r diseases.

MECHANISMS OF THE CARDIAC RESERVE

(A) Heart rate (HR) reserve

Jl ca rl acceleration is lhe jlrstmechanism c~/ the cordioc resen1e. The
heart rate may increase during exercise to 180-220 beats /minute (by ckprcs-
sion of the vaga l tone and increasing sympathetic stimulation) with an incr-
ease of the CO about 3 times in untrained individuals and 5 times in ath letes.
Ll M ITS : Tachycardia more than 220 beats I minute markedly shortens
the diastolic periods. so ventricular filling, SV and CO wi ll be tkcreased.

(B) Stroke volume (SV) reserve

The SV can be increased to 100 ml I beat or more. which results in
increase or the ejection fraction and CO. This is achieved by a n in crease of
(1) The ED\' (in response to increase or the VR. which increases the SV
through the Starling law) (2) Power of ve ntricular contractilit y (as a result
or sy mpatheti c stimulat ion).
LI M ITS : Overstretch or the cardiac muscle fibres beyond an optimal
length weakens myocardial contractility and decreases the SV (Starling law).
The power of myocardial contractility is also not unlimited..

:::2 The SV can be doubled by simultaneous increase of the EDV (th rough
Starling law) and decrease or the t:SV (through increase or the power or
myocardiu l contractility). During exercise, the heart is insign{ficant~r dilated
and its sii'c actually decreases due to reduction of the ESV, indicating that
the SV reserve is produced main~\' by increasing the po11·er c?f'contracti!ity.
 91
Chapter 7 The cardiac reserve

(C) Cardiac hypertrophy

This resu lts whenever the cardiac muscle fibres arc exposed to pressu re
or volume overloads for long periods. In pathological states, it either
increases the SV or keeps it constant. In case of pressure overl oads (e.g. in
hypertension and aortic stenosis), the left ventricular wall thickness
increases while the EDV remains constant (= concent ric hypertrophy). On
the other hand. in case of volume overloads (e.g. in aortic regurgitation), the
left ventricular wall thickness is not much increased while the EDV is
markedly increased (= eccentric hypertrophy).
Cardiac hypertrophy also occurs normally with some ventricular dilat-
ation in high~v-trained athletes (producing what is called the athlete 's heart).
Such effect increases the power or cardiac contraction, the SV and the CO.
LJMlTS : The card iac hypertrophy reserve mechanism is limited by the
ava ilable myocardial blood supply. When the increased ventricular 1/Jif.'\C:Ie
mass exceed~· a certain level, it will not he occompunied hy a proportional
increase in the myocardial hlood )loll', which decreases the cardiac
pe1jormance and may lead to heart failure.

(D) Other card iac reserve mechanisms

These include mainly an increase or the coronary blood flow and the
cardiac metabolic activity (page IJ I).

THE CARDIAC OXYGEN CONSUMPTION

During rest, a normal heart consumes about 29 rnl 0 2 I minute i.e. I 1.6 (Yo
or the total 0 2 consumption (250 ml/minute) although the heart const itut es
about 0.05 % or the body weight (about 300 gm).

Determinants of the myocardial 0 2 consumption

(1) T he heart rate : The magnitude of n1yocardia l 0 2 consumption is

directly proportionate to the heart rate.
(2) Generated tension in the ventricular wall : The magnitude of
myocardial 0 2 consumption is directly proportionate to the generated
tension in the ventricular wall.
(3) The stroke volume : The ejection of the stroke volume requires
much less 0 2 than that required to develop tension in the ventricular vvall
{only about 15 %) of the 0 2 consumption).
(4) T he co ntractile (inotropic) state : Enhanced myocardial contract-
ility by + ve inotropic factors (e.g. sympathetic stimulation) is accompanied
by an increase in 0 2 consumption.
 92
Chapter 7 The cardiac m eclut11ical e(ficieltCJ'

THE CARDIAC MECHANICAL EFFICIENCY (CME)

The CME is the'~·~~ ratio or the useful (~.:xtcnwl) cardiac work to th~.:
total card iac energy expenditure (or total o~ consun1rtion since the heart
depends almost completely on 0 :! for energy prodm:tion). 1onna lly. it is 15-
~5 °o during rest. and it increases up to 40 °1o in muscular exercise.

FACTORS THAT AFFECT THE CME

( I ) Type of con t raction: During isometric contraction , the 0 2 consump-

tion increases to deve lop tension in the ventricular wal l while no ex terna l
work is done, so the CM E is zero. On the other hand, during isotonic cont-
raction (ejection phases). an external (usefu l) work is performed and the
CMf- is increased.
(2} Type of work : The Cl\.1 1: is higher when doing' olume work (e.g. in
case or muscular excrcbe and aortic regurgitation) than" hen doing prc-;sun::
work (c.g. in hypertension and aortic stenosis) because thc 0~ consumpt ion
is much smaller in case ol' volumc work.
(3) T h e h ea r t rat e : The CM E decreases in tachycardia because the
mym:ardia l 0 2 consu mption is markedly increased.
(4) Ven t ri cu lar fact ors:
(a) Ve11tricular di/atatio11 : Th is is a disodi'Wtfllge to l'eJttricular jimclion
because the ventricu lar radius i~ increased which according to the la11' of
Laplace (page 93) increases the tension required to produce a gh·en iotra-
\'ell!ricular pressure. so more internal work is done and the 0 :! consumpti on
is JJwrkecl~\' increasc!d. wh ich tends to decrease the CM 1:.
(h) Ventricular hypertrophy: This is an admntage to \'£'1/fric:u/arjilllction
been use it increases the thi ckness of the ventricular wal l, which according to
the law of Laplace (page 93) decreases the 1ensio11 required 10 produce a
gil·eo intmw!Jltricular pressure. so less internal work is done and the 0 :!
consumption is not much increased. which tends to increase the CME.
 93
Chapter S Tire law o[Laplace

Figure 56 : The law of Laplace.

THE LAW OF LAPLACE

" The tension (7) developed in the wall of a hollow organ = Distending
pressure (P) x radius ofthe organ (r)" i.e.T = P x r and P = T/r (figure 56).
It applies to seveml sites in the body e.g. tire urinary bladder, lung alveoli,
stomach, blotJd ves.\·el~ and heart. In the heart, the element o f wall thickness
is also important, so the "Laplace law of the heart " states that the tension
(T) developed in the ventricular wall during ejection = intraventricular
pressure (P) x ventricular radius {r) divided by the wall thickness (h) i.e.
T = P x r I h.
Application of Laplace law in increased ventricular afterload
The ventricular afterload is produced by (a) Extracurdiac factors,
mainly the aortic impedance (b) Cardiac factors, mainly the ventricular
diameter and the ventricular muscle mass (i.e. the ventricular wall thick-
ness). Jn these cases, Laplace law of the heart applies as follows :
{I) Effect of aortic impedance : Increased aortic impedance increases the
intmventricular pressure (P) required to eject blood. This is a disadvantage
because according to Laplace law, a greater tension en develops in the
ventricu lar wall, so more en ergy (i.e. 0 2) is consumed, resulting in reduction
of the cardiac mechanjcal efficiency (page 92).
(2) Effect of ventricular diameter : Ventricular dilatation increases its
radius (r) and decreases its thickness (h). This is a disadvantage because
according to Laplace law, a f,'Teater tension (T) wi ll be required to achieve a
certain intraventricular pressure, so more internal work is done and the 0 2
consumption is markedly increase<L leading to reduction of the cardiac
mechanical effic iency (page 92).
(3) Effect of ventricu lar wall thickness : Ventricular hypertrophy i.e. an
increase in (h) is an advantage because according to Laplace law, a smaller
tension (T) will be required to produce a certa in intraventricular pressure, so
less internal work is done and the 0 2 consumption is not much increased,
leading to elevation of the cardiac mechanical efficiency (page 92). However
this occurs only if the blood s upply is p roportionately increased {page 9 1)
 94
CHAPTERB

E VASCULAR SYSTEM BIOPHYSI- _j

The systemic circula tion is made up of circuits or blood \esseb that me
arNm,s.:etl in parallel(figure I ). and each type of these vessds has a special
characteristic and a peculiar runcion (page 3).
The blood flo" rate (F) in blood vessels is direct I} propurtionnte to the
pressure gradtcnt (diiTerencc bet\\ cen the mean artenal blood pres~ure and
the atrial pressun:) and irnersd} proportionate to the pcriphcr.ll resistance :
prel.~ ure gradient
F = periph eral r esista nce
In the systemic circulation, (F) = cardiac output (CO), and t h~: pressure
gradient :::: mean syst~::mic arterial blood pressure (because the right atria l
presSllf'l.! is almost ;ero). fhus, CO= m ean S!'Siemic llflt!l'iii/IJ/ootf preSSIII't!
peripheral re.\i.\llmc:e
and mean !tystcmic arterial blood pressure = CO x peripheral r csist:-1nce

FACTORS THAT AFFECT THE PERIPHERAL RESISTANCE (R)

Most of the rt::sistam:c to blood Oow (R) occurs in the arterioles. From
the Poiseui//e-1/agen j(Jrmu/a , R = 8 L n \\'here L length of blood 'esse!.
t ....
n blood vist:osity. r radius of blood vessel, and t = 3. 1--1 (or 22 I 7).
Therefore. the main factors that affect (R) include the following :
( I) fhc diameter (or radius) ofthe blood \essd.
(2) rhc length of the blood 'esse!.
(J) fhc blood' iscosrt).
The ( R) is direct!) proportionate to the lcn~th of the vessel and the
blood 'isco~ity. and im ersely proponionate to the -t' 1 power of the radius of
the 'esse I. Because the lengths of blood vessels arc constant and the changes
in' iswsity arc normal!) sma ll, it fol lows that the diameters ofb/ootlves.,·e/s
comtitute tlte main factor tltat rexulates tlte peripheral resi.\ltmce.
~Since the pcripht.!ral resistance (R) varies ill\wscly with the -t'h power
or the radius {r) or the blood \CSSCI. the (R) in vi\O is markedly affected b)
smal l changes in the (r) e.g. if the (r) is doubled. the (R) is decreased to
about 6 no of its pre\ ious 'alue.
The unit of reststance (R unit) :This is the resistance that allows the
Ocm of I ml hlootl /~cco nd at a pressure gradi ent of I mmii J4. In the syst-
cmit: t:in;u lnti on, the resi stance is 1.1 R unit, while it is 0.14 R unit in the
pulmonary circulation (i.e. ohout 117 that in the systemic cirwlation).
 95
Cltapter 8 Blood velociQJamlviscositl'

FACTORS THAT AFFECT THE BLOOD VISCOSITY

The blood has a viscosity about 3 -4 times more than that of water. and
is affected by the fo ll owing factors :
( 1) The hematoc rit (H) : This is the main dctcm1inant of the blood visco-
sity. A high (H) increases the viscosity & peripheral resistance (e.g. in poly-
cythemia and dehydration) while a low (H) decreases both (e.g. in anemia).
(2) Composition of the plas ma : The plasma has a viscosity about 1.8
times more than that or water, which is primarily caused by fi brinogen and
some globulins. Thcre l'o rc, the blood viscosity is increased in cases or
marked elevation of the plasma proteins (e.g. hyper-gamm nglobulinemia).
(3) Blood temperature: Cooling increases the viscosit y, and vice versa.
(4) Diameter of the blood vessel : The bl ood viscos ity is low in the
vessels havi ng sma ll diameters (due to a low (H) in these vesse ls).
(5) Velocity of blood flow : The viscos ity increases at low veloc ity !low
rates. and vice vcrsa.

VELOCITY OF BLOOD FLOW

The blood veloc ity at any point in the circul atory system is in versely
proportionate to the total cross-sectional area at that point, and is calcul a-
ted by dividing the blood.flmv rate I cross sectimwl area.
In the aorta, the blood now rate(= CO) is about 90 ml / second and its
cross secti onal urea is about 4. 5 em:! , thus the blood velocity in the aorta is
90 I ./.5 = 20 em I second. In contrast. the total cross sectional area of the
capillaries t( all are open [whi ch docs not occ ur normally] is about I 000
times more than that of the aorta (4500 em:!). thus the blond 1•elocity in the
capillaries would be much slml'er (90 I 4500 = ().()2 em / second).

Estimation of the blood velocity

The blood velocity can be clinically estimated by measuring the circulati on
time between 2 points (i.e. the time taken by the blood to move from one
point to the other) using certain substances, dyes or isotopes. For exa mpl e::
( I) Arm to lung circulation time: A rew drops of ether arc injected into
an arm vein , and the time elapsing between rhc injecti on till smelling the
odour of ether in the expired air is measured. ormal ly it is about 6 seconds.
and it indicates the pumping power of the right ventricle (so it is prolonged
in right-sided heart fa il ure).
(2) Arm to tongue circulation ti me : i\ bile sa lt preparation (dccholin) is
injected into an arm vei n. and the time elaps ing between the injecti on till the
tasting its bitter taste is measured. Normally, it is about /5 seconds, and it
indi cates the pumping power of both ventricles (so it is prolonged in both
right and left sided heart railure. and if the arm to lung circulation time is
nonmtl , its prolongation indica tes left sided heart fa ilure).
 96
ChapterS Probability o[turbulence (The Revnold's number)

~The circulation times arc also prolonged in cases of obstruction in the

vascular system. On the other hand, they arc shortened in cases of hyper-
effective hearts (e.g. during exercise and in hyperthyroidism), and when the
blood velocity is increased (e.g. in anemia).

TYPES OF BLOOD FLOW

(I) Laminar blood now: This is the normal smooth (streamline) flow of
blood in the blood vessels. It is silent (i.e. producing no sounds) and laminar
i.e. the blood fl ows in severa l layers or laminae (figure 57 A}. The outermost
layer of blood in contact with the vessel wall is almost completely static (not
moving) while the other layers move by velocities that increase gradually till
becoming maximal in the central layer of the stream.
(2) Turbulent blood now : T his is disturbed blood now in the form of
eddies in various directions. It produces sounds ( bruits or murmurs) which
can be heard by the stethoscope. It specially occurs when a certain critical
velocity ofhloodjlow is exceeded, in addition to other factors (sec next).

--........
~
~

I
I Uplltttm () !c ) __\,_,-,___ __ )
-.J.---~-.......;. ...J,

/ lanw~tr Hot~~VtiO<oty
7

---
/
A
Vuwlwlll
Fl- -

Fie,urc 57: Streamline (A) and turbulent (B) blood flow, c - constriction.

Probability of turbulence (The Reynold's number)

In addition to the blood velocity, its viscosity and dens ity as well as the
diameter of the vessel arc also contributing facto rs in producing turbulence.
T he effects of these factors arc expressed as the Reynold's number (Rc):
Rc = pOV In where p - blood density, 0 = diameter of the vessel,
V velocity ofblood now, and n = blood viscosity.
 9R
Cltapter 8 Bemoulli's principle

The plethysmograph can also be used to (a) Demonstrate the phenomenon of

reactive hyperemia (page I 12) (h) Study the effects or vari ous drugs on the
arterio lar diameter (3) Detect the cause or an arterial ocdusion (page 11 5).

The critical closing pressure

When the pressure inside a small blood vesse l (= intraluminal pressure)
is decreased, the blood flow is decreased proportionately ti II it stops com-
pletely ultliouglt the intraluminal pressure die/ not drop to :ero. The intra-
luminal pres~un: in this ca~e is ca lled the critical closing pressure, and the
stoppage of blood llow is due to (a) The extraluminal pressure (= pressure
exerted by the surround ing tissues) exceeds the intmluminal pressure resu lt-
ing in collapse or the vessel (b) Drop or the intrahiminar pressure below the
pressure required to force the red blood cells through the narrow capillaries.

Figu re 59 : Demonstration of 8ernoulli's pri nciple.

THE FLUID ENERGY and BERNOULLI'S PRINCIPLE

When fluid moves inside a tube. it acquires 2 types of energy:

(I) Pressu rc energy (P E) which causes lateral prc~surc on the tubular wa II.
(2) Kinetic or llow energy (KE) which moves the lluid along the tube.
The pressure gradually drops as the fluid moves along the tube (dashed
line in figure 59) because of thc energy lost in overcoming resistance(= l'ric-
tional forces) and the energy that is converted into kinetic energy (since both
types or energy arc interchangeable). However, tlte total energy at fmy por-
ticm of the tube (= sum of both (vpes of energy) is coils/alii, and this i.,.
called Bernoulli's principle. According to this principle (a) If the kinetic
energy (i.e. the ve locity or llow) increases at n point (e.g. in a constricted
part ol" the vt:ssc l), the pressure is furth er decreased (midd le column in ligurc
59) (b) In a severely-d ilated area or an artery(= aneiiiJ'SIIl), the velocity is
decreased whi le the pressure increases (so these areas arc liabl e to rupture).
 99
CHAPTER9

I THE ARTERIAL BLOOD PRESSURE I

This is the Ioree exerted by the blood on the arterial walls. II normall y
oscillates during the cardiac cycle between a maximum called the systolic
B.P. (at the peak of the max imum ejection phase) and a minimum called the
di astoli c B.P. Uust before opening of the aortic valve). The ~ystcmic systolic
B.P. normally averages 120 mmH g in young adult males (range 100- 140
mmllg), and is produced by ejection of blood into th e aorta during left
ventricular ·'J'Stole. On the other hand .. the systemic diastolic B.P. nom1ttlly
averages 80 mmllg (range 60-90 mmHg). and is produced as a result of the
c lasti c recoi l of the aor1a (= Windkessel effect) during ventricu lar diastole.
The difference between the :.ystolic and diastolic B.P. is called the pulse
pressure. It normally averages 40 mmHg and its magnitude is dctcm1ined
by the stroke vo lume, the speed by which the stroke vo lum e is ej ect ed
and the co mplian ce (distensibility) of t he arteri es (page 40).

The mean arterial blood pressure

This is the average arterial pressure during the cardiac cyc le. II is the
pressure responsible lor tiss ue perfusion with blood, and al l pressure
regulatory mechanisms coopcrate to keep it constant. It is normal ly less than
I 00 mm Hg (the arithmetic mean or 120 + 80) hecause the arterial pressure
renwi11s closer to the diastolic pressure jar a longer pcm cl ti!C' cardiac
cycle than the systolic pressure (the diastolic period occupies about 213 or
the cardiac cyc le). The following formula is generall y used to calcu late th e
mean arterial blood pressure :
Mean B.J>. = Diastolic B.P. + 113 pulse press ure = 80 + 13 = 93 mmll g.

MEASUREMENT OF THE ARTERIAL B.P.

The arteria l B.P. should be measured in an artery placed at the le,·cl
of the heart to eliminate the effect of gravi ty. Therefore, it is usually
measured in the brachia l artery while the person is in the rec um bent
position. and one.! of the following methods can be used :
(1) Direct measurement : This is performed by inserting a canmi/a into the
artery and connecting it to a manometer. llm,·ever, 1his method is used only
in special cases.
(2) Indirec t measurement : This is performed routine~\· using an apparatus
ca ll ed the sphygmoma11o11wler (refer to the practica l book), which can
measure the arterial 13.P. by both a p alp atOIJ' m ethod (for rough
measurement o{ the .s:vstolic pressure) and an auscultatory method (for
accurate m easurement (~! both the systolic and diastolic pressures).
 100
Chapter 9 The arterial blood pressure

PHYSIOLOGICAL CHANGES OF THE ARTERIAL B.P.

The level of the arterial B.P. is nonnally changed by the followi ng factors :
(I) Site of measurem ent : It is highe r in the lower than in the upper limbs.
(2) Age : It is low at birth (about 70-80 I 40-50 mm Hg) then it rises till
about 120 I 80 mmHg at the age of 20 years. After that it gradually increases
becoming about 150 I 90 mm l lg after the age of 60 years.
(3) Sex : It is generally s lighlly higher in adult males than in females.
(4) Body built (constitution) : It is usually high in obese persons.
(5) Race : It is often high in western countries.
(6) Diurnal variation : It is low in the morning and high in the afternoon:
(7) Meals : lt increases slightly after meals.
(8) Exercise : It markedly increases during exercise (specially the systolic).
(9) Emotions: It increases in most emotions (specially the systo lic).
(1 0) Intercourse: It is o fie n increased during intercourse.
(II) Sleep: It is often slightly decreased during quiet sleep.
( 12) Temperature: In hot environments, the systolic pressure increases due
to tachycardia, but the diastolic pressure may fa ll due to cutaneous V .D ..
(13) G ravity : On standing, the fo rce of gravity increases the mean arterial
pressure below the heart level by about 0.77 mmHg I em.
( 14) Respiration : The arterial B.P. shows rhythmic fluctuations during the
respiratory cycle ca lled 7i·auhe-llering waves. It increases during inspiration
(due to the increase in VR and CO) a nd decreases during expiration.

FACTORS THAT DETERMINE & MAINTAIN THE ARTERIAL B.P.

Many factors determine and maintain (and also affect) the level of the
arterial B. P. The mai n determinants of the a rterial B.P. arc the cardiac out-
put (CO) and the resistance to blood now ofTercd by the vascular system
(specially the peripheral resistance i11 the arterioles). Therefore, the m ea n
systemic arterial B.P. = COx p eripheral resista nce (page 94). ln addition,
the elasticity (comp/iaflce or distensibility) of the aorta also contributes.

(1) CARDIAC OUTPUT (CO)

The arterial B.P. is directly proportionate to the CO [which equa ls the
product of the stroke volume (SV) x heart rate (HR)]. With a constant HR,
changes in the SV affect mainly the systolic pressure (an increase in the SV
increases the systolic pressure and vice versa). On the other hand, with a
constant SV, cha11ges in the HR affect mainly the diastolic pressure (an
increase in the HR increases the dias tolic pressure and vice versa).

Effect of the blood volume and vascular capacitance

These affect the arterial B.P. through changing the mean circulatory
pressure (MCP), the venous re turn (VR) and the SV. An inc rease of the
 101
Chapter 9 The baroreceptor.\· (pressoreceptor.\')

blood ~o lume or a decrease of the vascula r resistance (by venoconstriction)

~vould 111e~ease the MC P, so the VR is increased (page 8 1) leading to an
mcrease o l the EDV and SV, thus the systo lic pressure ri ses. Conversely, the
systolic pressure fall s in oppos ite conditions.

(2) F'ERIPHERAL RESISTANCE (PR)

The PR is essentia l for ma inte nance of the arteria l bl ood pressure

particularly the diastolic pressure. It is determi ned by: (a) The rad ius (or
diameter) of the vessel (b) Blood viscosity (c) T he leng th o f the vessel.
llowever, nom1a lly the arteriolar diameter is the main determinant factor
because the other 2 fac tors arc normally kept constant (page 94).

(3) ELASTICITY (COMPLIANCE) OF THE AORTA

Part of the pumping ene rgy o f the heart is expended in distention of the
aorta. T his energy is released during cardiac diasto le caus ing elastic recoil
of the aortic wall . Such effect is essential for ma inte na nce of a relatively
high diastolic B.P. and is ca lled the W indkessel effect.
In addition, the aortic e lastic ity prevents excessive rise o f the systolic
B.P.• and the e ffects o r its loss (in arteriosclerosis) arc (a) Rise o f the systo-
1ic pressure and Ia ll o f the di asto lic pressure leading to increase of the pulse
pressure (page 40) (b) The blood flow to the tissues becomes a/m()st only
during .\ ystoles (page 33) (c) T he velocity of pulse walle transmission is
increased (page 39).

THE BARORECEPTORS(PRESSORECEPTORS)

T hese are stretch receptors that provide the nervous system with in fonna-
tion about the level (?(the arterial blood pressure. T hey arc located in the
walls of certain h/ood vessels as well as the heart, and inc lude the following

( I ) T he arterial baroreccptors : T hese a rc located in the wall or a lmost

e1'el:l' large artetJ' in the tlwracic and neck regions, but particu la rly in the
walls of the carotid sinuses and aortic arch (page 7 1).

(2) The cardiopu lmonary baroreceptors : T hese arc located in the walls
of both atria, the left llentric:le and the pulmonary vessels. The ir stimul ati on
leads to the same effects produced by stimulation t~{ the arterial harorecep -
tors (te mporary apnea, bradycardia, genera lized V.D. and hypote ns ion).
 102
Cl/(1()I(!,. 9 Regulation (co ntrol) o[the arterial blood pressure

THE ARTERIAL BARORECEPTORS

These arc responsible for production of the cardiac: l'ftgaltone (page 70)
and play a major role in short-term regulation t~l the arterial blood
pres.m re (sec below). They provide signals to the vasomotor centre ahout
hoth the mean arterial pressure and the pulse pressure. Signals from the
~:aroutl sinus barorcccptors pro' ide infom1ation regardi ng the arterial press-
me 111thin the mnge <?{ ahout 50 /80 mmllg and arc transmitted b) a
h1anch of the glossopharyngeal ner\'c cal led the simt'i (or llering) nerl't.'
(page 71). On the other hand. the aortic homreceptors OfJ('/'llte at pressure
len•ls about 30 mmHg higher than the carotic/receptors and their signals arc
transmitted by a branch of the vagus nerve ca lled the aortic nerve (page 71).

REGULATION (CONTROL) OF THE ARTERIAL B.P.

\Vhenc\'cr the arterial blood pressure is altered. it ''ill be restored to the

normal le,·cl b) shor t and long term mechanisms.

(I) SHORT-TERM MECHANISMS

These arc rapidly act in g pressure control mec hanisms. They constitute
the first line of defense against alterations of the arterial B.P. (so they arc
life sm,ing). The) can be divided into (A) Mechanisms that start acting
within a few secomls (B) Mechani sms that start acting within a few minutes
(these can be ca lled int ermediat e-term press ure control mecha nisms).

(A) Mechanisms that start ·acting within a few seconds

These arc conccmcd \\ ith momellf to momellf control of the arterial

blood pressure, and arc mostly n ervous re}Texes. They become ful~)l active
~t •itltin a minute and include the l(,llowing :

(1) The baroreceptor reflex (buffer function of baroreceptors)

The arterial baroreceptor.,· and their connections constitute a control

. . ystcm that opposes changes in the arterial blood pressure . ..,o this system i..,
called the pressure buffer S)'>tcm. and the si nus and aortic 111.:1'\ Cs arc ca ll ed
the bu ffer nerve\. These receptor!> monitor am/ buffer t:lumges in tlw
arterial blood pressure by the following mechanism :
 103
Chapter 9 Short- term regulation o(the arterial blood pressure

(a) When the arterial blood pressure increases, the arterial wa lls arc
stretched and the barorcccptors arc stimulated resulting in an increase of
their discharge rate. Signals initiated from these receptors arc conducted by
the buffer nerves to the vasomotor centre where they lead to stimulat ion of
the CIC and VDC and inh ibition of the VCC. Such responses lead to
reduction of the arterial blood pressure by decreasing ( I) The peripheral
resistance (through producing V.D. in both the arterioles and venules) (2)
The CO (through decreasing the heart ra te and card iac contract il ity) and (3)
Catecholamine secretion from the adrena l medu llae.
(b) When the arterial blood pressure decreases (e.g. due to hemorrhage),
the discharge rate from the baroreceptors is decreased. Thi s relemoes the
VCC from their inhibitory effect ami decreases tlte activity of the CIC and
VDC. Accord ingly. the cardiac vaga l tone is decreased and the sympathetic
discharge to the heart and blood vesse ls is increased (and catccholam incs arc
released from the adrena l medul lae). These effects increase the heart rate
and contracti lity (so the cardiac output increases) and lead to arteriolar V.C.
(which increases the periphera l resistance) as well as venous V.C. (which
increases the venous tone and venous retum). All these responses help eleva-
tion of the arterial blood pressure toward the nom1al level.

Role of the arterial baroreceptors on changing the body posture

A sudden change from the recumbent to the upright posture tends to decrea-
se the arterial blood pressure due to reduction of the VR and CO as a resul t
of pool ing of blood in the lower li mbs by the effe ct of gr avity (page 86).
However. this decreases the discharge .from the baroreceptors, leading to
increased sympathetic discharge to the heart and blood vessels and the
resulting tachycardia, increased cardiac contractility and arteriolar and
''enous V. C. pre1·ent drop o.f the arterial blood pressure (page 126).

IMPORTANT REMARKS ON THE BARORECEPTORS

::::_ The arterial baroreceptors arc not important in long term regulation of the
arterial blood pressure because they become reset (adapted) IVithin I -2 days
::.:: The low pressure receptors in the atria and pulmomiiJ' vessels arc
stretch receptors similar to the arterial ba roreceptors, but they respond to
loH'er pressures. Tn fact, they are volu me r eceptors the primary function of
which is to regulate the blood volume but while doing so, they also minimi::e
changes in the arterial hlod pressure e.g. nn increase in the blood vo lu me
tends to increase the arteria l blood pressure. However. stimulation of the
volume receptors leads to generalized arteriolar and venous V. D. (but wit!t
tachycardia rather than bradycardia, page 74).ln addition, several effects
 104
Chapter 9 Short- term regulation o(the arterial blood pressure

known as the volume reflex arc produced in the kidneys. These include (a)
Increased glomerular filtration (due to V .D. of the glomeru lar capi llaries) (b)
Increased water excretion by the kidneys due to rcn ex inhi bi ti on of secretion
of the antidiuretic hormone (c) Increased renal Na' excretion due to
secretion of ANP (= atrial natriuretic peptide) from the distended atrial
wa lls. A II these effects decrease the blood volume and together with the
generalized V.D. they also minimize elevation ofthe arterial blood pressure.

** There arc intra-r ena l baroreccptors (the juxtaglomerular cells in the

;;Il ls of the afferent renal arterioles) which respond to a decrease in the
arterial blood pressure (or renal ischemia) by secreting r en in (sec below).
_::Cutting of the sinus nerves stops the signals from the arterial barorccep-
tors and is interpreted as a drop in the mean arterial pressure. Thus, generali-
zed v.e. together with increased heart rate and contractility occur resulting
in rise ofthe arterial blood pressure. On the other hand, subsequent stimula-
tion of the central end of the cut sinus nerves is interpreted as a rise of the
arterial blood pressure and this causes generalized V.O. together with decre-
ased heart rate and contractility, which leads to drop of the arterial pressure .
.:: Occlusion of the common carotid a rteries decreases the pressure in
the carotid sinuses. This leads to general ized V.C. and increased heart ra te
and contractility, which results in rise of the arterial hlood pressure.

The abdominal compression reflex : Whenever the baroreceptor (or

chemoreceptor) reflex is in itiated (in cases of drop of the arterial blood
pressure), stimulation o f the vee is associated with excitation of the
medullary reticular formation and this discharges signals via somatic nerves
to the abdominal muscles leading to their contract ion. This is an important
mechanism to increase the arterial blood pressure because it increases the
in traabdominal pressure which compresses the venous reservoirs of the
abdomen resulting in an increase of the venous return and cardiac output

(2) The chemoreceptor reflex

The receptors of this re n cx are located in the carotid and aortic bodies.
These arc stimulated when the arterial blood pressure is decreased below 80
mmllg (mainly as a result of local decrease in P02 which occurs secondary
to ischemia). In this case, they discharge signals in the buffer n erves that
stimulate the vee, which leads to e levation of the arteria l blood pressure.
llowcver, the c hc morcccptors play a much more important role in the
con trol of respiration than in regulation of the arterial blood pressure.
 105
Chapter9 Short- term regulation o[tlte arterial blood pressure

(3) The CNS ischemic response

In cases of severe reduction of the mean arterial blood pressure (below 50

or 60 mmHg), brain ischemia occurs, and the resulting increa'ie in PC01
and hypoxia stimulate the vasomotor centre, resulting in rise of the arterial
blood pressure that is associated with bradycardia (due to either simultane-
ous increase in vagal discharge or secondary to stimulation of the arteria l
baroreceptors). Such response is not a normal mechanism for arterial blood
pressure regulation because it becomes significant only at very low levels of
the arterial blood pressure. It operates only as an emergency pressure
control system when the cerebral blood flow decreases to fatal levels.
Cushing reflex (or reaction) : Rise of the intracranial pressure (i.e.
CSF pressure) results in rise of the arterial blood pressure and brady-
cardia. The rise of the intracranial pressure leads to brain ischemia (due to
compression of the ccrcbml blood vessels), and the resulting hypoxia and
increa'ie in PC01 stimulate the vasomotor centre, leading to rise of the
arterial blood pressure (which increases the cerebral blood flow) that is
associated with bradycardia as occurs in the CNS ischemic response.

(B) Mechanisms that start acting within a few minutes

These are autoregulatory intermediate-term mechanisms that arc

initiated within 20-30 minutes after alteration of the arterial blood pressure,
become maximal after several hours (during which the nervous mechanisms
almost disappear completely) and they last for a few days. They include :
(1) Capillary fluid shift mechanism : When the arterial blood press-
ure.is altered, the exchange of fluids in the capillaries contributes to its
return to the normal level e.g. elevation of the arterial blood pressure usually
increases the capillary hydrostatic pressure, and this increases fluid filtration
into the tissue spaces, thus the blood volume is decreased leading to reduc-
tion of the arterial blood pressure toward the normal level. The opposite
occurs when the the arterial blood pressure is decreased.
(2) Stress relaxation mechanism : Changes in the arterial blood
pressure gradually causes the blood vessels to attain new sizes that
accommodate the present amounts of blood e.g. rise of the arterial blood
pressure following massive blood transfusion initially stretches the arteries
and increases the tension in their walls. However, within a few minutes to an
hour the arteries relax and the tension in their walls decreases. This is called
stress relaxat ion of the arteries, and it helps loweri ng of the arterial blood
pressure When the arterial blood pressure falls, it can be elevated by an
opposite mechanism(= reverse stress relaxation).
 106
Chapter 9 Lonr:- term regulation o(llle arterial blood pressure

(3) Renin-angiotensm V.C. mechanism : i\ fall of the arterial blood

pressure leads to renal ischemia. This stimulates secretion of an en7yme
ca lled renin from the juxtaglomerular cells of the kidney, which acts on a
plasma alpha 2 globulin called a ngiotensinogcn (a polypeptide .syn thesized
by the li ver) form ing a decapcptidc called angiotensin I. An enzyme ca lled
cmgiotensin-con1•erting en::yme converts angiotensin I into an octapeptide
call ed angiotensin II (moslly in the lungs), which has a potent V.C. effect
that increases the anerial blood pressure. Angiotensin II also stimulates
secretion of' a hormone ca lled aldosterone from the adrenal cortex, which is
invoh cd in long-tem1 regulation of the arterial blood pressure (sec next).

(II) LONG-TERM MECHANISMS

These mechanisms con trol the arterial blood pressure over long periods
(months and years) by a renul body fluid mechanism i.e. by adjusting the
body fluids and blood volume through modifying the excretion of water and
salt by the kidneys. This occurs by changes in the mtes of glomerular
filtration and secretion of tlte aldosterone hormone as follows :
( 1) A fa ll of the arterial blood pressure l0ads to (a) Reduct ion of the
glomerular filtrati on rule (which promotes water and sa lt retention in the
body) (b) Secretion of renin , which stimulates aldosterone secret ion from
the adrenal concx through formation of angiotensin II (sec above). This hor-
mone increases a~ reabsorption from the renal tubules together with water,
and such effect together with reduction of the glomerular filtration rate
increases the body fluids and blood volume, which elevates the arterial
blood press ure toward the normal level.
(2 ) A rise of the arterial blood pressure im:rcascs glomerular filtration,
producing pressure diuresis (which leads to loss of water and sa lt in the
urine). At the same time. renin secretion is inhibited. so aldosterone
secretion is decreased. leading to loss of Na· and water in the urine. This
effect together with pressure diuresis decreases the body fluids and blood
vo lume. which reduces the arteria l blood pressure toward the normal leve l.

Hormones involved in regulation of the arterial blood pressure

(1) Catcc holamines : These arc secreted by the adrenal medullae whenever
the sympathetic system is activated secondary to stimulation of the vee and
they augment its cfTccts on the heart and blood vesse ls to elevate the art erial
blood pressme. They arc ilt1•oh•ed only in sltort-term regulation of the
arteria l blood pressure beca use their effects last for only 2- 3 minutes.
(2) Ald osterone: This is involved in i11termediate and long-term regulation
of the arterial blood pressure (see above).
 107
Clwpter 9 Experimental h}'pertension

(3) ADH (= antidiuretic hormone or vasop ressin) : Through its action on

the kidneys, AD II promotes water retention in the hru/1•. It ulso exerts a
considerable V.C. e.Oect and is important for elevation oi· th e arterial blood
pressure when it is severely decreased (e.g. in acute hemorrhage). ll o,vcver,
it is not in i'Oived in mome111 to moment regulation o,/the arleriol pressure.

Major differences between the short and long term mechanisms

involved in regu lation of the arterial blood pressure
(I) The short term mechanisms arc rapi dly acting (within ~eco nd s or
minutes) and arc concerned with correction of acute altera t ion~ of the arterial
blood pressure as well as its momem to moment control. On the other hand,
the long term mechanisms are slowly acting and are concerned with
maintenance of the arterial blood pressure constant over long peri ods.
(2) The short tcm1 mechani sms lose the ir cfTiciency rapi dly and almost
disappea r completely within n few days. On the other hand, the long term
mechanisms become steadily greater with time.
(3) The short term mechanisms cannot complete ly bring an altered
arteri al blood pressure back to the normal level. On the other hand, the long
term mechanisms nrc highly potent and can bring an nltercd arterial blood
pressure back to the normal level but at a longer time.

EXPERIMENTAL HYPERTENSION (INDUCTION OF HYPERTENSION)

ll ypcrtcnsion can be artifi cially-produced in ex perimenta l animals (lo r

research purposes) by one of the followin g methods :
( I) Producing rena l ischemia (by constricti ng the renal arteries or the aorta
just above the origin or the renal arteries). Such renal hypertension is part-
ia lly caused by salt and 1\'ater retemion (due to poor rena l blood fl O\\) but it
is mainl y the result of renin secretion, which leads to formation or angiotcn-
. in II. the actions of wh ich increa.<;e tbe arterial blood pressure (sec be low).
(2) Partial nephrectomy with a high sa lt intake : Thi s produces hyper-
tension due to decreased renal abil ity to excrete the excess salt.
(3) Denervnt ion of th e a rterial baroreccptors : Thi :, leads to tachyca rdia
and V.C., result ing in what is known as neurogenic hypertension .
(4) Ligati on of th e major cerebral arteri es (cerebral ischemia ) : This increa-
ses the arteri al blood pressure by the CNS ischemic re:,ponse (page I 05).
(5) Exposing the animal to repeated loud noises : This in creases the arterial
blood pressure due to exc itati on of' the vasomotor centre by cortical impulses
(6) Administration of large closes of mincralocorticoids e.g. aldosterone.
(7) Production of strains or animal s that easily develop hypertension either
spontaneously or when fed diets rich in sa lt (genetic hypertension).
 108
Chapter9 Actions ofangiotensin II and hypertension

ACTIONS OF ANGIOTENSIN II

(I) Generalized potent V.C. (4-8 times as active as norepinephrine).

(2) Facilitation of norepinephrine release from the sympathetic nerves.
(3) Stimulation of aldosterone secretion from the adrenal cortex.
(4) Decreasing glomerular filtration (by causing contraction of the mesangial
1
cells in the renal glomeruli) and increasing Na reabsorption by a direct ac-
tion on the proxima/tubules ofthe renal nephrom· {refer to kidney).
(5) Excitation of certain structures located above the brain stem in relation to
the hypothalamus known as the circumventricular organs (page 134),
wh ich lead to (a) Release of the antidiuretic hormone (helps water retention
in the body) (b) Thirst (increases water intake) (c) Secretion of ACTH (a
hormone that stimulates secretion of hormones from the adrenal cortex).
Angiotensins Ill and IV
An aminopeptidase removes one amino acid from the angiotensin II mole-
cule and the resulting heptapcptide is called angiotensin Ill. This has 40
%only of the pressor activity of angiotensin II but I 00% of iLo; aldosterone-
stimulating activity. Subsequent removal of another amino acid produces the
hcxapcptidc called angiotensin IV, which is said to have some activity.

HYPERTENSION (HIGH ARTERIAL BLOOD PRESSURE)

T his serious disease is djagnosed if the mean arterial hlood pressure of

a resting adult person exceed'! 110 mmHg {which occurs when the diastolic
pressure is greater than 90 mmHg and the systolic pressure is greater than
140 mmllg). Its severity is evaluated on the ba'iis of the diastolic pressure
(up to 100- 105 mmllg is mild, between I 05 and 11 5 mm llg is modemte,
and more than 11 5 mml-lg is severe). Both systolic and diastol ic pressures
are us ually elevated, but there are some cases of isolated increase in either.
Although hyperten sion can result from an increase in- th~ cardiac out-
put, the main cause in most cases is an increase in the tlJtal peripheral
resistance Generally, there arc 2 main types of hypertension:

(A) Primary (or essential) hypertension

T his constitutes about 90 % of cases. It is associated with narrowing o f

the resistance vessels (i .e. arterioles) of unknown cause. It is frequently
inherited but social and environme ntal factors arc also invol ved. In chronic
cases, the baroreceptor rc ncx regulatory mechanism (page I02) is reset to a
higher set point than normal (i.e. it acts to maintain. the elevated pressure).
 109
Chapter9 Hypertension

(B) Secondary (or symptomatic) hypertension

This is an elevation of the arterial blood pressure as a result of other
diseases (i.e. the cause is known), and it accounts for about 10% of cases.
The common diseases that cause hypertension include the following :
(1) Renal diseases associated with renal ischemia (and also tumours of juxta-
glomerular apparatus). Tn these cases, hypertension occurs mainly due to act-
ivation of the renin-angiotensin system(= renal or Goldblatt hypertension).
(2) Pheochromocytoma (= tumour of the adrenal medulla) : This causes
hypertension due to excessive secretion o f catecholamines by the tumour.
(3) Cushing'.\· and Conn's syndromes : These cause hypertension due to
excessive secretion of hormones from the adrenal cortex (glucocorticoids in
the former and aldosterone in the latter), and these hormones promote Na! .
and water retention in the body which elevates the arterial blood pressure.
(4) Toxemia ofpregnancy : Hypertension in this case is believed to be ·due
to release of toxic substances from the placenta (? as a rcsuilt of ischemia)
that cause general ized dysfunction of the vascular endothelial cells. This de-
creases the release of NO (and other vasodilator substances) from the endo-
thelial cells, which leads to generalized V.C. resulting in hypertension (due
to increased peripheral resistance and decreased glomerular liltratjon rate).
(S) Polycythemia : This increases the blood viscosity, so the peripheral resi-
stance is increased, resulting in elevation of the arterial blood pressure.
(6) Prolonged intake of contraceptive pills : This produces hypertension in
some women (= pill hypertension) due to an increase of the angiotensinogen
blood level (the production of which is stimulated by the estrogen hormone).
(7) Aortic coarctation : This is congenital narrowing of a segment of the
thoracic aorta. The arterial blood pressure is markedly elevated in the upper
part<; of the body. However, it is us ually not decreased in the lower parts
(and may even be sightly increased) because the resulting renal ischemi a
activates the renin-angiotensin system (which prevents drop of the arterial
blood pressure.in the lower parts of the body).

Complications of hypertension

(I) Excess work load on the heart. Left ventricular hypertrophy occurs in
chronic cases (in which it often terminates by heart failure).
(2) Degenerative changes and atherosclerosis in the blood vessels as a result
of the excessive pressure. This predisposes to :
(a) Thrombosis in the cerebntl vessels or cerebral hemorrhage (clinically
called a cerebra/stroke )
(b) Thrombosis in the coronary vessels (coronary heart disease) which
often terminates by a heart attack (myocardial in farction).
(c) Damage of the kidneys, which oflen terminates by renal failure.
 110
Chapter 9 1/vpotension

::.::._ Maligna nt hypertension is a term that refers to severe cases of

hypertension associated with extensive necrotic vascular lesions and prog-
ressive renal fai lure without an obvious ca use. Without treatn1cnt, it results
in rapid deterioration or the patient and death occurs in less than 2 years.

Physiological basis of treatment of hypertension

ll pertension definitely shortens life expectan(v. Secondary hypertension
can be prevented by treating the underlying cause. while primary hyperten-
sion can b~.: treated by solr resrriction and the following hypolensil·e drugs :
( I) Drugs thar decrease the peripheral resistance : These include vasodi Ia-
Ior drugs (that directly relax smooth musc le) as well as sympatholytic drugs
(e.g. reserpine and aldomet) .These drugs also improve the renal blood flow.
(2) Drugs rlwr decrease the strength ofcardiac conrracti!ity and hearr rare
(to decrease the cardiac output). These arc mostl y beta blockers e.g. utenolol.
(3) Drugs rhllf pret·ent .formation l?( angiotensin II specia ll y the angio-
tensin converring e/1=.\'llle (ACE) inhibitors e.g. caplopri I.
(4) Diuretic and natriureric drugs : These drugs increase Na ' and water
excretion by the renallubules(sec in kidncy)thus reducing the blood vo lume.

IIYPOTENSION
This is a state or low arterial blood pressure kss than I 00 I 60 mm llg.
lt is due to a decrease or either the peripheral resista nce or the cardiac ou tput
(or rarely both), and it may be primary or secondary. The primary type has
no obv ious causes and occurs spec ially in young indi vidua Is who have
asthenic (weak) slender bod ies.On the other hand, the secondary type occurs
as a result of disease or other conditions. which include the following :
( I) Cardiovascu lar diseases associated wit h low cardiac output e.g. mitral
or aortic stenosis.
(2) Ce11ain endocrine diseases e.g. hypothyroidism and adrenocortical
hypofunction(= Add ison's disease).
(3) Hypovolem ia e.g. due to acute severe hemorrhage or loss of large
quantities of ex tracellular Ouid (as occurs in severe diarrhea and vomiting).
(4) Excessive release of vasodilator substances (as occurs in severe infec-
tions and allergy).
(5) Loss of the sympathetic V.C. tone (the vasomotor tone). Thi s may
occu r in some emotions as a resu lt of impulses discharged from certain areas
in the cerebra l cortex that depress the vee. It leads to fainting known as th e
vasovagal syncope clue to cerebra l ischemi a (page 150) that can be reiicvcd
by lying down (which increases the venous return and cardiac output).
In general, hypotension can be treated by giving drugs that induce Y.C.
and by treatment of the ca use (in the secondary type).
 Il l
CHAPTER 10

IREGULATION OF THE ARTERIOLAR DIAMETER !

The arteriolar diameter determines the peripheral resistance as 1vel/ as
the blood.flow to the tissues. It is regulated by local a nd systemic facto rs.

(A) Local regulation of the arteriolar diameter

This is concerned with control of the loca l blood tlow rate in the
tissues and is produced by the effects of the following factors :
( I) L oca l 02 tension : A local decrease in P02 leads to arteriolar V.D.
directly (which increases the local blood now rate in active tissues).
(2) Metabolites : Most metabolites formed during activity cause arter-
iolar V.D. and relaxat ion of the precapillary sphincters. These metabolites
inc lude C0 2 , K-, H ' , histamine, lacti c acid, ADP and adenosine (the latter
is the most potent, and is formed spec ially in the cardiac muscle).
(3) Local tem perature : Rise of temperature in active tissues (by the
heat of metabolism) causes arteriolar V.D. that increases the blood now.
(4) Aut oregu lat ion : This is the ability to maintain a constant blood now
in spite of changes in the perfusion pressure. It is well developed in the
kidneys, and is explained by 2 theories :
(a) Metabolic theory : This is the most accepted theory. As the perfu-
sion pressure is decreased, the blood now is reduced leading to local 02 lack
and accumulation of metabolites. Both effects lead to V.D., thus the blood
now is increased and is kept relatively constant. Opposit e effects occur
when the perfusion pressure is im:rcascd (the metabo lites arc washed and
V.C. occurs, so the blood flow is reduced and is kept relatively constant ).
(b) Myogen ic theory : As the perfusion pressure increases, the arteri-
oles distend and in response. thei r smooth muscle fibres contract , so their
di ameters arc decreased and the blood flow is not much increased.
(5) Local~y-released (paracrin e) arteriolar regulators : The fo ll ow ing
substances arc released locally at tissues and affect the arteriol ar diameter :
a- Serotonin and rhromhoxane A 2 (V.C. substances released from platelets)
b- Prostaglandin 12 (prostacyclin), a V.O. substance form ed by the endo-
theli al cells that line the blood vesse ls (the vascular endothelium).
c- Endothelin I, a potent V.C. peptide form ed by the vascular endothelium.
d- Endothelium-Derived Relaxing Foetor (ED RF). This is a powcrl'ul V.D
substance secreted by the 1·o.w:ular endothelium, and chemi ca ll y it is nitric
oxide (N O). Many V.D. substances act through stimulating forma ti on of the
EDRF (e.g. acetylchol ine, bradykinin, VTP and substance P).
 11 2
Chapter 10 Svstemic regulation o{the arteriolar diameter

~ There are 3 types of eodotbelins (ET). They are produced primarily

in the ktdneys, brain and G IT, in which ET- 1 exerts a potent V.C. effect (see
above), while ET-2 and ET-3 exert developmental effects.
~ NO is synthesized from arginine by activity of NO-synthase enzyme.
It activates f:,TZJany lyl cyclase, which acLc; on GMP and the fonned c-GMP
relaxes the vascular smooth muscle leading to V.D. NO is also important
for brain functions as well as the cytotoxic activity of macrophages. Further-
more, penile erection induced by parasympathetic stimulation is believed to
be produced as a resul t of the V.D. effect of locally formed NO.

FUNCTIONS OF THE VASCULAR ENDOTHELIUM

In addition to preventing intravascular clotting, the vascular endothelium
releases (I) EDRF (NO) (2) Endothelins (3) Prostacyclin and ? throm-
boxane A 1 (4) Thrombomodulin (5) Von-Willebrand factor (6) Platelet
Derived Growth Factor (7) Some inlerleukins and colony-stimulating factors
(8) VEGF (vascular endothelial growth factor) (9) Kinins (see below).

Active and reactive hyperemia

Active hyperemia is the increase in the local blood flow that occurs in
an active organ (e.g. a skeletal muscle during exercise). It is due to Y.O. of
the arterioles and relaxation of the precapillary sphincters that occur sec-
ondary to the local decrease of P02 and the release ofV.D. metabol ites.
On the other band, reactive hyperemia is the increa'ie in the blood flow
to an organ that occurs after temporary blockage of its blood supply. Such
increase in blood flow occurs by the same mechanisms as in active hyper-
emia specially the local decrease of P02 . It can be demonstrated by the
plethysmograph (page 98) as follows : The arlerial blood supply to the
forearm is occluded (by raising the pressure in a sphygmomanometer cuff
above the systolic pressure) for a few minutes, then the pressure is released.
An increase in the volume of the forearm w ill occur due to an increase in the
blood flow, and is often associated with ischemic pain (refer to C.N.S.).

(B) Systemic regulation of the arteriolar diameter

This is concerned with control of the peripheral resistance allover the

body so as to maintain a cons/ant or/erial blood pressure. It includes
chemical and nervous regulation.
(I) CHEMICAL REGULATION
The main circulating V.C substances include catccholamines, vaso-
pressin (= antidiuretic hormone) and angiotensin II. The main circulating
V.D. substances include ANP {Atrial Natriuretic Peptide), VIP (Vasoactive
Inhibitory Polypeptide), histamine, substance P and kinins (see next).
 1.13
Chapter 10 Nervous regulation o[lhe arteriolar diameter

KININS
These arc potent V.D. peptides, of which there arc 2 types in the body
ca lled bradykinin and kalidin.They are fo rmed from 2 precursor proteins
call ed high and low molecular weight kininogens by activity of the protease
enzyme ka llikrein.(which is fo rmed from prekall ikrein by active fac tor XII)
The acti ons of kin ins arc similar to those of histamine, and include :
(1) Contraction of visceral smooth muscle (2) Relaxation of vascular smooth
musc le (v ia NO), leading to V.D. (3) Increas ing the capillary permeability
(4) Attraction of leukocytes (5) Sti mu lation of pain receptors.
Kinins are fom1ecl during activity of the salivary, sweat and exocrine pan-
creati c glands, causing V.D. and increase of the blood fl ow in these glands.
~ 2 en~ym es call ed kininase I a nd II inacti vate kinins !.note that
kininase 11 is itse((the angiotensin converting en zyme (ACE) ].

(II) NERVOUS REGULATION

Vasoconstrictor (V.C.) nerves

These are the sympathetic nerves allover the body except some
sympatheti c V.D . fibres (see below). The sympathetic discharge is cont-
rolled by descending signals fro m the vasomotor centre via the reticu lospinal
tract, and during rest there is a basal toni c discharge in the sympathetic ner-
ves known as the V.C. or vasomotor tone, which causes partial V.C. in the
arterioles allover the body. This produces peripheral resistance to blood
flow, which is essential to mai ntain the arterial blood pressure {page I 0 I).

Vasodilator (V.D.) nerves

The V.D. nerves in the body include the foll owing :
(1) All parasympathetic postganglionic nerve fibres.
(2) The sympathetic V.D. fibres , which innervate the coronary vessels and
some visceral bl ood vessels, as well as the skeletal muscle vessels via the
.s:vmpathetic V. D. system (refer to the autonomic nervous system).
(3) The antidromic somatic V.D. fibres : Exc itation or the cutaneous pain
receptors is frequently associated with V. D. of arterioles. The signals gener-
ated at the skin receptors are transmitted by an afferent nerve to the nervous
system, then they return antidromically (i.e.in the opposite direction) via a
branch of the afferent nerve and terminate at adj acent arterioles (figure 60)
causing V.D. by releas ing substance P. Such effect is known as flare, and is
well apparent in the triple response (page 12 1). This V.D. mechanism is
call ed a local axon reflex because the nervous system is not invo lved (so it
persists after secti on of the affe rent nerves central to the dorsal root ganglia).
 11 4
Chapter I 0 Factors tltat a[[ec:ttlte l'fl.wmwtor centre

Figure 60 : The antidromic somatic n1:-.odilator fibres.

Factors that affect the vasomotor centre (VMC)

( ) Nervous factor
( 1) Impulses from the baroreccptors inhibit the VCC and stimulate the CIC.
(2) Impu lses from the chcmorcccptors stimulate the VCC.
(3) Cortical impulses common!) stimulate the VCC in cases of :-.tress and
emotional cxciternent,increasing the arterial blood pressu re. l lowcver, hypo-
tcnsion and vasovaga l sy ncope may occur in some emotions (page II 0).
(4) Impulses from the hypothalamus may st imulate the vee (e.g. during
exposure to cold ) or the VDC (e.g. during exposure to heal).
(5) Impulses from the respiratory centre stimulate the vee. elevating the
ancrial blood prcs:-.ure during late inspiration and early c\piration.
(6) SomatiC signals from contracting mu cles and 111 case or moderate palll
stmllllate the VCC b) a so ma to\~ mpathctic rcfc\. caus1ng nse of the arter-
l<ll pressure (but se\ ere pam rna) mhibit the \'CC, lcadmg to h) potens1on ).
.,e'llica c tors
A decrease in the arterial PO:! stimulates the \'CC direct!) and through
stimulating the chcmurcceptors, causing rise of the arterial blood pressure.
An increase in the arterial PC02 or I I' also stimulate the vee (the Iarmer
direct!) and the Iauer through stimulating the chcmorccl!ptors ). It i., 1o he
JWted thai local decrease o/ P()_, in the !issue~ or mcn.•ase of PCO_, or II
lead' to ar/eriolar 1'. /J. (page I II}.
( ) ys1ca f1 0
II eat cause~ direct V.D. of the arteriole~ while cold produces direct V.C.
besides the role or thl! hypothalamus. Free=ing produce., I'. C. !lwt isj(JI/o"·-
ecl hy Jl.f). which occurs as a result of accumulati on or V.D.mctabolitcs (due
lO the decreased blood flow) and release of histam inl! from the damaged
tissues (so the nose. .linger liJJS and ear lobes appear r ed in ll'inter)
 115
Chapter I 0 E[{ects of vagotom•• am/ srmpalheclomr

The cold pressor test

Thi~ test demonstrates the VC efTect of cold impul ses {sec above). The
arteria l pressure is measured at one limb. then the other limb is immersed in
icc water for one minute. and the pressure is re-measured at the fir 1 limb. It
increases by 5-l 0 mml lg in normal . ersons. but in hypertensive patients and
1ndi' iduals with autonomic hyper-reacti vity (i.e. hahlc to develop h~ per-
tension), the arterial pn.:ssurc "ill increases by 25 mml lg or more.

Effects of bilateral vagotomy on the arterial pressure

Afferent vagal nerves can produce both VD (by impulst:s from the baro-
receprtors in the aortic arch) as well as VC (by impubcs from the chcmo-
reccptors in the aortic bodies). and during rest the I 'D effect predominates.
Bilateral vagotomy af'lccts the arterial blood pre~surc a. . folio"" :
(I) If the arterial blood pressure was high or normal. the VD 'agal
effect predominates, and bilateral vagotomy in such conditions abolishes this
eiTect, leading to aJimher increase ofthe arlerial hlood pressure.
(2) If th e arteria l blood pressure was low, the VC vagal effect
predominates. and 'agotomy in such conditi on abolbhes this ellect, leading
to aJ ill'tller decrease <~/th e art<.•rial blood pressure.

Arterial occlusion

fhi-. ma) occur a.\ a re.\ lllt of either a medumiml obstruction or

wm:ular spasm (I'C). The cau-.e can be delected b~ plethy,m o~ raphy (page
98) a-. follows : The organ at which the artery i'> occluded is "armed (or a
sympmholytic drug is gl\en) and the volume of the organ is measured. Its
'olume \\ ould increase if the occlusion was due to a 'ascular spasm
(because of the rc ulting VD). but it would not change if the occlu~ion \\as
due to a mechanical obstructi on.

Sympathectomy

This is an operation that is perfonned to induce V.D. in an organ (to

increa-;c its blood flow). The section should he in the preganglionic fibre.,
because if it was in the postganglionic fibres. the operation may fail since
arteriolar VC may occur again as a result of hyper-;ensitivity to the circu-
lating catccholamincs (according to the law ofdenerwttion) .
 11 6
CHAPTER 11

THE CAPILLARY (MICRO) CIRCULATION

AND LYMPH CIRCULATION & EDEMA

STRUCTURE OF THE MICROCIRCULATION

The arterioles divide into me/arterioles , and the capillaries arise from
both (figure 6 1). The metartcrioles are directly connected to the venulcs by
thorougl!fare vessels, and the capillaries drain in these vesse ls as well as in
the venules. The openings of the cap illaries arc sutTOLmded by smooth musc-
les called precapillary sphincters which respond to various stimuli.

F igure 61 : Structure of the microcirculation.

There arc about 40 billion capillaries in the body of an adult with a total
surface area exceeding 6300 m2, and normally only I0 billions arc open at a
time. The cross sectional area of all open capillaries is about 4500 cm 2 with
an average velocity of blood flow would be 0.2 mm I second (page 95).
Their walls are about one micron thick, and each is about 0.7 mm long.
Capillaries arc generall y made up of a si ngle layer of endothelial cells
surrounded by a basement membrane and certain cells call ed pericyte.\·. They
arc commonly divided into 3 ma in types {I) Continuous capillaries (in the
muscles and brain) (2) Fenestrated capillaries (in the kidneys, intestinal
villi and most endocrine glands) (3) Sinusoid al capillaries (in th e li ver,
spleen and bone marrow).
 117
Chapter I 1 Functions o[tlte capillaries and the capillar y pressure

:!:_Since the capill ary wa lls contain no smooth muscle fib res, they arc
passive (i.e. they do not contract or relax) and their dilatation or constricti on
depends on the state of the precapillary sph in cters (t heir contraction leads to
capillary constriction while their relaxation leads to capi ll ary dilatation).

VASOMOTION
Vasomotion means intennittent opening and closure of the capillaries. It
is a normal phenomenon that occurs every few seconds to few minutes as a
result of rhythmic comraction and relaxation of the metartcriolcs and precap-
illary sphincters. ll causes interminent blood now to the tissues, and its rate
is controlled mainly by the oxygen level in the ti ssues (02 lack prolongs the
capillary openi ng periods and shortens their closure periods. and vice versa).

FUNCTIONS OF CAPILLARIES
The capillaries contain only about 5 % of th e blood volume at a time
and they constitute the site at which the exchange of various substances
between the blood and interstitial fluid occurs. It is across the capi llary
wal ls that 0 2 and various nutrients enter the interstitial fluid, while C02 and
va rious waste products en ter the blood.

FACTORS THAT A FFECT THE CAPILLARY PRESSURE (CP)

The CP is normally averages 32-35 mmHg at the arteriolar ends and 12-
15 mmHg at the ven ous ends .. It can be measured at the fingernail beds
directl y (by a pipette inserted into a capil lary and connected to a manometer)
or indirectly (by finding the pressure necessa ry to occ lude the capi llaries). It
is affected by the following factors :

(A) Pre-capillary factors

(I) Precapillary resistance : This is. detem1ined by the degree of contrac-
tion of the arterioles and precapillary sphincters. If it increases (by V.C.). the
CP decreases and vice versa.
(2) Arteria l bl ood pressure : If this increases, the CP wou ld increase.
ll owcvcr, in chroni c hypertension the precapillary resistance is increased
(due to arteriolar V.C.) and the CP is usuaUy not significantl y increased.
(B) Postcapillary factors
(1) Postcapill ary resistance : The CP varies directly with thi s resistance.
(thus, if it increases e.g. due to partial venous thrombos is, the CP increases.
(2) Venous pressure :The CP va ries directl y with changes in the venous
pressure. Thus, if the venous pressure increases, the CP also increases (e.g.
in cases of congesti ve heart fa ilure and after prolonged standing).
 II X
Chapter If Transcapillarv exchange mechanisms

CAPILLARY FRAGILITY (CF)

The capi llaries arc normall y not fragile (i.e. they do not rupture easil y)
although they arc very dc lica tl:. This is because according to Laplace law
(page 93),thc tension in the capi llary walls is very low due to their ex tremely
small radii. The CF is increased in many diseases e.g. scurvy (vitamin C
defici ency) and purpura, and it can be checked by the followin g test:

Testing the capillary fragility (Hiss test)

The sphygmomanometer cuff is wrapped around the arm and inllatcd to
a pressure of 80 mml-lg for 8 minutes. This prevents the venous ret urn from
the forearm, resulting in rise of both the venous and capillary pressures.
which leads to rupture of some capi llaries fo rmi ng tiny hemorrhages called
petechiae. The latter arc counted at the cubital fossa in a circular area 5 em
in diameter, and the CF is considered hi gh if their number exceeds 3.

TRANSCAPILLARY EXCHANGE MECHANISMS

(1) DIFFUSION : This is the process by which substances move down a

concentration gradient (il'rom areas of hi gh to areas of low concentrat ion).
Water and water-soluble substances (e.g. glucose, a' . Cl' and K ) diffuse
on ly through the capillary pores whi le fat-so luble substances diffuse across
the whole capilla1y wall (so the diffusion of fat-so luble substances and 0 2
and C0 2 is normally greater and faster than water- soluble substances].

(2) FILTRATION : This is the process by which fluid and the disso lved
so lutes arc forced through the capi llary membrane due to n difference in
hydrostati c pressure on the 2 sides, and the amount of fluid filtered per unit
time is proportionate to the difference in pressure as well as the capillary
surface area and ca pillary permeability (sec below).

(3) TRANSCYTOSIS (CYTOPEMPSIS OR VESICULAR TRANSPORT)

This is the mechanism or transport of large molecul es across the capillary
membrane. These mo lecules arc transpo rted through the capi II aries by
endocytosis into their lining endothelial cells foll owed by cxocytosis at the
interstit ial side of these cells. Normally, small amounts of protein leave the
bloodstream to the intersti tial fluid by this mechanism.

(4) DIAPEDESiS :Th is is the mechanism of transport of a who le ce ll across

the cap illary membrane e.g. leukocytes wh ich leave the bloodstream toward
areas of in flammation by this mechanism (refer to blood).
 119
Chapter II Formation tmd drainage o[t!te interstitial fluid

FORMATION AND DRAINAGE OF THE INTERSTITIAL FLUID

(BULK FLOW ACROSS THE CAPILLARY MEMBRANE)

The interstitial Ouid (IF) is continuously rormcd and drained at the cap-
illaries, and it contains almost the same constituents ofthe plasma except rhe
plasma proteins (which arc minimally filtered because of their large sizes).

MECHANISM OF IF (= TISSUE FLUID) FORMATION AND DRAINAGE

2 main factors affect the IF(- tissue Ouid) f'orma tion and drainage. These
arc the Sta rling forces (= the hydrostatic and osmotic forces that act across
the capillary walls) and the capilla ry permeability.

THE STARLING FORCES

( I) Th e hydrostatic capilla ry pressure (hcp) : This promotes fluid move-

ment outwards from tbe capillaries, and it is normall y 32-35 mmHg at the
ancriolar ends of capillaries and 12-15 mmHg at their venular ends.
(2) The in terstitial fluid pressure (ifp) : This promotes lluid movement
into the capillaries, and it normally averages I mmHg (sec below).
(3) T he plasmn osmotic {or oncotic) press ure (pop) : This is produced
mainly by plasma albumin. lt averages 25 mmllg. and it promotes fluid
mo,ement into the capillaries.
(4) T he l F osmotic pressure (ifo p): This promotes nuid movement out-
wnrds from the capillaries, and it nonnally averages 3 mml lg.
The (hcp) and ({fop) favo ur .fluid flltralion.fi"om rile capillories '''hile the
(pop) cmd (ijj;) favmw.fluid reah.w)ly)fion inro the' capillaries.
Considering the ba lance of the Starling forces at both ends of the capilla-
ries. it is clear that at their arteriolar eml\·, rite .filtering jim·es exceed rite
reabsorbing forces hy 12 mmHg 1(35 + 3) - (25 + 1)I resu lting in Ouid
fi ltration. On the other hand, at rite capillm:r 1•enular end\·. the reahsorhinp,
.forces exceed rite .filtering forc·es hy about 8 111111/lg 1(25 + I) - ( 15 + 3 )1
resulting in nuid reabsorption.
Normally. about 24 litres of tlu id arc filtered daily through the capillar-
ies. ll owcver. since the net reabsorbing force at the capillary venular ends is
less than the net filterin g force at their arteriolar ends. only about 85 % of
the filtered fluid is reabsorbed into the capi llary venular ends. and the
remainder returns to the circulation l'ia the lymph ,·esse/.\ (sec below).
~ The Starl ing forces vary greatly in different organs depending on
their functions Also. there is evi dence th<lt tlte interstitial fluid pressure
(ijjJ) is n egative in certain areas e.g. subcutaneous tissues (-2 to -3 mm Hg)
 120
Chapter 11 Factors that affect the capil/arl' permeabilitv

FACTORS THAT AFFECT THE CAPILLARY PERMEABILITY (CP)

The CP varies in diffe rent organs depend ing on their functions, and the
wno 11111 rd' 1he form ed inters/i I ial.fluid is direct~~ ' proportionol to the CP. To-
gether with the ava il able area for filtration. the CP determines the filtration
coefficient i.e. the vo lume of nuid filtered I I mmHg I minute (normall y 12.5
ml in the kidneys). The factors that affect the CP include the follow ing :
( I) Plasma Ca 2+ co ncentration : If the Plasma Ca 1 concentration increa-
ses, the CP is decreased (by narrowing the capillary pores), and vice versa.
(2) Blood pH : In acidosis. the Ca1• in the capillary wall s is dissolved. so
t h~.: CP increases. Alkalo. is produces an opposite effect.
(3) Plasma protei ns : These partially close the capill ary pores, so in case of
hypoprotei nemia, the CP is increased.
(4) Vitamin C and glucocorticoid hormones : These arc essential for vitality
and proper development of the capillary membrane, so in scurvy (vitamin C
defic iency) and hypofunction of the adrenal cortex, the CP is increased.
(5) Capill ary diameter : Capillary dilatation (by relaxation of the precapi-
llary sphincters) widens the pores in their membranes, thus increasing the
CP. This occurs by 0 2 lack, some irritant gases (e.g. chlorine), excess heat or
cold (the latter due to accumulation of V.D. metabolites as a result of isch-
mia) and by release of histamine (in innammatory and all ergic conditi ons).

The white reaction (white line)

Striking the skin lightly with a pointed object leads to pa llor of the
stimulated pa rt within 15 seconds. This is due ro direct contraction of the
precapillary sphincters by the mechanical stimulus (whi ch is foll owed by
drai nage of the blood out of the capillaries and small veins leading to pallor).

MECHANISMS OF V.D. IN THE SKIN

{I) Inhi bition of the Y.C.C. e.g. in cases of exposure to heat
(2) Release of V.D. substances, including (a) Mew holites (e.g. in reacti ve
hyperemia. page 112) (b) Substance P (e.g. in the triple response (sec nex t)
(c) Brac~Fkinin which is released during sweat secretion (page 11 3) (d)
I listamine that is released from damaged cells in cases of skin injury.

'""" whe~ 1

Figure 62 : The triple response.

 12 1
Chapter 11 The triple respom;e and lvmph circlllation

The triple response

This is a response that results by firm ly-strikig the ski n with a pointed
object. It consists of3 reactions (figure 62):
(I) Red reaction (or red line) :This appears in about 10 seconds at the site
of the stroke. [t is due to capillary dilatation thar occurs as a direct
response ofthe capillaries to the stimulus.
(2) Flare : This is diffuse mottled reddening that appears after the red
reaction around the area of injury then gradually spreads outwards. It is due
to arteriolar V.D. that is produced by the antidromic local axon reflex
mechanism through liberation of substance P (page 1 13), so it does not
appear in locally anesthesized or denervated skin areas.
(3) Wbeal (swelling) : This is local edema that appears within a few min-
utes around the injured area. It is due to extravasation of fluid from the capi-
llaries and postcapi llary venules as a result of an increase of their permea-
bility (which is produced by histamine that is released from the local mast
cells and substance P that is released from the antidromic nerve terminals).

THE LYMPH CIRCULATION

This is concerned with return of the tissue flu id that is not reabsorbed at
the capillaries (which is called lymph) back to the bloodstream. Lymph. is
similar to the plasma except that it contains less proteins with a higher A/G
ratio (since albumin is more easily fi ltered) and is rich in lymphocytes.
Lymph circulates in non-innervated vessels that form the lymphatic
system. This system originates as minute bl ind lymphatic capi llaries in the
tissues, which unite forming larger lymphatic vessels, and these dmin in the
thoracic and right lymph duct~ that open in the subclavian veins at the base
of the neck. The lymph nodes are located along the course of the lymphatic
vessels, and these vessels have smooth muscle in their walls and contain
valves that allow unidirectional flow toward their central end.

FACTORS THAT MAINTAIN LYMPH FLOW

(1) Rhythmic contraction of the smooth muscle in the walls ofthe lymph-
atic vessels.
(2) Skeletal muscle contractions, which press on the lymphatic vessels {=
muscle pump).
(3) The negative intrathoracic pressure(= thoracic pump).
(4) Gravity (which helps lymph flow fro m the upper parts of the body only).
(5) The hydrostatic pressure of the interstitial flu id (in areas where it is +ve).
(6) Arterial pulsations (by pressing on the near lymphatic vessels).
 122
Chapter 11 Functions o(tlte lvmplwtic system and edema

FACTORS THAT INCREASE LYMPH FLOW

Tht: lymph flow increases whenever the tissue fluid increases uue to :
( I) V.D. of' the arterioles or relaxation of the precapillary sphincters.
(2) An increase or the venous pressure.
(3) Tissue activity (the metabolites produce V.D. and increase the tissue
fluid osmotic pressure, which causes more fluid filtrat ion and increases the
now of lymph).
(4) An increase or the bloou volume e.g. by inj ection of isotonic saline.
(5) Lymphagogues : These arc substances that increase the lymph flow.
Th0y include a va riety of agents that increase capil/my permeability (e.g.
histamine and bradyki11in) .. These substances were cal led first class lympha-
gogues in contrast to hypertonic solutions of glucose or NaCI, which were
called second class Iyrnphagogues. These solutions diffuse rapidly into the
tissue spaces when i.v. injected, so the osmotic pressure or the interstitia l
fluid increases resulting in more nuid liltration and increased lymph now.
Agents that cause contraction of smooth muscle also increase lymph
flow from the intestines.

FUNCTIONS OF THE LYMPHATIC SYSTEM

(I) Return of the tissue fluid that is not reabsorbed in the blood capillaries as
and the lillercd protein back into the bloodstream (the ~vmph capillaries are
much more permeable than Lhe blood capillaries).
(2) Removal of bacteria from rhe tissues by the lymph nodes. wh ich is an
important defense function.
(3) Drainage of lymphocytes from the lymph nodes into the bloodstream.
(4) Absorption of the long chain fatty acids from the sma ll intestine, which
m~1kes the lymph in the thoracic duct to have a milky appearance.

EDEMA

This is the presence of excess nuid in the bodt tissues. It is 2 types :

(A) Intracellular edema

This is is produced as a result of either :
(1) Depression of cell membrane metabolic activity (e.g.duc to ischemia).
1
In this case, the Na pump is depressed (clue to 0 2 lack) so that excess Na
is retained inside the ce ll s associated with water retention by osmosis
(2) Inflammation : This increases the cell membrane permeability. which
allows Na ' and other ions to diffuse into the cells associated with water
retention by osmosis
 123
Chapter 11 S afell' [actors agtdnst production o{edema

(B) Extracellular edema

This is accumulation of excessiw: amounts (~liwerstitial.fluid (mostly in the
dependent parts of the body by the effect of gravity). II has 2 main causes : :
(1) Excessive leaka ge of fluid from the capillaries due to either :
(a) An increase of the capillary hydrostatic pressure : This commonly
occur as a resu lt of elevation of the venous pressure e.g. due to heart failure
(producing cardiac edema ) or incompetenfl'enous 11a/ves
(b) Hypoproteinemia : This decreases the plasma osmotic pressun.:
whi ch reduces reabsorpti on of the ti ssue nuid. It may occur as a result of a
decrease of synthes is of the plasma proteins (e.g. in se\·ere fil ·er disease a11d
undernutrition) or excessive loss of plasma proteins (e.g. in the urine in case
of the nephrotic syndrome. producing renal edema ).
(c) An increase of capillary permeability : Th is increases filt ration of
both the tissue fl uid and the plasma proteins. The latter fu rther inc rea~cs
fi ltrati on by increasing lhc osmot ic pressure of the interstitial fluid. It occurs
due to either innammation, allergic reactions (due to release of histamine).
vitamin deficiency (specially vitami n C) and excessive heat.
(d) Sa lt & water r etention (specially in renal diseases) : This increases
the blood voiUJm:, capillary pressure and nuid fi lt ration int o the tissue spaces
(2) Inadequate lymph drainage
Blockage of the lymph vessels leads to accu mulation of flu id and protein
in the tissue spaces. The latter also increases fluid filtration by increasing the
osmotic pressure of the tissue fluid. This condition is ca lled lymphedema ,
and in chronic condi tions it leads to fibros is or the interstit ial tissue, and the
edema becomes non-pitting. It com monly occurs after certain surgica l oper-
ations (e.g. radical mastectomy) and by infection with the filaria •vorms.
These worms obstruct the lymphatics, causing massive swell ing or the affec-
ted organ (commonly the legs or scrotum). a condition called elepha ntiasis.

SAFETY FACTORS AGAINST PRODUCTION OF EDEMA

( 1) T he - vc interstitial fluid hydrostatic pressm·c (e.g. in subcu taneous
tissues, page 119). The ve pressure holds the tissues together th11s decreas-
illg its complia11ce (distensibility). Accordingly, small int:reascs in the tissue
fl uid marked ly increase the hydrostatic pressure or the. interstitial flu id,
which opposes further fluid filtration and also increases the lymph fl ow.
(2) In creasin g th e lymph flow : The lymph flow increases I 0-50 fold when
fl uid begins to acc umu late in the tissue spaces. This removes large amounts
of the interstitial fluid and limits development of edema.
(3) Washdown of in terstitial fluid prot ein :The increased lymph flow dec-
reases the protein content and osmotic pressure of the interstiti al nuid, which
reduces filtration in the capillaries and limits development of cden1a.
 124
CHAPTER 12

I THE VENOUS CIRCULATION

Veins arc thin-walled non-pulsatile vessels that contain more than 50 %
of the circulating blood volume under a low pressure. Their main functions
arc (1) Returning blood from the tissues to the right atrium (see factors that
affect the venous return, page 82) (2) Storage of variDhle amounts of blood
(acting as a blood reservoir bacause they are capacitance vessels).

TH.E NORMALVENOUS PRESSURE

(A) In the recumbent position (absent effect of gravity) : About 15

mmHg in the venulcs, 7 mmHg in the cubital veins, 12 mmHg in the ankle
veins, II mm llg in the upper abdominal veins, 6 mmllg in the vei ns just be-
low the diaphragm, 4.6 mmHg in the thoracic veins at their entrance into the
right"atrium (= central venous pressure ) and 2 mmHg in the right atrium
(B) In the standing position (under effect of gravity) : About 35
mmHg in the dependent veins of the hands, 80-90 mmllg in the ankle veins,
II mmH g in the upper abdominal veins, 4 rnmH g in the veins just below the
diaphragm, 2 rnml-lg in the thoracic veins (central venous pressure or CVP),
zero mmHg in the right atrium and head veins (but subatmospheric in the
dural sinuses e.g. it is -10 mmHg in the superior sagillal sinus).

MEASUREMENT OF THE VENOUS PRESSURE

(A) DIRECT METHODS : The peripheral venous pressure is measured

through a needle inserted into the vein and connected to a saline manometer.
The CYP is measured through a cardiac catheter introduced into the thoracic
veins (via the c ubital vein) and connected to the measuring device.
(B) INDIRECT METHODS : The peripheral venous pressure can be
measured by the hand to heart method. The examiner s lowly elevates the
patient's hand and observes the level at which iLc; dorsal veins collapse
(figure 63). T he venous pressure roughly equals the distance between that
level and the sternal ang le in em blood (I em blood = 0. 77 mmHg).
The CYP can be measured whi le the patient is in the semisitting po.vition
with his head raised 45 ° (figure 63). The upper level of the congested part
of the external jugular vein is noticed, and the CYP roughly equals the
distance between that level and the sternal angle (in em blood). Nommlly,
about the lower third of this vein is congested (level of the right atrium) and
it becomes more congested if the CVP is increased e.g. in heart failure.
 125
Chapter 12 Factors that a((ectthe venous pressure & eO'ect of acceleration

Figure 63: Indirect measurement of the CYP (lell), nnd peripheral venous
pressure by the hand to heart method (right).

FACTORS THAT AFFECT THE VENOUS PRESSURE

( I) Gravit y : On standing, the CVP drops \Vhi lc the periphera l venous press-
ure (PVP) increases e.g. in the ankle (see below).
(2) Blood vo lume : Both the CV P and PYP arc increased in hypervolemia
and decreased in hypovolemia.
(3) Arteriolar diameter : Arteriolar Y.D. increases both the PVP and CVP.
while arteriolar V.C. decreases them.
(4) Ca pilla ry diam eter : Widening of the capillary diameter (by relaxation
of the precapillary sphincters) leads to pooling of blood in the capillaries,
resulting in reduction of both the PVP and CVP.
(5) Venomotor tone: Its increase (i.e. venoconstricrivn) e.g. by sympathetic
stimulation increases both the PVP and CVP, and vice versa.
(6) Blood outflow from the vei ns : Its decrease leads to an increase of both
the CVP and PVP, and vice versa. A decrease of' blood flow from the vei ns
occurs in congestive heart l~tilure and when the intrapcricardial or intra-
thoracic pressure increasc5.
(7) Acceleration forces : Upward vertical acceleration causes blood to
move downwards, so the venous pressure is decreased in the head while it is
increased in the lower lim bs. On the other hand, downward vertical acce-
lerati on produces opposite cfrects (sec next).

EFFECTS OF ACCELERATION ON THE CVS

The force of acceleration is expressed in g (- gravity) units. Tt produces

no effects if it acts across the body in the che~t to back direction (so astro-
nnuts in the space crafts lie in the recumbent position). On the other hand.
gravitational forces acting along the vcrLical axis of' the body cause the
blood to move in a11 opposite direction to tlwt of acceleration leading to the
following effects ::
 126
Chapter 12 E[[ects o[gra vitv 0 11 tlte CVS

(a) Alteration of the venous press ure in the upper and lower parts of the
body (sec above).
(b) Blaclwut and redout reactions : If the directi on of the <H.:cekrat ion
fo rce was upwards, a positive g Ioree acts from head to fool. Th is shifts the
blood from the upper parts of the body to be pooled in the lower limbs, re-
sulting in temporary block of retinal function and loss of vision (=blac kout)
followed by fainting due to cerebral i. ehemia (blackout precedes fainting
because the intraocular pres urc is higher than the intracranial pressure).
On the other hand, if the direction or the acceleration force was downward,
a negative g force acts from loot to head. This shifts the blood from the
lower parts of the body to be pooled in the upper pmts, resul ti ng in severe
pain in the head and congestion of the retinal vessels, whi ch ca uses the visu-
al fie lds to appear reel(= redout) and may also lead to temporary bli ndness.

EFFECTS OF GRAVITY ON THE CVS

On changing from the recumbent to the upright posture, gravity leads to

pooling of 300-500 ml of blood in !he lower limbs. With prolonged quiet
sta nding, th is leads to the fo llow ing effects :
(1) An incrcnse or the arterial pressure below the hea rt level (becomin g 180-
200 mmll g in the feet) and its decrease 1lbovc the heart leve l due to reduc-
tion of the VR, SV and CO (becom ing 60-75 mmHg at the head leve l, wh ich
may lead to fa inting as a result of cerebra l ischemia)
(2) An increase of the venous pressure below the heart level (becoming 85-
90 mmllg in the feet) and its decrease above the heart level (becoming zero
mml-lg at the head level).
(3) An increase of the capillary pressure in the lower limbs (due to the incr-
eased venous pressure) wh ich leads to excess fl uid fi ltrat ion (ankle edema).
(4) lf the venous va lves arc abnormal or incompetent, prolonged standing
may also lead to occurrence of varicose veins.

Body adjustments against the effects of gravity

As long as the indh·iduo/ 1110\ 'es ahout ajier Standing. the effects or
gravity are greatly decreased by the follow ing mechanisms :
(1) A normal VR is almost maintained constant by the effects ol' the thora-
cic and IITIISCulor puiJips. the ve//OII/0/0r lone and the cardiac suction forces
(page RJ), so that the venous pressure at the !'eel remains below 30 mmH g ..
(2) Initi ation of arterial baror ellcxes : The initial drop of the art erial blood
pressure in the arterial baroreceptors results in :stimu lation of the vee,
which increases the arterial blood pressure by the fo llowing effects :
 127
Chapter 12 Orthostatic "''fJOtension

(a) llcart acceleration (which helps maintenance of the cardiac output)

(b) Arterio lar V.C. (which increases the periphera l resistance)
(c) Venoconstriction (which prevents pooling or blood in the IO\\ er
limbs and helps increasing the venous retum)
(d) Secretion of eatccholamincs from the adrena l medu llae (which aug-
ments all previous effects).
(3) Release of ren in from the kidn eys : This occurs as a result of rena l
ischemia caused by the initial drop or the cardiat: output and arterial blood
pressure. It leads to formation of angiotensin II . which causes potent V.C.
and stimulates aldosterone secretion from the adrena l cortex. in addition to
other cff<.;ct~ (page I 08). Aldosterone promotes a and water retention in
the body. which increases both the blood vo lume and arterial blood pressure.
(4) Cerebral a utoregulation : As a resu lt o r the decreased cerebra l blood
flow, the PC02 increases while the PO~ und pll decrease. TIH.:sc cfTects
cause locul V.D., so the eercbrn l blood flow is reduced only by 20 '>o. ln
addition, the 02 extruction ratio increases. !>O the cerebral 0 2 consumption is
not markedly decreaseu.

Orthostatic (postural) hypotension

This is 11t ll of the art<.:rial blood pressure that occurs on sucldt:n stand ing.
due to ineflicient amigradz1· cOIIJpen.wtOI:r mechanisms (sec above). lr is
accompanied by dimness or 'ision. dizzine s and even fainting (=
ortlwstatic sy11cope ). It is uncommom in normal persons, but it commonly
occurs as a r<.:sull or d('prcssion of the sympathetic fu nctions, which is
encountered in the following conditions :
(a) Patients receiving symptholyt ic drugs.
(b) Diseases that damage the sympathetic nervous system e.g. diabetes and
syphilis.
(c) Primary autonomic fai lu re (- a condition charactcri7ccl by a decrease
of production of catccholamincs due to congenital clelicicnc) or the
dopamine beta-hydroxylase cr11:yme).
 128
CHAPTER 13

I THE CORONARY CIRCULATION !

The coronary vascular system (vasculature)

(1) 2 coronary arteries supply the bean. T hey arise from the aorta just above
the aortic valve (figure 64).
(2) In 50 % or people, the right artery is dominan t i.e. has a greater blood
flow than the !eli artery (in 20 % of people. there is left dominance and in 30
0 • the now is equal in both arteries).
0

(3) The large coronary arteries arc present in the epica rdium. and they give
smaller branches that dip inwards towards the endocardium.
(4) The capillary density is high in the myocardium (300 capillaries I mm\
(5) The coronary venous blood is returned mostly to the right atrium by the
corolwl:\' sinus and w1terior cardiac veins. and a sma ll amount is drained
direct~\' into off mrdiac chambers by sma ll vessels called thcbesian veins.
(6) Few co llatcrals exist bct\vcen the coronary arterioles. They arc insuffici-
ent to co mpensate fo r acute obstructions in the large arteries (so the coromuy
arteries arc considered end a rteries). However. el'ficient collntcrals t:an deve-
lop if the arterial obst nH.:tion was ocCUlTi ng gradually ..

Le fl coronary
l li<]hl coronary
arlery
,lriPry -

Figure 6-t : The coronary arteries.

THE CORONARY BLOOD FLOW (CBF)

The tota l CnF (normally about 250 ml / minute) can be determined by
Kct y method which depends on applying the f ick principl e (page 79): The
subject breathes nitrous ox ide (N:!O), and an arteri al blood sample (obtained
!"rom any artery) and a venous blood sample from the hcnrt (obtained from
the coronary sinus by a cardiac catheter) are analysed fo r N20 cont:entration.
By app lying the Fick prin-ciple. the CBF = cm101111t f~/ N~O token by the
heart per 111inllle I tl rtaiof N:O concentration Venous N!O conc<>nlrotion.
 1::!9
Chapter 13 F(lctors that a((ectthe coronarr blood {7oll'

~ Estimation of the conmm:1· hlood.flou in d(tlerent regwm of the heart 1s

useful lo r detection ol' ischemit: areas. It can be done by i.\'. injection of
radioactive tracers (e.g. thallium -20 I) and lor the lirst I 0-15 minutes after
injecti on. its distribution in the hl!art is detected with radiation detectors pla-
ced on the chest. Its distribution is directly proportionate to the myoca rdial
blood now and areas or ischemia can be detected by their low intake.

AortiC
01000
prtHu rt

left
COI"onary
I low
Roght
coronary
Jrtt r, tlowO-------~---

Figure 65 : The CB F in both coronary arteries during the t:ardiac C) clc.

FACTORS THAT AFFECT (CONTROL) THE CBF

(A) METABOLIC FACTORS

The CBF is directly proportionate to the m yo~.:a rdial 0 2 req uirement. 1\~.: c­
ordingly. the CBF increases during cardiac activity and such increase occurs
as a result of V.O. of the coromll) 'esse Is by the produced. metabolites. The
major coronary V. D. metabolite is adenosin e (''hich is formed as a result or
1\ T P breakdown in response to() , lack). ll oweH!r. CO~ . K . II . prostaglan-
dms and NO (page 112) lllil) also contribute in \ '.0. of the coronal) \esse b.

Coronary autoregulation
Within a mean aortic prcssun.; range between 60-140 mmllg. the CB I· is
kept constant. Such auloregulotioll (~/tile CBF dejJellds 011 11/eloho/ic .fete!
ors (e.g. a fall of the aortic pres:-.ure decreases the CI3F. This leads to 0 ~ lad,
and accumulation or metabolites, and both cause V. D., so the CB F increases
and is kept almost constant ). The phenomenon of reactive hyperemia (pag<.:
112) also occurs in the cardiac muscle by effect of the V.D. metabolites.

(B) MECHANICAL FACTORS

( I) The CBF undergoes phasic change~ during th<.• ca rdiac cyc le.
During systo le. the corom11y vesse ls urc compressed by the contracting
myocardium leading to reduction of the CBF. This occurs special~\' in 1he
le/1 coronary arte1:1· due to the th1ck left \'entricu lar wall. I· or this reason.
 I.:W
C/lti[Jter 13 Factors that a{[ec:ttlle c:orollmT blood {lmv

11wsr o( the h/ood flo\\ ' in hit coronal:\' ort<.'l)' oc<'lll'.\ d11ring cliosJo/e, heing
llllt\'i11wl at the t'/1( 1 t!f the i.,·omelric relwuricm Jllwse (figure.: 75). Such
changl!s arl! not apparl!nt in the right coronary artery (be~.:ause the force ol'
contraction in the thin right ventricle is weaker than 111 the ld't ventricle) w1cl
the hlood flo\\' i11 right corm1w:1· arte1:1' occurs during hmll .\yswle and
dim tole. allll is CI'L'II greater during s_ntolt' ( figurl! 75 ).
(2) I hl! CBI· I'> afli:cted 0) changes Ill the hean r.tte In ca ...es or tach~ ­
~:an ita. there i.., shortening of the diastolic penods (dunng \dllch the coron-
ar) lhm h lll:t\llllal) . ..,o the CB I is decreased. \n opposite effect occur.., Ill
case.!-. ofhrad)cardia.

(C)NEURAL(NERVOUS)FACTORS
~t11nulation of the card1at..: sympathetic nen l!s t..::tll'>l!S coronary 1'. C by
a tlirecr ac:rio11 on the alpha receptors (\\ hidl tends to decrease the C'131· ).
lltme,·er. the stnH1ltaneou-. tncreasc of the ~..:ardtac acll\ 11y results in e\ce-
sst\e forma11on of metaboltte!-1 that counteract the direct V.C. effect and kad
to coronal) V.D .. n:!--ultmg in a net increase of the CB I·. \'agal stimulation
dtlates the.! corotHtr) 'esst.:b. but its role in the control of CBF is unsettled.

Regional distribution of myocardial blood flow

The intramyocardial pressure in the /e.fi l'elllricular \l'cdl durinf.!, coJIIraction

I\ IIIIlCh greater 111 rhe 11111er (\1/hendocordia/) larer them in the! ower (s uh-
tpwarclial) lorer Thus. during systole the blood 'l!sseb in the inner layer
;ue normal I~ s~\ ~rei~ cornprt.:-.scd and 1he C/31' 111 the \llhellclocurcliallara
o/ the left H!lllrille mut \lop complete~r. I lowe' cr. th1s I'> compensated b)
V.D. Juring diastole. so that a nonnal CBF in thi~ layer i-. maintained.

Why ischemia and infarction are common in the subendocardial

lnycr of the loft ventricle ? What is coronary steal ?

J'his is bccau!>c thl! -;ubendocardiallaycr of' the lcl't 'entridc rccei,es it~
blood supply duriug diastole o11l)' (while all other pan~ of the lcti and right
\entncular walls recei"e blood supply during both systole and diastole).
which renders this layer more liable to ischemia and inlitrction in cases or
coronary obstruction. J'his special ly occurs if' the cardiac acti' ity is increa-
sl!d because V. D. product.:d in the outt.:r normal myoca rdtal layers (by efTect
of thl! nwtaboJit l!S f'orttH.!d liS a result of cardiat: activity) leads to shirt of'
blood to these layers l·rom the already ischemi c inner layers, which further
decreases the blood supp ly to the subendothelia l layer. Th is shiti of blood
has been called. co ronar~· steal.
 13 1
Chapter 13 F unctional cltaracteristic.fi oftlte coroumT circulation

THE CORONARY FLOW RESERVE

Energy production in the heart requires a high rate or o 2 CO il ~Jmp ti on
be-cause it is almost completely dependent on aerobic (oxidative)
mechanisms.
The nom1al CBF at rest is about 250 ml I minute (5 % of the cardiac
output). and it delivers to the heart about 29 ml 0 2 I minute (page 91 ).
Normally, the card iac muscle extracts 70- 80 '% of the arterial 0 2 conten t as
blood nows through the heart muscle, and as a result of such lligh 0 :: extrac-
tion ratio, the venous 0 2 reserve (i.e. the amount of 0 2 present in the
coronary venous blood) is normally small. Accordingly, the venous 0 ::
reserve plays a minor role in supplying extra 0:: to the heart during actil·ity.
and additional 0 2 can be s upplied only by increasing the CBF. During
maximal card inc activity, the CBF can increase up to I000 ml I minute or
more as a result of coronary V.D. (wh ich increases the myocardial 0 2 consu-
mption 4-5 fo ld). a mec hani sm that is called coronary flow reserve.

Functional characteristics of the coronary circulation

(1) It is a vitnl circulation that is closely related to Caid iac function.
(2) It is a short rapid circulation.
(3) The high 0 2 ex tracti on by th e cardi ac muscle results in a small venous
0 2 reserve (so 0 :: consumption during cardiac actit'ity can he increased
significantly on~\' by increasing the CBF).
(4) lt is the only circulation in which blood f1ow in certain hea rt areas occurs
on ly during diastole (the Jell ventricular subenclocardialmuscle layer).
(5) There is poor and inefficient anastomoses between the <.:oronary vesse ls.
(6) It is a rich ci rcu lation (about 5 % of the ca rdiac output although the heart
weighs only about 300 gm i.e. 0.05 % of the body weight).
(7) lls regulation is mainly by metabolic (and not neural ) factors.

CORONARY HEART DISEASE

(CORONARY INSUFFICIENCY)
This is produced as a resu lt of narrowing or the coronary arteries common ly
due to atherosclerosis and it causes angina pectoris or myocardial infarction
Angina pectoris
This is severe attacks or precordial pain that occur when cardiac activity
increases (e.g. in cases of effort and excitement). It is most ly substernal and
it often radiates to the ten shou lder and len arrn. It is a type of ischemic
pain that is initiated as a result of stimulation of certain pain nerve endings
in the myocardium by a metabo lite called Lewis P factor (w hich might be
K+, H+, histam ine, proteolytic enzymes or otherwise). This pain is absent at
rest, and can also be relieved by rest (due to wash of the causi ng metabol ite).
 ... .,
I .)_
Chapter 13 Mrocardia/ in[arction

Angina nu~\· occur in ah.\'£'11C£' ol coro11w:1· ace/us io11 specwlly in cases of

aortic stenosis, because a stronger left ventricular contraction should occur to
expel blood through the narrow aor1 ic valve (which severely compresses the
coronary n:sscls and also im:n:ase~ the myocardial o ~ n:quirement)
The anginal pain can be relic\ cd by the following drugs :
( I) \'irrates (e.g. nitrog~t·cerin) : These substances arc the best coronary
\ '. D. dmgs. They abo dilate the "}stcmic arteriole-. and 'cnulcs. and this is
bendicial since artenolar V.D. dccrca5cs the cardiac alkrlnad while veno-
dilatatton decrease.., the 'cnou.., retum and the . . troke 'olume. and both
effects decrease the myocanhal aeti\ it) and 0~ consumptton
(2) Beta-atlrenerxic b/oc:J..er drugs (e.g. atenolol) : These reduce the myoc-
ardial o~ consumption by decreasing the heart rate and power of contraction.
(3) o/• channel blocker., : These act like the beta-adrenergic blockers and
in addition. they produ<.:e coronary V.D.

Myocardial infarction
This is necrosis (death) of a myocardial area as a result of se\'ere (or pro-
longed) tschcmia e.g. due to sudden occlusion of a coronary branch by a
thrombus .. Irreversible chang~.:s occur in the affectl!d muscle fibres ending
by tibro:-.is. Immediate death may occur due to either acute heart failure and
pulmonary edema or vl!n tricular fibrillati on. ll owcvcr. in long-standing
cases, the affected area gradually bulges out during systoles (= systolic
stretch ) and it may rupture suddenly leading to death.
The dead ca rd iac musck libn.:s kak certai n etvymes and other substances
into thl! bloodstream and llll.!<lSUI'ing the rises of their blood levels greatly
help~ in the diagnosis and prognosis of infarction. The commonly measured
substances an! the isomer of crea tine kinase as well as troponins T a nd I.
The effects of myocardi<tl infarction can be decreased [/'within the first
/c'll' lwurs t{/ier the allac/... an agl.!nt that accelerates lysis of the intracoronary
thrombus is i.v. administetn.:d e.g. TP/\ (tissue plasminogen activator).
In patients sulkring angina, th ~.: occurrence or inlim;tion can be pre-
vented by certain surgical proccdurl!s e.g. ( I) Angiop lasly i.e. stretching of
the narrowed coronary area by a balloon catht:ter (2) C oronary bypass i.e.
connecting the aorta to the coronal)' artery beyond the area of narrowing by
a gran tal-.cn from an) 'ern (commonly the saphenous \'cin).
Canlta<.: transplants arc tndicaled iI' the kft ventricular cjcction fraction is
lc~-. than 15 °o or ir thl!rc ts ~c, ·crc uncontrollable ventricular arrhythmia. !\
transplantcd heart can achtc\ l! 70 no of the maximal cardiac output produced
by normal hearts, although i1 is denervated and is controlled only chemically
and by thl! Starling mechanism
CHAPTER 14

EBRAL CIRCULATION
The cerebral vascular system (vasculature)

( 1) rhc brain receives arterial blood supply from the 2 intcmal carotid and
the 2 \Crtebral ancrit.:s (the: Iauer unite to form the hmilar artery). These
artene., constJtUh! tht.: circle of \\'illis at the base ur the br.lln (figure 66)
(2) I here is no crossing Ill thi s circuit i.c.substances inj~o:cted i111o one carotid
artel') arc distributed almost onl) to the cerebral hemisphere on that side.
(3) rhere arc fe'' anastomo!:.cs between the ccrl.!bral arterioles that art! in-
suf'licient to pre\cnt cerebral infarction if a large artery is obstructed. so thi!
cerebral arteries arc cons1dercd end arteries.
(4) The cerebra l capi llari es genera ll y have a low permeabi lity because (a)
They arc non-fenestrated (b) There are tight junctions between their l.!ndo-
thellal cells (c) The glial cells(- astrocyli!!:.) ha,·e end fi.:ct that co,er large
areas of the capillary walls (d) Transcytosis (vesicular transport) is minimal.
(5) Venous drainage from the brain occurs b) way or the deep \i!ins and
dural sinusl.!s, which empty mainly imo the intemalju~ular 1·eins.. 1\ small
amount of venous blood drains through the emissw:l' \'ei/1\ to the scalp.

' CXfrPI()jl
ctau••l
"'"'"

~,.T.,_UUUI
•aran

Figure 66: Thi! circle of Willis (circulus artl.!riosus).

 134
Chapter 1./ Th e blood brain harrier

THE BLOOD BRAIN BARRIER (BBB)

The low penneability of the cerebral capillaries limit~ the passage of many
substances and drugs fro m the blood to the brain. a phenomenon called the
blood brain barrier (888 ). floweYCr. \\'lHCf. Q~ . (Q:? and lipid-solubc
substances (as alcohol and anesthetic drugs) cross such barrier easily. On the
othcr hand. passive glucose transport across the HHB is slo''. but it is Hlc ili-
tatcd by 2 forms of gluco!>C transporter I (CiLUT I ).
The 81313 helps maintenance or the ionic composition and pi I of the neur-
al envi ronment constant It also protects the brain f"rom exogenous and endo-
genous toxu1s and prevents escape of the ncurotransminers into the blood. Lt
is IVI.!flk in inf ants, so infants having jaundice may suffer severe neurolo-
gical symptoms (because bi lirubin in this case crosses the BBB and causccs
damage spcctnlly to the ba:-;al ganglia. a condit ion call ed kern icterus).
rhe BBB breaks down in areas of infection. injury and tumours. Such dT-
c::ct helps to identify the location of tumours. When radioactive-iodine
labeled albumin (wh ich docs not penetrate normal brain tissue) is i.v.
injected. it enters the tumour tissue resulting in its radioacti\ it)' (the
detection or which greatly helps in loca li zation or the si te of the tumour).

The circumventricular organs

These arc 4 structures located above the brain stem in relation to the
h) pothalamus that ha,·e fenestrated highly-pcm1eable capillaries (so they arc
sa id to be outside the BB B). They arc 2 types :
(A) Ncu roh cma l organ s ( strm:turcs that secre te hormones which readily
enter the cin.:ulation). They include the n eurohypophysis (wh ich secretes the
A Dll and o~ytocin) and the ltypotha/am ic median eminence which secretes
the hypophysiotropic hormones (refer to endocrines).
(B) C hemoreceptor organs (=structures at whit:h circulating substam.:cs
act to initiate certain l!ffccts). They include the area postrcma (the cltemo-
recepiOr :one that ini tiates 'omiting). the suhforni ca l orga n and the
organum vasc ulosum of th e lamina tcrminalis. Angioll:nsin II induces
water intake and other effects by acting on the latter 2 organs (page l OH).

OXYGEN REQUIREMENT OF THE BRAIN

rhc 0 2 consumpti on or an adult brain at rcst is about 50 rnl I minute

(i.e. about 1/ 5 of the total o~ consumpti on). The brain is very sensitiYc to
hypox ia (specially the cerebral cortex anc..l basa l gnnglia), so occlusion or the
blood suppl y to the brain produces unconsciousness in about I0 scconc..ls.
 135
Chapter 14 The cerebral blood {low

BRAIN METABOLISM
The major source or energy of the brain is glucose, so the R.Q. or the
cerebra l tissue is 0.95-0.99 (refer to metabolism), and insulin is not recjllired
hy most cerebral cells .F>r its 11tili=cltion. During prolonged sta rvation, how-
ever, other substances can be metabolized (e.g. amino acids). Altho11g!J hoth
oxygen and glucose are neededfor hrain metaholic activity, it ca11 wirhsw11d
hypogzJicemia.for longer period\· than it c·a11 withstand hypoxia (see above).
The brain cells also take up g l11tamate .fi'om the h/ood. ll'here it
comhines ll'ith ammonia.fvnning gl11tomine. This is an important detox ifying
mechanism si nce ammonia is vel)' toxic to the nerve cells.

THE CEREBRAL BLOOD FLOW (CBF) & ITS CONTROL

The adult human brain weighs about 1400 gm and the total merage CBF i!:>
about 750 ml I minute. It can be measured by the Kety method , which
depends on application of the Fick principle after inhalation of nitrous oxide
(N 20), similar ro measurement of the coronary blood flow (page 128).
The total CBF is general ly maintained constant under varying conditions.
llowevcr, it is not uniform in all parts or the brain e.g. it is 11/1/c/1 greater ill
the grc~v matter lha11 ill the! white! matter. The regional CI3F also shows
marked fluctuations both in the normal condition (e.g. it increases in active
areas) as well as in disease (e.g. it increases in epileptic foci and decreases in
the parietal cortex and the neighbouring areas in Alzheimer's disease).
The CBF is controlled (regulated) by the fo llowing factors :
(A) PHYSICAL FACTORS
( 1) The arterial and venous pressures at t he brain level : The CBF i~
directly proportionate to the difference between these pressures (which is
called the effective fJe/fusion pressure).
(2) Blood viscosity : The CBF vati es inversely with the blood viscosity.
(3) Int racranial pr ess ure :The brain, CSF and cerebra l vessels arc en-
closed in the rigid skulL and normally their total volume is kept relatively
constant at any time (- Momo-Kellie doctrine). The brain tissue and CSF
arc incompressible while the cerebral vessels arc compressed whenever the
intracranial pressure rises (which decreases the CBF) and dilated whenever
the intracranial pressure falls (which increases the CBF).
_ (B) CHEMICAL FACTORS
The cerebral arterioles arc extremely sensi ti ve to ltypoxia am/ hyper-
capnia. These and ot her metabolites (e.g. K ' and adenosine) produce a
pote/11 V.D. effect in active areas. Rise of PCO~ exerts a particularly potent
dilator effect by increas ing the local H' concentration whi le a fall in PCO~
(e.g. during hyperventilation) has a Y.C. effect. On the other hand. a drop of
P02 causes Y.D. while a rise of PO~ causes mild Y.C.
 136
Chapter 14 The cerebrospinal fluid (CSJ-J

AUTOREGULATION OF THE CBF

Autoregulation in the brain maintains the CBF almost constnnt nt nn nrtcrinl
pressure range of 65- 140 mmll g. A fa ll in arteri al pressure redu~.:es the CBF,
leading to accumu lati on or metabolites that produce V.D. (sec above) so the
CBr tends to increase to the normal level. On the other hand. rise or the
arteri al pressure increases the CBF leading to wash or the V.D. metabo lites
which result s in V.C.. so the CBF tends to decrease to the norma l leve l..

(C) NERVOUS FACTORS

The cerebral vessels receive V.C. sympathetic and V.O. parasympathetic
nerves from the superior cervical and sphenopalatine ganglia respectively.
Although sympathetic stimulation causes V.C. yet the CBF is not reduced
due to the simultaneously-increased arterial pressure. Such sympathetic V.C.
ellccl is important "hen (a) The arterial pressure is much elevated e.g. in
severe e>.ercisc (to prevent rupture or the cerebral vesse ls and disruption or
the BBB) (b) A cerebra l vessel is injured (to limit intracranial hemorrhage).

THE CEREBROSPINAL FLUID (CSF)

Th is fluid (norma l volume about 150 ml) is rorm cd by an active transport
mechani sm (mostl y by the choroid plexuses in the latera l ventricles or the
~.:c n.: bral hemi spheres) .. It pusses to the 3rd ventricle then through the aque-
duct of Sy lvius to the 4th ventric le and central canal of the spinal cord . II
then flows outward to fi II the subarachnoid space around the brain and sp inal
cord. It is absorbed mainly through the arachnoid vi lli by bu lk flow into the
cerebral venous sinuses at a rate that is proportionate to its pressure (which
a,·eragcs normally about 130 mm water o r· 10 mmH g).

Composition of CSF
This is differem rrom the plasma due to a blood - CS F ba rri er (the CSF
pH is lower. and it has lower concentrations or K~. Ca1 . protein. glucose.
inorganic P. urea. cholesterol. uric and lactic acids). On th~.: other hand. it has
higher concentrations of Mg2 • cr and creatinine as well as u hi gher PC01 .

Functions of CSF
The main function of'CSF is protection of the brain from damage. The
brain actually floats in the CSF (so its net weight becomes only 50 gn1), and
the CSF l'o rms a lluid cushion around the brain. This absorbs mechanical
shocks applied to the head and prevents concussion, but strong blows may
cause brain injury at a point opposi te to that of the blow (contrecoup il!/111:1·).
The CSF also helps (a) Maintenance of the intracran ial pressure (b)
Brain nutrition (c) Removal of waste products from the bra in (d) Tra nsport
or various neuronal secret ions.
 137
CHAPTER 15

HE PULMONARY CIRCULATIO
runctions of the pulmcn - ry circula·ion
(I) Conduction of blood from the right side ofthe heart to its ldl side.
(2) Blood oxygenation and \\llSh or co~(= arteriali;ation of venous blood).
(3) Filtration of various emboli (e.g. thrombi) from the venous blood.
(4) Blood rese!\oir of a \llt)'ing capacity (specially the pulmonary veins).

Ona u~ ~ 5 D ·vaS 11 -e)

The lungs receive arterial blood from the pulmonw:r am/ hronchial arteries
(the latter arise from the aorta). and their venous blood is drained mainly by
the 4 pulmonw:r 1·eins. The pulmonary vascu lature is characteri;.ed by :
( I) The wall of the pulmonnry artery is thin whili.: the pulmonary arterioles
arc short, wide and contai n little smooth muscle. Thc'>e properties render the
pulmonary arterial tree highly-complia nt (i.e. easily distensible).
(2) The pulmonal) , ·eins arc . . hort and compliant a.., the sy'>temtc veins.
(3) Considerable anastomoses exist between the branches or the pulmon-
ary and bronchial arteries.
(4) The pulmonnry capillaric'> arc highly permeable and ha'e a large surf-
ace area (about 70 m1 ) as well a'> multiple anastomoses.

NorMal 'lressures in the pulmonary circulation

- In the right ventricle. the systolic pressure is about 25 mmllg. while the
diastolic pressure is about 0 mmllg.
- In t he pulmonary a rtery. the systolic pressure is 25 mmllg (about I 5
that in the aorta since the pulmonary 'essds offer smaller peripheral resista-
nce)." hilc the diastolic pre sure ts 9 mmllg (mean pressure 15 mmllg).
- In t he pulmon aq · capillaries, the pressure is 7- 10 mmllg.
- In the pul mo nary veins a nd left atriu m. the pressure is about 5 mmllg.

THE PULMONARY VASCULAR RESISTANCE (PVR)

The PVR is normally about 1/6 that in the syste mi c circ ul ation be-
cause or thc large distellsibilill' of' the pulmo11w:r l'llsmlatun•. Factors that
produce V.C. (e.g. symp.stimulation. angiotensin II and endothclin) increase
the PVR. while those producing V.D. (e.g. vagal stimulation, histamine and
bradykinin) decrease it (the lattcr 2 probably through releasing NO) ..
The PVR also increasc~ \ignilicantl} in certain lung disca\es e.g.
emphysema. pulmonar)' fibrosis and pulmonary embolio;m. as a result of (a)
Obliteration of the pulmonary vessels (b) Local hypoxta in the lungs (c)
Re fle x sympathetic stimulati on (in case of pulmonary embolism).
 13R
Chapter 15 Factors that affect the pulmonarv arterial pressure

REGULATION OF THE PULMONARY BLOOD FLOW (PBF)

The P13F equals the cardiac output, and it is regulated as fo llows :
( I) Overall reg ulation of t he PBF : This is a passil•u process e.g. during
exerc ise, the cardiac output increases and the pulmona ry vessels dil ate passi-
vely (d ue to the ir high distens ibility) so the PBF increases proportionately
(2) Regional regulation of t he PB F : This is controlled by 2 !actors :
(a) 0 2 tension : Local hypoxia causes V.C. by directly stimulating the vasc-
ular smooth musc le. Such effect shin s the blood away fro m the hypox ic area
to other normally ventilated alveo li without afTccting the total PI3F. Loca l
CO ~ accumul ation decreases the pi I in the area, which also causes V.C..
(b) Gravity : Under the effect of gravity in the upright position. the PBF in
the ap ices of the lungs is decreased, then it increases gradually from above
downwards becoming maxima l in the lung bases (= wntcrfall effect).

FACTORS THAT AFFECT PULMONARY ARTERIAL B.P.

(A) Pulmonary vascular resistance (PVR)

Factors that increase the PVR increase the pulmonary m1crial B.P. and
vice versa. These factors include the following :
(I) Nervo us factors : Sympat hetic stimu lation ca uses V.C. ol· the pulmo-
nary arterioles, whi ch inercascs the PVR and pulmonary arterial B.P. Vnga l
stimu lation produces opposi te effects.
(2) C hem ica l factors : Pulm. V.C. substanees (e.g. angiotensin 11 , endo-
thelin and thromboxane) increase the PVR and pulm. arterial B.P.while V.D.
substa nces (e.g. histamine, bradyk inin and AN P) produce opposite effects.
(3) Systemic hypox ia : This leads to V.C. allover the pu lmonary
arterioles. which increases the PVR and pulmonary arteri al B.P.
(~) Respirato ry move ments : During inspiration, the pulmonary arterio-
les dilate resul ting i11 reduction of both the PVR and pulmonary arterial B.P.
During expiration, opposite effects occur.
(5) Lun g diseases : The diseases that cause narrowing of the pulmonary
arterioles (e.g. emphysema, pu lmonary fibrosis and pulmonary emboli sm)
increase both the PVR and the pu lmonary arteri al B.P ..

(B) Left atria! pressure

A rise of the left atrial pressure (e.g. secondary to left ventricu lar failure
or severe mitral stenosis) leads to back pressure in the pulmonary vascular
system resu lting in elevation of the pulmonary arteria l B.P ..

(C) Cardiac output

An increase in the card iac output leads on ly to a small rise of the pulmonary
arterial B.P. because of the large capacity of the pulmonary vascu lar bed.
 139
Cltapter 15 Fluid exclwm:e in tlte pulmonarr capillaries

PULMONARY HYPERTENSION

This condition is di"gnos~.:d when the pulmonary arterial blood pr~.:s~ur~

cxccccb 30 I 15 mmllg. It may occur as a result of ( 1) Rise of thc !crt atrial
pressure e.g. due to lcfi ventricu lar fa ilure or scvcre mit ral stenosis (2) Lung
diseases that increase the PVR e.g. emphysema, diffuse pulmonary fibrosis
and pulmonary embolism. These diseases may lead to right ventricular
fa il ure, a condition that is called cor pulmona le (i.e. congestive heart fa ilure
secondary to a pulmonary di~casc).

FLUID EXCHANGE IN THE PULMONARY CAPILLARIES

The formation and drainage of interstitial fluid in the lungs arc controlled
by the Starling forc es as follows :
(1) Forces that fa vour fluid filtration :
a- The pulmonary capillary hydrostatic pressure (7-1 0 mml-lg).
b- Interstitial fluid colloid osmoric pressure (about I~ mml-lg).
c- Interstitial fluid pressure (-5 to -8 mmHg).
(2) Force that fa vour flui d ubsorption : This is the plasma col loid osmotic
pressure (25- 28 mm ll g).
Nomwl~r. the jilrrarion jcm:es exceed Ill<' reuhsorhing .f(m·c resulting
in slighr .fluidJI!tration in rhe pulmonm:1' inh•rstitium. However, the alveoli
arc kept dry i.e. free of fluids (for adequate gas exchange) by 2 mechanisms
(a) Tlte negative pressure in liTe hmg interstitial spaces such out cxces
fluid in the alveoli through openings between the alveolar epithe lial cell~.
(b) Tlt e riclt ~)lmplwtic druina~: e of liTe lungs removes excess !l uids that
may accumulate around the ulveoli.

PULMONARY EDEMA

This is accumulation ofe\cess tissue nuid in thc lungs. It starts in the inter-
stitial ~paces, then fluids may dil'fusc into the alveoli (leading to (ka th in
severe cases as a resu lt ol'suiToca tion). Its ma in ca uses arc :
(I ) Rise of the pu lmonary capil lary hydrostat i<.: pressu re (commonly due to
either left ventricular failure or severe mitral stenosis).
(2) Damage of the pu lmonary capillary membranes (due to infections e.g.
pneumonia. or inhalation or irri tant gases e.g. chlorine).
(3) Obstruction of lymph drainage from the lung~ e.g. by thoracic tumours.
~ Pulmonnry edema also o<.:curs in the n •.,piratm:r distress .\_\'lie/rome
(refer to respiration) and is./{woured hy hypopmleinemia (due to lowe rin g or
the plasma co lloid osmoti<.: pressure).
 140
Chapter 15 Functional clwrac:teristic:!i o(tlte pulmmwrr circulation

Safety factors that limit pulmonary edema

( I ) fhe normal 10\\ pulmonar) capillary pre::.sun.: and high plasma colloid
osmoti t: pressure : This provides a significant san.:ty l~lctor because pulmon -
ary edema will not occur except when the pu lmonary <.:ap illary pressure (7-
10 mmllg) cxceecb the plasma colloid osmotic pressure (:!5-2X mmHg).
(2) 1 he normal negati,·e Interstitial fluid prcs'>ure (-5 to -X mml lg) : This
'>licks out excess flu1d from the al,coli.
(3) I he rich suppl) of the lungs'' ith lymph \C'iscb : l hr'> drains excess
mterstitial fluid and decrease!'> the filtering force (by reducing the interstitial
fluid colloid osmotic pressure as a result of protein washdown).

Functional characteristics of the pulmonary circulation

( I ) The pulmonary vascular system is a dislensihle loll' pressure .\ys/('111.

(2) It I'> a high.flou circulation (the pulmonal') blood flO\\ cardiac outplll)
(J) Changes in tht pu/mmwn mscular resi\ltmce are limited due to the
poor smooth mu::.clc in the pulmonary arteriolar \\ails.
(4) II'> \'f!llous retum at the /eli atrium is I -] "o greater them rile righr
l'enrricular owput (due to e~ccss blood drained from the bronchial veins).
(5) It has a high compliam:c. acting as a hlood re.\c•n ·oir t~/ l'mTing capacity.
(6) The hlood.f/oll' in the pulmonm:1· capillaries is rapid (about 0.75 second
during rest and 0.3 second during exercise).
(7) It ha-.; an exrensil·(• pulmonorr capillary swjiwe area together \\'ith a high
c·api I/(//:\· permeahi Iizl'.
(8) The pulmonarr Mood /loll' i' a(/i:cte!d by gml'irr (it is much greater in the
b.t'>C'> of the lung than in thc1r .tplccs).
(9) 1 he alveoli arc nom1all} J..epr ch:r.
( I0) It has special reacrions ro gas changes i.e. hypoxia. hypercapnia and
excess II produce V.C. (and not V.D. as in other tissues)
 141
CHAPTER 16

!EFFECTS OF EXERCISE ON THE CIRCULATION I

An adequate o~ supply i essential for perfonnance of muscular cxcrcbe.
The resting 0~ consumption (250 ml 1 minute) may increase 20 times or
more during exercise. The circulatory adjustments during exercise aim at
increasing the muscular blood fl ow. This may increase 30-fold as n result of
both .~ystemic c:irculntmy clumges am/local cltallf.:t!S i11 tlte actil'e muscles.

(A) SYSTEMIC CIRCULATORY CHANGES

(1) Increase of the cardiac output {CO)

The CO increases due to an increase in the heart rate and stroke volume.
(a) T he hcurt rate: This increases up to 180-200 beats/minute asH result or
(I) Psychi c stimu li from the cerebral cortex (wh ich stimulate the VCC)
(2) Bainbridge reflex (which is initiated by the increased venous return).
(3) Alam smirk reflex (which is initiated by mu ck contraction).
(4) The increase in PC0 2 and H' (which activate the VCC through stimul-
ating the centra l and periphera l chcmoreceptors).
(5) Rise of the blood temperature (which stimulates the S-A node).
(b) T he stroke vo lume :This increases due to forceful ven tri cular con trac-
tion produced by the increased symp. activity and catecholamincs secretion.
(2) Increase of the venous return
This is increased as a resu lt of:(a) An increase in both the muscle and
respiratoty pumps (b) Mobili zati on of blood from the viscera and other
reservoirs (sec below). (c) Arteriolar dilatation in the active muscles (d)
Vcnoconstriction produced by the increased sympathetic activity.
(3) Increase of the arter"al olood ore 'Sure
The increased CO elevates the mean arterial pressure. The systolic pressure
increases markedly due to the increase in the stroke volume, whi le the diast-
olic pressure is unchanged or even litlls slightl y because the total periphera l
resistance decreases as a result of the marked V. D. in the acti ve must: lcs.
{t:f) Gene alizec V.C {redis ibutio f blood)
Generalized V.C. occurs in areas other than the acti ve muscles, spec ially
tlte splancltnic area and skin, so blood is shifted to the active muscles and
the heart (where V.D. occurs). This V.C. is produced by the increased symp-
athetic activity which occurs as a result of stimula tion of the VCC by the
psychic sti mu li and the ra ised PC02 and 11+ (sec above)
~ If the exercise is prolonged and the body temperature increases. the
cutaneous V.D. occurs to incrca c the rate of heat loss. Also the prolonged
V.C ofthe renal vessels may result in transient albuminuria.
 142
Chapter 16 Effects of exercise on tlte circulation

(B) LOCAL CHANGES IN THE ACTIVE MUSCLES

(1) V.D. of the muscle arterioles

This together with the above systemic c!fects, leads to a marked increase
in the muscle blood flow. It occurs even before starting the exercise tluough
act ivation of the sympathetic V.D. system (refer to the autonomic N.S.) ami
is then maintained and augmented by the effects of:
1
a- The V.D. metabolites e.g. (K and adenosine).
b- The local 0 1 1ack and increased PC02 and H+ (lactic acid).
c- The excess heat liberated in the active muscles.
d- The increased arteria l B.P. (which mechanically dilates the arterioles).

(2) Capillary changes

The precapillary sphincters are relaxed, so the open capill aries increase
10-100 times, and they become widely di lated. These efiects increase the
capillary pressure and penneability, which favours filtration of more fluid
that conta ins the nutrients required for muscle contraction.

(3) Increase of the lymph flow

Large amounts of lymph are formed in active muscles due to the exc-
essive filtrat ion or the interstitial fluid (sec above). This is associated with
increased lymph flow from the act ive muscles as a result of the increase of
their pumping power (which also increases the venous return). This effect
helps to decrease the local edema that may occur in active muscles

(4) Increase of the oxygen uptake

In active musc les, the 0 2 consumpti on increases markedly as a result of

the following effects :
(a) The marked increase in the muscle blood now rate (see above).
(b) More unloading of 0 2 from oxyHb : This is helped by the local increase
1
in C02, H and temperature, as well as by the increase in 2,3 DPG (= 2, 3
diphosphoglycerate) in the red cel ls. All these factors decrease the 0 2 affin-
ity to !lb. and shiji the 0 2 dissociarion curve to the righr, and at the same
time facilitates C02 carriage l'rom active muscles by the formed reduced Hb
through the Haldane's effect (refer to respi ration).
(c) The slow blood now (due to V.D .), which increases 0 2 extraction.
 143
CHAPTER 17

IHEMORRHAGE, SHOCK AND HEART FAILURE j

ll emorrhage means loss of blood from the CYS, and it is 2 types :
(1) C'hronic : T his is-loss of small amounts of blood over a long period in a
repeated manner (e.g. as a result of an infection with ankylostoma or
bilharzia wonns). It is not fa tal, and it onl y leads to hemorrhagic anemia.
(2) Acute : Th is is sudden loss ofa /cn ge volume <?/hlood. Mil d and mode-
rate cases can be compensated, but severe cases (loss of more than 30 % of
the blood volume) arc usually fata l (unless early and properly treated) as a
result of the hypotension that occurs secondary to hypovolemia.

COMPENSATORY REACTIONS IN ACUTE

HEMORRHAGE

(I) Immediate (short-term or rapid) reactions

These aim at rapid elevation of the arteri al B.P. by producing V.C. and inc-
reas ing the card iac output and blood volume. They include the foil owing :
(I) Excitation of the vee : This occurs within 30 Se(.;OIIds 10 one llli11Uie as
a resul t of (a) Its release .from the inhibit01y ej/ect of the arterial baro-
receptors (b) lts stimulation by impulses discharged from the chemorecep-
tors under effect of 0 2 lack (c) The CNS ischemic response, which acts only
when the at1erial blood pressure drops below 50 or 60 mmHg (page I05).
Excitati on of the YCC leads to activat ion of the sympathetic N.S. and
secretion of catecholamincs from th e adrenal medullae and both help ele-
vation of the arteria l blood pressure through producing the following e iTects:
(a) Increase of the stroke volume and heart rate (wh ich increases the car-
diac output).
(b) Generali zed arteriolar V. C. speciall y in the skin and viscera (but not in
the heart and brain) whi ch increases the periph eral res istance.
(c) Genera lized l'euoconstrictiou,which increases the mean circulatory pre-
ssure and the venous return, thus increasing the cardiac output.
(d) Contraction of the splenic capsul e, which shifts the stored concentrated
blood in the spleen (nom1all y about 50 ml) into the general circulation
(2) Reverse stress relaxation, which also leads to Y.C. (page I05).
{3) Activation of the r enin-angiotensin system : Renal ischemia and the
increased sympatheti c acti vity lead to secretion of renin and formation of
angiotensin II which causes V.C. and stimulates secretion of both aldo-
sterone (promotes renal Na-+ absorption) and ADH (= vasopressin) which
causes water retemion in the body and also a potent V. C. eff ect .
 144
Chapter 17 Delaved compensaton' reactions to acute lremorrlrage

(4) Fluid shift : The decrease of capillary pressure enhances fliiid absorp-
tion from the interstitial (ti ssue) spaces into the bloodstream (= auto-
trcmsjitsion). Fluids arc also absorhedfi'vm the intestinal tract.
(5) Mobilization of preformed protein (the labile reserve tissue proteins)
into the bloodstream.
(II) Delayed (long term or slow) reactions

These aim at restorati on of the blood vo lume and rhe various blood
clements in order to keep a normal arterial B.P. They include the followin g :
(1) Restor ation of the plasma volume : This occurs in 12 - 72 hours as a
result of :
(a) Secretion of aldosterone a nd ADH (under effect of angiotensin 11)
1
wh ich promote Na and water retention in the body (sec above). ADH is also
released as a result of decreased pressure in both the ri ght atrium as well as
the carotid si nus and aortic arch (page 73)
(b) Increased thirst sensation and salt appetite (which increases both
water and salt intake) as a result of stimu lation of the thirst and salt appetite
centres in the anterior hypothalamus under effect of angiotensin II as well as
secondary to decreased pressure in the right at rium (refer to kidney).
(c) Increased Na 1- retention by the kidneys as a result of de licient renal
excretion (due to decreased renal blood flow and glomeru lar filtrati on
secondary to hypovolemia and V.C. of the rena l arterioles) as well as by the
effects of aldoster·one and angiotensin II (page 108)
(2) Restoration of the plasma proteins : The plasma proteins arc restored
with in 3 - 4 days through increased synthesis by the li ver from the reserve
tissue proteins as well as the proteins supplied in the diet.
(3) Restoration of the red blood cells : The red blood ce ll count is
restored within 4 - 8 weeks through increased formation in the bone marrow
by effect of the erythropoietin hormone (which is secreted by the kidneys
in response to 0 2 lack) .
~ The hormon es in volved in the compensatory r eactio ns in cases
of acute hemorrhage include the following :
(I) Ca tccholamines (from the adrenal medullae).
(2) ADH (= vasopressin) from the posterior pi tuitary gland.
(3) Aldosterone (from the adrenal cortex) .
(4) Erythropoietin (from the kidneys as a result of hypoxia).
(5) ACTH (Adreno-Cortico-Trop ic Hom10ne) :This is secreted from the ant-
erior pit uitary gland in stress comlitions am/ also in response to
angiotensin 11. It stirnulates release of glucocorticoids from the adrenal
cortex, which increase the Y.C. effect of catecholamines and also cause Na '
retention like aldosterone but to a smaller ex rent (refer to endocrine glands).
 14 5
Chapter 17 Circulator!' shock

SIGNS & SYMPTOMS (MANIFESTATIONS) OF ACUTE HEMORRHAGE

(1) llypotcnsion.(decrease of both the mean and pulse pressures).
(2) Rapid weak pulse (th ready pulse, page 4 1) due to tachyca rdia (induct.:d
by sympathetic activi ty) assoc iated with decreast.: or lht.: stroke volume.
(3) Rapid respiration (tachypn ea ) : This is due to stimulation of the respira-
tory centre as a result of the increased PC01 am/ decreased P01 (through
stimulating the central and peripheral chemorcccptors respc<.:ti\ cl) ).
(4) Thirst !.>ensation and increased desire for water (sec ahm c).
(5) Pale and cold skin (due to cutaneous \'.C.).
(6) 1:.:-..cessive sweating (due to the increased sympathetic acti\ ity).
(7) Oliguria (due to V.C. of the renal vessels and water retemion by AD II ).
(8) Anxiety and restlessness (due to reticular forma tion cxcitntion by catec h-
olamincs) or quietness and apathy (due to cerebral ischemia and acidosis).

CIRCULATORY SHOCK
This is a clinical syndrome characterized by tissue hypopcr fusion "ith
blood due to decrease in the cardiac output and arterial Mood pressure. It
occurs as a result of either blood loss ( hypovolemic shock) or other
conditions in which the h/ood 1'0/ume is nomwl ( norm ovolcmic shock).
The latter include the cardiogcnic, obstructi ve and dist ributive shock.

THE HYPOVOLEMIC SHOCK ( = COLD SHOCK)

TillS occurs as a result of reduction of the blood 'olumc. Its rn:mi fcstations
arc those or acute hemorrhage (sec abo' e). Its mam <.:auscs indudc ( 1} A<.:utc
hemorrhage (hemorrllflgic.: \lwc.:k ) (2) Severe trauma (traumatic shnc/,) (3)
~ 1 ajor surge!) (surgical shock) (-t) Los of large amount!> of plasma e.g.
from extensive bums (bum shock) (5) Dehydration (e.g. as a resuh of
SC\ ere diarrhea. vomiting or S\\Cating). Because th~: skin is pale anti cold in
this type of shock (due to V.C.). it is also referred to as "cold shock".

THE CARDIOGENIC ( =CONGESTED) and OBSTRUCTIVE SHOCK

These occur as a result of inadequate pumping acuon of the hcan \\ h1ch
leads to reduction of the cardiac output and anerial blood prcs!>ure. The ma1n
causes of ca rdiogcnic shock include (1) ExtensiH~ Jell \entricular infarction
(2) Acute myocarditis (3) I teart failure. (-t) Cert:Jin 'entricular arrhythmias ..
Because there is congestion in the lungs and vi!>cera in this condition. it is
also referred to as "congested shock". Cases that limit card iac filling (e.g. a
massive peri cardia! effusion or a large pneumothorax) decrease the cardiac
outpu t and may also lead to shock that is called obst ructi ve shock.
 14(J
Chapter 17 Circulatorp shock

DISTRIBUTIVE (=LOW RESISTANCE, VASOGENIC or WARM) SHOCK

This type of shock is due to widespread arteriolar V.D. an d veno-

dilatation (while the blood volume is normal), which lead to acute drop of
the venous return , cardiac output and arterial blood pressure, resu ltong in
tissue hypoperfusion. It includes the following types :

(1) Neurogenic shock : This occurs in severe emotions (e.g. fear and grief)
as well as in cases associated with severe pain e.g. severe trauma and burns (so
traumatic and bu/'11 shock have both hypovolemic and neurogenic feature~). In
these cases, signal s from certain areas in the cerebral cortex inhibit the nor-
mal sympathetic V.C. tone. resu lting in gen eralized V.D. This leads to
shock, and fain ting also often occurs (a condition ca lled vaso-vagal attack)

(2) Septic shock : Thi s occurs in certain bacterial infections. II has both
distributive and hypovo lemic features because the endotoxin released from
the bacteria causes V.D. (which also occurs by effect of fev er) and increased
cap illary permeability with loss of plasma in the tissues. The endotox in also
causes red cell aggl utinati on & intravascular coagulation. This leads to mu l-
tiple organ failure and cardiac depression, which makes shock more worse

(3) Anaphylactic (allergic) shock : This occurs in severe allergic:

conditions due to widespread V.D. that is produced as a result of release of
histamine during antigen-antibody reactions(= histamine shock).
_:: Cases of distrihutive shock arc sometimes call ed wa r m shock
because the skin tempera ture in these cases is not co ld due to V.D . Also,
because of V.D., these conditi ons arc ca ll ed low resista nce shock.

TYPES (STAGES) OF HEMORRHAGIC SHOCK

(I) Reversible (nonprogrcssivc or compensated shock) : This occurs in

mild cases of hemorrhage, in wh ich the body compensatory mechanisms
(page 143) arc capable to restore the normal blood volume and arteria l blood
pressure even without helpji·om outside therapy.
(2) Progr essive shock : Th is occurs in moderate cases of hemorrhage in
which, >vithout externalthempv, shock progresses within a few hours to the
next stage. However, 11'ilh proper !rea/m en/, the condition is still reversihle.
(3) Ir reversible (uncompensated or refracto ry shock) : This occurs in
severe hemorrhage. In such cases. there wi ll be no response to vasopressor
dmgs or any other lines of treatment and death eventua lly occurs even if
the blood volume was restored (see next).
 147
Chapter 17 Hearl failure

Mechanism of progressive and irreversible shock

(+ve feedbacks and v icious circles of circulatory deterioration)

In cases of shock, there is a crit ical cardiac output above whi ch shock
recovers (in compensated shock) and below which shock persists. Tn the
progressive stage. shock progresses as a result of severa l +ve feed -back
mecha nisms (see below). In mild and modertc cases of shock, these
mechanisms can be blocked by proper treatment and the patient is saved.
However, in severe cases these mechanisms arc often so strong that they
develop into vicious circles of circulatory deterioration which leads to the
irreversible stage of shock that eventually terminates by death
Some of the +ve feed-back mechanisms a nd the vicious circles of
circulatory deterioration proceed as follows :
(1) Hypotension -7 cerebra l ischemia -7 depression of the vee and the
cardiac centres -7 V.D. and bradycardia -7 more hypotension (and the
events arc repea ted by a +ve feedback mechanism).
(2) llypotension -7 decrease of coronary blood now -7 cardiac depression
-7 decrease of the cardiac output -7 more hypotension (and the events arc
repealed by a +ve feedback mechanism).

:::_ There arc other factors that ca use cardiac depression and enhance
development of irreversible shock e.g. (1) Acidosis that occurs due to
excessive fom1ation of lactic acid as a resu lt of anaerobic glyco lys is (2)
Electrolyte disturbances that occur as a result of impairment of renal
function due to ischemia (3) Increased capi llary permeability (due to 0 :!
lack) which leads to nuid loss in the tissues and decreases the blood volume
(4) Blood clotting in microvcsse ls due to the sluggish blood now.

HEART FAILURE (HF)

Definition : HF is the inability of the heart to pump an adeq uate output lor
the normal body metabolic needs. This may be the result of either a defect in
systole (systolic HF) or in diastole (diastolic HF) or both (the commonest).
Grades : HF may be mild (signs of HF appear on ly during activity) or
seve1·c (signs of HF appear during rest). It may also be acute or chronic.
Causes : H F may occur as a result of either ( 1) Heart disease e.g. coron-
ary insufficiency, valvular diseases, myocarditis or myocardial depress ion
by certain toxins (2) Increased a ft crl oad (e.g. due to hyper1ension) or
preload (e.g. due to hyperthyroidi sm) (3) Massive perica rdia! effu sion
(which causes heart compression that leads to secondary heart failure).
 148
Chapter 1 7 Heart failure

Low output and high output failure

Most cases or liF arc associated wi th a low cardi ac output. ll owcver, in
some cases (e.g. anemia and hyperthyroidism) there is volume overload and
!IF may occur although the heart pumps a g rec11er output than normal. Thus,
such condition is called a high output failure and is characterized by wann
skin and a high pulse pressure (water hammer pulse. page 41 ) ..

LEFT SIDED HF(Ieft ventricular failure)

The commonest causes or left ventricular fa ilure arc corOIWI)' orte1y
disease, chronic arterial hypertension and certai11 valvular diseases e.g.
aortic stenosis and incompetence. lts main manifestations are ( 1) Left ven tr-
icular dilatation (2) Ga ll op rhythm (page 37) (3) Pulsus alternans (page 40)
(4) Signs offonvard failure : These are the result or the decreased ca rdiac
output. They include muscle weak ness and rapid fatigue (due to muscle
hypoperfusion), cold extremities. skin pa llor and periphera l cyanosis.
(5) Signs of backward failure : These arc the res ult of pulmonaiJ' conges-
tion (increase of the pulmonary venous & cap illary pressures) and include:
(a) Dysp nea : This first occurs on exertion. but later it becomes contin-
uous. It may occur only in the recumbent position (= ort hopnea) or as
severe night attacks (curd iac usthrna).
(b) Co ugh (d ue to irritation of the congested bronchial mucosa).
(c) Pu lmonary edema (may be fatal in acute cases) : This occurs due to
rise of the pulmona1y capillary hydrostatic pressure (page 139).
(d) Pu lmonary hypertension (139).

RIGHT SIDED HF (right ventricular failure)

Right ventruicular failure may occur on top o/ leji-sided heart /ailure
(due to loss of left ven tricular aid) or secondary to ,puimonary hypertension
e.g. due to mitral stenosis or lung diseases that cause cor pulmonale (page
139). It also occurs in cases of pu lmonary va lve stenosis. but it is rare~r due
to coronw:F inst([/iciency . Its main manifestations arc the foll ow ing :
(1) Right ventricular dilatation.
(2) Signs of forward failure (the same as those ca used by len ventri cular
f~1 ilure because the cardiac output is also decreased in this case).
(3) Signs of backward failure : These are the result of systemic congestion
(increase of CVP and peripheral venous & capillary pressures) and include :
(a) Systemic (body) edema: This initially occurs in the dependent parts of
the body (as a result of the fore~ or gravity). so it is first noted in the ankles.
but af't er prolonged recumbency it appears in the sacral region. Excess
filtra ti on of fluid in the peritoneum may also occur leading to ascites.
(b) Enlargement of the liver (hepatomegaly).
(c) Congested (d istended) neck vei ns.
 1-19
Clw{Jier 17 //earl [ailure

Physiological compensatory responses to HF

(A) Cardiac responses

( I) Increase of EO\' (due to low CO) : This allow-. u-.c of the Starlinl.!. lm\
to incrca~e the strol-c 'olumc b) beterometric autoregulation. -
(2 ) Increase of cardiac contractility (by homcomctril: auton:gulution).
(.3) C ardiac h~ pcrtroph~ (increases the cardiac contractile po" cr).

(B) Neuro-hormonal responses

( I) Stimulation of the'~ mpathetic :\.S. (through the artcnal barordk.\)
help~ inc reasing the cardiac output and arterial l3. J> . by (a) l ncrea~ i ng the
cardiac contracti lity and heart rate (b) Producing arteriolar V.C. ( incrca~cs
the pcnphcra l rc~istancc) and 'cnoconstriction ( increa:-.c-. the 'cnous return).
(2) Rena l r es ponses : rtu: rena l underperfus ion (due to the decrenscd cnr-
diac output) results in acti vation of the renin-angiotensin .\J•stem. Angioten-
sin II causes V .C. and Na and water retention in the body (page IOX) which
mcrcascs the EDV. thus the cardiac comracriliry and output arc increased.
(3) The atria/natriuretic: peptide (ANP) is secreted 111 case~ of I IF (as a
rc~u lt or stretch or the atria l \\ails). It fll'l'\'(' /1/S ('\'('('\,\il '<' salt (//1{/ll'a/er J'('-
/('11/ion in the hot~\'. ll'hich is importallf in chronic m .\'<'.\ (~/!IF (sec IH.:x t).

Exhaustion of the compensatory mechanisms (HF progression)

Without proper trentm~ nl. the compensat ory mechani sms to IIF will be
gradua ll} e.\hHUSICd (- decompensation ) as a result of the following :
( I) \\'11h prolonged ")mpathctic O\cracti\it). it~ \e Inotropic and chrono-
trnp•c cllcch ''Ill be gradually Jccrcased and the hean ''ill dcpcnd on I) on
the !· rank-Sta rl ing mcc han i ~m lor its perfom1ancc.
(2) I he Frank-Starling mechanism also has a limit beyond'' hich it fails.
(3) Cardiac hypcrtroph) also has a limit. beyond '' hich the ability or the
hy pertrophicd muscle to generate force is decreased (page 91 ).
(.t) The prolonged V.C. produced by sympatheti c 0\ cracti\ ity and angio-
tcn-.i n II increases the card iac afterload (by increas ing the periphera l
rc-.istance), and this deerca~c~ the cardiac contractilit).
(5) \\hen the cardiac output is decreased as a rc-.ult of cxhau~t i on of the
cardiac rcsen e mechanisms. the excess salt and '' atcr retention becomes a
disadva ntage. and its persistence represents an overland to the heart.

PHYSIOLOGICAL BASIS OF TREATMENT OF HEART FAILURE

Management or II F aims at decreasing the cardiac work and improving

the power or cnrdiac contractility. This can be achieved as l'ollows :
 150
Chapter 17 Srncope

(A) General measures

( I ) Rest (to d~:cn:ase th~ cardiac work).

(2) Low-suit diet (to decrease t1uid retention in the body, thus prc,enting
excessive increase of blood volume which decreases the cardiac work).

(B) Use of drugs

( 1) Ca rdia c glycosid e!> (e.g. digitalis) : Th~:!-.c drugs c:-.ert a ve inotropic

action. so they impro\ e tht.: power of cardiac contractility, page 26).
(2) Vaso dilator drugs (hdp reduction of the cardiac afterload)
(3) Diuretics (enhance sa lt and water excretion. thus helping reduction ol'
the blood volume. '' hich decreases the cardiac \\Ork).
(4) ACE inhibitors (page II 0) : These drugs inhibit formation uf angio-
tt:n~in II. This tkcrcascs both V.C. as well as aldosterone secretion, thus the
peripheral resistance and salt and water retention an.: decreased leading to
reduct ion of the cardiac work

FAINTING (SYNCOPE)

This is sudden transient loss or consciousness (fainting) duc to ccrcbral

ischl.!mia. Some of the causes of syncope include the following :
( I) Vas ovHgal syncope : This occurs in some individuals r..:xposcd to a
se,·erc emotion. Cortical impulses depress the \ 'CC and stimulate thc C IC
kading to bradycardia and widespread V.D. (specially in ske letal musck:-.
because the sympathetic V.D. system is also activated). These cf'li.:cts result
in hypotension which leads to ccn:bral ischemia and syncope.: (page II 0) ..
(2) Orthostal ic syncope (due to postural h) potcnsion. page 127).
(3) Carotid sinu s syncope (due to hypersensitivity of the barorcceptors
in the carotid sinus. page 73).
(4) Ca rdiogcnic syncope (syncope due to hcnrt block or sinu-.. arn.::st).
S) ncope may also occur a!-. a result or myocardial Infarction. 111 certain
arrhythmias and in the Stokes-Adams syndrome (page 67}.
(5) Effort S) ncopc (thi'i is common in paucnts h:n ing aortic 01 pulmo-
mll) stenosis).
(6) Micturition syncope (in men only) : This may occur in some
individuals due to orthostatic hypotension and rcllcx bradycardia induced by
voiding urine.
(7) Co ugh syncope (dul.! to decrease or tlw \enous return as a result or
rise of the intrathoracic pressure, which reduces the card iac output kading to
hypotension and syncope).
!AUTHOR'S AVAILABLE BOOKij

1. Human physiology for medical students : Autonomic nervous

system & Nerve and Muscle

2. Human physiology for medical students : Blood and body

fluids

3. Human physiology for medical students : Circulation (cardio-

vascular system, CVS)

4. Human physiology for medical students : Respiration

5. Human physiology for medical students : Digestion (GIT)

6. Human physiology for medical students : Central Nervous

System (CNS)

7. Human physiology for medical students: The special senses

8 . Human physiology for medical students : Endocrine glands

and Reproduction

9. Human physiology for medical students: Kidney, Electrolyte

balance and Acid -Base balance

10. Human physiology for medical students : Energy metabolism

11 . Oral and written questions and answers (volume 1 )

12 . Oral and written questions and answers ( volume 2 )

13 . M.C.Q.s and answers ( volume 1 )

14. M.C.Q.s and answers (volume 2)

15. A summarized guide to circulation

16. A summarized guide to CNS

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~)!.;.. Commorclol Pross· Kalyoub • Egypt

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