The cardiovascular system

Tuwilika Keendjele

1
Learning outcomes

• Describe the general organisation of the heart

• Understand the properties of the cardiac muscle function

• Explain the coordination of a heartbeat

• The cardiac cycle and cardiac output

• Explain neural regulation of cardiac activity

• Understand the alterations of cardiac output during exercise

c, the pericardium, and located in the chest ( Figure 12.6).
fibrous layer is also closely affixed to the heart and is called
e epicardium. The extremely narrow space between the
ricardium and the epicardium is filled with a watery fluid
at serves as a lubricant as the heart moves within the sac.
The wall of the heart, the myocardium, is composed
Anatomy of the heart
imarily of cardiac muscle cells. The inner surface of the car-
ac chambers, as well as the inner wall of all blood vessels, is
ed by a thin layer of cells known as endothelial cells, or
dothelium.
ventricular septum. Located between the atrium and ventri-
cle in each half of the heart are the one-way atrioventricular
(AV ) valves, which permit blood to flow from atrium to ven-
tricle but not backward from ventricle to atrium. The right AV
valve is called the tricuspid valve because it has three fibrous
flaps, or cusps ( Figure 12.7 ). The left AV valve has two flaps
and is therefore called the bicuspid valve. Its resemblance to
a bishop’s headgear (a “mitre”) has earned the left AV valve
another commonly used name, mitral valve.

cusps. T
during ve
Arteries to head and arms ing in th
Aorta
Like the
Right pulmonary artery Whether
differenc
Left pulmonary
Right pulmonary veins
artery Ano
Superior vena cava
is that, w
Left pulmonary
veins
Consequ
suffice to
Interatrial septum
Pulmonary trunk valve may
Left atrium Pulmonary a high re
semilunar valve contracti
Left (bicuspid) pressure
AV valve Openings to
Right atrium coronary arteries
The
Aortic semilunar and infer
valve
Right AV atrium, a
(tricuspid) valve Left ventricle Aortic ever, atri
semilunar valve veins bec
Papillary muscle
Inferior vena cava into the
(Actually
Interventricular septum
Chordae tendineae Left AV (bicuspid)
accounts
Myocardium valve neck vein
Right ventricle
Fig
Epicardium
the entire
Pericardial fluid/space
Pericardium
Right AV (tricuspid)
Pulmonary
semilunar valve
valve
Cardiac
Figure 12.7 Superior view of the heart with the atria The bulk
gure 12.6 Diagrammatic section of the heart. The arrows indicate the direction of blood flow.
removed, showing the heart valves. From R. Carola, J. P. Harley, and C. R. Noback, cells with
3
8 Chapter 12 Human Anatomy and Physiology, McGraw-Hill, New York. cle cells
so that this exchange can take place. ventricle. The blood leaving the lungs enters

PA Ao
RA
LA

RV LV
Pulmonary
Circulation

Systemic Circulation
■ FIGURE 1.1 Overview of the cardiovascular system. The right side of the heart, pulmonary circulation, 4
 The smooth muscles of the intestinal tract, uterus, (a)
and small-diameter blood vessels are examples of single-unit Striations
smooth muscles.

Multiunit Smooth Muscle

Nucleus
Multiunit smooth muscles have no or few gap junctions. Each
cell responds independently, and the muscle behaves as mul-
Cardiac muscle
tiple units. Multiunit smooth muscles are richly innervated
by branches of the autonomic nervous system. The con-
is a syncytium
Intercalated disks
tractile response of the whole muscle depends on the num-
ber of muscle cells that are activated and on the frequency
of nerve stimulation. Although stimulation of the muscle by
(b) Intercalated
neurons leads to some degree of depolarization and a con- disks
tractile response, action potentials do not occur in most mul-
tiunit smooth muscles. Circulating hormones can increase or
A functional
decreaseunit of contraction
contractile activity increated bysmooth
multiunit a network of but
muscle,
stretching
electrically does not cardiac
connected induce contraction in this type of mus-
muscles cells
cle. The smooth muscles in the large airways to the lungs, in
large arteries, and attached to the hairs in the skin are multi-
Intercalated
unit smoothdiscs = cell membranes separating cardiac
muscles. Mitochondrion Gap
muscle cellsIt must be emphasized that most smooth muscles do not Cardiac muscle junction
cell
show all the characteristics
Desmosomes of either&single-unit
hold cells together attach myo or multiunit
brils Nucleus
Gapsmooth muscles.
junctions These
allow two prototypes
di usion represent
of ions between the two
cells
extremes in smooth muscle characteristics, with many smooth
Sarcolemma
muscles having overlapping characteristics.
Two syncytiums: atrial syncytium and ventricular syncytium Desmosome

9.10 Cardiac Muscle

5
The third general type of muscle, cardiac muscle, is found

ff

fi

 The SA node is normally the pacemaker for the entire heart.

Its depolarization generates the action potential that leads to The action potential i
depolarization of all other cardiac muscle cells. As we will see throughout the myocardium
later, electrical excitation of the heart is coupled with contrac- of gap junctions. Depolariz
Heartbeat coordination
tion of cardiac muscle. Therefore, the discharge rate of the SA muscle cells of the atria, wit
the right and left atria contra
The spread of the a
Superior Atrioventricular node
cles involves a more comp
vena cava
Bundle of His Figure  12.10 and Figure  12
Sinoatrial
node
cardiac cells that have lost co
duct action potentials with l
Internodal
pathway
Left atrial depolarization and ven
atrium
tion of the conducting syst
Right
atrium (AV ) node, located at the bas
potential is conducted relativ
the AV node through intern
Right
bundle
an elongated structure with
branch Left teristic: The propagation of act
Right
ventricle is relatively slow (requiring ap
ventricle allows atrial contraction to
excitation occurs.
Purkinje
fibers After the AV node h
potential propagates down th
Inferior
vena cava pathway has conducting-sys
His (pronounced “hiss”), o
Interventricular Left bundle AV node and the bundle of
septum branch 6
cal connection between the
Excitation sequence:

- the pacemaker of the heart

- initiates depolarisation that generates action potentials

- discharge rate of SA determines the heart rate: number of times the heart
contracts per minute

- action potential propagates internodal pathways to the atrioventricular (AV)

node

-action potential propagation through the AV node is relatively slow

- From the AV node action potentials propagate down the interventricular

septum via the bundle of His

- Bundle of His separates into right and left bundle branches which connect to
the Purkinje bres

-the Purkinje bres make contact with ventricular myocardial cells

8
fi
fi
ure 12.10 Conducting system of the heart (shown for this pathway, the atria are completely separated from
low). ventricles by a layer of nonconducting connective tissue

Atrial excitation Ventricular excitation Ventricular relaxation

Begins Complete Begins Complete

SA node AV node Atrial

relaxation

9
10
 The rapid conduction along the Purkinje fibers and the

Membra
Rev. Confirming Pages
diffuse distribution of these fibers cause depolarization of
all right and left ventricular cells to occur nearly simultane-
Cardiac action potentials
ously and ensure a single coordinated contraction. Actually,
though, depolarization and contraction do begin slightly ear-
–100
0 0.15 0.30
lier in the apex of the ventricles and then spread upward. The Time (sec)
result is an efficient contraction that moves blood toward the (b)
exit valves,
(a) like squeezing a tube of toothpaste from the bot-
tom up. +
Transient K exit
Ca2+ enters and K+ exits

Relative membrane permeability

10.0
(Plateau) PNa+
Cardiac Action Potentials and Excitation
0
Membrane potential (mV)

of the SA Node
The mechanism by which action potentials are conducted
PK+ PCa2+(L)
along the Na membranes
+ enters of heart cells is basically
K+ exitssimilar to
other excitable tissues like neurons and skeletal muscle cells. 1.0
(Depolarization) (Repolarization)
As was described in Chapters 6 and 9, it involves the con-
–50
trolled exchange of materials (ions) across cellular mem-
branes, which is one of the general principles of physiology
introduced in Chapter 1. However, different types of heart
cells express unique combinations of ion channels that pro-
duce–100
different action potential shapes. In this way, they are 0.1
0 0.15 0.30
specialized for particular roles in the spread of excitation
through the heart. Time (sec)
0 0.15 0.30
(b)
Figure 12.12a illustrates an idealized ventricular myo- Time (sec)
cardial cell action potential. The changes in plasma membrane 11
Ionic concentrations and equilibrium potentials in cardiac muscle cells:

Extracellular Intracellular
Equilibrium potential
Ion concentrations
concentrations

(mV)
(mmol/L) (mmol/L)

Na+ 145 10 71

K+ 4 135 -93

Ca2+ 2 10-4 129

12
13
 Electrical activity from nodal cell
d, they are often referred to as L-type
Pacemaker potential brings the
(a)
long lasting). These channels are modi-
membrane potential (Vm)
dihydropyridine (DHP) receptors that to
nsors threshold
in excitation–contraction coupling

Membrane potential (mV)

0
e Figure 9.12). The flow of positive cal- 2+
C a enters K + exits
l just balances (R epolariz ation)
Sodium,thepotassium
flow of positive
andpotas-
calcium (D epolariz ation)
Threshold
ell and keeps the membrane
ion channel mechanisms depolarized
contribute to pacemaker potential
olarization does occur due to the even- –50
21 N a + enters
he L-type Ca channels and the open- C a 2+ enters
1 1
e of K channels. These K channels are (Pacemaker potential)
escribed in neurons and skeletal muscle;
to depolarization (but after a delay) and –100
rrent has repolarized the membrane to 0 0.15 0.30
Time (sec)
entials of atrial muscle cells are similar (b)
14
described for ventricular cells, but the

e to depolarization (but after a delay) and –100

rrent has repolarized the membrane to 0 0.15 0.30
Time (sec)
entials of atrial muscle cells are similar (b)
t described for ventricular cells, but the
eau phase is shorter.
1. Progressive reduction in K+ permeability
10.0
re are extremely important differences

Relative membrane permeability

2. F-type
ntials of cardiac “funny” channels
muscle cells mainly
and conduct
those
inward Na+ current
conducting system. Figure 12.13a illus-
ential 3.ofT-type
a cellCafrom the SA(T=transient)
2+ channels node. Note P C a 2+ (L)
does contributes
not have ainward
steady resting
Ca2+ currentpotential
oes a slow depolarization. This gradual 1.0
P N a + (F) PK +
wn as a pacemaker potential; it brings P C a 2+ (T)
ial to threshold, at which point an action
Pacemaker potential provides SA node with
automaticity; capacity for spontaneous, rhythmic
nnel mechanisms,
self-excitation.
which are shown in
ribute to the pacemaker potential. The 0.1
1 1
reduction in K permeability. The K
during the repolarization phase of the
ntial gradually close due to the mem- 0 0.15 0.30
Time (sec)
egative
15 potentials. Second, pacemaker

 increasing potassium conductance. rate

Nonneural mechanisms also alter pacemaker ions
activity (Table 2-2). For example, circulating in S
Regulation of SA node activity catecholamines (epinephrine and norepineph- brad
rine) cause tachycardia (abnormally high heart whe
rate) by a mechanism similar to norepinephrine pha
Positive and negative chronotropy
CARDIOVASCULAR PHYSIOLOGY CONCEPTS dia,
duc
TABLE 2-2 FACTORS INCREASING OR depo
DECREASING THE SA NODE
SA Nodal Cell FIRING RATE
brad
ity.
INCREASING DECREASING
Sympathetic Normal Vagal lead
Sympathetic Parasympathetic
0 stimulation stimulation rhyt
V

Muscarinic receptor Muscarinic receptor SA n

antagonist agonists for
Normal
mV Threshold b-Adrenoceptor
agonists
b-Blockers L-ty
inw
Circulating cat- Ischemia/hypoxia pha
echolamines or a
-50 Hypokalemia Hyperkalemia M2 r
nist
Hyperthyroidism Sodium and calcium
Normal Maximal channel blockers
brad
Hyperpolarization activ
Hyperthermia Hypothermia
K+-A
E 2.7 Effects of sympathetic and parasympathetic (vagal) stimulation on sinoatrial (SA) nodal pace-
16
tivity. Sympathetic stimulation increases the firing rate by increasing the slope of phase 4 and lower-Cardiovascular Physiology Concepts (Second Edition)

The electrocardiogram (ECG)

A tool for evaluating the electrical events within
the heart.

Electrocardiograms are recorded by

electrocardiograph machines that have
electrodes connected to a processing unit.

Electrodes detect electrical currents and

compute the ECG lead (a graphical
description of the electrical activity of the
heart).

17

18
 Rev. Confirming Pages

ECG lead placement

(–) Lead I (+)

(–)
(–) (+) (+) (–)
aVR aVL

(–)
Lead II (–) Lead III

aVF
(+)

V1 V2
V6
V5
V3 V4

Ground
(+) (+)

(a) (b) 19
TABLE 12.2 Electrocardiography Leads

Name of Lead Electrode Placement

Standard Limb Leads Reference (2) Electrode Recording (1) Electrode

Lead I Right arm Left arm
Lead II Right arm Left leg
Lead III Left arm Left leg

Augmented Limb Leads

aVR Left arm and left leg Right arm
aVL Right arm and left leg Left arm
aVF Right arm and left arm Left leg

Precordial (Chest) Leads

V1 Combined limb leads 4th intercostal space, right of sternum
V2 " " " 4th intercostal space, left of sternum
V3 " " " 5th intercostal space, left of sternum
V4 " " " 5th intercostal space, centered on clavicle
V5 " " " 5th intercostal space, left of V4
V6 " " " 5th intercostal space, under left arm

20
 ermines how quickly threshold is reached and the (a)
n potential is elicited. The inherent rate of the SA Rev. Confirming +1 Pages R ECG

Potential (mV)
e rate exhibited in the total absence of any neural
The
nal input electrocardiogram
to the node—is approximately 100 (ECG)
depo-
per minute. (We will discuss later why the resting T
P
in humans is typically slower than that.)
A tool for evaluating the electrical
use other cells of the conducting system have events within the
0 heart.
Q
erent pacemaker rates, they normally are driven to S
by action potentials from the SA node and do not
(b) Atrial action potential
heir own(a) rhythm. However, they can do so under +20
rcumstances +1 and are then called ectopic pacemak- Ventricular
ECG

Membrane potential (mV)

R action potential
l that excitation travels from the SA node to both
Potential (mV)

only through the AV node; therefore, drug- or

duced malfunction of the AV node may reduce or
y eliminate the transmission of action potentials
tria to the ventricles. This is known as an AV con-
isorder. If this occurs, P
T
autorhythmic cells in the
His and Purkinje network, no longer driven by
de, begin to initiate
0 excitation at their own inher-
–90
nd become the pacemaker for the Q ventricles. Their
te slow, generally 25 to 40 beats/min. S Therefore,
0.3
AV node is disrupted, the ventricles contract com- Time (sec)
(b)
of synchrony with the atria, which continue at the
Atrial action potential
e of the SA +20 node. Under such conditions, the atria Figure 12.14 (a) Idealized electrocardiogram
21
4 SECTION VI Cardiovascular Physiology

P wave: SA node discharge & atrial

R depolarisation
1.0

Isoelectric
PR interval:aVR
atria to ventricular conduction aVL
line time (through the Bundle of His)
0.5 V1 V2
PR segment ST segment
V3
QRS complex: ventricular depolarisation
T
mV

P (atrial repolarisation)
U
0 V4 V6
V5

Q ST segment: early phase of ventricular

PR interval
repolarisation
−0.5 S
QRS duration T wave: ventricular repolarisation
QT interval
0 0.2 0.4 0.6
Time (s)
U wave: unclear (may represent repolarisation
of Purkinje bres); indication of hypokalaemia
GURE 30–5 Waves of the ECG. aVF

FIGURE 30–6 Unipolar electrocardiographic leads.

22
fi

(>0.1 seconds), conduction is impaired
within the ventricles. Impairment can occur
with defects (e.g., bundle branch blocks) or
Summary of ECG waves, intervals and segments
TABLE 2-4 SUMMARY OF ECG WAVES, INTERVALS, AND SEGMENTS
ECG COMPONENT REPRESENTS
tions). This calculation allows the QT interval
to be assessed independent of heart rate. Nor-
mal corrected QTc intervals are <0.44 seconds.
NORMAL DURATION (S)

P wave Atrial depolarization 0.08–0.10

QRS complex Ventricular depolarization 0.06–0.10
T wave Ventricular repolarization 1

PR interval Atrial depolarization plus AV nodal delay 0.12–0.20

ST segment Isoelectric period of depolarized ventricles 1

QT interval Length of depolarization plus repolarization— 0.20–0.40 2

corresponds to action potential duration

1
Duration not normally measured.
2
High heart rates reduce the action potential duration and therefore the QT interval.

23
 Atrial excitation Ventricular excitation Ventricular relaxation

Begins Complete Begins Complete

SA node AV node Atrial

relaxation

Time Time Time Time Time

Electrocardiogram 24
25
 QT interval QRS complex
10 sec
not seen in the ECG. For this reason, the segments and intervals are
R R
but begin with the first wave of the QRS complex.
P T P T

(1) Normal ECG (

10 sec
ECGRAnalysis: Questions
R to ask
R when analyzing ECG
R tracings. R
P P P P P P P P P P P P P P P
1. What is the rate? Is it within the normal range of
60–100 beats per minute?
(
(2) Third-degree block
2. Is the rhythm regular?
26
(2) Third-degree block

(3) Atrial fibrillation

(3) Atrial fibrillation

(4) Ventricular fibrillation

(4) Ventricular fibrillation
FIGURE QUESTION
FIGURE QUESTION
2. Three abnormal ECGs are shown above.
27
Calculating heart rate from an ECG tracing

5 big boxes = 25 mm = 1 sec

1 big box = 5 mm = 0.2 sec (200 msec)
1 small box = 1 mm = 0.04 sec (40 msec)
300 big boxes = 60 sec (1 min)
1. Use rhythm strip (lead II); recorded in 10 seconds HR = the number of
R waves in rhythm strip multiplied by 6
2. Count the number of big boxes between two R-waves (RR-interval) => 300 /
RR-interval
3. Count the number of small boxes between two R-waves => 1500 / RR-
interval
28

Calculate the heart rate from the rhythm strip below:

29
 Unit III The Heart

Excitation-contraction
coupling Extracellular
Ca++
Ca++ Na+ K+
fluid
ATP
Extracellular Ca2+ enter cardiac cells during
Ca++ Na+
plateau of action potential

Ca2+ trigger release of more Ca2+ form RyR

receptors (in the SR) Sarcoplasmic
reticulum
Sarcoplasmic
reticulum
Ca++
Ca++
Ca2+ binds to troponin & exposes cross-bridge T Tubule stores

for binding Ca++ ATP

spark
Ca++
Cross-bridge cycling, force generation and
sliding of laments = contraction Ca++
signal

Ca++
Contraction relaxation

Figure 9-5 Mechanisms of excitation-contraction coupling and relaxation in cardiac muscle.

30
extracellular fluid that is in the cardiac muscle interstitium after the action potential ends. Therefore, th
fi

 The cycle is divided into two major phases, both named

for events in the ventricles: the period of ventricular contraction “equal” or in this context “unchanging”). The ventric

(a) Systole Isovolumetric ventricular contraction Ventricular ejection

Blood flows out of ventricle

Cardiac cycle Atria Atria

relaxed relaxed

The cardiac events beginning at the P wave

and continuing until the next P wave.

Divided into two categories; Ventricles

contract
Ventricles
contract

(a) Systole: events associated with

AV valves: Closed Closed
Aortic and

ventricular contraction & ejection pulmonary valves: Closed Open

(b) Diastole: rest of the cardiac cycle (b) Diastole

Isovolumetric ventricular relaxation Ventricular filling
inclusion ventricular relaxation and Blood flows into ventricles

lling Atrial contraction

Atria Atria Atria

relaxed relaxed contract

Ventricles
relaxed Ventricles Ventricles
relaxed relaxed
31
fi

 Dias Sys Dias

Phase: 1 2 3 4 5 6 7
Wiggers diagram Aortic
Valve
Aortic Closes
120 Valve AP
Opens
Illustrates changes in the left side of the heart
as a function of time 80
Pressure Mitral LVP
(mmHg) Valve
Pressure & volume changes in the right side of 40 Closes Mitral
the heart are similar, with a difference in a c
LAP
v
Valve
Opens
pressures 0
x x’ y
120 LVEDV
7 phases in the cardiac cycle:
1. Atrial systole LV
Volume 80
2. Isovolumetric contraction (ml)
R
3. Rapid ejection LVESV
40
4. Reduced ejection P T
ECG Q
5. Isovolumetric relaxation S
Heart
6. Rapid lling Sounds S4 S1 S2 S3
7. Reduced lling
0 0.4 0.8
32 Seconds
fi

fi

 Isovolumic
relaxation
Rapid inflow Atrial systole
Isovolumic Ejection
Diastasis
contraction

120 Aortic Aortic valve

valve closes
100
Pressure (mm Hg)

opens
Aortic pressure
80
60 A-V valve
A-V valve
40 closes opens

20 Atrial pressure
a c v
0 Ventricular pressure
130
Volume (ml)

Ventricular volume
90
R
50
P
T Electrocardiogram
Q
1st 2nd 3rd S

Phonocardiogram

Systole Diastole Systole

33
igure 9-6 Events of the cardiac cycle for left ventricular function, showing changes in left atrial pressure, left ventricular pressure, aortic
 CHAPTER 4 • CARD
Intra-cardiac pressures

120/80 25/10 ventricular ejection

relaxation (d). The E
Ao ume achieved at the
LA is the minimal volum
RA PA 8 of the ventricle foun
The width of the lo
4 120/8 the difference betwee
LV the SV. The area wit
loop is the ventricula
RV
The filling phase m
25/4 tolic pressure–volum
or passive filling cur
slope of the EDPVR
■ FIGURE 4.3 Summary of normal pressures curve is the reciproc
34
Heart sounds

Two heart sounds from cardiac contractions are normally heard.

• 1st heart sound: soft, low-pitched lub associated with closure of the AV
valves
•2nd heart sound: louder dub associated with closure of pulmonary & aortic
valves
3rd heart sound: during ventricular lling, represent tensing of chordae tendineae
and AV ring; normal in children but pathologic in adults
4th heart sound:heard during atrial contraction; when ventricle compliance is
reduced; common in older individuals

35

fi

 Normal open valve Stenotic valve

on
he
ut Laminar flow = quiet Narrowed valve
is Turbulent flow = murmur

he Normal closed valve Insufficient valve

he
n-

No flow = quiet Leaky valve

Turbulent backflow = murmur
(a) (b)
nd 36
 Chapter 9 Cardiac Muscle; The

Ventricular pressure-volume Period of ejection

relationship 120

Aortic valve
closes
A->B: ventricular lling
100 D

Left intraventricular pressure (mm Hg)

B->C: Isovolumetric contraction

EW
Aortic valve
C->D: Ventricular ejection
80
C
opens

D->A: Isovolumetric relaxation

Isovolumetric
relaxation
60
EDV: maximal volume at the end of lling
Stroke volume Isovolumetric
contraction
ESV: minimal volume (residual volume) at end 40
of ejection

SV= EDV - ESV 20 End-systolic End-diastolic

volume Period of volume B
Mitral valve filling Mitral valve
A
opens closes
0
0 50 70 90 110 130
Left ventricular volume (ml)

37
fi
fi
 200
ESPVR Increased
LV Pressure (mmHg)
Venous
Return

100
Control
Loop

!SV

! EDV
0
0 100 200
LV Volume (ml)
38
Cardiac output (CO)

The volume of blood pumped by each ventricle as a function of time.

In steady state: CO is the same in systemic and pulmonary circuits

Cardiac output (mL(L)/min) = stroke volume (mL(L)/beat) x heart rate (beats/min)

In a resting adult CO = 4.8 - 7.3 L/min

39

(CO; mL/min) calculations from measure-

ments of arterial and venous blood oxygen Preload
Measurement of cardiac output:
content (CaO2 and CvO2, respectively; mL O2/ myocytes
mL blood),
Thermodilution and whole
technique usingbody oxygen consump-
a thermistor-tipped related
catheter (Swan-Ganz) to
.
inserted into pulmonary artery via peripheral vein. tole. Sarc
tion (VO2; mL O2/min). This method is based
on the
Fick following
Principle: relationship
allows time-averaged (Fick ofPrinciple):
calculations cardiac output by the intac
measurements of arterial and venous blood O2 content & whole body Osuch 2 as v
consumption
! used. Th
VO2
CO = because t
(CaO2 - CvO2 )
length be
mechanic
where: CO; mL/min, CaO2 & CvO2; mL O2/mL blood and VO2; mL O2/min
Influence of Heart Rate and limitation
Stroke Volume on Cardiac Output sure and
40

Swan-ganz catheter

41
Questions:

1. If each ventricle has a heart rate of 72 beats/min and ejects 70 mL of

blood with each beat, what is the cardiac output?

2. Calculate the left ventricular SV in millilitres/beat when the cardiac output

is 8.8 L/min and the heart rate is 110 beats/min.

42

Factors affecting determinants

of cardiac output
60
Control of heart rate (HR)
a, b, and c are pacemaker potentials:

Membrane potential (mV)

• inherent autonomous discharge rate of SA a = control
node is ~100 beats/min
b = during sympathetic stimulation
c = during parasympathetic stimulation
• HR is slower or faster due to in uence of
nerves and hormones
0

Threshold
potential
–40
b a
c
–60

Time

Figure 12.22 Effects of sympathetic and parasympathetic

nerve stimulation on the slope of the pacemaker potential of an
43
SA nodal cell. Note that parasympathetic stimulation not only
reduces the slope of the pacemaker potential but also causes the
fl
Control of stroke volume

Stroke volume (SV) = the volume of blood ejected during each

contraction

Factors that change force of ejection of SV:

1) changes in the end-diastolic volume (preload)
2) changes in magnitude of sympathetic nervous system input
3) changes in arterial pressure against which ventricles pump (afterload)

44

 Frank-Starling mechanism
• The relationship between stoke volume (SV) & end-diastolic volume (EDV) = Frank-Starling
mechanism

• If all other factors remain constant; SV increases as EDV increases

• Signi cance of Frank-Starling mechanism: at any given HR, an increase in venous return
automatically forces an increase in CO by increasing EDV and SV

200
Increased

Stroke volume (mL)

stroke
volume

100

Normal Increased
resting venous return
value
0 100 200 300 400
Ventricular end-diastolic volume (mL) 45
fi

 receptors also increases myocardial contractility. Thus, the

skeletal muscles, but is on the rising phase of the curve. For
this reason, greater filling causes additional stretching of the
cardiac muscle fibers and increases the force of contraction.
Sympathetic regulation
The mechanisms linking changes in muscle length to
changes in muscle force are more complex in cardiac muscle
than in skeletal muscle. In addition to changing the overlap
of thick and thin filaments, stretching cardiac muscle cells
Sympathetic nerves distributed to entire myocardium
toward their optimum length decreases the spacing between
thick and thin filaments (allowing more cross-bridges to bind
during a twitch), increases the sensitivity of troponin for
Norepinephrine and epinephrine act on beta-adrenergic receptors to
binding Ca21 , and increases Ca21 release from the sarcoplas-
mic reticulum.
increase contractility
(a)
increased force of contraction and stroke volume result-
ing from sympathetic nerve stimulation or epinephrine are
independent of a change in end-diastolic ventricular volume.
A change in contraction force due to increased end-
diastolic volume (the Frank–Starling mechanism) does not
reflect increased contractility. Increased contractility is spe-
cifically defined as an increased contraction force at any given
end-diastolic volume.
The distinction between the Frank–Starling mechanism
and sympathetic stimulation is illustrated in Figure  12.25a.
The green ventricular-function curve is the same as that shown
in Figure  12.24. The orange ventricular-function curve was
(b)

During stimulation
of sympathetic nerves
Sympathetic to heart
stimulation

during contraction
Force developed
200
Stroke volume (mL)

Increased
contractility

Control
100 Control

Normal
resting
value

0 100 200 300 400

Ventricular end-diastolic volume (mL) Time
46
Figure 12.25 Sympathetic stimulation causes increased contractility of ventricular muscle. (a) Stroke volume is increased at any given

Norepinephrine Epinephrine Extracellular fluid

L-type Ca2+ channel

β-adrenergic Adenylyl
Plasma membrane
receptor α α cyclase
β
γ β
γ
1 Intracellular fluid
Ca2+ Ryanodine receptor
cAMP ATP
Inactive
cAMP-dependent 2
protein kinase + Active
cAMP-dependent
protein kinase
Sarcoplasmic
Ca2+ reticulum

3
4
Cross-bridge cycling, Thin filament
thick and thin filament sliding, activation
force generation (Ca2+–troponin)

Force and Velocity of Contraction 47

 Effects of autonomic nerves on the heart
TABLE 12.3 Effects of Autonomic Nerves on the Heart

Sympathetic Nerves Parasympathetic Nerves

Area Affected (Norepinephrine on b-Adrenergic Receptors) (ACh on Muscarinic Receptors)

SA node Increased heart rate Decreased heart rate

AV node Increased conduction rate Decreased conduction rate

Atrial muscle Increased contractility Decreased contractility

Ventricular muscle Increased contractility No significant effect

Afterload Begin
An increased arterial pressure tends to reduce stroke vol-
End-diastolic Activity of sympathetic
ume. This is because, like a skeletal muscle lifting a weight, ventricular volume nerves to heart
the arterial pressure constitutes a “load” that contracting
ventricular muscle must work against when it is ejecting
blood. A term used to describe how hard the heart must
Plasma Activity of
work to eject blood is afterload. The greater the load, the epinephrine parasympathetic
less contracting muscle fibers can shorten at a given con- nerves to heart 48
Afterload

• The amount of pressure the heart needs to exert to eject the blood out
during contraction

• Increased systemic vascular resistance and increased aortic pressure =>

increased afterload

• Decreased stroke volume => increased end-systolic volume => increased

afterload

49

Ejection fraction (EF) = a way to quantify contractility

• EF = SV/EDV ; expressed as a percentage

• EF normally averages between 50% and 75% in resting individuals

• Increased contractility, increases EF

50

 Begin
reduce stroke vol-
End-diastolic Activity of sympathetic
cle lifting a weight, ventricular volume nerves to heart
” that contracting
when it is ejecting
rd the heart must
Plasma Activity of
eater the load, the epinephrine parasympathetic
en at a given con- nerves to heart
or will not be dealt
t, several inherent
ce of arterial pres-
e sections on high Cardiac muscle SA node
see that alterations Stroke volume Heart rate
vations of arterial
by influence stroke
Cardiac output
rs that determine
ry of the control of Cardiac output = Stroke volume × Heart rate

Figure 12.27 Major factors determining cardiac output.

51
Distribution of cardiac output CHAPTER 7 • ORGAN BLOOD FLOW 149

Blood ow in the major organs of the body :

TABLE 7-1 BLOOD FLOW IN MAJOR ORGANS OF THE BODY
PERCENT BODY PERCENT CARDIAC NORMAL FLOW MAXIMAL FLOW
ORGAN WEIGHT OUTPUT AT REST (mL/min PER 100 g) (mL/min PER 100 g)

Heart 0.5 5 80 400

Brain 2 14 55 150
Skeletal muscle 40 18 3 60
Skin 3 4 10 150
Stomach, intestine, 6 23 30 250
liver, spleen, pan-
creas
Kidneys 0.5 20 400 600
Other 48 16 — —
Normal and maximal flows are approximate values for the whole organ. Many organs (e.g., brain, muscle, kidney, and intes-
tine) have considerable heterogeneity of flow within the organ depending on the type of tissue or region of organ being
52
perfused. The liver receives blood flow from the gastrointestinal venous drainage as well as from the hepatic artery (only
fl
 A
muscles. However, there are also increases in flow to the heart,
p
to provide for the increased metabolism and workload as car-
i
diac output increases, and to the skin, if it becomes necessary
f
to dissipate heat generate by metabolism. The increases in
w
flow through these three vascular beds are the result of arteri-
Cardiovascular physiology in health & disease olar vasodilation in them. In both skeletal and cardiac muscle, t
P
a
s
Exercise:
Flow during
strenuous exercise
s
c
(mL/min)

Flow 750 (4%)

• Cardiac output increases from ~5 L/min to ~35 L/min at rest
(mL/min) 750 (4%)

in trained athletes Brain 650 (13%)

Heart 215 (4%) 12,500 (73%)

Local metabolic factors mediate vasodilation

Skeletal muscle 1030 (20%)
•
Skin 430 (9%)

Reduction in TPR
Kidneys 950 (20%)
•
Abdominal
1200 (24%)
organs 1900 (11%)

Other 525 (10%)

Total 5000 600 (3%)

600 (3%)
400 (2%)
17,500

Figure 12.61 Distribution of the systemic cardiac output at 53

 750 (4%)
Exercise
3000
750 (4%)

12,500 (73%)
1030
Skeletal muscle blood flow
(mL/min)
93 113
Mean arterial pressure (mmHg)
180
120
Systolic arterial pressure (mmHg)
80
Diastolic arterial pressure 80
(mmHg)
18.6
Total peripheral resistance
(mmHg • min/L)
1900 (11%) 10.3
11

600 (3%) 5
Cardiac output (L/min)
600 (3%) 130
400 (2%)
17,500 72
Heart rate (beats/min)
70 85
Stroke volume (mL/beat)
f the systemic cardiac output at 135
. The values at rest were previously End-diastolic ventricular volume 148
(mL)
m Chapman and Mitchell.

Time 54
Factors promoting venous return during exercise:
1) Increased activity of skeletal muscle pump
2) Increased frequency of inspiration
3) Increase in venous tone
4) Greater ease of blood ow from arteries to veins

55
fl

is under way represents active hyperemia as a result of local existing at rest. The reason is that one neura

Begin

Brain E xercising skeletal muscles

“E xercise centers” Contractions

Afferent Stimulate
Local chemical
input mechanoreceptors
Arterial baroreceptors Medullary changes
in the muscles
Reset upward cardiovascular
center Figure 12.63
Afferent of the cardiovascu
input Stimulate Dilate during exercise. T
chemoreceptors arterioles
in the muscles in the muscle
outflow to the sy
Parasympathetic output to heart
Sympathetic output to heart, veins, parasympathetic
and arterioles in abdominal pathways from “e
organs and kidneys Muscle blood flow in the brain. Affe
from mechanorec
chemoreceptors i
Cardiac output muscles and from
Vasoconstriction in baroreceptors als
abdominal organs autonomic neuro
and kidneys
medullary cardio
Cardiovascular
56
 Chapter 25 • Integrated Control of the Cardiovascular System 601

2. Cardiac output. Intense vagal output to the heart causes

bradycardia and decreased stroke volume, resulting in a Contracting muscles
marked decrease in cardiac output. Because atropine, a
muscarinic receptor blocker, does not reliably prevent
• How exercise affects
syncope, decreased sympathetic tone to the heart may
also play a role in causing bradycardia.
Mechanical Chemical

cardiovascular
3. Arterial pressure. The combination of a sudden decrease
in both total peripheral resistance and cardiac output
causes a profound fall in mean arterial pressure.
function
Muscle pump Metabolites
4. Cerebral blood flow. The fall in mean arterial pressure
causes global cerebral ischemia. If the decreased cerebral PO 2 PCO2 pH
blood flow persists for only a few seconds, the result is
dizziness or faintness. If it lasts for ∼10 seconds, the
subject loses consciousness. The stress underlying the
• EDV: end-diastolic
common faint also may provoke hyperventilation, which
lowers arterial PCO2 (see Chapter 31). The resulting con-
Venous return Local vasodilation
of active muscle
striction of cerebral blood vessels (see Chapter 24) further
volume
impairs cerebral blood flow, which increases the likeli-
hood of a faint. Right atrial pressure Arterial pressure
5. Other manifestations of altered ANS activity. Pallor of
the skin and sweating (beads of perspiration) are signs
that often appear before the loss of consciousness. Intense End-diastolic pressure
vagal stimulation of the gastrointestinal tract may cause
epigastric pain that is interpreted as nausea. Mydriasis
(pupillary dilation) as well as visual blurring can also EDV Arterial baroreceptor
result from parasympathetic stimulation.

Fainting is more likely to occur in a warm room, after

Stroke volume
a volume loss (e.g., dehydration or hemorrhage), or after
standing up or other maneuvers that tend to lower mean Heart rate
arterial pressure. You might think that these stresses would
trigger baroreceptor responses that increase cardiac output
and vascular resistance, thereby making fainting less likely. Vasoconstriction of
However, the same integrated pattern of brain activity that • Inactive muscle
orchestrates VVS also appears to suppress the expected Cardiac output • Splanchnic
baroreceptor reflexes that would otherwise counteract the • Cutaneous
syncope. • Renal circulations
After regaining consciousness, the patient often notices
oliguria (reduced urine output), caused by high plasma
Figure 25-6 An early model of how exercise affects cardiovascular
levels of AVP (also known as antidiuretic hormone; see 57
function.
Boron W. F. & Boulpaep E. L. (2012). Medical physiology : a cellular and molecular approach (UpdatedEDV, end-diastolic
second). volume.
Saunders/Elsevier.
Chapter 38). Elevated levels of AVP can result in part from

endurance exercise), contributing to a large increase in mean striction, arteriolar vasodilation) to increase ventricular filling
arterial pressure during the contraction. Frequent exposure of further during the very short time available.

Cardiovascular
TABLE 12.8
changes during moderate
Cardiovascular Changes During Moderate Exercise
exercise
Variable Change Explanation

Cardiac output Increases Heart rate and stroke volume both increase, the former to a much greater extent.

Heart rate Increases Sympathetic stimulation of the SA node increases, and parasympathetic stimulation decreases.

Stroke volume Increases Contractility increases due to increased sympathetic stimulation of the ventricular
myocardium; increased ventricular end-diastolic volume also contributes to increased
stroke volume by the Frank–Starling mechanism.

Total peripheral Decreases Resistance in heart and skeletal muscles decreases more than resistance in other vascular
resistance beds increases.

Mean arterial pressure Increases Cardiac output increases more than total peripheral resistance decreases.

Pulse pressure Increases Stroke volume and velocity of ejection of the stroke volume increase.

End-diastolic volume Increases Filling time is decreased by the high heart rate, but the factors favoring venous return—
venoconstriction, skeletal muscle pump, and increased inspiratory movements—more than
compensate for it.

Blood flow to heart Increases Active hyperemia occurs in both vascular beds, mediated by local metabolic factors.
and skeletal muscle

Blood flow to skin Increases Sympathetic activation of skin blood vessels is inhibited reflexively by the increase in body
temperature.

Blood flow to viscera Decreases Sympathetic activation of blood vessels in the abdominal organs and kidneys is increased.

Blood flow to brain Increases Autoregulation of brain arterioles maintains constant flow despite the increased mean
slightly arterial pressure.
58
420 Chapter 12