circulatory system...heart is a pumping organ of the circulatory system. it is mesodermal in origin...
TRANSCRIPT
CIRCULATORY SYSTEM
Table of Contents
Introduction
Structure of Heart
Pericardium
Heart Wall Working Cardiac Muscle Cells structure Conducting system
Origin and conduction of impulses
Sinoatrial node
Internodal pathways
Atrioventricular node
Bundle of HIS
Purkinje fiber
Ventricular muscle fibers
One way conduction of impulses
Excitation conduction coupling
Coronary Circulation
Cardiac Cycle
Mid diastole
Late diastole
Early systole
Late systole
Early diastole
Cardiac Output
Definition
Stroke volume
Cardiac index
Factors that affect cardiac output
Exercise
Surface Area
Age
Sex
Methods to measure cardiac output
The Fick principle
Dilution method
Control of cardiac out put
Stroke volume
Heart rate
Nervous control of Heart rate
Autonomic control
Cardiac reflexes
Chemical control of Heart Beat
Electrocardiogram (ECG)
Principle of Electrocardiography
Recording of electrocardiogram
Components of ECG
Blood circulation
Blood pressure
Definition
Measurement of blood pressure
Auscultatory metnod
Oscillometric method
Pulse pressure
Regulation of Blood pressure
Summary
Exercises
Glossary
References
Learning objectives
To describe the structure of heart as a pumping organ.
Its structural and functional components
Structure of heart wall and pericardium
Blood supply to the heart -coronary circulation
Describe the events of the cardiac cycle
Cardiac output and the factors that affect it.
Frank Starling law of heart
Nervous and chemical control of heart rate.
Electro cardiogram, its recoding and components
Blood pressure, its measurement and regulation
Introduction
Heart is a pumping organ of the circulatory system. It is mesodermal in origin and is of the
size of a closed fist. As the heart beats, it pumps blood through a system of blood vessels,
which are elastic and muscular tubes .They carry blood to every part of the body from the
heart and back into it.
Heart continuously pumps oxygen and nutrient-rich blood throughout the body to sustain
life. It beats (that is expands and contracts) nearly 100,000 times per day and pumps five
to six liters of blood each minute ( about 2,000 gallons per day).
It is the first organ that that becomes functional in a developing embryo. It is because all
the living cells in the embryo or the adult body require continuous supply of oxygen,
nutrients, heat, hormones and vitamins, and remove their metabolic end products. This
function is performed by blood. Therefore, it is essential that the blood is circulating
continuously for which it requires a pump. Heart serves as a pump that imparts pressure to
the blood to flow in vessels and reach cells.
Structure of Heart
All vertebrates have myogenic heart. It is a hollow muscular organ about 300 g (250 – 450
g) in weight. In warm blooded animals, heart is four chambered consisting of two auricles
and two ventricles. It is placed in between the two lungs in the mediastinum cavity. The
human heart is blunt cone shaped. The base of the cone is formed by the atria that lie
slightly towards the right. Nearly two third of the heart is towards the left of the midline of
the body consisting mainly of the ventricles. The left ventricular tip forms the apex of the
heart.
Its total volume is 700 ml, of which 400 ml is formed by the muscles and 300 ml is lumen
filled with blood. The atrioventricular septum consists of valves that prevent the back flow
of blood. Left side auricle is separated from the ventricle by bicuspid valve (Mitral Valve)
and right side by tricuspid valve. Since these valves have either two or three cusps (cup)
shaped depression towards the ventricular side. The valve between the aorta (left) and the
pulmonary trunk (right) and the two ventricles are called semilunar valves as they are
crescent shaped when closed. All the valves help in the unidirectional flow of blood with in
the heart.
Fig. Anterior view of opened heart (semidiagramatic)
Source: http://www.sharinginhealth.ca/biology/cardiovascular.html(creative
commons)
Pericardium
Heart and the great vessels entering and leaving it are enclosed in the double walled sac
called pericardium. The pericardial sac consists of two layers : (i) Fibrous pericardium
(ii) Serous pericardium.
Fibrous pericardium: It consists of very heavy fibrous connective tissue and prevents
heart from over distension and also anchors it in the mediastinum
Serous pericardium: It is made up of two layers, the parietal pericardium and the
visceral pericardium. These layers are separated by a pericardial cavity that is filled with
the pericardial fluid. The parietal pericardium is inseparably fused to the fibrous
pericardium. The epicardium of the heart wall is made by visceral pericardium. The
visceral layer (becoming one with the parietal layer) extends where the aorta and
pulmonary trunk leave the heart and the superior and inferior vena cava and pulmonary
veins enter into the heart.
Value addition: Did you Know
Heart diseases Pericarditis ; It is the inflammation of pericardium.
Cardiac temponade: When excessive fluid accumulates in the pericardium in
pericarditis condition, it compresses the heart , since pericardium can’t stretch that much.
Source: Tortora, G.J. & Grabowski, S. (2006). Principles of Anatomy & Physiology.
XI Edition John Wiley & sons, Inc.
Fig. Pericardium
Source: http://www.knowyourbody.net/serous-pericardium.html
Heart wall
The wall of the heart is made up of three layers:
1. Epicardium (outer),
2. Myocardium (middle)
3. Endocardium (inner)
Epicardium is the visceral layer of the pericardium.
Myocardium is cardiac muscle tissue that constitutes the main bulk of the heart. The cardiac
muscle cells are involuntary, striated, branched and arranged in interlacing bundles of fibres
as described below.
Endocardium is a thin layer of epithelial cells towards the inner side of the myocardium and
lines the lumen of the heart, it is continuous with the endothelial lining of the blood vessels.
Fig. Section of Heart wall showing components of the outer pericardium (heart
sac), muscle layer (myocardium) and inner lining (endocardium) Source: http://www.arthursclipart.org/medical/circulatory/page_03.htm
Structure of Cardiac muscle cell
The heart muscle is not a syncytium but made up of discrete cells of different types. Their
special structure imparts them innate rhythmicity for contraction. These cells are also
sensitive to the direct action of neurotransmitters. On the basis of their function they can
be classified into the following two types:
a. Working myocardial cells
b. Specialized Conducting myocardial cells
Further all the working or the conducting myocardial cells are not identical. For example
the atrial cells are different from the ventricular cells and the AV nodal fibers are different
from the Purkinje’s fiber, as discussed below.
Working Myocardial cells
Working myocardial cells make a bulk of structurally and functionally the contractile
component of the atria and ventricles. These cells are arranged in columns. Each cell has a
central nucleus with many myofibrils aligned along the cell axis. These cells are rich in
mitochondria and are enclosed by membrane called sarcolemma. Structure of cardiac
sarcomere resembles that of the skeletal muscle consisting of protein actin hexagonally
arranged around the myosin myofilaments. The modulating proteins troponin and
tropomyosin are also present. There are slight structural differences in these proteins of the
skeletal and cardiac muscles.
The myocardial cell membrane that is sarcolemma, resembles other cell membranes in
structure but has the following unique characteristics for the relatively low electrical
resistance between the adjacent cells:
Sarcolemma is folded between the adjacent cells in the form of intercalated discs to
hold them together
The actin filaments are attached to the inner surface of these intercalated discs between the cells.
Along the longitudinal axis of the cell there are tight junctions between the cells
without the intercellular space, called nexuses or tight junctions.
Sarcolemma extends into the cell and forms transverse tubules of the sarcoplasmic reticulum.
The longitudinal tubules (which are the true endoplasmic reticulum) are less
developed than in the skeletal muscles and form terminal cisternae near the Z line. Terminal cisternae and the transverse tubules form diads and triads near the Z line.
Fig. Detailed three dimentional structure of working myocardial cells.
(Source: Modified from G H Bell, D.E. Smith and C R Patterson Text book of
Physiology and Biochemistry)
Special Conducting Myocardial cells
Sino-atrial Node( or SA node or Sinus node)
Atrio-ventricular node
Inter-nodal fibers
Bundle of HIS or AV bundle
Purkinje Fibers.
(Details will be discussed in the next section)
Origin and conduction of impulses
The heartbeat originates in specialized myocardial cells at the opening of the precava into
the right auricle called sino-atrial node (SA node). Sinoatrial (SA) node also called as the
pacemaker of the heart coordinate the spontaneous contraction of cardiac muscle cells.
These contractions are coordinated by the .From the SA node the impulses travel fastest
into the AV node where they are slowed down before entering into the ventricle. Bundle of
HIS emerges from the AV node that sends Purkinje fibers to the both the ventricles.(fig)
Structure of Conducting muscle cell
Sinoatrial node (SA node)
It is a ellipsoidal strip of specialized muscle about 3mm wide, 15 mm long and 1 mm thick.
These fibers have no contractile filaments and are 3 to 5 micrometer in diameter. SA nodal
fibers are directly connected to the atrial muscle fibers.
Self Excitation of the sinoatrial node: The cardiac cell membranes are different from the
other membranes and have the following properties:
i) Their resting membrane potential is higher than other membranes. It is -55 to -60
millivolts in contrast to other membranes that have -85 to -90 millivolts.
ii) This is because three types of membrane channels play an important role in causing
the voltage changes of the action potential.
Fast sodium channels Slow calcium - sodium channels
Potassium channels
iii) Resting nodal fibers have a moderate number of channels that are already open to the
sodium. This leakiness of the nodal fibers to the positively charged sodium ions causes a
slowly rising membrane potential thus rising the resting membrane potential.
iv) As the resting membrane potential reaches the threshold voltage of about - 40 mV the
calcium – sodium channels become activated causing action potential, by the rapid influx of
calcium and sodium ions.
v) These channels become inactivated within 100-150 millisecond so that the membrane
does not remain depolarized for long due to the leakiness of the membrane to sodium ions.
Secondly a large number of potassium channels open to prevent the permanent
depolarization of nodal fibers.
vi) An excess of efflux of potassium causes hyperpolarization that is excess negativity
inside the membrane.
Fig Specialized conducting system of the heart.
Source: Guyton, A.C. & Hall, J.E. (2006). Textbook of Medical Physiology. XI
Edition. Hercourt Asia PTE Ltd. / W.B. Saunders Company.
Fig 5.6 Rhythmical discharge of impulses at SA node and its comparison with
ventricular muscle action potential.
(Source: Guyton and Hall, Text book of Medical Physiology, tenth edition
2000)
Internodal pathways
Even though the ends of the sinus nodal fibres connect directly with the surrounding atrial
muscles fibers, some of them are highly modified for the rapid conduction of impulses from
SA node to the AV node. They conduct the impulses at a rate of 1 meter per second
whereas, in other fibers conduction velocity is 0.3 m/sec. These are anterior, middle and
posterior internodal pathways. They resemble Purkinje fibers of the ventricle. Anterior
intermodal pathways transmit the impulses rapidly to the left atrium.
Atrioventricular node
Atrioventricular node is located in the wall of the right atrium immediately behind the
tricuspid valve adjacent to the opening of the coronary sinus. Function of AV node is to
delay the transmission of impulses to the ventricles. Impulses after originating at the SA
node reach in 0.03 sec at AV node. There is a delay of 0.09 sec in the further transmission
of impulses to the AV bundle. A delay of 0.04 seconds occurs when the impulses pass from
fibrous atrioventricular septum. Thus a total delay from AV node to ventricular muscle is
0.16 sec. and from SA node to ventricles is 0.19 sec.
Fig: Showing the time of appearance of cardiac impulses in different parts of the
heart. Source : Author
Slow rate of conduction at AV complex is because of two reasons:
Small size of these fibers
Reduced gap junctions between the succeeding cells that offers great resistance to the
conduction of impulse
Table Showing the time taken by the conducting system to receive, delay and relay
impulses from their origin at SA node to ventricular muscle cells.
Cardiac muscle Tissue
Time taken to arrive/ delayed/
relay by impulses
SA node
Left auricle
AV node (complex)
Delay at Av node
Penetrating portion of the
AV bundle
Delay at AV bundle
Ventricular muscles
Apex of ventricle Inner Base of the ventricle
Outer of the base of the
ventricle
0 .0 sec
0.03 sec
0.03 sec 0.09 sec
0.12 sec
0.04 sec
0.16 sec
0.17 sec
0.19 sec
0.22 sec
AV Bundle or Bundle of HIS
Bundle of HIS or AV bundle is the bundle of specialized cardiac muscle fibers that begins at
the atrioventricular node and passes through the right atrioventricular fibrous ring to the
membranous part of the interventricular septum. In 1893, Swiss cardiologist Wilhelm His,
Jr. discovered these specialized muscle fibers in the heart and hence they were named as
bundle of HIS. It conducts the electrical impulse that regulates the heartbeat from the right
atrium to the ventricles. It divides into right and left branch entering into right and left
ventricle respectively
.
Fig: Bundle of HIS
Source:http://medicaldictionary.thefreedictionary.com/Atrioventricular+bundle+
of+His
Value addition: Did you Know
Third degree Heart block When the Bundle of His is blocked, there is dissociation between the activity of the atria and ventricles; it is called a third degree heart block. A blockage of the right, left anterior, and left posterior bundle branches can also cause of a third degree block. A third degree block is a very serious medical condition that requires urgent medical attention
Source: Tortora, G.J. & Grabowski, S. (2006). Principles of Anatomy & Physiology. XI Edition John Wiley & sons, Inc.
Value addition: Did you Know
Third-degree AV block In this medical condition, the impulse generated in the SA node in the atrium does not propagate to the ventricles. It is also known as complete heart block. It can be treated by the use of dual chamber artificial pace maker.
Source: Tortora, G.J. & Grabowski, S. (2006). Principles of Anatomy & Physiology.
XI Edition John Wiley & sons, Inc.
Purkinje fibers
The distal portion of the AV bundle divides into the left and right branches beneath the
endocardium giving out the Purkinje fiber that pass through the ventricular muscles. They
have the following characteristics: These fibers have a very high conduction velocity, of 1.5 to 4 m per second. They are very large in size
They have large number of gap junctions to increase the permeability at intercalated
discs for rapid conduction of impulses Purkinje fibers have very few myofibrils so they hardly contract during the
transmission of impulses. Purkinje fibers at their end finally become continuous with the cardiac muscle cells
Conduction of impulses in Ventricular muscles
The conduction velocity of the ventricular fiber is reduced to 0.3 to 0.5 m/sec. The cardiac
muscle wraps around the heart in a double spiral with the fibrous septa. Therefore the
cardiac impulses travel spirally to the surface and it takes 0.3 sec. for the impulses to reach
the epicardium from the endocardium. Thus the total time for transmission of the cardiac
impulses from the AV bundle to the last ventricular muscle fiber is 0.06 sec.
Unidirectional conduction of impulses: The unidirectional flow of impulses by the AV
bundle is important for the unidirectional flow of blood in the cardiac cycle. The fibrous
atrio-ventricular septum acts as an insulator and does not allow the back flow of impulses.
Excitation-contraction coupling
Like unmyelinated nerve fibers the myocardial cell membranes are also excited by the
generation of local circuit current by the membrane action potential. This current is
propagated by self-perpetuating action potential. The intercalated discs and tight junctions
between the adjacent cells have a low resistance because of their high permeability to the
current carrying K+. The current moves from the surface of the cell membrane into its
interior. In the regions of the triads the electrical impulse allows the calcium from the
nearby cisternae of the longitudinal tubule to move out into the myofibrils. Calcium helps
in binding ATP to active sites between actin and myosin filaments. ATP is split by myosin-
ATPase in the presence of Mg ++ and the filaments are propelled past each other to the
successive new sites for the reaction with making or breaking of actin myosin bonds. The
sarcomere shortens and the myofibril contracts. Immediately calcium moves back from the
vicinity of the myofibrils back into the cisternae and the myofibril relaxes by inhibiting the
action of troponin and tropomyosin.
Fig. Excitation-contraction coupling in myocyte
Electrical excitation at the sarcolemmal membrane activates voltage-gated Ca2+channels,
and the resulting Ca2+entry activates Ca2+ release from the sarcoplasmic reticulum (SR) via
ryanodine receptors (RyRs), resulting in contractile element activation. NCX, Na+/Ca2+
exchange; ATP, ATPase; PLB, phospholamban; SR, sarcoplasmic reticulum. Inset shows the
time course of an action potential, Ca2+ transient and contraction. Source: http://static.wikidoc.org/d/dc/Excitation_Contraction_Coupling.png
Coronary circulation
Fig. Showing coronary circulation
(Source: http://www.cvphysiology.com/Blood%20Flow/BF001.htm)
Coronary circulation is the blood circulation in the blood vessels of the myocardium (heart
muscle). Coronary arteries are the vessels that deliver oxygen-rich blood to the
myocardium whereas Cardiac veins remove the deoxygenated blood from the heart
muscle.
The left and right coronary arteries originate at the base of the aorta from openings called
the coronary ostia located behind the aortic valve leaflets The left coronary artery
originates from the left aortic sinus, while the right coronary artery originates from the right
aortic sinus. The major vessels of the coronary circulation are the left main coronary artery
that divides into left anterior descending and circumflex branches, and the right main
coronary artery.
The coronary arteries that run on the surface of the heart are called epicardial coronary
arteries. These arteries, when healthy, are capable of autoregulation to maintain coronary
blood flow at levels appropriate to the needs of the heart muscle. These relatively narrow
vessels are commonly affected by atherosclerosis and can become blocked, causing angina
or a heart attack The coronary arteries that run deep within the heart muscle are referred to
as subendocardial.
Travels down T
tubules
Entry of small amount
of Ca++ from ECF cells
Release of Ca++from
sarcoplasmic reticulum
Increase in
cytosolic Ca++
Action potential in
the cardiac working
Troponin
tropomyosin complex
in thin filaments
Cross bridge cycling
between the thick
and thin filaments
Thin filaments slide
inwards between
thick filaments
Contraction occurs
5.11. Flow diagram showing excitation- contraction coupling in cardiac working
cells Source : Author
Cardiac cycle
The cardiac events that occur from the beginning of one heart beat to the next are called
cardiac cycle. The human heart beats at a rate of 72 beats per minute, that is rate at which
the impulses are generated by the SA node (70 to 75 is the range). Two main events of the
cardiac cycle are systole the contraction phase and diastole the relaxation phase of the
cardiac muscles.
During diastole the heart receives the blood from major veins and during systole it pumps
the blood into the body through the left aorta (left ventricle) and to the lungs through the
pulmonary trunk (right ventricle).
The total duration of each cardiac cycle is 0.8 second. Auricular systole is 0.1 sec and
diastole is 0.7 sec. Ventricular systole is 0.3 sec and diastole is 0.5 sec. in duration. The
cardiac cycle function on the simple principle of flow of fluid from higher to lower pressure.
The cardiac cycle can be studied in the following five steps of the left ventricle: 1. Mid diastole
2. Late diastole 3. Early systole (Isovolumetric contraction)
4. Mid to Late systole (ejection phase)
5. Early diastole
Mid diastole (left side)
Atria and ventricles both are relaxed. Left atrial
pressure is more than the left ventricular pressure.
The atrium is continuously receiving the blood from
the lungs through the pulmonary vein.
Atrioventricular (AV) valves are open allowing a
continuous filling of ventricles rapidly. Nearly 80% of
the ventriclular filling takes place in this phase. Semilunar (SL) valves are closed, as the aortic
pressure is more than the ventricular pressure.
Fig. Mid diastole
Late diastole of ventricle
Fig. Late diastole of ventricle
Early ventricular systole
Atrium is contracted (atrial systole). It occurs
during the ‘P’ Wave of the Electrocardiogram. Ventricle is still relaxed (diastole).
AV valves are open
Nearly 20- 25% of the blood flows from the atria into the ventricle.
SL valves are closed as still the pressure in the
aorta is more than in the ventricle. The total volume of blood in the ventricles at the
end of the diastole is called End Diastolic Volume (EDV).
It is also called isovolumetric (isometric) contraction because the volume of ventricles remains constant as both the valves that is AV and SL are closed ventricle is a closed chamber. The blood can’t flow in or out of the ventricle. The pressure is built up in the completely closed ventricular lumen due to its depolarization and beginning of contraction phase (QRS Complex of ECG)
Atria relaxed due to its repolarization
AV valves are still closed because the atria have still not received enough venous blood from the lungs and blood pressure is lower than ventricular pressure.
SL valves are closed, as the pressure in the ventricular lumen is still less than blood pressure in the aorta.
Fig. Early ventricular systole
Mid to late ventricular systole (ejection phase)
Ventricles are contracted (systole) but atria are relaxed (diastole)
SL valves are open due to reduction in the pressure as the blood is continuously flowing out into the arteries and there the ventricular pressure has increased due to their contraction.
AV valves closed as the atrial filling from the pulmonary vein is still not enough to open them.
The blood is pumped by ventricle into the aorta as the SL valves are open Initially the ejection of blood is rapid and then it becomes slow.
Fig. Mid to late ventricular systole
Early diastole
Fig. Early diastole
SL valves closed as the ventricular pressure falls below the aortic pressure
Both atria and ventricle are relaxed.
AV valves are still closed as the as the ventricular pressure is more than the atrial pressure.
This is called isovolumetric ventricular relaxation (mirror image of Isovolumetric ventricular contraction)
As the ventricular pressure falls below the atrial due to their complete relaxation, AV valves open and the blood starts flowing from the atria into the ventricles.
‘T’ wave of ECG indicating the repolarization of both the atria and ventricle.
(Fig. cardiac cycle
Source:http://academic.kellogg.edu/herbrandsonc/bio201_mckinley/f22-
11_cardiac_cycle_c.jpg)
Fig. Pressure changes during the various events of the cardiac cycle on the left
and right side of the heart separately. Source: Author
Cardiac output (Q or CO)
Definition
Cardiac output can be defined as the volume of blood being pumped by left or right ventricle
in one minute. Cardiac output may be measured in dm3/min where 1 dm3 equals 1000 cm3
or 1 liter. An average resting cardiac output would be 5.6 L/min for a human male and 4.9 liter / min for a female.
Cardiac output or Q = Stroke Volume × Heart rate
Effect of Stroke volume on cardiac output
Stroke volume is the amount of blood pumped out by each ventricle during each heartbeat.
The average stroke volume in a healthy individual is 70 ml under resting conditions and the
heart rate is 70 to 72 beats per minute
The cardiac output is calculated as:
Heart rate x Stroke Volume
70 x 72 = 4914 ml nearly 5 liters of blood per min
The total volume of the blood in the body is approximately 5 to 5.5 liters. Therefore, each
half of the heart pumps the entire blood volume per minute pulmonary arteries during the
cardiac cycle
Fig. Summary of events in the left heart and aorta during the cardiac cycle. The
contracting portions of the heart are shown in dark red. Source: Author
Cardiac index
The cardiac output changes with the body size therefore, it is given as per unit surface area
of a person for comparison. A normal human being weighting 70 kg has a surface area of
about 1.7 square meters. Cardiac index is the cardiac output per square meter. For an
average adult it is 3 L / min / m 2
Factors that influence or affect the cardiac output
Activities - like exercise During exercise the cardiac output can increase up to 20 to 25 liters per minute .
In trained athletes it has been observed even up to 40 liters per minute.
Body Size /surface area: Smaller animals have a higher cardiac out put
Value addition: Did you Know
Cardiac output Surface area can be calculated from this formula
S = W 2.425 x H 0.725 x 0.007184
Where S= surface area in square meter, H is height in cm, W is Weight.
Source: Text book of physiology and Biochemistry by Bell, Smith and Paterson
Age: Cardiac output rises rapidly up to age of 10 years from 2.5 to more than 4. At the age of 80, it declines to about 2.4 l / min.
.
Body metabolism
Basal metabolic rate decreases with age as a result of this, the cardiac output / index also
declines.
Methods to measure cardiac output
The Fick Principle
The principle was given by Adolf Eugen Fick in 1870. It is based on calculation of the oxygen
consumed over a given period of time by measuring the oxygen concentration of the venous
blood and the arterial blood. Cardiac output can be calculated from these measurements.
Value addition: Did you Know
Heart beat Up to an age of 66 years human heart beats about 2.5 billion times
Source: Text book of physiology and Biochemistry by Bell, Smith and Paterson
Equation
VO2 = (Q×CA) - (Q×CV) where
VO2 consumption of oxygen per minute, which can be determined with the help of a
spirometer (with the subject re-breathing air and a CO2 absorber), is 250 mL/min.
CA = Oxygen content of arterial blood is 19 mL /100mL, (of blood taken from the pulmonary
artery.) CV = Oxygen content of venous blood (14 ml /100ml)
Thus the cardiac output is calculated as
Q = (VO2 / [CA - CV] )*100
= 250 / [( 19- 14)] 100 = 5000 ml
The calculation of the arterial and venous oxygen content of the blood is done by using
formula:
(Hb content) x (1.34 ) x (% saturation of Hb) + ( 0.0032 x p O 2 )
(Hb is measured in gm /100 mLof blood and 1.34 mLof oxygen is transported per gram of
haemoglobin)
Dilution methods
This method was initially described using an indicator dye and assumes that the rate at
which the indicator is diluted reflects the Q. The method measures the concentration of a
dye at different points in the circulation, usually from an intravenous injection and then at a
downstream sampling site, usually in a systemic artery. More specifically, the Q is equal to
the quantity of indicator dye injected divided by the area under the dilution curve measured
downstream (the Stewart (1897)-Hamilton (1932) equation):
The trapezoid rule is often used as an approximation of this integral.
Cardiac output = quantity of indicator
∫ ∞ 0 Conc. of indicator.
Control of cardiac output
Fig.5.19 Summary Control of Cardiac output Source: Author
The cardiac output is controlled by: i) Stroke volume
ii) Heart rate
Stroke volume
It is controlled by the end diastolic volume. It is explained by the Frank Starling Law of
heart.
Frank Starling law of the heart
Starling's law states that the heart will pump out all the blood, during systole which is
delivered to it by the veins during diastole. Hence, it highlights the relationship between
end-diastolic volume and stroke volume.
Fig. Relationship between EDV and Stroke Volume (Source: page 385 Sherwood)
It states that the heart normally pumps out during systole the volume of blood returned to
it during diastole, the increased venous return results in increased stroke volume. If the
end-diastolic volume doubles then stroke volume will double. It can be compared with the
filling of a balloon with water. If more water is filled it is stretched more. The main
determinant of the cardiac muscle length is the degree of its diastolic filling. An increase in
the end diastolic volume results in greater stretching of the cardiac muscle. The increased
length requires a greater force on subsequent cardiac contraction (systole) and thus
increased stroke volume. This intrinsic relationship between EDV and stroke volume is
explained by Frank Starling law
Heart Rate
Both sympathetic and parasympathetic nerve fibers innervate the SA node of the heart.
Under resting conditions, the parasympathetic fibers release acetylcholine, which slows
down the pacemaker potential of the SA node and thus heart rate is reduced. Under
conditions of physical or emotional activity, sympathetic nerve fibers release
norepinephrine, which enhances the pacemaker potential of the SA node and hence heart
rate is increased.
Fig. 5.21: Effect of sympathetic and parasympathetic nerves on the pacemaker potential indicating the stimulatory and inhibitory effect. Source: author
An increase in sympathetic activity increases stroke volume. The ventricular
myocardium cardiac muscle cells are richly innervated by sympathetic nerve fibers. Release
of norepinephrine by these nerve fibers increases the strength of myocardial contraction,
thus increasing stroke volume. Norepinephrine increases the intracellular concentration of
calcium in myocardial cells which causes faster actin/myosin cross bridge formation. Also, a
general sympathetic response by the body induces epinephrine release from the adrenal
medulla. Like norepinephrine, epinephrine also increases in the strength of myocardial
contraction and thus increase stroke volume and hence the cardiac output.
Fig.5.22 Summary of Factors controlling Cardiac Output
Source: author
Nervous control of Heart Beat
A.A
Fig. Simplified diagram of the nerve supply of the heart. C.I.=cardio-inhibitory
centre, C.A.=cardioaccelaratory centre. M=medulla oblongata. L.H.=lateral horn of
spinal cord, D=depressor fiber (afferent vagal), V=efferent vagal fibre,
C.S.=carotid sinus, H=heart, AA= aortic arch. Source: Author
Small animals have a higher heart rate than the larger ones. The heart rate of a canary is
1000, an elephant 25 and human 60 to 75 per minute. Children have a higher heart rate
than adults i.e. 130 beats per minute. Even though the heart beat originates in the cardiac
muscles but it is regulated by the autonomic nervous system. The heart beat is controlled
by the autonomic nervous system as well as by the various reflexes
Autonomic control
The cardiac center located in the medulla has a cardio inhibitory center and a cardio -
acceleratory centre.
Parasympathetic (vagus) Nerve
The heart receives outgoing branches of the vagus nerve coming from the cardio inhibitory
centre.
The fibers from the right vagus end mainly at SA Node and those from the left at AV node.
The impulses are continually passed the vagus nerve to retard the heart rate This is called vagal tone
Simulation of vagus retards the heart rate, increases the diastolic interval and ventricular filling. This increases the stroke volume
Sympathetic Nerves
The sympathetic nerves ordinate at cardioacceleratory centre and pass from the upper
thoracic region of the spinal cord.
Stimulation of sympathetic nerve affect mainly the SA node and increases the heart rate.
Sympathetic nerve also constantly transmits impulses like vagus, called sympathetic tone
Excitement fear, anger and fright increase the heart rate and cardiac output.
Cardiac Reflexes
Stimulation of any sensory nerve (afferent) in the body may cause a change in the cardiac
rate. Depending on the nature of the stimulus it may result in an increase or decrease in it.
For example, a pungent odor may inhibit the heart rate. This effect is mediated by the
stimulation of the fifth cranial nerve in the nose. Sinus nerve endings are situated in the
carotid sinus. This nerve is stimulated by an increase in the arterial blood pressure and
causes reflex slowing of the heart rate.
Afferent and efferent fibers contained within the vagus nerve are responsible for
bringing about the reflexes.
Afferent fibers in the aortic arch and the left side of the heart are stimulated by a
rise in the arterial blood pressure and the impulses increase the tone of the cardioinhibitory centre.
Afferent nerves on the right side are stimulated by arise in the venous blood in the great veins and auricle. They cause acceleration of the heart rate by inhibiting the cardioinhibitoy centre.
Bainbridge reflex: This results in an increase in the heart rate due to arise in the
venous blood pressure. As the heart is filled with the venous blood , the vagal
afferent nerve endings situated in the right auricle are stimulated and set up
impulses that depresses the tone of the cardioinhibitory centre. The heart rate is
automatically adjusted to the quantity of the venous blood flowing through the heart.
Bainbridge reflex increases the heart rate during exercise to adjust the pump to
increased blood brought to it from exercising muscle.
Marey’s law; It states that heart rate is inversely related to the arterial blood
pressure. A rise in the blood pressure decreases the heart rate and fall in blood
pressure increases it. These effects are brought about by afferent vagal in aorta
and sinus nerve
Value addition: Did you Know
Heart rate Tachycardia: Increased heart rate Bradicardia: Decreased heart rate
Source: Tortora, G.J. & Grabowski, S. (2006). Principles of Anatomy & Physiology. XI Edition John Wiley & sons, Inc.
Chemical control of Heart Beat
The heart rate is influenced by the action of adrenaline, noradrenaline and acetylcholine.
These effects are similar to the stimulation of sympathetic and parasympathetic(vagus)
nerves . Adrenaline increases the heart rate and acetylcholine decreases it. A low oxygen
pressure in the blood causes an increase in the heart rate. But if there is prolonged anoxia
the heart muscles are not able to contract for long and the rate is slowed down
Electrocardiogram (ECG)
Einthoven a Dutch physiologist is considered to be the father of electrocardiography. ECG is
a tool for evaluating the electrical events taking place within the heart.
As discussed in the previous segment, human heart is myogenic and heart beat originates
at SA node, from where it spreads into the entire heart in a definite sequence
Principle of Electrocardiography
The electrical currents (action potential) generated at the heart travel into the whole body
which acts as a volume conductor. Blood and the tissue fluids have a high electrical
conductivity and the impulses travel down the surface of the body, which can be recorded
on the galvanometer.
These electrical events are recorded on an instrument called electrocardiograph. The
electrocardiograph paper is calibrated to record the amplitude and duration of each event.
X- axis is calibrated for time and Y- axis for amplitude.
Fig. Three Bipolar Limb leads
Source:http://www.open-ecg-project.org/tiki-index.php?page=ecg+leads
Recording of the Electrocardiogram
Two types of lead systems are used to record electrocardiogram, namely unipolar and
bipolar. In unipolar system one of the electrode called “p” is placed away from the exploring
electrode “e”. The exploring electrode is used to measure the potential in any part of the
body (volume conductor) which is placed at various positions on the chest, right arm, left
arm and left foot.
Bipolar lead system is commonly used to record the ECG in which both the electrodes are
placed on the surface.Right arm, left arm and left leg are used to measure the potential.
Lead I (- ve )electrode at right arm and (+ ve) electrode at left arm. The voltage recorded is 0.5 mv
Lead II (- ve ) electrode at right arm and (+ve) electrode at left leg. The voltage
recorded is 1.2mv
Lead III ( -ve ) electrode at left arm and (+ve) electrode at left leg. The voltage
recorded is 0.7
R A Lead I (-0.5mv) LA
Lead II Lead III
(1.2mv) (0.7mv)
LL
Components of ECG
Fig. Einthoven triangle
Source: Author
‘P’ wave: It is due to depolarization of the atria. It is measured in seconds from the
beginning to the end of the wave. Its duration is 60 to 100 msec. It represents the
depolarization wave of the auricular musculature which spreads readily from SA node to
AV node and entire atrium.
PR interval: It is measured from the beginning of P wave to the beginning of QRS
complex. It lasts for 120 to 200 m sec.
QRS complex: It is the depolarization of the ventricular musculature It lasts for 0,1 sec.
QRS interval: It is measured from the beginning of the Q wave to the end of the S wave.
‘T’ wave: It is the wave of ventricular repolarization.
Fig.The events of a normal electrocardiogram
Source: Author
Significance:
(i) A change in the sequence, duration or amplitude in the ECG recording indicates an
abnormality in the functioning of the heart. For example myocardial infaction causes
abnormal ECG recording.
(ii) The heart beat rate can be determined from the ECG the heart rate is reciprocal of the
time interval between the successive beats. If the interval is 1 msec the rate is 60 beats per
second. The normal interval observed is 0.83 sec. So rate is 72 beats per min
1 x 60 = 0.83 sec.
72
34 Institute of Life Long Learning, University of Delhi
Value addition: Did you Know
Myocardial infarction Myocardial infarction (MI) or acute myocardial infarction (AMI), commonly
known as a heart attack, is the interruption of blood supply to a part of the heart,
causing heart cells to die. This is most commonly due to occlusion (blockage) of a
coronary artery following the rupture of a vulnerable atherosclerotic plaque, which is
an unstable collection of lipids (fatty acids) and white blood cells (especially
macrophages) in the wall of an artery. The resulting ischemia (restriction in blood
supply) and oxygen shortage, if left untreated for a sufficient period of time, can cause damage or death (infarction) of heart muscle tissue (myocardium).
Source: Tortora, G.J. & Grabowski, S. (2006). Principles of Anatomy & Physiology. XI Edition John Wiley & sons, Inc.
Blood Circulation
Oxygenated and deoxygenated blood is completely separated in the heart due to the
complete partioning of the ventricles. That is why it is called double circulation
Pulmonary circulation: Right pulmonary artery takes the deoxygenated blood from the
right ventricles to the lungs. Pulmonary vein brings back the oxygenated blood into the left
arrium
Systemic circulation: deoxygenated blood from the body is brought back into the right
atrium by the veins and from the left ventricle the oxygenated blood is pumped into the
body
Fig. Double circulation
Source: http://txacupuncturedoc.blogspot.com/2010/11/10-things-your-doctor-
doesnt-know-about.html
Blood pressure
Definition
Blood pressure (BP) is the pressure exerted by circulating blood upon the walls of blood
vessels. It changes with the systole and diastole of the cardiac cycle.
Systolic and Diastolic blood pressure:During systole of the heartbeat, it is maximum and called systolic pressure and during diastole it is minimum and is known as diastolic pressure.
The mean blood pressure decreases as the circulating blood moves from the heart
through the arteries due to resistance to flow in blood vessels,
Blood pressure decreases as the blood passes through the small arteries and arterioles,
and continues to drop as the blood reaches the capillaries and back to the heart through veins.
Arterial pressure may vary in individuals from moment to moment.
Gravity and pumping from contraction of skeletal muscles, are some other influences on
blood pressure at various places in the body. Blood pressure is the pressure measured at a person's upper arm's (inside of an
elbow) major blood vessel, brachial artery, that carries blood away from the heart.
Table. Blood pressure under normal and hypertension
CATEGORY SYSTOLIC, mm Hg < 120
DIASTOLIC, mm Hg < 80
Normal 120 – 139 80 – 89
Stage I, Hypertension 140 – 159 90 – 99
Stage II, Hypertension 160 - 179 100 - 109
Hypertensive crisis ≥ 180 ≥ 110
Measurement of Blood pressure
Fig. Aneroid
Sphygmomanometer with Stethoscope
Fig Mercury manometer
Auscultatory method
The auscultatory (Latin word meaning "listening") method uses a stethoscope and a
sphygmomanometer to measure the blood pressure of a person. It is used for the clinical
measurement of hypertension in high-risk patients, such as pregnant women.It comprises
of an inflatable cuff which is placed around the upper arm at roughly the same vertical
height as the heart. It is attached to a mercury or aneroid manometer which measures the
height of a column of mercury giving an absolute result.
Procedure:
A cuff of appropriate size is fitted smoothly around the upper arm at roughly the
same vertical height as the heart.
The cuff is then inflated manually by repeatedly squeezing a rubber bulb until the
artery is completely occluded.
The pressure is slowly released in the cuff by simultaneously listening to the sounds
in the stethoscope . When blood just starts to flow in the artery, the turbulent flow creates a "whooshing"
or pounding (first Korotkoff sound). The pressure at which this sound is first heard is the systolic blood pressure.
The cuff pressure is further released until no sound can be heard (fifth Korotkoff sound). It is the diastolic arterial pressure.
Oscillometric method
The observation of oscillometric method involves the oscillations in the sphygmomanometer
cuff pressure caused by the oscillations of blood flow, i.e., the pulse. It was first
demonstrated in 1876. The electronic version of this method is sometimes used in long-
term measurements and general practice. It uses a sphygmomanometer cuff, like the
auscultatory method, but with an electronic pressure sensor (transducer) to observe cuff
pressure oscillations. These oscillations are then automatically interpreted with automatic
inflation and deflation of the cuff. The pressure sensor should be calibrated periodically to
maintain accuracy.
Oscillometric measurement requires less skill than the auscultatory technique and may be
suitable for use by untrained staff and for automated patient home monitoring.
Pulse pressure
Pulse pressure is the difference between the systolic and diastolic pressure i.e. (120 - 80 )
= 40mmHg.
The up and down fluctuation of the arterial pressure results from the pulsatile nature of the
cardiac output, i.e. the heartbeat. The pulse pressure is determined by:
The interaction of the stroke volume of the heart,
Compliance (ability to expand) of the aorta, and
The resistance to flow in the arterial tree or the speed of ejection of the stroke volume.
By expanding under pressure, the aorta absorbs some of the force of the blood surge from
the heart during a heartbeat. In this way the pulse pressure is reduced from what it would
be if the aorta wasn't compliant. The loss of arterial compliance that occurs with aging
explains the elevated pulse pressures found in elderly people.
Mean Arterial Pressure
The mean arterial pressure is the average over the entire cardiac cycle and is very
impotant in driving the blood into the tissues. It is measured as
MAP = DP + 1/3 (SP – DP)
= 80 + 1/3(40) = 93.3
Regulation of Blood pressure
Three mechanisms of regulating arterial pressure have been well-characterized:
Baroreceptor reflex: In the left and right carotid sinuses and aortic arch, arterial
baroreceptors are located which are most important for baroreceptor reflexes. The
changes in arterial pressure are detected by the Baroreceptors which sends the
signals to the medulla of the brain stem. The medulla alters both the force and speed
of the heart's contractions, as well as the total peripheral resistance thereby
adjusting the mean arterial pressure , through the autonomic nervous system.
Renin-angiotensin system (RAS): RAS is known for its long-term adjustment of
arterial pressure. The kidney activates an endogenous vasoconstrictor known as
angiotensin II that allows compensating for loss in blood volume or arterial pressure
drop.
Aldosterone release: Aldosterone, released from the adrenal cortex in response to
angiotensin II or high serum potassium levels, stimulates sodium retention and
potassium excretion by the kidneys. Since the amount of fluid in the blood vessels by
osmosis is determined by sodium ion, aldosterone increases fluid retention, and
indirectly, increases arterial pressure.
Summary
Heart is a hollow muscular organ of about the size of a clenched fist in the thoracic
cavity. It serves as a pump that imparts pressure for the blood to flow to the tissues.
Even though heart is a single organ , the right and left side of the heart act as two separate pumps.
It is enclosed in a double walled pericardial sac.
Heart wall is made up of three layers- epicardium ,myocardium and endocardium
There are two types of myocardial cells – working myocardial cells and conducting
myocardial cells
Atrioventricular valves(AV valves) between the atrium and ventricle prevent the flow
of blood from the ventricle into the auricle Semilunar valves between the ventricle and aorta prevent the flow of blood from
aorta back into the ventricle.
The SA node manifests a pace maker potential which brings its membrane potential
to threshold and initiates an action potential. Calcium mainly released from the sarcoplasmic, (diads and triads) reticulum
functions as excitation – contraction coupling reaction.
Cardiac muscle can not undergo summation of contractions because it has a very
long refractory period. Cardiac cycle is divided into two main events- systole (contraction) and diastole
(relaxation).
Atria continuously receive the venous blood from the pulmonary vein (left) and body (right) during diastole.
Through the atrio-ventricular valves the blood enters into the ventricles- ventricular
filling takes place during atrial systole the ventricles are completely filled with blood
and their increases , AV valves are closed. The amount of blood in the ventricles
just before diastole is called end diastolic volume
During early ventricular systole, which is isovolumetric contraction as the AV valves
and SL valves are closed ventricular, there is an increase in ventricular pressure.
This then causes the opening of the SL valves and rapid ejection of blood into the
aorta. This is followed by a slow ejection phase
As the pressure in aorta exceeds the ventricular pressure, SL valves close. AV
valves are still closed as the ventricular pressure is greater than atrial pressure.
Ventricle enter into diastole. This is isovumetric relaxation of the ventricles.
As there is a further decrease in ventricular pressure due to their relaxation AV
valves open Equal volume of the blood is pumped out by both the ventricles, which is known as
Stroke volume.(70 ml/beat) The amount of blood pumped out by heart per minute is called as cardiac out put
The cardiac center located in the medulla has cardio- acceleratory and cardio- inhibitory center. Vagal branches are connected at the cardio- inhibitory center. The cardio-acceleratory centre is connected through nerve tract to the spinal gray matter in the upper five thoracic segments
The postganglionic nerve fibers arise from stellate ganglion and the, middle and
superior cervical ganglion of sympathetic cord. They pass to the heart from the
upper two thoracic ganglion.
Heart receives continuous impulses from the sympathetic and vagus nerves.
ECG , records the electrical events of the heart and used as a diagnostic tool for the
cardiac diseases
Arterial blood pressure changes with the systole and diastole of the cardiac cycle
Systolic pressure:During systole of the heartbeat, the pressure is maximum and called systolic pressure It amounts to 120 mm of Hg.
Diastolic blood is observed during diastole of heart It is minimum and It imesures
80 mm of Hg.
The Mean Blood Pressure decreases as the circulating blood moves from the heart through the arteries due to resistance to flow in blood vessels,
Glossary
Atrio -ventricular node (AV node): It is located in the wall of the right atrium
immediately behind the tricuspid valve adjacent to the opening of the coronary sinus.
Function of AV node is to delay the transmission of impulses to the ventricles. Impulses
after originating at the SA
Auscultatory method: The auscultatory (Latin word meaning "listening") method uses a
stethoscope and a sphygmomanometer to measure the blood pressure of a person. It is
used for the clinical measurement of hypertension in high-risk patients, such as pregnant
women. It comprises of an inflatable cuff which is placed around the upper arm at roughly
the same vertical height as the heart. It is attached to a mercury or aneroid manometer
which measures the height of a column of mercury giving an absolute result.
Bainbridge reflex: This results in an increase in the heart rate due to arise in the venous
blood pressure. As the heart is filled with the venous blood, the vagal afferent nerve
endings situated in the right auricle are stimulated and set up impulses that depresses the
tone of the cardioinhibitory centre. The heart rate is automatically adjusted to the quantity
of the venous blood flowing through the heart. Bainbridge reflex increases the heart rate
during exercise to adjust the pump to increased blood brought to it from exercising muscle.
Cardiac cycle: The cardiac events that occur from the beginning of one heartbeat to the
next are called cardiac cycle. Two main events of the cardiac cycle are systole the
contraction phase and diastole the relaxation phase of the cardiac muscles.
Cardiac index. Cardiac index is the cardiac output per square meter. For an average adult
it is 3 liters / min / m 2
Cardiac output: It is the volume of blood being pumped by the by a left or right ventricle
in the time interval of one minute. Cardiac output may be measured in many ways, for
example dm3/min (1 dm3 equals 1000 cm3 or 1 liter). An average resting cardiac output
would be 5.6 liters /min for a human male and 4.9 liters / min for a human female.
Coronary circulation is the circulation of blood in the blood vessels of the heart muscle
(the myocardium). The vessels that deliver oxygen-rich blood to the myocardium are known
as coronary arteries. The vessels that remove the deoxygenated blood from the heart
muscle are known as cardiac veins.
Fibrous pericardium: It consists of very heavy fibrous connective tissue and prevents
heart from over distension and also anchors it in the mediastinum.
Frank Starling law of the heart It states that the heart will pump out all the blood,
during systole which is delivered to it by the veins during diastole.
Internodal Pathways: Some of the are highly modified atrial fibers conduct the impulses
from SA node to the AV node very rapidly and are called Internodal pathways. They conduct
the impulses at a rate of 1 meter per second whereas in other fibers conduction velocity is
0.3 m/sec. Anterior intermodal pathways transmit the impulses rapidly to the left atrium.
Marey’s law: It states that heart rate is inversely related to the arterial blood pressure. A
rise in the blood pressure decreases the heart rate and fall in blood pressure increases it.
These effects are brought about by afferent vagal in aorta and sinus nerve
Mean Arterial Pressure: The mean arterial pressure is the average over the entire
cardiac cycle and is very impotant in driving the blood into the tissues. It is measured as
MAP = DP + 1/3 (SP – DP) , ( = 80 + 1/3(40) = 93.3 ). The mean blood pressure
decreases as the circulating blood moves from the heart through the arteries due to
resistance to flow in blood vessels,
Myogenic heart : The heart beat originates with in the cardiac muscles in contrast to the
neurogenic heart in which the heart beats only on receiving the nervous stimulus.
Purkinje fibers The distal portion of the AV bundle divides into the left and right branches
beneath the endocardium giving out the Purkinje fiber that pass through the ventricular
muscles.
Renin-angiotensin system (RAS): The kidney compensates for loss in blood volume or
drops in arterial pressure by activating angiotensin II (an endogenous vasoconstrictor). It is
generally known for its long-term adjustment of arterial pressure.
SA node: It is located in the superior wall of the right atrium where the superior vena cava
opens into it. It is a ellipsoidal strip of specialized muscle about 3mm wide, 15 mm long and
1 mm thick. These fibers have no contractile filaments and are 3 to 5 micrometer in
diameter. SA nodal fibers are directly connected to the atrial muscle fibers.
Serous pericardium: It is made up of two layers, the parietal pericardium and the
visceral pericardium separated by a pericardial cavity that is filled with the pericardial fluid
Systolic and Diastolic blood pressure: During systole of the heart beat, the pressure is
maximum and is called systolic pressure and during diastole it is minimum and is known as
diastolic pressure.
The wall : The heart is made up of three layers Epicardium
and Endocardium (inner) layer
(outer), Myocardium (middle)
Vagal tone: It is the continuous discharge of impulses from the cardioinhibitory center
through the vagus nerve to the heart
Working myocardial cells:They are structurally and functionally the contractile myocardial
cells and make up the main bulk of the atria and ventricles
Exercises
1. Give the differences between conducting and working myocardial cells
2 Describe the structure of heart wall.
3. Explain the differences between cardiac and skeletal muscle cells.
4. What are the functions of intercalated discs and its nexus?
5. Explain by what mechanism does SA node function as a pace maker for the entire heart.
6. Describe the sequence of events leading to excitation contraction coupling in cardiac
muscle cells.
7. What prevents heart from undergoing summation of contraction?
8. What is an electrocardiogram? How is it recoded? Explain its clinical significance.
9. With the help of suitable diagram explain the pressure changes on the left side of the
heart during cardiac cycle.
10. What is cardiac output ?How can it be calculated ? Difference between cardiac output
and cardiac index.
11 Explain Frank Starling law of heart. How does it control the stroke volume?
12. How does the autonomic nervous system control the heart in mammals when it is
myogenic?
13. Summarize the various factors that that control the cardiac output.
14. What is isovolumetric contraction of the heart and when does it occur during cardiac
cycle?
15. Explain the reflex control of heart beat.
16. Give various methods used to measure the blood pressure?
17. What is the effect of sympathetic stimulation on end diastolic pressure?
18. With the help of flow diagram give the path of blood flow through the entire
cardiovascular system.
19. What is end diastolic pressure? How does it help in determining the stroke volume?
20. How is blood pressure regulated in the body?
21. Where is AV node located? What is its function?
Works Cited
References
Tortora, G.J. & Grabowski, S. (2006). Principles of Anatomy & Physiology. XI
Edition John Wiley & sons, Inc. Text book of physiology and Biochemistry by Bell, Smith and Paterson
Guyton, A.C. & Hall, J.E. (2006). Textbook of Medical Physiology. XI Edition.
Hercourt Asia PTE Ltd. /W.B. Saunders Company.
Ganong, William F. Review of Medical Physiology. XXI Edition. Mc Graw Hill