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