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INTRODUCTION

Circulatory System consists of three basic components:-

Heart-Serves as pump that establishes the pressure gradient needed for blood to flow to tissues;

Blood vessels-Passageways through which blood is distributed from heart to all parts of body and back to heart;

Blood is a transport medium within which materials being transported are dissolved or suspended

Cardiovascular system has only one function that to transport the following via blood:-Gases (CO2,O2), nutrients (glucose, amino acids), immune cells and immune bodies (WBCs), hormones, waste products (urea, creatinine), procoagulants and anticoagulants, drugs, heat from actively metabolizing organs (liver) to the skin so that heat of internal environment of the body is dissipated to the external environment.The cardiovascular system is divided into two circuits:- Pulmonary circuit that transports blood to and from the lungs and Systemic circuit that transports blood to and from the rest of the body.

Vessels carry the blood through the circuits-Arteries carry blood away from the heart,Veins carry blood to the heart and Capillaries permit this exchange.

HISTORY

William Harvey (1578-1657) of England –discovered that blood circulates driven by the heart

Frank-Starling law was discovered by Otto Frank of Germany in 1896. Ernst Henry Starling(1866-1927) of England showed that this law is applicable in mammals.(1914)

First paper on cardiac electrophysiology was published in 1870 by John Scott Bourdon-Sanderson(1825-1905) of Great Britian.

Stethoscpe was discovered by-Renne Lannec in 1816.

Andre Cournad ,Dickinson Richard ,Werner Frossmann in 1956 were awarded nobel prize for cardiac catheterization.

DEFINITIONS

Heart- The viscus of cardiac muscle that maintains the circulation of the blood. also called cor

Heart sounds-defined as relative,brief, auditory vibrations of variable intensity, frequency and quality

Blood pressure- is the lateral pressure exerted by the blood on the arterial walls.

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GROSS ANATOMY OF HEART AND BLOOD FLOW THROUGH THE HEART

Human heart consists of four chambers, two atria and two ventricles. The superior venacava, draining the body from above the diaphragm as well as the inferior venacava, draining the body from below the diaphragm both open into the right atrium. From the right atrium, blood enters the right ventricle. In between the right atrium and right ventricle there is right atrioventricular orifice, guarded by the right atrioventricular valve.

The right ventricle then pumps out the blood so that the blood enters the pulmonary artery→ the pulmonary artery divides into the right and left branches to supply right and left lungs respectively. In the lungs the venous blood is purified.

From the lungs the purified blood returns by four pulmonary veins to the left atrium. The orifice of the pulmonary artery is guided by pulmonary valve.

FUNCTIONS OF THE HEART:- Generating blood pressure, Routing blood (Heart separates pulmonary and systemic circulations and Ensures one-way blood flow),Regulating blood supply

Changes in contraction rate and force match blood delivery to changing metabolic needs

Blood Flow Through Heart

Autorhythmic cells

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ELECTRICAL ACTIVITY OF HEART

Heart beats rhythmically as result of action potentials it generates by itself .This is known as autorhythmicity.

Two specialized types of cardiac muscle cells are present which are:

a. Contractile cells that constitute 99% of cardiac muscle cells and are responsible for the mechanical work of pumping. These normally do not initiate own action potentials.

b. Autorhythmic cells which do not contract and are specialized for initiating and conducting action potentials responsible for contraction of working cells.

Myocardial cells are elongated, branching cells containing 1-2 centrally located nuclei.They contain actin and myosin myofilaments .Each myocardial cell is joined to the other at Intercalated disks that are specialized cell-cell contacts. Desmosomes hold the cells together and gap junctions allow action potentials to move from one cell to the next.

ELECTRICAL PROPERTIES OF MYOCARDIAL FIBERS

Electrically, cardiac muscle of the atria and of the ventricles behaves as single unit. There are three phases of the cardiac muscles:

1. Rising phase of action potential -Due to opening of fast Na+ channels

2. Plateau phase in which there is closure of sodium channels and opening of calcium channel. Slight increase in K+ permeability is also present which prevents summation and thus tetanus of cardiac muscle.

3. Repolarization phase-Calcium channels are now closedand an increased K+ permeability occurs.

Mitochondria comprise 30% of volume of the cell in the myocardial cells as compared to 2% in skeletal muscle cells.

CONDUCTION SYSTEM OF HEART

Heartbeat is actually the rhythmic contraction of the heart's four chambers. Each heartbeat is stimulated by electrical signals that travel through a specific nerve pathway in the heart

Approximately 1% of the cardiac muscle cells are autorhythmic rather than contractile. These specialized cardiac cells donot contract but are specialized to initiate and conduct impulses through the heart to coordinate

Conduction system of heart

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its activity. These constitute the intrinsic cardiac conduction system and generate spontaneous action potentials .

These autorhythmic cells constitute the following components of the intrinsic conduction system:-

1. The heart's electrical signal begins at the sino-atrial node, or SA node. Sinoatrial (SA) node located just inferior to the entrance of the superior vena cava into the right atrium serves as the heart's pacemaker, emitting an impulse that results in an action potential. Action potential spreads immediately into the atrial cardiomyocytes and is transmitted through the entire atrial muscle mass transporting of the conductive impulse to the atrial-ventricular (A-V) node within 30 msec. The signal that travels to both the right and left atria, causes them to contract and push blood into the lower chambers, or ventricles.

2. Atrioventricular node (AV) node is located just above the tricuspid valve in the lower part of the right atrium.

3. Atrioventricular bundle (bundle of HIS), located in the lower part of the interatrial septum and which extends into the interventricular septum (passes through hole in cardiac skeleton to reach interventricular septum) where it splits into

4. right and left bundle branches which continue toward the apex of the heart (extend beneath endocardium to apices of right and left ventricles) and

5. the purkinje fibers which branch off of the bundle branches to complete the pathway into the apex of the heart and turn upward to carry conduction impulses to the papillary muscles and the rest of the myocardium. The Purkinje fibers have large diameter cardiac muscle cells with few myofibrils and many gap junctions. They conduct action potential to ventricular muscle cells. These large cells that are able to transmit the action potential at 2−4 m/s ( rate six times that of normal ventricular cardiomyocyte). The impulse is transmitted through the entire Purkinje fiber system within 30 msec .

Although all of these are autorhythmic, they have different rates of depolarization. For instance, the SA node depolarizes at a rate of 75/min. The AV node depolarizes at a rate of 40 to 60 beats per minute, Action potentials are conducted more slowly here than in any other part of system. This ensures ventricles receive signal to contract after atria have contracted. Atrioventricular (AV) node delays the impulse approximately 0.1 second. Delay of

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130 msec in the A-V node and bundle of his occurs during which time the atria can contract, filling the ventricles. The rest have an intrinsic rate of around 30 depolarizations/ minute. Because the SA node has the fastest rate, it serves as the pacemaker for the heart. The conducting impulse is then propagated through the specialized Purkinje cells of the conduction system- rhythmic and concerted ejection of blood from the ventricles take place to the lungs and body, completing the heartbeat. The conduction system functions as the body's own pacemaker and keeps the heart beating at a normal rate of 60 to 100 beats per minute.

THE CARDIAC CYCLE

Cardiac cycle refers to all events associated with blood flow through the heart from the start of

one heartbeat to the beginning of the next. During a cardiac cycle each heart chamber goes through systole (contractile phase) and diastole (relaxation phase). Correct pressure relationships are dependent on careful timing of contractions.It lasts 0.8 sec ( atrial systole-

0.1sec and atrial diastole-0.7sec) and its purpose is to effectively pump blood. The volume of blood ejected by right ventricle to lungs is same to the volume of blood ejected by the left

ventricle. Heart is two pumps that work together, right and left half.Repetitive contraction

(systole) and relaxation (diastole) of heart chambers occurs. Blood moves through circulatory system from areas of higher to lower pressure.

Phases of the Cardiac Cycle

Atrial diastole and systole: During atrial diastole and systole blood flows into and passively out of atria (80% of total).The AV valves are open. Atrial systole pumps only about 20% of blood into ventricles. Ventricular filling occurs during mid-to-late diastole. Heart blood pressure is low as blood enters atria and flows into ventricles. About 80% of blood enters ventricles passively. AV valves are open, then atrial systole begins . It pumps the remaining 20% of blood into ventricles.

Ventricular systole: During the ventricular systole atria relax. Rising ventricular pressure results in closing of AV valves (1st heart sound - ‘lubb’).This is the Isovolumetric contraction phase where the ventricles are contracting but no blood is leaving as ventricular pressure is not great enough to open semilunar valves.

The ventricular ejection phase opens the semilunar valves. Ventricular pressure is now greater than pressure in arteries (aorta and pulmonary trunk)

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Ventricular diastole: During this phase ventricles relax. The backflow of blood in aorta and pulmonary trunk closes semilunar valves (2nd hear sound - “dubb”). Dicrotic notch is seen asd a brief rise in aortic pressure caused by backflow of blood rebounding off the semilunar valves. The blood once again starts flowing into relaxed atria and passively into ventricles and this Cardiac cycle is repeated over 100,000 times daily.

Cardiac Cycle-Mechanical Events

HEART SOUNDS

First heart sound or “lubb” signals beginning of ventricular systole (0.09-0.16sec). It can be heard over left 5th

intercostal space, medial to mid clavicular

line. AV valves close and surrounding ventricles and blood vibrates at systole. It coincides with R wave of ECG.

Second heart sound or “dupp”is of high pitch and can be heard over left 2nd or 3rd intercostal

space, close to border of sternum.It results from closure of aortic and pulmonary semilunar valves at ventricular diastole,(0.01-0.04sec|).

Third sound can be heard sometimes in the rapid ventricular filling phase when intraventricular pressure is very low and AV valves open.

Fourth heart sound is an atrial sound that signifies the last rapid filling phase(atrial contraction).

REGULATION OF THE CARDIAC CYCLE

Sympathetic and parasympathetic autonomic nervous systems are responsible for the regulation of cardiac cycle.

Parasympathetic :- The parasympathetic fibres arise from medulla oblongata and are lodged in

START Late diastole: both sets ofchambers are relaxed andventricles fill passively.

Atrial systole: atrial contraction forces a small amount of additional blood into ventricles.

Isovolumic ventricular contraction: first phase of ventricular contraction pushes AV valves-closed but does not create enough pressure to open semilunar valves.

Isovolumic ventricularrelaxation: as ventricles relax, pressure in ventricles falls, blood flows back into cups of semilunar valves and snaps them closed.

Ventricular ejection: as ventricular pressure rises and exceeds pressure in the arteries, the semilunar valves open and blood is ejected.

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the vagus nerve.This nerve branches to S-A and A-V nodes and secretes acetylcholine (slows rate of the heart ). Parasympathetic activity can increase (which will cause a slow heart rate) or decrease (which can increase heart rate)

Sympathetic nervous system :-supplies through celiac plexus to heart and secretes norepinephrine which increases force of contractions of heart.

Cardiac control center in medulla oblongata helps to maintain balance between the two. Normally both sympathetic and parasympathetic function at a steady background level.

BLOOD PRESSURE: It is the force that is exerted by blood against blood vessel walls. Resistance of the vessel wall depends on size of blood vessel and thickness (viscosity) of blood. The rising pressure stretches receptors. (Baroreceptors detect changes in blood pressure).Blood pressure is highest in large arteries and it rises and falls as heart pumps.It is highest with ventricular systole and is lowest with ventricular diastole.

Pulse pressure is the difference between the two (systole-diastole).

Resistance is highest in the capillaries.

CARDIAC OUTPUT (CO)

Cardiac Output can be of two types :- stroke volume and minute volume.

Stroke Volume is the volume of ejection/ventricle/beat and normally stroke volume of right ventricle (RV) = stroke volume of left ventricle (LV). Normal resting value of cardiac output is about 70 ml.

Minute volume is the output of one ventricle in one minute ,i.e.it is stroke volume x heart rate. Normal resting value is 70 ml x70 = about 5 litres/min. Normally, cardiac output means minute volume (or output).

Cardiac Output is the product of heart rate (HR) and stroke volume (SV)

CO = HR x SV

(ml/min) = (beats/min) x ml/beat

Heart rate is the number of heart beats per minute.

Stroke volume is the amount of blood pumped out by a ventricle with each beat.

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Cardiac reserve is the difference between resting and maximal Cardiac Output.

The cardiac output changes according to the demands of the body. Cardiac output at rest ranges between 4 to 6 liters per minute; it can increase to 25 litres/min with strenous exercise or fall when tissue demand is low. Thus, it is adjustable and the adjustment occurs through the controlling mechanisms of heart.

Demand pump: The fundamental job of the heart is to act as a pump to produce cardiac output. But the volume of the output( the pumping action of the heart) depends on the demands of the body.

Reciprocating pump: The heart acts as a reciprocating pump. The events of the pumping action of heart follow a cyclic pattern, same sequence of events occur cycle after cycle.

The cardiac output is a fundamental determinant of blood pressure, which in turn determines the supply of blood to various tissues including the vital tissues. So, if the cardiac output falls, the vital tissues suffer (in conditions like shock).

FACTORS AFFECTING CARDIAC OUTPUT

Cardiac Output = Heart Rate X Stroke Volume

Heart rate : It chiefly depends on ANS activity. Increase of heart rate, upto a point increases cardiac output but severe increase ( >180/min) reduces the cardiac output as in a state where there is severe tachycardia,the diastole is shortened leading to drastic reduction of ventricular filling leading to fall of cardiac output. Heart rate depends on the following :-

1. Autonomic innervation 2. Hormones - Epinephrine (E), norepinephrine(NE), and thyroid hormone (T3)3. Cardiac reflexesStroke volume : It depends on central venous pressure (CVP) ,which is the preload .Greater is the CVP ,by Frank Starling’s mechanism greater is the cardiac output. Cardiac inflow rises in conditions like physical exercise/ i.v fluid transfusion. Conversely, the CVP falls sharply in severe hemorrhage. Stroke volume also depends on myocardial contractility. It increases in sympathetic stimulation (due to increase influx of calcium ions within the myocardial cells). Contractility diminishes in hyperkalemia. Main factors that influence the stroke volume thus can be summarized as under:-

1. Starlings law2. Venous return3. Cardiac reflexesIntrinsic factors : results from normal functional characteristics of heart - contractility, HR, preload stretch-Frank-Starling mechanism (law) of the heart.

Extrinsic factors : involves neural and hormonal control – Autonomic Nervous system.

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Factors Affecting Cardiac Output

HEART RATE (HR)

Homeostasis of heart rate is necessary as both high heart rates and low heart rates are bad for health. Very high heart rates can produce low stroke volume, attacks of ischemic heart disease,etc.Pulse is the surge of pressure in an artery. Infants have a heart rate of 120 beats per minute or more. Gross bradycardia can also produce low cardiac output, syncopal attacks ,etc. Young adult females have an average heart rate of 72 - 80 beats per minute. Young adult males have an average heart rate of 64 to 72 beats per minute. Heart rate rises again in the elderly.

Tachycardia is an increase in the heart rate when the resting adult heart rate is above 100 beats per minute. Tachycardia is seen in the conditions of stress, anxiety, with use of certain drugs (sympathomimetics-alpha and beta-2 agonists like adrenaline, salbutamol & parasympathetics), heart disease or rise in body temperature.

Bradycardia is a decrease in heart rate when the resting adult heart rate is less than 60 beats per minute. Bradycardia is physiologically seen in sleep and endurance trained athletes.

Both sympathetic and parasympathetic nerves supply the heart. They produce opposite effects on the heart. All neural influences are mediated via ANS. The sympathetic and parasympathetic nerves are called as the final effector nerves. These are influenced by higher centres in the brain and various reflexes from the periphery.

EXTRINSIC INNERVATION OF THE HEART

Vital centers of medulla:-

Control of sympathetic system by brainstem areas-

Extrinsic Innervation of the Heart

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In the medulla, there is an area on the either side called RVLM (rostral ventro-lateral medulla). From the RVLM, fibers called bulbospinal pathway, emerge and terminate on the lateral horn cells also called as intermediolateral gray column.

From the lateral horn cells, the preganglionic sympathetic fibers arise. The neurotransmitter released at the end of bulbospinal fibers are glutamate .

The Nucleus tractus solitarius (NTS), via CVLM (caudal ventrolateral medullary) area is connected with the RVLM (rostral ventro-lateral medulla). NTS via neural connections are influenced by various cardiovascular reflexes. At the endings of afferent nerves of these cardiovascular reflexes (terminating on NTS), the usual neurotransmitter is glutamate. The VMC (vaso motor center) also receives many fibers from other parts of brain.

These vital centers includes the cardiac center which has the cardio accelerator center and cardioinhibitory center. Cardio accelerator occupies the dorsal and lateral regions of medulla. It activates sympathetic neurons that increase heart rate.

Cardioinhibitory center situated caudal and ventromedial to the pressure area i.e cardio accelerator center activates parasympathetic neurons that decrease heart rate, it inhibits the sympathetic system by inhibiting the pressure area of medulla as well as as direct inhibition of lateral horn cells.

Brainstem control of vagal parasympathetic – both dorsal motor nucleus of the vagus and nucleus ambiguous are situated in the medulla. From them parasympathetic fibers of vagus arise and supply the heart. Nucleus tractus solitarius inhibits both dorsal nucleus of vagus and nucleus ambiguous.

Cardiac center receives input from higher centers (hypothalamus), monitoring blood pressure and dissolved gas concentrations.

REGULATION OF HEART RATE :

Cortical and Peripheral Influences

Cerebral cortex impulses pass through medulla oblongata

Neural regulation: is by both sympathetic and parasympathetic nerves.

Parasympathetic stimulation – The parasympathetic fibres supplying the heart are lodged in the right and left vagus. These vagal parasympathetic fibres, arise from nucleus ambiguous or dorsal nucleus of the vagus in the brainstem. These fibres are preganglionic fibers that enter to

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form cardiac plexus and then relay in the ganglia situated very close to the heart or in the walls of the heart. The post-ganglionic vagal fibres ,therefore , are very short. These fibres supply the sinoatrial node, AV node, atrial muscles but not the ventricles.

Vagal stimulation has no direct effect on the ventricles. The parasympathetic stimulation is a negative chronotropic factor. The rate of impulse conduction becomes slower on SN node, on AV node, the delay in conduction becomes more intense and on atrial cardial myocytes the atrial contraction becomes weak.

Supplied by vagus nerve, it decreases heart rate on the whole, causing cardiac inhibition. Neurotransmitter secreted at vagal nerve endings is acetylcholine and receptors are muscarinic –M1 type. So this type of stimulation hyperpolarizes the heart.

Hence, all effects of vagal stimulation on the heart can be cancelled by atropine.

At molecular level, the acetylcholine inhibits cyclic AMP leading to inhibition of entry of calcium ions in the sinoatrial node and atrioventricular node which in turn inhibits the development of action potential in sinoatrial node and atrioventricular node. The vagal nerves exert a strong tonic influence on the heart. So, atropinization produces tachycardia.

Sympathetic stimulation – It comes from lateral horn cells of the spinal cord of T1 to T5

segments. The preganglionic nerves relay in the sympathetic trunk and the cervical sympathetic ganglia. The post ganglionic fibers supply sinoatrial node, atrioventricular node, bundle of His and ventricular contractile myocardial cells. The postganglionic sympathetic fibers are therefore, long. The sympathetic fibers mix with vagal fibers to make cardiac plexus, from where sympathetic fibers emerge to supply the heart. Sympathetic stimulation has a positive chronotropic effect (means it increases heart rate; Chrono - time), it also increases contractility of myocardial cells (positive inotropic effect) and causes increased conductivity of SN node, AV node, His-Purkinje system and increased excitability.

All these effects produce tachycardia, increased force of contraction of myocardium leading to increased cardiac output and increased susceptibility to cardiac arrhythmias. It also causes venoconstriction leading to narrowing of capacitance vessels causing rise in velocity of blood in the veins. Increased force of contraction causes a lower end-systolic volume; heart empties to a greater extent. Limitations are that heart has to have time to fill.

The neurotransmitter secreted at the postganglionic nerve endings are epinephrine and norepinephrine. These are catecholamines. The receptors at heart are β1 adrenergic receptors. Noradrenaline is an agonist (can combine with receptor β1 adrenergic receptors and produce stimulatory effects). Propranolol, atenolol, etc. are antagonists of β1 receptors.

At molecular level, the sympathetic stimulation releases catecholamines that increase the concentration of cyclic AMP in cardiac cells and increase the sodium and calcium ion influx within the cardiac cells.

The effect of vagal stimulation ,compared to that of sympathetic ,is quick to appear but also quick to disappear. At rest, vagal fibers exert a more dominant effect on heart.

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Intrinsic heart rate: When the tonic effects of both vagus and sympathetic nerves are abolished (by giving concomitantly full doses of atropine and propranolol) then the heart rate becomes about 100/minute. This is the intrinsic heart rate.

Applied Physiology:

- β blockers like atenolol are used to reduce workload on heart, reducing load on coronary arteries, but can cause gross bradycardia.

Heart rate regulation by chemicals/ Hormonal regulation :

Hormones like epinephrine and norepinephrine endogenously secreted from the adrenal medulla and thyroxine from thyroid can increase heart rate.

Many drugs like digitalis, atropine can alter heart rate.

Temperature and heart rate:- Increased temperature also increases heart rate. Fever can raise heart rate. High temperature, when bathing the sinoatrial node increases the rate of generation of impulse by sinoatrial node.

Occurs in response to increased physical activity, emotional excitement, stress

Ions and heart rate: An excess of potassium decreases the heart rate and an excess of calcium increases it.

Pain and heart rate: pain can produce variable effects on heart rate and blood pressure. So, intense pain can produce bradycardia, but mild pain produces tachycardia.

Sinus rhythm: Basic heart rate established by pacemaker cells. Sinus rhythm is a term that means that the seat of impulse generation is at SA node which establishes baseline(sinus rhythm);if damaged-AV node can act as pacemaker ;if impulse not conducted via AV node ,bundle of his begin to generate impulses and where bundle of his is defunct-Purkinje fibres act as pacemaker (ie that sets the pace for others). Normal sinus rhythm is 50-100/minute. Ectopic rhythm is when pacemaker is a spot other than SA node. Sinus arrhythmia means, pacemaker is at SN node but the intervals in between the beats is not regular. Commonest variety of sinus arrhythmia is respiratory sinus arrhythmia where the heart rate increases during inspiration and decreases during expiration. It is seen in normal children and young adults.

Modified by ANS: If all ANS nerves to heart are cut, heart rate jumps to about 100 b/min-intrinsic rhythmicity of heart

Sleep and heart rate: during sleep heart rate falls.

Change of posture and heart rate: when a person assumes an erect posture from a supine state, the heart rate becomes faster. This is a part of postural adjustment. Such changes may not be seen in older people or in diabetics suffering from diabetic neuropathy.

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Control by reflexes of heart rate:

a. Baroreceptor reflex- Baroreceptors are stretch receptors that are located in the adventitia of carotid sinus and aortic arch (also called as pressor receptors mechanoreceptors).

When BP rises these receptors are stimulated and discharge impulses to brainstem at nucleus tractus solitarius via afferent nerves. From the brainstem efferent impulses go to vagal centres of medulla and via vagal parasympathetic fibres terminate on LHC of spinal cord. These produce inhibition of LHC causing vasodilatation and cardioinhibition.

b. Cardiopulmonary reflexes/mechanoreceptors - i. Low pressure cardiac receptors/mechanoreceptors are located in

junction of superior/inferior venacava & right atrium (venoatrial junctions). Distension of venous system by blood or iv saline sets up Bainbridge reflex. This causes tachycardia as impulses are carried by afferent vagal fibers. Decrease in the release in ADH release from posterior pituitary causes dieresis and also renal vasodilatation.

ii. Bezold-Jarisch reflex/Coronary chemoreflex: Mechanoreceptors in ventricular walls are stimulated when ventricles contract powerfully or come in contact with chemicals (serotonin,veratrum alkaloids). This leads to bradycardia & vasodilatation (it is responsible for hypotension after MI). The reflex was described by von Bezold in 1867 and later studied in 1940s by Jarisch.

iii. J-receptors:These are present in lung capillaries and are stimulated when there is pulmonary edema to cause trachycardia and tachypnea .

c. Atrial chemoreceptors These are the 2 Carotid bodies-one on each side at bifurcation of common carotid artery and 3 aortic bodies on arch of aorta (glomus caroticum). These analyze PaCO2 ,PaO2 & [H+] of blood.

Blood PaO2 or pH falls or PaCO2 rises can lead to the chemoreceptors being stimulated and as the impulse travels via the afferent fibers to respiratory centre it results in hyperpnea and can also cause bradycardia and vasoconstriction.

d. Diving reflexAs a lung breathing animal dives under water inhibition of respiratory centre occurs causing bradycardia and vasoconstriction. The bradycardia ensures that load on heart is reduced, metabolism in the periphery greatly reduced (due to lack of oxygen supply and fall of ph), yet brain remains alert (due to rise of PaCO2 because of asphyxia causes cerebral vasodilatation). The arterial chemoreceptors are stimulated that result in bradycardia and vasoconstriction.

STROKE VOLUME (SV)

Stroke Volume is the volume of ejection/ventricle/beat and normally stroke volume of right ventricle (RV) = stroke volume of left ventricle (LV). Stroke volume is determined by the extent

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of venous return and by sympathetic activity. It is influenced by two types of controls which are intrinsic control and extrinsic control. Both controls increase stroke volume by increasing strength of heart contraction.

INTRINSIC FACTORS AFFECTING STROKE VOLUME (SV)

Contractility – cardiac cell contractile force due to factors other than EDV affect the stroke volume.

Preload –It is the amount ventricles are stretched by contained blood.

Afterload –Resistance to ejection of blood by the ventricle or back pressure exerted by blood in the large arteries leaving the heart is known as the afterload.

SV= end diastolic volume (EDV) minus end systolic volume (ESV)

SV = EDV - ESV

EDV = end diastolic volume

It is the amount of blood in a ventricle at end of diastole.

ESV = end systolic volume

It is the amount of blood remaining in a ventricle after contraction.

Ejection Fraction is the percentage of EDV that is pumped by the ventricle and it is an important clinical parameter. Ejection fraction should be about 55-60% or higher normally.

End diastolic volume (EDV) is affected by venous return which is the volume of blood returning to the heart and preload which is the of amount ventricles are stretched by blood.

End systolic volume (ESV) is affected by contractility (myocardial contractile force due to factors other than EDV) and afterload (back pressure exerted by blood in the large arteries leaving the heart).

FRANK-STARLING LAW OF THE HEART

It states that the greater the initial length of the heart muscle fiber or the chamber of heart , greater will be the force of contraction.

Preload, or degree of stretch, of cardiac muscle cells before they contract is the critical factor controlling stroke volume. An increase in end diastolic volume leads to increase in the stretch of myocardial muscle.

Therefore an increase in the preload results in an increase in stretch of muscle leading to an increased

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force of contraction causing greater stroke volume. Unlike skeletal fibers, cardiac fibers contract more forcefully when stretched thus ejecting more blood (increased stroke volume). If stroke volume is increased, then end systolic volume is decreased.

Slow heartbeat and exercise increase venous return (VR) to the heart, increasing stroke volume.

CENTRAL VENOUS PRESSURE (CVP) is the venous pressure in the terminal part of superior venacava. Greater the CVP, greater is the cardiac inflow, greater is the end diastolic fiber length and as according to the frank-starling law, greater is the cardiac output. On the other hand greater the cardiac output, greater is the cardiac inflow. So both cardiac output and central venous pressure are interdependent. At rest and equilibrium the both remain constant. CVP is about +2 mm of Hg and cardiac output is about 5 l/min. If one changes, the other changes too.

Venous return changes in response to blood volume, skeletal muscle activity, alterations in cardiac output.

Suction action- Respiratory pump : Normally, the mediastinal pressure is subatmospheric (negative) and the intraabdominal pressure is positive. Therefore, venous blood flows from the abdomen to the inside the inferior venacava.

This negativity of mediastinum increases during deep respiration resulting in blood from the abdominal veins being more forcibly sucked in inside the thorax. This is the respiratory pump.

Also, during isotonic ventricular contraction, the AV valves are drawn in, closer to the ventricular apex. This causes expansion of atrial vertical diameter leading to the venous blood being sucked into the atrium.

An increased venous return results in a greater end diastolic volume and a reduced venous return causes a fall in end diastolic volume. Any reduction in end diastolic volume results in a reduction in stroke volume

Hence, blood loss and extremely rapid heartbeat decrease stroke volume.

Preload, or degree of stretch, of cardiac muscle cells before they contract is the critical factor controlling stroke volume.

EXTRINSIC FACTORS INFLUENCING STROKE VOLUME

CONTRACTILITY is an increase in contractile strength, independent of stretch and EDV. Here, influencing factor is from some external source ,so it is an extrinsic factor.

Increase in contractility can be due to:

a. Increased sympathetic stimulib. Hormones- epinephrine and thyroxine c. Ca2+ and some drugsAgents or factors that decrease contractility are:

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a. Acidosisb. Increased extracellular K+ c. Calcium channel blockersEFFECTS OF AUTONOMIC ACTIVITY ON CONTRACTILITY

Parasympathetic stimulation :- It is via Vagus Nerve (X) . The stimulation releases acetylcholine. It has a negative inotropic effect and causes hyperpolarization and inhibition of cardiac reflexes

So the force of contractions is reduced, and therefore the ejection fraction is also decreased.

Sympathetic stimulation :- It occurs by the release of norepinephrine from sympathetic postganglionic fiber and also, epinephrine and norepinephrine from adrenal medulla. It has positive ionotropic effect.

Ventricles contract more forcefully, increasing SV, increasing ejection fraction and decreasing ESV

Contractility and Norepinephrine-

Sympathetic stimulation releases norepinephrine and initiates a cyclic AMP 2nd-messenger system

EFFECTS OF HORMONES ON CONTRACTILITY

Epinephrine, Norepinephrine and Thyroxine all have positive ionotropic effects and thus increase contractility.

Digitalis elevates intracellular Ca++ concentrations by interfering with its removal from sarcoplasm of cardiac cells.

Beta-blockers (propanolol, timolol) block beta-receptors and prevent sympathetic stimulation of heart (neg. chronotropic effect)

UNBALANCED VENTRICULAR OUTPUT : It can lead to either systemic or pulmonary edema.

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Factors Involved in Regulation of Cardiac Output

CONDITIONS ASSOCIATED WITH CHANGES OF CARDIAC OUTPUT

Physiological :-

1. Exercise

2. Sympathetic stimulation due to rage/panic.

3. Posture

4. Sleep

Pathological : reduced Cardiac Output is seen in

1. CHF

2. Shock due to fluid loss (hemorrhage/ diarrhea)

3. Acidosis(diabetic ketoacidosis)

Drug induced

EXAMPLES OF CONGENITAL HEART DEFECTS

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APPLIED ASPECTS

ADJUSTMENTS ON STANDING: Forces of gravity oppose return of venous blood to heart, about 700 ml of blood is pooled in veins of inferior extremities and abdomen. Cerebral ischemia is prevented by compensatory mechanism located in baroreceptors that cease to send inhibitory signals to vasomotor area that becomes hyperactive and sympathomimesia develops leading to rise in BP & tachycardia. A failure in this mechanism leads to postural hypotension which is seen in old age (sluggish activity of baroreceptor reflex), Diabetic autonomic neuropathy ,treatment by some antihypertensive drugs(prazosin-α1receptors blocker-inhibits sympathetic system)

CARDIOMYOPATHIES are the conditions with insufficient cardiac output due to fault of ventricular muscles. These can be due to-chronic alcoholism, SLE, peripartum stage etc.

They are of 3 types:

Restictive cardiomyopathy : Endomyocardial fibrosis occurs in this condition due to which myocardium doesnot dilate and so ventricular filling suffers and cardiac output falls.

Hypertrophic cardiomyopathy : Interventricular septum undergoes hypertrophy due to which the ventricular filling suffers causing syncopal attacks and angina.

Dilated cardiomyopathy : Ventricles are dilated and loss of power of ventricular contraction occurs. Symptoms of congestive heart failure occurs due to this.

CONGESTIVE HEART FAILURE

In congestive heart failure the cardiac output either falls or can be maintained only with a higher central venous pressure.

Causes : Ischemic heart disease is the most commonest cause leading to loss of myocardium due to myocardial infarction or chronic ischemia.

Pathological changes: As cardiac output falls, blood supply to vital organs falls. Compensatory changes occur that tide over the crisis temporarily, but are counter productive and cause harm.

Compensatory changes: This consists of neuro-humoral mechanisms that are as under:-

1. Sympathetic stimulation- It leads to vasoconstriction and production of rennin from kidney. Vasoconstriction helps to tide over the ill effects of fall of cardiac output (cerebral ischemia).

2. Activation of rennin-angiotensin system- This leads to production of angiotensin causing vasoconstriction and aldosterone that causes fluid retension leading to hypervolemia. This leads to increased central venous pressure and an improvement in cardiac output.

3. Release of endothelin- This causes vasoconstriction. This along with hypervolemia lead to over working of heart and apoptosis of myocardial cells.

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Treatment : It consists of –diuretics (to reduce hypervolemia);ACE inhibitors (it inhibits rennin-angiotensin axis); β1blockers; digitalis (improves myocardial contractility).

SUMMARY

The heart is a double pump, delivering blood to the lungs for oxygenation, and then to the body. Blood leaves the heart through arteries, and returns to the heart through veins. The heart rate is regulated by a conducting system (the heart beats about 100,000 times per day!)

The cardiac cycle is regulated by the cardiac center in the medulla oblongata which regulates sympathetic and parasympathetic input. Exercise (i.e., needs), temperature and ion balance also affect heart rate .

Cardiac rate is also controlled by long-term responders such as ADH, angiotensin, EPO and ANP

Blood (arterial) pressure is affected by heart action, blood volume, peripheral resistance, and blood viscosity. Inability to regulate blood pressure can contribute to disease. Arteries and veins have structural characteristics appropriate to bringing blood to the cells and then back to the heart. Circulatory system allows for adjustments to exercise, digestion and other necessary functions.

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REFERENCES

1. Concise medical physiology- Sujit K. Chaudhari-6th edition2. Manual of practical medicine-R Alagappan- 2nd edition3. Catie Chang, Influence of heart rate on the BOLD signal: The cardiac response

function, NeuroImage 44 (2009) 857–8694. Cardiac Output. Web: http://www.ebme.net/arts/cardop/