Disha .J. Parikh

M.Pharm (Pharmacology)

Cardiovascular system

Cardiovascular system is divided into two main parts:

Circulatory system: consisting of heart, which pumps the blood and the blood vessels which circulates the blood.

Lymphatic system: consisting of lymph nodes and lymph vessels through which the colorless lymph flows.

The heart pumps the blood into two separate systems: - pulmonary circulation - systemic circulation

The right side of the heart is involved in pulmonary circulation where CO2 leaves the blood and enters the lung and O2 leaves the lung and enters the blood.

The left side of heart is involved in systemic circulation which supplies to rest of the body, where tissue waste are passed in blood for excretion and body cells extracts the nutrition and O2.

ANATOMY OF HEART

The heart is roughly cone-shaped hollow muscular organ, which is about the size of the owner’s fist.

POSITION: • It lies in the thoracic cavity in the mediastinum (space between the two

lungs). • It lies obliquely a little more toward left with the base above and apex

below.• The apex is about 9 cm to left of the midline at the level of 5th

intercostal space.

ORGANS ASSOCIATED:

Inferiorly: apex rest on the diaphragm.

Superiorly: aorta, superior vena cava, pulmonary artery and pulmonary vein.

Posteriorly: oesophagus, trachea, left and right bronchus, descending aorta, inferior vena cava, thoracic vertebrae.

Laterally: the lungs- the left lung overlaps the left side of the heart

Anteriorly: sternum, ribs and intercostal muscles.

COVERINGS OF THE HEART:

Pericardium – a double-walled sac around the heart composed of:

1. A superficial fibrous pericardium

2. A deep two-layer serous pericardium

a. The parietal layer lines the internal surface of the fibrous pericardium

b. The visceral layer or epicardium lines the surface of the heart

They are separated by the fluid-filled pericardial cavity

The Function of the Pericardium:Protects and anchors the heartPrevents overfilling of the heart

with bloodAllows for the heart to work in a

relatively friction-free environment

Myocardium – cardiac muscle layer forming the bulk of the heart.

Endocardium – endothelial layer which lines the chambers of the heart. It consist of flattened epithelial cells and continues with the endothelial linings of the blood vessels.

INTERIOR OF THE HEART

• Right atrium tricuspid valve right ventricle

• Right ventricle pulmonary semilunar valve pulmonary arteries lungs

• Lungs pulmonary veins left atrium

• Left atrium bicuspid valve left ventricle

• Left ventricle aortic semilunar valve aorta

• Aorta systemic circulation

BLOOD FLOW THROUGH HEART AND LUNGS

Ductus arteriosus:• It is cord like structure between arch of aorta and pulmonary trunk

passing underneath the aorta.• During foetal life it works as the link between the two vessels to by-pass

the pulmonary circulation.• After the birth the blood changes the route and starts circualting

through the lungs and therefore the link gets closed• In rare cases the duct may remain open and the deoxygenated blood

may mix with the oxygenated blood of aorta.• It can be corrected by surgery.

Septum ovale:• The atria are seperated by the septum called as inter-atrial septum and

the ventricals are seperated inter-ventrical septum.• The foramen ovale is the small opening at the inter-atrial septum which

remained open during the foetal life to avoid the blood circulate in the lungs.

• After the birth, with the first breath the foramen ovale gets closed which is then called as septum ovale.

• In rare case it remains open after the birth which can be corrected surgically.

Blood vessels:

Arteries: • Vessels which carry blood from heart to body parts.• Usually carry oxygenated blood except pulmonary arteies which carries

deoxygenated blood. • The arteries divide into arteriols and the finally into capillaries.

Veins: • Brings the blood from various parts of the body into the heart.• Usually carries deoxygenated blood except pulmonary veins which

brings the oxygenated blood into the left atrium• The veins divide to form venules and finally venous capillaries.

Histology of blood vessels:

Consist of 3 layers:

• Tunica externa/ adventitia (elastic layer)• Tunica media (muscular layer)• Tunica intima (serous layer)

Tunica externa: made up of areolar connective tissue. Thicker in veins than in arteries.

Tunica media: made up of smooth muscle fibres. Thicker in artery than in veins.

Tunica intima: made up of endothelial cells.

The lumen in the artery is wide open than in vein.

BLOOD CIRCULATIONSystemic circulation:

Arterial system

Venous system

Pulmonary circulation:

Coronary circulation:

PHYSIOLOGY OF HEART

PROPERTIES OF CARDIAC MUSCLES

Excitability or irritability:Property of a tissue to respond to a stimulus.

Contractibility:Property to contract in response to a stimulus.

Automaticity:Property of cardiac muscle to generate its own impulse. The SA-node initiates the impulse which is conducted to whole heart by other junctional tissues.The property of conducting the impulse is known as conductivity. Although the impulse in the heart comes through junctional tissue, each part of cardiac muscle can generate its own impulse.

Rhythmicity:Heart beats in a regular fashion as a result of its automaticity and conductivity. The atria and ventricals alternatively produce contraction and relaxation at a perticualr rate i.e. 70-80 beats/min. This is called as rhythmicity.

All or none phenomenon:Either it contracts to its maximum ability or it does not contract at all. This rule is applicable to whole heart.

Refractory period: Period at which the heart does not respond to the external stimuli. It has two phases• Absolute refractory period: it is the period during systol when heart do

not respond to any stimuli however strong it be.• Relative refractory period: it is during diastole , a strong extra stimulus

can provoke a response.During the refractory period the heart gets time to recover and overcome fatigue.

Tonicity: The special feature of the cardiac muscle to exert certain amount of pressure on the blood it contains.

Nutrition of cardiac muscle:

ATP: Cardiac muscles gets its energy in form of ATP by glycolysis and mostly by oxidation of glucose, free fatty acids and amino acids.

Oxygen: it is the most imp. Gaseous nutrition that regulates the oxidative process for cardiac energy. Lack of O2 cause hypoxia followed by anoxia which is painful.

Sodium ion: it initiates and maintains the beat.

Calcium ion: it strengthens the systole and inhibits the diastole. Excessive Ca+2 stops the heart at systole

Potassium ion: it inhibits the contraction and prolongs the relaxation, i.e. diastole. Excessive K+ stops the heart at diastole.

JUNCTIONAL TISSUES

These are the specialized tissues that generate and conduct the impulse.

• Sino- atrial node (SA-node)• Atrio- ventricular node (AV-node)• Atrio- ventricular bundle (AVB) or bundle of His• Right and left branches of AVB• Purkinjee fibres (PF)

CARDIAC CYCLE

• It is the sequence of the events during one cardiac beat• On an average hearts beats 72 times in a minute, hence it takes 0.8 sec

for one beat• Both atria and ventricle goes systolic and diastolic phase with every

beat.

Atrial events: • Includes atrial systole and diastole.• Systole occurs for 0.1 sec where atria contract to pour the blood in the

ventricals which is followed by diastole for 0.7 sec where atria relax and blood from superior and inferior vena cava fill right atrium and blood from pulmonary veins fills the left atrium.

Ventricular events:After the atrial systole the ventricular systole starts which continues for 0.3 sec followed by diastole for 0.5 sec

Isometric ventricular contraction period:• At the start of the ventricular systole AV valve of the ventricles gets

closed (first heart sound).• As s result the ventricles form the close cavities and the pressure inside

rises without decreasing the volume. This is isometric contraction period.

The onset is marked by closure of AV- valves and terminated by opening of the SL-valves (0.05 sec). Intraventricular pressure is highest.

Rapid and slow ejection period:• After 0.05 sec the SL valves gets opened and the blood is ejected to the

respected arteries. This is rapid ejection period (0.15 sec)• The intraventricular pressure starts rising but the volume steps down• In the late phase the pressure lowers and there is slow ejection (0.1 sec)

Prodiastolic and isometric relaxation period:• The pulmonary artery and aorta recoil and the blood tries to rush back.• There is sudden closure of the SL valve (second heart sound)• The interval between the start of ventricle diastole and closure of SL

(0.04 sec) valve is called prodiastolic period.• Next is isometric relaxation period (0.08 sec) where AV and SL valves are

closed and both the atria and ventricles are at diatole. Thus intra-ventricular pressure is minimum and heart is relaxing.

Rapid and slow inflow period:After the isometric relaxation the AV-valve opens and rapis inflow of the blood starts as the ventricles are at diatole (third heart sound) (0.03 sec), followed by slow inflow (0.2 sec) also called as diastasis.

When the ventricular diastole ends the atrial systole starts which overlaps for 0.1 sec. Atria contracts and rapid filling of ventricle stars (rapid inflow period) (fourth heart sound).

ELECTROCARDIOGRAM (ECG)The graphical record of electric changes occurring during the cardiac cycle is known as electrocardiogram.The instrument recording ECG is known as electrocardiograph.

Pair of connection called as leads are used to measure electrical activity of the heart. 2 types of leads:• Bipolar limb leads/ standard leads• Unipolar leads

The bipolar limb leads are obtained by placing two electrodes on the extremities to record the electrical activity of the heart facing them. These leads are:

Lead I: right arm and left armLead II: right arm and left legLead III: left arm and left leg

Unipolar leads are obtained by placing the electrodes at the closer proximity of the heart2 types: unipolar limb lead and unipolar chest leads.

Unipolar limb leads :

Lead aVR: right arm leadLead aVL: left arm leadLead a VF: left leg lead

Unipolar chest leads:

V1: 4th inter-coastal space, right sternal boarderV2: 4th inter-coastal space, left sternal boarderV3: between V2 and V4V4: 5th inter-coastal space in mid clavicular lineV5: 5th inter-coastal space in anterior axillary lineV6: mid axillary line at a level of V4.

NORMAL ECG:

Impulse originate from the SA node which is not observed. When it reach the atrial musculature (0.04 sec) potential rises by 0.2mV (P wave). Followed by repolarizationNow the impulse from AV node to bundle of His and pirkinjee fiber. No deflection so isoelectric line is obtained. When impulse reach intermuscular septum-negative deflection (Q wave). Impulse immediately spreads to ventricular musculature, big wave of 1.8mV (R wave). After these there is ventricular repolarization of 0.4 mV (T wave)

CARDIAC OUTPUT:

The amount of blood pumped by the heart in one beat is called as stroke volume (SV).Now the heart rate (HR) is 70 beats per minute, so cardiac output (CO)is :CO= SV X HRThe amount of blood pumped out by the heart in one minute is called as minute output of the heart

Factors controlling the CO:

• Venous return: quantity of blood reaching the heart via superior and inferior vena cava.

• Force of contraction of heart (inotropic action)• Frequency of heart beats (chronotropic action)• Peripheral resistance

CO varies with age, sex, surface area, exercise, posture.

CO increases with: pregnancy, anxiety, anger, hyperthyroidism, anemia, angina pectoris.

CO reduces with: tachycardia, auricular fibrillation, A-V block, hemorrhage, myxedema, surgical shock, pneumothorax, arterial hypertension and postoperative conditions.

HEART RATE

Diff. phases of life Heart rate (beats/ min)

foetus 140-150

children 100-110

Adult 70-80

old 65-75Factors affecting the heart rate:

• Autonomic nervous system: The sympathetic nerves increases force and frequency hence known as cardio accelerator mechanism. The parasympathetic nerves decreases the heart rate.

• Higher centers of the brain:Excitement increases and shock decreases the HR

• Respiration:Inspiration increases and expiration decreases the HR

Reflex stimulation:Stimulation with pain, cold or heat increases, however severe pain decreases the HR

• O2 supply:Anoxia increase the HR but if there is no O2 supply the heart may stop

• CO2 supply:Moderate CO2 increases while high CO2 decreases the HR and may poison the heart

• Blood Pressure:Increase in BP decrease the HR

• Temperature: Every degree rise in the temperature increases the HR by 10 beats/min

• Exercise:It increases the HR as well as force

• Drugs:Adrenaline and thyroxine increases the HR and force of contraction. Digitalis decreases the rate, but increases the force and hence increase CO.

BLOOD PRESSURE

Definition:• The pressure exerted by the blood on the walls of the blood vessels.

• May be regarded as

1. Arterial B.P.2. Venous B.P.3. Capillary B.P.

The phases of the blood pressure are

• Systolic B.P: max pressure during the systole of the heart

• Diastolic B.P: min pressure during the diastole of the heart

• Pulse pressure: diff. between systolic and diastolic pressure

Normal range of B.P. (mmHg)

Standard B.P. (mmHg)

SP 110-145 125

DP 70-90 80

PP 40-55 40

Significance of BP:

Systolic pressure:

• It indicates the force with which the heart works. • It is highly variable• Increases with excitement, exercise, meals and decreases with shock,

sleep, rest etc.

Diastolic pressure:

• It indicates the extent of peripheral resistance (peripheral resistance that heart has to withstand)

• It is generally constant• Variations in diastolic pressure are of great clinical importance

Pulse pressure:

• It indicates the strength of stroke volume of cardiac output.• Does not have any clinical significance

Methods of B.P. measurement:

It is commonly measured by sphygmomanometer

Two methods for the measurement of B.P:• Palpatory method• Ausclatory method

Palpatory method:

• The cuff is tied at the lower part of upper arm.

• The arterial pulse at the wrist is felt• BP is raised upto 200mmHg till pulse

stops• The bulb is unscrewed and pressure

is lowered till reappearance of the pulse

• The reading in the sphygmomanometer is recorded when the pulse reappears

• It gives the systolic pressure.

Ausulatory method:

• The cuff is tied and the pressure is raised up to 200 mmHg.• The stethoscope is placed in cubital fossa at the bifurcation of the

brachial artery • The first sound heard at lowering of the pressure indicates the systolic

pressure• Now the pressure is further lowered , the disappearance of the sound

indicates the diastolic pressure.

Factors maintaining B.P:

Heart: The force and frequency of the heart affects the pumping of the heart which indeed maintains the B.P.

Cardiac output:Depends on the venous return and pumping capacity of the heart.

Peripheral resistance:It is governed by the elasticity and lumen of the blood vessels as well as the velocity and viscosity of the blood. The peripheral resistance maintains the diastolic blood pressure.

Blood volume:Total circulating blood also affects the B.P. the increase in the volume raise where as decrease in volume lower the pressure

Vasomotor center: Situated in medulla oblongataIt receives the information about the pressure through baroreceptors and chemoreceptors

Baroreceptors are found at the arch of aorta and at the base of the bifurcation of each common carotid artery (carotid sinus).Chemoreceptors are found at the aortic body (the nodule present at the lower part of the arch of aorta) and carotid body (nodule present on occipital artery)

Baroreceptors are sensitive to decrease in BP, where as chemorecetors are sensitive to increase in CO2 or decrease in O2 supply.

The impulse from the carotid sinus and carotid body are taken to vasomotor centres through IX cranial nerves (glossopharyngeal nerve)

The X cranial nerve (vagus nerve) carry the impulse from aortic arch and aortic body

Vasomotor centers:Medulla oblongata have two centers – pressor and depressor

Pressor center stimulates of sympathetic nerve and cause vasoconstriction

Depressor center decrease the activity of the sympathetic nerve and inhibit the pressor center.

Thus when there is fall in BP the baroreceptors and chemoreceptors are stimulated and they increase the activity of the pressor center

If BP is high, the depressor center inhibits the pressor center to inhibit the sympathetic nerve and produce vasoconstriction.

Physiological variations:

The physiological variation occur for systolic pressure only.For the change in diastolic pressure one must seek medical treatment.Diastolic BP<90 is called mild hypertensiveDiastolic BP<100 is called clinical hypertensive

Age:

Phases of life Systolic BP (mmHg)

Infancy 70-90

Childhood 90-110

Puberty 110-120

Adult 120-130

Old age 140-150

Body built:Over weight have a tendency to have higher BP. As well as its is hereditary in nature

Climate:BP is higher in cold climate than in hot

Diurnal:BP is max in day, low in morning and lowest during sleep at night

Excitement and shock:BP increases with excitement and decreases with the shock

Food:Small rise in BP after meals

Gravity:Standing> sitting> lying

Hormones:Adrenaline secreted from adrenal medulla increases the BP by increasing CO and vasoconstrictionAdrenal cortex secretes glucocorticoids and aldosterone which cause fluid and salt retention and hence increase the BP.Thyroxin (thyroid gland) and renin- angiotensin (kidney) also increase blood pressure.

Sleep:BP is 10-15 mmHg less during sleep

Sex:Women have slightly lower BP than men.

Renin angiotensin system:Renin is secreated from the juxtaglomerular cells of kidney found in afferent arterioles and distal tubules.Secreted in response to decrease in renal perfusion pressure, mechanical stress, hypoglycemia, exercise, emotional stress.

Actions of Angiotensin-II:

• Rapid increase in BP due to altered peripheral resistance• Slow pressure response due to altered renal function• Vascular and cardiac hypertrophy due to altered cardiovascular

structure.

The altered peripheral resistance occurs due to direct vasoconstriction, enhanced sympathetic- noradrenergic transmission leading to raise in BP

Angiotensin-II also cause increase in Na+ reabsorption from proximal tubules, relase of aldosterone from adrenal cortex and constriction of renal blood vessels. Thus produce sustained rise in BP

Besides Angiotensin-II by acting on the AT-1 receptors also cause increase in growth factors thereby causing cardiac hypertrophy and hyperplasia leading to cardiac remodeling.

CARDIOVASCULAR DISORDERS

Hypertension:

It is chronic increase in arterial blood pressure.

Hypertension

2 types :

Primary hypertension: Not link to a single aetiology. It may be due to stess, high fat diet, high sodium diet, etc. the exact cause is unknown. Also called as ‘Essential Hypertension’

Secondary hypertension:Condition secondary to some disorder.May be associated with disorder like pheochromocytoma, Cushing syndrome, primary aldosteronism, hyperthyroidism, myxoedema, renal vascular disorder, etc.

Hypotension:It is decrease in arterial blood pressure where systolic BP< 100 mmHg and diastolic< 60mmHg.Chronic in nature and often associated with weak and thin anemic patients.

diastolic pressure >90mmHgSystolic pressure >150mmHg

VASCULAR DISORDERS

Postural hypotension:When a subject changes the posture from lying down to upright position there is momentary hypotension due to the gravitational pull of the blood to lower extremities. As a result there is reflux rise in blood pressure.Thus lowwering of BP due to change in the posture is called as postural hypotension.

Ischemia:It is temporary sudden loss of blood supply to a particualr part of body, leading to partial damage to that part due to lack of oxygen supply.If it is in the heart it is cardiac ischemia.

Aneurysm:Bulging of the artery due to weakness of the arterial wall or increased pressure or both.In relation to aorta it is aortic aneurysm.

Arteriosclerosis:Hardening and narrowing of the arteries due to fatty deposits resulting in the decreased blood supply to that part.In case of brain it is called as cerebral arteriosclerosis.

Peripheral vascular diseases:It is obliterate disease of arteries of the limbs leading to the functional disorder of small peripheral vessels.

Thrombosis:Process of formation of solid clot during the circulation. The solid clot is called as thrombus. It is usually initiated by platelet aggregation and mainly composed of fibrin.If formed in vein it is called as venous thrombosis and in case of artery -arterial thrombosis.Arterial thrombosis is dangerous if it is coronary, cerebral or renal artery.

Embolism:It is impaction of the embolus in the blood vessels.An embolus is the sub transported from thrombus part of the circulation to another part where it is impacted, cutting off the blood supply. Sometimes the hear thrombosis may result in cerebral embolism.

Thrombo- angitis obliterans:Adversely affects blood flow, characterized by acute inflammation with thrombosis affecting both arteries and veins, following infection.

Raynaud’s disease:Spasm of arteries and arterioles specially in digits, nose and tongue with intermittent pallor or cyanosis. Often stops the functioning of the part.

Haemorrhage: Escape of blood from artery ,vein or capillary. Dangerous if capillary hemorrhage in brain is involved

Varicose – vein:Abnormally dilated tortuous veins with incompetent valves.It occurs frequently in lower extremities.

CARDIAC DISORDERSAngina pectoris:Clinical syndrome due to myocardial ischemia producing the sensation of chest pain, pressure or strangling sensation. May characterize due to exertion.

Myocardial infraction:It is ischemic type of myocardial necrosis resulting from abrupt reduction in coronary blood flow. It id more intense and prolonged than angina pectoris. The pain is the warning cry of heart for oxygen.

Congestive cardiac failure (CCF):Decreased force of contraction of the heart leading to the inadequate cardiac output, resulting in diminished blood flow to the tissues and congestion of pulmonary and systemic circulation. Characterized by progressive breathlessness on exertion. Also cause edema and enlargement of the orangs thus decreasing their efficiency.

Heart failure:Condition in heart is unable to function adequately to supply the metabolic needs of the peripheral tissues. Primary dysfunction occurs in left or right ventricle.

Left ventricular failure can occurs due to due hypertension, ischemic heart disease etc. The common cause of right ventricular failure is left ventricular failure.

Cardiac arrhythmias:It is the disorder of origin, rate, rhythm, conduction and spread of impulse in the heart.

Tachycardia: increase in hear rate

Bradycardia: decrease in heart rate

Palpitation: continuous and fast beating of the heart

Extrasystole: the premature beat that occurs before the next expected beat. This may be atrial, ventricular or nodal depending on the sight of origin.

Paroxysmal supraventricaular tachycardia: it is condition in which the heart rate suddenly rise 150-200 beats/min.

Atrial flutter: rapid and but regular beating of atria at a rate 240-400 beats/min

Atrial fibrillation: rapid , irregular continuous, chaotic beating of atria. More dangerous

Ventricular fibrillation: it is rapid irregular and chaotic beating of ventricles. There is disorganized spread of impulse throughout the ventricles

Heart block: condition in which the nerve impulse are delayed of failed to get through from their source in the right atrium and ventricle. It is obstruction in conduction of impulse in the heart leading to decrease in heart rate and pulse rate.

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