CARDIOVASCULAR SYSTEM

AND DISEASES

BY

SHAH FAHAD HUSAMI

ANATOMY AND PHYSIOLOGY OF THE CARDIOVASCULAR SYSTEM

What does cardiovascular system mean?

Cardio mean related to heart and vascular means related to blood vessels

What does CVS consists of ?

The Cardiovascular system consists of the following :

Heart and
Blood vessels
Arteries
Veins
Capillaries

What is the function of CVS?

The main function of the Cardiovascular system is to supply oxygenated blood and
nutrients to all parts of the body and simultaneously collect the deoxygenated blood and
bring it back to the lungs to enrich with oxygen from the atmospheric air.

Describe the anatomy of the Heart

THE HEART

Heart is situated in the thoracic cavity. It is a small roughly cone shaped hollow muscular
organ, 10 cm long and is about the size of the owner's fist.

POSITION

The heart is in the thoracic cavity in the media sternum between the lungs. The heart is
positioned in a way that it is inclined more to the left. The base of the heart is at the level
of 2nd rib while the apex is at the level of the 5th intercostal space.

Walls of the Heart

The heart is composed of three layers of tissues : Pericardium , Myocardium and

Endocardium.

Pericardium : It is the outermost layer of the heart. There are two layers of pericardium;
parietal pericardium and visceral pericardium. The parietal pericardium is a fibrous layer
which is reflected back from the base of the heart, and surrounds it like a loose sac.
Visceral pericardium, as the name suggests is a membrane which is closely adherent to
the heart.

Myocardium It is composed of cardiac muscle.The myocardium of the heart forms the

muscular walls of the heart. The cardiac muscle is a special type of smooth muscle. It is
an involuntary muscle but shows striations similar to voluntary muscle.

The myocardium is thickest at the apex and thins out towards the base. In general, the
ventricles have the thickest walls ; the walls of the left are thicker than those of the right
ventricles, because the force of contraction of the left ventricle is much greater.

Endocardium : This forms the lining of the myocardium and the heart valves. It is a thin
smooth glistening membrane which permits smooth flow of blood inside the heart. It
consists of flattened epithelial cells continuous with the endothelium that lines the blood
vessels.

What are the unique properties of the heart muscle?

The cardiac muscle has unique properties and these are:

i) Automaticity beats continuously for 24 hrs throughout life

ii) Rhythmicity beats regularly all the time
iii) Conductivity Impulse generated in one part of heart travels to the other
iv) All or none phenomenon. Entire heart beats or none part of the heart

What is the interior of the heart made up of? (FIG FROM ANATOMY CD)

The heart is divided into two sides, right and left by a septum. There is normally no
communication between these two sides after birth. Each side is further sub divided into
two chambers. The upper chambers on either side are referred to as atrium. While the
lower chambers as ventricles. Thus, there are four chambers in the heart.

The atria and ventricles of each side communicate with one another through the
atrioventricular openings which are guarded by one way valves. On the right side there is
a tricuspid valve and on the left the mitral valve. These valves being unidirectional, the
blood always flows from atrium to ventricle.

The Heart Valves

The heart valves are formed by double folds of endocardium ,strengthened by a little
fibrous tissue. The right atrioventricular valve, tricuspid valve has three flaps or cusps
and the left atrio- ventricular valve, mitral valve has two cusps.
Blood Flow Through the Heart

The left ventricle of the heart pumps the blood into the aorta, the largest artery in the
body. This aorta divides into smaller arteries and further into the capillaries. The
capillaries have very thin walls so that exchange can take place between the plasma and
the interstitial fluid. These capillaries then unite and form venules which pick up
deoxygenated blood from the tissues. Venules unite to form veins. Veins carry blood
back to the heart.

The largest veins, superior and inferior vena cava collect the blood from the entire body.
The superior vana cava collects the blood from the head and upper extremities; while the
inferior vana cave collects the blood from the trunk and lower extremities. Both superior
and inferior vena cava empty the deoxygenated blood into the right atrium of the heart.

From right atrium, blood passes into the right ventricle. Now it enters into the pulmonary
artery which carries blood from right ventricle to the lungs.

In the lungs, these arteries (right and left) break up into pulmonary capillaries. The
pulmonary capillaries surround the alveoli and gaseous exchange takes
place. This converts deoxygenated blood into oxygenated blood. Oxygenated blood is
then poured into the pulmonary vein. Pulmonary veins pour the oxygenated blood into
the left atrium.

The blood then passes into the left ventricle. Left ventricle contracts to pump the
oxygenated blood into the aorta. The circulation then continues.

Flow chart of blood flow through the Heart

Superior and inferior venacava

right atria

right ventricle

through pulmonary artery

lungs

through pulmonary veins

left atria

left ventricle
 body

What is the Nerve Supply to the Heart

The myocardium has a very unique feature of intrinsic stimulation i.e. the heart muscle
can automatically generate an impulse and initiate contraction. Apart from this
spontaneous impulse, the heart is influenced by certain nerves.

In the medulla oblongata of the brain, we have a center called the cardiac center. The
nerves from this center reach the heart through sympathetic (adrenergic) and
parasympathetic (cholinergic ) nerves.

The sympathetic stimulus could be compared with responses to a situation of fight,

fright, or flight. It tends to increase the rate an force of contraction while the vagal or
parasympathetic stimulus reduce it. Normally, the heart is all the time being inhibited by
the vagus. It is only at the time of excitement or emotional excitement, the rate of heart
contraction increases.

How does the impulse travel throughout the heart

CONDUCTING SYSTEM OF THE HEART (DIAGRAM FROM ANATOMY CD)

The cardiac muscle differs from other muscles by virtue of its unique properties such as
Automaticity, Rhythmicity, and All-or-none response. The property of automaticity
indicates the capacity of the heart muscle to generate an impulse on its own. Normally
other muscles contract or relax in response to a stimuli from the brain. The heart , on the
contrary, responds to impulse generated by the heart muscle itself. This is in addition to
response to the autonomic nervous system.

The automaticity of the heart is due to a small group of specialized neuromuscular cells
in the myocardium which initiate and conduct impulses over the heart .

These are referred as the sinoatrial (SA) node and the atrioventricular (AV) node. The SA
node generates an impulse which spreads all over the atrial muscle. The impulse is then
conducted to the AV node. Further it passes over the ventricular septum and on the entire
ventricular muscle. This results in ventricular contraction.fig

Sinoatrial node (SA node)

As the name suggests, this is a mass of specialized cells in the wall of the right atrium
near the opening of the superior vena cava. The SA node is often described as the 'pace
maker' of the heart. This center initiates the impulse of contraction more rapidly than
other group of neuromuscular cells.

Atrioventricular node (AV node)

Situated in the wall of the atrial septum near the atrioventricular mass, AV node is
stimulated by the impulse of contraction that sweeps over the atrial myocardium. It also
can initiate impulses of contraction but at a lower rate.

Atrioventricular bundle (AV bundle) or bundle of His

This is the bundle of fibres that originate from the AV node. The AV bundle crosses the
fibrous ring that separates atria and ventricles at the upper end of the ventricular septum.
Within the ventricular myocardium it divides into right and left branch bundles. Further
the branches break up into the fine fibres called the Purkinje fibres.

Definitions

Systole : The contraction of the heart is called as systole. Usually, it refers to the
contraction of the ventricles. During systole the blood is pushed out into the aorta.

Diastole : The relaxation of the heart is called as diastole. Usually it refers to the
relaxation of the ventricles. During diastole, the blood enters the into the ventricles.

Cardiac Cycle : Period of one systole to the of next is called as cardiac cycle. Each
cardiac cycle lasts for 0.8 secs.

Ejection Fraction : The fraction of the end diastolic volume ejected is called as the
ejection fraction which is about 60% (70/110 = 63%)

Ejection fraction=Stroke volume/end-diastolic volume

Preload : It is defined as the tension on the cardiac muscle before it begins to contract.
This corresponds to the end diastolic pressure when the ventricles has become filled.
Venous return ( Blood pumped out of heart ) determines the preload.

After load : It is the load against which the ventricles have to contract. It is determined
by the peripheral resistance.

Cardiac Output : It is the amount of blood pumped out of the heart per minute. In a
healthy adult at rest,
CO = Heart Rate X Stroke Volume.

Cardiac output is affected by End diastolic volume, venous return, strength of myocardial
contraction, and blood volume. Heart rate is affected by Autonomic stimulation.

The stroke volume is approximately 70 ml and if the heart rate is 72 per minute, the
cardiac output is 5 lit per minute. This can be greatly increased to meet the demands of
exercise to around 25 lit per minute and in athletes upto 35 lit per minute. This increase
during exercise is called the cardiac reserve.
Peripheral resistance : The diameter of the blood vessels varies from place to place,
aorta being the largest and capillaries being the smallest blood vessels. The progressive
decrease in the diameter of vessels from heart to periphery, offer resistance to the blood
flow. In other words, the heart has to overcome this resistance in order to pump the
blood into the blood vessels.

The Circulatory System

Functions : The circulatory system is involved in haemostasis as it ensures continuous

supply of blood to all body cells.
Control of this system enables rapid response to changes that affect delivery of adequate
blood to the tissues.

Blood : Blood is the body’s major transport system. It has the following important
functions :
It carries respiratory gases, nutrients and wastes.
It passes through different organs and enables detection of variation in hormone
levels, pH and temperature.
It protects against infections and tumours

Blood is classified as a connective tissue and is a thick suspension of cells in watery

electrolyte solution. When whole blood is centrifuged it separates into plasma and cells.

Plasma is a clear liquid that remains after the blood cells are removed. The plasma
constituents are :
Water 90%
Protein 8%
Inorganic ions 1% in the form of sodium chloride and sodium bicarbonate.
Organic acid and other substances 1%

Plasma proteins are divided into three major types :

Albumin 4.5 gms%
Globulin 2.5gms%
Fibrinogen 0.3 gms %

The primary function of albumin is to prevent the plasma from leaking out of the
capillaries into interstitial spaces

The globulins perform diverse functions like transporting various substances, protecting
the body against various infections.

The fibrinogen plays an important role in clotting mechanisms. Fibrinogen is a high

molecular weight protein polymer occurring in plasma in quantities 100-700 mg/100ml.
Fibrinogen is formed in the liver, and liver disease occasionally decrease concentration of
circulation fibrinogen. Fibrinogen is converted to fibrin, which is a monomer by protein
enzyme thrombin. Fibrin threads form a mesh work in which the blood cells get
entangled resulting in formation of a clot.

There are three types of blood cells :

Red Blood Cells (RBC) : The RBC contains hemoglobin which gives the blood red color
and transports oxygen . In normal man, the average number of red blood cells per cubic
millimeter is 5,200,000 and in normal women 4,700,000.

White Blood Cells (WBC) :The WBC protect the body from various infections. The
adult human being has 7000 WBC/mm3. The WBC are of following types

Neutrophils 62%
Eosinophils 2.3%
Basophils 0.4%
Monocytes 5.3%
Lymphocytes 30%

The neutrophils, monocytes and the lymphocytes attack and destroy the invading
bacteria. The eosinophils destroy some of the inflammation mediating substance released
by the damaged tissue. The basophils liberate heparin which is a powerful anti
-coagulant.

Platelets: Platelets or thrombocytes are small cells without nucleus and play a very
important role in blood clotting. A normal human contains about 1,50,000 -
3,00,00 platelets per cubic millimeter of blood

Blood vessels

These vary in size and function. They are:

arteries,arterioles, veins, venules and capillaries.

Arteries and arterioles

These are the blood vessels that transport blood away from the heart. Arteries have
thicker walls than veins and this enables them to withstand the high pressure of arterial
blood.

Veins and Venules

The veins are the blood vessels that return blood to the heart. The walls of the veins are
thinner than those of arteries but have the same three layers of tissue

Capillaries and sinusoids

The smallest arterioles break up into number of minute vessels called capillaries.
Capillary walls consists of a single layer of endothelial cells through which water and
other small molecular substances can pass. Blood cells and large molecule substances
such as plasma protein do not normally pass through capillary walls. The capillaries form
a vast net work of tiny vessels which link the smallest arterioles to the smallest venules.

AUTONOMIC NERVOUS SYSTEM (ANS)

It is a part of the nervous system which controls the vital functions of the body and
functions of viscera. The term viscera refers to the organs situated in various body
cavities, eg. lungs, heart, intestine, kidney, uterus etc.

ANS functions without our knowledge and independent of our “will”. This system helps
to control vital functions like temperature regulation, blood pressure variation, secretion
of various organs, sweating etc.

The ANS is under the control of various centers (specialized areas where the nerve cells
perform a definite function of decision making) situated in spinal cord, medulla, pons and
hypothalamus. In addition to this the cerebral cortex sends impulses to these centers

exerting a supreme control over the functioning of ANS.

The autonomic nervous system has two major subdivisions:

1) Sympathetic nervous system
2) Parasympathetic nervous system

All the important viscera of the body are innervated by both sympathetic and
parasympathetic nervous system. Broadly speaking, the actions of sympathetic and
parasympathetic are opposing each other. This helps in regulation of visceral functions.
The relative predominance of sympathetic or parasympathetic decides the end result
result in the functioning of viscera.

The autonomic nervous system operates via certain chemical substances called as
neurotransmitters.

The neurotransmitters for the SNS are adrenaline and noradrenaline

The neurotransmitters for the PNS is acetylcholine.

When the neurotransmitters are released from the nerve endings, they combine with
certain receptors present on the endorgans.

Receptors of SNS are : adrenergic receptors. They are divided into two types ; alpha and
beta blockers. Alpha receptors are further divided into alpha one and alpha two and beta
also similarly. Once the neurotransmitter combines with the receptor , it produces its
activity such as vasodilatation, vasoconstriction etc.

Receptors of the PNS are : Muscarinic receptors and nicotinic receptors.

 BLOOD PRESSURE

The blood circulating in the vascular bed is constantly kept within a definite range of
pressure. The mechanisms involved in its regulation are interdependent and are rather
complex.

The blood pressure (B.P.) always shows a rhythmic variation in its magnitude showing a
peak and trough pattern. These changes are related to the contraction (systole) and
relaxation (diastole) of the heart. Values of B.P. are always mentioned in pairs
indicating systolic blood pressure and diastolic blood pressure, in that order, e.g. 120/80
mm Hg.

Blood pressure can be defined as the lateral pressure exerted by blood on the vessel walls.

Systolic blood pressure - it is the maximum pressure during systole (contraction of heart).

Diastolic blood pressure - It is the minimum pressure attained during diastole (relaxation
of heart). The diastolic measurements is by far the more important of the two in cases of
high blood pressure, as it indicates the state of arteries and the amount of peripheral
resistance which has to be overcome.

B.P. is measured by an instrument called a sphygmomanometer or simply a B.P.

apparatus. By convention, a column of mercury (Hg) is used as measure to express B.P.
values. When we say that the B.P. is 120/80 mm Hg. then it means that the systolic
pressure is 120 and the diastolic pressure is 80 mm of mercury.

What parameters affect BP?

Blood Pressure = Cardiac Output X Peripheral Resistance

Thus, if there is an increase in either the cardiac output (CO) or the peripheral resistance
(PR) it will lead to an increase in B.P. The increase in Cardiac Output reflects by
increasing the systolic B.P. whereas, the increase in the peripheral resistance reflects by
increasing the diastolic B.P.There are a number of factors which control these two
parameters.

Factors controlling cardiac output

1. Force of contraction of heart

2. Rate of contraction of heart
3. Venous return.
4. Volume of circulating blood.
1. Force of contraction

A forceful contraction of heart would naturally increase the blood pumped out every
heart beat. This would ultimately lead to an increase in cardiac output. By the same
logic, the cardiac output will decrease should the force of contraction decrease.

2. Rate of contraction :

Within limits, the cardiac output will increase as the heart rate increases. Similarly, the
cardiac output will decrease as the heart rate is decreased.

3. Venous return :

The deoxygenated blood reaches the right atrium through the superior and inferior
venacava. The amount of blood reaching back to the heart per minute is called as the
venous return. Thus the venous return provides an input to the heart. If we consider heart
as a pump, then the input and output must be equal in order to maintain the efficiency of
the pump. Thus, within physiological limits, cardiac output proportionally increases as
the venous return increases.

4. Blood Volume
An adult male has about 5 liters of blood circulating in his body. The venous return
increases as the blood volume increases ultimately showing an increase in the cardiac
output.

Factors controlling the peripheral resistance :

1.Velocity of blood.
2.Viscosity of blood.
3. Elasticity of blood vessel.
4. Lumen/Caliber of blood vessel.

1. Velocity :
As the speed of blood flow increases, the friction between blood and

vessel wall increases. This increase in friction will proportionally increase the resistance.
Hence, the blood pressure in aorta is high as the velocity of blood flow is high and the
blood pressure in capillaries is low as the velocity of blood flow is low.

2. Viscosity :

Viscosity or thickness of a fluid also significantly contributes to resistance when flowing

through a vessel. The viscosity of blood (which is more than water) also plays an
important role in maintaining the peripheral resistance. More the viscosity, more
peripheral resistance.

3. Elasticity of vessel walls :

The blood vessels, except capillaries, have elastic fibres in their walls. These fibres
enables the blood vessel to dilate as the blood flow or the pressure increases, thus
accommodating larger volume of blood. This property of a vessel further helps to
minimize the friction.

As the age advances, elasticity of the vessels decreases and the arteries become thick and
offer more resistance to the blood flow. This leads to an increase in the peripheral
resistance.

4. Lumen of the vessel :

Peripheral resistance is inversely proportional to the diameter of the blood vessel i.e.
smaller the diameter, more is the resistance. By this logic, capillaries should offer a
maximum resistance to the blood flow. However, this is not so, as the velocity of blood
flow is considerably low in capillaries helping to prevent increasing the peripheral
resistance.

To summarize, the relation of blood pressure to various factors is as follows :

Blood pressure = Cardiac outputx Peripheral resistance

(Maintains systolic (Regulates diastolic
blood pressure) blood pressure.)

1. Venous return 1. Velocity

2. Force of contraction 2. Viscosity
3. Heart rate 3. Elasticity of vessels
4. Blood pressure 4. Lumen of vessels.

CONTROL OF BLOOD PRESSURE

Let us now understand the mechanisms involved in controlling the blood pressure. For
understanding purpose, we can divide the control mechanisms into 4 parts. Please note
that all these mechanisms cannot control the blood pressure in isolation. They are
interrelated. The controls are as follows

• Central Nervous System

• Vaso Motor Center
• Baroreceptors
• Renin Angiotensin - Aldosterone System (RAAS)

If the blood pressure falls, baroreceptors present on the arch of the aorta and the carotid
arteries are stimulated, they pass the information to the vasomotor center and this sends
the impulses to the heart , kidney and the blood vessels. The heart increases its force of
contraction and rate, kidney release renin which increases BP and the blood vessels are
constricted. All these together increase the BP. Opposite effect occurs when there is an
increase in the BP.

Central Nervous System

Cerebrum of the brain is also known as large brain. The cortex region of this cerebrum
has centers which get stimulated during situations like stress, anger, tension etc. This
results in stimulation of sympathetic system and as a result increase in blood pressure.

Vaso Motor Center

Adjacent to the hypothalamus in our brain we have a center called vaso motor
center(VMC). This center is primarily involved in controlling the tone of the blood
vessels. In other words, VMC causes constant state of partial contraction of blood
vessels. VMC sends continuous sympathetic stimuli to various organs. The sympathetic
stimuli show following effects.

Increase in heart rate

• Increase in force of contraction of the heart
Vasoconstriction
• Increase in renin release

The net effect of this is rise in blood pressure.

As you know, neither an abnormal rise nor a drastic fall in blood pressure is desirable.
Hence as the blood pressure starts rising beyond optimum level there are some control
mechanisms which come into picture. One such important mechanism is baroreceptors.

Baroreceptors

As the name suggests, these are the receptors sensitive to changes in pressure. These
receptors are sensitive to the stretch in the vessel wall and hence rise in blood pressure.
As the blood pressure starts rising cardiac output increases. This causes stretch in the
vessel walls and thereby stimulate the baroreceptors which are present in carotid sinus
and arch of aorta (Fig. 10). As the heart pumps the blood into the body, aorta is the first
artery to receive it. Since, this aorta has baroreceptors, any alteration in blood pressure is
immediately sensed.

The baroreceptors when stimulated start sending a negative impulse to the VMC. As a
result the sympathetic outflow to various organs is cut off. This stops further rise in
blood pressure. Thus this reflex stimulation of baroreceptors helps maintain our blood
pressure at desired level.
Renin Angiotensin Aldosterone System (RAS )

As mentioned earlier, a significant fall in blood pressure is also not desirable. Whenever
the blood pressure starts falling below normal RAS gets stimulated and it corrects the
blood pressure back to normal.

Renin is produced by a special type of cells of nephron .These cells are called Juxta
Glomerular (JG) cells. (Juxta = adjacent, Glomerulus = network of capillaries in
Bowmen capsule). These cells (JG) are sensitive to fall in BP. Whenever, there is
reduction in the blood supply to kidney, JG cells get stimulated and start producing renin.
This brings the BP back to normal. Moreover, JG cells have ß1 receptors. Hence, due to
sympathetic stimulation renin is produced as well. The net effect is rise in BP.

Liver produces an inactive peptide called angiotensinogen. This gets converted to a

substance called angiotensin I in presence of renin which is produced by kidney. This
angiotensin I is also an inactive decapeptide. It is the Angiotensin Converting Enzyme
(ACE) which converts angiotensin I to an active octapeptide angiotensin II.

Angiotensin II, thus produced is a potent vasoconstrictor. It therefore, reduces the lumen
of the blood vessel and increase the peripheral resistance. This in effect increases the
blood pressure.

Another important pharmacological effect of angiotensin II is that it causes release of

aldosterone from adrenal cortex. Aldosterone thus released causes retention of sodium
and water. This increases the blood volume and hence cardiac output, leading to rise in
blood pressure.
 HYPERTENSION

Hypertension is defined as an elevation of systolic and/or diastolic blood pressures to

above 140/90 mm Hg.

Individuals may be subdivided according to their blood pressure levels into normal and
hypertension stages 1,2,3, and 4 ( Joint National Committee on Detection , Evaluation
and Treatment of High Blood Pressure)

Category SBP(mmHg) DBP(mmHg)

Normal <130 <85

High Normal 130-139 85-89
Stage 1 (mild) 140-159 90-99
Stage 2 (Mod) 160-179 100-109
Stage 3 (Severe) 180-209 110-119
Stage 4 (Very severe) >210 >/= 120

Further hypertension can be classified into two categories:

Essential Hypertension Nearly 80 to 90% of the hypertensive patients belong to this

category. In these patients a specific cause for hypertension cannot be identified.

Factors causing essential hypertension:

Heredity, Environment, Salt intake, Obesity, Occupation, Family size and crowding, Age,
Race, Sex, Smoking, Serum, Cholesterol, glucose intolerance and weight may all alter the
prognosis of this disease.

Secondary hypertension: Secondary hypertension is hypertension due to a specific cause.

Primary renal disease, reduced ability to excrete sodium, tumor of adrenal cortex
(Cushing’s syndrome) are some of the causative factors.

In addition to the above mentioned factors, presence of diabetes, hyperlipidaemia and

smoking are known to aggravate hypertension and related complications.

Complications of Hypertension

Hypertension predisposes to atherosclerosis and has specific effects on particular organs.

 Heart :The rate and force of cardiac contraction are increased to maintain the
cardiac output against a sustained rise in arterial pressure. The left ventricle
hypertrophies and begins to fail when compensation has reached its limit. This is
followed by back pressure and accumulation of blood in the lungs, hypertrophy of
 the right ventricle and eventually to right ventricular failure. Hypertension also
predisposes to ischaemic heart disease and aneurysm formation.

 Brain : Stoke, caused by cerebral hemorrhage is common, the effects depending

on the position and size of the ruptured vessel. when a series of small blood
vessels rupture eg microaneurysms at different times there is progressive
disability. Rupture of a large vessel causes extensive loss of function or possibly
death.

 Kidneys: Essential hypertension causes kidney damage. If sustained for only a

short time recovery may be complete. Otherwise the kidney damage causes
further hypertension, progressive loss of kidney function and kidney failure.

 Eyes :High blood pressure can ultimately lead to blindness due to hemorrhage or
retinopathy.

Management of hypertension:

Today, there is a consensus that antihypertensive therapy should be aimed at lowering of

diastolic B.P and to maintain the same at around 90mm of Hg. In case of secondary
hypertension the cause should be thoroughly investigated and treated accordingly.

Class MOA

1. Diuretics hydrochlorthiazide excretes water and sodium

2. ACEIs enalapril/Ramipril inhibits the Ag II formation
3. Beta blockers atenolol/ Metoprolol blocks the beta receptors
4. alpha blockers prazosin blocks the alpha receptors
5. calcium channel blockers amlodipine/Diltiazem blocks the entry of calcium
6.Angiotensin receptor blocker Losartan / Candesartan Inhibits Ag II formation by
acting at the final step

Management of hypertension consists of:

I. Non drug management:

a) relief of stress
b) weight reduction
c) Regular exercise
d) reduced salt intake
e) control of concomitant disease, hypercholesterolemia.

II. Drug therapy:

CURRENTLY AVAILABLE TREATMENTS FOR HYPERTENSION

Classification of antihypertensive drugs by their primary site or mechanism of action

1) Diuretics : Diuretics act by decreasing reabsorption of sodium Na+ from the

glomerular filtrate. Thus it increases the loss of Na+ in the urine which cause an osmotic
effect thus increasing the loss of fluid. however, along with increased excretion of Na+,
the excretion of K+ is also increased. This action of diuretics can lead to hypokalaemia,
an important and potentially dangerous side effect.

Different types of diuretics

Thiazides K+ sparing Loop or high ceiling

Chlorthiazide Spironolactone Frusemide

Hydrochlorthiazide Triamterene
Benzthiazide Amiloride

Diuretics are contraindicated in type II diabetes, in hyperlipiiaemic patients or in patients

with an abnormal lipid profile. In general diuretics are not recommended for young
patients because they are more likely to have high renin hypertension and secondly, they
are likely to require long term therapy which may lead to a greater risk of developing
metabolic complications.

2) Beta adrenergic antagonists/ß-blockers.

There are different drugs available which act by blocking either the ß1-receptors or both
ß1 & ß2 receptors. ß blockers can be classified as selective or non selective ß blockers.
The drugs acting predominantly on ß1 receptors are called as cardio selective ß blockers
as the ß1 receptors are predominantly found in the heart. When these receptors are
blocked, it reduces the force and rate of contraction of heart and the blood pressure is
lowered.

Non selective ß blockers act on both ß1 and ß2 receptors. Thus, non-selective ß-blockers
cannot be used in patients suffering from asthma, diabetes or peripheral vascular disease
concomitantly. In these cases, cardioselective ß-blockers would be used.

ß-blockers are contraindicated in congestive cardiac failure, and in patients with an

abnormal lipid profile.

3)Vasodilators: These agents act directly on the smooth muscles of the arteries causing
relaxation. This leads to a decrease in peripheral resistance and reduction in blood
pressure eg: alpha antagonists,hydralazine.

4) Calcium channel blockers: They act by blocking the entry of calcium inside the
smooth muscle cells, causing reduction in the amount of free calcium inside the vascular
smooth muscles. This action leads to the relaxation of the vascular smooth muscle
causing decrease in the peripheral resistance and reduction in the elevated blood pressure.

Eg: Nifedipine. Nitrendipine, Nicardipine, Nimodipine and Amlodipine.

5) Angiotensin converting enzyme Inhibitors: eg: Enalapril, Lisinopril, Captopril These

drugs inhibit angiotensin converting enzyme ACE which catalyses the conversion of
angiotensin I to angiotensin II. Angiotensin II is a vasoconstrictor substance.
Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. Aldosterone
causes increased Na+ and H2O retention. Thus ACE inhibitors by blocking the
formation of Angiotensin II reduce vasoconstriction and peripheral resistance leading to
decreased BP. As aldosterone secretion is also reduced, there is increased loss of Na and
H2O. Thus a reduction in blood volume leading to a decrease in blood pressure.

6. Angiotensin receptor Antagonist :

Eg Losartan, Valsartan, Candesartan

There are two Ag11 receptors , AT1 and AT2. These drugs block the AGII receptor ie
AT1.

However since it has no effect on the RAAS system, it does not have any effect on the
Bradykinin levels. Since it does not produce bradykinin, it doesn't lead to cough
production, thus indicated in patients who cannot tolerate ACE inhibitors induced cough

It can also prevent the action Ag11 produced by non ACE pathways ie AGII produced by
chymases and tonins.

7) Alpha receptor blockers : Prazosin, These block the alpha receptors on the peripheral
circulation and thus produces vasodilation, fall in peripheral resistance and thus reduction
in BP. One of the major drawback is first dose hypotension which is corrected by a slow
release formulation. It also has beneficial effects such as improving dyslipidemia and
insulin sensitivity.

.
 Ischaemic Heart Disease/Coronary Artery Disease

What does IHD/CAD mean?

Coronary artery disease is the disease of the coronary artery. It occurs because of
ischemia and /or infarction in the coronary artery.

What is Cardiac Ischaemia

Cardiac ischemia is an impairment of the coronary blood supply, which results in the
shortage of oxygen and the nutrient supply to the cardiac tissues accompanied by
inadequate removal of metabolites consequent to reduced perfusion. The main reason for
ischemia is blockade of the coronary arteries.

Normally, the cardiac muscle undergoes aerobic respiration to produce energy, it utilizes
fatty acids and glucose to produce CO2 and water, however in the absence of oxygen,
the cardiac muscle respires anaerobically, ie it breaks down glucose to lactic acid, leading
to a reduction in pH, and ATP stores. Thus the cardiac muscle are unable to contract.
Anaerobic respiration occurs for only for a short period of time, since the by products of
such metabolism are toxic to the cells. The build up of these toxic substances can cause
localized cellular damage and sometimes even cell death or infarction.

Infarction: Infarction relates to total occlusion of the coronary blood vessel and leads to
death of the cardiac cell.

What are the Causes of Cardiac Ischemia/infarction

Cardiac ischemia occurs because of an imbalance between the myocardial oxygen supply
and demand.The cause for reduced coronary blood flow , leading to coronary obstruction
 Atherosclerosis
 coronary artery vasospasm.
 Thrombosis

Atherosclerosis

Atherosclerosis is a complex progressive process of multiple etiology that takes place in

the endothelium of the blood vessels, which includes interaction between plasma lipids,
lipoproteins, monocytes, platelets as well as the endothelium and smooth muscle cells of
the arterial wall. In the coronary vessels , it is the epicardial arteries which are usually
affected by atherosclerosis.`

A complex cascade of events gradually leads to narrowing of coronary arteries ending in

thrombosis and coronary infarction.

Atherosclerosis is characterized by formation of foam cells, fatty streaks, fibrous plaques

and complicated lesions.

The endothelial cells lining the intima are exposed to repeated or continuing insults to
their integrity. Egs of injury include chemical injury as in chronic hypercholesterolemia,
mechanical stress eg. Hypertension, immunologic injury as seen after cardiac or renal
transplantation.
Endothelial injury

High plasma LDL

Adherence of platelets LDL infiltration into intima

Release of PDGF OLDL

Other growth factors

Cell proliferation Macrophage

Advanced lesions Foam cells

Fatty streak

Steps in atherosclerosis

1. Entry of LDL cholesterol into the endothelial cells.

2. Oxidation of LDL cholesterol by free radials produced by endothelial cells.

The injury to the blood vessel due to mechanical , chemical or immunological reasons,
activates the platelets with the release of a growth factor and the monocytes bind to the
injured cells. they then migrate into the arterial wall to get converted to macrophages.
The macrophages have a scavenger receptor that has a high affinity for oxidized LDL.

3. binding of OLDL to the scavenger receptor on the macrophage and not LDL receptor
on the cell.

The scavenger receptor is not under feedback regulation and thus accumulates massive
amount of cholesterol as free and esterified form. This leads to the formation of the
foam cells.

4. The platelet growth factor along other factors stimulate both the migration of the
smooth muscle cells from the middle layer to the intima and their proliferation at these
sites. They also synthesize an extra cellular matrix, which can accumulate lipid. (this
process is enhanced by hyperlipidemia). this leads to the formation of fatty streak.
They appear as yellowish/whitish patches on the intimal surface. It causes little
obstruction and no ymptoms.

5. The lesion shortly progresses involving a gradual increase in smooth muscle cells,
macrophages, connective tissue lipid leading to formation of plaques. These are raised
lesions or pearly plaques. They are elevated areas of intimal thickening and represent the
most characteristic lesion of advancing atherosclerosis. It is firm, elevated and dome
shaped with an opaque surface that bulges into the lumen. It consists of a central core of
extra cellular lipid and necrotic cell debris covered by a fibromuscular layer or cap
containing large number of smooth muscle cells, macrophages and collagen.

Thrombosis : Thrombosis is a process for the cessation of blood flow. Thrombus is

defined as an abnormal clot produced at an abnormal place and at an abnormal time. It
generally leads to obstruction of blood flow and thus coronary artery disease or
cerebrovascular disease.

Coronary Artery Disease CAD / Ischaemic Heart Disease IHD / Acute Coronary
syndrome – ACS :

It consists of Stable angina , unstable angina and finally leading to Myocardial

infarction

Stable angina Unstable angina Myocardial infarction ( H.Attack )

A patient may progress from one condition to the other or he may directly get MI and die.
The basis of all these diseases is atherosclerosis.

Difference between stable and Unstable Angina Pectoris : Chest Pain only at exercise
and not during rest is called stable angina and unstable angina occurs both during
rest and exercise .

Risk Factors

Risk factors can be divided into modifiable and non modifiable risk factors

Modifiable Risk Factors

Smoking
Hypertension
Diabetes mellitus
Elevated lipid levels
Obesity
Physical inactivity

Non Modifiable Risk Factors

Age >55 yrs

Male Sex and
Premature Family history

Prevention of CAD

Coronary artery disease is not entirely treatable but it is preventable.

Primary prevention : People who have the above risk factors are highly prone to CAD. To
prevent a person from getting CAD, one must reduce the risk factor effect. This is called
as primary prevention. ie preventing the high risk person from getting the first attack.

Secondary prevention : To prevent the further attacks. Here the patient already suffers
from CAD (it may be Stable, unstable angina) and to prevent its progression.

Prevention of MI

Primary prevention : Usually CAD is progressive. A patient of Stable angina and unstable
angina is at a high risk of getting an AMI. To prevent him from getting an attack, he is
protected by certain therapies.

Secondary prevention : a patient who has already suffered from MI, needs to be protected
from further attack.

Stable and Unstable Angina Pectoris

Presence of a stable plaque usually leads to stable angina pectoris, The major cause of
Chronic stable angina pectoris is narrowing of the coronary artery due to atherosclerosis.

 It is a discomfort in the chest or adjacent areas ( Usually Left and right arm).
 It is caused by myocardial ischemia
 In all these conditions, however coronary obstruction is already present, and
increases in the myocardial oxygen demand in the presence of a fixed or limited
O2 supply precipitates ischemia and chest discomfort.
 The episodes are relieved by rest.
Treatment

Treatment consists of the following.

1. Identification and treatment of aggravating conditions:

Eg conditions such as obesity, hypertension , hyperthyroidism may be identified and
treated to reduce the frequency of angina attacks.
Cigarette smoking, anemia or pulmonary disease decreases myocardial O2 supply which
need to be identified and treated.

2. Adaptation of Activity
Since angina episodes are due to an imbalance in the O2 supply and demand. This basic
principle can be used to adapt the patients to their activities.

3. Treatment of Risk factors

All the modifiable risk factors such as hypertension, diabetes mellitus, obesity, smoking ,
hyperlipidemia should be treated and controlled.

4. Drug therapy :
Three categories of drugs are used for the management of Stable angina. These are :

 Nitrates
 Beta blockers
 Calcium channel blockers
 Trimetazidine

Nitrates :They cause systemic venodilatation thus reducing myocardial wall tension and
oxygen requirements . Dilate the epicardial coronary vessels and increase the blood flow
in collateral vessels.

Eg : Nitro glycerin or triglyceryl nitrate , Isosorbide dinitrate ,Isosorbide mononitrate

Beta Adrenergic Blockers

They reduce myocardial oxygen demand by inhibiting the increases in heart rate and
myocardial contractility caused by adrenergic activity.

Propranolol
Metoprolol
Atenolol and others.

Calcium Channel Blockers

They reduce myocardial oxygen demand by reducing contractility and peripheral

resistance. They also cause coronary vasodilatation
Verapamil, nifedipine, amlodipine, nitrendipine, diltiazem.

SECONDARY PREVENTION

1.Low dose aspirin, Clopigrel or ticlopidine. These are given since the patient is a high
risk patient and may get an event at any time..

2. Statins : for stabilization of plaque which inturn will reduce mortality

3. ACEI s; they reduce mortality and cardiac events and stroke

Acute Myocardial Infarction

It occurs when there is a abrupt decrease in coronary blood flow following a thrombotic
occlusion of a coronary artery previously narrowed by atherosclerosis. The damage to the
tissue is permanent because cardiac muscle cannot regenerate and the dead tissue is
replaced with non functional fibrous tissue.

Slowly developing high grade coronary artery stenoses usually do not precipitate acute
infarction because of the development of a rich collateral network over time.

Symptoms

Crushing Pain, which is prolonged, lasting for more than 30 minutes and frequently for a
number of hours and not relieved by rest.

Management

• Nitrates : Sublingual; long acting to be avoided initially. IV nitrates reduces the

infarct size in AMI patients
• Analgesics
• Oxygen for hypoxemia
• Beta blockers : Used to limit the size of the infarct
• Thrombolytic drugs eg Streptokinase, urokinase
• Anti platelet drugs : Low dose aspirin 150 mg to prevent further clot formation
and reocclusion., clopigrel, ticlopidine
• Anti coagulants : IV Heparin or LMWH
• ACEI prevents LV remodeling and incidences of cardiac failure.
• Percutaneous coronary intervention or coronary artery bypass Surgery

Secondary prevention

Antiplatelets such as low dose aspirin, clopidogrel, ticlopidine

 Statins
ACEI
Beta blockers
All these above protect the patient from getting a second attack.

HEART FAILURE

CARDIAC FAILURE : Cardiac failure is defined as the failure of the heart to pump
enough blood to satisfy the metabolic needs of the tissues of the body .

Cardiac failure or 'heart failure can result from any condition that reduces the ability of
the heart to pump blood. Cardiac failure may involve either side of the heart, but as both
sides pump in parallel, failure of one side usually results in failure of the other.

In mild cases, cardiac output is adequate at rest & becomes inadequate only when
increased cardiac output is required.

In normal individuals , the heart employs several compensatory mechanisms to maintain

pumping ability when metabolic demands are increasing (i.e during exercise, emotional
stress). The myocardium can adapt by stretching the cardiac cells to increase the
ventricular end-diastolic volume and / or by increasing the contractile strength of the
myofibrils. Factors that alter the end-diastolic volume include total blood volume, body
position, venous tone, etc. Factors that increase the contractile strength of the
myocardium cells include sympathetic nerve stimulation of myocardial cells and
elevation of circulating catecholamines to increase heart rate.

The causes of cardiac failure may be due to

 Work overload or mechanical abnormalities such as high systemic arterial

pressure, aortic stenosis and valvular regurgitation

 Myocardial abnormalities or loss of myocytes due to infarction , toxins, and

metabolic disorders like diabetes

 Altered cardiac rhythm or conduction disturbances.

Cardiac failure can be either acute or chronic.

Acute Cardiac Failure

A sudden diminution in output of blood from both ventricles causes acute reduction in the
oxygen supply to all the tissues. Recovery from the acute phase may be followed by
chronic failure, or death may occur due to anoxia of vital centers in the brain. The
commonest causes are :

Severe damage to an area of cardiac muscle due to ischemia caused by sudden occlusion
of one of the large coronary arteries by atheroma or atheroma with thrombosis.

Pulmonary embolism
Acute toxic myocarditis
Severe cardiac arrhythmia
Rupture of a heart chamber or valve cusp
Severe malignant hypertension.

Chronic Cardiac Failure

This develops gradually and in the early stages there may be no symptoms because the
heart compensates by increasing the rate and force of contraction and ventricles dilate.
Myocardial cell hypertrophy increases the strength of the muscle. When further
compensation is not possible there is a gradual decline in myocardial efficiency. During
the development of chronic failure, hypoxia and venous congestion cause changes in
other systems, making still greater demands on the heart, e.g. renal, endocrine,
respiratory.

ARRHYTHMIA

The word arrhythmia in simple words means variation from normal rhythm of the heart
beat. The variation could be either way, increase in heart beat i.e. tachycardia or decrease
in heart beat i.e. bradycardia.

Arrhythmia includes an abnormality of rate, regularity or site of origin of the cardiac

impulse or a disturbance in conduction.

 TACHYCARDIAS : Tachycardia is a type of arrhythmia at heart rates

exceeding 100 beats per minute. Usually tachycardia occurs in structurally
diseased heart than in normal hearts.
 Bradycardia : Bradycardia is defined as a heart rate less than 60 beats per minute.
Bradycardia may be due to vagal tone in athletes or more commonly as an
unwanted effect of beta adrenoceptor blocking drugs.