A) CARDIOVASCULAR DISEASE

1) Normal Cardiac Cycle

Phase Blood Flow AV Semilunar Significant Heart sound ECG
(Direction) valves valves volume
I Atrium Open Close At least 2/3 of the No heart Beginning of P
Rapid ventricle blood flows from sound wave
ventricular atrium *3rd heart
filling ventricle sound
(diastole) (abnormal)
II Atrium Open Close 1/3 of the No heart End of P
Atrial systole ventricle remaining blood sound wave
(contraction) (faster) flows to the *4th heart beginning of R
No more ventricle sound wave
blood in (abnormal)
atrium,
ventricle full
III No blood Close Close End diastolic 1st heart QRS complex
Isovolumetric flow, all the volume (EDV) sound-‘LUB’ *Ventricle
contraction blood in (closure of supercharged
ventricle 130mL AV valves) *Electrical
impulse passes
through AV
node
IV Ventricle Close Open Stroke volume 3rd heart QT interval
Ventricular atrium (EDV-ESV) sound can *Refractory
systole occur in period:
(Ejection) 70mL normal, ventricle
healthy cannot be
person charged
V Blood flows Close Close End systolic 2nd heart End of T
Isovolumetric out from the volume (ESV) sound- ’DUP’
Relaxation ventricle (closure of
body/lungs 60mL semilunar
valves)
Cardiac Conduction System:

1
Sounds:
S1: Mitral and tricuspid valve closure. Loudest
at mitral area
S2: Aortic and pulmonary valve closure.
Loudest at left sternal border
S3: In early diastole during rapid ventricular
filling phase. Associated with ↑filling pressures
(e.g. mitral regurgitation, CHF) and more
common in dilated ventricles (but normal in
children and pregnant women)
S4 (“atrial kick”): In late diastole. High atrial
pressure. Associated with ventricular
hypertrophy. Left atrium must push against stiff
LV wall.

Jugular venous pulse (JVP):

a wave: Atrial contraction
c wave: RV contraction (closed tricuspid valve
bulging into atrium)
x descent: Atrial relaxation and downward
displacement of closed tricuspid valve during
ventricular contraction. Absent in tricuspid
regurgitation
v wave: ↑right atrial pressure due to filling
against closed tricuspid valve.
y descent: Blood flow from RA to RV

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 2) Congenital Heart Disease ( VSD, ASD, PDA, CoA, ToF)
VentricularSeptal Defect
Definition  Ventricular septal defect describes one or more holes in the wall (septum) that
separates the right and left ventricles of the heart.
 Ventricular septal defect is one of the most common congenital (present from birth)
heart defects, approximately around 25%-30% of all CHD.
 It may occur by itself or with other congenital diseases.

Pathophysiology In VSD, blood in each ventricle has 2 possible systolic pathways: through the usual outflow
tract of that ventricle or through the VSD to the outflow tract of the other ventricle. In
normal pulmonary vascular resistance and a large, non-restrictive VSD, the sum of resistors
from the LV to the pulmonary artery is very low compared with the resistance of flow to the
systemic circulation, resulting in a large left-to-right systolic flow across the defect. If the
VSD is very small (restrictive VSD), there is high resistance at the defect itself, limiting the
left-to-right shunt, even with low pulmonary resistance.

A left-to-right shunt at the ventricular level has 3 hemodynamic consequences:

 Reduced systemic cardiac output

 Increased LV volume load
 Excessive pulmonary blood flow

Left-to-right shunt at the ventricular level→ right ventricular hypertrophy→ enter the
pulmonary artery→ ↓ LV output by the amount of the shunt→ ↓cardiac output → body
compensatory mechanisms→↑intravascular volume in response to↓ cardiac output until
LV end-diastolic volume is sufficient to pump both a normal cardiac output and the
proportionate left-to-right shunt → addition of the extra blood to the normal pulmonary
flow from the vena cava→ ↑ blood flow to the lungs→ pulmonary hypertension→
↑pulmonary venous return into LA→ significant LV volume overload→↑ LV dilatation and
hypertrophy→↑ LV volumes elevate LA filling pressures → pulmonary venous congestion
at rest or during periods of exertion→ both PA pressure and pulmonary venous pressure
are ↑→ lungs receive too much blood under too much pressure→ arterioles (small
arteries) in the lungs thicken →permanent damage to the lungs→ irreversible pulmonary
vascular disease → suprasystemic blood pressure→ reversal of shunt→ cynotic→
Eisenmenger’s syndrome

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Signs & Left to right shunt→ ↑ pulmonary circulation→ ↓systemic blood flow→ lung blood flow is
Symptoms enormous → tiny ventricles cannot pump such a volume→ congestive heart failure→
activate renin-angiotensin-aldosterone system & sympathetic system→↑work of breathing

Other Signs and symptoms

 Shortness of breath
 Fast breathing
 Hard breathing
 Paleness
 Failure to gain weight
 Fast heart rate
 Sweating while feeding
 Frequent respiratory infections

Diagnosis Lab tests

 It is not specific but may offer insight into the severity of the disease.
 The CBC may show polycythemia, especially in patients with Eisenmenger’s
syndrome.
 Arterial blood gas results may demonstrate hypoxemia.

Imaging studies

 ECG finding vary in accordance with the size of the VSD and depend on whether
pulmonary hypertension is present. With large VSDs with pulmonary hypertension,
right axis deviation is seen along with right ventricular hypertrophy.
 Chest X-ray shows:
 Cardiomegaly that results from left ventricular volume overload that directly
relates to the magnitude of the shunt.
 The enlargement of proximal pulmonary arteries along with the

4
 redistribution and pruning of the distal pulmonary vessels as a result of
sustained pulmonary hypertension.
 Echocardiography is the imaging modality of choice for the diagnosis of VSD:
 2-D echocardiography and colour Doppler display the side and location of
the VSD, the chamber size, ventricular function, the presence of aortic valve
prolapsed or regurgitation, outflow tract obstruction and tricuspid
regurgitation.
 Continuous-wave Doppler approximates the gradient between the left and
the right ventricles and estimates the pulmonary artery pressure.
 The magnitude of shunt can be determined by the calculation of the
pulmonary-to-systemic flow ratio.
 MRI and computed tomography scanning can be useful to assess the pulmonary
artery, pulmonary vein, and to confirm the anatomy of unusual VSD that are not
seen well in echocardiography.
 Heart sound: A ventricular septal defect produces a holosystolic murmur or
pansystolic murmur. Blood abnormally flows from the LV (high pressure) to the RV
(low pressure) creating turbulent blood flow and a holosystolic murmur heard best
at "Erb's point". The smaller the ventricular septal defect, the louder the murmur. A
very small VSD can cause a palpable thrill (vibration on the chest). A small VSD with
a loud murmur is called "Maladie de Roger”.A prominent murmur heard through a
stethoscope is usually the only sign that brings the VSD to attention. This murmur is
commonly noted during the first week of life.

Managements How is a small VSD treated?

&Treatments
One-third to one-half of all small VSDs close spontaneously (on their own). This seemingly
miraculous event occurs most often before the baby is 1 year old, almost always before age
4 (75% by 2 years of age). The closure is due to the small VSD being located between heart
fibers that increase in size in time, thus encroaching upon the opening in the ventricular
septum.

Even if a small VSD does not close spontaneously, surgical repair is usually not
recommended. However, long-term follow-up is required.

How is a large VSD treated?

Ultimately, the patient with a large VSD will need surgery to close the septum with stitches
or a special patch the ventricular septum. The timing of surgery is an individualized decision
based upon several factors. These include

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 Medical management. Some children have no symptoms, and require no medication.
However, some children may need to take medications to help the heart work better, since
the right side may be under strain from the extra blood passing through the VSD.
Medications that may be prescribed include the following:

 Digoxin. A medication that helps strengthens the heart muscle, enabling it to pump
more efficiently.
 Diuretics. The body's water balance can be affected when the heart is not working
as well as it could. These medications help the kidneys remove excess fluid from the
body.
 ACE inhibitors. Medications that lower the blood pressure in the body, making it
easier for the blood to be pumped from the left ventricle into the body (because of
its lowered blood pressure) rather than that blood being pumped from the left
ventricle across the VSD into the right ventricle then into the lungs.

Adequate nutrition. Infants with a larger VSD may become tired when feeding, and are not
able to eat enough to gain weight. Options that can be used to ensure baby will have
adequate nutrition include the following:

High-calorie formula or breast milk. Special nutritional supplements may be added to

formula or pumped breast milk that increases the number of calories in each ounce,
thereby allowing baby to drink less and still consume enough calories to grow properly. the
nose, down the esophagus, and into the stomach, can either supplement or take the place
of

Supplemental tube feedings. Feedings given through a small, flexible tube that passes
through bottle feedings.

Surgical repair. The goal is to repair the septal opening before the lungs become diseased
from too much blood flow and pressure.

Interventional cardiac catheterization. . One method currently being used to close some
small muscular VSDs is the use of a device called a septaloccluder. During this procedure,
the child is sedated and a small, thin flexible tube is inserted into a blood vessel in the groin
and guided into the heart. Once the catheter is in the heart, the cardiologist will pass the
septaloccluder across the VSD. The septaloccluder closes the ventricular septal defect
providing a permanent seal.

Complications  Eisenmenger's syndrome: increased blood flow to the lungs causes high blood
pressure in the lung arteries (pulmonary hypertension) if the defect left untreated.
Over time, permanent damage to the lung arteries develops and the pulmonary
hypertension can become irreversible. This complication, called Eisenmenger's
syndrome. People with Eisenmenger's syndrome, there is a significant portion of
blood flows through the ventricular septal defect from the right ventricle to the left
and bypasses the lungs. This means deoxygenated blood is pumped to the body and
leads to a bluish discoloration of the lips, fingers and toes (cyanosis) and other

6
 complications. Once a person has Eisenmenger's syndrome, it is too late to surgically
repair the hole because irreversible damage to the lung arteries has already
occurred.
 Heart failure: Infants who have large VSDs may develop heart failure because the
left side of the heart pumps blood into the right ventricle in addition to its normal
work of pumping blood to the body. The increased workload on the heart also
increases the heart rate and the body's demand for energy.
 Endocarditis: People with a ventricular septal defect are at increased risk of an
infection of the heart (endocarditis) due to the high velocity, turbulent jet of blood
into the right ventricle.
 Growth failure: A baby may not be able to eat enough to keep up with his or her
body's increased energy demands. As a result, the baby may lose weight or not grow
and develop normally.
 Arrhythmias (irregular heartbeats): The extra blood flowing through the heart can
cause areas of the heart to stretch and enlarge. This can disturb the heart's normal
electrical activity, leading to arrhythmias.
 Stroke. People with large defects, especially occurring with Eisenmenger's
syndrome, are at risk of a stroke due to a blood clot passing through the hole in the
heart and going to the brain.

Atrial Septal Defect

Definition An atrial septal defect (ASD) is a hole in the part of the septum that separates the whereby
hole allows oxygen-rich blood from the left atrium to flow into the right atrium instead of
flowing into the left ventricle.

The three major types of ASDs are:

 Ostium secundum. This defect is in the middle of the atrial septum result of
excessive reabsorption of septum primum. It is the most common form of ASD. At
least half of all secundum ASDs close on their own or by simple suturing or
placement of a patch of tissue to completely close the opening. It is less likely if the
defect is large.
 Ostium primum. This defect is in the lower part of the atrial septum due to the
deficiency of endocardial cushion tissue. It often occurs along with problems in the
heart valves that connect the upper and lower heart chambers. Primum defects
aren't very common, and they don't close on their own.
 Sinus venosus. This defect is in the upper part of the atrial septum, near where the
superior vena cava resulting from an error in the incorporation of the sinus venosus
chamber into the RA results in simple closure would not allow proper drainage of
blood into the appropriate sides of the heart. Sinus venosus defects are rare, and
they do not close on their own.

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Pathophysiology The blood flow is predominantly left to right. In ASD → LA pressure is higher than RA→ left
to right shunt→ when ASD become larger→ pressure in both atria are almost equal→
therefore flow of blood depend on the distensibility (compliance) of both ventricles→ as
RV is more distensible → blood flow from LA to RA and then to the RV

In newborn, there is no flow across ASD. With the onset of respiration, the lungs expand
and pulmonary resistance↓→ pulmonary involute & pulmonary vascular resistance ↓
further→ ↑RV compliance→ RV cavity becomes thinner→ at the same time with the
elimination of placenta circulation→ systemic resistance↑→ LV cavity mass ↑→ LV
hypertrophy & ↓compliance→ RV compliance is more than that of LV→ left to right
shunt→ ↑pulmonary flow→ ratio of pulmonary-to-systemic blood flow or shunt
fraction↑( Qp>Qs) → pulmonary venous return will exceed systemic venous return→
increased RV afterload → pulmonary hypertension &incomplete ventricular emptying → RV
will be hypertrophied and less compliant→ reversal of shunt→ cynotic→ Eisenmenger’s
syndrome

8
Signs & ASD in fetal life→ high pulmonary vascular resistance→ allow nearly unidirectional right-to-
Symptoms left flow at the atrial level→ RV noncompliance→ Immediately after birth→ with RV
compliance comparable to that of the LV→ little net shunting through an ASD→ Over
several months→ physiological fall in pulmonary vascular resistance→ RV thins &
compliance falls→ left-to-right shunt → LV myocardium become more hypertrophied and
less compliant→ inefficiency of a continuously preload-reduced LV & volume overload in
the pulmonary circulation→ ↓maximum oxygen consumption

Other Signs and symptoms

 Shortness of breath on exertion

 Fatigue
 Frequent lung infections
 Stroke
 Bluish skin colour
 Swelling of legs, feet or abdomen (due to heart failure)
 Heart palpitations
 Poor feeding
 Slow growth rate

Diagnosis  Radiograph: show volume overload of the right side of the heart and increase
pulmonary vascularity.
 ECG: right axis deviation and right ventricular hypertrophy due to diastolic overload
(incomplete right bundle branch block pattern). Occasionally, conduction defect of
the sinus and atrio-ventricular node may be present.
 2-D echocardiography:show drop-out of the atrial septum where each defect is
located. Anomalies of the pulmonary and systemic veins should be sought. Colour
flow Doppler imaging helps to identify left to right shunt.
 Cardiac catheterization: it is unnecessary for diagnosis but used if there is a
question about an associated defect or if pulmonary vascular disease is suspected.
 chest X-ray: reveals enlargement of the right side of the heart
 Heart sound: As the pressure in the left atria initially exceeds that in the right, the
blood flows in a left to right shunt. This high volume of blood next passes into the
right ventricle, and the ejection of the excess blood through a normal pulmonary
valve produce the prominent mid-systolic flow murmur known as ejection systolic
murmur. This murmur is best heard over the “pulmonic area” of the chest, and may
radiate into the back which can mimic pulmonary stenosis.The most characteristic
feature of an atrial septal defect is the fixed- split S2.

Managements Medications
&Treatments
 beta blockers (Lopressor, Inderal) and digoxin (Lanoxin): Keep the heartbeat
regular
 Anticoagulants: Reduce the risk of blood clots, can help reduce the chances of
developing a blood clot and having a stroke. Anticoagulants include warfarin
(Coumadin) and anti-platelet agents, such as aspirin.

9
 Surgery

It is recommended to repair the atrial septal defect during childhood to prevent

complications as an adult. For adults and children, surgery involves plugging or patching the
abnormal opening between the atria through two methods:

 Cardiac catheterization. A thin tube (catheter) is inserted into a blood vessel in the
groin and guided to the heart. Through the catheter, a mesh patch or plug is put
into place to close the hole. The heart tissue grows around the mesh, permanently
sealing the hole.
 Open-heart surgery. This type of surgery is done under general anesthesia and
requires the use of a heart-lung machine. Through an incision in the chest, surgeons
use patches or stitches to close the hole

Complications  Right heart failure. This defect intact it permits an extra amount of the blood flow
across the two upper chambers. This adds more blood to the pumping
responsibilities of the right heart, causes the right side of the heart to work harder
because it has to pump extra blood to the lungs. Over time, the heart may become
tired from this extra work and not pump well.
 Atrial arrhythmias. Extra blood flowing into the right atrium through an ASD can
cause the atrium to stretch and enlarge, stretching the conduction system. Over
time, this can lead to arrhythmias (irregular heartbeats) due to progressive dilation
of the right heart chambers
 Stroke. Lungs usually filter out small blood clots that can form on the right side of
the heart. An opening between the heart chambers raises the risk of a blood clot
migrating into the left sided heart circulation and travel to the brain, causing a
stroke.
 Pulmonary hypertension (PH). PH is increased pressure in the pulmonary arteries.
These arteries carry blood from heart to lungs to pick up oxygen. Over time, PH can
damage the arteries and small blood vessels in the lungs. They become thick and
stiff, making it harder for blood to flow through them. Severe PH can lead to right to
left shunt, resulting oxygen levels in the blood decrease, leading to a condition
known as Eisenmenger’s syndrome.
 Eisenmenger’s syndrome. In rare cases, pulmonary hypertension can cause
permanent lung damage, and it becomes irreversible. This complication, called
Eisenmenger syndrome. People with Eisenmenger's syndrome, there is a significant
portion of blood flows through the septal defect and bypasses the lungs. This means
deoxygenated blood is pumped to the body and leads to a bluish discoloration of
the lips, fingers and toes (cyanosis) and other complications.
 Endocarditis: People with an artrial septal defect are at increased risk of an infection
of the heart (endocarditis) due to the high velocity, turbulent jet of blood into the
right atrium. Atrial septal defect at the ostium secundum has a low or even no
probability of infective endocarditis when compared to that of defect at the ostium
primum which has a larger defect.

10
 Patent DuctusArteriosus
Definition The ductus arteriosus,is a tubular arterial structure connecting the aorta and main
pulmonary artery. In the fetal circulation, ductus allow RV blood to bypass the non-
expanded & non-ventilated lungs. Both the low PO2 of the blood & high level of circulating
prostaglandins in the fetus inhibit the constriction of the ductus. The high levels of
prostaglandins result from the little amount of pulmonary circulation and the high levels of
production in the placenta. In the normal newborn, the lung expansion occurs immediately
on delivery. As a result, most of the RV blood diverted immediately to the now lowered-
resistance pulmonary vascular bed. This obligatory flow through the lungs allows circulating
prostaglandins in the fetus to be cleared by the lungs and permits immediate oxygenation
of the blood, thereby increasing the circulating PO2, resulting the normal constriction of the
ductus.
Within 72 hours of birth, the ductus closes in most newborns through the contraction of an
arteriolar smooth muscle layer due to the rise in postnatal systemic oxygen levels. If the
lumen of the ductus is not fully obliterated, an arterial connection remains between the
systemic and pulmonary circulations, called “patent” ductusarteriosus (PDA).

Pathophysiology Patent ductus arteriosus→↑ aortic pressure→ systemic resistance is significantly higher
than pulmonary resistance→ left to right shunt→ blood flow from aorta to the pulmonary
artery→ overloading of pulmonary circulation→ pulmonary engorgement → ↓pulmonary
compliance→ blood return to the left side of the heart, pass via the lungs & is pump out to
the aorta once again→ severe volume overload of the left side of the heart→ LA & LV must
accommodate the↑ pulmonary venous return→ ↑filling pressure & workload on the left
side of the heart→ LV & LA dilatation& hypertrophy→ progressive myocardial
deterioration→ left sided congestive heart failure → untreated→ blood pressure in the
lungs ↑→ pulmonary hypertension→ dilatation of RV→ suprasystemic pressure→ reversal
of shunt→ cyanosis→ Eisenmenger’s syndrome

11
Signs & Left-to-right shunting → pulmonary over-circulation → left heart volume overload→
Symptoms congestive left heart failure→ Pulmonary edema

↑ Pulmonary flow from the ductal shunting→ ↑ pulmonary fluid volume→↓ lung
compliance→↑work of breathing

↑ Flow returning to the left heart →↑LA and LV end-diastolic pressures→ LV compensates
by↑ stroke volume → LV hypertrophy to normalize wall stress→ neuroendocrine
adaptations →↑sympathetic activity and circulating catecholamines →↑contractility and
heart rate→ tachycardia

Other Signs and symptoms

 Fast breathing
 Poor feeding habits
 Rapid pulse
 Shortness of breath
 Sweating while feeding
 Tiring very easily
 Poor growth

 Thrill palpable at the left sternal border caused by the shunting of blood from the
aorta to the pulmonary artery.
 Prominent left ventricular impulse due to left ventricular hypertrophy.
 Bounding pulse (Corrigan’s pulse) due to high flow state

Diagnosis  Chest X-ray: show increased pulmonary vascular marking, prominent pulmonary
arteries and enlargement of left ventricle and aorta.
 Electrocardiography (ECG): it may be normal or may indicate left atrial or
ventricular hypertrophy and, in pulmonary disease, biventricular hypertrophy.
 Echocardiography: detect and estimate the size of PDA. It also reveals an enlarged
LA and LV or RV hypertrophy from pulmonary disease.
 Cardiac catheterization: shows higher pulmonary arterial oxygen content than right
ventricular content because of the influx of aortic blood. Increased pulmonary
artery pressure indicates a large shunt or, if it exceeds systemic arterial pressure,
severe pulmonary vascular disease. It allows for the calculation of blood volume
crossing the ductus and can aid in ruling out associated cardiac defects. Injection of
a contrast agent can conclusively demonstrate PDA.
 Heart sound: a classic machinery, or Gibson, murmur can be identified. This murmur
is continuous and is heard throughout systole and diastole due to shunting of blood
from the aorta to the pulmonary artery throughout systole and diastole. It is best
heard at the base of the heart, at the second intercostal space under the left
clavicle. The murmur may obscure the second heart sound. However, this murmur
may be absent in the right to left shunt.

12
Managements & Medications
Treatments  Indomethacin (prostaglandin inhibitor), ibuprofen: induce dustus spasm and
closure in premature infants. NSAIDs block the hormone-like chemicals in the body
that keep the PDA open.
Surgery
 Left thoracotomy: to ligate the dusctus if medication management cannot control
heart failure.
 Visual assisted thoracoscopic surgery (VATS): to ligate the ductus as an alternative
to surgery with a thoracotomy.
 Open-heart surgery. If medications do not the PDA, and baby's condition has caused
health problems, open-heart surgery may be recommended.
 Catheter procedures. Catheter procedures, which are less invasive than open-heart
surgeries, they are not an immediate option for premature babies because they are
too small. However, if baby does not have any health problems related to his or her
PDA, it is recommended to wait until baby is about a year old to perform a catheter
procedure to correct the PDA. Catheter procedures tend to have fewer
complications and a shorter recovery time than do open-heart surgeries. In a
catheter procedure, a thin tube (catheter) is inserted into a blood vessel in the groin
and threaded up to the heart. Through the catheter, a plug or coil is inserted to
close the ductus arteriosus.

Complications  High blood pressure in the lungs (pulmonary hypertension). Too much blood
continues to circulate through the heart's main arteries through a patent ductus
arteriosus, it can lead to pulmonary hypertension. Pulmonary hypertension can
cause permanent lung damage. A large patent ductusarteriosus can lead to
Eisenmenger's syndrome, an irreversible type of pulmonary hypertension.
 Heart failure. A patent ductus arteriosus can eventually cause the heart to enlarge
due to extra blood flow and may cause the muscle to weaken, leading to heart
failure.
 An infection of the heart (endocarditis). Infectious endocarditis is an inflammation
of the inner lining of the heart caused by a bacterial infection due to turbulent of
blood.
 Irregular heartbeat (arrhythmia). Enlargement of the heart due to a patent ductus
arteriosus increases the risk of arrhythmias. The development of systemic
hypertension, with its rise in systemic resistance, increases shunting at the PDA.
This, combined with diminishing LV compliance (as the ventricle hypertrophies),
may substantially increase LV filling pressures and lead to pulmonary venous
congestion, disturb the electrical activity of the heart.
 Eisenmenger’s Syndrome. With long-standing left-to-right shunting, exposure of the
pulmonary artery system to high-pressure and increased flow leads to progressive
morphological changes in the pulmonary vasculature. When pulmonary vascular
resistance approaches and exceeds systemic vascular resistance, ductal shunting
reverses and becomes right to left. Microvascular injury stimulates production of
growth factors and enzymes that result in intimal proliferation and medial
hypertrophy. Endothelial dysfunction and platelet activation may also play a role in
the obliteration of pulmonary arterioles result in Eisenmenger’s syndrome.

13
 Coarctation of the Aorta
Definition Coarctation means narrowing. It describes a localized narrowing of the proximal aorta that
restricts blood flow into the distal aorta. The constriction usually located distal to the origin
of the large arteries arising from the arch of the aorta. It can be also found just below the
left subclavian artery, near the site where the ligamentum arteriosum (remnant of the
ductus arteriosus) joins the pulmonary artery to the aorta.

Pathophysiology Spasm or constriction of the smooth muscles in ductus arteriosus when it closes→
contractile tissue extends into the aortic wall→ narrowing of aorta→ obstruction→
restriction of blood flow through the narrowed aorta→ ↑pressure load on the LV→
dilatation of proximal aorta→ LV hypertrophy→ ↑blood pressure in the aortic branches
above the constriction(arms, neck & head)→ ↓ pressure in the vessels below the
constriction→ collateral circulation develop to bypass the obstruction→ supply circulation
to lower extremities

Signs &  Pale skin

symptoms  Irritability
 Heavy sweating
 Difficulty breathing
 High blood pressure
 Shortness of breath, especially during exercise
 Headache
 Muscle weakness
 Leg cramps or cold feet
 Nosebleeds
 Chest pain
 Poor growth

Narrowing can occur anywhere in the aorta, but usually occurs in the segment just beyond
the aortic arch—beyond the vessels that bring blood to the upper body, and before the
vessels that bring blood to the lower body. This is why in COA, blood pressure in the arms
will be high, and blood pressure in the legs and ankles will be low (radio radial delay &
radio femoral delay)

14
Diagnosis  Electrocardiography (ECG): It may be normal between angina episodes. During
angina, it may show ischemic changes such as T wave inversion, ST segment
depression and arrhythmias. ST segment elevation suggests either MI or
Prinzmetal’s angina. An ECG test records the electrical activity in your heart each
time it contracts. If the coarctation of the aorta is severe, the ECG will show that you
might have a thickened heart muscle (ventricular hypertrophy).
 Electron-beam computed tomography scan: identify calcium deposits in coronary
arteries. The calcium scoring correlates with the degree of CAD.
 Coronary angiography: it reveals the location and degree of coronary artery
stenosis or obstruction, collateral circulation and the condition beyond the
narrowing.
 Intravascular ultrasound: used to further define the coronary anatomy and luminal
narrowing.
 Myocardial perfusion imaging with thallium201: it is performed during treadmill
exercise to detect ischemic areas of the myocardium; they appear as ‘cold spots’
which normalize during rest, indicating viable tissue.
 Echocardiography: show abnormal wall motion in ischemic areas. Echocardiograms
use high-pitched sound waves to produce an image of your heart. An
echocardiogram may detect the location and severity of the aortic coarctation and
can show other heart defects, such as a bicuspid aortic valve.
 Chest X-ray. A chest X-ray may show an enlarged heart or a narrowing in the aorta
at the site of the coarctation.
 Magnetic resonance imaging (MRI). An MRI of the chest will reveal the location of
the coarctation of the aorta and determine whether it affects other blood vessels in
the body.
 Cardiac catheterization. During this procedure, doctor inserts a thin flexible tube
(catheter) into an artery or vein in the groin and threads it up to theheart. A dye is
injected through the catheter to make the heart structures visible on X-ray pictures.
Cardiac catheterization helps determine the severity of the aortic coarctation.
 Heart sound: a systolic murmur may be heard over the left anterior chest and
between the scapular posteriorly.

Managements & Medication

Treatments
 Nitrate (nitroglycern): it is given sublingually, orally, transdermally or topically in
ointment form) to reduce myocardial oxygen consumption.
 Beta-adrenergic blocker: to reduce heart workload and oxygen demands by
reducing the heart rate and peripheral resistance to blood flow.
 Calcium channel blocker: to prevent coronary artery spasm.
 Antiplatelet drug: to minimize the platelet aggregation and the risk of coronary
occlusion.

Surgery

 Resection with end-to-end anastomosis. This method involves removing the

narrowed segment of the aorta (resection) followed by connecting the two ends of
the aorta together (anastomosis).

15
  Patch aortoplasty. Doctor may treat the coarctation by cutting across the
constricted area of the aorta and then attaching a patch of synthetic material to
widen the blood vessel. Patch aortoplasty is useful if the coarctation involves a long
segment of the aorta.
 Left subclavian flap angioplasty. A portion of the left subclavian artery, the blood
vessel that delivers blood to your left arm, may be used to expand the narrowed
area of the artery.
 Bypass graft repair. This technique involves bypassing the narrowed area by
inserting a plastic tube called a graft between the portions of the aorta. It is to
restore the blood flow by bypassing an occluded artery using another vessel
 Key hole’ surgery: an alternative to traditional CABG using fibre optic cameras
inserted through small cuts I the chest, to correct blockages in one or two accessible
arteries

Balloon angioplasty and stenting

Balloon angioplasty is an option for initially treating aortic coarctation or for treating re-
narrowing (re-coarctation) that has occurred after surgery. During this procedure, doctor
inserts a thin flexible tube (catheter) into an artery in the groin and threads it up through
the blood vessels to the heart. An un-inflated balloon is placed through the opening of the
narrowed aorta. When the balloon is inflated, the aorta widens and blood flows more
easily. In some cases, a mesh-covered hollow tube called a stent is inserted to keep the
narrowed part of the aorta open.

Complications The most common long-term complication of coarctation of the aorta is high blood
pressure. Although the blood pressure usually falls after the aortic coarctation has been
repaired, it may still remain higher than normal. Occasionally, the segment of the aorta that
has been repaired will become weak and bulge (aortic aneurysm) and may eventually
rupture. In some cases, the coarctation will recur, possibly even years after treatment.

Complications of coarctation of the aorta include:

 Heart failure due to abnormal increase of pressure work of the LV

 High blood pressure
 Stroke
 Rupture of the aorta
 Premature coronary artery disease — narrowing of the blood vessels that supply the
heart
 Weakened or bulging artery in the brain (cerebral aneurysm)
 Organ failure (kidney, liver) due to decrease perfusion
 Infective endocarditis due to turbulent of blood

16
 Tetralogy of Fallot
Definition Tetralogy Fallot refers to a spectrum of anatomic abnormalities that have 2 features in
common:
 Large and unrestrictive ventricular septal defect
 Right ventricular outflow tract obstruction
It is results when the aorticopulmonary septum that divides the truncus unequally, results
the pulmonary artery is smaller than it should be and the aorta is too large. The upper part
of the ventricular septum which is formed in part from the aorticopulmonary septum does
not connect properly to the aorta and the pulmonary artery that extend from the
ventricles. The failed connection results in large ventricular septal defect that is straddled
by the enlarged aorta and receives blood ejected from both ventricles.
The 4 abnormalities composing the tetralogy are
 A ventricular septal defect
 Pulmonary stenosis
 An enlarged aorta that overrides the septal defect
 Right ventricular hypertrophy due to pulmonary stenosis

Pathophysiology Pulmonary stenosis→ impede the flow of blood to the lungs→ ↑ pressure in RV→
↑workload on the RV→ RV hypertrophy→ blood flow through the ventricular septum→
right to left shunt→ deoxygenated blood is pumped into the LV & arteries in the body→
overriding aorta receive blood form both RV & LV→ cyanosis

17
Signs &  ↑in the degree of right to left shunt→ ↑cardiac output→ ↓systemic arteriolar
symptoms resistance→ ↓ systemic arterial oxygen saturation→ Cyanosis (mild or
undetectable at rest but becomes apparent with increase of physical activity)
 squatting→ kinking and compression of the major arterial circulation to the lower
extremities→ ↑systemic arterial resistance→ ↑peripheral resistance→ ↓the
degree of right to left shunt→ ↑pulmonary blood flow→↑systemic arterial oxygen
saturation→ less cyanosis
 physical activity, sudden fright or injury→ ↑ right to left shunt→ ↓pulmonary
blood flow→ ↑cyanosis→ hypercyanotic→ tetralogy spells

Other Signs and symptoms

 Blue color to the skin (cyanosis), which gets worse when the baby is upset
 Clubbing of fingers (skin or bone enlargement around the fingernails)
 Difficulty feeding (poor feeding habits)
 Poor development
 Squatting during episodes of cyanosis
 Shortness of breath and rapid breathing, especially during feeding
 Loss of consciousness (fainting)
 Poor weight gain
 Tiring easily during play
 Irritability
 Prolonged crying
 A heart murmur

Diagnosis  Chest X-ray. A typical sign of tetralogy of Fallot on an X-ray is a "boot-shaped" heart,
because the right ventricle is enlarged and the concavity of the upper left heart
border resulting from the absence main pulmonary artery segment. May show
decrease pulmonary vascular marking.
 Blood test. Measures the number of each type of cell in the blood, called a

18
 complete blood count. In tetralogy of Fallot, the number of red blood cells may be
abnormally high (erythrocytosis) as the body attempts to increase the oxygen level
in the blood.
 Echocardiography. A large ventricular septal defect is easily visualized, and the
aorta overriding the ventricular defect is apparent. The infundibular narrowing of
the right ventricular outflow tract or a thickened and abnormal pulmonary valve can
be demonstrated. Doppler echocardiography shows an increased in velocity of
blood flow in the main pulmonary artery and it is useful to estimate the gradient
across the right ventricular outflow tract.
 Electrocardiogram. This test helps determine if the right ventricle is enlarged
(ventricular hypertrophy) and if the heart rhythm is regular.
 Cardiac catheterization. It is to define the severity of the stenosis in the right
ventricular outflow tract and pulmonary artery and to predict whether the repair is
successful.
 Heart sound: pansystolic mumur may be heard at the mid lower left sternal norder

Managements & Surgery is the only effective treatment for tetralogy of Fallot. There are two types of
Treatments surgery that may be performed, including intracardiac repair or a temporary procedure that
uses a shunt. Most babies and children will have intracardiac repair.

Intracardiac repair

Tetralogy of Fallot treatment for most babies involves a type of open-heart surgery called
intracardiac repair. This surgery is typically performed during the first year of life. During
this procedure, the surgeon places a patch over the ventricular septal defect to close the
hole between the ventricles. He or she also repairs the narrowed pulmonary valve and
widens the pulmonary arteries to increase blood flow to the lungs. After intracardiac repair,
the oxygen level in the blood increases and your baby's symptoms will lessen.

Temporary surgery

Occasionally babies need to undergo a temporary surgery before having intracardiac repair.
If your baby was born prematurely or has pulmonary arteries that are underdeveloped
(hypoplastic), doctors will create a bypass (shunt) between the aorta and pulmonary artery.
This bypass increases blood flow to the lungs. When your baby is ready for intracardiac
repair, the shunt is removed.

Complications All babies with tetralogy of Fallot need corrective surgery. Without treatment, baby may
not grow and develop properly. He or she is also at increased risk of serious complications,
such as infective endocarditis, an inflammation of the inner lining of the heart caused by a
bacterial infection.

Untreated cases of tetralogy of Fallot usually develop severe complications over time,
which may result in death or disability by early adulthood.

19
 3) Acute Rheumatic Fever (Aseptic)
Causative Agent β-haemolytic streptococcal pharyngitis
Pathogenesis Streptococcal pharyngitis infection  Ab against M-proteins of Gp A strep cross-react
with normal protein in the heart, joints and other tissue (neural)
Clinical Pancarditis
manifestation Endo = Vegetation
Myo=Myocardial Aschoff body (Granulomatous inflammation, Anitschkow cell +
macrophage)
Epi=Fibrous pericarditis

Nonspecific arthritis

Skin
- Aschoff nodule
- Erythema marginatum

Aseptic Endocarditis: Small warty vegetation averaging few millimeters, form along the
line of valve closure over areas of endocardial inflammation

20
Diagnostic Criteria Must Have: Positive Lab result
- +ve ASOT (Anti Streptolysin O Titer)
- +ve DNAse B
- +ve throat culture

Jones Criteria: (2 major / 1 major + 2 minors)

Major:
- Carditis
- Migratory polyarthritis
- Subcutaneous nodules (e.g. Aschoff bodies)
- Erythema marginatum
- Chorea (St. Vitus Dance/ Sydenham chorea)

Minor:
- Fever
- Arthralgia
- Previous ARF history
- Increase serum acute phase protein
- Abnormal ECG

3) Chronic Rheumatid Heart Disease (Left Heart Involvement, Aseptic vegetation)

Pathogenesis Acute rheumatic fever  pancarditis (endocarditis)  deformed heart valve  chronic
rheumatic heart disease

Chronic Deformed Heart Valve – Fishmouth Shape (Mitral stenosis) with marked
shortening and thickening of chordae tendineae & Mural thrombi (right) and enlarged
left atrium (Left)

Clinical - Irreversible deformity of cardiac valve

Manifestation - Stenosis &/or regurgitation
- Increase risk of infective endocarditis
- Cardiac failure

21
Complication (Left Heart Involvement only)
Aortic stenosis: LVH  congestive heart failure

Aortic regurgitation LVH hypertrophy and dilation

Mitral stenosis(fish mouth deformities): LAH and dilation  congestive lung  RV and
RAH and dilation  mural thrombi

Mitral regurgitation: LVH and dilation

Deformed valve increase risk of:

- Atrial fibrillation
- Thromboembolism (stasis)
- Cardiac hemolytic anaemia
Type of Murmur Murmur Best heard area Abnormality
Pansystolic Apex radiating to axilla - MR
- VSD
Mid Diastolic Apex - MS
Early Diastolic Left lower sternal edge - AR
Ejeculation Right upper sternal edge - AS
(Crescendo-
Descendo)

Treatment/ ARF: Penicilin (During + Life long)

Management
(Propylysis) CRHD: Penicilin (During + Life long) + Gentamycin

22
 4) Infective Endocarditis (Right Heart Involvement, Septic vegetation)
Predisposing Turbulence of blood flow (Diseased Heart):
Factor - Artificial heart valve
- Damaged heart valve (Rheumatic fever, infection, etc)
- Congenital heart disease
IVDU (Normal Heart)
History of IE (Right Heart involvement)
Causative Agent - Streptococcus viridian, Haemophilus influenza, etc (dental surgery)
- Staphylococcus aureus (IVDU)
Pathogenesis Inoculation through skin break/ gum  bacteria transmission in blood  pass through
heart  attached to (roughened, damaged) surface of heart valve  Septic vegetation
 IE
Diagnostic DUKEs criteria ( 2 M / 1 M + 3 m / 5 m )
Criteria
Major Minor
Positive blood culture Predisposing factors

Microorganisms consistent with IE from persistently

positive blood cultures defined as:
• 2 positive cultures of blood samples drawn >12
hours apart, or
• all of 3 or a majority of 4 separate cultures of
blood (with first and last sample drawn 1 hour
apart)

Evidence of endocardial involvement: Vascular/ Immunologic

 Valve involvement phenomena:
 Pericardial effusion  Osler’s node
Positive echocardiogram for IE defined as :  Janeway lesion
• oscillating intracardiac mass on valve or  Roth’s spot
supporting structures, in the path of regurgitant High grade fever
jets, or on implanted material in the absence of an Positive blood culture (Positive
alternative anatomic explanation, or but does not meet the major
• abscess, or criteria)
• new partial dehiscence of prosthetic valve ECHO findings (Consistence but
does not meet the major
criteria)
Complication - Loose vegetation  septic embolism  travel to brain, lung, kidney, septic infarct
 stroke and end organ damage/ abscess formation causing infection)
- Damaged heart valve  heart failure
- Septic embolism  Osler’s node, Janeway lesion, Splinter hemorrhage, Roth’s
spots, Pulmonary abcess

Treatment - 4 weeks I/V penicillin (common)

- Nafcilin + gentamicin (IVDU)
- Lifelong penicillin

23
 5) Ischemic Heart Disease
Definition Imbalance of supply and demand of the heart for oxygenated blood (>90% due to reduce
coronary blood flow secondary to atheroma)
Risk Factor Modifiable:
(Endothelial - Diabetic Mellitus
dysfunction) - Hypertension
- Dyslipidemia
- Smoking
- Alcohol
- Obesity
- Stressfull/ Sedentary Life style

Non-modifiable:
- Age
- Sex (Male)
- Family history
Complication of - Cardiac rupture  cardiac tamponade
AMI - Cardiac arrhythmia
- LV failure  pul. Edema
- Pericarditis
- Mural thrombosis
- Aneurysm
- Mitral regurgitation
- Chronic heart failure (dilated/ fibrous scarring)
- Septal infarct  VSD  death

Pathogenesis Mostly (90%) due late manifestation of atherosclerosis that begins in early life:
(10%) due to vasospasm, emboli or vasculitis

24
Atherosclerosis leading to IHD:

Endothelial
Dysfunction LDL in the blood is LDL induce Macrophage
(increase uptake into Tunica inflammatory engulf lipid
permeability) Intima response
Atheroma

Formation of Foam cells stimulate recruitment Deposition of Collagen

Foam Cells of smooth muscle cells and and Proliferation of
fibroblast from T. Media smooth muscle cells
Fatty streak

Unstable Atherosclerosis
Stable plaque plaque
plaque
Athero: Protude into
lumen
Chronic
Stable Angina
Intrinsic Factor: Extrinsic Factor
(Calcified
lipid) - Large lipid core (>50% of - Blood pressure
plaque volume) - Platelet reactivity
- High macrophage density - Local vasospasm
- Low smooth muscle - Intense emotional
density stress
- High tissue factor content
- Thin, disorganized
collagen in the fibrous cap

Endothelial Plaque Plaque

erosion Fissuring Rupture

Haematoma/ Thrombosis/
Emboli formation

Narrowing/ Occlusion of coronary artery

Decrease O2 supply

Ischemic Heart Disease

25
 Type of Ischemic Heart Disease
Chronic Acute
Stable Angina Unstable NSTEMI STEMI (Acute
Angina (Subendocardial/ Myocardial Infarct)
non-Q wave Infarct)
Fibrous cap Thick (stable) with Thin Thin Thin
underlying calcified
lipid
Thrombus No Small Big Big
Formation
(sudden)
Lumen Occlusion Minimal Small Near complete Complete
Cardiac Infarct No No (Ischemia Subendocardial Transmural (wall might
only) (tissue furthest break)
from coronary art.)
Cardiac Pain Pain on exertion Severe, sudden, > 30 mins even at rest
ECG Charges ST depression ST depression ST depression ST segment elevation
(on exertion) (at rest) (might have)

T wave Deep T wave

inversion inversion
Cardiac Markers Not raise Not raise (no Elevated Troponin-I Elevated Troponin-I
infarct) (Most sensitive)

CK, AST, LDH (Still Elevated CK, AST and

normal, low LDH (In chronological
sensitivity) order)
Treatment Reduce heart Anti-coagulant Anti-platelet Thrombolytic agent
workload (Nitrates, (Heparin) aggregation (e.g. Streptokinase,
β-blocker, CCB) (Glycoprotein IIb, Urokinase, Anistreplase)
IIIa inhibitor, e.g.
Abciximab)
Angioplasty
Angioplasty
Infarct Related Arteries
Abnormal ECG Leads Pathologic Arteries Area of Infarction
II, III, avF Right Coronary Artery Inferior Myocardial Infarction
V 3, V 4 Anterior Descending Artery Anterior Septal Infarction
V 5, V 6 Left Circumflex Artery Anterior Lateral Infarction

26
 6) Arrhythmia

Normal lead II
Lead II
1) Rate R wave to R wave 3 to 5 boxes only
2) Rhythm Equal R wave to R wave
3) PR interval 0.12-0.20 seconds/ no longer than 2 squares (1cm)
Long means heart block
4) QRS complex <0.1 seconds/ no longer than 5mm
Long means bundle branch block
5) T wave/ QT interval T inversion in ischaemic heart disease
Other lead
1) Axis deviation Lead I down= right deviation= Right ventricular hypertrophy
Lead III down= left deviation= left ventricular hypertrophy

2) Bundle branch block rsR’ or Rsr’

V1 and V2= Right ventricle
V3 and V4= Interventricular septum
V5 and V6= Left ventricle

27
3) Left ventricular hypertrophy V1+V6>7 / V2+V5>7

4) Right ventricular hypertrophy Positive V1 and V2

5) Atrial hypertrophy Lead II, lead III, aVF, P pulmonale= right atrial hypertrophy

28
 V1, P mitral= left atrial hypertrophy

Bradycardia
Sinus bradycardia

R wave to R wave more than 5 square .

Heart rate less than 60 beats per min.
10 Heart block

P wave constantly far from QRS complex.

20 Mobitz type 1 or Wenckebach Heart block

29
P wave far and farther from QRS complex.

20 Mobitz type 2 Heart block

Few P wave before QRS complex.

30 Complete Heart block

Very long R wave to R wave

30
 Tachycardia
Sinus tachycardia

Less than 3 boxes.

>100 beats per min.
Atrial flutter

150-300 beats per min.

Saw tooth appearance.
Still can see T wave.
Atrial fibrillation

>350 beats per min.

Use DC cardioversion to treat.
Ventricular tachycardia

150-350 beats per min.

No cardiac output.

31
Ventricular fibrillation

>350 beats per min.

No cardiac output.
Use DC cardioversion to treat.
Nodal tachycardia
Presence of accessory pathway connecting atria and ventricles.
The accessory pathway conducts impulses faster than normal, producing a short PR interval.
The accessory pathway also acts as an anatomical re-entry circuit, making patients susceptible to re-entry
tachyarrhythmias.
Patients present with episodes of paroxsymal supraventricular tachycardia (SVT), specifically atrioventricular
re-entry tachycardia (AVRT), and characteristic features on the resting 12-lead ECG.

1) Wolff Parkinson White Syndrome

Can cure by burning around AV node.

Prolong QRS, short PR interval.
Delta wave present.
2) Lown Ganong Levine Syndrome

Normal QRS complex, short PR interval.

Delta wave absent.

32
 7) Metabolic Syndrome
 Also known as Syndrome X, insulin resistance syndrome consists of a constellation of metabolic
abnormalities that confer the increased risk of cardiovascular disease (CVD) and diabetes mellitus.
 Clinical features: central obesity, hypertriglyceridemia, low HDL cholesterol, hyperglycemia and
hypertension.
 Factors contributing to cardiometabolic risk:

Prevalence  Increases with increasing age.

 The highest recorded prevalence worldwide is with nearly 60% of women ages
45-49 and 45% of men ages 45-49

Diagnostic criteria

33
Risk Factors 1. Overweight/ obesity:
 Central obesity: waist circumference and ↑adiposity.
 Normal weight person can also be insulin resistant and have the syndrome.
2. Sedentary lifestyle:
 ↑adipose tissue, ↓HDL cholesterol, ↑TG, BP and glucose especially in the
genetically susceptible person.
3. Age:
 A greater percentage of women >50 have the syndrome than men of same age.
4. Diabetes mellitus (DM) /Impaired glucose tolerance (IGT):
 Patients who develop this syndrome due to DM/IGT have higher prevalence of
getting cardiovascular disease.
5. Coronary heart disease (CHD):
 The approximate prevalence of the metabolic syndrome in patients with CHD is
50% with a prevalence of 37% ≤ 45 years of age, particularly in women.
Etiology 1. Insulin resistance:
 The onset of insulin resistance is heralded by the post-prandial hyperinsulinemia
 fasting hyperinsulinemiahyperglycemia.
 Actions of insulin:
a) Insulinactivate lipoprotein lipase (LPL)lipolysis of TG rich
lipoprotein muscle could uptake FA for usage and adipocyte for TG
stores
b) Insulininhibit hormone sensitive lipaseanti-lipolysis (within
adipocytes) for TG stores in adipocyte
 Insulin resistancecells could not uptake glucose↑lipolysis↑ fatty acids
(FA) further ↓ anti-lipolytic effect of insulin
 FA impair insulin mediated glucose uptake accumulate as TG in both skeletal
muscle and cardiac muscle; ↑ glucose production and TG accumulation are
seen in liver.
2. Oxidative stress hypothesis:
 An imbalance between the systemic manifestation of reactive oxygen species
and a biological system's ability to readily detoxify the reactive intermediates or
to repair the resulting damage.
 A defect in mitochondrial electron transport chain (ETC)  accumulation of TG
and related lipid molecules in muscleassociated with metabolic syndrome.
3. Increased waist circumference:
 ↑ visceral adipose tissueFA directly enters liver
 Subcutaneous adipose tissue FA enters systemic circulation and avoids direct
effects on hepatic metabolism.
4. Dyslipidaemia:
 ↑ flux of free FA to the liver↑circulating levels of VLDL 
hypertriglyceridemia
 Also, in presence of hypertriglyceridemia, a decrease in cholesterol content of
HDL is a consequence of reduced cholesteryl ester content of the lipoprotein
core in combination with cholesteryl ester transfer protein mediated
alternations in triglyceride making the particle small and dense.
 This change in lipoprotein composition ↑ clearance of HDL from the

34
 circulation.
 With fasting TG> 2.0 mM a predominance of small dense LDLs which are more
atherogenic increased atherogenic risk in metabolic syndromes.
 Small dense lipoproteins more prone to oxidation, thus, binds to scavenger
receptorfoam cellscause injury to endothelial layeratherosclerotic plaque
5. Glucose intolerance:
 Defects in insulin action impaired suppression of glucose production by the
liver and kidney + reduced glucose uptake and metabolism in insulin sensitive
tissues; muscle and adipose tissue.
 To compensate for defects in insulin action, insulin secretion/clearance must be
modified to sustain euglycemia.
6. Hypertension:
 Insulin is a vasodilator with secondary effects on sodium reabsorption in the
kidney.
 In insulin resistancevasodilatory effect is lost, but the renal effect is
preserved↑sodium reabsorption ↑vascular volumehypertension
 Insulin also ↑ the activity of sympathetic nervous system which is retained in
insulin resistance.
 Finally, insulin resistance is characterised by pathway specific impairment in
phosphatidylinositol 3-kinase signalling in the endothelium  imbalance in the
production of nitric oxide and secretion of endothelin-1↓blood flow.
7. Proinflammatory cytokines:
 ↑ proinflammatory cytokines including, IL-1, IL-6, IL-8, resistin, TNF- α and C-
reactive protein, reflect overproduction by the expanded adipose tissue mass.
 Adipose tissue derived macrophages may be the primary source of pro-
inflammatory cytokines locally and in the systemic circulation.
 A prothrombotic state, characterized by increased plasma plasminogen
activator inhibitor (PAI)-1 and fibrinogen, also associates with the metabolic
syndrome.
 Fibrinogen, an acute-phase reactant like CRP, rises in response to a high-
cytokine state. Thus, prothrombotic and proinflammatory states may be
metabolically interconnected.

35
8. Adiponectin:
 Adiponectin is an anti-inflammatory cytokine produced exclusively by
adipocytes, ↓in metabolic syndrome due to suppression by other
proinflammatory cytokines produced by adipocytes.
 Action of adiponectin:
a) It enhances insulin sensitivity and inhibits many steps in the inflammatory
process.
b) In the liver: inhibits the expression of gluconeogenic enzymes and the rate
of glucose production.
c) In muscle: ↑ glucose transport and enhances fatty acid oxidation, partially
due to activation of AMP kinase.
 Insulin resistance in obesity↑adipocyte size ↑proinflammatory
cytokines ↓adiponectinenhance gluconeogenesis + ↓glucose
transportthus, in obese person, difficult to utilize circulating fatty acids and
glucose.

36
Treatment 1. Insulin resistance:
Antidiabetics MOA
Biguanides, thiazolidinediones (TZDs) ↑ insulin sensitivity
Metformin and TZDs Enhance insulin action in the liver and
suppress endogenous glucose production.
TZDs Improve insulin mediated glucose uptake in
muscle and adipose tissue.

2. LDL-cholesterol:
Drugs MOA
HMG CoA reductase inhibitors 20-60% ↓ LDL cholesterol
E.g. Statins
Cholesterol absorption inhibitor 15-20% ↓ LDL cholesterol
E.g. ezetimibe
Bile acid sequestrants  More effective than ezetimibe
E.g. cholestyramine & colestipol  Used in caution in patients with metabolic
syndrome because they often ↑TG.
 Binds with bile acids form insoluble
complexes in the intestineprevent
reabsorption in the GITexcreted in faeces
loss of bile acidplasma cholesterol converted
to bile acids in the liver to normalize
levels↓plasma cholesterol levels.

3. TG:
 A fibrate (gemfibrozil or fenofibrate): to ↓ fasting TG and typically achieve a 35-
50% reduction.
 Other drugs that ↓ TG: statins, nicotinic acid and higher doses of ω-3 fatty
acids.
4. HDL cholesterol:
 Beyond weight reduction, exercise ↑ HDL. Don’t smoke.
5. Blood pressure:
 ACE inhibitor or Angiotensin II receptor blocker: ↓ incidence of new onset type
2 diabetes.
6. Obesity:
 Weight loss drugs:
Drugs MOA
Appetite suppressants Phentermine: Sympathomimetic amine;
E.g. phentermine & sibutramine induces anorectic effect via release of
norepinephrine in the hypothalamus↑
blood leptin concentrationappetite
suppressed
Sibutramine: a neurotransmitter
reuptake inhibitor that ↓the reuptake of
serotonin, norepinephrine, and
dopamine ↑ the levels of these

37
 substances in synaptic clefts enhance
satiety
Lipase inhibitors Inhibit pancreatic lipaseno degradation
E.g. orlistat of TGprevent the absorption of
TGTG excreted out from body

7. Lifestyle:
 Weight loss includes a combination of calorie restriction, ↑physical activity and
behaviour modification.
 Evidence suggests that the addition of exercise to calorie restriction may
promote relatively greater weight loss from the visceral depot.
8. Diet:
 It is important to emphasise that it takes a longer time for a patient to achieve
an expanded fat mass. Thus, the correction need not occur quickly.
 On the basis of ~3500kcal = 1lb of fat, thus ~500kcal restriction daily equates to
a weight reduction of 1lb per week.
 Diet restricted in carbohydrate typically provides a rapid initial weight loss.
Complications  Type 2 Diabetes Mellitus:
Occurs when body no longer make enough insulin/unable to use insulin
properlyhyperglycemiakidney failure/cardiovascular disease.
 Cardiovascular disease:
Fatty acid deposit on arterial wallatherosclerosisblock narrow
arteriesrestrict blood flow↓blood supply to major organs
(heartangina/heart attack, brainstroke)

38
 8) Myocardial Disease - Cardiomyopathy
Definition • Cardiac diseases attributable to intrinsic myocardial dysfunction.
• Literally, it is also known as heart muscle diseases
• Cardiomyopathies can be primary, which is, principally confined to the
myocardium; or secondary, presenting as the cardiac manifestation of systemic
disorders.

Causes 1. Primary cardiomyopathy

1. Idiopathic dilated c.
2. Idiopathic hypertrophic c.
3. Idiopathic restrictive c.
i. Cardiac amyloidosis
ii. Endocardial fibroelastosis
iii. Endomyocardial fibrosis
iv. Loeffler’s endocarditis
2. Secondary cardiomyopathy
1. Nutritional disorders (alcoholic c, beri-beri)
2. Toxic chemicals (cobalt, arsenic, lithium etc.)
3. Drugs (cyclophosphamide, catecholamines)
4. Metabolic diseases (amyloidosis, haemochromatosis, glycogen storage
diseases)
5. Neuromuscular (muscular dystrophies)
6. Infiltration (leukaemia, carcinoma)
7. Connective tissue disease (SLE, Rh arthritis)

Clinicopathological classification
1. Dilated cardiomyopathy = congestive cardiomyopathy (most common)
2. Hypertrophic cardiomyopathy
3. Restrictive cardiomyopathy (least common)

39
 A) Dilated Cardiomyopathy
Definition • Most common cardiomyopathy (90% of cases)
• It is characterized by progressive cardiac dilation and contraction (systolic)
dysfunction, usually with concurrent hypertrophy; regardless of cause, the
clinicopathologic pattern is similar.

Etiology • Idiopathic or congenital (most often) [Inherited genetic abnormalities are

responsible for 20-30% of cases including many previously consigned to the
idiopathic category. Mutation in genes coding for cytoskeletal protein.]
• Chronic alcohol abuse
• Wet Beriberi
• Coxsackie B virus myocarditis
• Chronic cocaine use
• Chagas disease
• Doxorubixin toxicity (Chemotherapeutic agents)
• Hemochromatosis
• Peripartum cardiomyopathy (occurring in late in pregnancy or several weeks to
months postpartum)

Risk factors • Any age, most common in 20-60 yrs.

• Mostly sporadic although familial cases are being recognised with increasing
frequency.
• Male>Female, possibly reflecting association with alcohol abuse.

Pathogenesis Genetic causes:

• Autosomal dominant inheritance is the predominant pattern, most commonly
involving the mutation in encoding cytoskeletal proteins or proteins that link the
sarcomere to the cytoskeletal (α-cardiac actin)
• X-linked DCM is most frequently associated with dystrophin gene mutations
affecting the cell membrane protein that physically couples the intracellular
cytoskeletal to ECM.

40
Pathophysiology As ventricular stroke volume and cardiac output decline because of impaired myocyte
contractility, two compensatory effects are activated:

(1) the Frank–Starling mechanism, in which the elevated ventricular diastolic volume
increases the stretch of the myofibers, thereby increasing the subsequent stroke
volume;

(2) neurohormonal activation, initially mediated by the sympathetic nervous system.

The latter contributes to an increased heart rate and contractility, which help to buffer
the fall in cardiac output.

These compensations may render the patient asymptomatic during the early stages of
ventricular dysfunction; however, as progressive myocyte degeneration and volume
overload ensue, clinical symptoms of heart failure develop.

Damaged myocardial muscle fibers→ ↓ contractility of lefventricle→Persistent

↓cardiac output, systolic function, ejection fraction & stoke volume→ ↓ renal blood
flow → kidneys secrete ↑ amounts of renin. →activation of the renin-angiotensin-
aldosterone axis→ ↑peripheral vascular resistance (mediated through angiotensin II)
and intravascular volume (because of increased aldosterone) → buffering the ↓cardiac
output→ however, “compensatory” effects of neurohormonal activation prove
detrimental→ Arteriolar vasoconstriction and ↑ systemic resistance → render it more
difficult for the LV to eject blood in the forward direction & the ↑ in intravascular
volume→ further burdens the ventricles→ pulmonary and systemic congestion→
chronically elevated levels of angiotensin II and aldosterone→ directly contribute to
pathological myocardial remodelling and fibrosis→ cardiomyopathic → ventricles
enlarge over time→ the mitral and tricuspid valves may fail to coapt properly in
systole→ valvular regurgitation ensues→ regurgitation has three detrimental
consequences: (1) excessive volume and pressure loads are placed on the atria, causing
them to dilate, often leading to atrial fibrillation; (2) regurgitation of blood into the left
atrium further decreases forward stroke volume into the aorta and systemic circulation;
and (3) when the regurgitate volume returns to the LV during each diastole, an even
greater volume load is presented to the dilated LV.

41
Clinical features • It is typically manifests with signs of progressive CHF
• Dyspnea (due to decreased tissue perfusion)
• Fatigue
• Poor exertion capacity
• Lightheadedness
• Cool extremities (due to decreased cardiac output & peripheral
vasoconstriction)
• dyspnoea, orthopnea, and paroxysmal nocturnal dyspnea (due to Pulmonary
congestion)
• ascites and peripheral edema (due to chronic systemic venous congestion)
The fundamental defect in DCM is ineffective contraction. Therefore, in end-stage
DCM, the cardiac ejection fraction is typically less than 25%  progressive CHF which
becomes refractory to therapy.
Diagnosis • Secondary mitral regurgitation
• Abnormal cardiac rhythm
• Embolism from mural thrombi
• Heart failure
• S3
• Dilated heart (four-chamber cardiac enlargement )on echocardiogram
• Balloon appearance of heart on CXR
• Electrocardiogram (ECG) usually demonstrates atrial and ventricular
enlargement. Patchy fibrosis of the myofibers results in a wide array of
arrhythmias, most importantly atrial fibrillation and ventricular tachycardia.
Conduction defects (left or right bundle branch block) occur in most cases.
Diffuse repolarization (ST segment and T wave) abnormalities are common. In
addition, regions of dense myocardial fibrosis may produce localized Q waves,
resembling the pattern of previous myocardial infarction.

42
Morphology Gross
• Heart is enlarge (up to 2-3 times the normal weight)
• Flabby, with dilation of all chambers
• Mural thrombi are often present

Dilated cardiomyopathy (enlarged, globoid, flabby) Wt >900g. Poor contractile function

predispose to stasis  mural thrombi and embolism.

Four chambers dilation and hypertrophy. A small mural thrombus can be seen at the
apex of the left ventricle(arrow)

Histology
• Nonspecific, do not typically point to a specific etiologic entity
• Marked accumulation of intramyocardial hemosiderin stained with Prussian
blue can be seen in DCM secondary to iron overload

43
 Myocyte hypertrophy and interstitial fibrosis(collagen is blue in this Masson trichrome-
stained )
Treatments  Na+ restriction
 ACE inhibitors
 Beta-blockers
 Diuretics
 digoxin
 implantable cardioverter defibrillator (ICD)
 heart transplant (life –saving)

44
 B) Hypertrophic cardiomyopathy
Definition It is characterized by myocardial hypertrophy, defective diastolic filling and ventricular
outflow obstruction.

Etiology • 60-70% of cases are familial, autosomal dominant (commonly a β-myosin heavy
– chain mutation)
• Rarely associated with Friedreich ataxia
• Can cause sudden death in young athletes due to ventricular arrhythmia

Risk factors • Any age, typically manifests during the postpubertal growth spurt

Pathogenesis HCM is fundamentally a disorder of sarcomeric proteins. Of these, beta-myosin heavy

chain is most frequently affected, followed by myosin-binding protein C and troponin T.
Mutation of gene→ affect sarcomeric proteins → ↑ myofilament activation→ myocyte
hypercontractility with concomitant ↑ in energy use & net negative energy balance

Pathophysiology Hypertrophied ventricle become stiff→ hypertrophy of intraventricular septum→ non-

compliance→ rapid & forceful contraction of left ventricle→ unable to relax during ventricular
filling→ obstruction of left ventricular outflow→ ↓ ventricular filling→ ↑left ventricle filling
pressure → forceful ejection of blood→ draw the anterior leaflet of mitral valve to
intraventricular septum→ early closure of the outflow tract→ ↓ ejection fraction→ ↑left atrial
& pulmonary venous pressure→ venous congestion→ further ↓ in ventricular filling time→
↓cardiac output→ papillary muscle become hypertrophied→ cannot close completely during
contraction→ mitral insufficiency

45
Clinical features It is characterized by a massively hypertrophied left ventricle that paradoxically
provides a markedly reduced stroke volume. This condition occurs as a consequence of
impaired diastolic filling and overall smaller chamber size due to the abnormally stiff
thick-walled ventricle.
 S4
 ↓ cardiac output & secondary ↑ pulmonary venous pressure→ exertion
dyspnoea
 Anterior leaflet of mitral valve & dynamic obstruction to the left ventricular
outflow→ harsh systolic ejection murmur
 Massive hypertrophy + high left ventricular pressure + compromised intramural
arteries→ myocardial ischemia (with angina) even in the absence of CAD
 Mural thrombus → atrial and ventricular fibrillations
 Infective endocarditis of mural valve
 CHF
 Death
Morphology Gross
• Massive myocardial hypertrophy without ventricular dilation
• Disproportionate thickening of the ventricular septum relative to left ventricle
free wall (asymmetrical septal hypertrophy)
• Concentric hypertrophy (10%)
• Longitudinal section→ ventricular cavity loses its usual round-to-ovoid shape→
compressed into banana-like configuration
• Endocardial plaque in the left ventricular outflow tract
• Thickening of anterior mitral leaflet

Septal muscle bulges into left ventricular outflow tract, give rise to a banana shaped
ventricular lumen. The left atrium is enlarged

46
 Histology
• Myocyte hypertrophy
• Haphazard myocyte disarray
• Interstitial fibrosis

Disarray, extreme hypertrophy and characteristic branching of myocytes and interstitial

fibrosis
Treatments  Cessation of high intensity athletics
 Use of beta-blockers or non-dihydropyridine calcium channel blocker
(verapamil)
 ICD if patient is high risk
 Therapy that promotes ventricular relaxation
 Partial surgical excision
 Controlled alcohol-induced infarction of septal muscle to relieve outflow tract
obstruction

47
 C) Restrictive cardiomyopathy
Definition It is characterized by a primary decrease in ventricular compliance, resulting in
impaired ventricular filling during diastole.

Etiology • Idiopathic
• Endomyocardial fibrosis (most common)
• sarcoidosis
• amyloidosis
• postradiation fibrosis
• endocardial fibroelastosis (thick fibroelastic tissue in endocardium of young
children)
• LÖffler syndrome (endomyocardial fibrosis with a prominent eosinophilic
infiltrate)
• Hemochromatosis (dilated cardiomyopathy can occur)
Pathophysiology Reduced compliance of the ventricles, whether due to infiltration or fibrosis, results in
an upward shift of the passive ventricular filling curve, leading to abnormally high
diastolic pressures. This condition has two major consequences:
(1) elevated systemic and pulmonary venous pressures, with signs of right- and left-
sided vascular congestion, and
(2) Reduced ventricular cavity size with decreased stroke volume and cardiac output.

Left ventricular hypertrophy & endocardial fibrosis and thickening→ Stiffness of ventricle→ ↓
ability of ventricle to contract→↓ ventricular filling during diastole & ↑ diastolic ventricular
pressure→ rigid myocardium fails to contract completely during systole→ ↓ cardiac output &
venous congestion

48
Clinical features • Heart failure
• Stiff and inelastic ventricle that can be filled only with great effort. (resemble
hypertrophic cardiomyopathy but systole is not forceful)
• Fatigue, exertional dyspnea, decreased exercise tolerance and chest pain. (due
to decrease in cardiac output)
• arrythmias and AV block (when fibrosis or infiltrative process encroaches on
conduction system)
• Jugular venous distension, peripheral edema, and ascites with a large, tender liver due
to systemic congestion )
• Myocardial contractility declines in later stages  CHF
• Haemodynamic derangements are quite similar to constrictive pericardial
disease but the latter may be amenable to surgery.

Morphology Gross
Ventricles are approximately normal size or slightly enlarge
Cavities are not dilated
Firm myocardium
Biatrial dilation (due to poor ventricular filling and pressure overload)

Histology
Variable degrees of interstitial fibrosis

Morphology varies with the cause eg haemochromatosis, amyloidosis.

Tropical endomyocardial fibrosis:
• Atria dilated, ventricles normal sized
• Endocardium thickened & opaque
• Valve may be thickened ± thrombi
• ± eosinophils.
Endocardial fibroelastosis
• Abundant fibroelastic tissue  porcelain-like endocardial surface.
• Associated congenital cardiac valvular abnormalities are common.

49
Haemochromatosis : Perls stain for haemosiderin

50
 8) Myocardial Disease - Myocarditis
Definition • Diseases that is intrinsic to myocardial fibers.
• Inflammatory disorders
• Encompasses a diverse group of clinical entities in which infectious agents and/
or inflammatory processes primarily target the myocardium.
• The heart muscle becomes inflamed and weakened, causing symptoms of heart
failure, which may mimic a heart attack.

(The presence of inflammation alone is not diagnostic of myocarditis because it can be

a secondary phenomenon in conditions such as ischaemic injury. In myocarditis, the
inflammatory process plays a primary role in the development of myocardial injury.)

Causes Infections
• Viruses (e.g., coxsackievirus, echovirus, influenzavirus,
 human immunodeficiency virus, CMV)
• Chlamydia (e.g., C. psittaci )
• Rickettsia (e.g., R. typhi [typhus fever])
• Bacteria (e.g., Corynebacterium [diphtheria], Neisseria [meningococcus],
 Borrelia [Lyme ds]
• Fungi (e.g., Candida)
• Protozoa (e.g., Trypanosoma [Chagas disease], toxoplasmosis)
• Helminths (e.g., trichinosis)
Immune-Mediated Reactions
• Postviral
• Poststreptococcal (rheumatic fever)
• Systemic lupus erythematosus
• Drug hypersensitivity (e.g., methyldopa, sulfonamides)
• Transplant rejection
Unknown
• Sarcoidosis
• Giant cell myocarditis

Pathogenesis • Direct injury eg enterovirus cause cytoskeletal abnormalities within cardiac

myocytes.
• Toxins eg. C. diptheriae
• T-cell mediated injury
• Antibody-mediated eg rheumatic fever

51
Pathophysiology Most cases of myocarditis are caused by viral infection
Mechanism of action:
1. Initially there is a direct viral invasion of myocytes. Virus can be detected in the
myocardium and interstitium where macrophages are activated.
2. This is followed by activation of the immune system in which CD4 T-helper cells
and CD8 cytotoxic T cells are stimulated along with pro-inflammatory cytokine
formation. Nitric oxide is produced by the myocytes and play a role in the
damage to myocardial tissue. Persistence of viral RNA responsible for the
dilated cardiomyopathy.
3. Finally, lymphocytes are activated and autoantibody formation ensues.
4. Direct damage to myoctes and inflammatory reaction leads to loss of myoctes
and fibrous tissue formation, thus diminishing the contractility of the
myocardium.

Clinical features • Range from asymptomatic to severe congestive heart failure (CHF).
• Many patients present with a nonspecific illness characterized by fatigue, mild
dyspnea, and myalgias.
• Arrythmias
• Mimic myocardial infarction
• SCD due to arrythmia
Diagnosis Chest X –ray: cardiomegaly and increased pulmonary vascular markings or frank pulmonary
edema
Electrocardiogram (ECG): sinus tachycardia, low voltage QRS complexes and T wave inversion,
ST segment changes.
Echocardiography: dilated left ventricle with decreased systolic function. Present of
mitral valve regurgitation and pericardial effusion.
Gross
• Heart may appear normal or dilated
• Myocardium is flabby and pale, with small areas of hemorrhage  mottled
appearance. (advanced stage)
• Frank myocardial abscesses in case of bacterial infection.

52
Microscopic
• Edema
• Interstitial infiltrates
• Myocyte injury
• Diffuse lymphocytic infiltrate
Viral: Edematous myocardium infiltrated by monocytes and mononuclear cells,
myocyte degeneration / necrosis, viral inclusions eg CMV.
(In chronic cases: marked ventricular dilation, less conspicuous inflammation, more
myocardial fibrosis indistinguishable from idiopathic dilated cardiomyopathy.)
Parasites: organism demonstrable eg. trypanosomes.
Bacteria: neutrophilic infiltrate / abscess.
Giant cell myocarditis (unknown cause)

A. lymphocytic myocarditis with edema and associated myocyte injury

B. hypersensitivity myocarditis characterized by perivascular eosinophil-rich
inflammatory infiltrate
C. Giant cell myocarditis with lymphocyte and macrophage infiltrate, extensive myocyte
damage and multinucleate giant cells
D. Chagas myocarditis with a myofiber distended with tryoanosomes(arrow), along with
mononuclear inflammation and myofiber necrosis

53
 9) Vasculitis
Classification 1. Direct Infection
based on  Bacterial (e.g., Neisseria)
Pathogenesis  Rickettsial (e.g., Rocky Mountain spotted fever)
 Spirochetal (e.g., syphilis)
 Fungal (e.g., aspergillosis, mucormycosis)
 Viral (e.g., herpes zoster-varicella)
Pathogenesis:
 Direct invasion of vessel wall
 Haematogenous spread (septicaemia) or embolisation (eg. Infective endocarditis)
 Important because infarction worsen the initial infection eg. Bacterial meningitis
extends into brain.
2. Immunologic (non-infectious)
Immune complex-mediated:
a) Infection-induced (e.g., hepatitis B and C virus)
b) Henoch-Schönlein purpura
c) Systemic lupus erythematosus and rheumatoid arthritis
d) Drug-induced
e) Cryoglobulinemia
f) Serum sickness
Antineutrophil cytoplasmic autoantibody-mediated (ANCA):
a) Wegener granulomatosis
b) Microscopic polyangiitis (microscopic polyarteritis)
c) Churg-Strauss syndrome
Direct antibody attack-mediated:
a) Goodpasture syndrome (anti-glomerular basement membrane antibodies)
b) Kawasaki disease (antiendothelial antibodies)
Cell-mediated:
a) Allograft organ rejection
b) Inflammatory bowel disease
c) Paraneoplastic vasculitis
Pathogenesis:
 Immune complexes
 ANCA (anti neutrophil cytoplasmic antibodies)
a) c-ANCA in Wegener granulomatosis
b) p-ANCA in microscopic polyangiitis and Churg-Strauss syndrome.

 Antiendothelial cell antibodies e.g. SLE, Kawasaki disease.

54
 3. Unknown pathogenesis
 Giant cell (temporal) arteritis
 Takayasu arteritis
 Polyarteritis nodosa (classic polyarteritis nodosa)
Classification 1. Small Vessel Vasculitis
based on vessel  Wegener’s granulomatosis: Upper & lower respiratory tracts & kidneys. c-ANCA
calibre present
 Churg Strauss syndrome: Lower respiratory tract; asthma; blood eosinophilia
 Leukocytoclastic vasculitis: Hypersensitivity vasculitis involving skin
 Henoch Schonlein purpura: IgA dominant immune complex deposition in skin, gut &
kidney
 Microscopic polyarteritis: strongly associate with p-ANCA
2. Medium-sized vessel Vasculitis
 Polyarteritis nodosa (classic)
 Kawasaki disease: Usually children; coronary artery involvement
 Buerger disease: Occurs in heavy smoker
3. Large Vessel Vasculitis
 Giant cell arteritis: Granulomatous arteritis of aorta and large branches.
Patients >50 years old
 Takayasu’s arteritis: Granulomatous inflammation of aorta & large branches.
Patients < 50 years old

55
 A) Small-Vessel Vasculitis
Granulomatosis Epidemiology:
with polyangiitis  Mostly 40-year old men
(Wegener)  Systemic vasculitis involving nasal sinuses, lungs and kidneys.
 Initiated as a cell-mediated hypersensitivity response directed against inhaled
infectious or environmental antigens.
 Recruitment and activation of neutrophilspresence of proteinase 3 (PR3), a
neutrophil azurophilic granule constituent that shared homology with numerous
microbial peptidesgeneration of PR3-ANCAsdisease manifestations
 High risk for relapses.
Morphology:
 Upper respiratory tract lesions range from granulomatous sinusitis to ulcerative
lesions of the nose, palate, or pharynx
 Lung findings vary, ranging from diffuse parenchymal infiltrates to granulomatous
nodules.
 Multifocal necrotizing granulomatous vasculitis with a surrounding fibroblastic
proliferation
 Multiple granulomata can coalesce to produce radiographically visible nodules with
central cavitation
 Destruction of vessles haemorrhage + hemoptysis
 Lesionprogressive fibrosis and organization
 Renal lesions range from mild, focal glomerular necrosis with thrombosis of isolated
glomerular capillary loops (focal and segmental necrotizing glomerulonephritis) to
more advanced glomerular lesions with diffuse necrosis and parietal cell
proliferation forming epithelial crescents (crescentric glomerulonephritis)

56
Clinical Features:
 Bilateral pneumonitis with nodules and cavitary
lesions (95%)
 Chronic sinusitis (90%)
 Mucosal ulcerations of the nasopharynx (75%)
 Renal disease (80%)
 Upper respiratory tract: perforation of nasal septum,
chronic sinusitis, otitis media, mastoiditis
 Lower respiratory tract: hemoptysis, cough, dyspnea
 Renal: hematuria, red cell casts, proteinuria, renal
failure
 Skin rash, muscle pain, articular involvement,
polyneuritis, fever
Lab investigation:
 Necrotizing vasculitis characterized by specific triad of findings:
a) Focal necrotizing vasculitis
b) Necrotizing granulomas in the lung and upper airway
c) Necrotizing glomerulonephritis
 CXR: Large nodular densities
 PR3-ANCA/ c-ANCA (antiproteinase 3) present in 95% of casesdrive tissue injury. It
is a good marker of disease activity.

57
 Treatment:
Drugs MOA
Alkylating agents Covalently X-link (interstand) DNA at
e.g. cyclophosphamide guanine N-7. Require bioactivation by liver
Corticosteroids Depresses formation, release, and activity
of endogenous mediators of inflammation,
including prostaglandins, kinins, histamine,
liposomal enzymes, and complement
system. Modifies body's immune response.
TNF inhibitors Suppresses response to tumor necrosis
factor (TNF), which is part of the
inflammatory response
anti-B cell antibodies Monoclonal antibody against CD20, which
e.g. Rituximab is found on most B-cell neoplasm
Microscopic Epidemiology:
polyangiitis/  Group of vascular disorders thought to be in response to exogenous substances,
hypersensitivity e.g., bacterial products, drugs or tumour antigen
vasculitis/  Antibody responses to antigens (exogenous substances) secondary immune
leukocytoclastic responses production of MPO-ANCA/p-ANCA against myeloperoxidase (MPO), a
vasculitis lysosomal granule constituent involved in oxygen free radical generation disease
manifestations
 All lesions tend to be of the same age in any given patient
 Cutaneous lesions: leukocytoclastic vasculitis
 Systemic lesions: microscopic polyarteritis, inflammation restricted to the arterioles,
capillaries & venules
 Necrotizing vasculitis commonly involving lung, kidneys, and skin with pauci-
immune glomerulonephritis and palpable purpura.
 Can be a feature of some immune disorders, such as Henoch Schonlein purpura or
Lupus Erythematosus.

58
 Morphology:
 Segmental fibrinoid necrosis of the media with focal transmural necrotizing lesions
 No granulomas.
 In some areas (typically postcapillary venules), only infiltrating neutrophils that
frequently undergo fragmentation are seenleukocytoclastic vasculitis
 Most skin lesions are “pauci-immune” (show little or no antibody)
Clinical Features:
 Presentation similar to granulomatosis with polyangiitis but without nasopharyngeal
involvement.
 Depend on the vascular bed involved
 Hemoptysis, hematuria, proteinuria, abdominal pain/bleeding, muscle
pain/weakness and palpable cutaneous purpura.
 With the exception of patients with widespread renal or CNS involvement,
immunosuppression and removal of the offending agent induce durable remissions.
Lab Investigations:
 Presence of MPO-ANCA/ p-ANCA (anti-myeloperoxidase)
Treatment:
 cyclophosphamide and corticosteroids
Churg-Strauss Epidemiology:
syndrome  A small vessel necrotizing vasculitis classically associated with asthma, allergic
(allergic rhinitis, lung infiltrates, peripheral eosinophilia, extravascular necrotizing
granulomatosis granulomas, and a striking infiltration of vessels and perivascular tissues by
and angiitis) eosinophils.
 Rare disorder
 Hyperresponsiveness to some normally innocuous allergic stimulus production of
MPO-ANCA/p-ANCA
Morphology:
 Granulomatous
 Necrotizing vasculitis with eosinophilia

Clinical Features:
 Cutaneous involvement (with palpable purpura)
 Gastrointestinal bleeding
 Renal disease (primarily as focal and segmental glomerulosclerosis, pauci-immune
glomerulonephritis)
 Myocardial eosinophilic infiltrates  cytotoxicitycardiomyopathy
 Peripheral neuropathy (e.g. wrist/foot drop)
Lab Investigations:
 Presence of MPO-ANCA /p-ANCE
 ↑IgE level

59
Henoch-  Most common childhood systemic vasculitis. Often follows URI
Schonlein  Classic triad:
purpura a) Skin: palpable purpura on buttocks/legs

b) Arthralgias
c) GI: abdominal pain, melena, multiple lesions of same age
 Vasculities secondary to IgA complex deposition
 Associated with IgA nephropathy
B) Medium-Vessel Vasculitis
Polyarteritis Epidemiology:
nodosa (PAN)  Mostly in young adults
 An acute, necrotizing vasculitis affecting medium and smaller, muscular arteries
typically renal & visceral vessels (coronary, hepatic, mesenteric), sparing the
pulmonary circulation
 No association with ANCAs,
 Associate with Hepatitis B infection (30 % of patients)formation of immune
complexes containing hepatitis B antigensdeposit in affected vessels
Morphology:
 Segmental transmural necrotizing inflammation of small to medium-sized arteries,
often with superimposed thrombosis
 Kidney, heart, liver and GIT vessels are affected in descending order of frequency
 Lesions involve only part of the vessel circumference and have a predilection for
branch points
 Impaired perfusions ulcerations, infarcts, ischemic atrophy or hemorrhages
 Inflammatory processweakens arterial wallaneuryms (palpable nodules) and
rupture
 Acute stage: Fibrinoid necrosis, acute transmural inflammation of the arterial wall
with neutrophils , eosinophils and mononuclear cells.
 Healing stage: Transmural scarring, organized thrombus, macrophages and plasma
cells
 Healed stage: Marked fibrotic thickening of vessel wall
 All stages may coexist in same vessel

60
 Clinical Features:
 Episodic, long symptom-free intervals
 Fever, weight loss, malaise, headache
 Vascular gastrointestinal lesions: abdominal pain, melena
 Renal involvement: accelerating hypertension
 Neurologic dysfunction, cutaneous eruptions, renal damage
 Absent small vessel involvement no glomerulonephritis
Lab Investigations:
Innumerable microaneuryms and spasm on arteriogram
Treatment:
 corticosteroids, cyclophosphamide
 Immunosuppression can yield remission /cure in 90% of the cases.
Kawasaki Epidemiology:
disease  Acute, febrile, usually self-limited illness of infancy and childhood (80% of patients
(mucocutaneous <4 years old, mostly Asians)
lymph nodes  Involvement of coronary arteries, coronary arteritisaneurysms, thrombosis
syndrome) rupture, myocardial infarction
 Genetically susceptible persons, infectious agents (mostly viral) may trigger the
disease
 Cross-reactive/newly uncovered vascular antigendelayed-type
hypersensitivitycytokine productionpolyclonal B cell

61
 activationautoantibodies to endothelial cells and smooth muscle cells vasculitis
Morphology:
 Resembles that is seen in polyarteritis nodosa
 Dense transmural inflammatory infiltrate, fibrinoid necrosis less prominent
 Healed lesions can exhibit obstructive intimal thickening
Clinical Features:
 Conjunctival and oral erythema and blistering, edema of the hands and feet,
erythema of the palms and soles, a desquamative rash, fever, and cervical lymph
node enlargement
 Changes in lips/oral mucosa (“strawberry tongue”)

 20% develop cardiovascular sequelae Coronary artery aneurysms with

rupture/thrombosis/myocardial infarction
Treatment:
 Treat with IV immunoglobulin and aspirin (Irreversibly inhibit COX-1 and COX-2)
Buerger disease Epidemiology:
(thromboangiitis  Occurs in heavy tobacco smokers, develops before age 35, males
obliterans)  May be due to direct endothelial cell toxicity by some component of
tobaccomodify vessel wall componentsinduce immune response in
hypersensitivity person
 Results in severe vascular insufficiency and gangrene of the extrimities
 Focal acute and chronic inflammation of medium-sized and small arteries, especially
the tibial and radial arteries, associated with thrombosis, occasionally, secondary
extension into adjacent veins and nerves
Morphology:
 Sharply segmental acute and chronic transmural vasculitis of medium-sized and
small arteries, predominantly those of the extremities.
 Early stages: mixed inflammatory infiltrates of all coats of vessel wall are
accompanied by luminal thrombosis; small microabscesses, occasionally rimmed by
granulomatous inflammation within the thrombus
 Inflammation often extends into contiguous veins and nerves
 Thrombi can recanalize, and eventually the artery and adjacent structures become
encased in fibrous tissue.

62
 Clinical Features:
 Early manifestations: cold-induced Raynaud phenomenon, instep foot pain induced
by exercise (instep claudication), and a superficial nodular phlebitis (venous
inflammation)
 Vascular insufficiency accompanied by severe pain (even at rest) due to neural
involvement
 Chronic extremity ulcerations gangrene
 Autoamputation of digits
Treatment:
Treat with smoking cessation.
C) Large-Vessels Vasculitis
Temporal (giant Epidemiology:
cell) arteritis  Most common form of vasculitis among the elderly >50 years old (especially in
females)
 It takes the form of focal, chronic, typically granulomatous, inflammation of large to
small size arteries, mainly those supplying the head (especially temporal arteries) or
branches of carotid artery
 Vertebral and ophthalmic arteries, aorta (giant cell aortitis) also can be involved
 Ophthalmic artery occlusion permanent blindness
 Associated with polymyalgia rheumatic
Morphology:
 Artery is cord-like and nodular
 Pathologic changes are notoriously patchy along the length of affected vessels
 Involved arterial segments nodular intimal thickening+ thrombosis↓lumen
diameterdistal ischemia
 Granulomatous inflammation within the inner media centered on the internal
elastic membrane; infiltrate of lymphocytes and macrophages, with multinucleated
giant cells, and fragmentation of the internal elastic lamina
 Healing: medial and adventitial fibrosis and intimal thickening
 Characteristically, lesions at different stages of development are seen within the
same artery.

63
Clinical Features:
 Fever, fatigue, weight loss
 Facial pain/unilateral headache, most intense along the course of the superficial
temporal artery painful to palpation

 Visual symptoms (blurred, double vision or blindness) in 50% of patients when the
ophthalmic artery is affected
 Jaw claudication
Lab Investigation:
↑ESR
Treatment:
Treat with high-dose corticosteroids prior to temporal artery biopsy to prevent vision loss
Treatment with anti-TNF therapies

64
Takayasu Epidemiology:
arteritis  < 50 years old , mostly Asian females
(pulseless  May be due to autoimmune
disease)  Characterized principally by ocular disturbances and marked weakening of the
pulses in the upper extremities
 Manifests with transmural scarring and granulomatous thickening of the aorta
(particularly the aortic arch and great vessels) with severe luminal narrowing of the
major branch vessels
Morphology:
 Pulmonary arteries are involved in 50% of patients, and renal and coronary arteries
also can be affected.
 Takeoffs of the great vessels can be markedly narrowed and even obliterated
upper extremity weakness + faint carotid pulse
 Adventitial mononuclear infiltrates (later to media) and perivascular cuffing of the
vasa vasorum, to intense transmural mononuclear inflammation, to granulomatous
inflammation, replete with giant cells and patchy medial necrosis.
 Inflammation associated with irregular thickening of the vessel wall, intimal
hyperplasia, and adventitial fibrosis obliteration of lumen + thrombosis

Clinical Features:
 Fatigue, weight loss, fever, night sweats, arthritis, myalgias, skin nodules
 ↓upper extremity blood pressure and pulse strength; neurologic deficits and ocular
disturbances, including visual field defects, retinal hemorrhages, and total blindness
 Distal aorta disease: leg claudication
 Pulmonary artery: pulmonary hypertension
 Narrowing of coronary ostia myocardial infarction
 Renal arteries: systemic hypertension
Lab Investigations:
 ↑ESR
Treatment:
Treat with corticosteroids

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 10) Shock
 A medical emergency in which the organs and tissues of the body are not receiving an adequate flow
of blood. This deprives the organs and tissues of oxygen (carried in the blood) and allows the build-up
of waste products
 Pre-shock:
Tachycardia
Peripheral vasoconstriction
Modest increase or decrease is systemic blood pressure
 Shock:
Tachycardia
Dyspnoea
Restlessness
Diaphoresis
Metabolic acidosis
Oliguria
Cool clammy skin
Hypotension
Hypovolemic Caused by plasma loss due to burns, dehydration, traumatic shock due to blood loss
Shock and major tissue damage.
(Most common)
Pathophysiology:
↓ Intravascular volume Blood and /or fluids have left the body.

↓ venous return Lack of fluid in the vascular space.

↓ ventricular filling

Ventricles do not have as much blood as

↓ SV
normal to pump out.

↓ CO ↑HR to compensate for the diminished

SV and resulting poor CO and BP.
Eventually, if the fluid or blood loss
Inadequate tissue perfusion continues, the HR will not be able to
compensate for the ↓SV.

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 Treatment:
 Fluids in minor cases:
a) Colloids: albumin (Produces faster and greater intravascular volume
expansion)
b) Crystalloids: osotonic saline, Lactate Ringer’s solution, compound
sodium lactate (Hartmann’s solution)
 May require multiple blood transfusions in severe cases.
a) During resuscitation
- Low central venous oxygen saturations
- Haematocrit <30%
b) After resuscitation
- Hb level <7 g/dL (with no coronary artery disease). Target 7-9g/dL
- If there is presence of CAD, Target 9-10g/dL
 The underlying cause of the bleeding must also be identified and corrected.
Cardiogenic Shock  Diagnosed when systolic BP <90mmHg for more than one hour that is not
responsive to fluid administration
 Cardiac index <2.2 l/min/m2. (Normal 2.6-4.2 L/min)
CI = Cardiac output/BSA= SV x HR/BSA
 Elevated end diastolic filling pressure and pulmonary oedema
 Caused by:
a) Myocardial diseases (Myocardial infarction or ischaemia /
Cardiomyopathies / Myocarditis)
b) Obstructive (Pulmonary embolism / Tension pneumothorax /
Constrictive pericarditis / Pericardial temponade)
c) Valvular diseases (Acute aortic regurgitation / Critical aortic stenosis /
Mitral regurgitation caused by rupture of a papillary muscle or chordae
tendinae / Ventricular septal defect)
d) Arrythmias (Ventricular more commonly than supraventricular)

Pathophysiology:
Less blood being pushed
from the ventricle during
Impaired pumping ability systole left ventricle
Injured left ventricle gradually fills with more
of the left ventricle
blood

↑HR to compensate
for ↓CO and BP, but
↓SV Inadequate systolic emptying
will eventually be
insufficient to
compensate ↓SV. ↓CO ↑ left ventricular filling
pressure
Pumping is
ineffective, less ↓BP
blood is pushed out ↑ left atrium pressure
with each heartbeat.
↓tissue
perfusion ↑ pulmonary venous pressure

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 Pressure ‘backs up’ into ↑ pulmonary capillary pressure
pulmonary vasculature

Pulmonary interstitial edema

Intra-alveolar edema

Treatment:
 Identifying and treating the underlying cause.
 Heart attack: Require cardiac catheterization to unblock an artery.
 Congestive heart failure: medications to support and increase the force of the
heart's beat.
 In severe or prolonged cases: heart transplant.

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 Distributive/vasodilatory Shock
Ineffective tissue oxygen extraction + loss of vasoregulatory controlInappropriate vasodilation and mal-
distribution of blood flow + CO is preserved or increased
Management:
 Monitor patient in a critical care environment: Blood Oxygen saturations / Blood pressure /
Respiratory rate / Core body temperature / Electrocardiography
 Invasive monitoring: Urinary catheter / Intra-arterial monitoring – ABGs / CVP line – vasoactive drugs,
IV Fluids
 Non-invasive: Cardiac monitoring
 General measures: Oxygen / Fluid therapy / Glycaemic control
 Inotropic and vasoactive drugs: Norepinephrine / Vasopression / Dopamine / Phenyephrine /
Levosimendan
Neurogenic Shock Caused by loss of sympathetic control (tone) of resistance vessels, resulting in the
massive dilatation of arterioles and venules, due to general or spinal anesthesia, spinal
cord injury, pain, and anxiety.

Pathophysiology:
Loss of sympathetic tone

Blood pools in
the distensible Massive vasodilation
veins and does
not return to the
larger veins.

Venous dilation Arteriolar dilation

↓ venous return ↓ Peripheral vascular

resistance

↓ SV

Helps the heart to pump with less

↓ CO energy, however, there is no
driving force to get blood, O2 and
nutrients to the cells small
↓ Tissue perfusion degree of arterial blood pooling 
↓amount of blood returning to
the heart.

Treatment:
 Damage to the spinal cord irreversible and causes problems with the natural
regulatory functions of the body.
 Fluids and monitoring
 Immobilization (keeping the spine from moving)
 Anti-inflammatory medicine such as steroids
 Surgery

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Anaphylactic Caused by severe allergic antigen-antibody reaction to substances such as drugs,
Shock contrast media, blood products, or insect or animal venom, food products such as
seafood, nuts, peanuts, peanut butter, and MSG.

Pathophysiology:

Exposure to antigen

Activation of sensitized antibodies

Antigen-antibody reaction

Release of vasoactive mediators

Massive vasodilation ↑ capillary permeability

Venous and arterial dilation Interstitial edema

Relative hypovolemia

↓ Blood return to the heart

Treatment:
Drugs Examples MOA
H1 - Diphenhydramine Reversible inhibitors of H1 histamine
antihistamines receptors
Corticosteroids Methylprednisolone Depresses formation, release, and activity
of endogenous mediators of
inflammation, including prostaglandins,
kinins, histamine, liposomal enzymes, and
complement system. Modifies body's
immune response.
H2 blocker cimetidine Reversible block of histamine H2 receptors
 ↓H+ secretion by parietal cells.
 Inject epinephrine for emergency allergic reaction

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Septic Shock Occur when the sepsis has progressed to the point where it is affecting many organ
systems.
Pathophysiology:
Infection
Not adequate to
eliminate infection
Immune and inflammatory response  causes ↑ damage

Released of cytokines, vasodilators,

complement factors and free radicals
by the body
+
Released of endotoxins/exotoxins by Further harm the
the organism organs and tissues

Peripheral vasodilation ↓ ability of cells and tissues to take

up oxygen and nutrients

Interstitial edema
↓ blood return to the heart

To get O2 + nutrients ↑HR, CO

to the cells, however,
immune response
and compensatory Multi-organ dysfunction syndrome (MODS)
Multi-system organ failure (MSOF)
mechanisms may not
be enough to combat
infection cellular
destruction.

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 Treatment:
 Prompt administration of antibiotics depending on the source and type of
underlying infection.
 Require large amounts of fluids to increase and maintain blood pressure.
Obstructive Shock Caused by obstruction of blood flow outside of the heart, as in the conditions below:
a) Cardiac tamponade: fluid in the pericardium prevents inflow of blood into the
heart (venous return). Constrictive pericarditis, in which the pericardium shrinks
and hardens, is similar in presentation.
b) Tension pneumothorax: increased intrathoracic pressurebloodflow to the
heart is prevented (venous return).
c) Pulmonary embolism is the result of a thromboembolic incident in the blood
vessels of the lungs and hinders the return of blood to the heart.
d) Aortic stenosis hinders circulation by obstructing the ventricular outflow tract

Results in signs of right heart failure:

↑right heart pressure
Impaired venous return

Treatment:
 Relief of the obstruction
 Cardiac temponade: pericardiocentesis
 Tension pneumothorax must be treated promptly
 Pulmonary embolism: anticoagulation therapy and thrombolytic therapy
 Maintainence of intravascular volume
 Avoid diuretics
Summary:

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Differences:

Distributive Shock Hypovolemic / Cardiogenic Shock

(Neurogenic/Anaphylactic/Septic Shock)
High-output failure (↓TPR, ↑CO, ↑ venous return) Low-output failure (↑TPR, ↓CO, ↓ venous return)
↓PCWP PCWP ↓ in hypovolemic
PCWP ↑ in cardiogenic
Vasodilation (warm, dry skin) Vasoconstriction (cold, clammy patient)
Failure to ↑ BP with IV fluids BP restored with IV fluids
* PCWP – Pulmonary Capillary Wedge Pressure (An indirect indication of left atrial pressure)

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Complications Acute Respiratory Distress Syndrome (ARDS)
Acute Renal Failure (ARF)
Gastrointestinal complication
Disseminated Intravascular Coagulation (DIC)
Multiple Organ Dysfunction Syndrome (MODS)
Acidaemia decreases cardiac output and alters cellular metabolic processes
Restlessness evolves to agitation, obtundation and coma

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 11) Hypertension
Definition Blood pressure greater than 140/90 on two or more blood pressure readings taken
at each of two or more visits after initial screening.
th th
Prehypertension  120-139 mm Hg/80-89 mm Hg (adults), 90 -95
percentile values/90th-95th percentile values (children),
greater than 120/80 mm Hg (adolescent)
Stage 1 hypertension  140-159 mm Hg/90-99 mm Hg
Stage 2 hypertension  160 mm Hg or greater/100 mm Hg or greater
Essential hypertension  90% of patients with hypertension with no
(primary or idiopathic identifiable secondary cause.
hypertension)  A heterogeneous disorder, with different patients
having different causal factors that lead to high
BP.
 Linked to genetics, poor diet, lack of exercise and
obesity.
 There are no specific symptoms of raised blood
pressure, only those attributable to damage to
target organs.
Secondary hypertension  High blood pressure that's caused by another
medical condition.
 Has an identifiable cause, such as renal
disease, endocrine illness, coarctation of the
aorta, renovascular disease and drugs.
 Tends to appear suddenly and cause higher
blood pressure than does primary
hypertension.
 Renal disease is the most common cause of
secondary hypertension.
Hypertension in children Systolic blood pressure equal to or greater than the 95th
and adolescents percentile value for gender, age, and height.
Renal hypertension  Hypertension that is associated with disease of the
kidneys and is caused by kidney damage or
malfunctioning.
Preoperative ≥160/95mm Hg immediately before, during, or after a
hypertension surgical procedure.
Hypertension in a) Gestational hypertension - pregnancy-induced
pregnancy hypertension which develops after 20 weeks of
(preeclampsia) gestation and may be either transient
hypertension of pregnancy or chronic
hypertension identified in the latter half of
pregnancy.

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  Pre-eclampsia: pregnancy-induced hypertension
in association with proteinuria and/or oedema or
both.
 Eclampsia: occurrence of one or more
convulsions superimposed on pre-eclampsia.
b) Pre-existing hypertension: 140 mm Hg or
greater/90 mm Hg or more, either pre-pregnancy
or at booking (before 20 weeks).
 Pre-eclampsia in addition to pre-existing
chronic hypertension.
Malignant hypertension  Extremely high blood pressure that develops
suddenly and rapidly and causes some type of organ
damage.
 Blood pressure that's typically above 180/120.
Causes Primary hypertension
 No identifiable cause of high blood pressure.
Secondary hypertension
 Kidney problems
 Adrenal gland tumors
 Certain defects in blood vessels you're born with (congenital)
 Certain medications, such as birth control pills, cold remedies, decongestants,
over-the-counter pain relievers and some prescription drugs
 Illegal drugs, such as cocaine and amphetamines
Risk factors  Age - The risk of high blood pressure increases as you age. Through early middle
age, high blood pressure is more common in men. Women are more likely to
develop high blood pressure after menopause.
 Race - Common among blacks, often developing at an earlier age than it does in
whites. Serious complications, such as stroke and heart attack, also are more
common in blacks.
 Family history - High blood pressure tends to run in families.
 Being overweight or obese - ↑weight → ↑blood to supply oxygen and nutrients to
your tissues → ↑blood volume → ↑blood pressure.
 Not being physically active - People who are inactive tend to have higher heart
rates. ↑heart rate → the harder your heart must work with each contraction →
↑cardiac output → ↑blood volume → ↑blood pressure. Lack of physical activity
also increases the risk of being overweight.
 Using tobacco - Not only does smoking or chewing tobacco immediately raise your
blood pressure temporarily, but the chemicals in tobacco can damage the lining of
your artery walls. This can cause your arteries to narrow, increasing your blood
pressure. Secondhand smoke also can increase your blood pressure.

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  Too much salt (sodium) in your diet - Too much sodium in your diet can cause your
body to retain fluid, which increases blood pressure.
 Too little potassium in your diet - Potassium helps balance the amount of sodium
in your cells. If you don't get enough potassium in your diet or retain enough
potassium, you may accumulate too much sodium in your blood.
 Too little vitamin D in your diet - Vitamin D may affect an enzyme produced by
your kidneys that affects your blood pressure.
 Drinking too much alcohol - Over time, heavy drinking can damage your heart.
Having more than two drinks a day can raise your blood pressure.
 Stress - High levels of stress can lead to a temporary, but dramatic, increase in
blood pressure. If you try to relax by eating more, using tobacco or drinking alcohol,
you may only increase problems with high blood pressure.
 Certain chronic conditions - High cholesterol, diabetes, kidney disease and sleep
apnea increases blood pressure.
 Pregnancy (sometimes)
Pathophysiology
of hypertension

a) Genetics
 Single gene mutations → altering renal salt handling → Mendelian forms of
high and low blood pressure.
 Liddle syndrome – A rare but clinically important disorder. Constitutive
activation of the epithelial sodium channel → inappropriate sodium
retention at the renal collecting duct level → severe, treatment-resistant
hypertension.
b) Autonomic nervous system
 Excess activity of the sympathetic nervous system → ↑blood pressure →
hypertension.
 Angiotensin II → arterial baroreceptors are reset to a higher pressure and
decreased baroreceptor sensitivity → activation of aortic baroreceptor nerves
→ suppression of sympathetic inhibition → ↑heart rate and vasodilation
(↓total peripheral resistance) → ↑cardiac output → ↑blood volume →
↑blood pressure.
 Reactive oxygen species and endothelin → suppress baroreceptor activity →
exaggerated sympathetic drive in hypertension.

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  Genetic mutation → ↑circulating norepinephrine level → no downregulation of
noradrenergic receptor.
 Stress → ↑catecholamines → sympathetic outflow and repeated stress-induced
vasoconstriction → vascular hypertrophy → ↑peripheral resistance → ↑blood
pressure.

c) Renin-angiotensin-aldosterone system (RAAS)

 ↑renin level in blood → ↑angiotensin I → ↑angiotensin II → vasoconstriction
→ ↑ peripheral resistance → ↑blood pressure.

 ↑renin level in blood → ↑angiotensin I → ↑angiotensin II → ↑aldosterone →

↑ re-absorption of salt and water → ↑blood volume → ↑blood pressure.

d) Endothelial dysfunction

 Balance between the vasodilators and the vasoconstrictors is upset → changes

in the endothelium → endothelial activation and damage → ↑local nitric oxide
and endothelin → ↑vascular tone, vascular reactivity, and changes in
coagulation and fibrinolytic pathways → ↑blood pressure.

 ↑Angiotensin II → ↑Superoxide and other reactive oxygen species (ROS) →

inactivation of nitric oxide (NO) → vasoconstriction and decrease blood flow →
↑blood pressure

Hypertension in elderly

 Aging → ↑aortic cross-sectional thickness → ↑aortic impedance and resistance

and ↑ vascular stiffness → ↑pulse pressure → left ventricle pumps harder →
↑left ventricular afterload → left ventricular hypertrophy → left ventricular
diastolic dysfunction.

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Systemic a) Heart
symptoms
- ↑blood pressure → ↑heart muscle to thicken → ↑total peripheral resistance
→ ↓blood flow to the heart muscles → ↓oxygen to the heart muscles → chest
pain

- ↑blood pressure → ↑heart muscle to thicken → ↑total peripheral resistance

→ less space for the oxygen-rich blood to flow from the lungs into the chamber
or ventricle that pumps it to the rest of the body → blood back up into the lungs
→ shortness of breath.

- ↑blood pressure → ↑heart muscle to thicken and become stiff → ↓blood flow
to the whole body → heart failure → palpitation

- ↑blood pressure → ↑heart muscle to thicken and become stiff → less effective
at pushing the blood round → fluid builds up in lower legs and ankles → swelling
of the legs

b) Kidney

- Hypertension → damage arteries in the kidney → kidney disease → dysuria, nocturia

and frequency of micturition

c) Central Nervous system

- ↑blood pressure → ↑heart muscle to thicken and become stiff → ↓blood flow to
the brain → dizziness

- Hypertension → traction to the blood vessels in the head → activates nociceptors →

headache

- Hypertension → blood vessels rupture → blood moves into the deep tissue in the
brain or in the space between the brain and the skull → haemorrhagic stroke → brain
can’t function normally to transmit nerve impulses to the limb → hemiplegia

- Hypertension → ↑heart muscle to thicken → ↑peripheral resistance → ischemic

stroke → brain can’t function normally to transmit nerve impulses to the limb →
hemiplegia

- Hypertension → stroke → brain can’t function normally to transmit nerve impulses to

the eye → homonymous hemianopia

79
 d) Fundus

- Hypertension → Branch and central vein occlusion → blurring of vision.

Physical a) Cardiovascular Examination

examination
 Aortic heart sound is loud
findings
 Fourth heart sound may be heard due to decrease distensibility of the left
ventricle from thickened left ventricular muscle.

 Congestion in the lungs can be detected by auscultation.

b) Examination of the fundus of the eye

 Arteriolar narrowing, irregularity and arteriovenous nipping (for nickling)

 Haemorrhages and exudates are seen in the retina (advanced stages)

 Papilloedema with blurring of the disc margins (end stage).

c) Central Nervous System

 No abnormality could be detected (early stages)

 When brain damage occurs from severe hypertension, evidence of hemiplegia

may be detected.

 On examination, plantars may be up going with weakness of the paralysed side.

d) Kidneys

 Urinary symptoms may occur from renal disease.

 Long standing hypertension causes shrinkage of the kidney size and scarring of
the glomeruli affecting the function.

 Kidneys are enlarged and palpable in polycystic disease.

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Laboratory a) Urinalysis
investigations
 Proteinuria occurs in renal disease.

 Specific gravity around 1010 ( fixed specific gravity) suggest chronic renal
failure.

 Granular casts & pus cells appear in the urine.

 Bacterial culture examination done. Positive culture is found in urinary tract

infection or chronic pyelonephritis.

b) Blood tests

 In kidney disease, blood urea nitrogen and serum creatinine are elevated.

 Serum potassium level is low in primary aldosteronism.

c) Radiological Examination

i) Chest X- ray: Sometimes heart size may be normal as the

muscle mass of the left ventricle may have increased
concentrically. Usually left ventricular enlargement is seen on
the border of the heart.

ii) Intravenous pyelogram : This test may give evidence of renal

parenchymal disorder or renal artery stenosis as a cause of
hypertension.

d) ECG: Most useful investigation in confirming the left ventricular hypertrophy. I t

is a reliable investigation even though chest x-ray may not show any evidence of
the left ventricular enlargement. ECG shows evidence of hypertrophy and not
dilatation.

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 Test Purpose of investigation

Urine Evidence of kidney disease.

BUN: a) To assess kidney function

a) Serum creatinine b) Low in primary

hyperaldosteronism; High in
b) Potassium
chronic renal failure.

Haemoglobin Low in chronic renal disease

Chest x-ray Evidence of left ventricular enlargement

or/ and failure.

ECG To assess left ventricular hypertrophy

I.V.P To assess renal pathology and function

Treatment and Medications (anti-hypertensive drugs)

drugs
a) Thiazide diuretics – Diuretics (water pills) act on your kidneys to help your body
eliminate sodium and water, reducing blood volume. Often the first, but not the
only choice in high blood pressure medications.

b) Beta blockers - Reduce the workload on your heart and cause vasodilation,
causing your heart to beat slower and with less force. When prescribed alone,
they don't work as well in blacks or in older adults, but they're effective when
combined with a thiazide diuretic.

c) Angiotensin-converting enzyme (ACE) inhibitors - Relax blood vessels by

blocking the formation of a natural chemical that narrows blood vessels.

d) Angiotensin II receptor blockers (ARBs) - Relax blood vessels by blocking the

action, not the formation, of a natural chemical that narrows blood vessels.

e) Calcium channel blockers - Relax the muscles of your blood vessels. Some slow
your heart rate. They may work better for blacks and older adults than do ACE
inhibitors or beta blockers alone. Grapefruit juice interacts with some calcium
channel blockers, increasing blood levels of the medication and putting you at
higher risk of side effects.

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 f) Renin inhibitors - Aliskiren (Tekturna) slows down the production of renin.
Tekturna works by reducing the ability of renin. Due to a risk of serious
complications, including stroke, you shouldn't take aliskiren with ACE inhibitors
or ARBs.

 If combinations of the above medications can’t decrease your blood pressure:

a) Alpha blockers - Reduce nerve impulses to blood vessels, reducing the effects of
natural chemicals that narrow blood vessels.
b) Alpha-beta blockers - In addition to reducing nerve impulses to blood vessels,
alpha-beta blockers slow the heartbeat to reduce the amount of blood that
must be pumped through the vessels.
c) Central-acting agents - Prevent your brain from signaling your nervous system
to increase your heart rate and narrow your blood vessels.
d) Vasodilators - Work directly on the muscles in the walls of your arteries,
preventing the muscles from tightening and your arteries from narrowing.

 Once your blood pressure is under control, take a daily aspirin to reduce your
risk of cardiovascular disorders.
 Combination of low-dose medications rather than larger doses of one single
drug is better.
Lifestyle changes
 Eating a healthier diet with less salt (the Dietary Approaches to Stop
Hypertension, or DASH, diet), exercising more, quitting smoking and losing
weight.

Prevention  a) Maintaining a healthy weight

 b) Getting regular exercise
 c) Reducing salt intake
 d) Drinking alcohol in moderation, if at all
 e) Reduce stress
 f) Potassium - Fruits, vegetables, dairy foods, and fish.
 g) Calcium - 1,000 mg/day for adults (19-50 years old) and 1,200 mg for those over 50
(pregnant and breastfeeding women also need more). Dairy foods like low-fat milk,
yogurt, and cheese. Low-fat and nonfat dairy products have even more calcium.
 h) Magnesium - Whole grains, green leafy vegetables, nuts, seeds, and dry peas and
beans.
 i) Fish oils - "omega-3 fatty acids" is found in fatty fish like mackerel and salmon. Taking
fish oil pills is not recommended, because high doses can cause unpleasant side effects.
 j) Garlic

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Complications a) Heart attack or stroke - ↑blood pressure → hardening and thickening of the
arteries (atherosclerosis) → heart attack, stroke or other complications.
b) Aneurysm - ↑blood pressure → blood vessels to weaken and bulge →
aneurysm. If an aneurysm ruptures, it can be life-threatening.
c) Heart failure - Pump blood against the higher pressure in your vessels → your
heart muscle thickens → difficult to pump enough blood to meet your body's
needs → heart failure.
d) Weakened and narrowed blood vessels in your kidneys - Prevent these organs
from functioning normally.
e) Thickened, narrowed or torn blood vessels in the eyes - Result in vision loss.
f) Metabolic syndrome - This syndrome is a cluster of disorders of your body's
metabolism, including increased waist circumference, high triglycerides, low high-
density lipoprotein (HDL), or "good," cholesterol, high blood pressure, and high
insulin levels. The more components of metabolic syndrome you have, the greater
your risk of developing diabetes, heart disease or stroke.
g) Trouble with memory or understanding - Uncontrolled high blood pressure may
also affect your ability to think, remember and learn. Trouble with memory or
understanding concepts is more common in people who have high blood pressure.

84