ARTERIOSKLEROSIS

Oleh:
Ruchiyyih Diah Palupi, S.Ked

Pembimbing:
dr. Bambang Supriadi, Sp.S

KEPANITERAAN KLINIK SMF NEUROLOGI

RSUD dr. DORIS SYLVANUS PALANGKA RAYA
FAKULTAS KEDOKTERAN UNIVERSITAS PALANGKA RAYA
2017
 TERMS
Arteriosclerosis : the stiffening or hardening
of the artery walls.
Atherosclerosis : the narrowing of the artery
because of plaque build-up. Atherosclerosis is
a specific type of arteriosclerosis.

All patients with atherosclerosis have

arteriosclerosis, but those with arteriosclerosis might
not necessarily have atherosclerosis.
 DEFINITION
The condition in which an artery wall
thickens as the result of a build-up of fatty
materials such as cholesterol (defined as
total cholesterol levels 200 mg/dL)
Commonly referred to as a hardening or
furring of the arteries.
Caused by the formation of multiple plaques
within the arteries
 ETIOLOGY
Etiology is unknown
Caused by macrophage white blood cells and fat
that accumulate in arteries - the white blood cells
are originally sent by the bodys immune system
to clean up LDL cholesterol pockets.
When they stick to an artery they secrete a
molecule called netrin-1, this stops normal
migration of macrophages out of the arteries.
The result is a mixture of clumped up cholesterol
pockets and white blood cells, the plaque that
can disrupt blood flow
 RISK FACTOR
Influenced Cannot be influenced
1. Hyperlipidemia 1. Age
2. Hypertension 2. Male sex
3. Smoking 3. A genetic
4. Diabetes mellitus predisposition
5. Hyperhomocysteinemia
6. Clamydia infection ?

Subordinate factors are overweight and a sedentary or

stressful lifestyle.
 EPIDEMILOGY
Remains the most important cause of death in
developed and underprivileged nations.
In US : CAD causes approx.1 of 6 deaths,
accounting for more than 400,000 deaths
annually
Each year, an estimated 785,000 Americans
have an initial myocardial infarction and
470,000 Americans have a recurrent attack
 SYMPTOMS
Signs and symptoms of atherosclerosis are not
visible until the arteries are severely narrowed
or blocked.
Signs and symptoms differ depending on the
arteries affected by atherosclerosis
coronary, carotid or cerebrovascular,
peripheral and abdominal
 Symptoms
1. Coronary Artery Disease (CAD)
Once the arteries supplying blood to heart are blocked, the cells in
the heart begin to die and a heart attack may occur. The most
common symptoms of Coronary Artery Disease (CAD) are:

Chest pain with a heavy, squeezing or crushing sensation with

possible burning or stabbing pain
Abdominal, neck, back, jaw or shoulder and arm pain
Nausea and vomiting sensation
Fatigue
Weakness
Perspiration
Shortness of breath
Depression and anxiety
 Symptoms
2. Carotid Artery Disease or Cerebrovascular Disease:
Caused due to reduced supply of oxygen rich blood to brain leading to
transient ischemic attack (meaning sudden loss of brain function and
complete recovery within a day) and stroke.

Paralytic stroke on one side of the body

Inability to comprehend speech, or to have garbled speech
Loss of vision in one of the eyes
Muscle weakness
Impairment of facial muscles
Poor coordination
Involuntary and jerky movements on one side of the body
Rapid and iterative involuntary eye movement
Vertigo
 Symptoms
3. Peripheral Artery Disease (PAD):
Accumulation of plaque in the arteries supplying blood to the hands
and feet lead to PAD. Some of the symptoms :

Pain, cramps, numbness and sense of fatigue in muscles of limbs

Diminished pulses in the hands and feet
Reduced muscle mass
Blowing sounds that can be heard with the help of a stethoscope
indicating turbulence in blood flow (also called as Bruits)
Loss of hair
Thickening of nails
Smooth and shiny skin surface
Gangrene
 Symptoms
4. Abdominal Angina and Bowel Infarction:
Narrowing of intestinal arteries leads to
abdominal angina and bowel infarction.
Some of the symptoms are:
Cramping pain in the middle of the abdomen
Severe abdominal pain with vomiting and
diarrhea or abdominal swelling
 PATHOPHYSIOLOGY
Fatty streaks are the earliest visible sign of Ath. (as
early as childhood).
- They are subendothelial accumulations of large,
lipid-containing cells (foam cells)
Later, fibrous plaques or atheroma form, which are
the cause of the clinical manifestation of Ath.
- These plaques consist of an accumulation of
monocytes, macrophages, foam cells, T
lymphocytes, connective tissue, tissue debris, and
cholesterol crystals. Plaques are often infected with
the bacterium Chlamydia pneumoniae
 PATHOPHYSIOLOGY
The consequences of plaque deposition are
narrowing of the lumen that can lead to ischemia.
a. Coronary heart disease as well as chronic occlusive
arterial disease of the limbs with painful ischemia on
exercise (intermittent claudication)
b. stiffening of the vessel wall (calcification),
c. thrombus formation that obstructs the residual lumen
and can cause peripheral emboli (e.g., cerebral
infarction, stroke) as well as bleeding into the plaques
(additional narrowing by the haematoma) and the
vessel wall.
 PATHOPHYSIOLOGY
Thus weakened, the wall may be stretched
(aneurysm) and even rupture, with dangerous
bleeding into the surrounding tissues, for
example, from the aorta or cerebral vessels
(massive intracerebral bleeding, stroke)
 PATHOPHYSIOLOGY
An aneurysm is a circumscribed bulging of an
arterial vessel due to congenital or acquired wall
changes.
It takes on the following forms:
- True aneurysm with extension to all three wall layers
(intima, media, and adventitia). In 9095% of cases it
is caused by atherosclerosis with hypertension.
Frequently the abdominal aorta is affected. In rare
cases it may be congenital or caused by trauma, cystic
medial necrosis (Marfans, EhlersDanlos, or
syndrome), or infection (syphilis, mycosis in immune-
deficient patients).
 PATHOPHYSIOLOGY
- False aneurysm (pseudoaneurism), consisting of a
perivascular hematoma over a tear in the intima
and media, connected with the vessel lumen. It is
caused by trauma or infection (accident, operation,
arterial catheterization).
- Dissecting aneurysm usually in the ascending aorta
in which, after perforation of the intima, blood
under high (arterial) pressure burrows a path
within the (usually degenerative) media so that
intima and adventitia become separated along an
advancing length of wall.
 PATHOPHYSIOLOGY
- Dissecting aneurysm usually in the ascending aorta
in which, after perforation of the intima, blood
under high (arterial) pressure burrows a path
within the (usually degenerative) media so that
intima and adventitia become separated along an
advancing length of wall.
 PATHOPHYSIOLOGY
One of the catastrophic complications of an aneurysm is
rupture. If it occurs in a large vessel, hemorrhagic shock
will dominate the clinical picture. Rupture of an
intracranial artery (often the anterior communicating
artery) together with subarachnoid bleeding is an acute
risk to cerebral function. Rupture of an aneurism near
the heart (especially a dissecting aneurism) can cause
acute pericardial tamponade
if the aortic root is involved, aortic regurgitation. Other
complications are thrombosis in the aneurism, occlusion
at the orgin of an artery as well as emboli to distal vessels
(ischemia or infarction)
 DISORDER OF CEREBRAL BLOOD
FLOW, STROKE
Complete cessation of cerebral blood flow causes
loss of consciousness within 1520 seconds) and
irreversible brain damage after seven to 10 minutes.
Occlusion of individual arteries results in deficits in
circumscribed regions of the brain (stroke).
The basic mechanism of damage is always energy
deficiency caused by ischemia (e.g., atherosclerosis,
embolism). Bleeding (due to trauma, vascular
aneurysm, hypertension also causes ischemia by
compressing neighboring vessels.
 DISORDER OF CEREBRAL BLOOD
FLOW, STROKE
By inhibiting Na+/K+-ATPase, energy deficiency
causes the cellular accumulation of Na+ and Ca2+ as
well as an increased extracellular concentration of
K+, and thus depolarization. This results in the
cellular accumulation of Cl, cell swelling, and cell
death . It also promotes the release of glutamate,
which accelerates cell death via the entry of Na+ and
Ca2+.
 DISORDER OF CEREBRAL BLOOD
FLOW, STROKE
Cell swelling, release of vasoconstrictor mediators,
and occlusion of vessel lumina by granulocytes
sometimes prevent reperfusion, despite the fact that
the primary cause has been removed. Cell death
leads to inflammation that also damages cells at the
edge of the ischemic area (penumbra).
The symptoms are determined by the site of the
impaired perfusion, i.e., the area supplied by the
vessel.
 HOW TO DIAGNOSE
Medical and family history
Physical exam
Listening to the arteries for an abnormal
whooshing sound (broo-E)
Weak or absent pulses in leg or foot can be sign of
a blocked artery
Diagnostic test
 HOW TO DIAGNOSE
Medical and family history
Physical exam
Listening to the arteries for an abnormal
whooshing sound (broo-E)
Weak or absent pulses in leg or foot can be sign of
a blocked artery
Diagnostic test
 Diagnostic test

- Blood tests : level of certain fats, cholesterol, sugar, and
protein
- EKG
- Chest X ray
- Ankle/brachial index : help diagnose P.A.D
- CT Scan : can show hardening and narrowing of large
arteries
- Angiography : showing whether plaque is blocking
- Stress test : using treadmill or stationary bike; to notice
how good heart works while physical activity
PREVENTION
 TREATMENT
Non medicamentosa
1.Diet
- Increase unsaturated fatty acids like MUFA
and PUFA (high in fish)
- Reduce consumption of crackers, cookies,
doughnuts, fries and fried chicken that
processed in hydrogenated oil
- Increase high fiber carbo diet : nuts, fruits,
vegetables, cereal
 TREATMENT
2. Physical activity
Purpose : To reach ideal weight, reduce
metabolic syndrome incidence and control
coronary heart disease risk factor.
Recommended:
- Walking fast (4.8 6.4 km/hr) for 30-40 minutes
- Swimming for 20 minutes
- Cycling 8 km in 30 minutes
- Playing volley for 45 minutes
- Sweeping the yard for 30 minutes
- Cleaning the house
- Dancing for 30 minutes
 Treatment
3. Weight loss
Body mass index and waist circumference are used
as size to assess obesity. The patients with excessive
weight need to reduce 10% of the weight.
Normal waist circumference for Asia is <90 cm for
male and <80 cm for female.
Every reduction of 10 kg of body weight is related
with the reduction of LDL up to 8 mg/dL
 Treatment
Body mass index classification for adult Asia population
 Treatment
4. Stop smoking
Increase HDL up to 5%-10%
Smoking is associated with TG enhancement
but TG reduction by stop smoking is doubtful
5. Suplemen diet (fitosterol, soya bean, rich
fiber food, PUFA omega-3)
 Treatment
Medicamentosa
1. Statin (HMG-CoA reduktase inhibitor)
Best tolerated and most effective way to reduce
LDL cholesterol levels and are considered the first-
line medication choice toward this end
Increaase HDL cholesterol and reduce TG level
Reduce LDL cholesterol level up to 18-55%,
Increase HDL cholestrol level up to 5-15%, dan
reduce TG up to 7-30%.
 Treatment
Statin works by inhibiting HMG-CoA reductase
The effect in regulating CETP causes reduction of LDL
and LDL cholesterol concentration so that can
increase LDL cholesterol cleaning.
Early study which used statin to reduce LDL
cholesterol level showed the reduced coronary heart
disease and the mortality, myocard infarct, stroke
and peripheral vascular disease
Treatment
 Treatment
Statin dose for patient with chronic kidney disease
 Treatment
2. Cholesterol absorption inhibitor (Ezetimibe)
The first drug that can inhibit cholesterol intake
from diet and bile cholesterol without influence
the nutrition absorption.
Recommended dose of ezetimibe is 10 mg/day
and must be used along with statin except patient
with statin intolerance and can be used single.
Can be combined with bile acid sequstrant or
nicotinic acid for patient with statin intolerance
 Treatment
3. Bile acid sequestrant
Three kinds of bile acid sequestrant : kolestiramin,
kolesevelam and kolestipol
Bile acid sequestrant binds bile acid in intestine so it inhibits
enterohepatic circulation from bile acid and increase
cholesterol changing to be bile acid in liver.
Daily dose of kolestiramin, kolestipol and kolesevelam in
row is 4-24 gr, 5-30 gr and 3.8-4.5 gr
High dose using (24 gr of kolestiramin or 20 gr of kolestinol)
decrease LDL cholesterol concentration up to 18-25%
 Treatment
3. Fibrat
An agonist of PPAR-. Through this receptor fibrat
decreases apoC-III gen regulation and increase
apoA-I and A-II regualtion.
The decreased apoC-III synthesis causes increasing
TG catabolism by lipoprotein lipase, decreasing
VLDL cholesterol forming, and increasing kilomikron
cleansing.
Increasing apoA-I and apoA-II regulation increases
HDL cholesterol concentration
 Treatment
Given to patient whose LDL cholesterol concenration
has reached target by statin but the TG still >200
mg/dL
Fenofibrat dose is 200 mg/day with max dose is 200
mg/day. Gemfibrozil dose is 600 mg given twice a
day with max dose 200 mg/day
 Treatment
4. Nicotinic acid (niacin)
Inhibits fatty acid mobilization from perifer fat
tissue to hepar so that TG synthesis and secretion
of VLDL cholesterol decreased
Prevents VLDL cholesterol converts to LDL, changes
LDL from small, dense particle to be big particle
and decreases Lp concentration
The most used is extended release which is used
before sleeping
 Treatment
Early dose is 500 mg/day for 4 weeks and raised
every next 4 weeks (500 mg) as long as can be
tolerated till the wanted lipid concentration reached.
Max dose is 2000 mg/day can decrease TG up to 20-
40%, LDL 15-18% and increase HLDL 15-35%
 Treatment
6. Inhibitor CETP
Cholesteryl ester transfer protein helps cholesteryl
ester transfer from HDL to VDL and LDL then cleansed
from circulation through LDL receptor in liver.
The effect of therapy: increase HDL and decrease LDL
through reversed cholesterol transport.
Among 3 CETP inhibitors (torcetrapib, dalcetrapib and
anacetrapib), torcetrapib has been withdrawn from
market which increased death rate.
Monotherapy of anacerrapib 40 mg, 150mg or 300 mg
for 8 weeks decreased LDL 16%, 27%, 40% and 39%
and in creased HDL 44%, 86% 129% and 133%
 Treatment
7. LDL cholesterol apheresis
Addressed to them with severe HoFM or
HeFH
Expensive but effective because LDL and
Lp(a) eliminated from plasma during
extracorporeal circulation every once in 1 or
2 weeks
 COMPLICATION
1. Plaque complication
Erosion, ulceration and fissure
Calcification in necrosis and plaque area
Mural thrombosis caused by disruption of
blood flow around plaque and the projection
of lumen. This also cause disruption of
endotel.
Plaque haemorrhage caused by the ruptured
fibrous cap or blood vessel
 Complication
2. Atherosclerosis complication
Acute occlusion : can cause infarct in the area that
gets the blood supply.
Chronic blood vessel lumen narrowing : marked by
organ atrophy ( unilateral renal artery stenosis
with renal atrophy, intestinal stricture of artery
mesenterica atherosclerosis, atrophy ischaemia of
DM patient skin with severe vascular disease
 Complication
Aneurysm : often in aorta abdominalis and
can cause rupture or perforation
Emboli : thrombus of atherosclerosis plaque
can release and clog in distal called embolus.
 REFERENCES
1. British heart foundation. Atherosclerosis your quick guide. England. 2014
2. National Heart, Lung and Blood Institute. At A Glance: Atherosclerosis.
National Institute of Health. USA. 2009.
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treatment of high-risk lipid abnormalities in children and adolescents.
Jornal de Pediatria. Vol.85(1). 2009.
4. Silbernagl S, Lang F. Color Atlas of Pathophysiology. Theme: New York.
2000. p.230
5. PERKI. Pedoman Tatalaksana Dislipidemia. Ed.1.2013.
6. Lewis SJ. Prevention and Treatment of Atherosclerosis: A Practitioners
Guide for 2008. The American Journal of Medicine. 2008.
7. Lumongga F. Atherosclerosis. Departemen Patologi Anatomi Universitas
Sumatera Utara Medan.2007.
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Atherosclerosis- A Review. Pharmacologyonline 3: 420-442.2009