Atherosclerosis

PROGRAM MAGISTER ILMU BIOMEDIK

FAKULTAS KEDOKTERAN UNIVERSITAS ANDALAS

NAMA : MIRNAWATI
BP : 2020312003
Mata kuliah : patologi dasar
Dosen : dr. Tofrizal, Sp. PA, P. hD, M. Biomed
Defenition

 Ateroslerosis adalah penyakit pada arteri dengan karakteristik terganggunya keseimbangan dan akumulasi
abnormal dari lipid, sel inflamasi, deposit matrik dan proliferasi sel otot polos pada dinding arteri yang
berukuran sedang dan besar  arteri menjadi sempit dan keras
 Akumulasi ini paling sering terdeteksi selama dekade kedua kehidupan dan bertambah seiring
bertambahnya usia.
 Lesi pada pembuluh darah yang progresif ini menurunkan aliran darah.
 Lesi aterosclerotik dapat terjadi dimana saja sepanjang arteri tetapi lebih sering terjadi pada pembuluh
darah yang bercabang.
Epidemiology

 Aterosklerosis biasa ditemui di negara maju dan meningkat pesat pada negara sedang berkembang
 American Heart Association mempublikasikan bahwa lebih dari 17 juta orang meninggal pada tahun 2013
karena penyakit kardiovaskuler, menjadi penyebab pertama kematian secara global
 Di USA, penyakit kardiovaskuler menyebabkan 800.937 kematian yang merupakan 31 % dari total
kematian di negara tersebut pada tahun 2013.
 Diperkirakan bahwa pada tahun 2030 rata-rata biaya perawatan untuk penyakit kardiovaskuler akan
meningkat menjadi sekitar 1.044 $ secara global
Risk Factor
Risk factor
• Family history is the most important

Genetic independent risk factor for atherosclerosis

• Between ages 40 and 60, the incidence of myocardial infarction

Age
increases five-fold.
• Death rates from ischemic heart disease rise with each decade
even into advanced age

• Other factors being equal, premenopausal women are relatively

Gender
protected against atherosclerosis
• After menopause, however, the incidence of atherosclerosis
related diseases increases in women and at older ages actually
exceeds that of men.
 • more specifically hypercholesterolemia—is a
Hyperlipidemia major risk factor for atherosclerosis

• Another major risk factor for atherosclerosis; both systolic

and diastolic levels are important.
Hypertension • On its own, hypertension can increase the risk of ischemic
heart disease by approximately 60% versus normotensive
populations

• A well-established risk factor in men and likely accounts for the

increasing incidence and severity of atherosclerosis in women.
Cigarette smoking • Prolonged (years)smoking of one pack of cigarettes or more daily
doubles the death rate from ischemic heart disease
• Smoking cessation reduces that risk substantially

• Diabetes mellitus induces hypercholesterolemia and

Diabetes mellitus markedly increases the risk of atherosclerosis.
 Pathophysiology
• Atherosclerosis develops as a chronic
inflammatory response of the arterial wall to
endothelial injury.
• Lesion progression occurs through interactions of
modified lipoproteins, monocyte-derived
macrophages, T-lymphocytes, and the normal
cellular constituent of the arterial wall.
• The contemporary view of atherosclerosis is
expressed by the response-to-injury hypothesis.
 Response-to-injury hypothesis
• following are the
The
steps involved in the
hypothesis:
1. Chronic endothelial
injury
2. Accumulation of
lipoproteins
3. Monocyte adhesion to the
endothelium
4. SMC proliferations and
ECM production
5. factor release
6. platelet adhesion
 Response-to-injury hypothesis

1. Chronic endothelial injury

• with resultant endothelial dysfunction,

causing increased permeability, leukocyte
adhesion, and thrombosis
 Response-to-injury hypothesis
2. Accumulation of lipoproteins
• (mainly LDL and its oxidized forms) in the
vessel wall. Low-density lipoprotein molecules
(LDL) becoming oxidized (ldl-ox) by free
radicals, particularly oxygen free (ROS). When
oxidized LDL comes in contact with an artery
wall, a series of reactions occur to repair the
damage to the artery wall caused by oxidized
LDL. Cholesterol can move in the bloodstream
only by being transported by lipoproteins
 Response-to-injury hypothesis
3. Monocyte adhesion to the endothelium
• followed by migration into the intima and
transformation into macrophages and foam cells. The
body's immune system responds to the damage to the
artery wall caused by oxidized LDL by sending
specialized white blood cells (macrophages and T-
lymphocytes) to absorb the oxidized-LDL forming
specialized foam cells. Unfortunately, these white
blood cells are not able to process the oxidized-LDL,
and ultimately grow then rupture, depositing a greater
amount of oxidized cholesterol into the artery wall.
This triggers more white blood cells, continuing the
cycle.
 Response-to-injury hypothesis
4. platelet adhesion

5. factor release
• from activated platelet,
macrophages and vascular wall
cells, inducing SMC recruitment,
either from the media or from
the circulating precursors
Response-to-injury hypothesis
6. SMC proliferations and ECM production.
• Eventually, the artery becomes
inflamed. The cholesterol plaque causes
the smooth muscle cells to enlarge and
form a hard cover over the affected area.
This hard cover is what causes a
narrowing of the artery, reduces the
blood flow and increases blood pressure.
Response-to-injury hypothesis
7. Lipid accumulation
• both extracellularly and within cells
(macrophages and SMC’s). accumulation if
lipid-containing macrophages in the intima
gives rise to “fatty streaks”, with further
evolution, a fibrofatty atheroma consisting of
proliferated SMC, foam cells, extracellular
lipid, and ECM is formed.
Micrograph of an artery that supplies the heart With
significant atherosclerosis and marked luminal narrowing
 Symptoms
• Atherosclerosis develops gradually, typically
begins in early adolescence, and is usually
found in most major arteries. There are usually
no atherosclerosis symptoms until an artery is
so narrowed or clogged that it can't supply
adequate blood to your organs and tissues.
Sometimes a blood clot completely obstructs
blood flow, or even breaks apart and causes
blood clots that can trigger a heart attack or
stroke.
 Symptoms
Atherosclerosis symptoms depend on which arteries are
affected. For example:
• Atherosclerosis in heart arteries, have symptoms similar
to those of a heart attack, such as chest pain (angina).
• Atherosclerosis in the arteries leading to brain, have
symptoms such as sudden numbness or weakness in your
arms or legs, difficulty speaking or slurred speech, or
drooping muscles in your face.
• Atherosclerosis in the arteries in arms and legs, produces
decreased blood flow is called peripheral artery occlusive
disease (PAOD).have symptoms such as leg pain when
walking
• Sometimes atherosclerosis causes erectile dysfunction in
men.
Symptoms
Symptoms
 Complications
The complications of atherosclerosis depend on the
location of the blocked arteries. For example:
• Coronary artery disease. When atherosclerosis
narrows the arteries close to your heart, you may
develop coronary artery disease, which can
cause chest pain (angina) or a heart attack.
• Carotid artery disease. When atherosclerosis
narrows the arteries close to your brain, you may
develop carotid artery disease, which can cause
a transient ischemic attack (TIA) or stroke.
 Complications
• Peripheral artery disease. When atherosclerosis narrows the arteries
in your arms or legs, you may develop circulation problems in your
arms and legs called peripheral arterial disease. This can make you
less sensitive to heat and cold, increasing your risk of burns or
frostbite. In rare cases, poor circulation in your arms or legs can cause
tissue death (gangrene).
• Aneurysms. Atherosclerosis can also cause aneurysms, a serious
complication that can occur anywhere in your body. An aneurysm is a
bulge in the wall of your artery. Pain and throbbing in the area of an
aneurysm is a common symptom. If an aneurysm bursts, you may face
life-threatening internal bleeding. Although this is usually a sudden,
catastrophic event, a slow leak is possible. If a blood clot within an
aneurysm dislodges, it may obstruct an artery at some distant point.
 Tests and diagnosis
Doctors may find signs of narrowed, enlarged or hardened
arteries during a physical exam. These include:
• A weak or absent pulse below the narrowed area of the
artery
• Decreased blood pressure in an affected limb
• Whooshing sounds (bruits) over the arteries, heard with a
stethoscope
• Signs of a pulsating bulge (aneurysm) in the abdomen or
behind knee
• Evidence of poor wound healing in the area where blood
flow is restricted
 Tests and diagnosis
Depending on the results of the physical exam,
doctors may suggest one or more diagnostic tests,
including:
• Blood tests.
• Doppler ultrasound
• Ankle-brachial index.
• Other imaging tests.
• Angiogram.
• Electrocardiogram (ECG).
 Tests and diagnosis
• Blood tests. Lab tests can detect increased levels of cholesterol and
blood sugar that may increase the risk of atherosclerosis.
• Doppler ultrasound. Uses a special ultrasound device (Doppler
ultrasound) to measure blood pressure at various points along arm or
leg. These measurements can help doctor gauge the degree of any
blockages, as well as the speed of blood flow in the arteries.
• Ankle-brachial index. This test can tell if one have atherosclerosis in
the arteries in your legs and feet. Doctor may compare the blood
pressure in ankle with the blood pressure in the arm. This is known as
the ankle-brachial index. An abnormal difference may indicate
peripheral vascular disease, which is usually caused by
atherosclerosis.
 Tests and diagnosis
• Electrocardiogram (ECG). An electrocardiogram records electrical
signals as they travel through your heart. An ECG can often reveal
evidence of a previous heart attack or one that's in progress. If signs
and symptoms occur most often during exercise,
• Angiogram. To better view blood flow through heart, brain, arms or
legs, doctor may inject a special dye into your arteries before an X-
ray. This is known as an angiogram. The dye outlines narrow spots
and blockages on the X-ray images.
• Other imaging tests. doctor may use ultrasound, a computerized
tomography (CT) scan or a magnetic resonance angiogram (MRA) to
study the arteries. These tests can often show hardening and
narrowing of large arteries, as well as aneurysms and calcium deposits
in the artery walls.
 Treatments and drugs
Lifestyle changes, such as eating a healthy diet and exercising,
are often the first line of defense in treating atherosclerosis.
But sometimes, medication or surgical procedures may be
recommended as well.
Various drugs can slow — or sometimes even reverse — the
effects of atherosclerosis. Here are some common choices:
• Cholesterol medications. Aggressively lowering low-
density lipoprotein (LDL) cholesterol, the "bad" cholesterol,
can slow, stop or even reverse the buildup of fatty deposits
in arteries. Boosting your high-density lipoprotein (HDL)
cholesterol, the "good" cholesterol, may help, too.
cholesterol medications includes drugs known as statins and
fibrates.
 Treatments and drugs
• Anti-platelet medications. Doctors may prescribe anti-
platelet medications, such as aspirin, to reduce the
likelihood that platelets will clump in narrowed arteries,
form a blood clot and cause further blockage.
• Anticoagulants. An anticoagulant, such as heparin or
warfarin (Coumadin), can help thin blood to prevent
clots from forming.
• Blood pressure medications. Medications to control
blood pressure — such as beta blockers,
angiotensin- converting enzyme (ACE) inhibitors
and calcium channel blockers — can help slow the
progression of atherosclerosis
 Treatments and drugs
Other medications, doctor may suggest certain
medications to control specific risk factors for
atherosclerosis, such as diabetes. Sometimes
medications to treat symptoms of atherosclerosis,
such as leg pain during exercise, are prescribed.
Sometimes more aggressive treatment is needed. If
you have severe symptoms or a blockage that
threatens muscle or skin tissue survival, you may be
a candidate for one of the following surgical
procedures:
 Treatments and drugs
• Angioplasty. In this procedure, your doctor inserts a long, thin
tube (catheter) into the blocked or narrowed part of your artery.
A wire with a deflated balloon is passed through the catheter to
the narrowed area. The balloon is then inflated, compressing the
deposits against your artery walls. A mesh tube (stent) is usually
left in the artery to help keep the artery open. Angioplasty may
also be done with laser technology.
• Endarterectomy. In some cases, fatty deposits must be
surgically removed from the walls of a narrowed artery. When
the procedure is done on arteries in the neck (the carotid
arteries), it's known as carotid endarterectomy.
 Treatments and drugs

• Thrombolytic therapy. If you have an artery that's

blocked by a blood clot, your doctor may insert a
clot-dissolving drug into your artery at the point of
the clot to break it up.
• Bypass surgery. Your doctor may create a graft
bypass using a vessel from another part of your
body or a tube made of synthetic fabric. This allows
blood to flow around the blocked or narrowed artery.
 Lifestyle and home remedies
Lifestyle changes can help prevent or slow the
progression of atherosclerosis.
• Stop smoking.
• Exercise most days of the week.
• Eat healthy foods
• Manage stress
• manage the condition of high cholesterol, high
blood pressure, diabetes or other chronic
disease
 Prevention
• The same healthy lifestyle changes recommended
to treat atherosclerosis also help prevent it. You've
heard it before — stop smoking, eat healthy foods,
exercise regularly, maintain a healthy weight,
drink less alcohol. Just remember to make
changes one step at a time, and keep in mind
what lifestyle changes are manageable for you in
the long run.
 Conclusion
• Although atherosclerosis is considered a heart disease it
can happen in any part of the bodies.
• Atherosclerosis can be prevented by life style factor
and home remidies by eating healthy diet.
• Atherosclerosis is a preventable and treatable
condition.
 References:
• Robbin and cotran. (2015). Phatologic basis of disease professional edition ninth
edition. Elsevier saunders.
• Harrison’s principle of internal medicine, 17th edition.
• William Insull, Jr., MD. The Pathology of Atherosclerosis: Plaque Developmentand
Plaque Responses to Medical Treatment. The American Journal of Medicine, Vol 122,
No 1A, January 2009
• Mota, Roberto; Homeister, Jonathon W; Willis, Monte S; andBahnson, Edward M
(October 2017) Atherosclerosis:Pathogenesis, Genetics and Experimental Models. In:
eLS. JohnWiley & Sons, Ltd: Chichester.DOI:
10.1002/9780470015902.a0005998.pub3
• www.mayoclinic.com/atherosclerois