Aterosklerosis

* Arteri ke otak stroke

(cerebrovascular disease)
* Arteri koroner serangan
jantung (coronary artery
disease/coronary heart
disease, penyakit jantung
koroner, PJK)

Penebalan dinding arteri:

dinding arteri menebal ke bagian
dalam penyempitan lumen
(stenosis)

Stenosis aliran darah terganggu

Mengenai arteri ukuran

sedang-besar:

-a. Coroner
-a. Carotis
- a. Femoral
-a. Iliaca
- aorta

Stages in the development of atherosclerotic

lesions
Peter Libby., Paul M Ridker., Gran K. Hansson (Nature 473, 317325)

The normal muscular artery and the cell changes that occur during disease progression
to thrombosis are shown. Peter Libby., Paul M Ridker., Gran K. Hansson (Nature 473,
317325)
a,
The normal artery contains three layers. The inner layer, the tunica intima, is
lined by a monolayer of endothelial cells that is in contact with blood overlying a
basement membrane. In contrast to many animal species used for atherosclerosis
experiments, the human intima contains resident smooth muscle cells (SMCs). The
middle layer, or tunica media, contains SMCs embedded in a complex extracellular
matrix. Arteries affected by obstructive atherosclerosis generally have the structure of
muscular arteries. The arteries often studied in experimental atherosclerosis are elastic
arteries, which have clearly demarcated laminae in the tunica media, where layers of
elastin lie between strata of SMCs. The adventitia, the outer layer of arteries, contains
mast cells, nerve endings and microvessels.
b,
The initial steps of atherosclerosis include adhesion of blood leukocytes to the
activated endothelial monolayer, directed migration of the bound leukocytes into the
intima, maturation of monocytes (the most numerous of the leukocytes recruited) into
macrophages, and their uptake of lipid, yielding foam cells.
c,
Lesion progression involves the migration of SMCs from the media to the
intima, the proliferation of resident intimal SMCs and media-derived SMCs, and the
heightened synthesis of extracellular matrix macromolecules such as collagen, elastin
and proteoglycans. Plaque macrophages and SMCs can die in advancing lesions, some
by apoptosis. Extracellular lipid derived from dead and dying cells can accumulate in
the central region of a plaque, often denoted the lipid or necrotic core. Advancing
plaques also contain cholesterol crystals and microvessels.
d,
Thrombosis, the ultimate complication of atherosclerosis, often complicates a
physical disruption of the atherosclerotic plaque. Shown is a fracture of the plaque's
fibrous cap, which has enabled blood coagulation components to come into contact
with tissue factors in the plaque's interior, triggering the thrombus that extends into the

Inflammation and
Atherosclerosis
Atherosclerosis,
* dahulu diduga
disebabkan oleh
penimbunan lipid
(kolesterol)
* Kini diketahui sebagai
penyakit
Padainflamatorik
models hewan
atherosclerosis,
* Inflamasi terjadi disertai
dengan terjadinya
penimbunan lipid pada
dinding arteri.
* Misalnya, leukosit darah,
mediator inflamasi, ditemui
di daerah lesi dini
atherosclerosis,

Inflamasi
terlibat
pada
*
Inisiasi
dan
perkembangan
ateroma,
* juga terlibat pada
komplikasi nya pada
pembentukan trombus
akut

Oxidized Lipoproteins and

Inflammation
Menurut hipotesis
Lipid termodifikasi dapat
menginduksi:
oksidasi lipid,
ekspresi adhesion
low-density lipoprotein
molecules, chemokines,
(LDL) terakumulasi di
proinflammatory
intima, sebagian
cytokines, dan mediators
terikat pada
of inflammation in
proteoglycan,
macrophages and vascular
mengalami modifikasi
wall cells.
oksidatif menjadi lipid
hydroperoxides,
lysophospholipids,
Hipotesis
carbonyl
compounds)
Pemberian
antioksidan
oksidasi LDL
dapat menghambat
pada manusia
perkembangan lesi
masih sulit
aterosklerosis
dibuktikan

Dyslipidemia and
Inflammation
Lipoprotein lain:
* very lowdensity
lipoprotein (VLDL) and
intermediate-density
lipoprotein (IDL) juga
berpotensi aterogenik
* Lipoprotein ini juga
dapat mengalami
modifikasi oxidatif
seperti LDL.
* Partikel yg mengalami
oksidasi dpt
mengaktifkan fungsi
inflamasi & fungsi selsel endotel

High-density lipoprotein
(HDL) memproteksi thd
atherosclerosis.
* Transpor balik
kolesterol fungsi
ateroprtektif
* Dapat mentranspor
enzim antioksidan :
platelet-activating
factor acetylhydrolase &
paraoxonase, yang dapat
memecah lipid teroksidasi
& menetralkan efek
proinflamatorinya

Hypertension and
Inflammation
Angiotensin II (AII), in addition to its
vasoconstrictor properties, can
instigate intimal inflammation. For
example, AII elicits the production of
superoxide anion, a reactive oxygen
species, from arterial endothelial
cells and SMCs. AII can also increase
the expression by arterial SMCs of
proinflammatory cytokines such as
interleukin (IL)6 and MCP-1 and of
the leukocyte adhesion molecule
VCAM-1 on endothelial cells

Diabetes and Inflammation

The hyperglycemia associated
with diabetes can lead to
modification of macromolecules,
for example, by forming advance
glycation end products (AGE)
By binding surface receptors such as RAGE
(receptor for AGE), these AGE-modified
proteins can augment the production of
proinflammatory cytokines and other
inflammatory pathways in vascular
endothelial cells. Beyond the hyperglycemia,
the diabetic state promotes oxidative stress
mediated by reactive oxygen species and
carbonyl groups

Obesity and
Inflammation
Obesity not only predisposes to insulin
resistance and diabetes, but also
contributes to atherogenic
dyslipidemia. High levels of free fatty
acids originating from visceral fat
reach the liver through the portal
circulation and stimulate synthesis of
the triglyceride-rich lipoprotein VLDL
by hepatocytes. The resulting elevation
in VLDL can lower HDL cholesterol by
augmenting exchange from HDL to
VLDL by cholesteryl ester transfer
protein. Adipose tissue can also
synthesize cytokines such as TNF- and
IL-6

Infection
* Acute infections can alter hemodynamics and
the clotting and fibrinolytic systems in ways
that can precipitate ischemic events.
* Chronic extravascular infections (eg, gingivitis,
prostatitis, bronchitis, etc) can augment
extravascular production of inflammatory
cytokines that may accelerate the evolution of
remote atherosclerotic lesions.
*
Intravascular
infection
might
also of
provide
a
Many
human plaques
show
signs
infection
by
local inflammatory
stimulus
that could
microbial
agents such
Chlamydia
pneumoniae.
accelerate atherogenesis
Chlamydiae,
when present in the arterial plaque,
may release lipopolysaccharide (endotoxin) and
heat shock proteins (HSP) that can stimulate the
production of proinflammatory mediators by
vascular
endothelial
cells
and
SMCs
and
infiltrating leukocytes alike.

Komplikasi

Aterosklerosis kronis asimptomatik

Komplikasi atherosclerotic plaque rupture trombosis

membuntu lumen iskhemia simptomatik (manifestasi
klinis)
Komplikasi
aterosklerotis karotid
Komplikasi
STROKE
aterosklerosis koroner
*cerebrovascular
SERANGAN JANTUNG
accident, CVA)
(Sindrom Koroner Akut ,
* Transient Ischemic Attack
SKA)
(TIA)
(Acute Coronary Syndrome,
ACS)
Tanda klinis:
*
Nyeri
dada
(angina
pectoris)
* Infark miokardial akut
(IMA)
* sudden death

Serangan Jantung

Serangan Jantung (heart attack)

Mortalitas no 1
Global killer 2020
Faktor resiko konvensional :
(multifaktorial 50 - 60% kasus)
- hiperkolesterol - hiperlipidemia
- diabetes
- obesitas
- hipertensi
- stres
- familial
- merokok
50 % kasus belum jelas ???
Infeksi ??

Serangan Jantung =
heart attack = infark miokardial
Terjadinya kematian otot jantung yang disebabkan oleh
penyumbatan secara tiba-tiba a. koroner oleh trombus.
Arteri koroner : memasok darah & oksigen ke jantung.

Aterosklerosis ruptur plak trombosis IM

Trombus oklusif iskemia IM

Angina pektoris

Pain zones in MI
merah tua : paling sering
merah muda : lebih ringan

Unstable angina IMA

dyspnea
Sweating
Headedness
Nousea
Vomiting
Palpitation
Loss consciousness
Sudden death

Stroke

(cerebrovascular accident,CVA)

Klasifikasi

Simptom

Kena CNS saraf kranial: Perubahan fungsi

penglihatan, membau, mendengar, rasa, emosi,
gangguan motorik, berkurangnya refleks, dll
Kortex cerebrii: apasia (kemam verbal, membaca, menulis,
dll), memori, perilaku hiperseks, disorganized thinking.
Cerebelum: perubahan berjalan, bergerak, vertigo. Dll, dll

Decussatio
pyramidum

Transient Ischemic
Attack (TIA)
A transient ischemic
attack is often called
a mini-stroke.

TIA
is a medical
emergency

A transient ischemic attack

(TIA) is a temporary blockage
of blood flow in the brain that
causes brief stroke symptoms

They may include weakness

on one side of the body,
dizziness, blurred vision,
confusion, and speech
problems.

Penyebab
Long-standing
high blood pressure or
diabetes may damage smaller
blood vessels in the brain,
causing a clot to form within
the blood vessels and block
flow.
Ablood
blood
clot can form in
an artery that supplies
blood to the brain.
Blood clots usually
form in arteries
damaged by plaque
buildup, which is a
process called
atherosclerosis. See a
picture of
how high blood pressure
damages arteries

Blood clots that temporarily

block blood flow to the brain are
the most common cause of
transient ischemic attacks
(TIAs). Blood clots may develop
for a variety of reasons.
A blood clot can form in
another part of the body (often
the heart) and travel through
the bloodstream to an artery
that supplies blood to the
brain. For example, clots may
form: After a heart attack.
As a result of other conditions
that alter how blood flows
through the heart. These
conditions include abnormal

A tear in the wall of a blood

vessel located in the neck.
Clumps of bacteria, tumor
cells, or air bubbles that
move through the
bloodstream.

Inflammation in the blood

vessels, which may
develop from conditions
such as syphilis,
tuberculosis, or other
inflammatory diseases.

Also, an artery that is partially

blocked with plaque can reduce
blood flow to the brain and cause
symptoms
Conditions that cause blood cells to
stick together. For example, having
too many red blood cells
(polycythemia), abnormal clotting
factors, or abnormally shaped red
blood cells, such as those caused
by sickle cell disease, may cause
blood clots to form
A head or neck injury that results in
damage to blood vessels in the
head or neck