Atherosclerosis

Atherosclerosis
is characterized by localized
fibrous thickenings of the arterial
wall associated with lipidinfiltrated plaques that may
eventually calcify.
calcify

Pathogenesis
initial event is : Infiltration of lowdensity lipoproteins (LDL) into the sub
endothelial region.
endothelium is subject to shear
stress, tendency to be pulled along or
deformed by flowing blood.

 LDL are oxidized or altered in other

ways, then taken up by macrophages,
forming foam cells .
foam cells form fatty streaks.
streaks
in the first decade of life, the streaks
appear in the aorta, in the second
decade in the coronary arteries, and
in the third and fourth decades in
the cerebral arteries.

 Vascular smooth muscle cells in the

vicinity of foam cells are stimulated
and move from the media to the
intima,
intima where they proliferate, lay
down collagen and other matrix
molecules, and contribute to the bulk
of the lesion.
Smooth muscle cells also take up
oxidized LDL and become foam cells.

 As plaques mature, a fibrous cap

forms over them.
plaques with defective or broken
caps are most prone to rupture.
The lesions alone may distort vessels
to the point that they are occluded,
but it is usually rupture or ulceration
of plaques that triggers thrombosis,
blocking blood flow.

Atherosclerosis: A Progressive Process

Normal

Fatty
Streak

Fibrous
Plaque

Occlusive
Atherosclerotic
Plaque

Plaque
Rupture/
Fissure &
Thrombosis

Unstable
Angina

MI
Coronary
Death
Stroke
Effort Angina
Claudication

Clinically Silent

Increasing Age
Courtesy of P Ganz.

Critical Leg
Ischemia

Risk Factor
Male gender (and female after
menopause) : Lack of LDL-lowering
effect of estrogens; estrogens probably
act by increasing the number of LDL
receptors in the liver.
Family history of ischemic heart
disease, stroke : Probably multiple
genetic mechanisms.

 Primary hyperlipidemia and

Secondary hyperlipidemia
(Increased circulating triglycerides
produced by diuretics, b-adrenergic
blocking drugs,
drugs excess alcohol intake)
Cigarette smoking:
smoking Probably carbon
monoxide-induced hypoxic injury to
endothelial cells.

 Hypertension:
Hypertension Increased shear stress,
with damage to endothelium.
Diabetes mellitus (types 1 and 2):
Decreased hepatic removal of LDL from
the circulation; increased glycosylation
of collagen,
collagen which increases LDL binding
to blood vessel walls.

 Obesity,
Obesity particularly abdominal obesity:
Nephrotic syndrome:
syndrome Increased hepatic
production of lipids and lipoprotein(a).
Hypothyroidism:
Hypothyroidism Decreased formation
of LDL receptors in the liver.

Pathophysiology

Acute Coronary
Syndrome
(ACS)

Dr Abdul Majid SpPD-KKV

 Koroner normal
Pasokan seimbang dengan kebutuhan
(aliran darah koroner)

(kebutuhan miokard)

PJK Pasokan ,
tetap

kebutuhan

Pasokan tetap, kebutuhan

When flow through a coronary artery

is reduced to the point that the
myocardium it supplies becomes
hypoxic, "P factor"
factor accumulates and
angina pectoris develops .
If the myocardial ischemia is severe
and prolonged, irreversible changes
occur in the muscle, and the result is
myocardial infarction.
infarction

Partially occluded coronary arteries can

be constricted further by vasospasm,
producing myocardial infarction.
The most common cause of myocardial
infarction is rupture of an
atherosclerotic plaque, or hemorrhage
into it, which triggers the formation of
a coronary occluding clot at the site of
the plaque.

When myocardial cells actually die,

they leak enzymes into the
circulation, and measuring the rises in
serum enzymes and isoenzymes
produced by infarcted myocardial cells
also plays an important role in the
diagnosis of myocardial infarction.
The enzymes most commonly
measured today are the MB isomer of
creatine kinase (CK-MB), troponin T,
and troponin I.
I

Mechanism of
Atherosclerosis

ACS: physiopathology

 at rest, to produce cellular ischemia

arterial lumen must be decreased to 90%
when exercise, a 50% reduction in lumen
size can lead to symptoms.
In unstable angina,
angina fissuring of the
atherosclerotic plaque can lead to platelet
accumulation and transient episodes of
thrombotic occlusion, usually lasting 10
20 minutes.

 platelet release of vasoconstrictive

factors such as thromboxane A2 or
serotonin and endothelial dysfunction
may cause vasoconstriction and
contribute to decreased flow.
In myocardial infarction,
infarction deep
arterial injury from plaque rupture
may cause formation of a relatively
fixed and persistent thrombus.

Plaque Rupture Leads to Thrombus Formation

Unstable Plaque

Thin Fibrous Cap

Lipid Core

Ruptured Plaque
Inflammatory
Cells
Thrombu
s

Few
SMCs
Activated
Macropha
ges

Loss of the extracellular matrix and cellular necrosis

due to the inflammatory response appear to be the key
mediators for plaque rupture

Plaque Rupture Leads to Thrombus Formation

Yeghiazarians Y et al. N Engl J Med. 2000;342:101-114.

Role of Platelets in Thrombus

Formation
in Acute Ischemic Events

Lipid
Core

Atherosclerotic
Vessel

Plaque
Rupture

Platelet Adhesion,
Activation, and
Aggregation

Thrombus
Formation

Vessel wall injury Plaque rupture

Exposure of subendothelial collagen and
other platelet-adhering ligands

Schafer AI. Am J Med. 1996;101:199209.

Thrombotic
Occlusion

MI
Stroke
Vascular
Death

a cross-section of the coronary artery. Most of its wall is

filled with smooth muscle cells that can contract and relax.

Nitroglycerin dilates constricted arteries.

atherosclerotic plaque( consists of cholesterol, inflammatory cells,

and fibrosis, and it reduces the space for blood flow in the artery.)

A spasm can suddenly develop in an atherosclerotic

coronary artery ( angina pectoris)

Patofisiologi SKA
Agregasi trombosit,
akumulasi lipid & makrofag
Plak stabil

Plak tak
stabil
Injury &
disfungsi endotel

Hipertensi
Merokok
DM
Dislipidemia
Zat vasoaktif
dll
Disfungsi endotel

disrupsi
Trombosis akut
APTS
Oklusi koroner
IMA

Platelet & thrombin

dependent vasoconstriction

Vasokonstriksi

Atherosclerosis: A Progressive Process

Normal

Fatty
Streak

Fibrous
Plaque

Occlusive
Atherosclerotic
Plaque

Plaque
Rupture/
Fissure &
Thrombosis

Unstable
Angina

MI
Coronary
Death
Stroke
Effort Angina
Claudication

Clinically Silent

Increasing Age
Courtesy of P Ganz.

Critical Leg
Ischemia

Spectrum of Acute coronary syndromes

AcuteCoronary
CoronarySyndrome
Syndrome
Acute
NoST
STElevation
Elevation
No

STElevation
Elevation
ST

Non ST Elevation MI

UnstableAngina
Angina
Unstable

Myocardial Infarction
Infarction
Myocardial
NonQw
QwMI
MI
QwMI
MI
Non
Qw
(NSTEMI)
(NSTEMI)

Braunwald E et al. J Am Coll Cardiol 2000;36:9701062.

(STEMI)
(STEMI)

Cardiac serum marker in Acute Myocardial Infarction

Acute Coronary
Syndrome
Ischemic Discomfort
Unstable Symptoms

No ST-segment
elevation

Unstable
angina

History
Physical Exam

ST-segment
elevation

Non-Q
AMI

Q-Wave
AMI

ECG

Acute
Reperfusion

Plaque Rupture with Thrombosis

Thrombus

Fibrous cap

1 mm

Illustration courtesy of Frederick J. Schoen,

M.D., Ph.D.

Lipid core

Let it
beat!