Sirkulasi Koroner

Departemen Fisiologi
Fakultas Kedokteran
Universitas Sumatera Utara
 Coronary circulation
• Cardiac muscle cannot extract O2 or nutrients
from the blood within its chambers , because:
1. watertight endocardial lining does not permit
blood to pass from chamber into myocardium.
2. heart walls are too thick to permit diffusion of
O2 and other supplies from blood in chamber
to cardiac cells.
Coronary Circulation: Arterial Supply

•Coronary flow at rest in

humans is about 250
mL/min (5% of the
cardiac output).

•Cabang pembuluh
nadi utama ( Aorta ).

•Membawa darah
(Oksigen) ke otot
jantung.

Figure 18.7a
 2 pembuluh utama koroner :

* Koroner kiri mempunyai 2 cabang : * Koroner kanan, memperdarahi bagian kanan,

= cabang pembuluh depan kiri bawah dan belakang kiri otot jantung.

= cabang pembuluh belakang kiri

• The heart muscle receives most
of its blood supply during
diastole (70%).
• Blood flow to the heart muscle
cells is substantially reduced
during systole because:

1. Contracting myocardium compresses the

major branches of coronary arteries,
2. The open aortic valve partially blocks the
entrance to the coronary vessels.
3. Pressure inside left ventricle is slightly higher
than in aorta during systole
 Special Features of Cardiac
Muscle Metabolism
• Most important, under resting conditions,
cardiac muscle normally consumes fatty acids to
supply most of its energy instead of
carbohydrates (about 70 per cent of the energy
is derived from fatty acids).
• However, as is also true of other tissues, under
anaerobic or ischemic conditions, cardiac
metabolism must call on anaerobic glycolysis
mechanisms for energy.
• Glycolysis consumes tremendous quantities of
blood glucose and at the same time forms
large amounts of lactic acid in cardiac tissue,
which is probably one of the causes of cardiac
pain in cardiac ischemic conditions
• In severe coronary ischemia, the ATP
degrades first to adenosine diphosphate, then
to adenosine monophosphate and adenosine.
• Because the cardiac muscle cell membrane is
slightly permeable to adenosine, much of this
can diffuse from the muscle cells into the
circulating blood.
• Koroner normal
Pasokan seimbang dengan kebutuhan

(aliran darah koroner) (kebutuhan miokard)

PJK  Pasokan , kebutuhan tetap

Pasokan tetap, kebutuhan 

 Coronary Artery Disease
• CAD can cause myocardial ischemia and
possibly lead to acute myocardial infarction by
three mechanisms:
• (1) profound vascular spasm of the coronary
arteries,
• (2) formation of atherosclerotic plaques, and
• (3) thromboembolism.
 (1) Vascular spasm
• Vascular spasm is an abnormal spastic
constriction that transiently narrows the
coronary vessels.
• Vascular spasms are associated with the early
stages of CAD and are most often triggered by
exposure to cold, physical exertion, or anxiety.
• When too little O2 is available in the coronary
vessels, the endothelium (blood vessel lining)
releases platelet-activating factor (PAF).
vascular spasm
 (2) Atherosclerosis
• Atherosclerosis is a
progressive, degenerative
arterial disease that leads to
occlusion (gradual blockage) of
affected vessels,
• is characterized by localized fibrous
thickenings of the arterial wall associated with
lipid-infiltrated plaques that may eventually
calcify.
 DEVELOPMENT OF
ATHEROSCLEROSIS
• An atherosclerotic plaque
consists of a lipid-rich core
covered by an abnormal
overgrowth of smooth muscle
cells, topped off by a
collagen-rich connective
tissue cap.
• As plaque forms, it bulges
into the vessel lumen
• 1. Atherosclerosis is believed to
start with injury to the blood
vessel wall, which triggers an
inflammatory response that sets the
stage for plaque buildup.

• Such as oxidized cholesterol, free

radicals, high blood pressure,
homocysteine, chemicals released from
fat cells, or even bacteria and viruses
that damage blood vessel walls.
• 2. Typically, the initial stage of atherosclerosis is
characterized by the accumulation beneath the
endothelium of excessive amounts of low-density
lipoprotein (LDL), the so-called “bad” cholesterol, in
combination with a protein carrier.
• As LDL accumulates within the vessel wall, this
cholesterol product becomes oxidized, primarily by
oxidative wastes produced by the blood vessel
cells.
• These wastes are free radicals, very unstable
electron-deficient particles that are highly reactive.
• 3. In response to the presence of oxidized LDL
and/or other irritants, the endothelial cells
produce chemicals that attract monocytes, a type of
white blood cell, to the site.
• These immune cells trigger a local inflammatory
response.
• 4. Once they leave the blood and enter the
vessel wall, monocytes settle down
permanently, enlarge, and become large
phagocytic cells called macrophages.
• Macrophages voraciously phagocytize the oxidized
LDL until these cells become so packed with
fatty droplets that they appear foamy under a
microscope.
• Now called foam cells, these greatly engorged
macrophages accumulate beneath the vessel
lining and form a visible fatty streak, the earliest
form of an atherosclerotic plaque.
• 5. The disease progresses as smooth
muscle cells within the blood vessel
wall migrate from the muscular layer
of the blood vessel to a position on
top of the lipid accumulation.

• At their new location, the smooth muscle cells

continue to divide and enlarge, producing
atheromas, which are benign (noncancerous)
tumors of smooth muscle cells within the blood
vessel walls.
• Together the lipid-rich core and overlying
smooth muscle form a maturing plaque.
• 6. As it continues to
develop, the plaque
progressively bulges
into the lumen of the
vessel.

• 7. Further contributing to vessel narrowing,

oxidized LDL inhibits release of nitric oxide from
the endothelial cells.
• 8. A thickening plaque also interferes with
nutrient exchange for cells located within the
involved arterial wall, leading to degeneration
of the wall in the vicinity of the plaque.
• The damaged area is invaded by fibroblasts
(scar-forming cells), which form a connective
tissue cap over the plaque.
• 9. In the later stages of the disease, Ca2+ often
precipitates in the plaque. A vessel so afflicted
becomes hard and cannot distend easily.
 Atherosclerosis: A Progressive Process
Plaque
Occlusive Rupture/
Atherosclerotic Fissure &
Fatty Fibrous Thrombosis Unstable
Streak Plaque Plaque
Normal
Angina

MI

Coronary
Death

Stroke
Effort Angina
Clinically Silent Critical Leg
Claudication
Ischemia

Increasing Age

Courtesy of P Ganz.
 a cross-section of the coronary artery. Most of its wall is atherosclerotic plaque( consists of cholesterol, inflammatory cells,
filled with smooth muscle cells that can contract and relax. and fibrosis, and it reduces the space for blood flow in the artery.)

Nitroglycerin dilates constricted arteries. A spasm can suddenly develop in an atherosclerotic coronary artery (
angina pectoris)
 THROMBOEMBOLISM AND OTHER
COMPLICATIONS OF ATHEROSCLEROSIS

• In the brain, atherosclerosis is the prime cause

of strokes, whereas in the heart it brings about
myocardial ischemia and its complications.
• The following are potential complications of
coronary atherosclerosis:
– Angina pectoris
– Thromboembolism
– Heart attack
Angina pectoris.
• Although the heart cannot
normally be “felt,” pain is
associated with myocardial
ischemia.
• Such cardiac pain, known
as angina pectoris (“pain
of the chest”), can be felt
beneath the sternum and is • The symptoms of angina pectoris
often referred to (appears recur whenever cardiac O2
demands become too great in
to come from) the left relation to the coronary blood
flow—for example, during
shoulder and down the left exertion or emotional stress.
arm.
 Thromboembolism.
• Foam cells release chemicals that can weaken
the fibrous cap of a plaque by breaking down the
connective tissue fibers.

Plaques with thick fibrous caps are considered stable,

because they are not likely to rupture. However, plaques
with thinner fibrous caps are unstable, because they are
likely to rupture and trigger clot formation.
• Such an abnormal clot attached to a vessel wall is
called a thrombus.
• The thrombus may enlarge gradually until it
completely blocks the vessel at that site, or the
continued flow of blood past the thrombus may
break it loose.
• As it heads downstream, such a freely floating clot,
or embolus, may completely plug a smaller vessel .
• Thus, through thromboembolism atherosclerosis
can result in a gradual or sudden occlusion of a
coronary vessel (or any other vessel)
Plaque Rupture Leads to Thrombus Formation

Unstable Plaque Ruptured Plaque

Inflammatory
Thin Fibrous Cap Thrombus Cells

Lipid Core
Few
SMCs
Activated
Macrophage
s
Heart attack.
• When a coronary vessel is completely
plugged, the cardiac tissue served by the
vessel soon dies from O2 deprivation, and a
heart attack occurs, unless the area can be
supplied with blood from nearby vessels.
• Sometimes a deprived area is lucky enough to
receive blood from more than one pathway.
• Collateral circulation exists when small
terminal branches from adjacent blood vessels
nourish the same area.
• These accessory vessels
cannot develop suddenly
after an abrupt blockage
but may be lifesaving if
already developed.

• Such alternate vascular pathways often develop

over a period of time when an atherosclerotic
constriction progresses slowly, or they may be
induced by sustained demands on the heart
through regular aerobic exercise
• In the absence of collateral circulation, the
extent of the damaged area during a heart attack
depends on the size of the blocked vessel.
• The larger the vessel occluded, the greater the
area deprived of blood supply.
• Left coronary-artery blockage is most
devastating because this vessel supplies blood
to 85% of the cardiac tissue.
• A heart attack has four possible outcomes:
immediate death, delayed death from
complications, full functional recovery, or
recovery with impaired function.
Role of Platelets in Thrombus Formation
in Acute Ischemic Events

Lipid
Core
Atherosclerotic Plaque Platelet Adhesion, Thrombus Thrombotic
Vessel Rupture Activation, and Formation Occlusion
Aggregation

MI
Vessel wall injury  Plaque rupture 
Stroke
Exposure of subendothelial collagen and
other platelet-adhering ligands Vascular
Death

Schafer AI. Am J Med. 1996;101:199–209.

Patofisiologi SKA
Agregasi trombosit,
akumulasi lipid & makrofag
Plak stabil Plak tak
stabil
Injury &
disfungsi endotel
disrupsi
Trombosis akut
Hipertensi
Merokok APTS
DM Oklusi koroner
Dislipidemia
Zat vasoaktif IMA
dll Platelet & thrombin
dependent vasoconstriction
Disfungsi endotel Vasokonstriksi
Acute Coronary Syndrome
Ischemic Discomfort History
Unstable Symptoms Physical Exam

No ST-segment ST-segment
ECG
elevation elevation

Unstable Non-Q Q-Wave Acute

angina AMI AMI Reperfusion
Let it beat!