Pathogenesis ACS

7/27/2019 Pathogenesis ACS

1/32

Presenter: Dr LiuSupervisor: Dr Nik Arif

PATHOGENESIS OF ACS


2/32

INTRODUCTION

Acute coronary syndrome is a clinical

spectrum of ischemic heart disease

ranging from unstable angina, NSTEMI to

STEMI depending upon the degree and

acuteness of coronary occlusion

Coronary artery disease (CAD) is the

nations leading cause of death.


3/32

TERMINOLOGY

Arteriosclerosis

-thickened and stiffened arteries of all sizes

Atherosclerosis

-is the descriptive term for thickened and

hardened lesion of the medium and large

muscular and elastic arteries

Atherothrombosis

-atherosclerotic plaque with superimposed

thrombosis


4/32

Causes of coronary artery disease.

Type CommentsAtherosclerosis Most common cause. Risk factors include hypertension,

hypercholesterolemia, diabetes mellitus, smoking, and a

family history of atherosclerosis.

Spasm Coronary artery vasospasm can occur in any population but

is most prevalent in Japanese. Vasoconstriction appears tobe mediated by histamine, serotonin, catecholamines, and

endothelium-derived factors. Because spasm can occur at

any time, the chest pain is often not exertion-related.

Emboli Rare cause of coronary artery disease. Can occur from

vegetations in patients with endocarditis.

Congenital Congenital coronary artery abnormalities are present in 2%

of the population. However, only a small fraction of these

abnormalities cause symptomatic ischemia.


5/32

PATHOGENESIS OF ACS

The arterial lumen must be decreased by90% to produce cellular ischemia when the

patient is at rest.

With exercise, a 50% reduction in lumen sizecan lead to symptoms


6/32

Platelet release of vasoconstrictive factors

such as thromboxane A2 or serotonin and

endothelial dysfunction may cause

vasoconstriction and contribute todecreased flow.


7/32

Normal artery


8/32

Progression of human coronary atherosclerotic

plaque.


9/32

1. Normal artery


10/32

2.-Endothelial cells injury,

activated by risk factors such asDyslipidaemia, Hypertension,

Smoking, DM

-recruit inflammatory leukocytes

such as monocytes and T

lymphocytes.

-Extracellular lipid begins to

accumulate in intima at thisstage.


11/32

3. -Monocytes become macrophages

-Macrophages engulfing modified

lipoproteins become foam cells.-Leukocytes and resident vascular

wall cells secrete inflammatory

cytokines and growth factors that

amplify leukocyte recruitment and

cause smooth muscle cell migration

and proliferation.


12/32

Dyslipidaemia, Hypertension, Smoking, DM

Endothelial injury

Recruitment of monocyte and T-lymphocyte to vessel wall

Activated macrophage

Engulf oxidised LDL

Foam cells

Accumulation of foam cells to form fatty streak

Release of various cytokines

Smooth muscle migration from t.media to intima (lay down collagen)

Smooth muscle proliferate and produce extracellular matrix

Forming a fibrous cap


13/32

4. As lesion progresses,

inflammatory mediators cause

expression of tissue factor, a

potent procoagulant, and of

matrix-degrading proteinasesthat weaken fibrous cap of

plaque.


14/32

5. If fibrous cap ruptured, causing

thrombosis on nonocclusiveatherosclerotic plaque.

-If balance between prothrombotic

and fibrinolytic unfavorable,

occlusive thrombus causing acutecoronary syndromes may result.


15/32

6. When thrombus resorbs, productsassociated with thrombosis such as

thrombin and mediators released fromdegranulating platelets can cause healing

response, leading to increased collagen

accumulation and smooth muscle cell

growth.-In this manner, the fibrofatty lesion can

evolve into advanced fibrous and often

calcified plaque, one that may cause

significant stenosis, and producesymptoms of stable angina pectoris.


16/32

7. In some cases, occlusive thrombi

arise not from fracture of fibrous

cap but from superficial erosion ofendothelial layer. Resulting mural

thrombus, again dependent on

local prothrombotic and fibrinolytic

balance, can cause acutemyocardial infarction.


17/32

Plaque rupture

Intraplaque

hemorrhage

Tissue factor

releasedSubendothelial collagen

exposure

Lumennarrowing

Coagulation cascade

activation

Coronary

thrombus

Platelet

adhesion,

activation

Platelet

aggregation

Reduced

vasodilator

effect

Vasoconstriction

Antithrombic

effect

Dysfunctional

endothelium

Artherosclerosis


18/32


19/32
http://www.google.com/url?sa=i&rct=j&q=mechanism+platelet+aggregation&source=images&cd=&cad=rja&docid=NrgWmo4jZ2XIZM&tbnid=-80jlv6HVLxzYM:&ved=0CAUQjRw&url=http%3A%2F%2Fwww.medscape.org%2Fviewarticle%2F582623&ei=TdfcUZjXDs2CrgfC6YHwAg&psig=AFQjCNF1RLbrHPLgeh4RtWgWiyKVbDoxxw&ust=1373513843764628


20/32

The role of lipid in artherosclerosis

directly impair endothelial cell function

through increase production of free

radicals.

Lipoproteins accumulate within the intima

at sites of increase endothelial

permeability

Chemical changes of lipid induced by free

radicals yield oxidized LDL


21/32

Oxidized LDL

i) Ingested by macrophages to form foam

cells

ii) Increases monocytes accumulation in

lesions

iii) Stimulates release of growth factors and

cytokines

iv) Induce endothelial cell dysfunction


22/32

Role of macrophages

Adhere to endothelium

Migrate btwn ECs to localize in the intima

Engulf lipoproteins, largely oxidized LDL tobecome foam cells


23/32

Role of SMC proliferation

Convert a fatty streak into a mature

fibrofatty atheroma and contribute to the

progressive growth of atherosclerotic

lesions


24/32


25/32

PATHOPHYSIOLOGY

CHEST PAIN

SHOCK

BRADYCARDIA NAUSEA/VOMITING

TACHYCARDIA


26/32

Chest pain

Traditionally due to ischemia.

70-80% are asymptomatic.

Mediated by sympathetic afferent fibersthat richly innervate the atrium and

ventricle.

Trigger for nerve stimulation- adenosine


27/32

Factors for asymptomatic :

1) dysfunction of afferent nerves,

2) transient reduced perfusion, and3) differing pain thresholds


28/32

SHOCK

Cardiac failure- obstruction of the left main

coronary or LAD artery.

Myocardial rupture

Pericardial effusion and tamponade

Rupture of the papillary muscles


29/32

BRADYCARDIA

a/w inferior MI- occlusion of the right

coronary artery


30/32

NAUSEA AND VOMITING

Activation of the vagus nerve


31/32

TACHYCARDIA

Raised catecholamines to maintain stroke

volume


32/32

THANK YOU

Documents

Pathogenesis ACS