PATHOGENESIS OF ACS

Presenter: Dr Liu Supervisor: Dr Nik Arif

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.

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

Causes of coronary artery disease.

Type Comments Atherosclerosis 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 to be mediated by histamine, serotonin, catecholamines, and endothelium-derived factors. Because spasm can occur at any time, the chest pain is often not exertion-related. Rare cause of coronary artery disease. Can occur from vegetations in patients with endocarditis. Congenital coronary artery abnormalities are present in 2% of the population. However, only a small fraction of these abnormalities cause symptomatic ischemia.

Emboli Congenital

PATHOGENESIS OF ACS
The arterial lumen must be decreased by 90% to produce cellular ischemia when the patient is at rest. With exercise, a 50% reduction in lumen size can lead to symptoms

 Platelet release of vasoconstrictive factors such as thromboxane A2 or serotonin and endothelial dysfunction may cause vasoconstriction and contribute to decreased flow.

Normal artery

Progression of human coronary atherosclerotic plaque.

1. Normal artery

2.-Endothelial cells injury, activated by risk factors such as Dyslipidaemia, Hypertension, Smoking, DM -recruit inflammatory leukocytes such as monocytes and T lymphocytes. -Extracellular lipid begins to accumulate in intima at this stage.

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.

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

4. As lesion progresses, inflammatory mediators cause expression of tissue factor, a potent procoagulant, and of matrix-degrading proteinases that weaken fibrous cap of plaque.

5. If fibrous cap ruptured, causing thrombosis on nonocclusive atherosclerotic plaque. -If balance between prothrombotic and fibrinolytic unfavorable, occlusive thrombus causing acute coronary syndromes may result.

6. When thrombus resorbs, products

associated with thrombosis such as thrombin and mediators released from degranulating 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 produce symptoms of stable angina pectoris.

7. In some cases, occlusive thrombi arise not from fracture of fibrous cap but from superficial erosion of endothelial layer. Resulting mural thrombus, again dependent on local prothrombotic and fibrinolytic balance, can cause acute myocardial infarction.

Artherosclerosis
Plaque rupture

Dysfunctional endothelium
Subendothelial collagen exposure Platelet adhesion, activation Antithrombic effect

Intraplaque hemorrhage

Tissue factor released

Lumen narrowing

Reduced vasodilator effect Coagulation cascade activation Platelet aggregation Vasoconstriction

Coronary thrombus

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

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

Role of macrophages
Adhere to endothelium Migrate btwn ECs to localize in the intima Engulf lipoproteins, largely oxidized LDL to become foam cells

Role of SMC proliferation

Convert a fatty streak into a mature fibrofatty atheroma and contribute to the progressive growth of atherosclerotic lesions

PATHOPHYSIOLOGY
CHEST PAIN SHOCK BRADYCARDIA NAUSEA/VOMITING TACHYCARDIA

Chest pain
Traditionally due to ischemia. 70-80% are asymptomatic. Mediated by sympathetic afferent fibers that richly innervate the atrium and ventricle. Trigger for nerve stimulation- adenosine

 Factors for asymptomatic : 1) dysfunction of afferent nerves, 2) transient reduced perfusion, and 3) differing pain thresholds

SHOCK
Cardiac failure- obstruction of the left main coronary or LAD artery. Myocardial rupture Pericardial effusion and tamponade Rupture of the papillary muscles

BRADYCARDIA
a/w inferior MI- occlusion of the right coronary artery

NAUSEA AND VOMITING

Activation of the vagus nerve

TACHYCARDIA
Raised catecholamines to maintain stroke volume

THANK YOU