Porth's Essentials of Pathophysiology, 4e

447

Disorders of Cardiac Function

C h a p t e r 1 9

Adventitia

Lumen

Media

Asymptomatic atherosclerotic plaque

Intima

Stable fixed atherosclerotic plaque

A

Stable angina

Plaque disruption and platelet aggregation

Thrombus

Unstable plaque

FIGURE 19-2. Atherosclerotic plaque. (A) Stable fixed atherosclerotic plaque in stable angina and (B) unstable plaque with plaque disruption and platelet aggregation in the acute coronary syndromes.

Unstable angina

Non–ST-segment elevation MI

ST-segment elevation MI

B

Acute coronary syndromes

of the lipid core, smooth muscle cells, macrophages, and collagen. The lipid core provides a stimulus for plate- let aggregation and thrombus formation. 6 Both smooth muscle and foam cells in the lipid core contribute to the expression of tissue factor in unstable plaques. Once exposed to blood, tissue factor initiates the extrinsic coagulation pathway, resulting in the local generation of thrombin and deposition of fibrin (see Chapter 12). Platelets are critical to the events following plaque disruption in acute CAD. Platelets adhere to the endo- thelium and release substances (i.e., adenosine diphos- phate [ADP], thromboxane A 2 , and thrombin) that promote further aggregation of platelets and thrombus formation. Glycoprotein receptors expressed on the platelet surface bind fibrinogen and cross-link platelets, contributing to thrombus formation. Platelet adhesion and aggregation occurs in several steps. First, release of ADP, thromboxane A 2 , and thrombin initiates the aggregation process. Second, activation of glycoprotein IIb/IIIa receptors on the platelet surface occurs. Third, fibrinogen binds to the activated glycoprotein receptors, forming bridges between adjacent platelets. Acute Coronary Syndrome Acute coronary syndrome (ACS) represents a spectrum of acute ischemic heart diseases ranging from unstable ischemia to acute MI based on the presence or absence of an ST-segment elevation or depression on the ECG. 11,12 This criterion allows for immediate classification of risk and guides whether a person should be considered for acute reperfusion therapy. The evaluation of serum

biomarkers (e.g., troponin I) is then used to determine whether an acute MI has occurred. Electrocardiographic Changes The classic ECG changes that occur with ACS include ST-segment elevation, T-wave inversion, and development of an abnormal Q wave 11,12 (Fig. 19-3). These changes may not be present immediately after the onset of symp- toms and vary considerably depending on the duration of the ischemic event (acute versus evolving), its extent (sub- endocardial versus transmural), and its location (anterior versus inferior posterior). Because these changes usually occur over time and are seen on the ECG leads that view the involved area of the myocardium, provision for con- tinuous and serial 12-lead ECG monitoring is indicated. The T wave and ST segment, which represent the ventricular repolarization phase of the cardiac action potential on the ECG, are usually the first to be involved during myocardial ischemia and injury. 13 During myo- cardial ischemia, repolarization is altered as the involved area becomes ischemic. This leads to T wave abnormali- ties, such as T-wave inversion. ST-segment changes also occur with acute ischemic myocardial injury. Normally, the ST segment of the ECG is nearly isoelectric (i.e., does not deviate from the baseline) because healthy myocar- dial cells attain the same resting membrane potential during early repolarization. Acute ischemia reduces the resting membrane potential and shortens the duration of the action potential of the cells within the ischemic area. The voltage difference in the cell membranes between the normal and ischemic areas of the myocardium leads to a “current of injury” between these regions.

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