Acute coronary syndrome Flashcards
Explain the pathogenesis of acute coronary syndrome!
Most of ACS result from the disruption of an atherosclerotic plaque wit subsequent platelet aggregation and formation of an intracoronary thrombus. The form of ACS that result depends on the degree of coronary obstruction and associated ischemia.
Explain the normal hemostasis! What is the difference between primary and secondary hemostas?
When a normal blood vessel is injured, the endothelial surface becomes disrupted and thrombogenic connective tissue is exposed. Hemostasis begins within seconds of vessel injury and is mediated by circulating platelets, which adhere to collagen in the vascular subendothelium and aggregate to form a “platelet plug”. While the primary hemostatic plug forms, the exposure of subendothelial tissue factor triggers the plasma coagulation cascade, initiating the process of secondary hemostasis. The plasma coagulation proteins form a fibrin clot by the action of thrombin.
What is anti-thrombin and how does it work?
Anti-thrombin is a plasma protein that irreversibly bind to thrombin and other clotting factors, inactivating them and facilitating their clearance from the circulation. The effectiveness of antithrombin is increased by binding to heparin sulfate.
Protein C, protein S, and thrombomodulin – inactivates the “acceleration”
How do protein C, protein S and thrombomodulin work? Where are they synthesised?
Protein C, protein S, and thrombomodulin – inactivates the “acceleration” factors of the coagulation pathway (factor Va and VIIIa). Protein C is synthesized in the liver and circulated in an inactive form. Thrombomodulin is a thrombin-binding receptor normally present on endothelial cells. Thrombin bound to thrombomodulin can’t covert fibrinogen to fibrin. Instead, the thrombin-thrombomodulin complex activated protein C (which degrades Va and VIIIa). Protein S enhances inhibitory function of protein C.
What is Tissue factor pathway inhibitor?How does it work?
TFPI is a plasma serine protease inhibitor that is activated by coagulation factor Xa. The combined factor Xa–TFPI binds to and inactivates the complex of tissue factor with factor VIIa that normally triggers the extrinsic coagulation pathway.
Give an example of a protein that lysis fibrin clot! How does it work?
Tissue plasminogen activator (tPA) is a protein secreted by endothelial cells in response to many triggers of clot formation. It cleaves plasminogen to form plasmin, which in turn enzymatically degrade fibrin clots. When tPA binds to fibrin, its activity enhances.
List couple of endogenous anti-thrombotic mechanism!
Anti-thrombin, protein C, protein S, thrombomodulin, TFPI, lysis of fibrin clot, endogenous platelet inhibition and vasodilation including prostaglandin I2 and NO
How does prostaglandin I2 work?
Prostaglandin I2 increases platelet level of cyclic AMP and thereby strongly inhibit platelet activation and aggregation. It indirectly inhibits coagulation via its potent vasodilating properties (augmenting blood flow and reducing shear stress).
How does NO work as an anithromb?
NO act locally to inhibit platelet activation.
What causes plaque disruption?
The causes of plaque disruption are (1) chemical factors that destabilize atherosclerotic lesion and (2) physical stresses to which the lesions are subjected. Substance released from inflammatory cells within the plaque can compromise the integrity of the fibrous cap (T-cell produce INF-γ which inhibits collagen synthesis by smooth muscle cells and thereby interferes with the usual strength of the cap). Additionally, cells within atherosclerotic lesions produce enzyme that degrade the interstitial matrix.
The activation of the sympathetic nervous system increases the blood pressure, heart rate, and the force of ventricular contraction – actions that may stress the atherosclerotic lesion, thereby cause the plaque to fissure or rupture.
What activates platelets? What do platelets release once activated?
Activated platelets release the contents of their granules, which include facilities of platelets aggregation (ADP and fibrinogen), activators of coagulation cascade (factor Va), and vasoconstrictors (thromboxane and serotonin).
List couple of non-atherosclerotic cause of acute myocardial infarction!
Coronary emboli from mechanical or infected cardiac valves may lodge in the coronary circulation, inflammation from acute vasculitis can initiate coronary occlusion, or patients with connective tissue disorders, or peripartum women, can rarely experience a spontaneous coronary artery dissection (a tear in the vessel wall that may lead to occlusion).
Cocaine increases sympathetic tone (HR and BP) by blocking the presynaptic reuptake of the noradrenaline and enhancing the release of adrenal catecholamines, which can lead to vasospasm and therefore decrease in myocardial oxygen supply.
Which part of the heart that is most subject to ischemia?
Transmural infarcts span the entire thickness of the myocardial wall and result from total, prolonged occlusion of an epicardial coronary artery. Conversely, subendocardial infarcts exclusively involve the innermost layers of the myocardium. The subendocardium is particularly susceptible to ischemia because it is the zone subjected to the highest pressure from the ventricular chamber, has few collateral connections that supply it, and is perfused by vessels that must pass through layers of contracting myocardium.
What determines if the tissue will go necrosis during vessel occlusion?
(1) mass of the myocardium perfused by the occluded vessel, (2) the magnitude and duration of occluded vessel, (3) the oxygen demand of the affected region, (4) the adequacy of collateral vessel (5) the degree of tissue response that modifies the ischemic process.
Explain the pathological evolution of infarction after: 1-2 min 10 min 20-24 min 1-3 h 4-12 h 18-24h 2-4 d 5-7 days 7+ days 7 wks
Early changes
1–2 min ATP levels fall; cessation of contractility
10 min 50% depletion of ATP; cellular edema, decreased membrane potential, and susceptibility to arrhythmias
20–24 min Irreversible cell injury
1–3 h Wavy myofibers
4–12 h Hemorrhage, edema, PMN infiltration begins
18–24 h Coagulation necrosis (pyknotic nuclei with eosinophilic cytoplasm), edema
2–4 d Total coagulation necrosis (no nuclei or striations, rimmed by hyperemic tissue); monocytes appear; PMN infiltration peaks
Late changes
5–7 d Yellow softening from resorption of dead tissue by macrophages
7+ d Granulation tissue forms, ventricular remodeling
7 wk Fibrosis and scarring complete
What are the early changes in infarction?
As oxygen levels fall in the myocardium supplied by an occluded coronary vessel, there is a rapid shift from aerobic to anaerobic metabolism. Because mitochondria can no longer oxidize fats or products of glycolysis. Anaerobic glycolysis leads to the accumulation of lactic acid, resulting in a lowered pH.
The decrease in ATP concentration will impair the Na+-K+-ATPase, with resultant elevation in the concentrations of intracellular Na+ (cause cellular edema- develops within 4-12 hours) and extracellular K+ (contributes to alteration in transmembrane electrical potential, predisposing the myocardium to lethal arrhythmias). Intracellular calcium accumulates and cause the activation of lipases and proteases. Proteolytic enzyme leak across the myocyte’s altered membrane, damaging adjacent myocardium.
Contraction band can be seen near the border of the infarct: sarcomeres are contracted and consolidated.
Acute inflammatory response begins after 4 hours and causes further damage.
What are the later changes in infarction?
These include (1) the clearing of necrotic myocardium and (2) the deposition of collagen to form scar tissue. Irreversibly injured myocytes do not regenerate; rather, the cells are removed and replaced by fibrous tissue. Macrophages invade the inflamed myocardium shortly after neutrophil infiltration and remove necrotic tissue. The phagocytic clearing, combined with the thinning and dilation of the infarcted zone, results in structural weakness of the ventricular wall and the possibility of myocardial wall rupture. 1 week after infarction, granulation tissue appears, representing the beginning of the scarring process.
What does hypokinetic, akinetic and dyskinetic means?
- Hypokinetic – a localized region of reduced contraction
- Akinetic – a segment that doesn’t contract
- Dyskinetic – is one that bulges outward during contraction of the remaining functional portion of the ventricle.
Explain the process of ventricular remodeling works?
In the early post-MI period, infarct expansion may occur, in which the affected ventricular segment enlarges without additional myocytes necrosis. Infarct expansion represents thinning and dilation of the necrotic zone of tissue. Infarct expansion can be detrimental because it increases ventricular size, which (1) augments wall stress, (2) impairs systolic contractile function, and (3) increases the likelihood of aneurysm.
Remodeling of the ventricle may also involve dilation of the overworked noninfarcted segment, which is subjected to increased wall stress. Initially, chamber dilatation serves a compensatory role because it increases cardiac output via the frank-starling mechanism, but progressive enlargement may lead to heart failure and ventricular arrhythmias.
Intervention that stop ventricular remodeling can reduce short- and long-term mortality after infarction (these include renin-angiotensin antagonist).
What are the consequences of ventricular wall dilation and thinning?
(1) augments wall stress, (2) impairs systolic contractile function, and (3) increases the likelihood of aneurysm.
