Flashcards in Acute Coronary Syndromes Deck (62):
What do endothelial cells start to express when exposed to inflammatory mediators?
Contact activation pathway
Factor XII converted into XIIa, which turns factor XI into XIa, which IX into IXa, which complexes with factor VIIIa.
This complex converts factor X into factor Xa. Xa and Va convert prothrombin into thrombin. Thrombin converts fibrinogen into fibrin. And we have a cross linked fibrin clot
Factor VII converted to VIIa by trauma. Simultaneously Tissue factor exposed due to trauma. VIIa and Tissue factor cleave X to Xa.
Xa, along with Va, convert prothrombin to thrombin, which converts fibrinogen to fibrin.
Plasma protein that inactivates thrombin
Thrombin receptor on endothelial cells so its unable to cleave fibrinogen to fibrin
Tissue factor pathways inhibitor (TFPI)
Yeah its pretty much what it sounds like
Mechanisms of clot lysis
Blood clots initiate the secretion of TPA from endothelial cells, which converts plasminogen to plasmin. Plasmin degrades fibrin clots.
How do plaques adhere to injured epithelium
Bind to von Willibrand factor and collagen.
Pro-thrombotic factor that binds to platelets
Causes platelet aggregation
How does endothelium prevent the actions of ADP?
Turns it into adenosine.
Two factors released by endothelial cells that prevent platelet aggregation and increase blood flow
Prostacyclin and NO. Also convert ADP.
How does prostacyclin and NO induce vasodilation prevent thrombus formation?
Because increased blood flow prevents contact between procoagulant factors.
Major cause of coronary artery thrombosis?
Two chemical factors that destabilize fibrous caps?
MMP (matrix metalloproteinase)
T-lymphocyte cytokines that inhibit collagen synthesis
Most prone part of cap to rupture?
Shoulder of cap due to stress. Can also rupture because of myocardial contraction or high intraluminal blood pressure
When do MIs usually occur
Early morning hours because physiologic stress is highest. High BP, high blood viscosity, high sympathetic tone
What is the first step in coronary thrombogenesis?
Dysfunction of the endothelium. Vasoconstriction becomes the favored state. Thromboxane and serotonin will promote vasoconstriction.
Functional sequellae of MI
Impaired contractility (systolic dysfunction)
Impaired relaxation (diastolic dysfunction)
How do MIs cause systolic dysfunction
Hypokinesis (reduced contraction) or Akinesis, or dyskinesis (bulging out during contraction)
How do MIs cause diastolic dysfunction
Reduced compliance because its energy dependent too.
Reversible injury to myocytes after MI. Contractile function is restored days to weeks later.
Episodes of ischemia actually make tissue resistant to subsequent episodes. This occurs during stable angina.
Remodeling definition and process
Process of ventricular reorganization after infarct. First the infarct zone will thin and elongate. This is also known as infarct expansion. Then spherical dilation will occur with increased interstitial collagen
Why is infarct expansion so dangerous?
Because its associated with higher mortality and a higher rate of complications like HF.
Signs: new gallop sounds, new/worsening pulmonary congestion
What is the product that stimulates ventricular hypertrophy during late remodeling
Local ang II release
Nonatherosclerotic causes of ACS in young patients or somebody with no risk factors
Mechanical valves or infective endocarditis -- cause emboli that occlude coronaries.
Inflammatory disorders like vasculitis
Peripartum female (can have spontaneous coronary dissection)
How does cocaine abuse cause ACS?
Vasospasm decreases oxygen supply, increased HR + inotropy cause increased demand. Also associated with increased atherosclerosis.
Types of Myocardial Infarction
Type 1 -- classic case of plaque rupture
Type 2 -- Supply/demand imbalance without plaque rupture
Type 3 -- Cardiac death
Type 4/5 -- MI in the setting of a revascularization procedure.
Types of type 2 MI
Vasospasm or endothelial dysfunction (prinzmetal/cocaine)
Fixed atherosclerosis causing supply-demand imbalance
Supply-demand balance alone (syndrome X)
Non q-wave MI.
Subendocardial ischemia -- few collaterals there and exposed to highest pressures from ventricle
Presentation of ACS?
Ischemic discomfort at rest
Sign of ACS
Either ST segment elevation or non ST segment elevation
Non ST segment elevation ACS
Can be unstable angina, Non-q wave MI, or even a Q wave MI (very rarely)
ST segment elevation ACS
Generally a q-wave MI, but sometimes (rare) can be a non-q wave MI.
Nonocclusive ruptured plaque leading to thrombus causes
Unstable angina, NSTEMI
Occlusive ruptured plaque leading to thrombus causes
Increasing severity of ACS
Unstable angina -> NSTEMI -> STEMI
Most critical distinction to make
NSTEMI or STEMI
Clinical symptoms of MI
Chest pain more severe, longer duration, with greater radiation than normal. Does not improve with rest or nitroglycerin.
Sympathetic discharge (diaphoresis, tachycardia, nausea, clammy skin)
Shortness of breath (LV volume rises, so backs up to lungs)
Who is likely to have an MI without symptoms?
Physical findings of MI
S4 (noncompliant LV)
S3 (volume overload and systolic dysfunction)
Systolic murmur (may come from papillary muscle dysfunction leading to MR)
Why can an MI cause MR?
Because papillary muscle doesn't function properly.
Differential for MI
Pericarditis, pleuritis (pain w/inspiration and diffuse ST ele)
Aortic dissection (ripping pain, BP asymmetry, widened mediastinum on CXR)
ECG findings of USA or NSTEMI
T wave inversion, ST depression or normal
Are biomarkers elevated in USA?
Are biomarkers elevated in NSTEMI
ECG evolution with STEMi
Definition of STEMI
Prolonged chest discomfort unrelieved by nitroglycerin with ST segment elevation on EKG and rise in cardiac markers
Definition of NSTEMI
Angina at rest for longer than 20 minutes without ST segment elevation but with cardiac biomarkers.
Pathophysiology of STEMI
Total or near total occlusion of coronary artery
Pathophys of NSTEMI
Abrupt decrease in myocardial O2, thrombus formation or an atherosclerotic plaque
Management of STEMI
Immediate reperfusion with a preferred door to balloon time of <90 minutes
Management of NSTEMI
Depends on TIMI score
Troponin (T, I, or C)
Creatine Kinase Myocardial Band (CK-MB)
Control calcium mediated interactions between actin and myosin that are released into circulation from muscle and cytosolic reserves during necrosis. TNI and TNT are highly sensitive and specific for myocardial necrosis.
Where is troponin released from first?
Cytosolic pool, but if injury persists, then muscular pool
When do levels of troponin rise and peak?
Rise within 3-4 hours. Peak at 18-36 and decline slowly
Enzyme involved in ATP generation. Found in heart (CK-MB) but also in muscle (MM) and brain (BB). Also in uterus prostate gut.
Kinetics of CK
Faster release and peak (24h) then cTn, returns to normal faster.