Endothelium, Plaque Rupture / ACS

Question 1

1. Recognize that the normal endothelium is anti-inflammatory, anti-thrombotic, and vasodilatory.

Answer 1

Anti-inflammatory by resisting leukocyte adhesion
Secrete NO (using L-Arg as precursor)
- Decreased NO leads to upreg of inflamm. proteins

(Smooth muscle can migrate into subintimal state in diseased state)
ACTIVATED/abnormal endothelial cells are permeable to ox-LDL, inflame cells, secretes cytokines to recruit inflammatory cells & up regulate adhesion molecules,

Question 2

How do atherosclerotic plaques form?

Answer 2

Monocyte adheres to cell wall
Become activated into Macrophage
After engulfing ox-LDL in subintimal space, now a FOAM cell.
FOAM cell become pro-apoptotic, pro-fibrotic, pro-inflamm pro-thrombotic
Via cytokine release they promote smooth muscle dysfunction
SM cells migrate into subintimal space and also have cytokine-like activities

Question 3

2. Understand that there are different mechanisims of ischemia depending on the vascular bed, all of which involve endothelial dysfunction.

Answer 3

Stroke: atheroEMBOLISM (from carotid) or thrombo-embolic from a-fib

Claudication: trauma, in situ thrombosis

Renal Artery disease: fixed stenotic disease, often no clinical manifestation.

Atherosclerosis often causes stenoses but it’s also degenerative –> aneurysm (esp. in infrarenal abdominal aorta)

Coronary Art Dis: Stable plaque = agina, ruptured w/ thrombis = ACS (unstable, non/STE-MI)

Peripheral Art Dis: claudication (exertional calf discomfort) or acute limb ischemia

Question 4

What’s the main difference in treating venous thromboses vs. arterial?

Answer 4

Arterial = anti-PLATELET
Venous = anti-COAG

Venous Arterial
Fibrin-rich Platelet
RBC Plaque rupture
Areas of stasis Areas of high flow
Genetic & Env predisp. Atherosclero, trauma

Question 5

90% occlusion presents with

Answer 5

INTERMITTENT paint
ST DEPRESSION (not elevation)
BETTER w/ therapy

Question 6

Be able to distinguish non-ST elevation myocardial imfarction (NSTEMI), ST-elevation myocardial infarction (STEMI) and unstable angina (UA).

Answer 6

STEMI: complete coronary vessel occlusion

NSTEMI: PARTIAL coronary vessel occlusion WITH myocardial necrosis

UA: Partial coronary vessel occlusion, escalating symptoms without myocardial necrosis

Question 7

Be able to clinically diagnose ACS based on symptoms, ECG and biomarkers.

Answer 7

Draw graph

Question 8

Know the basis behind the treatment of STEMI

Answer 8

Artery is occluded→ Open it! If artery can be opened within 90 minutes, go to cardiac cath lab to open mechanically (cardiac catheterization).

If cannot be opened within 90 minutes, consider fibrinolytics

If hemodynamically stable, consider oral beta blockers or nitrates to decrease myocardial oxygen demand

Question 9

Know the basis behind the treatment of NSTEMI & UA.

Answer 9

Artery is partially occluded→halt the thrombotic process from completely occluding the artery by giving anticoagulant and antiplatelet agents

Anticoagulants: unfractionated heparin, low-molecular weight heparin, fondaparinux

Antiplatelets: P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor), GIIb/IIIa inhibitors

PLUS Aspirin

If hemodynamically stable, consider oral beta blockers or nitrates to decrease myocardial oxygen demand