cv 2 Flashcards
stroke mechanism
atheroembolization from carotid birfucation lesion (below jaw)
OR
thromboembolization from left atrial appendage in a-fib
MI mechanism
plaque rupture from a non-occlusive thrombosis -> occlusion
DVT, PE mechanisms
venous thromboembolism
Venous vs Arterial thrombi
venous: fibrin rich, areas of stasis, env+genetic predispositions TX: Anticoag
arterial: platelet rich, areas of high flow, atheroscerlosis/anti-phospholipid Abs/trauma, TX: Antiplatelets
Peripheral arterial dz mechanism
claudication: stable plaque with >70% diameter reduction
acute limb ischemia: obstructs blood flow w/o prior development of collateral flow, can be atheroembol or thromboembol
Vasospastic disorders
Raynauds, pernio; causes dysfxnal endothelium contributing to start of thrombus :(
N.O formed from
L-arginine
CK-MB rise, peak, fall
4-6 hrs, 18 hrs, 2-4 days
C-Troponin I rise, peak, fall
4-6 hrs, 12 hrs, 3-10 days
C-Troponin T rise, peak, fall
4-6 hrs, 12-48 hrs, 7-10 days
Acute Coronary syndrome can be one of these 3
UA, NSTEMI, STEMI
does unstable angina present with biomarkers?
no you fuckin nerd
Agitated saline/microbubbles purpose
use with echo to determine if there’s a shunt - inject into vein, should only see it go into RIGHT side of heart as it should be breathed out, if seen in left you got problems homie
pharmacologic stress test chemicals
dobutamine/dipyridamole
when is a stress test have good Dx value, vs bad Dx value?
Good: Left main or 3 vessel coronary artery dz
bad: 2 or 1 vessel CAD (and then its better if LAD>RCA>CIRC)
what is M mode
records movement of heart muscle on a 2D axis in an echo
is RA, RV more anterior or posterior
anterior, left side is more posterior
pt is sensitive to radiation, what imaging test should you order
MRI, dweeb
ANP vs BNP vs CNP
ANP in atria, 28 AA
BNP in ventricles, 32 AA released with stretch (correlates with LVEDV+P; can be ^ in renal insuff and old, women
-GOOD NEGATIVE predictive value
CNP in endothelium, 53 or 22 AA
Why would troponin remain elevated, even in HF
renal failure - cleared by kidneys
at what level of stenosis do you get Sx
> 70% diameter reduction
at what level of stenosis do you become unstable
> 90% diameter reduction
mechanism of reperfusion injury
blood flow restored after ischemia, typically hemorrhagic because you’re pushing blood back through damaged microvasculature ya goofball; so will get accel. infl. and fibrosis
(as well as get mitochondrial dysfxn, myofibril hypercontracture, cytoskeletal dmg, cell death)
what’s the R coronary supply
posterior LV, septum
what’s the L circumflex supply
lateral LV wall
CHANGES IN MI:
0-30 min: 1-2 hrs: 4-12 hrs: 18-24 hrs: 24-72 hrs: 4-7 days: 10 days: 4-8 weeks:
0-30 min: REVERSIBLE changes, structural and biochemical
1-2 hrs: irreversible - swollen mitochondria, release of intracellular proteins
4-12 hrs: wavy fibers - (You should have no trouble telling these heart fibers are dead, because the nuclei are gone. The extra-dark pink staining of the cytoplasm also indicates necrosis. As the still-beating live heart pulls at the dead portion, it makes some of the fibers crumpled or “wavy”)
18-24 hrs: coag necrosis, neutrophilic infiltrate, dark discoloration -> worry about damage to nodal tissue/creation of arrhythymias
24-72 hrs: maximum neutrophil infiltrate, yellow pallor
4-7 days: macrophages w/ disintegration of necrotic myocytes
10 days: granulation tissue with many blood vessels, plump fibroblasts, collagen
4-8 weeks: fibrosis - worry about this because it’s weaker than the wall of myocardian, can rupture/aneurysm
Htn causes __ hypertrophy
concentric (pressure overload), sarcomeres added in parallel
Pulm htn often due to
COPD. less often CF, chest disorders kyphoscoliosis
Aneurysms are
weakening of vessel wall -> dilation of vessel wall, due to systemic dz (vasculitis), developmental (berrry aneurysm); infxn, congenital (Marfans)
Berry aneurysms
congenital defects in tunica media at bifurcation of cerebral vessels
Aortic dissection
intimal tear of aorta, followed by blood dissects into media
blood can then dissect back into lumen (double-barrel aorta), or pericardial sac (tamponade)
Medium vessel vasculites (Chapel Hill classification)
Polyarteritis Nodosa: kidneys, GI, heart. P-ANCA
Kawasaki’s: coronary arteries, young Asians
Small vessel vasculites (Chapel Hill classification)
Wegener’s granulomatosis: idiopathic, upper+lower resp. tracts and kidneys. C-ANCA
Churg-strauss - asthma+eosinophilia, mostly in lungs
Leukocytoclastic/hypersenstivitiy: drugs, infxns
Large vessel vasculitis (Chapel Hill classification)
Giant cell/temporal arteritis: segmental chronic granulomatous vasculitis of temporal A., +/- opthalmic A.
Heparin
binds AT III to inhibit 2, 9, 10, 11, 12, 13; IV or SC, avoid IM, monitor with aPTT. bleeding, hard on thrombocytopenics
USE: prevent hypercoagulability following vasc. injury/venous stasis, can be adjunct in Tx of coronary occlusion in UA/acute MI
faster than LWMH, safer for renal insuff. (reticuloendothelial elim.)
LWMH (Enoxaprin)
bind AT III to inhibit 10 only; IV or SC, avoid IM, no monitoring. bleeding, less bad on thrombocytopenics
longer acting than heparin and less variable response, less thrombocytopenia, first order renal elim.
Fondaparinux
binds AT III to inhibit 10 only; SC, NO thrombocytopenia, renal elim.
Protamine
reversal of Heparin; incomplete reversal of LWMH (Enoxaparin)
Warfarin/Coumadin
blocks liver synthesis of vit-K -> no gamma-carboxylation so blocks 2, 7, 9, 10, C, S (note that C has shortest t1/2 so get early PROcoag effect)
USE: a-fib, prophylaxis of venous thromboembolism
Oral OD, 99% protein bound, CYP450 met.
monitor with aPTT, see max effect in 3-5 days. if INR creeps up, administer vit K orally, if major bleed, give vit K IV, and stop that shit
gotta worry about Abx (kill vit K microorganisms), ASA, avoid in preg.
Dabigatran
direct inhibition of Da Big one, thrombin/factor 2
USE: lower risk of stroke and systemic embolism in patients w/ non-valve a-fib
(poor, polar prodrug) Oral BID, renally dose, needs dessicant container
reversal w/ Praxbind
no monitoring really, can monitor w/ ECT but expensive and hard to find
faster than warfarin
Rivaroxaban/Xarelto, Apixaban/Eliquis, Edoxaban/Savaysa
Direct factor 10 inhibitors (Xa is in the name)
USE: lower risk of stroke, systemic embolism in pt w/ non-valve a-fib
Oral, renally dose Edoxaban, CYP3A4 Rivaroxaban
no reversal agent, no monitoring at all, shorter-acting than warfarin
ASA
Irreversibly inhibit COX1 so less TXA2 is made, biggest effect on circulating platelets as opposed to tissue endothelials
USE: STEMI, UA/NSTEMI, PCI, secondary prevention of MI or stroke
Antiplatelet agent. Oral. care for GI bleed, N/V
Clopidogrel/Plavix, Ticagrelor, other -grel names
Irreversible inhibit platelet ADP receptor to block aggregation
USE: STEMI, NSTEMI, PCI, all w/ ASA
Plavix is Oral OD, CYP450 met: Avoid if pt. taking PPIs as PPIs block Plavix
Ticagrelor is NOT CYP450 and is reversible inhibition, but Oral BID
Dipyridamole
Inhibits phosophodiesterase -> increased cAMP levels -> better anti-agg effects of PGI2
USE: secondary prevention of ischemic stroke w/ ASA
Oral TID
Abciximab (human monoclonal antibody), Tirofiban (non-peptide)
GPIIb/IIIa receptor antagonists on platelets, blocking all platelet aggregation, most legit blocking
USE: PCI w/ ASA + ADP antag
IV
Alteplase, Reteplase, Tenectaplase
All activate plasmin via tPA activation (t,p,a is in name)
Alteplase is selective for EXISTING clots (All teh clots)
USE: Acute MI - prompt use with adjunctive drugs (Betas, ACEI, ASA), as well as DVT, pulm. emboli
Friedewald formula (calculate LDL)
LDL = total chol. - HDL - (TG/5)
TG/5 is estimate for vLDL, but only if TG
average LDL
130 mg/dL, though majority of CHD occurs in pt. around here, though increasing does increase risk
Exogenous lipoprotein
eat fat, intestines package to chylomicron w/ B-48, goes to lymph then vasc., fat gets hydrolyzed by lipoprotein lipase
Free fatty acid goes to use/storage, chylomicron remant recycled by liver into bile
Endogenous lipoprotein
liver packages chol + TGs into vLDL, HDL turns into triglycerides and FFAs (use+strorage), becomes intermediate density LP which looks like chylomicron remnant and some goes to liver while the rest has lipoprotein lipase turn it into LDL w/ B-100, goes to LDL receptor at liver
HDL metabolism
nascent HDL (no lipids) adds cholesterol ester to become mature HDL, either goes to liver OR CETP transfers cholesterol + triglycerides to LDL which is cleared DIFFERENTLY than via LDL receptor
decreasing preload and decreasing afterload will change…
preload will increase diastolic filling (less pressure against walls, less compression of veins),; afterload decreases O2 demand
Tx of stable angina (vasodilators)
beta-blockers, nitrates, Ca++ channel blockers (decrease demand)
Tx of unstable angina (vasodilators)
antithrombotics first, beta-blockers, nitrates, Ca++ channel blockers (decrease demand and increase supply)
Tx of variant angina (eg caused by Raynauds)
Ca++ channel blockers, nitrates (prevent vasospasm)
Nitrates
NO -> PKG -> guanylate cyclase -> increase cGMP -> increase myosin LC phosphatase activity -> myocyte relaxation; mostly venous
USE: acute angina, prophylaxis for stable angina
sublingual, but poor oral
isosorbide = chronic; nitroglycerin stat = acute
Adverse rxn: extension of vasodilation, so headaches, orthostatic hypotension, flushing, and CAN build tolerance - so intermittent period is necessary
Ca++ channel blockers
Verapimil, Diltiazem, Nifedipine
block L-types in cardiac or VSMCs, decreasing vasoconstriction (mostly arteriole) and inotrophy, HR
Nifedipine (DHPR) is most VSMC selective and most vasodilation, though can cause reflex tachycardia via activation of sympathetic baroreceptors
Diltiazem is next most VSMC selective, Verapimil is least, and most selective for myocytes
USE: vasospastic angina, stable angina
Adverse rxn: cardiac depression (bradycardia, CHF) - less likely with DHPR due to selectivity, hypotension, edema, flushing
Ranolazine/Ranexa
Inhibits late Na+ current which prevents NCX from exchanging more Ca++ in and prevents Ca++ overload - often happens in ischemia
USE: ischemia or hypertrophy ONLY, no vasodilatory effect
P-glycoprotein substrate, CYP3A4 met.
Adverse rxn: can prolong QT interval because inhibits phase 3 K+ outward current
Beta blockers (-olol)
B1: metoprolol, atenolol (at lower doses is selective)
B1, B2: propanolol (pro: was before the good shit)
Blocks B1 in heart (vs B2 in lung, blood vessels), decreasing HR, inotropy and thus O2 demand, no vasodilatory at all
USE: first-line for stable angina
AVOID: asthma, peripheral vasc dz, bradycardia
Adverse rxn: abrupt withdrawal can cause oversympathetic activity
4 scenarios for statin Tx indication
- PT w/ known clinical ASCVD (prev MI, TIA, angina)
- LDL > 190 mg/dL (recall avg is 130)
- PT w/ DM, age>40, LDL>70
- 10 yr. ASCVD risk >7.5% (det. by M>F, age, race, total chol, BP, DM, smoker)
Moderate risk? get into FHx, CRP (>2), LDL>160, coronary calcium score
atheroprotective diets
DASH diet, mediterranean diet (more veg, fruit, whole grains, less fats)
aPTT measures + NL values
intrinsic pathway; NL is 25-35 sec
PT measures + NL values
extrinsic pathway; NL is 10-15 sec
INR is
(Pt. PT/mean NL PT) ^ some number
Thrombin Time
measures thrombin inhibition, used to measure Dabigatran toxicity
Fatty streak formation
damaged endothelium can’t keep shit out so LDL accumulates in the INTIMA, apolipoprotein B gets oxidized and monocytes are recruited, become macrophages, phagocytose LDL, they lose mobility and as they eat more and more LDL via a mutated receptor mechanism (not the normal way they do things), they become foam cells in the intima
Fibrous plaque formation
Foam cells, platelets, and epi cells release growth factors which cause smooth muscle and fibroblasts to move in and grow; smooth muscle deposits connective tissue
Plaque progression
Plaque grows and central region becomes necrotic as all this infl. shit accumulates, while the fibrous cap is chilling. as it grows can occlude artery, and can rupture (esp. if calcified) via stressors, releasing it’s pro-infl. factors and causing thrombus, or can even be reabsorbed into intima to form bigger plaque
Stable vs. Vulnerable Plaque
Stable will have a thick fibrous cap, calcified, low lipid content, and less infl. content, less apoptosis.
Vulnerable is the exact opposite…
Plaques often form in the abdominal aorta
Normal endothelium provides
Protective surface with anti-inflammatory and anti-thrombogenic qualities
Familial hypercholesterolemia
mutated LDL receptor causes increased LDL in blood
Cardiac supply determined by:
prevent hypotension (maintain diastolic perfusion pressure)
increase diastolic time (slow rate)
decrease coronary resistance (vasodilate)
increase O2 content (Tx anemia, hypoxemia)
Cardiac demand determined by:
lower systolic BP (lower need for work)
lower heart rate
lower wall tension (decrease preload) T=(Pr)/(wall thickness)
lower inotropy
Most important mechanism for coronary vasoregulation
Autoregulation: dilate to increase blood flow or constrict to decrease, mainly via local metabolites (adenosine)
The heart receives blood during
diastole you fuckin lamer
When doing an angiography, you stick two catheters in, one in front of the stenosis and one past it, and then you dilate resistance vessels with
adenosine. R=(nL)/r^4
