Pathophysiology of MI and Pharmacotherapy Flashcards
(73 cards)
1
Q
What are the gender trends with ischemic heart disease?
A
- women have less anatomically obstructive CAD but have higher rates of MI mortality than men of same age
- women are more likely to have **“atypical” symptoms **
- greater hsCRP values compared to men (high sensitive C reative protein-very robust inflammatory response)
- women have greater frequency of coronary plaque erosion (coronary endothelial and microvascular dysfunction)
2
Q
What are the types of plaques in acute coronary syndrome (ACS)
A
- ruptured (70%) —> non-stenotic (50%) and stenotic/reduction in lumen (20%)
- nonruptured (30%) —-> erosion, calcified nodule
3
Q
which are the three favorite arteries for an MI, and what areas of the heart do they supply?
A
- Left Anterior Descending (50%): infarct of apical, anterior, and anteroseptal walls of left ventricle
- Right coronary (30%): infarct of posterior basal region of left ventricle and posterior third of interventricular septum
- Left circumflex (20%): infarct of lateral wall of left ventricle
4
Q
Sudden occlusion of coronary artery often results in what type of infarction?
A
transmural (wall to wall)
-the area affected depends on the amount of collateral circulation
5
Q
What do you see subendocardial necrosis?
A
-confined to the inner half of the left ventricle with a very thin layer of viable munscle present immediately beneath the endocardium
6
Q
What is immediately expressed after the onset of MI?
A
- HIF, activates genes involved in angiogenesis and energy metabolism
- also see heat shock proteins, ubiquitin, fas, cytokines
7
Q
Criteria for definition of MI (1 + 5)
A
- detection of a rise and/or fall of cardiac biomarker values (preferably cardiac troponin) WITH atleast one of the following:
a. ischemic symptoms
b. new significant ST segment changes
c. pathological Q waves
d. imaging evidence of new loss of viable myocardium
e. identification of intracoronary thrombus (by angiography or autopsy)
8
Q
Major consequence of anoxia
A
anoxia –> less ATP –> impacts Ca pump –> Ca accumulates in myocardium cell –> free radicals from reperfusion –> cell death
9
Q
What are serum biomarkers, why do we measure them, what are 3 important ones
A
- when myocardial cells increase permeability due to alterations in plasma membrane, stuff gets out based on molecular weight (smaller MW get out first)
- troponins, myoglobin, creatine kinase MB, and new markers (MB iosforms, CRP, MPO, sCD40, Annexin V)
10
Q
For the following serum markers, list their relative molecular weight and detectability: Myoglobin, Cardiac Troponin T, Cardiac Troponin I, Creatine kinase MB (CK-MB)
Which troponin is not cardiac specific?
A
- see figure
- myoglobin is not cardiac specific, so not useful
- troponin C is not cardiac specific
11
Q
Which serum marker is highest at 8 hours after MI? 20 hours?
A
6 hours: Myoglobin
20: troponin
12
Q
MI histopathology:
reversible damage:
irreversible damage:
A
reversible- cell swelling, hydropic and fatty change
irreversible - wavey appearance of myocardial fiber, cytoplasmic hypereosinophilia, contraction bands, nuclear pyknosis and karyolysis, chromatin half moon crescents
waviness of myocardial fiber = FIRST SIGN THAT SOMETHING IS WRONG!
13
Q
given the timeline, what do you expect to see under light microscopy?
0-1/2 hours:
1/2-4 hours:
4-12 hours:
12-24 hours:
1-3 days:
A
see chart
recall: karyolysis = nuclear fading; pyknosis - nuclear shrinking; karyorrhexis- nuclear fragmentation
14
Q
eline, what do you expect to see under light microscopy?
3-7 days:
7-10 days:
10-14 days:
2-8 weeks:
>2 months:
A
3-7 days: macrophages
7-10 days: granulation
10-14 days: granulation and collagen
2-8 weeks: collagen deposition
>2 months: scar
15
Q
roughly what stage of MI is does this slide show
A
healing MI with granulation tissue: day 7-10
16
Q
roughly what stage of MI is does this slide show
A
Healing MI with macropahges chewing up dead fibers, apoptotic PMNS: 3-7/10-14 days
17
Q
What are the importance of contraction bands with respect to an MI
A
- necrosis with contraction bands at time of reperfusion = irreversible injury to cardiomyocytes
- the bands are eosinophilic transverse bands, made of hypercontracted sarcomeres
18
Q
reperfusion injury
- what type of death
- cause of damage
A
- after blood flow resumes, variable number of cells die mostly by apoptosis
- damage by free radicals
19
Q
how long does it take for an MI to become recognizable on a gross examination?
What is the most common pattern of acute ischemic necrosis
A
- 12-24 hours
- regional infarction, i.e. a large single area of coagulative necrosis
- measures atleast 3 cm along one of axes and involves 50% of ventricular wall thickness
20
Q
list the 7 most common complications of MI
A
- pain
- ventricular remodeling and dysfunction
- cardiogenic shock
- arrhythmias
- pericarditis
- thromboembolism
- free wall rupture
21
Q
which ventricle is most likely to rupture and why
A
Left ventricle is 7x more likely than right: even though it’s thicker, the idea is that hypertension may be a risk factor and high BP in LV increases local wall stress
22
Q
What is mechanically occuring when you see symptoms with exertion (exertional angina) vs. symptoms at rest (unstable angina/MI)
A
exertional angina- clot that has not ruptured
unstable angina- ruptured clot with blood clot forming
23
Q
definition of ischemia
- symptoms
- rarer symptoms
A
O2 demand >>>> O2 supply
- chest pain, dyspnea, nausea, diaphoresis
- *last two believed to result from vagal stimulation, more common with inferior wall ischemia**
- more rare: urge to defecate, weakness, dizziness, palpitations, cold perspiration, send of impending doom
24
Q
causes for sudden death from ischemia
A
- usually caused by coronary artery disease
- younger patients: hypertrophic cardiomyopathy (HCM)
25
What are the risk factors for ischemia? (7)
1. prior coronary disease
2. coronary risk equivalents (diabetes, peripheral artery disease, chronic kidney disease)
3. hypertension
4. hyperlipidemia
5. family history
6. smoking
7. obesity, sedentary lifestyle
26
explain the concept of ST depressions
- in figure: you see RV and LV in first drawing, blue portion is subendocardial ischemia
- ischemia creates electrical currents going **away** from it
- when lead looks at LV, it will see current heading **towards** it (since current is being driven away from the subendocardium)
- raises baseline initially so then the EKG appears to have an ST depression
27
One important ischemic EKG change is T wave inversions. There are many causes for this, but list the 4 important ones. Why do you see the inversion?
- raised intracerebral pressure (cerebral T waves)
- resolving pericarditis
- bundle branch blocks
- ventricular hypertrophy
mechanism: normally subendocardium repolarizes first, so you get a wave of repolarization from sub to epicardium = upwards T wave as it heads towards the lead facing from the outside.
In subendo ischemia, it gets damaged and gets repolarized last. This reverses the wave.
28
Explain the mechanisms behind ST elevations
- ST elevation indicates transmural ischemia = entire wall is ischemic
- see the wave going **away** from the EKG lead
- now baseline is below the normal line
- the heart depolarizes then repolarizes, making it look more elevated than the initial baseline
29
at what point duringdo you start to see inverted T waves in an ST elevation MI (STEMI)
1-2 days
30
in an anterior MI, which leads would you expect to see ST elevation?
V1, V2, V3, V4
31
in a lateral MI, which leads would you expect to see ST elevation?
Leads I, aVL, V5, V6
32
in an inferior MI, which leads would you expect to see ST elevation?
Leads aVF, II, III
33
List the 5 ischemic syndromes
1. ST-Elevation Myocardial Infarcion (STEMI)
2. Non-ST-Elevation Myocardial Infarction (NSTEMI)
3. unstable angina
4. Variant/Prinzmetals angina
5. stable angina
34
Changes with infarction-gross and micro
0-4 hours:
4-12 hours:
12-24 hours:
5-10 days:
7 weeks:
0-4 hours: micro: hydropic and fatty change, t hen wavey myofibers
4-12 hours: gross: mottled; micro: necrosis, edema, hemorrhage
12-24 hours: gross: hyperemia; micro: surrounding tissue inflammation
5-10 days: gross: central yellowing; micro: granulation tissue
7 weeks: gross: gray-white scar; micro: scar
35
Risks after infarction:
1-4 days:
5-10 days:
Weeks later:
1-4 days: arrhythmia
5-10 days: free wall rupture, tamponade, papillary muscle rupture, VSD (septal rupture)
Weeks later: dressler's syndrome, aneurysm, LV thrombus/Cerebrovascular accident (CVA)
36
3 causes for papillary muscle rupture
2 causes for septal rupture + type of murmur
* papillary
* acute mitral regurgitation (holosystolic)
* heart failure, respiratory distress
* inferior MIs
* septal rupture
* hypotension
* right heart failure (increase JVP,edema)
* loud, holosystolic murmur (thrill)
37
weeks after an MI, the EKG shows ST elevation, PR segments are depressed. Name and describe the syndrome (5) + treatment
-a cause for ST elevations weeks after an MI can be due to pericarditis. This indicates **_Dressler's syndrome_**
* **chest pain** (sharp, pleuritic, worse when lying flat, improved when sitting up/lean forward)
* **pericardial friction rub** (scratchy sound)
* fever, **leukocytosis**
* high **ESR** (erythrocyte sedimentation rate)
* **immune-mediated** (details not known)
* Tx: NSAIDs or steroids
38
What are differenes/similarties between dressler's and fibrinous pericarditis?
- fibrinous can occur days after MI, not immune, extension of myocardial inflammation
- dressler's occurs WEEKS after, the pericarditis is considere a "post cardiac injury"
- **neither syndrome is life threatening,** so DONT pinpoint it as a cause of death
39
Secondary prevention for risk reduction of STEMI, NSTEMI, stable angina etc.
* **aspirin** (low dose, 81 mg), less bleeding with lower dose
* **statins** (atorvastatin, rosuvastatin) - pleiotrophic effects beyond LDL leveling, stabilize coronary plaques
40
2 problems/complications with stents
* restenosis
* scar tissue over stent
* re-occludes, usually not lifethreatening
* slow return of angina
* can use drug eluting stent to prevent this
* thrombosis
* acute closure of stent
* same as STEMI- LIFE THREATENING
* dual anti-platelet therapy for prevention
41
Describe the antiplatelet therapy for preventing stent thrombosis
* typically _one year_ of:
* **aspirin** (325 mg daily)
* **clopidogral** (75 mg daily)
* alternatives: prasugrel, ticagrelor
* after one year, stent metal no longer exposed to blood
* endothelialization
* risk of thrombosis is lowered
* cut back on antiplatelet therapy, most will still take **lower dosed** **aspirin **
42
tombstoning
see this in a STEMI: tombstoning effect "goes up then down"
**-ST elevation through V1-V5 =** anterior myocardial infarction
43
EKG suggest which artery is blocked by which leads show ST elevation
* LAD
* LCX
* RCA
* LAD: V1-V4 (anterior)
* LCX: I, aVL, V5, V6 (lateral)
* RCA: II, III, avF (inferior)
44
"time is muscle" in STEMI
* occluded coronary artery by blood clot
* the longer it remains occluded:
* more muscle dies
* more likely pt dies
* heart failure symptoms
* hospitalization
## Footnote
**aka MEDICAL EMERGENCY**
45
Treatment of STEMI
* main objective
* 2 options
* objective is revascularization = open the artery
* option 1: emergency angioplasty
* mechanical opening of artery
* should be done \<90 min
* more effective
* option 2: thrombolysis
* lysis of thrombus with drug
* should be done \<30 min
46
supportive drug treatment for STEMI-given while you work to open the artery
Remember: STEMI is a **thrombotic** and an **ischemic **problem
thrombotic:
* aspirin (inhibit platelet aggregation) 325 mg
* heparin (inhibit clot formation)
ischemic:
* beta blocker (to reduce O2 demand) i.e. metropolol
* nitrates (reduce O2 demand) i.e. nitro drip
47
alarms/cautions for when using beta blockers and nitrates
- inferior MI stimulates vagal nerve + beta blocker --\> bradycardia and AV block
- nitrates lower preload, but if you have an RCA infarction, RV doesnt work to preload the LV, so LV becomes heavily dependent on volume in the body --\> hypotension
48
3 other STEMI treatments (aside from aspirin, heparin, beta blockers, and nitrates)
* platelet inhibitor --\> ADP receptor blocker --\> **clopidogrel**
* platelet inhibitor --\> IIB/IIIA receptor blocker --\> **Eptifibatide**
* anticoagulant --\> direct thrombin inhibitor --\> bivalarudin
49
What is a Non-ST-Elevation Myocardial Infarction (NSTEMI)? What do you see on EKG and lab work?
- damage to tissue but EKG shows _no ST elevation_
- lab work shows elevated cardiac biomarkers (signs of heart damage)
* troponin
* I and T are most common; increase 2-4 hours after MI
* stay elevated for **weeks**
* CK
* CK-MB
* increase 4-6 hours after MI
* normalize wtihin **2-3 days**
50
creatinine kinase is found in multiple tissues, what ratio can be used in ischemia?
Several types of CK:
* MM-skeletal muscle*
* MB-cardiac*
* BB-brain *
**ratio of MB to total CK** can be used in ischemia, (because high CK levels alone doesn't necessarily mean MI, could be the MM type from a muscle disorder, i.e. rhabomyolysis)
51
abdominal pain with isolated increase in AST levels
-need to rule out MI, some AST found in cardiac cells
52
what is the most important difference between STEMI and NSTEMI?
there is no "ticking clock" with NSTEMI
* artery not completely occluded
* some blood flow **distal** to myocardium
* no need for emergency angioplasty
* no benefit to thrombolysis
53
unstable angina:
- symptoms
- EKG
- lab work
- sudden onset substernal chest pain, nausea, diaphoresis
- EKG: no ST elevation, but ST depression and T wave inversions
- lab work: normal cardiac biomarkers
*_signs of chest pain at rest = on verge of having an NSTEMI_*
54
stable angina:
symptoms
EKG
biomarkers
- substernal chest pain **with exercise**
- normal EKG and biomarkers
- stress test: walks on treadmill--\> chest pain --\> EKG changes
55
symptoms generally do not occur in stable angina until \_\_% of artery is occluded
-70%
stress test produces symptoms
56
why is there no role for heparin, tPA, and other antithrombotics in stable angina?
because blood clotting isn't an issue, you have a stable plaque and that's it.
57
medical therapy for stable angina if you dont want/cant have vascularization procedures
-you have to rectify the oxygen supply/demand problem--like a SEESAW
* increase O2 supply
* vasodilate coronary arteries
* increase diastole (recall coronary arteries are diffused during diastole)
* decrease O2 demand--main determinants of work
* decrease HR
* decrease contractility
* decrease afterload (BP)
* decrease preload
58
* preload definition
* what is the marker of preload
* how to increase volume (3)
* how to decrease preload (3)
* def: how much blood the heart must pump, how much stretch is on fibers prior to contraction
* marker = LV end diastolic volume (LVEDV)
* increase preload:
* add volume (blood, IVF)
* slow heart rate --\> more filling --\> more volume
* constrict veins (forces blood back to heart)
* decrease preload:
* remove volume (bleeding, dehydration)
* raise heart rate
* pool blood in veins (nitrates-dilators)
59
* afterload definition
* how to decrease afterload
* forces that resist forward flow of blood
* blood pressure
* aortic stenosis, HCM, etc.
* decrease afterload:
* lower BP
* treat aortic valve disease, hypertrophic cardiomyopathy, etc.
60
2 effects of HR with impact on O2:
-faster HR --\> effect on diastole? ---\> effect on O2 delivery?
2 effects of HR with impact on O2:
- more beats/min --\> more O2 needed
- length of diastole: faster HR --\> shorter diastole --\> less O2 delivery
61
ejection time
- definition
- what its associated with
- time to eject blood
- tracks with LVEDV (another marker of preload)
- more LVEDV = more ejection time = increase O2 demand
62
nitrates
- two mechanisms
- effect on preload
- reflex effect of nitrates, supplemental therapy
* predominant mechanism: venous dilation
* bigger veins = hold more blood = takes blood away from LV = lowers LVEDV
* also dilates arteries (but way less than veins)
* increases coronary perfusion
* peripheral vasodilation --\> BP will fall
* preload DECREASES
* preload falls --\> reflex tries to maintain CO --\> increase HR and contractility (increases O2 demand, exactly what we DONT want for angina
* nitrates improve angina, but preload effects dominate
* can administer BB or CCB to blunt reflex effect
63
nitrates side effects (3)
- headache (meningeal vasodilation)
- flushing (skin vasodilation)
- hypotension
64
Monday disease
-workers in nitroglycerin manufacturing facilities
**-regular NTG exposure --\> tolerance**
-lose tolerance over weekend
**-monday morning headache due to reexposure**: vasodilation, tachycardia, dizziness, headache
\*tolerance with nitrates--drugs stop working after frequent use, avoid by not using drug continuously for more than 24 hours
\*tolerance not demonstarted with once-daily **isosorbide mononitrate**
65
CCB
- action
- drugs and their specific actions
* negative inotropes
* slow HR, decrease contractility
* similar to beta blockers
* verapamil, dilitiazem
* vasodilators
* decrease peripheral vascular resistance (afterload)
* directly dilate coronary arteries
* nifedipine (dihydropyridines)
66
quiz self
see front
67
quiz self
see front
68
\<4 hours:
gross changes
microscopic changes
complications
gross: none
microscopic: none
complications: cardiogenic shock (massive MI), CHF, arrythmias
69
4-24 hours:
gross changes
microscopic changes
complications
gross: dark discoloration
microscopic: neutrophils
complications: arrhythmia
70
1-3 days:
gross changes
microscopic changes
complications
gross changes: yellow discoloration
microscopic changes: neutrophils
complications: fibrinous pericarditis, presents as chest pain with friction rub
71
4-7 days:
gross changes
microscopic changes
complications
gross changes: yellow discoloration
microscopic changes: macrophages
complications: rupture of ventricular free wall --\> cardiac tamponade, rupture of IV septum --\> shunt, rupture of papillary muscle --\> mitral insufficiency/murmur
72
1-3 weeks
gross changes
microscopic changes
complications
gross changes: red border emerges as granulation tissue enters from edge of infarct
microscopic changes: granulation tissue with plump fibroblasts, collagen, and blood vessels
complications: xx
73
months:
## Footnote
gross changes
microscopic changes
complications
gross changes: white scar
microscopic changes: fibrosis
complications: aneurysm, mural thrombus, or dressler syndrome
