Ischemia and MI Flashcards
Relative pressures of RV and LV
LV pressure is approx 5x higher
Cardiomyocyte substrates and preferred route of ATP generation
~ 40% carbs (glucose and lactate)
~60% lipids (FFAs)
The heart is an obligate aerobic organ- it makes all it’s ATP through aerobic metabolism because anaerobic metabolism cannot sustain it.
Determinants of myocardial oxygen supply
- coronary blood flow (perfusion pressure + resistance)
- coronary oxygen content and availability
Determinants of coronary blood flow
- coronary perfusion gradient (aortic pressure-LV pressure)
- coronary resistance (myocardial compression, tone of resistance vessels, stenoses)
Types of coronary vessels
- conductance vessels (penetrate from epicardium to endocardium and give off:
- resistance vessels ( have smooth muscle cells): maybe called this because they are closest to endocardium and feel resistance on pumping?
Factors that change the tone of resistance vessels
Metabolic- adenosine causes relaxation
Endothelial- endothelin (constrict), PGI2 & EDRF (relax)
Neurogenic: vagus (relax), B (relax), alpha-1 (constrict)
Myogenic (autoregulation- response to acute changes in BP)
Determinants of coronary oxygen content
Sa02, Hb concentration, 2,3-BPG
Determinants of myocardial oxygen demand
- heart rate
- wall stress (AKA wall tension)
- contractility
- preload
- afterload
Determinants of wall stress and their effect on oxygen demand
- increased radius and/or pressure increase wall stress, increased O2 demand
- increased thickness decreases wall stress, decreased O2 demand
Why does coronary blood flow need to be closely coupled to myocardial oxygen demand?
- myocardium depends on aerobic metabolism
- myocardium already maximally extracts O2, so this variable cannot be modified to deliver more O2 to the tissue the way it can in skeletal muscle
- myocardium cannot incur a significant O2 debt
When does ischemia occur?
When oxygen demand exceeds oxygen supply.
Examples of primary and secondary ischemia
Primary: a coronary spasm in which the SUPPLY changes
Secondary: a clot.. the DEMAND changes
What is the cause of the majority of MIs?
- erosion/rupture of an atherosclerotic plaque and subsequent thrombosis
Atherosclerotic arteries are _____ and cannot ____
narrower and cannot dilate as well
Two ways that thrombosis occurs
- Plaque fissure
- Plaque rupture (part of the fibrous cap lifts, atheroma spills into lumen)
Fates of a thrombus in a coronary artery
- thrombus can be stable
- thrombus can be integrated into the plaque
- thrombus can grow and occlude the lumen
- thrombus can embolize and occlude a smaller downstream vessel (or several…)
Definition of an MI
- The rise and fall of a cardiac biomarker (in temporal order: CK-MB, troponin C,lactate dehydrogenase). Plus:
- Sx of ischemia OR
- ECG suggestive of ischemia OR
- Imaging suggestive of ischemia
Pathophysiology of ischemia –> MI
1) occlusion deprives cells of oxygen
2) dysfunction of cells
4) build-up of ADP
5) ion-pump cessation
5) membrane disruption, cell death
Timeline for ischemia–> infarction
- Dysfunction begins within 2 minutes of occlusion
- necrosis begins at 20 min and may take 2-4 hrs
What is the wavefront phenomenon?
Occlusion results in an area at risk. The infarct develops from the subendocardium to the epicardium. The lateral borders are pre-determined, but the depth is not.
What are collateral vessels?
Vessels that have developed to relieve narrowing of other vessels.
Why does an infarct develop first in the subendocardial zone?
- blood has to pass through more contracting muscles
- fewer collaterals
- higher metabolic demand
- increased wall tension compared to epicardium
STEMI vs. NSTEMI infarct types
STEMI: transmural
NSTEMI: subendocardial
Types of infarction based on region…
Regional (segmental): only one vessel is occluded
Diffuse: multivessel or shock or inotropic drug overdose
% distribution of regional MIs
LAD- 50%
RCA- 30%
Cx- 20%
Determinants of infarction size
1) severity and duration of ischemia
2) size of the area at risk
3) presence/absence of collateral coronary circulation
4) Reperfusion of ischemic area
5) Pre-ischemic state of myocardium (e.g chronic low grade ischemia is better outcome for acute MI)
6) concurrent cardiac physiology (e.g. aortic stenosis)
7) systemic conditions
8 histopathologic stages of an MI
1/2: wavy fibers and intercellular edema
3: contraction bands. pumps stop working, Ca overload. nuclei dissolve. pink strips of accordioned z-bands
4: neutrophillic infiltrate: PMNs release enzymes that eat the dead myocytes
5: coagulation necrosis: hypereoisinophillic cardiomyocytes
6: macrophage phagocytosis of dead myocytes
7: granulation tissue forms. neovascularization
8: Healed MI, residual scar
Gross anatomical changes following an MI
1-3 days: pale and mottled, yellow
1-2 wks: depressed, gelatinous from granulation
3-4 weeks outer edges are white, scar tissue
Months: all white
When and why does reperfusion injury happen?
-appearance on gross specimen?
- Delayed reperfusion (>6hrs)
- Introducing oxygen into necrotic tissue enhances cell death from radicals
-appears hemorrhagic on gross specimen
Consequences of an MI
1) arrhythmias: ischemia promotes ectopic arrhythmias
2) ventricular dysfunction
3) myocardial stunning
4) myocardial hibernation
5) cardiogenic shock
6) Infarct extension
7) Infarct expansion
8) ventricular aneurysm
9) myocardial rupture
10) cardiac tamponade
11) right ventricular infarction
12) mural thrombus (can embolize)/DVT
13) Pericarditis (more likely in transmural)
14) Sudden cardiac death (e.g. arrhythmia)
15) Congestive heart failure
What is myocardial stunning?
When it takes a long time (days to weeks) for ischemic (not0 necrotic) tissue to return to normal after reperfusion.
What is myocardial hibernation?
Chronically impaired myocardium due to persistently reduced blood supply. Can eliminate with revascularization
What is cardiogenic shock?
When the heart can’t pump enough blood out for the body. Hypotension, cool extremities…
What is infarct extension?
-new infarcts at the margin of the original infarct
What is infarct expansion?
-physiological effects of expansion
-Stretching/thinning of the original infarct
- increased wall stress from increased radius, decreased thickness, increased LVEDV=LVEDP
- impairment of systolic contraction
- increased chance of ventricular aneurysm
What kind of infarcts produce ventricular aneurysms?
-likelihood of rupture
- transmural
- usually multivessel
-they don’t usually rupture because they are really calcified
When do most myocardial ruptures happen?
1-3 days post-MI
Types of myocardial rupture
-how does this happen
Free wall of LV
Interventricular septum
Papillary muscle
-blood erodes a path through soft, dead tissue
Clinical consequences of a interventricular septum rupture post-MI
- congestive heart failure
- systolic murmur
Clinical consequences of papillary muscle rupture
- acute mitral regurgitation
- surgical emergency
Clinical consequence of a left free wall rupture
- cardiac tamponade
Things that contribute to plaque instability and rupture
- inflammation
- shear stress
- oxidative stress
Why is there blood in myocardial infarction histopathological specimens?
Because of capillary rupture
What is the determining factor on whether to operate on an abdominal aortic aneurysm?
-size of the aneurysm
Complicated vs. simple atherosclerosis
Simple atherosclerosis will still have a smooth lining in the vessel
Complicated looks like an ulcer, the endothelial lining is not present anymore
