Pathology of Ischemic Heart Disease

Question 1

What branch of the right main coronary artery supplies the heart areas of right dominant hearts? Where would this come from otherwise?

Answer 1

Posterior descending coronary artery

• > supplies posterior 1/3 of IV septum, posterior and inferior walls of left ventricle
• > otherwise this would come from left circumflex artery

Question 2

Is ischemia or hypoxemia worse? How are they related?

Answer 2

Related - both are causes of tissue hypoxia

Ischemia = poor blood flow
Hypoxemia = low blood oxygen (pulmonary function, anemia, etc)

Ischemia is worse because you cannot properly carry in nutrients and remove waste

Question 3

Why does tachycardia exacerbate ischemic heart disease?

Answer 3

1. Increases myocardial oxygen demand

2. Reduces diastolic filling time

Question 4

Is unstable angina considered reversible? How does it occur?

Answer 4

Yes -> due to acute atheromatous plaque disruption via hemorrhage, erosion, or rupture leading to PARTIALLY occluded vessel.

Often destabilized by mechanical stress + plaque inflammation w/metalloprotease activation via macrophages.

Question 5

What is the clinical progression of unstable angina?

Answer 5

Progressively worsening episodes of anginal pain with increasing frequency, duration, and severity. Eventually will even occur at rest.

This is why it is called “crescendo” angina

Question 6

What is the mechanistic difference between what usually causes a subendocardial and transmural infarct?

Answer 6

Both are totally occlusive super imposed thromboses on atherosclerotic plaques causing irreversible myocardial ischemia.

Difference: Subendocardial myocardial infarct has coronary artery thrombolysis before myocardial necrosis can evolve into a full thickness infarct

Question 7

Other than a superimposed thrombosis, what are some less common pathophysiologic mechanisms for an acute MI?

Answer 7

1. Coronary artery vasospasm w/o atherosclerosis -> cocaine abuse
2. Coronary artery thromboembolism (from left sided mural thrombus) or paradoxical embolus from DVT
3. Intramyocardial coronary artery pathology, i.e. vasculitis

Question 8

What is one protective factor against MI in chronic stable angina?

Answer 8

Often, collateral circulation develops over long periods of time

Question 9

When myocardial ischemia occurs, how quick is function lost, and when does irreversible injury occur? When is infarct size determined?

Answer 9

Functional loss: within 1-2 minuntes after myocardium has to switch to anaerobic glycolysis and lactic acid accumulates

-> organelle and cytosolic swelling occurs with loss of function and irritability

Irreversible injury: Begins at 30 minutes, infarct size is determined by around 6 hours

Question 10

What is the most common coronary artery to be affected via MI? What areas of the heart will be affected grossly and microscopically early on?

Answer 10

Left anterior descending (LAD)
-> anterior IV septum, anterior wall of LV, and LV apex

Microscopically, subendocardium will be affected first because it is farthest from epicardial arteries

Question 11

In order for the right ventricle to be affected via an RCA thrombus, where must the stenosis occur?

Answer 11

Very proximal -> more distally it will wrap around to supply the posterior portion of the LV in most people

Question 12

How will an MI appear grossly in 1-3 days, 3-10 days, 2 months?

Answer 12

1-3 days: Pale infarct -> end-organ lack of perfusion

3-10 days: Soft, yellow-tan area with a red, hyperemic border (due to formation of granulation tissue and capillary growth)

2 months: After scar has formed from periphery inward, will appear a contracted, white rubbery scar

Question 13

Why can some of the cells which appear to have undergone coagulative necrosis appear “wavy” in an MI?

Answer 13

If they are close to neighboring myocardial cells which are contracting, they may be pulled into wave-like formations

Question 14

What cells are we trying to save with reperfusion?

Answer 14

The cells which have undergone myocytolysis change -> equivalent of reversible hydropic change in ischemia, which will die if oxygen is not restored

Question 15

What is myocardial stunning?

Answer 15

The observation that even when reperfused, myocardial cells will take some time to regain their contractility (appear stunned)

Question 16

What is contraction band necrosis? What causes it?

Answer 16

Finding of intracytoplasmic, deeply eosinophilic transverse bands

Occurs in some cells with coagulative necrosis due to exposure to very high intracellular Ca+2 levels prior to death -> increased myofibril contraction

Question 17

What are some reperfusion-induced injuries?

Answer 17

1. Additional cell death
2. Microvascular injury w/ endothelial swelling
3. Cardiac arrhythmias

Question 18

How does reperfusion look in infarcted areas?

Answer 18

Infarcted areas will have hemorrhage due to buildup of RBCs between coagulative necrosis

Question 19

What patient populations are most likely to have silent MIs?

Answer 19

Diabetics and women

Question 20

What troponins are useful for cardiac infarction monitoring and why?

Answer 20

TnI and TnT, but not TnC

-> form of TnC is not specific to cardiac muscle

Question 21

Why is CK-MB useful?

Answer 21

This MB isozyme of creatine kinase is fairly specific for cardiac muscle, and will return to normal 3 days after infarct -> about 1 week faster than troponins, to show that a new infarction has occurred if patient has new onset chest pain.

Question 22

How can an MI cause worsening of an MI?

Answer 22

Poor coronary artery perfusion from a drop in cardiac output due to decreased contractility or arrhythmias can lead to extension of the area of necrosis

Thrombus can also expand or embolize downstream.

Question 23

What is a likely complication 2-3 days after a transmural infarct? Why is it specific to this type of infarct?

Answer 23

Fibrinous percarditis, due to inflammatory response entering the pericardial sac

Subendocardial infarcts will not allow access of inflammatory cells to the pericardial sac

Question 24

When is myocardial rupture most likely to happen and why?

Answer 24

4-5 days post infarct -> wall is soupy and necrosed as macrophages are eating it up.

Very weak wall with massive tissue disintegration

Question 25

Who is most likely to undergo a ventricular free-wall rupture? What is most likely to cause it?

Answer 25

Older women (they have the most tender hearts)

Caused by LAD occlusion -< anterior wall?

Question 26

What are the possible complications of a left ventricular free-wall rupture?

Answer 26

Most commonly: hemopericardium with cardiac tamponade (high mortality)

Uncommonly: False aneurysm (hematoma formed by <3 layers of cardiovascular wall)

Question 27

Give two other structures likely to rupture in MI and their complications?

Answer 27

1. IV septum -> acute left to right shunt due to pressure differential
2. Papillary muscle rupture -> acute mitral valve regurgitation

Question 28

Why do MI’s predipose to systemic thromboemboli?

Answer 28

Because endocardial injury and abnormal blood flow predisposes to mural thrombus formation

Question 29

Other than rupture, what are a few other reasons for papillary muscle dysfunction in MI? What’s the result of all of these?

Answer 29

Mitral valve regurgitation is the outcome

1. Acute ischemia -> can’t contract
2. Chronic fibrosis and shortening -> due to healing with fibrosis post-MI
3. LV dilatation -> weak, healing wall must dilate.

In 2/3 the valve leaflets won’t be able to reach to close.

Question 30

What is Dressler syndrome and what causes it?

Answer 30

Immune-mediated pericarditis weeks to months after MI, usually transmural (different than fibrinous pericarditis)
-> due to exposure of antigens from myocardial cells during necrosis

Question 31

What is a left ventricular aneurysm? When after an MI does this occur? What is the most likely complication?

Answer 31

Occurs very late, after an anterior, transmural myocardial infarct. The wall repairs via fibrous scarring and stretches outward.

Likely complication -> mural thrombosis (Due to exposed collagen) but NOT rupture because it is dense collagen (vs false aneurysm)

Question 32

What causes sudden cardiac death in ischemic heart disease? How do you presume the cause of death?

Answer 32

Ischemic myocardium is very irritable -> can cause fatal arrhythmia

Autopsy generally shows myocardial fibrosis and subendocardial myocytolysis, but no acute infarction visible.

Question 33

What is Chronic Ischemic Heart Disease?

Answer 33

Progressively worsening heart failure due to chronic ischemic injury. They may have no history of MIs, but subclinical irreversible ischemic damage.

-> LV hypertrophy and dilatation, severe atherosclerosis, and multiple areas of fibrosis with subendocardial myocytolysis

Question 34

What is the ultimate outcome of all ischemic heart disease?

Answer 34

Sudden cardiac death, presumably due to ischemia