Ischemia and Infarction

Question 1

Factors contributing to decreased incidence of coronary artery disease and stroke in recent decades

Answer 1

1. Prevention through changes in lifestyle, including reduced smoking, altered dietary habits, control of hypertension
2. Improved treatment of myocardial infarction and related complications
3. Prevention of recurrence in patients with history of atherosclerosis

Question 2

Approximately ___ of deaths in the Western world are attributed to atherosclerosis.

Answer 2

Approximately ⅓ of deaths in the Western world are attributed to atherosclerosis.

Question 3

Two most common pathologic consequences of atherosclerosis

Answer 3

1. Myocardial infarction
2. Stroke

Question 4

Ischemia is an imbalance of ____ and ____.

Answer 4

Ischemia is an imbalance of blood supply and blood demand.

Question 5

If ____ cannot be increased to meet an increase in demand, then ischemia will result

Answer 5

If perfusion cannot be increased to meet an increase in demand, then ischemia will result

Question 6

Causes of decreased blood supply

Answer 6

1. Vascular narrowing or obstruction
2. Acutely decreased blood pressure (hemorrhage or shock)

Question 7

Causes of increased blood demand

Answer 7

1. Exercise
2. Hypertrophy
3. Tachycardia
4. Dilation of the heart

Question 8

Biochemical components of ischemia

Answer 8

1. Hypoxia
2. Inadequate supply of metabolic substrates
3. Accumulation of metabolic waste products

Question 9

Four intracellular systems most vulnerable to ischemia

Answer 9

1. Genetic substrate integrity
2. Cell membrane structure and function
3. Aerobic respiration system
4. Synthesis and maintenance of structural proteins

Question 10

Three distributions of heart infarction

Answer 10

Question 11

Strokes tend to be ___ in origin.

Answer 11

Strokes tend to be embolic in origin.

Question 12

Myocardial infarctions tend to be ___ in origin.

Answer 12

Myocardial infarctions tend to be thrombotic in origin.

Question 13

Common causes of shock

Answer 13

• Sepsis
• Cardiac failure
• Hypovolumetric shock

Question 14

Shock can be thought of as essentially ____.

Answer 14

Shock can be thought of as essentially whole-body hypoperfusion.

Question 15

Watershed Infarction

Answer 15

Watersheds are tissues which have poor perfusion at baseline. Typically these areas do not have their own vasculation system, but are sandwiched between the vascular territories of two other tissues. These are the tissues most at risk during shock.

Many watersheds are in the brain, and the subendocardium is another prominent example.

Question 16

Prolonged or repeated shock may result in ____.

Answer 16

Prolonged or repeated shock may result in ischemic encephalopathy. This is associated with gradual degradation of watershed areas and decline in brain function.

“Bubbles” shown in picture attached are areas of necrosis.

Question 17

The liver receives __% of its blood supply from portal circulation and __% from the hepatic arteries.

Answer 17

The liver receives 80% of its blood supply from portal circulation and 20% from the hepatic arteries.

Question 18

Tissues with dual blood supplies

Answer 18

• Liver (portal veins, hepatic arteries)
• Lungs (pulmonary arteries, bronchial arteries)

Question 19

____ is classically seen in organs with either a dual blood supply, or extensive collateral circulation.

Answer 19

Hemorrhagic infarction is classically seen in organs with either a dual blood supply, or extensive collateral circulation.

Question 20

Ischemic cardiac myocytes shift to anaerobic respiration within ___ of ischemia onset. Cell death does not occur until after ___.

Answer 20

Ischemic cardiac myocytes shift to anaerobic respiration within 3-5 minutes of ischemia onset.

Cell death does not occur until after at least 20-30 minutes.

Question 21

Although myocardium does not have a true dual circulation, there is extensive ____, providing a potential lifeline to ischemic cells at ____.

Answer 21

Although myocardium does not have a true dual circulation, there is extensive collateral circulation, providing a potential lifeline to ischemic cells at the periphery of an infarct zone (sometimes called the “penumbra”).

This results in a gradient of ischemic damage

Question 22

Tissue viability and functionality as a function of bloodflow and time

Answer 22

Question 23

Plaques causing around 60% stenosis are ____ to rupture than those causing 90% stenosis

Answer 23

Plaques causing around 60% stenosis are more likely to rupture than those causing 90% stenosis

Question 24

Plaques at highest risk of rupture may be ____

Answer 24

Plaques at highest risk of rupture may be asymptomatic

Question 25

Early changes in myocardial infarction

Answer 25

• Loss of glycogen
• Sarcomere relaxation

These are both reversible changes.

Question 26

___ is the key event that results in the shift from reversible to irreversible injury

Answer 26

Cell membrane damage is the key event that results in the shift from reversible to irreversible injury

Question 27

Troponin I (TnI)

Answer 27

Component of the cardiac myocyte contractile apparatus. Upon irreversible myocardial injury and loss of membrane integrity, it is released into circulation.

Serum troponin I is a highly sensitive and specific marker of myocardial infarction.

Question 28

Most hospital MI protocols require ____, over a period of at least ____, before “ruling out” MI in a patient. This is because ___.

Answer 28

Most hospital MI protocols require three negative troponin I tests, over a period of at least four to six hours, before “ruling out” MI in a patient. This is because troponin I may not appear abnormal early in MI, prior to cell rupture and prior to escape from the tissue into the bloodstream.

Question 29

Myocardial infarction histology: Day 1 to Day 10

Answer 29

Question 30

Myocardial infarction histology: Week 2 to Week 8 and beyond

Answer 30

Question 31

Wavefront of myocardial damage

Answer 31

Question 32

The penumbra of myocardial damage can be ____.

Answer 32

The penumbra of myocardial damage can be saved if perfusion is restored quickly.

Question 33

The goal of therapy for myocardial infarction should be . . .

Answer 33

. . . to intervene as early as possible, to reperfuse tissue and limit infarct size.

Question 34

Clinical benefit of reperfusing therapy drops off precipitiously if greater than ___ pass between the initiating event and reperfusion.

Answer 34

Clinical benefit of reperfusing therapy drops off precipitiously if greater than 3 hours pass between the initiating event and reperfusion.

Question 35

“Door to needle” time goal for most hospitals

Answer 35

30 minutes

Question 36

Reperfusion was first accomplished using ___.

Answer 36

Reperfusion was first accomplished using thrombolytic drugs – first streptokinase and urokinase, and later tPA

Question 37

Today, reperfusion is usually accomplished by ___

Answer 37

Today, reperfusion is usually accomplished by percutaneous coronary intervention (PCI)

Essentially, this means physically opening the vessel by inserting a catheter into the vasculature and inflating a balloon at the site of the obstruction (angioplasty) to reopen the vessel

Question 38

contraction bands

Answer 38

The remnants of reperfusion injury

Question 39

Myocardial stunning

Answer 39

Function of reperfused myocardium is not fully restored immediately, resulting in a period of post-ischemic ventricular dysfunction. May create turbulent flow that predisposes to aneurysm or mural thrombus.

Question 40

Ischemic pre-conditioning

Answer 40

One potential way to reduce the risk of myocardial stunning and reperfusion injury

Deliberately causing brief episodes of myocardial ischemia and reperfusion prior to a major and predictable period of ischemia (e.g. cardiac surgery) to allow the myocardium to “adapt” in advance

Currently in clinical trials. Experimental trials in mammals have produced astounding results (~6 fold smaller infarct size)

Question 41

Coronary Artery Disease: the big picture

Answer 41

Question 43

Answer 43

Hemosiderin. Deposit of free, oxidized heme groups that broke off of hemoglobin following erythrocyte lysis. Cleared by macrophages.

Common in myocardial infarction H and E.

Question 44

Treatment for acute coronary artery thrombosis

Answer 44

1. If <3 hours since incidence, ONAH + stenting
2. If >3 hours since incidence, hemolytic treatment: streptokinase, urokinase, tPA

Question 45

ONAH

Answer 45

Oxygen (100%, gas mask)

Nitroglycerin (vasodilator)

Aspirin (Irreversibly inhibit TxA₂ synthase in thromboytes)

Heparin (hemolytic activator and inhibitor of platelet aggregation)

Question 46

Strokes: When to give tPA?

Answer 46

If there is hemorrhage/intracranial bleeding, DO NOT give tPA.

tPA should be given for nonhemorrhagic lesions, particularly thrombosis, atherosclerotic ischemia, or thromboembolism.