Cv 10: Ischemic Heart Disease Pathology

Front 1

What is the definition of Ischemic Heart Disease (IHD)?

Back 1

Imbalance between supply and demand for oxygen and nutrients and removal of metabolites

Front 2

What is the difference between ischemia and hypoxemia? Which is worse?

Back 2

- Ischemia causes a lack of perfusion, prevents delivery of nutrients (in addition to oxygen) and removal of metabolites
- Hypoxemia is just a lack of delivery of oxygen
- Ischemia is worse than hypoxemia

Front 3

What is the leading cause of death and disability in the USA?

Back 3

Ischemic Heart Disease (IHD)

Front 4

How has the death rate from Ischemic Heart Disease (IHD) changed over time? Why?

Back 4

- Decreased since 1960s
- Preventative measures against development of atherosclerosis (smoking, cholesterol, HTN, lifestyle)
- Therapeutic advances (medical and surgical)

Front 5

What is the cause of Ischemic Heart Disease (IHD)?

Back 5

- ≥ 90% atherosclerotic narrowing
- Reduced coronary blood flow
- Other causes: ↓ systolic BP, vasculitis, structural anomalies, severe HTN, diminished oxygenation, or diminished oxygen-carrying capacity

Front 6

What are some causes of decreased blood flow (leading to Ischemic Heart Disease (IHD))?

Back 6

- Fixed atherosclerotic narrowing
- Acute plaque change
- Thrombosis overlying ruptured plaque
- Vasospasm

Front 7

What percentage of the lumen needs to be compromised to cause symptoms in Ischemic Heart Disease (IHD)?

Back 7

- >70% narrowed → symptomatic ischemia w/ EXERCISE
- >90% stenosis → ischemia at REST

Front 8

What are the most commonly affected Coronary Arteries?

Back 8

1. First several cm of Left Anterior Descending (LAD) = widow maker
2. Left Circumflex (LCX)
3. Entire length of R Coronary Artery (RCA)

Front 9

How is the effect of a fixed obstruction to blood flow modified?

Back 9

Collateral circulation - if there is time to adapt, collaterals can help provide blood supply to heart, but if it is an acute obstruction, no help

Front 10

What are the characteristics and outcomes of an acute plaque change in Ischemic Heart Disease (IHD)?

Back 10

- Unpredictable, abrupt conversion of stable plaque to an unstable athero-thrombotic lesion

- E.g., Rupture / fissures / ulcerations - expose underlying thombogenic substances (leads to more clotting)
- E.g., Hemorrhage into atheroma - expands plaque and narrows lumen

- Results in acute coronary syndrome: MI, unstable angina, sudden cardiac death

Front 11

What intrinsic factors can contribute to an acute plaque change?

Back 11

- Large areas of foam cells / lipid (lipid core)
- Thin fibrous cap
- Most dangerous lesions are moderately stenotic, lipid rich atheromas (soft core)
- Abundant inflammation
- Few smooth muscle cells
- Mechanical stress (at junction of fibrous cap and adjacent normal wall)

Front 12

What is the most dangerous size of lesion / stenosis for an acute plaque change? Why?

Back 12

- Moderately stenotic (50-75%)
- They are getting beaten by turbulent blood flow which can predispose to an acute plaque change
- A larger plaque would not be affected by turbulent flow because there is not room for turbulence
- A smaller plaque is obviously less troublesome

Front 13

What extrinsic factors can contribute to an acute plaque change?

Back 13

Adrenergic stimulation:
- Upon awakening
- Emotional

Front 14

How does a coronary thrombosis cause a decrease in blood flow?

Back 14

Thrombosis can partially or totally superimpose on a partially stenotic plaque

Front 15

What are the possible outcomes of a coronary thrombosis?

Back 15

- Total occlusion → Acute Transmural MI or Sudden Death
- Incomplete occlusion → Mural Thrombus → Unstable Angina, acute subendocardial infarction, sudden death or may emboli into more distal coronary artery

Front 16

How does vasoconstriction cause a decrease in blood flow? Outcomes?

Back 16

- Compromises lumen size and increases mechanical forces that contribute to plaque rupture
- Leads to severe but transient reduction in coronary blood flow

Front 17

What stimulates vasoconstriction of coronary arteries?

Back 17

- Adrenergic agonists in circulation
- Locally released platelet contents
- Endothelial dysfunction leading to impaired secretion of endothelial relaxing factors
- Mediators released from mast cells

Front 18

What is the progression of acute coronary syndromes?

Back 18

1. Normal
2. Atherosclerosis → fixed coronary obstruction → Typical Angina
3. Plaque Disruption → healing leads to larger / severe fixed coronary obstruction → Chronic Ischemic Heart Disease
4. Thrombus (either mural or occlusive)
- Mural: variable obstruction → Unstable Angina, Acute Subendocardial MI, or Sudden Death
- Occlusive: complete obstruction → Acute Transmural MI or Sudden Death

Front 19

What are the clinical syndromes / outcomes of Ischemic Heart Disease (IHD)?

Back 19

- Angina pectoris (chest pain)
- Myocardial infarction
- Chronic ischemic heart disease
- Sudden cardiac death

Front 20

What is the definition of Angina Pectoris?

Back 20

- Manifestation of Ischemic Heart Disease (IHD)
- Paroxysmal (sudden) and recurrent attacks of chest pain caused by transient MI
- Lasts 15 seconds to 15 minutes
- No cellular necrosis (no lasting damage)

Front 21

What are the three patterns of Angina Pectoris?

Back 21

- Stable
- Prinzmetal
- Unstable

Front 22

What are the characteristics of Stable Angina Pectoris?

Back 22

- Produced by physical activity or emotional excitement
- Attributed to chronic stenosing coronary artery syndrome
- Demand for O2 and nutrients exceeds supply

Front 23

What are the characteristics of Prinzmetal Angina Pectoris?

Back 23

Due to coronary artery spasm at rest

Front 24

What are the characteristics of Unstable Angina Pectoris?

Back 24

- Occurs w/ progressively increasing frequency and progressively less effort
- Often at rest and of prolonged duration
- Induced by disruption of plaque w/ superimposed partial thrombosis
- Often prodrome (early symptom) of acute MI

Front 25

What happens in a Myocardial Infarction (MI)?

Back 25

Death of cardiac muscle d/t ischemia
- 90%: acute plaque change results in thrombus and occlusion of coronary artery
- 10%: vasospasm, emboli, or unexplained

Front 26

What are the risk factors for a Myocardial Infarction (MI)?

Back 26

- Increasing age
- M > F (premenopausal)
- HTN
- Cigarettes
- DM
- Increased cholesterol and/or lipids

Front 27

What are the two types of Myocardial Infarctions (MI)?

Back 27

- Transmural
- Subendocardial

Front 28

What are the characteristics of a Transmural Myocardial Infarction (MI)?

Back 28

- Full thickness of ventricular wall
- Confined to distribution of one vessel
- Fixed coronary obstruction with superimposed acute plaque change and complete obstructive thrombosis

* Localized obstruction in flow *

Front 29

What are the characteristics of a Subendocardial Myocardial Infarction (MI)?

Back 29

- Necrosis limited to inner 1/3
- May extend laterally beyond perfusion of one vessel
- Fixed coronary obstruction w/ acute plaque change
- Non-occlusive thrombus or lysis of thrombus or hypotension

* Global decrease in flow *

Front 30

Which kind of MI causes a localized obstruction in flow as opposed to a global decrease in flow?

Back 30

- Localized: Transmural
- Global: Subendocardial

Front 31

Which kind of MI causes necrosis limited to inner 1/3 and which causes a full thickness injury?

Back 31

- Global: Subendocardial
- Full thickness: Transmural

Front 32

What is the response to a Myocardial Infarction (MI)? Timeline?

Back 32

- Immediately: loss of blood supply (reversible damage in early stages)
- 60 sec of ischemia: loss of contractility (may precipitate acute heart failure)
- 20-40 minutes: irreversible damage (coagulative necrosis)
- 3-4 hours: early thrombolytic therapy → reperfusion and limiting of size of infarct
- Later: arrhythmias (induced by myocardial irritability secondary to ischemia/infarction - ventricular fibrillation) → sudden death

Front 33

How much time of ischemia is necessary to cause loss of contractility in a Myocardial Infarction (MI)?

Back 33

60 seconds

Front 34

How much time does it take to cause irreversible damage (coagulative necrosis) in a Myocardial Infarction (MI)?

Back 34

20-40 minutes

Front 35

How soon should early thrombolytic therapy occur? Benefits?

Back 35

- Hopefully within 3-4 hours
- Reperfusion
- Limits size of infarct

Front 36

What are some outcomes that can be caused by myocardial irritability secondary to ischemia and infarction?

Back 36

- Arrhythmias (eg ventricular fibrillation)
- Can lead to sudden death

Front 37

How does the progression of necrosis occur in a Myocardial Infarction (MI)?

Back 37

- Endocardium is furthest from coronary artery so is first to necrose
- Last epicardium (closest to coronary artery)
- Occurs in zone / area supplied by coronary artery

Front 38

Which coronary arteries are involved in Myocardial Infarctions (MI)? How frequently?

Back 38

- LAD: most often (40-50%)
- RCA: next most often (30-40%)
- LCA: least common (15-20%)

Front 39

What kind of infarct is this? Cause?

Back 39

- Regional sub-endocardial infarct
- Non-transmural infarct
- Cause: Transient / partial obstruction

Front 40

What kind of infarct is this?

Back 40

- Circumferential sub-endocardial infarct
- Non-transmural infarct
- Cause: Global hypotension

Front 41

What kind of infarct is this?

Back 41

- Micro-infarcts
- Non-transmural infacts
- Cause: small intramural vessel occlusions

Front 42

Morphologically, what happens in the first 12 hours of a Myocardial Infarction?

Back 42

- Not apparent
- Tetrazolium stain shows pale areas 2-3 hours post-occurrence

Front 43

Morphologically, what happens 12-24 hours after a Myocardial Infarction?

Back 43

Dark red-blue mottling (due to stagnant blood)

Front 44

Morphologically, what happens 1-14 days after a Myocardial Infarction?

Back 44

- Early: sharply defined yellow-tan area
- Late: still yellow-tan centrally but with hyperemic peripheral zone

Front 45

Morphologically, what happens >2 weeks after a Myocardial Infarction?

Back 45

Gray-white scar begins to form

Front 46

Histologically, what happens in the first 24 hours of a Myocardial Infarction?

Back 46

- Presence of wavy fibers
- Coagulative necrosis

Front 47

Histologically, what happens 12 hours - 7 days after a Myocardial Infarction?

Back 47

- Coagulative necrosis becomes well-established and ongoing
- Initially pyknotic nuclei, hyper-eosinophilic myocytes
- Followed by neutrophils (max 1-3 days), loss of nuclei and striations
- By 7 days, macrophages are at border

Front 48

Histologically, what happens 7-14 days after a Myocardial Infarction?

Back 48

- Granulation tissue well-established
- Collagen begins to deposit

Front 49

Histologically, what happens >14 days after a Myocardial Infarction?

Back 49

- Progressively more collagen deposition
- Eventually dense fibrous scar

Front 50

When does reperfusion injury occur?

Back 50

After thrombolysis, balloon angioplasty, or bypass grafts

Front 51

How soon does reperfusion need to occur to prevent necrosis from an MI?

Back 51

Within 20 minutes

Front 52

What is the microscopic evidence of reperfusion injury? Why?

Back 52

Microscopically: necrosis with contraction bands - permanent (due to influx of Ca2+)

Front 53

What is the cause of reperfusion injury?

Back 53

- Oxygen free radicals released from leukocytes
- Microvascular injury causes hemorrhage and endothelial swelling that occludes capillaries (no flow)
- Platelet and complement activation

Front 54

What are the clinical features of MI?

Back 54

- Chest pain (severe, crushing, substernal)
- Pain may radiate into left arm, neck, jaw, epigastrium
- Lasts several minutes to hours
- No relief by nitroglycerin or rest
- Rapid weak pulse
- Diaphoresis (sweating)
- Dyspnea d/t pulmonary edema
- 10-15% without symptoms

Front 55

What are the diagnostic features for evaluating a possible MI?

Back 55

- ECG patterns
- Elevated cardiac enzymes (MB-CK and Troponins), C-reactive protein

Front 56

How does nitroglycerin and rest help someone having an MI?

Back 56

No relief

Front 57

What are the complications of an MI?

Back 57

- Contractile dysfunction (proportionate to damage)
- Cardiogenic shock (pump failure)
- Arrhythmia (early, may lead to sudden death)
- Myocardial rupture (3-7 days)
- Pericarditis (2-3 days)
- Mural thrombus and thromboembolism
- Ventricular aneurysm (late)
- Papillary muscle dysfunction (secondary to scarring/fibrosis)
- Progressive heart failure (late)

Front 58

How common is cardiogenic shock (pump failure) in an MI? What is it associated with?

Back 58

- 10-15%
- Associated with damage to 40% or more of LV
- Correlates w/ size of infarct

Front 59

When does myocardial rupture occur after an MI? Where can it occur and what are the outcomes of those locations?

Back 59

- 3-7 days post-MI
- Free wall: hemopericardium, tamponade, aneurysm
- Ventricular septum: L → R shunt
- Papillary muscle: mitral regurgitation

Front 60

What are the possible outcomes of a myocardial rupture of the free wall? When does this occur?

Back 60

- Hemopericardium (blood in the pericardial sac of the heart)
- Tamponade (compression of the heart by an accumulation of fluid in the pericardial sac)
- Aneurysm (excessive, localized enlargement)

- 3-7 days post-MI

Front 61

What are the possible outcomes of a myocardial rupture of the ventricular septum? When does this occur?

Back 61

- Left → Right shunt

- 3-7 days post-MI

Front 62

What are the possible outcomes of a myocardial rupture of the papillary muscle? When does this occur?

Back 62

- Mitral Regurgitation

- 3-7 days post-MI

Front 63

When does pericarditis occur? What is it?

Back 63

- 2-3 days post-MI
- Inflammation of the pericardium of the heart

Front 64

What are some late complications of MI?

Back 64

- Ventricular aneurysm
- Progressive heart failure

Front 65

What is a mural thrombus?

Back 65

- Mural thrombi are thrombi adherent to the vessel wall
- They are not occlusive and affect large vessels, such as heart and aorta

Front 66

What is the prognosis of acute MI?

Back 66

- Depends on infarct size, site, and transmural extent
- Long-term prognosis depends on quality of LV function and extent of vascular obstruction

Front 67

What are the morphological characteristics of Chronic Ischemic Heart Disease?

Back 67

- Enlarged heavy heart
- LV hypertrophy and dilation (blood back up leads to dilation)
- Coronary AS
- Scars
- Subendocardial myocyte vacuolization

Front 68

What kind of patient gets chronic ischemic heart disease?

Back 68

Elderly patient w/ progressive heart failure d/t ischemic myocardial damage

Front 69

What are the two causes of Chronic Ischemic Heart Disease?

Back 69

- Post-infarction cardiac decomposition (exhausts remaining hypertrophic fibers)
- Severe coronary artery disease w/o infarction but w/ myocardial dysfunction

Front 70

What happens in Sudden Cardiac Death?

Back 70

- Unexpected death from cardiac causes, early after or without onset of symptoms
- Caused by lethal arrhythmia (asystole or V fib)

Front 71

What is the most common cause of Sudden Cardiac Death?

Back 71

- Lethal arrhythmia (asystole or V fib)
- Most often d/t ischemic heart disease

Front 72

What percentage of people who die from sudden cardiac death had ischemic heart disease?

Back 72

80-90%

Front 73

What are the non-atherosclerotic causes of Sudden Cardiac Death?

Back 73

- Hypertrophy
- Cardiac conduction system abnormality
- Mitral valve prolapse
- Congenital abnormality
- Myocarditis
- Cardiomyopathy
- Pulmonary HTN

Front 74

What are the morphological characteristics of Sudden Cardiac Death?

Back 74

- Coronary atherosclerosis
- Acute plaque change
- MI
- Scars from old MIs
- Pathology associated with non-atherosclerotic causes

Front 75

What are the potential outcomes of coronary artery disease progression?

Back 75

- Immediate myocardial ischemia
- Acute plaque change → coronary artery thrombosis → myocardial ischemia of increased severity and duration

Front 76

What can precipitate a myocardial infarction?

Back 76

- Coronary Artery Disease →
- Acute plaque change; coronary artery thrombosis →
- Myocardial ischemia of increased severity and duration →
- Myocardial Infarction (MI)

Front 77

What are the outcomes of a Myocardial Infarction?

Back 77

- Infarct healing
- Ventricular remodeling
- Hypertrophy, dilation of viable muscle

All progress to chronic ischemic heart disease

Front 78

What events precipitate chronic ischemic heart disease?

Back 78

- Myocardial ischemia progression
- MI followed by infarct healing, ventricular remodeling, or hypertrophy / dilation of viable muscle

Front 79

What are the outcomes of chronic ischemic heart disease?

Back 79

- Immediate sudden cardiac death
- Congestive heart failure → sudden cardiac death

Front 80

What can precipitate sudden cardiac death?

Back 80

- Myocardial ischemia
- Congestive heart failure
- Chronic ischemic heart disease
- Myocardial ischemia of increased severity and duration
- Myocardial infarction