Seventeen

Question 1

What are 3 general categories of things that can lead to ischemic heart disease? What are examples of each?

Answer 1

1. Conditions that alter balance between oxygen supply and demand to the heart can lead to myocardial ischemia.
   a. Decreased blood flow

i. Coronary Artery Disease (CAD): In 90% of cases, IHD is usually due to coronary artery obstruction by atherosclerotic coronary artery (CA) lesions. IHD is often used synonymously with CAD.
1. Aggravated by
a. Increased demand (i.e., hypertrophy, tachycardia)
b. Hypoxia, hypotension
b. Decreased oxygen supply
c. Increased myocardial oxygen demand (i.e., increased cardiac work)
ii. CA emboli
iii. CA spasm
iv. Small myocardial vessel injury (e.g., vasculitis as with polyarteritis nodosa or Kawasaki disease)
v. Low systemic blood pressure (i.e., hypotension, shock)

b. Decreased oxygen supply
i. Anemia (also increases workload because increased output is required to oxygenate organs.)
ii. Cyanide intoxication
iii. Carbon monoxide intoxication: The high affinity of CO for hemoglobin displaces oxygen. This decreases tissue oxygen. Cigarette smoking increases CO in blood.

c. Increased myocardial oxygen demand
i. Hypertension
ii. Valve stenosis or insufficiency
iii. Hyperthyroidism increases metabolic and heart rate.
iv. Fever increases BMR, CO, and HR
v. Thiamine deficiency
vi. Catecholamines

Question 2

Generally, what happens in CAD?

Answer 2

There is chronic progressive atherosclerotic plaques in the epicardial CA. Eventually, there is an acute plaque change that occurs with thrombosis or vasospasm.

Question 3

Explain the chronic atherosclerosis that occurs in CA?

Answer 3

Fixed obstruction with slow development of plaque build up in CA. Less than 75% occluded will still receive maximal blood flow. More than 75% will be symptomatic only during exertion. Over 90% obstruction will be symptomatic at rest. Slow development allows growth of collateral circulation.

Question 4

Explain the acute plaque changs that occur in CAD?

Answer 4

Disruption: Plaque rupture, superficial erosion, ulceration, fissuring, or hemorrhage can turn a stable plaque unstable and thrombogenic. With acute syndromes (MI, unstable angina, or sudden cardiac death), the pt. generally has a history of preexisting fixed atherosclerotic plaque with a new superimposed thrombus and/or vasospasm. Thrombus occurs when thrombogenic plaque lipids are exposed to blood coagulation. Hemorrhage into a plaque can increase its volume and be an initiating event.

Question 5

What is the clinical presentation of IHD?

Answer 5

1. Angina Pectoris
2. MI
3. Chronic IHD with heart failure
4. Sudden Cardiac Death

Question 6

What is angina pectoris?

Answer 6

Chest pain. Most common symptom of IHD. Pts have substernal, paroxysmal, recurrent pains or discomforts due to ischemia (squeezing, constricting, etc.). Not sufficient to cause cell death.

Question 7

Describe 3 overlapping patterns of angina.

Answer 7

Stable, typical: Pain occurs 1-15 minutes during exercise (75% obstruction). Not associated with acute plaque change. Typically due to subendocardial ischemia. Can also occur due to CA vasospasm, aortic stenosis, aortic insufficiency. Relieved by rest or nitroglycerin.

Prinzmetal, variant angina: Less common. Occurs at rest due to CA spasm. Relieved by vasodilation. Likely due to CA atherosclerosis, but there is also increased reactivity of vessels leading to vasoconstriction and platelet activity (TXA2). Transmural ischemia.

Unstable, crescendo, accelerated, or preinfarction: Increasingly frequent pain caused by progressively less activity or at rest. Usually associated with a non-occlusive thrombus over a plaque. Due to disruption of a plaque with partial (mural) thrombosis with or w/o embolization or vasospasm. Warning of an acute MI.

Question 8

What is a myocardial infarction? What is the incidence, risk factors? Describe the symptoms. What is a silent MI/what causes one? How commonly do MI lead to death? What labs indicate an MI and what is the timetable?

Answer 8

Discrete focus of necrosis or cardiac muscle due to prolonged ischemia (not due to drugs toxins, etc.

Incidence rises with age, smoking, obesity, diabetes. More in men than women (premenopausal). Whites and AAs equally affected.

Severe substernal chest pain radiating to neck, jaw, epigastrium, or left arm for 20 min. to several hours. Not relieved by nitroglycerin. Diaphoresis, nausea, dyspnea..

Silent MI: No symptoms. Common in diabetics, elderly, and heart transplant pts.

TnI and TnT are in blood after 2-4 hours. Peak at 48 hours and stick around for 7-10 days
CK-MB in blood after 2-4 hours. Peak at 24 hours. Gone after 72 hours.
If these levels are unchanged at 24 hours, its not an MI.

Question 9

What is the general pathogenesis of an MI?

Answer 9

Atherosclerosis causes CA Occlusion

1. Sudden change in plaque-hemorrhage, erosion, ulcer, rupture, fissure.
2. Platelets adhere to subendothelial collagen, necrotic plaque contents, and activate and aggreggate leading to microthrombi.
3. Mediators from platelets cause vasospasm.
4. Tissue factor activates coag pathway leading to thrombus and occllusion.
5. Some occlusions resolve on their own due to fibrinolysis and/or relaxation of spasm.

Question 10

What is the pathogenesis of an MI without significant atherosclerosis? What are some causes?

Answer 10

1. Vasospasm (platelet aggregation, cocaine)
2. Embolus from left heart with afib, mural thrombus, vegetations, prosthetic material, paradoxical embolus.
3. Small vessel disease as in vasculitis, hematogic disorders, amyloid deposition in vessels, shock.

Question 11

What is the myocardial response to the reversible changes of ischemia

Answer 11

1. Aerobic metab. stops in seconds leading to decreased ATP and the accumulation of metabolites (lactic acid)
2. Cell, mitochondrial swelling, glycogen depletion seen by EM in minutes.
3. Severe ischemia causes loss of contractility in 1 minute which can lead to acute heart failure before cell death.

Question 12

What is the myocardial response to the irreversible changes of ischemia? Treatment.

Answer 12

20-30 min more of severe ischemia leads to myocyte necrosis in the distribution of the obstructed vessel:

1. Defects in the sarcolemmal membrane allow macromolecules to leak from the cell into the interstitium, microvasculature.
2. Permanent damage occurs if perfusion is severely reduced for an extended interval (at least 2-4 hours) and necrosis is complete after 6 hrs. of severe ischemia.

Rapid treatment (angioplasty, streptokinase or tPA, stent) can estabilish reperfusion, salvage ischemic myocardium.

3. Necrosis occurs first in subendocardium (zone that is least perfused) progressing in most cases to transmural necrosis.

Question 13

Explain what transmural and subendocardial necrosis is, where most MIs are and what patterns of necrosis this leads to?

Answer 13

a.Most MIs are transmural and involve part of the LV.

b. Isolated infarctino of the RV or atria is unusual (increased SVR and greater thickness of the LV wall).
i. if there is RV hypertrophy, the risk increases.

c. subendocardial infarcts can also occur with severe global hypoperfusion (shock superimposed on CA stenosis). This leads to a circumferential infarct, not just in distribution of a CA.
d. A .1 mm rim of subendocardium is maintained by diffusion of oxygen and nutrients from ventricular lumen.

Question 14

What do the location, size, morphology of acute Mi depend on?

Answer 14

1. Location, rate, and severity of CA
2. Size of vascular bed supplied by obstructed CA.
3. Duration of occlusion
4. Amt. of collateral vessels (can increase time to necrosis)
5. myocardium metabolic/oxygen requirements
6. Present, site, and severity of CA spasm
7. HR, rhythm, oxygenation

Question 15

Describe the stepwise morphology of an MI including timeline.

Answer 15

1. Less than 12 hrs, nothing on gross exam, by EM see edema, mitochondrial swelling, and loss of glycogen.
2. 12-24 hours. Mottled red-blue due to pooled up blood. Coag necrosis, early inflammatory response.
3. 1-3 days. Mottled with yellow pale tan center. Coag necrosis with acute inflammation with karyorhexis.
4. 3-7 days. Mottled, sharpyly outlined. Macrophages remove necrotic myocytes. This is the point where rupture is most likely to occur.
5. 10-14 days. Sharply defined yellow tan soft area with surrounding hyperemic granulation tissue.
6. 2-8 weeks: Grey white scar from edge to center, depressed.
7. greater than 2 months, Fire contracted scar complete.

Question 16

What are some consequences of MI?

Answer 16

Non-infarcted Mi undergoes remodeling (hypertrophy then dilatation). Hypertrophic myocytes have a higher oxygen demand which increases chances of ischemia and less efficient contraction.

Question 17

What are some complications after MI?

Answer 17

1. Contractile dysfunction: cardiogenic shock leads to death.
2. Arrhythmias
3. Extension of infarct-occurs in first 2 weeks after event.
4. Myocardial rupture: LV free wall ruptures with hemopericardium, tamponade, and rapidly fatal course. Risk increased with women over 60 with preexisting hypertension. Risk decreased with history of prior MI due to scarring. Interventricular septum can rupture leading to acute VSD. Papillary muscles can rupture with acute MR.
5. Fibrinous Pericarditis: Transmural Mi affect the epicardium and cause inflammation of the pericardium in 10-20% of pts. Dressler syndrome (post MI syndrome) occurs 2-10 weeks after MI (or cardiac surgery), due to muscle antibodies directed to heart muscle antigens.
6. Mural thrombus: a thrombus forms over the area of infarction in about 1/3 to 1/2 of pts. Local stasis due to poor contractility +endocardial damage with thrombogenic surface due to the adjacent inflammation of the transmural infarct promotes platelet adhesion leading to mural thrombus.
7. Ventricular eneurysm: late complication of large transmural infarct occurs in 10-15% of pts. It is the result of localized thinning and stretching of the free wall of the ventricle in the region of the healing MI. Mural thrombi often develop in the aneurysm.

Question 18

Explain the clinical aspects and pathology of Chronic Ischemic Heart Disease.

Answer 18

Clinical: Progressive congestive heart failure due to ischemic myocardial damage. Usually there has been a prior MI and now there is functional decompensation of hypertrophied, noninfarcted myocardium. May progress to transplant (1/2 of transplants have IHD). These patients may die suddenly or die of progressive pump failure or multiorgan failure.

Pathology: Large, heavy heart with Lv hypertrophy and dilation and CA atherosclerosis, often with healed infarcts.

Question 19

What is sudden cardiac death? What causes it? How do you treat it?

Answer 19

Death due to lethal arrythmia (systole or vFib)

Usually caused by coronary artery atherosclerosis which will cause ischemia but not an MI. Also could be caused by vent. hypertrophy or a healed infarct.

Treat with pacemaker or cardioverter defibrillator.

Question 20

What are some non-atherosclerotic conditions associated with SCD?

Answer 20

Congenital heart malformations or CA abnormalities
Aortic valve stenosis
MVP
Myocarditis
Dilated or HCM (of any cause)
pulmonary hypertension
Hereditary or acquire arrythmia (long QT)
Drugs, including cocaine and meth

Question 21

What is the pathophysiology and pathology of SCD?

Answer 21

Pathphys: arrhythmia (ventricular) due to acute MI. Usually due to acute ischemia induced electrical instability of arrhythmogenic foci of myocardium distant from conduction system, sometimes near MI scars.

Path:CA atherosclerosis with greater than 75% obstruction. Might have acute plaque change.

May have CA disease with or w/o acute plaque disruption with thrombosis and 25% have acute MI changes.