SM 127a/128a - Ischemic Heart Disease Pathogenesis and Pathology Flashcards
Which anti-ischemic agents work to decrease O2 demand and increase O2 supply?
Nitrates
Ca2+ channel blockers
What is hypoxia?
Common causes?
Decreased oxygen supply to a tissue with normal perfusion
Cyanotic congenital heart disease, anemia, CO poisoning
Describe the morphology of the heart 1 week - 1 month after infarction
- Necrotic muscle is resorbed
- Fibrous tissue becomes a myocardial scar
- Thin, strong
- Low risk of rupture
- Prone to aneurysm
What is the gold standard for diagnosing ischemic heart disease?
Why isn’t it always performed?
Coronary angiography
- Catherization
- Inject radiographic dye for contrast
It is not used all the time because it is invasive
Describe the morphology of a later (6-12 hour) myocardial infarction
- Contraction band necrosis
-
Coagulative necrosis (cell outlines but no centers)
- Muscle fibers are eosinophilic (red)
- Pyknosis of nuclei
- Shrinkage and darkening
Thrombosis in ____________ would cause infarction in the Lateral LV wall
Left Circumflex Artery
How would increased intraventricular pressure affect coronary blood flow?
Increased intraventricular pressure would decrease coronary blood flow
Describe Class II Angina
Slight limitation of ordinary activity
Angina with…
- Walking or climbing stairs rapidly
- Walking uphill
- Exertion after meals
- Cold weather
- Emotional stress
- The first few hours after awakening
Describe the characteristics of a subendothelial MI
- Ischemic necrosis in the inner 1/3-1/2 of the ventricular wall
- NOT associated with intraluminal thrombosis
What are the indications for myocardial revascularization?
- Failure of pharmacologic therapy
- Progression of symptoms
- Intolerable side effects of pharmacologic therapy
- Compelling anatomy
- Severe cardiac dysfunction
- Ejection fraction < 40%
- Low threshold for ischemia
- Ex: at rest, or more severe classification
How do renin/angiotensin inhibitors work to treat ischemic heart disease?
Renin/Angiotensin agents…
- Decrease blood pressure -> reduce chance of thrombotic event
- Inhibit progression of atherosclerosis -> Increase vascular integrity (prevent rupture)
This reduces the risk of clot formation that could completely occlude a coronary artery
After MI, when is the heart most vulnerable to rupture? Why?
(When is its mechanical integrity weakest?)
- 3-7 days after infarct
- Dead muscle is replaced by macrophages and reparative cells
- Everything is soft and inflammed
- Repair has not yet begun
What 4 clinical syndromes may result from ischemic heart disease?
- Angina pectoris
- Myocardial infarction
- Chronic ischemic heart disease
- Sudden cardiac death
Describe the timeline of ATP loss due to cardiac ischemia
- <2 min: Noticible decrease in contractility
- 10 min: 50% ATP loss
- 40 min: 90% ATP loss
- 1 hour: Myovascular injury
- Reperfusion at this point leads to hemorrhage
Which angina class is described as:
“Ordinary activity does not cause angina - Angina with strenuous, rapid, or prolonged exertion only”
Angina Class I
What is CABG?
Coronary Artery Bypass Surgery: Surgical intervention for ischemic heart disease
- Arterial and/or venous conduits are places in the mid to distal coronary arteries
- The stenosis is proximal to the conduit
- Leave occlusion in place; make new paths around it
- This increases blood flow to the ischemic myocardium
- Vein remodels and becomes revascularized
- Use in more severe cases or if multiple occlusions exist
After MI, when would you begin to see infiltration by neutrophils?
12-24 hours
(peak 3 days after infarct)
List the 4 major causes of myocardial infarction
- Thrombosis of a coronary artery (leading cause)
- Usually due to ulceration or rupture of an atheromatous plaque
- Infarct without thrombosis
- Lysis of thrombus or arterial spasm (rare)
- Thromboembolism
- Arteritis or dissection (rare)
Describe the mechanism of action of Ranolazine
Ranolazine closes the late inward Na+ gate
- Less Na+ in = less Na+/Ca2+ exchange
- Prevents Ca2+ overload that leads to arrythmia
- Does not alter HR or BP
What are the pros and cons of PTCA as treatment for ischemic heart disease?
- Pros
- It is effective!
- Cons
- Metal may induce re-occlusion due to proliferation of endothelium in response to inflammation
- It must damage the vessel in order to expand the lumen
- This can cause rupture or hemorrhage
When would you expect total creatine kinase to rise, peak, and return to normal after MI?
What about the MB subform of creatine kinase?
- Total Creatine Kinase
- Rise after 4-6 hours
- Peak 24h
- Return to normal after 3-4 days
- MB subform
- Peak <24h
- Return to normal after 2 days
What 3 cell types would you expect to find in an ischemic myocardium?
- Necrotic myocytes
- Interstitial hemorrhage
- Reversibly injured “stunned” myocytes
What is anoxia?
Complete lack of oxygen supply to a dissue despite normal perfusion
What is atypical angina?
Angina in an atypical location, or not related to typical provoking factors
More common in women, diabetic patients
Desribe the mechanism of action of Nitrates
Nitrates increase cGMP to promote myocardial relaxation and aterial dilation to decrease O2 demand and increase O2 supply
- Venodilation
- -> Decreased myocardial wall tension
- -> Increaesd myocardial blood flow
- -> Decreased myocardial wall tension
Which coronary is the most common site for thrombosis?
Left anterior descending artery (40%)
Right coronary artery (27%)
Left circumflex artery (11%)
What structures of the heart are supplied by the right coronary artery (RCA)?
- Anterior right ventricle
- Posterior 1/3 fo the IV septum
- Posterior right ventricle
- Part of the posterior left ventricle
Which anti-ischemic agent prevents arrhythmia and does not alter blood pressure or heart rate?
Ranolazines
(works by closing late inward Na+ gate -> reduces Na+/Ca2+ exchange -> prevents Ca2+ overload)
Describe the mechanism of action of Ca2+ channel blockers in treating ischemia
Ca2+ channel blockers decrease Ca2+ entry into myocardial and atrial smooth muscle
- Decreases oxygen demand
- Decrease HR
- Decrease blood pressure
- Decreaes contractility
- Increases oxygen supply
- Increase ventricular relaxation
- Increase dilation of coronary arteries
- Prevents coronary arterial spasm
When would you expect myoglobin to rise, peak, and return to normal after MI?
- Rise 2h after infarction
- Peak 6-8 h
- Return to normal after 20-36
When would you expect lactate dehydrogenase to rise, peak, and return to normal after MI?
- Rise begins at 24h
- Peak after 3 days
- Return to normal after 8-9 days
How would reduced aortic diastolic pressure affect coronary blood flow?
Reduced aortic diastolic pressure would reduce coronary blood flow
What is ischemia?
O2 deprivation + inadequate removal of metabolites due to reduced perfusion
Describe the morphology of an early (1-6 hour) myocardial infarction
- No gross or light microscope findings
- Electronic microscope reveals…
- Wavy “lasagna noodle” muscle fibers
- Leakage of myocardial enzymes (can be detected with dye)
After myocardial infarction, rupture of which walls would most likely lead to cardiac tamponade?
When is this likely to occur?
Free walls
- Anteror, lateral, or posterior walls of LV
Most likely to happen 3-7 days after infarction, when the heart is most vulnerable
- Everything is soft and inflammed
- Repair has not yet begun
When would you expect Troponin to rise, peak, and return to normal after MI?
- Rise in 4-6h
- Peak 12-16 h
- Return to normal after 10+ days
What are the goals of treatment for angina pectoris?
- Symptom control to increase quality of life
- Prevention of life-threatening complications
- MI, death
- Prevention of disease progression
Which enzyme assay to diagnose MI rises most quickly after infarction?
Myoglobin
What pathology are myocardial scars prone to?
Aneurysm
How do lipid lowering agents (statins) work to treat ischemic heart disease?
- Inhibit progression of atherosclerotic lesions
- Prevent further coronary artery occlusion
- Reduce the risk of plaque rupture -> thrombosis -> complete occlusion
- Promotre regression of atherosclerotic lesions
After MI, how when would you begin to see coagulative necrosis?
6-12 hours
Describe the mechanism of action of beta-blockers
Beta blockers are competitive antagonists of epinephrine/norepinephrine
- They block beta 1 receptors in the heart
- Decrease pulse
- Decrease arterial blood pressure
- Decrease myocardial contractility
-
This decreases myocardial O2 demand
- Prevents exercise-incuced increase in contractility
In a myoglobin assay to diagnose MI, what might cause a false positive?
Renal failure
Skeletal muscle injury
What are the two major types of anti-ischemic Ca2+ channel blockers?
How are they different?
- Dihydrophyridines
- Arterial vasodilators
- Side effect = Pedal edema
- Non-Dihydropyridines
- Decrease HR
- Less effect on blood pressure
- Side effect = bradycardia, heart failure
- Do not prescribe with other medications that lower HR (beta blokers), or in patients with LV dysfunction
Describe Class III Angina
Marked limitations of ordinary physical activity
Angina on…
- Walking 1 or 2 blocks on level ground
- Climbing 1 flight of stairs at a normal pace under normal conditions
What structures of the heart are supplied by the Left Anterior Descending Artery (LAD)?
- Anterior surface of the left ventricle
- Partial anterior surface of the right ventricle
- Anterior 2/3 of the IV septum
- Apex
Describe the morphology of an MI 3-7 after the initial infarct
- Dead muscle is replaced by macrophages and reparative cells
- Proliferating fibroblasts and capillaries
- Low mechanical integrity
- Most prone to rupture, especially after transmural MI
- Everything is soft and inflammed
- Repair has not yet begun
- Rupture -> Cardiac tamponade -> Death
How would decreased right atrial pressure affect coronary blood flow?
Decreased right atrial pressure would increase coronary blood flow
Thrombosis in the Left Anterior Descending artery would cause infarction which sections of the myocardium?
- Anterior LV wall
- Anterior interventricular septum
Which anti-ischemic agents work to decrease O2 demand (without changing O2 supply)?
Beta blockers
Why does hypertension increase one’s risk of myocardial infarction?
High blood pressure puts additional stress on the fibrous caps of any existing atherosclerotic plaques
- This increases the chance of plaque rupture
- Plaque rupture -> thrombosis
Thrombosis of a coronary artery = leading cause of MI
Which angina class is described as:
“Marked limitations of ordinary physical activity - Angina on walking 1 or 2 blocks on level ground or 1 flight of stairs at a normal pace under normal conditions”
Class III Angina
Describe the characteristics of a transmural MI
- Ischemic necrosis affecting nearly all of the ventricular wall thickness
- Severe fixed atheromas + intraluminal thrombosis
- Develops from endocardium -> outward
- Subendocardial myocardium is the first affected, because it is at the most distal end of the coronary artery
What are anginal equivalents?
Symptoms of myocardial ischemia other than angina
- Dyspnea
- Nausea
- Fatigue
- Faintness
More common in women, elderly people, diabetics
Which angina class is described as:
“Slight limitation of ordinary activity - Angina with walking or climbing stairs rapidly, walking uphill, or exertion after meals, in cold weather, under emotional stress, or only during the first few hours after awakening”
Class II Angina
What enzymes can be used to diagnose MI?
Which are most commonly used?
- Troponin T (most commonly used)
- Troponin I
- Troponin L (new)
- Creatine kinase
- Total or MB (specific for cardiac muscle)
- Lactate dehydrogenase
- Myoglobin (not commonly used)
What is PTCA?
Percutaneous transluminal coronary angioplasty: surgical intervention for ischemic heart disease
- Dilate coronary artery
- Insert a metal stent
- May be drug-eluting
What are the major side effects of Nitrates in treating ischemic heart disease?
Lightheadedness
Headache
Tolderance develops (don’t take the medication at night, allows for re-set)
Which angina class is described as:
“Inability to carry on any physical activity without discomfort, or angina at rest”
Class IV Angina
What are the major classes of pharmacologic intervention for ischemic heart disease?
List major drug types in each class
- Anti-Ischemic agents
- Nitrates
- Beta-blockers
- Ca2+ Channel blockers
- Ranolazine
- Antiplatelet agents
- Anti-hypertension medication
- Renin/angiotensin inhibitors
- Lipid lowering agents
How do antiplatelet agents work to treat ischemic heart disease?
Decreaseing platelet aggregation prevents thrombotic events that could cause complete occlusion of a narrow artery
What causes the majority of all myocardial infarctions?
Thrombosis of a coronary artery
Forms at the site of an ulcerated or ruptured atheromatous plaque
Thrombosis in ____________ would cause infarction in the anterior LV wall and/or the anterior interventricular septum
Left Anterior Descending artery
In a lactate dehydrogenase assay to diagnose MI, what might cause a false positive?
Lactate dehydrogenase is found in many different muscle types
- Heart muscle
- Skeletal muscle
- Liver
- RBC
- Kidney
- Neoplasms
Which isoenzymes of lactate dehydrogenase are relevant to MI?
LD1: Heart, RBC, renal
LD2: Reticuloendothelial
Reversal lf LD1 : LD2 implies MI
Describe Class I Angina
“Ordinary activity does not cause angina - Angina with strenuous, rapid, or prolonged exertion only”
What is angina pectoris?
Pain or discomfort in the chest or adjacent areas caused by insufficient blood flow to the heart
- May be stable or unstable
- 4 clinical types
- Chronic, stable angina
- Atypical angina
- Anginal equivalents & silent ischemia
- Other
What are the 2 types of myocardial infarction?
Transmural
Subendothelial
Which patients should not recieve non-dihydropyridine Ca2+ channel blockers as treatment for ischemic heart disease?
Patients with LV dysfunction
Patients taking another medication that lowers heart rate
(non-dihydropyridine Ca2+ channel blockers lower HR)
Which structures of the heart are supplied by the left circumflex artery?
- Lateral left ventricle
When is CABG used over PTCA?
In more severe cases, or if multiple occlusions exist
How would increased myocardial contraction affect coronary blood flow?
Increased myocardial contraction would decrease coronary blood flow
What would happen to perfusion if there was no difference between the aortic diastolic pressure and the right atrial pressure?
Perfusion would cease
Thrombosis in ____________ would cause infarction in the posterior LV wall and/or the posterior 1/3 of the interventricular septum
Right Coronary Artery
Describe the morphology of a 12-24 hour myocardial infarction
- Infiltration by neutrophils (peak in 3 days)
- Sign of inflammation
- Muscle cells lose nuclei and cross-striations
How can reperfusion injury after surgery be prevented?
- Use cardioplegic solution
- Selective perfusion agent that helpts ot prevent reperfustion injury
- Hypothermia during surgery
- Decrease the O2 needs of the heart to reduce imbalance between demand and supply
What causes reperfusion injury?
After ischemia, reinroduction can cause death to vulnerable myocardial tissue
Possibly due to ion mismatch: Ca2+ rushes in, causing Z-lines to condense
Also may be due to rapid generation of ROS
Thrombosis in the Right Coronary artery would cause infarction which sections of the myocardium?
- Posterior LV wall
- Posterior 1/3 of the interventricular septum
List the 5 possible pathogenesis of ischemic heart disease
- Stenosing atherosclerosis of coronary arteries
- Platelet aggregation + formation of intramural thrombus
- Coronary vasospasm
- Nonatherogenic coronary disease
- Hemodynamic derangements
How what tools and evidence help to diagnose ischemic heart disease?
- ECG
- “Exercise stress test”
- ST depression or elevation
- T wave changes
- Scintigraphy (Radioactive tracer)
- “Nuclear stress test”
- Can see which areas are not perfused
- Echocardiogram
- Ischemic area will contract poorly -> wall motion abnormality
- CT Angiography
- Coronary angiography (Gold standard, but invasive)
What are the 2 major clinical presentations of coronary atherosclerosis?
- Sudden reduction in blood flow due to plaque rupture -> Acute coronary syndrome
- Progressive narrowing due to negative remodeling -> Angina upon exertion
- Vessel cannot increase blood flow to meet increased oxygen demand due to exercise
Why are Troponin T and Troponin I assays the most popular for diagnosing MI?
- They are specific to cardiac muscle
- They are both sensitive and specific
- Assay only takes 30 min to 1 hour
What are the 3 major categories of treatment for ischemic heart disease?
- Lifestyle modification
- Pharmacologic intervention
- Myocardial revascularization
What are the clinical types of angina?
- Chronic, stable angina
- Atypical angina
- Anginal equivalents & silent ischemia
(Shortness of breath) - Other
Decubitus, nocturnal, refractory, unstable, microvascular, neoplastic….
Describe Class IV Angina
- Inability to carry on any physical activity without discomfort
OR
- Angina at rest
Thrombosis in the Left Circumflex artery would cause infarction which sections of the myocardium?
Lateral LV wall
What complications may arise after MI?
SACC PDF
- Sudden cardiac death
- Aneurysm with mural thrombus formation
- Congestive heart failure
- Cardiac arrhythmia
- Papillary muscle dysfunction with valvular (esp. mitral) valve dysfunction
- Dressler’s syndrome (fibrinous pericarditis)
- Free wall rupture -> Tamponade
What are the major risk factors for ischemic heart disease?
“HAS LIPIDS”
- Heretity
- Age
- Sex (male)
- Lipidemia
- Increased weight
- Pressure (is high)
- Inactivity
- Diabetes
- Smoking
List some examples of Ca2+ channel blockers
In general: -dipine, -il- (somewhere in the word_
Amlodipine
Felodipine
Nifedipine
Verapamil
Diltiazem
What kind of drug is Nifedipine?
An anti-anginal Ca2+ channel blocker
(and other -dipine drugs)