SM 127 Ischemic Heart Disease: Pathology Flashcards
When is a myocardial infarct most likely to rupture?
Between 3-7 days after onset of ischemia, due to replacement of dead cardiomyocytes with fibroblasts
Why are women less likely to develop IHD?
Protective effects of Estrogen; wears off in PMP women
What time frame is an early MI?
Early MI is < 6 hours after the onset of ischemia
Where do thrombi form on stents?
Thrombi form directly on the implanted stent, ironically causing the same issue the stent is trying to fix
What is LDH?
Lactate Dehdyrogenase is an enzyme found in heart, skeletal muscle and liver, erythrycoytes, and kidney
Commonly elevated in MI but also other diseases in many organs
Peaks in 3 days, several isozymes L1-L5
Why is cardioplegia able to avoid reperfusion injury?
Inhibits ischemic injury by reducing the oxygen needs of the heart via asystole
Why does cardiac surgery involve myocardial injury?
Cardiac surgery requires a bloodless field, achieved by clamping the Aorta
Aortic clamping leads to ischemic injury, unclamping leads to reperfusion injury
How is MI diagnosed in lab?
Cardiac enzymes are used to diagnose an MI, but elevations in enzyme levels are not specific for any mechanism of injury
Need to correlate with ECG and clinical findings
What encompasses coagulative necrosis in an MI?
Muscle fibers stain more intensely red and their nuclei under go pyknosis, between 6-12 hours
Compare and contrast transmural to subendocardial MI?
Transmural MI involves most or all of the ventricular wall, usually due to a fixed lesion with severe occlusion of a coronary artery due to a thrombi
Subendocardial MI involves the inner half of the ventricular wall, and is not associated with intraluminal thrombosis; due to high sensitivity of subendocardium to ischemia
What causes Ischemic Heart Disease?
A mismatch between oxygen supply and demand
What factors reduce coronary blood flow?
Decreased aortic diastolic pressure Increased IV pressure and myocardial contraction Coronary artery stenosis Aortic valve stenosis/regurgitation Increased right atrial pressure
How does cardiac tamponade follow MI?
Transmural infarcts during the period of time 3-7 days after an MI are very likely due to fibroblasts not yet fully replacing dead cardiomyocytes, making the dead portion of the heart susceptible to rupture
If the ruptured portion of the heart is on any face of the LV that faces the outside of the heart (not the IV septum), blood can escape and fill the pericardial sac, resulting in cardiac tamponade and SCD
Why can reperfusion be dangerous following a period of ischemia?
Injury may be reversible or irreversible, and although eventual reperfusion is necessarycan lead to myocardial stunning and irreversible cell damage
Why are occlusions early in arteries more dangerous?
More dependent tissue downstream at higher portions of an artery, leading to greater effect/ischemia in earlier occlusions
What is the LD1/LD2 ratio?
Ratio of LD1 (heart LDH) to LD2 (reticuloendothelial LDH)
Reversal of LD1/LD2 ratio indicates MI
Infarcts of the LAD affect what areas?
Anterior LV free wall and anterior Septum
What are “stunned” myocytes?
Myocytes that are not contracting due to lack of oxygen supply but have not yet undergone irreversible damage or cell death
What are the risk factors for IHD?
HASLIPIDS
Heredity Age Sex (M > F) Lipidemia Increased Weight (Obesity) Pressure (Hypertension) Inactivity Diabetes Smoking
How do coronary stents give rise to plaques?
Insertion of a foreign object promotes plaque formation, as does vessel stretch caused by stent insertion which can tear the vessel itself and predispose clot formation
When does coagulative necrosis occur in an MI?
Changes begin around 6-12 hours following onset of ischemia
Why do venous grafts form thrombi if atherosclerosis is restricted to arteries?
Venous grafts link arteries using transplanted veins, and the transplated venous vessel is subjected to high pressures, “arteriolizing” them and predisposing atherosclerosis
What is Troponin?
A contractile protein of the myofibril with highly specific cardiac isoforms; frequently assess Troponin I and L
Peaks in 12-16 hours
What is cardioplegia?
Stopping cardiac activity, often given as a solution that avoid ischemic injury through hypothermia and asystole
What findings can be found in an early MI?
Mitochondrial changes can be observed with EM
“Wavy” muscle fibers due to stunned myocytes not contracting and instead being pulled around by other contracting myocytes
What factors effect infarction size and location?
Duration of occlusion, size of artery and vascular bed effected, extent of collaterals, extent of spasm
What portion of the cardiac wall is most susceptible to injury?
The subendocardium
When do cardiac myocytes lose their nuclei and cross-striations?
Between 12-24 hours, and the infarct becomes infiltrated with neutrophils
What does the Right Coronary Artery supply?
Anterior right ventricle
Posterior 1/3 of the IV Septum
Posterior surface of the right and left ventricle
Are there anastomoses between the three major coronary arteries?
Yes, but they are poorly developed
Infarcts of the Right Coronary affect what areas?
Posterior LV free wall, posterior Septum
What is vascular remodelling and why does it not protect against most MI?
Following occlusion, vascular bed remodels to compensate for loss of blood flow; slow process that cannot respond to rapid onset MI
Compare and contrast: Hypoxia, Anoxia, Ischemia?
Hypoxia = reduced Oxygen supply with normal perfusion Anoxia = absence of oxygen despite normal perfusion Ischemia = oxygen deprivation due to reduced perfusion
How can an aneurysm lead to MI?
Aneurysms allow for blood to pool in the thin ballooned out portion of an artery, which can result in thrombi formation that blocks a coronary vessel leading to MI
What plaques are most likely to cause an MI?
MI is frequently due to thrombosis of a coronary artery, with the thrombi dislodging from a ruptured atheromatous plaque
Plaques that are contained with a thin fibrous cap or in high pressure change areas are more likely to rupture
How do scars form following an MI?
Fibroblasts invade 3-7 days after ischemia ensues and replace dead cardiomycotes, forming a thin but stable scar that may form an aneurysm
What are the presentations of Ischemic Heart Disease?
Chest Pain
Myocardial Infarction
Chronic Ischemic Heart Disease = scarring and heart failure
Sudden Cardiac Death
What does hypertrophy of the heart indicate?
Increased systemic oxygen demand
Outline the pathogenesis of Ischemic Heart Disease?
Stenosing atherosclerosis of coronary arteries
Platelet aggregation and formation of intraluminal thrombi
Coronary vasospasm
Nonatherogenic coronary disease
Hemodynamic derangements
What is myoglobin?
Protein found in striated muscle, in circulation after damage to skeletal or cardiac muscle
Peaks 6-8 hours after MI
False positives due to skeletal muscle injury and renal failure
Why is oxygen delivery dependent on coronary flow?
The heart extracts nearly all oxygen from blood at baseline, so increased flow is the only way to increase oxygen delivery
Define Sudden Cardiac Death
Death within 1 hour of symptoms, often times the first manifestation of IHD
Infarcts of the Left Circumflex affect what areas?
Later LV free wall
What does the Left Circumflex supply?
Lateral left ventricle
What is the MB fraction?
The fraction of total CK that is from heart muscle, rises and normalizes sooner than total CK
How can cardiac ischemia lead to hemorrhage?
After 1 hour of cardiac ischemia, microvascular injury occurs
Once vessels are injured and “leaky”, reperfusion results in blood escaping the vessels and hemorrhaging
What attributes of a plaque set the risk for life threatening outcomes?
Composition and vulnerability of a plaque to rupture matter more than volume or severity of stenosis in progression to MI
Lipid rich and soft plaques are more likely to rupture than collagen rich and hard plaques, generating thrombi that block coronary arteries and lead to MI
What are the most common sites of thrombosis in the coronary circulation?
LAD, Right Coronary, Left Circumflex in a 3:2:1 ratio
What is contraction band necrosis?
Common in MI, due to thickened increased Calcium permeability causing influx and a thickened Z line
How is CK used to detect MI?
Creatine Kinase is found in the heart, skeletal muscle, and brain
CK is commonly elevated in MI, but can also be elevated in muslce trauma and delirium
Peaks 24 hours after MI and returns to normal after 4 days
Where are coronary arteries normally found, and what pathologies can be associated with them?
Coronary arteries normally found on epicardium
May be found in the walls of muscle as well, which predisposes occlusion during contraction leading to SCD
What is the preferred marker for MI and why?
Troponin T and I, the contractile proteins of myofibril with specific cardiac isoforms not present in healthy individuals
What are the complications following MI?
SCACFDP
Sudden Cardiac Death Congestive Heart Failure Aneurysm with Mural Thrombus Cardiac Arrythmia Free wall rupture into cardiac tamponade Dressler's syndrome Papillary muscle dysfunction
What does the Left Anterior Descending artery supply?
Anterior surface of and right ventricles
Anterior 2/3 of IV septum
Apex
