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64 Cards in this Set
- Front
- Back
What is Ischemia?
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*Deficiency of blood flow in a part, due to functional constriction or actual obstruction of a vessel.
*An imbalance between supply and demand for oxygen. |
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What are the 4 Ischemic Cardiac Syndromes?
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1. Angina Pectoris:
-Stable (Typical) -Unstable (Crescendo...much more serious) -Variant (Prinzmetal--includes spasm of vessels) 2. Myocardial infarction. 3. Chronic IHD with CHF. 4. Sudden cardiac death. |
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Discuss Atherosclerotic IHD:
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*There is fixed narrowing:
-In 90% of patients with IHD. -Most lesions are PROXIMAL and epicardial. *There are acute plaque changes. *There is thrombosis. *There is vasospasm. |
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Diagram of CORONARY ARTERY DISTRIBUTION:
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A, anterior; AL, anterolateral; AS, anteroseptal; I, inferior; IL, inferolateral; P, posterior; PL, posterolateral; PS, posteroseptal; S, septal.
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*This is an autopsy specimen of a left main coronary artery with severe occlusion due to atherosclerosis.
*Yellow = plaque. |
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ATHEROMATOUS PLAQUE and its features.
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*ATHEROSCLEROSIS
*Note that the intima is NOT the only layer involved in atherosclerosis. *Fibrous cap (F). *Necrotic (lipid) core (C) --soft, prone to rupture. |
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What is the meaning of vascular narrowing?
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AREA = πr2
REDUCING THE DIAMETER BY 50% = REDUCTION OF AREA BY 75% |
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Discuss Fixed Lesions in CAD.
significant-- critical-- which ones are associated with angina? |
*A significant lesion has at least 50% reduction in diameter (75% x-s area).
*A critical lesion has at least 75% reduction in diameter (90% x-s area). *Stable angina pectoris is associated with fixed lesions (50 and 75%). *The demand is met at rest. *Symptoms develop with exertion. |
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Discuss Erosion as related to Unstable Angina:
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*Without penetration into the lipid core, partial occlusion secondary to PLATELET AGGREGATION may occur. *Microthrombi with microemboli to more peripheral coronary artery branches may also occur.
*Ischemia is exacerbated by vasoconstriction if endothelium secretes more vasoconstricting than vasodilating factors. |
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How do Acute Plaque Changes develop? What do they result in?
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1) Erosion of endothelium.
2) Plaque rupture. 3) Hemorrhage into necrotic core. 4) Thrombosis of blood in lumen. --> Thrombosis. |
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Discuss Rupture vs. Erosion:
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*When rupture occurs through the fibrous cap, blood is exposed to the contents of the highly thrombogenic core.
*Significant thrombosis is much more likely in rupture than in erosion. |
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Why Do Plaques Rupture?
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*In the atherosclerotic lesion, macrophages releasing metallo-proteinases contribute to destabilization and rupture. The released enzymes digest collagen in the fibrous cap.
*More likely if there's a greater than 40% core, a thin fibrous cap, many macrophages, few smooth muscle cells in fibrous cap – “vulnerable plaques.” |
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Pathogenesis of Coronary Thrombosis:
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1) Plaque rupture exposes blood to thrombogenic core and damaged endothelium.
2) Increase in thromboxane A and other platelet contents. 3) Platelets are activated. 4) Tissue thromboplastin is released. |
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What happens when you have an occlusive thrombus?
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*If there's penetration of blood into the lipid core, thrombosis results with partial or total occlusion.
*You see this in unstable/crescendo angina. |
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CORONARY ARTERY THROMBOSIS. Lumen of the coronary vessel is totally occluded. Pt died of acute MI.
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*Recent Coronary Thrombosis With Total Occlusion.
*Huge core in the plaque (~70% of plaque is core). *Note the irregularly shaped lumen, filled with thrombus. |
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L: Ruptured vulnerable plaque: note large lipid core, thin fibrous cap and thrombosis containing crystals from lipid core.
Middle: Plaque erosion with superficial thrombus. Note many SM cells and no lipid core. R: Large complicated atherosclerotic plaque with narrowed lumen. Note calcifications (blue areas). *Imaging techniques are being developed to identify vulnerable plaques in vivo. |
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*Recanalized Atherosclerotic Coronary Artery.
*Irregular space on right had had calcium deposition; the Ca fell out during specimen prep. *The smaller space on the left is the recanalization that the body achieved on its own. |
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Evidence For Thrombosis As Cause of Myocardial Infarction:
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*Wasn't recognized until about 100 years ago.
*Pathological studies helped point the finger. *Clinical studies of coronary arteriography in patients with acute MI before and after thrombolytic agents also pointed to thrombosis. *We now know it's the cause. |
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Summary of Coronary Artery Pathology In Two Ischemic Syndromes:
angina, both forms-- MI-- |
*Angina:
-Chronic stable: you see fixed lesions with at least one having > 75% reduction. -Unstable: you see plaque erosion or rupture, mural thrombi (arterial), and possibly microemboli. *Myocardial infarction: you see plaque rupture followed by thrombosis with complete occlusion. |
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Infarcts: Transmural vs Subendocardial:
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*Transmural:
-Involves entire wall. -Caused by plaque rupture and coronary thrombosis. -Q waves (usually). -Usually begin in sub-endocardial region. *Subendocardial: -Usually involves inner 1/3 to 1/2 of wall. -Not limited to a coronary branch zone. More spotty. -Non-Q wave. -Related to global reduction in coronary blood flow. *In the case of total occlusion, if reperfusion is timely, necrosis can be limited to a localized subendocardial infarct. |
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DISTRIBUTION OF MYOCARDIAL NECROSIS in different types of infarcts: 6
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Red dots= occluded vessels.
*Transmural: -Involves entire wall. -Caused by plaque rupture and coronary thrombosis. -Q waves (usually). -Usually begin in sub-endocardial region. *Subendocardial: -Usually involves inner 1/3 to 1/2 of wall. -Not limited to a coronary branch zone. More spotty. -Non-Q wave. -Related to global reduction in coronary blood flow. |
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WHAT ARE THE EARLY BIOCHEMICAL FINDINGS IN MI?
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What happens to MYOCARDIAL VIABILITY after an MI?
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*Reversible phase is very limited.
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Ischemic Myocardium: what is the Timecourse of injury to about 6 hours?
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*In a few minutes cell swelling, mitochondrial swelling, glycogen depletion.
*20-40 minutes for irreversibility; EM defects in sarcolemmal membranes. *Myocytes die in a wavefront from sub-endocardium to subepicardium in about 6 hours; effectiveness of thrombolytic agents is therefore limited to this period. |
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PROGRESSION OF MYOCARDIAL NECROSIS diagram:
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What are the Determining Factors of severity of Myocardial Infarction?
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*Location, severity, and rate of occlusion.
*Size of vascular bed, e.g. left main CA. *Duration of survival. *Metabolic demands. *Presence of collateral vessels. *Spasm. *Heart rate, rhythm, BP. |
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MI: What do we see on Gross Pathology?
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*Source of frustration in forensic path--if person dies immediately, there's nothing to see!
*Nothing in 1st 12 hours. *With special dyes after 2-3 hours. *Pallor or red blood hue @ 12-24 hours. *Yellow with red-tan border @ 3-10 days. *Yellow area rimmed by granulation tissue appearing hyperemic. *A white scar after a few weeks. |
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*Lateral MI; Several Days post MI. Yellow lesion at left.
*Also note significant LVH. |
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*4 days post MI with TTC stain.
*Red=dye oxidation (good tissue) *Tan= dead tissue. *Firm, white areas are fibrosis/scarring. Prior MI! *Significant LVH; pressure overload pattern. |
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*Extensive anteroseptal MI (ASMI).
*Several Days post MI. |
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MI: what do we see on Histopathology?
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*Wavy fibers as early as 1-3 hours.
*Coagulation necrosis: hypereosinophilia, then loss of striations in 4-12 hours. *Nuclear changes as early as 5 hours. *Nuclear disappearance @ 24-48 hours. *Polys as early as 6-8 hours; Peak @ 48 hrs. *Macrophages 4 days; Peak 6 days. *Proliferation of vessels as early as 3 days. *Fibroblasts as early as 4 days. *Collagen fibers as early as 9 days. *Early granulation tissue 7-10 days. *Granulation tissue peaks 2-4 weeks. *Advanced scarring 6 weeks. |
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*MYOCARDIAL INFARCT (1 DAY).
*Right is normal. *Left are wavy fibers. Some are anucleate. EARLIEST SIGN OF MI ON HISTOLOGY. |
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*MYOCARDIAL INFARCT (3-4 DAYS).
*Anucleate fibers= dead cells. *Loss of striations; fibers look eosinophilic. *Background cells are neutrophils. |
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*MYOCARDIAL INFARCT (7-10 DAYS).
*Increasing number of macrophages. *This correlates with highest risk of spontaneous cardiac RUPTURE post MI; high amount of tissue removal by macrophages. |
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*MYOCARDIAL INFARCT (10-14 DAYS)
*Red = capillaries *Blue = collagen *This is granulation tissue; this is healing. |
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*MYOCARDIAL INFARCTION (HEALED).
*Bottom right part is scarred. Mostly collagen. *"Replacement Fibrosis." *There's compensatory hypertrophy adjacent to the area of necrosis. |
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*HEALED MYOCARDIAL INFARCT on trichrome stain showing abundant collagen (blue).
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Discuss Myocytolysis:
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*Vacuolar degeneration or colliquative myocytolysis.
*Appears as a nucleus in an empty sarcolemmal tube. *Seen in LV subendocardium and at perimeter of MIs. *These cells are thought to be still viable. *Unlike fibers in coagulation necrosis, stain for creatine kinase and lactic dehydrogenase. |
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*Subendocardial myocytolysis.
*Cells on left half have a central nucleus with a halo around them. This is myocytolysis. |
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What happens to cardiac function with reperfusion after occlusion of a vessel?
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*Salvage can occur if caught in time. Still loss of function.
*But injuries in reperfusion can occur. |
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Discuss Myocardial Reperfusion:
what do experiments show? |
*Occlude proximal LCX in dogs
*Reperfuse: -At 40 minutes – infarct size was reduced by 60-70%. -At 3 hours – less reduction. -At 6 hours – NO REDUCTION. *When present, reduction was in subepicardial region. |
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Discuss Thrombolysis for Acute MI:
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*Streptokinase or tissue-type plasminogen activator (tPA).
*Resulting patency in about 70%. *Reperfusion injury and STUNNED myocardium can follow. *Hemorrhage in the infarct is more common but not clinically important. |
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Diagram of REPERFUSION:
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*MI (S/P REPERFUSION).
*Triphenyl tetrazolium stain *Pt died after reperfusion. *You can see the dark infarction (think hemorrhage). *LVH. |
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Discuss Reperfusion Injury:
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*Can cause lethal injury to cells which might have survived.
*Generation of reactive oxygen species, intracellular calcium overload, and inflammation which combine to facilitate cell death. *Studies underway to find therapies which will block these mediators of injury. *Contraction bands are a manifestation. |
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What is Contraction Band Necrosis?
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*Accelerated necrosis of irreversibly injured myocytes.
*Hypercontraction with massive influx of calcium. *Appear after as little as 2 minutes of reperfusion. *There are margins of infarcts between dead and viable zones. *They are more numerous in infarcts after reperfusion. *You sometimes see them in the myocardium of sudden death cases. *Perioperative ischemia during cardiac surgery. |
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*Contraction band necrosis in a 1 day old myocardial infarct; occasional PMN, nuclear loss, focal myocytolysis.
*Linear areas of horizontal staining are the bands. |
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Discuss Myocardial Stunning:
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*Reperfused myocytes are viable but temporarily have biochemical changes and are unable to contract.
*May be stunned for hours or days. *There are NO abnormalities at the level of light microscopy. *Temporary assist devices may be indicated. |
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Summarize MIs:
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*A dynamic process that begins with the transition from reversible to irreversible ischemic injury and culminates in replacement of dead myocardium by a fibrous scar.
*Myocytes die in a wavefront from inner to outer layer; a process which takes about 6 hours. *Reperfusion is more likely to salvage the outer layer. |
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Discuss the RELEASE OF MYOCYTE PROTEINS after MI:
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What are the Complications of MI?
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*Tachyarrhythmias, AV block with bradycardia, shock, congestive heart failure, rupture, thromboembolism, ventricular aneurysm, pericarditis.
*Pericarditis of 2 types: 1) Acute fibrinous pericarditis with transmural infarct. 2) Post-MI syndrome (Dressler's syndrome) autoimmune. |
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*ANTERIOR MYOCARDIAL RUPTURE post MI.
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*VENTRICULAR SEPTAL RUPTURE post MI.
*AV is visible above the rupture. |
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*RUPTURE OF PAPILLARY MUSCLE post MI.
*Pt developed MR due to ruptured muscle post MI. *Same risk profile (time-wise) as rupture of free wall. |
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*FIBRINOUS PERICARDITIS post MI. NOT Dressler's.
*Lots of fibrin deposition; Pt would also have a friction rub. |
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*MURAL THROMBUS post MI. Can lead to stroke and death, which is what happened here.
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*VENTRICULAR ANEURYSM post MI.
*In the vulnerable spot where the MI occurred. |
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Discuss Chronic Ischemic HD:
findings? |
*May have been asymptomatic and present with heart failure or have a history of angina/prior MIs.
*Diffuse myocardial atrophy, but more commonly hypertrophy with dilatation; subendocardial vacuolization, replacement fibrosis (healed MIs). *Insist on objective evidence before making diagnosis of IHD; an elderly person might have another cause of heart failure and cardiomegaly. |
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Discuss Sudden Cardiac Death:
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*80-90% have severe IHD.
*> 75% stenosis in more than one vessel. *Usually > 90% in one vessel. *Acute plaque changes and thrombosis in 75-80% and old MI in 40%. *A long list of causes other than IHD. *Fatal arrhythmia due to reduced blood flow is usual cause of death in these patients. |
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PATHWAYS OF PROGRESSION OF ISCHEMIC HEART DISEASE diagram:
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What is Graft Arteriopathy?
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*Limits the long-term success of cardiac transplants.
*Marked progressive diffuse intimal thickening of coronary arteries with luminal narrowing. *The denervated heart does not allow the patient to note anginal warning symptoms. *Similar to accelerated atherosclerosis. |
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Graft Arteriopathy. Note elastin (IEM) and thickened intima. You develop this after a transplant.
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