cardiology3 Flashcards

Question

The characteristic features of ruptured plaques

Answer 1

a thin fibrous cap; a higher ratio of macrophages to vascular smooth muscle cells (VSMCs) in the cap; less collagen, the main strength-giving component, in the cap; and a large, lipid-rich, collagen-poor necrotic core

Answer 2

Plaques vulnerable to rupture have thin fibrous caps, an excess of macrophages over vascular smooth muscle cells, large lipid cores, and depletion of collagen and other matrix proteins form the cap and lipid core. Production of matrix metalloproteinases from macrophages is prominent in human plaques, and studies in genetically modified mice imply a causative role for metalloproteinases in plaque vulnerability. Loss of collagen and other extracellular matrix (ECM) components occurs in the highly-inflamed regions of plaque cap thereby reducing tensile strength; it also occurs in the lipid core, which promotes transfer of hydrodynamic forces during the cardiac cycle to the high-strain, shoulder regions of the plaque. Apart from scavenging cholesterol to form foam cells, plaque macrophages participate in an arterial immune-inflammatory reaction most likely initiated by oxidised phospholipids and cholesterol derivatives derived from low-density lipoprotein (LDL). Enzymic and oxidative modification of LDL triggers both innate and acquired immunity. Among the lymphocytes, CD4+ T-helper (Th) cells predominate in plaques. Initially present in a Th0 ground state, Th cells can differentiate to Th1 cells, which secrete and respond to interferon (IFN-γ) or to Th2 cells, which secrete and respond to interleukin (IL)-4. Not surprisingly, therefore, IFN-γ promotes atherosclerosis formation.

Answer 3

Unstable angina. Near-complete occlusion of vessel with thrombus. “Threatened” heart attack. Biomarkers (e.g., troponin) usually negative. May not result in permanent myocardial damage if treated successfully. High risk of recurrent events in first year. Persistent and severe coronary flow reduction. Thrombus usually with complete vessel occlusion. Wavefront of myocardial necrosis; leads to cardiac dysfunction and failure; biomarkers (troponin) elevated. Cardinal symptom: severe and unremitting chest discomfort at rest (although 30% of MI’s are “silent”). Early reperfusion is key to treatment, but may also provoke additional injury (reperfusion injury). High early mortality: 1/3 of patients don’t get to hospital. Late mortality related to extent of LV dysfunction

Answer 4

inflamed arterial atheroma have inflammatory markers (e.g. CRP). Down stream myocardial injury have cardiac markers such as troponin and creatine kinase.

Answer 5

Increased Resistance to blood flow accelerates atherosclerosis, leads to LV hypertrophy – more muscle and thicker heart. LVH ultimately leads to LV dilation & heart failure. Hypertension is the No. 1 risk factor for Heart Failure. LV mass greater in pre hypertensives than in normotensive. CRP as a marker of inflammation may be increased. BP and lipid control account for the 40% decline in CVD mortality in the last decade.

Answer 6

Raising HDL with drugs reduces CVD. Tight glycemic control reduces CVD events in Type II DM. Aspirin reduces CVD events in Type II DM. Smoke-free policy definitively reduces the risk of acute myocardial infarction

Answer 7

any array of clinical symptoms resulting from underlying acute myocardial ischemia

Answer 8

Atherosclerotic plaque rupture with thrombus, Coronary embolism, Congenital anomalies Coronary trauma or aneurysm, Severe coronary artery spasm (e.g. cocaine), Increased blood viscosity, Spontaneous coronary dissection, and Markedly increased myocardial 02 demand

Answer 9

Inflammation + risk factors promote atherosclerosis Primary risk factors include: Diabetes, hypertension, hyperlipidemia, tobacco Other possible risk factors: poor diet, inactivity, obesity, kidney disease, family history. Atherosclerosis promotes a dysfunctional endothelium Dysfunctional endothelium has decreased vasodilator effect and decreased antithrombotic effect compared to normal endothelium. Inflammatory mediators weaken the atherosclerotic fibrous cap; if cap bursts, thrombogenic tissue factor is released, activating the coagulation cascade and creating platelet aggregation. Dysfunctional endothelium + coagulation + platelet aggregation = Coronary thrombosis

Answer 10

Regulatory proteins involved in actin-myosin interaction. Felt specific to heart. Released into bloodstream with myocyte necrosis. Myocardial necrosis leads to release of Troponin into blood within 3-12 hours, peaking in 18-24 hours. Troponin felt to be more specific, remains elevated longer. Look for rise and fall in appropriate time frame (prolonged in renal failure)

Answer 11

Complete coronary vessel occlusion: ST elevation myocardial infarction (STEMI). Partial coronary vessel occlusion with myocardial necrosis: non ST elevation MI (NSTEMI). Partial coronary vessel occlusion, escalating symptoms without myocardial necrosis: Unstable angina.

Answer 12

time to initial elevation is 4-6 hous. Time to peak elevation is 18 hours. Time to return to normal 2-4 days.

Answer 13

time to initial elevation is 4-6 hours. Time to peak elevation is 12 hours. Time to return to normal is 3-10 days.

Answer 14

time to initial elevation is 4-6 hours. Time to peak elevation 12-48 hours. Time to return to normal is 7-10 days.

Answer 15

Necrosis of myocardial tissue causes intracellular leak of molecules into the bloodstream. Detection of these molecules, especially cardiac troponin is important to diagnose MI. Cardiac troponin is very sensitive and specific for myocardium.

Answer 16

discomfort due to myocardial ischemia classically experienced as substernal chest pain or tightness, but may be less classicàleft arm pain, shortness of breath, nausea, weakness

Answer 17

present when there is increased demand for myocardial oxygen in a reproducible fashion

Answer 18

discomfort which is new in onset or is increased in duration, frequency or intensity with less exertion or at rest compared to previous episodes of discomfort

Answer 19

relief of ischemia by reducing myocardial oxygen demand and opening the artery or prevent further arterial occlusion. And prevent adverse outcomes.

Answer 20

Artery is occluded so need to open it. If artery can be opened within 90 minutes, go to cardiac cath lab to open mechanically (cardiac catheterization). If cannot be opened within 90 minutes, consider fibrinolytics. If hemodynamically stable, consider oral beta blockers or nitrates to decrease myocardial oxygen demand

Answer 21

Artery is partially occluded need to halt the thrombotic process from completely occluding the artery by giving anticoagulant and antiplatelet agents. Anticoagulants: unfractionated heparin, low-molecular weight heparin, fondaparinux Antiplatelets: P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor), GIIb/IIIa inhibitors PLUS Aspirin If hemodynamically stable, consider oral beta blockers or nitrates to decrease myocardial oxygen.

Answer 22

History: chest pain, dyspnea, risk factors. Physical examination: May be normal, or reveal evidence of cardiac dysfunction from prior myocardial damage (congestive heart failure), evidence of atherosclerosis in other vascular beds. Electrocardiogram at rest or with exercise (stress test). Non-invasive imaging: echocardiography, nuclear medicine (perfusion imaging), ultrafast CT. Coronary angiography

Answer 23

Resting ECG: ST segment changes (usually depression), T wave inversion, and Q-waves (indicate prior infarction). Exercise ECG (stress testing): dynamic ST segment changes

Answer 24

Resting ECG is insensitive. Exercise ECG: Sensitivity and specificity still suboptimal (~70% and 75%, respectively)

Answer 25

Ischemic response: horizontal or downsloping ST depression with exercise, reflecting subendocardial ischemia. Functional information (exercise time and intensity) and accompanying symptoms help to interpret the results. Concurrent imaging of myocardial perfusion (radiopharmaceuticals) or wall motion (echocardiography) improves sensitivity and specificity of stress ECG

Answer 26

Picture of the vessel lumen -- but does not tell us about the vessel wall. Good for diagnosis of coronary obstruction causing anginal symptoms; not as good for predicting future events. Guides therapeutic intervention (angioplasty, bypass surgery)

Answer 27

Risk factor modification (for prevention AND treatment of overt disease) such as diet, exercise, smoking cessation. Drugs to treat angina, blood pressure, lipids, platelets. Revascularization with coronary angioplasty or coronary artery bypass surgery

Answer 28

Lipid-modifying: Statins. Anti-platelet: Aspirin, clopidogrel. Anti-anginal: Nitrates, beta blockers, calcium channel blockers. LV dysfunction: ACE inhibitors or angiotensin receptor blocker

Answer 29

Hospitalization, Intravenous nitroglycerin, Beta blockers, Aspirin and other anti-platelet agents, Anticoagulation (heparin), and Usually early catheterization and coronary intervention

Answer 30

Problem: acute occlusion. Solution: stents and antiplatelet drugs. Problem: Restenosis. Solution: Stents, particularly those that elute antiproliferative drugs

Answer 31

Treatment may be initiated in the field. Immediate aspirin, nitroglycerin, ± beta blocker. Reperfusion therapy ASAP: Usually coronary angioplasty, if unavailable thrombolytic therapy.

Answer 32

Not all coronary obstructions can be treated percutaneously (angioplasty); some require bypass surgery (CABG). In randomized clinical trials, bypass surgery has been shown to reduce mortality in selected patients, compared to medical therapy, and may be better than angioplasty when there are multiple blockages. Principal types of grafts: Internal mammary artery, Saphenous vein, and Prosthetic materials have not proven successful as coronary grafts

Answer 33

normal: impermeable to large molecules, anti-inflammatory, resist leukocyte adhesion, promote vasodilation, and resist thrombosis. Activated/abnormal: increased permeability, increased inflammatory cytokines, increased leukocyte adhesion molecules, decreased vasodilatory molecules, decreased antithrombotic molecules.

Answer 34

normal: normal contractile function, maintain extracellular matrix, and contained in medial layer. Activated/abnormal smooth muscle cell: increased inflammatory cytokines, increased extracellular matrix synthesis, and increased migration and proliferation into subintima.

Answer 35

Expressed on luminal side of endothelium. Responds to multiple stimuli. NO from Arginine. Multiple cofactors. NO diffuses to smooth muscle in media. cGMP-mediated vasodilatation.

Answer 36

triggers such as acetylcholine, serotonin, thrombin, bradykinin, and shear stress. Nitric oxide, known as the 'endothelium-derived relaxing factor', or 'EDRF', is biosynthesized endogenously from L-arginine, oxygen, and NADPH by various nitric oxide synthase (NOS) enzymes. Reduction of inorganic nitrate may also serve to make nitric oxide. The endothelium (inner lining) of blood vessels uses nitric oxide to signal the surrounding smooth muscle to relax, thus resulting in vasodilation and increasing blood flow. Nitric oxide is highly reactive (having a lifetime of a few seconds), yet diffuses freely across membranes. These attributes make nitric oxide ideal for a transient paracrine (between adjacent cells) and autocrine (within a single cell) signaling molecule.

Answer 37

There are several mechanisms by which NO has been demonstrated to affect the biology of living cells. These include oxidation of iron-containing proteins such as ribonucleotide reductase and aconitase, activation of the soluble guanylate cyclase, ADP ribosylation of proteins, protein sulfhydryl group nitrosylation, and iron regulatory factor activation. NO has been demonstrated to activate NF-κB in peripheral blood mononuclear cells, an important transcription factor in iNOS gene expression in response to inflammation. It was found that NO acts through the stimulation of the soluble guanylate cyclase, which is a heterodimeric enzyme with subsequent formation of cyclic-GMP. Cyclic-GMP activates protein kinase G, which causes reuptake of Ca2+ and the opening of calcium-activated potassium channels. The fall in concentration of Ca2+ ensures that the myosin light-chain kinase (MLCK) can no longer phosphorylate the myosin molecule, thereby stopping the crossbridge cycle and leading to relaxation of the smooth muscle cell.

Answer 38

decreased NO and oxidative stress causes signals at the endothelial cell leading to transcription and translation of pro-inflammatory proteins. Such molecules include selectins, cell adhesion molecules for monocyte, and cytokines. Initial damage to the endothelium results in an inflammatory response. Monocytes enter the artery wall from the bloodstream, with platelets adhering to the area of insult. This may be promoted by redox signaling induction of factors such as VCAM-1, which recruit circulating monocytes, and M-CSF, which is selectively required for the differentiation of monocytes to macrophages. The monocytes differentiate into macrophages, which ingest oxidized LDL, slowly turning into large "foam cells" – so-called because of their changed appearance resulting from the numerous internal cytoplasmic vesicles and resulting high lipid content. Under the microscope, the lesion now appears as a fatty streak. Foam cells eventually die, and further propagate the inflammatory process. There is also smooth muscle proliferation and migration from the tunica media into the intima responding to cytokines secreted by damaged endothelial cells. This causes the formation of a fibrous capsule covering the fatty streak. Intact endothelium could prevent the proliferation by releasing nitric oxide.

Answer 39

first, a fatty streak develops leading to endothelial dysfunction, lipoprotein entry and modification, leukocyte recruitment, and foam cell formation. Next, plaque progression occurs leading to smooth muscle cell migration and altered matrix synthesis and degradation. Disruption of the plaque integrity leads to thrombus formation.

Answer 40

a layer of fibrous connective tissue, which is thicker and less cellular than the normal intima, found in atherosclerotic plaques. The fibrous cap contains macrophages and smooth muscle cells. The fibrous cap of an atheroma is composed of bundles of muscle cells, macrophages, foam cells, lymphocytes, collagen and elastin. The fibrous cap is prone to rupture and ulceration which can lead to thrombosis. In advanced lesions further complications may arise including calcification of the fibrous cap. Foam cells release MMPs, causing degradation of the fibrous cap.

Answer 41

Atherosclerotic lesions, or atherosclerotic plaques, are separated into two broad categories: Stable and unstable (also called vulnerable).[4] The pathobiology of atherosclerotic lesions is very complicated but generally, stable atherosclerotic plaques, which tend to be asymptomatic, are rich in extracellular matrix and smooth muscle cells, while, unstable plaques are rich in macrophages and foam cells and the extracellular matrix separating the lesion from the arterial lumen (also known as the fibrous cap) is usually weak and prone to rupture. Stable plaques are rich in fibrous tissue, calcified, and have less lipid content, inflammation, and apoptosis. Vulnerable plaques have less fibrous tissue and calcification and more lipid content, inflammation, apoptosis. A rupture of a plaque can lead thrombus formation. Much of thrombosis is regulated by molecules expressed on surface of or secreted by endothelium. Such molecules include heparin sulfate, thrombin, NO, platelet activation, and prostacyclin.

Answer 42

Atheroembolization from carotid bifurcation lesion. Source lesion does not need to be obstructive (<70% diameter reduction). Often lodged in the ophthalmic artery. Thromboembolization from left atrial appendage in setting of atrial fibrillation.

Answer 43

Myocardial infarction and chronic stable angina are both manifestations of CAD. However, vascular pathology is different. MI – ruptured plaque, in-situ thrombosis, not necessarily obstructive prior to rupture. Angina – stable, obstructive (>70% diameter reduction) lesion

Answer 44

Not all the same severity. Plaque rupture à non-occlusive thrombosis à some flow but intermittent occlusion or embolization à stabilize with anticoagulation / vasodilators. Plaque rupture à occlusive thrombus à no flow à clinical emergency à recanalize

Answer 45

Coronary thrombus can be small (non-flow limiting), partially occlusive, or completely occlusive. Small thrombus have no ECG changes and can lead to either healing and/or plaque enlargement. Partially occlusive thrombus have ST segment depression and/or T wave inversion with or without serum markers. When serum biomarkers are present, it is a non-ST-segment elevation MI. When it is not present, there may be an unstable angina. Occlusive thrombus may be transient (similar presentation as partially occlusive thrombus) or prolonged presenting as ST elevation (Q waves later). Serum biomarkers are also present here for ST segment elevation MI

Answer 46

Claudication and acute limb ischemia are manifestations of PAD. However, underlying endothelial pathology differs. Claudication: obstructive (>70% diameter reduction), stable plaque. Acute limb ischemia: acute event obstructs blood flow without prior development of collaterals, could be atheroembolization or thromboembolization, rarely in-situ thrombosis.

Answer 47

less biologically active. Cause angina and claudication (exertional ischemia) if obstructive (>70% diameter reduction). less likely to cause thrombotic and embolic events

Answer 48

more biologically active, cause MI and stroke, and more likely via thrombotic and embolic mechanisms

Answer 49

Includes deep venous thrombosis and pulmonary embolism. Venous thrombosis different than arterial thrombosis

Answer 50

Venous Thrombosis is Fibrin rich, RBC, Areas of stasis, Genetic predisposition, Environmental predisposition, Treated with anticoagulation. Arterial Thrombosis is Platelet rich, Plaque rupture, Areas of high flow, Atherosclerosis, trauma, APLA. Focus more on antiplatelet therapy.

Answer 51

Raynaud’s (primary vs secondary), Pernio, Erythromyalgia, Acrocyanosis. Dysfunctional endothelium involved but not necessarily thrombosis or atherosclerosis

Answer 52

Red blood cells ~ 6 - 8 µm in diameter. Micro-bubbles < 10 µm pass through pulmonary capillaries. Agitated saline: Creates micro-bubbles ~ 16 µm in diameter. Do not pass through pulmonary capillaries. Do not show up in left heart unless right to left communication and flow. If they do show up it is a sign of either intra-cardiac shunt or Intra-pulmonary shunt

Answer 53

Asymptomatic, non-obstructive CAD, Ischemia (Stable exertional angina or Unstable angina), Myocardial infarction (MI), cellular necrosis

Answer 54

Precipitate ischemia by increasing myocardial oxygen demand (stress). Identify ischemia by changes in: blood pressure, ECG, symptoms, blood flow (perfusion) imaging, and wall motion (echocardiography) imaging.

Answer 55

Screening for coronary artery disease (CAD), Evaluate chest pain, Exercise capacity, Prognosis, and Evaluation after revascularization

Answer 56

Unstable angina, Untreated life-threatening arrhythmias, Uncompensated heart failure, Advanced AV block, Acute myocarditis, pericarditis, Critical aortic stenosis, Significant HOCM, Uncontrolled HTN, and Acute systemic illness

Answer 57

Radionuclide or Echocardiography. Exercise with either Treadmill or Bicycle. Pharmacologic Vasodilator (Dipyridamole (Persantine), Adenosine (Adenocard), and Regadenoson (Lexiscan)) and Dobutamine. Patient preparation: Nothing to eat or drink ³ 4 hrs, Dipyridamole, adenosine, regadenoson (if No significant reactive airways dz and No caffeine, theophylline for at least 24 hrs)

Answer 58

Abnormal baseline ECG, digoxin, Wolf-Parkinson-White, Increase sensitivity, Localization, Preoperative cardiac risk assessment, and Myocardial viability

Answer 59

Unstable angina, Untreated life-threatening arrhythmias, Uncompensated heart failure, Advanced AV block, Acute myocarditis, pericarditis, Critical aortic stenosis, Significant HOCM, Uncontrolled HTN, and Acute systemic illness.

Answer 60

Tracer deposited based on blood flow. Imbalance between supply and demand results in relative decreased perfusion. Compare perfusion during increased demand (stress) and decreased demand (rest). Reversible perfusion defects indicate reversible ischemia. Fixed perfusion defects indicate infarction, scar

Answer 61

Thallium-201: Potassium analog, Initial accumulation µ blood flow, Continuous exchange across cell membrane. Technetium-99m-Sestamibi (Cardiolite): Lipophilic monovalent cation, Initial accumulation µ blood flow, Rapid hepatic accumulation,Biliary clearance, One pass, Gating – LV ejection fraction and wall motion

Answer 62

Imbalance between supply and demand results in wall motion abnormality. Compare increased demand (stress) wall motion to decreased demand (rest) wall motion. Normally left ventricle should beat faster and thicken more with exercise or dobutamine

Answer 63

Strong magnetic field, 3D, tomographic images, No ionizing radiation, Contraindications: Metallic implants and Kidney dysfunction for Gadolinium contrast. Anatomic imaging (spin echo). Functional imaging (cine CMRI)

Answer 64

Catheter inserted into artery or vein, advanced to heart or coronary arteries. Measurements of: pressure, gradients, saturation, intracardiac shunt. Inject contrast for angiography

Answer 65

Found only in the cardiac ventricles. Released in response to stretch, increase in volume in the ventricle. BNP levels correlate with: Left ventricular end-diastolic pressure, New York Heart Association (NYHA) classification, and Objective heart failure diagnosis in patients 55 or older. BNP levels tend to be higher in women, elderly. BNP levels elevated in renal insufficiency. BNP < 100 pg/ml 90% sensitivity, 76% specificity, 83% accuracy for non-HF cause

Answer 66

Ultrasound sent into body, strikes objects and returns to transducer. Returned ultrasound can be transformed into: 2-Dimensional motion picture, M-Mode, Color Doppler map of blood flow, Echocardiogram and Spectral Doppler map of blood or tissue velocity

Answer 67

coronary arteries leading to ischemic heart disease. When complicated by thrombosis, it can lead to MI. cerebral arteries, leading to brain infarcts (strokes), neurologic disease. Aorta, leading to abdominal aortic aneurysms. Critical ischemia of intestines. Ischemia of lower extremities.

Answer 68

most occur in abdominal aorta, below renal arteries. Atherosclerosis weakens wall. Mass effect can simulate tumors causing compression and erosion of adjacent structures. Risk of rupture is related to size of aneurysm.

Answer 69

is an autosomal dominant disorder of large arteries. A degenerative breakdown of collagen, elastin, and smooth muscle caused by aging contributes to weakening of the wall of the artery. In the aorta, this can result in the formation of a fusiform aneurysm. There is also increased risk of aortic dissection. Can be seen in marfan syndrome

Answer 70

Aortic dissection occurs when a tear in the inner wall of the aorta causes blood to flow between the layers of the wall of the aorta, forcing the layers apart. In most cases this is associated with severe characteristic chest or abdominal pain described as "tearing" in character and radiating pain to the back, and often with other symptoms that result from decreased blood supply to other organs. Aortic dissection is a medical emergency and can quickly lead to death, even with optimal treatment, as a result of decreased blood supply to other organs, heart failure, and sometimes rupture of the aorta. Aortic dissection is more common in those with a history of high blood pressure, a known thoracic aortic aneurysm, and in a number of connective tissue diseases that affect blood vessel wall integrity such as Marfan syndrome and the vascular subtype of Ehlers–Danlos syndrome. The diagnosis is made with medical imaging (computed tomography, magnetic resonance imaging or echocardiography). In an aortic dissection, blood penetrates the intima and enters the media layer. The high pressure rips the tissue of the media apart along the laminated plane splitting the inner 2/3 and the outer 1/3 of the media apart. This can propagate along the length of the aorta for a variable distance forward or backwards. Dissections that propagate towards the iliac bifurcation (with the flow of blood) are called anterograde dissections and those that propagate towards the aortic root (opposite of the flow of blood) are called retrograde dissections.

Answer 71

Anterograde dissections may propagate all the way to the iliac bifurcation of the aorta, rupture the aortic wall, or recanalize into the intravascular lumen leading to a double barrel aorta. The double barrel aorta relieves the pressure of blood flow and reduces the risk of rupture. Rupture leads to hemorrhaging into a body cavity and prognosis depends on the area of rupture. Retroperitoneal and pericardial ruptures are both possible.

Answer 72

Originates in ascending aorta, propagates at least to the aortic arch and often beyond it distally. It is most often seen in patients less than 65 years of age and is the most lethal form of the disease.

Answer 73

Originates in ascending aorta and is confined to the ascending aorta.

Answer 74

Originates in descending aorta, rarely extends proximally but will extend distally. It most often occurs in elderly patients with atherosclerosis and hypertension.

Answer 75

a group of disorders that destroy blood vessels by inflammation, which can lead to fibrinoid necrosis, vessel wall inflammation and damage. One or few vessels may be affected due to localized infection, irradiation, trauma, or Arthus reaction. Viruses have been localized in lesions. DNA-anti-DNA immune complexes and complement is seen in SLE. Systemic vasculitis classification depends on: – size of the blood vessels, anatomic site, microscopic characteristics of the lesion, and clinical manifestations

Answer 76

Medium to small arteries | – All stages of activity may coexist

Answer 77

Arterioles, capillaries, venules | – All lesions tend to be at same stage

Answer 78

effects arteries of the head including temporal arteries, ophthalmic branches. May lead to blindness. Granulomatous inflammation is present. Effects mostly elderly people above the age of 50.

Answer 79

this is vasculitis plus granulomas. Can involve both lungs and kidneys. Can involve both lungs and kidneys. If untreated, there is over a 90% mortality in 2 years.

Answer 80

affects aorta, main branches and pulmonary arteries. Causes narrow orifices of great vessels leading to pulseless. Coldness and numbness of fingers and legs also present. Younger people (under the age of 40), females more than males, and asains are more likely to be effected.

Answer 81

Infancy and early childhood. Fever, erythema of palms and soles, rash. In most cases, coronary arteries are affected. Many cases are self limited; 0.5-1% develop MI.

Answer 82

Male cigarette smokers. Femal incidence also increases with smoking. Leads to thrombosis of medium-sized vessels, tibial and radial arteries. Can lead to gangrene and severe pain, even at rest, due to nerve involvement.

Answer 83

is a venous disorders. Clots forming within deep leg veins leading to death from pulmonary emboli (saddle embolus). Can be due to prolonged bed rest, immobilization, or cancer (hypercoagulability).

Answer 84

a medical sign involving episodes of vessel inflammation due to blood clot (thrombophlebitis) which are recurrent or appearing in different locations over time (thrombophlebitis migrans or migratory thrombophlebitis). The location of the clot is tender and the clot can be felt as a nodule under the skin. Trousseau's sign can be an early sign of gastric or pancreatic cancer, typically appearing months to years before the tumor would be otherwise detected. Heparin therapy is recommended to prevent future clots. The Trousseau sign of malignancy should not be confused with the Trousseau sign of latent tetany caused by hypocalcemia.

Answer 85

a type of local type III hypersensitivity reaction. Type III hypersensitivity reactions are immune complex-mediated, and involve the deposition of antigen/antibody complexes mainly in the vascular walls, serosa (pleura, pericardium, synovium), and glomeruli.

Answer 86

a form of necrosis, or tissue death, in which there is accumulation of amorphous, basic, proteinaceous material in the tissue matrix with a staining pattern reminiscent of fibrin. It is associated with conditions such as immune vasculitis (e.g. Polyarteritis nodosa), malignant hypertension, preeclampsia, or hyperacute transplant rejection.

Answer 87

caused by reduction in blood supply due to atherosclerosis of coronary arteries, coronary vasculitis, emboli from valve vegetations. Symptomatic disease due to critical stenosis. Compensatory vasodilation is insufficient for O2 demand. Superimposition of clots and vasospasm also present. Demand ischemia is caused by hypotension due to infection. Syndromes include angina pectoris, myocardial infarction, chronic ischemic heart disease leading to congestive heart failure, and sudden cardiac death.

Answer 88

intermittect chest pain caused by reversible myocardial ischemia. Typical (stable) angina pectoris is episodic chest pain associated with exertion. Unstable angina pectoris have increased frequency and intensity of attacks by less exertion and harbinger of irreversible myocardial ischemia. Prenzmetal’s (variant) angina is due to vasospasm and chest pain that occurs at rest (sleep).

Answer 89

is myocardial necrosis caused by ischemia that lasts several hours and is not relieved by nitoglycerine. Most infarcts caused by clot superimposed on plaque. Necrosis begins about 20-30 minutes after occlusion. Necrosis begins in the subendocardial region progressing outward. The location of occlusion determines severity; the more proximal occlusion produces larger infarcts. Collateral circulation to lessen the severity. Chronic ischemia may recruit additional vessels over time, limiting damage when main vessel is finally 100% occluded.

Answer 90

after four hours there are no gross changes, microscopic changes shoe coagulation necrosis. After one day tissue appears pallor and neutrophils appear. After one week, macrophages appear. After 10 days tissue appear yellow, soft, and sunken and microscopicly granulation tissue develops. after two months, a firm grey scar appears and tissue becomes fibrotic. In less than two weeks of rupture, patients are at risk for ventricular aneurysms and mural thrombus.

Answer 91

in most cases, death due to marked atherosclerosis. Plaque ruptures lead to clot, vasospasm can lead to fatal arrhythmia. Arrhythmias due to other reasons such as hypertrophy.

Answer 92

most people are right dominant circulation, meaning that right coronary artery supplies posterior left ventricle. Left dominant circulation meaning that left circumflex coronary artery branches supply posterior left ventricle.

Answer 93

are composed mainly of fibrin and trapped red blood cells with relatively few platelets

Answer 94

are composed mainly of platelet aggregates held together by small amounts of fibrin

Answer 95

Drugs of choice for prevention and treatment of venous thromboembolism and for prevention of cardioembolic events in patients with atrial fibrillation. Anticoagulants are also effective for arterial thrombosis and their effects can be additive with antiplatelet agents

Answer 96

Drugs of choice primarily for prevention and treatment of arterial thrombosis (primary and secondary prevention and treatment of acute coronary syndrome).

Answer 97

with risk factors, aspirin. Without risk factors, aspirin in men over 45 and in women over 65.

Answer 98

Aspirin (clopidogrel if aspirin intolerant)

Answer 99

Aspirin ± clopidogrel

Answer 100

Aspirin ± clopidogrel or prasugrel or ticagrelor ± UFH or LMWH or fondaparinux ± GPIIb/IIIa inhibitor

Answer 101

Aspirin + clopidogrel or prasugrel or ticagrelor + UFH or LMWH or fondaparinux ± GPIIb/IIIa inhibitor

Answer 102

Aspirin + clopidogrel or prasugrel or ticagrelor + UFH or LMWH or bivalirudin ± GPIIb/IIIa inhibitor

Answer 103

Congestive HF-Hypertension-Age ≥ 75- Diabetes-Stroke-Vascular disease-Age 65-74-Sex (female) OR

Answer 104

Congestive HF-Hypertension-Age ≥ 75-Diabetes-Stroke

Answer 105

Warfarin or dabigatran or rivaroxaban or apixaban (aspirin can be used for patients at low risk)

Answer 106

LMWH or UFH or fondaparinux + warfarin

Answer 107

Low-dose UFH or LMWH or fondaparinux for medical patient or general surgery. Fondaparinux or rivaroxaban or dabigatran or LMWH or warfarin for orthopedic surgery.

Answer 108

Aspirin (clopidogrel if aspirin intolerant)

Answer 109

Involves endothelial cells of vasculature, circulating platelets, coagulation factors, fibrinolytic system.

Answer 110

Escaping blood increases mechanical pressure on normal tissues collapsing surrounding venules and capillaries, thus limiting blood loss. Damage to vessel exposes collagen of subendothelium (normal vasculature is not thrombogenic).

Answer 111

Transient vasoconstriction (mediated by vasoactive substances released by platelets, 5HT, TXA2). Reduced lumen diameter reduces blood loss / facilitates obstruction by platelets.

Answer 112

Biochemical reaction involving collagen of endothelial wall and von Willebrand factor that activates platelets upon adhesion

Answer 113

cause release of aggregating substances which cause further release in other platelets (serotonin [5-HT], thromboxane A2 [TXA2], ADP). “Chain reaction” of platelet adhesion and aggregation eventually produces a thrombus plug that obstructs leak in damaged vessel (must be reinforced by fibrin for long-term effectiveness).

Answer 114

Aggregated platelets provide surface for fibrin deposition and coagulation. Platelets then release additional factors to initiate and/or sustain coagulation process. [Details next page]

Answer 115

Undamaged endothelial cells release antiaggregatory and vasodilatory prostacyclin (PGI2), reversing initial vasoconstriction. Fibrinolysis occurs, clot digested by enzymes from plasma (Plasmin).

Answer 116

Platelet membrane receptors include the glycoprotein (GP) Ia receptor, binding to collagen (C); GP Ib binding von Willebrand factor (vWF), and GP IIb/IIIa, which binds fibrinogen resulting in platelet aggregation. Antiplatelet prostacyclin (PGI2) and nitric oxide (not shown) are released from the endothelium. Pro- aggregatory substances released from the degranulating platelet [adenosine diphosphate (ADP), thromboxane A2 (TXA2), and serotonin (5-HT)] increase expression of GIIb/IIIa receptors.

Answer 117

Tissue damage exposes tissue factor (TF aka thromboplastin) then TF + Ca++ + PLs + VIIa, which activates Xa. [Xa also activated by action of IXa in concert with VIIIa + Ca++ + PLs]. Xa then catalyzes conversion of prothrombin (II), creating thrombin (IIa). Thrombin catalyzes conversion of fibrinogen (I), creating fibrin (Ia) [Fibrinogen links platelets via GIIb/IIIa receptors]. End result is fibrin reinforcement of aggregated platelet plug. Extrinsic pathway involves tissue factor from subendothelial cells. Probably the more important pathway in vivo, results in formation of factor Xa within seconds. Intrinsic pathway involves factors in plasma. Triggered by activation of factor XII by contact in vitro with glass or charged surface (subsequent formation of factor Xa in minutes).

Answer 118

Inhibit synthesis of Vit K-dependent clotting factors II, VII, IX, and X

Answer 119

Combines with antithrombin III (ATIII) to inactivate active clotting factors (IIa, IXa, Xa, XIa, XIIa)

Answer 120

Combine with antithrombin III (ATIII) to inactivate Xa

Answer 121

Directly inactivate IIa (thrombin)

Answer 122

Directly inactivates Xa

Answer 123

[normal: 26-33 seconds]. Components: Citrated plasma, kaolin, negatively charged phospholipids, Ca++. Prolonged clotting time indicates defect in intrinsic pathway. Used to monitor heparin therapy [aPTT not significantly affected by LMWHs]

Answer 124

[normal: 12-14 seconds]. Components: Citrated plasma, thromboplastin (tissue factor + phospholipid), Ca++ . Prolonged clotting time indicates defect in extrinsic pathway. Used to monitor oral anticoagulant (warfarin) therapy. Variability in activity of thromboplastin preparations necessitates a correction factor (ISI = international sensitivity index) to allow comparison of values between different labs. Thus, values are now reported as an International Normalized Ratio (INR), not in seconds: INR = (patient PT / mean normal PT)ISI.

Answer 125

Components: Primary reagent is ecarin, derived from the venom of the saw-scaled viper. The ECT is prolonged in a specific and linear manner with increasing concentrations of hirudin or dabigatran in the patient’s plasma sample. Can be used to monitor anticoagulant therapy with direct thrombin (IIa) inhibitors (hirudin and dabigatran)

Answer 126

Blood coagulation and thrombus formation must be limited in order to avoid impaired blood flow. This is accomplished by several small molecules and endogenous proteins acting as natural anticoagulants that prevent coagulation in an intact vessel.

Answer 127

Reverse vasoconstriction and inhibit platelet aggregation.

Answer 128

Antithrombin III: Serine protease inhibitor that binds to and inactivates IIa, IXa, Xa, XIIa. This activity is greatly accelerated by the endothelial cell surface and by heparin. Protein C / Protein S system: Thrombin binds to thrombomodulin on endothelial cell surface and activates Protein C. Activated protein C [Cact] (with cofactor protein S and phospholipid) inactivates factors Va and VIIIa, diminishing rate of prothrombin and factor X activation.

Answer 129

Central process is activation of plasminogen (released by damaged endothelial cells) to plasmin by tissue plasminogen activator (tPA). Plasmin proteolyzes fibrin and limits thrombosis.

Answer 130

Large, highly negatively charged molecule (sulfated mucopolysachharides). Mechanism of Action: Acts in plasma to inhibit activated clotting factors. Acts indirectly by binding to and accelerating the activity of antithrombin III (AT III) 1000-fold in inhibiting the activated clotting factor proteases. (High molecular weight fractions). Antithrombin III-heparin complex inhibits action of activated factors IIa, IXa, Xa, XIa, XIIa, XIIIa, ultimately preventing conversion of prothrombin to thrombin and fibrinogen to fibrin.

Answer 131

Enoxapirin (Lovenox), Dalteparin (Fragmin)]. Bind to AT III and inactivate factor Xa, but not IIa (thrombin). Claimed to have equal efficacy as regular heparin for VTE with less tendency for bleeding complications and less effects on platelets (i.e., thrombocytopenia). No effect on aPTT, thus monitoring not routinely required, and can be dosed reliably on mg/kg basis. Antifactor Xa activity can be tested for patient groups requiring special dosing (renal failure, older age, obesity)

Answer 132

(Arixtra) a pentasaccharide activator of AT III - inactivates factor Xa only

Answer 133

(no combination with AT III needed). Argatroban (Aggrastat), bivalirudin (Angiomax), lepirudin (Refludan), desirudin (Aprivask) given parenterally

Answer 134

Not absorbed from GI tract; given IV or SC (if given IM, there is a high incidence of hematomas). [Increased bioavailabilty with LMWH] Does not cross placenta, drug of choice in pregnant patient. Must give IV loading dose for immediate anticoagulant effect. Half-life of heparin is dependent on dose given, usually 50-150 min; cleared-degraded by reticulo- endothelial system. [LMW heparins have longer durations of activity (once-twice daily dosing) and first-order renal elimination kinetics.]. Peak action 2-4 hrs with intermittent SC. Continuous infusion preferred for heparin for constant therapeutic effect; less bleeding complications (higher doses needed with intermittent therapy).

Answer 135

General action to prevent state of hypercoagulability that follows vascular injury / venous stasis. LMWH generally preferred over heparin due to less variable response (no monitoring) and less thrombocytopenia, but heparin effect more rapidly and completely reversed by protamine and may be safer in patients with renal impairment. Adjunct in treatment of coronary occlusion in unstable angina / acute MI. Prophylaxis / treatment of venous thromboembolism [VTE] (deep vein thrombosis and pulmonary embolism). Prevention of cerebral thrombosis in evolving stroke. Low dose prophylaxis of post-operative thromboembolism (SC)

Answer 136

Hemorrhage chief complication (10%) at any site (elderly women more prone). Hypersensitivity (obtained from beef lungs, pork intestines): Commonly chills, fever, urticaria. Thrombocytopenia – more likely with heparin than LMWH - NOT with fondaparinux. Can be mild via weak platelet activation and sequestration [up to 30% of patients] and is generally of no clinical consequence. Occurs within first 4 days of therapy and returns to normal with continued heparin administration. Or severe, potentially life-threatening via immune-mediated reaction [1-2% of patients] within 5-10 days of initiation of therapy. Antibody-platelet-heparin complex activates platelets and leads to thromboembolic sequelae in 30-80% of patients. If platelet count < 100,000 then D/C heparin, continue with oral anticoagulants. Osteoporosis. Reported in patients taking heparin for longer than six months due to reduction in bone mineralization - unknown mechanism

Answer 137

Hypersensitivity, active bleeding, hemophilia, thrombocytopenia, purpura, severe hypertension, bacterial endocarditis, ulcerative GI lesions, threatened abortion.

Answer 138

``` Bleeding chief sign, such as nosebleeds, hematuria, or tarry stools 1st sign; bruising may precede. Treatment: Protamine (strongly basic protein with + charge) complexes and neutralizes heparin within 5 min (1 mg neutralizes about 100 U). Give IV very slowly (1-3 min); do not exceed 50 mg/10 min (if too rapid, there can be hypotension, anaphylactoid reactions). Incomplete reversal of LMWH overdose. ```

Answer 139

Increase bleeding tendencies with drugs that interfere with platelet aggregation (main hemostatic defense of heparinized patients): Aspirin, indomethacin, ibuprofen, dextran

Answer 140

Oral Anticoagulant Agents. Mechanism of Action: Acts in liver to prevent synthesis of clotting factors. Blocks liver synthesis of vitamin K-dependent clotting factors (II, VII, IX, X, Ca++-dependent factors) via preventing the reactivation of vitamin K. This step is necessary to continue the reaction that adds a carboxyl group to glutamyl residues of the clotting factor. This enzyme, vitamin K epoxide reductase complex 1 (VKORC1), displays genetic polymorphisms that can result in differential sensitivity to warfarin among patient groups. Genetic test for variants is available. Onset of anticoagulant effect delayed to allow turnover of existing clotting factors, dependent on half- lives of clotting factors: II: 60 hrs, VII: 6 hrs, IX: 24 hrs, X: 40 hrs. Warfarin also inhibits protein C synthesis; this can result in early procoagulant effect. Increased prothrombin time in 8-12 hrs, reaching steady state of maximum effect in 3-5 days.

Answer 141

Essentially 100% oral absorption. 99% bound to plasma proteins, but crosses placenta and contraindicated in pregnancy. Metabolized by CYP2C9 to inactive metabolites (potential source of drug interactions). Genetic polymorphisms exist that can affect selection of initial dose and potential for bleeding reactions during induction of therapy. Genetic testing available, clinical role uncertain at this time.

Answer 142

Atrial fibrillation: prevention of thromboembolic complications. Advantages: Long history of clinical experience, Once-daily dosing, and Reversal of effect with vitamin K. Disadvantages: Variability in dosage requirements, Dietary restrictions (attention to vitamin K), INR monitoring required, Many drug interactions. Prophylaxis / treatment of venous thromboembolism. Prophylaxis: use generally limited to patients with prosthetic heart valves. Treatment of established disease: heparin for 1st 7-10 days, 3-5 day overlap with warfarin, then warfarin for 6 weeks (1st episode) to 6 months (recurrent episode)

Answer 143

Hemorrhage. Necrosis of fatty soft tissue (esp. females in 1st 10 days of therapy, [?] decrease in protein C). GI (nausea, vomiting, diarrhea, cramping); osteoporosis (effects on bone matrix proteins). Contraindicated in pregnancy (crosses placenta); other contraindications similar to heparin

Answer 144

Early signs: Hematuria, excessive menstrual bleeding, gum bleeding after brushing. Managing High INRs and/or Bleeding: INR > therapeutic but < 4.5 / no bleeding: Reduce or skip dose, monitor, resume when therapeutic. INR 4.5 - 10 / no bleeding: Hold 1-2 doses, monitor, resume at lower dose when therapeutic. Vitamin K not routinely recommended; can be used if urgent surgery needed (1-2.5 mg po). INR > 10 / no bleeding: Hold warfarin, administer Vitamin K (2.5-5 mg po) even if not bleeding, resume at lower dose when INR in therapeutic range. Major bleeding: Hold warfarin. Vitamin K 5-10 mg slow IV infusion over 20 minutes (rapid infusion can produce dyspnea, chest and back pains, even death; effect of vitamin K delayed for 1-2 hrs but complete by 24 hrs). Prothrombin complex concentrate (PCC) suggested over FFP (fresh frozen plasma) due to FFP disadvantages (slower onset, risks of allergic reactions-infection transmission, longer prep time, higher volume); recombinant factor VIIa also used

Answer 145

(Increased Prothrombin Time / INR): Pharmacokinetic (inhibit metabolism, thereby increasing levels): Amiodarone, Cimetidine Fluconazole, Fluoxetine, Metronidazole, Rosuvastatin. Pharmacodynamic (interfere with platelet or Vitamin K function): Aspirin (high doses). Oral antibiotics (eliminate intestinal bacteria that contribute to vitamin K levels)

Answer 146

Decreased Prothrombin Time / INR): pharmacokinetic. Increased metabolism: Barbiturates, Carbamazepine, Phenytoin, Rifampin, St. John’s Wort. Decreased absorption: Cholestyramine, Colestipol. Pharmacodynamic (antagonizes warfarin action): Vitamin K (dietary factors)

Answer 147

Newer Oral Anticoagulants (NOAC) | (Non-Vitamin K Antagonists). Approved late 2010, first oral anticoagulant introduced in 50 years.

Answer 148

Acts in the plasma to directly inhibit the activity of thrombin (Factor IIa). Inhibits both free and clot-bound thrombin as well as thrombin-induced platelet aggregation. More rapid onset of action than warfarin, steady state levels of anticoagulant activity in 2-3 days. Does not require frequent monitoring and dosage adjustments as with warfarin (good news). If it is necessary to assess bleeding risk of patients on dabigatran, measurement of ECT is expensive and not widely available at this time (bad news). No antidote for rapid reversal of effect.

Answer 149

Absorption: Highly polar drug with poor oral bioavailability. Prodrug (etexilate) is rapidly absorbed from GI tract and converted to active form by plasma and liver esterases. Eliminated primarily by renal excretion (80-85%); requires dose adjustment if CrCl < 30 ml/min

Answer 150

FDA indication for reducing risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation. NOT yet approved for venous thromboembolism (VTE). Atrial fibrillation: prevention of thromboembolic complications. Advantages relative to warfarin: Evidence for lower rates of strokes and intracranial bleeding, Does not require INR monitoring, and No dietary restrictions. Disadvantages: No method for determining extent of anticoagulation. No specific antidote for reversal Twice daily dosing . Shorter-acting, therefore missed doses could increase risk of thrombosis Dose adjustment in renally impaired patients. Must be dispensed and stored in original container (desiccant in lid to protect against deterioration from humidity)

Answer 151

some type of bleeding occurs in 17% of patients, 3% have a major bleeding event. GI complaints (dyspepsia and gastritis-like symptoms) in 1/3 of patients. May be due to tartaric acid that is added to formulation to improve absorption. Not a CYP450 substrate, fewer drug or food interactions than with warfarin. Anticoagulant effect is irreversible – use hemostatic measures-FFP, then PCC or rVIIa

Answer 152

Acts in the plasma to directly inhibit the activity of factor Xa. Also does not require frequent monitoring and dosage adjustments as with warfarin. No antidote for rapid reversal of effect.

Answer 153

All given orally. Rivaroxaban: metabolized by CYP3A4 (65%) plus renal excretion (35%). Apixaban: metabolized by CYP3A4 (50%) plus renal excretion (25%). Edoxaban: High renal clearance – minimal metabolism, therefore drug should not be used in patients with CrCl > 95 ml/min (variability in maintaining effective plasma levels)

Answer 154

Prevention of DVT in patients following hip-knee replacement surgery and reducing risk of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Rivaroxaban approved for prevention of VTE and treatment of DVT/PE. Atrial fibrillation: prevention of thromboembolic complications. Advantages relative to warfarin: Evidence for lower rates of strokes and fatal bleeding. Does not require INR monitoring. No dietary restrictions. Once-daily dosing for rivaroxaban. Shorter-acting means missed doses could increase risk of thrombosis. Disadvantages: No method for determining extent of anticoagulation. No specific antidote for reversal. Apixaban requires bid dosing. Dose adjustment in renally impaired patients

Answer 155

Bleeding most common effect; major bleeding in <1%. Anticoagulant effect is difficult to reverse – use hemostatic measures-FFP, then PCC or rVIIa

Answer 156

Single dose (40-80 mg) inhibits platelet aggregation up to 8 days (inhibition of COX-1 synthesis of thromboxane in platelets) as nonnucleated platelets cannot synthesize new COX enzyme and new platelets must be formed. Largest concentration of acetylsalicylic acid is in portal vein, thus greater effect on circulating platelet COX-1 (thromboxane A2 synthesis) relative to tissue endothelial cell COX-2 (prostacyclin synthesis) resulting in a decreased tendency for clotting.

Answer 157

ADP (purinergic-P2Y12) receptor antagonists that interfere with ADP-induced platelet aggregation. Clopidogrel is prodrug converted to active metabolite by CYP450, which then irreversibly inhibits receptor. Synergistic actions with aspirin. Ticagrelor is a reversible inhibitor that does not require activation by CYP450.

Answer 158

Blocks phosphodiesterase breakdown of cAMP, elevating cAMP levels and potentiating prostacyclin’s anti-aggregatory action. Combined with aspirin as Aggrenox. Little or no apparent benefit as antithrombotic agent.

Answer 159

Blocks IIb/IIIa receptors on platelet thus preventing integrin and fibrinogen binding that facilitates aggregation (platelet-platelet binding). Advantage of blocking all pathways of platelet activation.

Answer 160

Effective orally in low-dose daily administration (irreversibly inhibits enzyme).

Answer 161

Given orally 3-4 times daily before meals or twice daily as Aggrenox.

Answer 162

are dosed once daily orally; ticagrelor is given orally 2 times daily with meals. Slow onset to maximal inhibition so often given with loading dose

Answer 163

Administered by continuous intravenous infusion

Answer 164

Side effects are generally rare with low dose therapy. Dyspepsia, nausea, vomiting may be dose limiting in some patients; GI bleeding may occur.

Answer 165

Clopidogrel: GI upset, headache, dizziness, upper respiratory infection, bleeding; concomitant use of proton pump inhibitors (PPIs) may inhibit activation of clopidogrel by CYP2C19. Prasugrel: Bleeding (> clopidogrel). Ticagrelor: Bleeding, dyspnea, bradyarrhythmias

Answer 166

Side effects are minimal and transient; some dizziness and GI distress

Answer 167

Major side effect is bleeding

Answer 168

aspirin (chewed and swallowed) plus ADP antagonist

Answer 169

aspirin ± ADP antagonist

Answer 170

aspirin plus ADP antagonists ± GIIb/IIIa inhibitors]

Answer 171

aspirin (enteric coated); secondary prevention of | ischemic stroke: aspirin ± dipyridamole

Answer 172

The central process of fibrinolysis is the conversion of inactive plasminogen to the active proteolytic enzyme plasmin. Proteolytic digestion of fibrin by plasmin then limits extension of thrombus. The regulation of fibrinolysis by plasmin is important site for therapeutic an intervention.

Answer 173

All fibrinolytic drugs produce rapid lysis of thrombi by increasing formation of plasmin from plasminogen resulting in a generalized lytic state, i.e., a tendency towards bleeding rather than clotting. Streptokinase activates both circulating (free) and fibrin-bound plasminogen while tPA (and variants) activate bound plasminogen several hundredfold more rapidly than circulating plasminogen limiting induction of a systemic lytic state

Answer 174

(obtained from streptococcal cultures) Inactive by itself, but forms 1:1 complex with plasminogen (proactivator above), this complex then converts uncomplexed plasminogen to active plasmin. Generally results in systemic activation of plasmin.

Answer 175

Alteplase (Activase). Human tPA from recombinant DNA technology: tPA binds to fibrin and selectively activates bound plasminogen under physiological conditions (i.e., “clot-selective”, but therapeutic levels are 100 times higher)

Answer 176

Newer, modified forms can be given as bolus (reteplase: 2 doses 30 minutes apart; tenecteplase: single bolus) and have prolonged duration of action. Reteplase is less fibrin specific than tPA, while tenecteplase slightly more.

Answer 177

Acute myocardial infarction: Emergency treatment of coronary artery thrombosis; prompt use [within 2 hours] associated with better clinical outcomes. Further reduction in mortality with use of adjunctive drugs (beta-blockers, ACE inhibitors, aspirin). Percutaneous Coronary Interventions [PCI] (balloon angioplasty or stent placement) may be preferred to thrombolytic therapy in some instances. Deep vein thrombosis. Multiple pulmonary emboli

Answer 178

Hemorrhage. Results from two factors: Lysis of physiologic thrombi at sites of vascular injury. Systemic formation of plasmin producing destruction of fibrinogen and factors V and VIII. Frequency similar with all fibrinolytic drugs. Intracranial hemorrhage is most serious complication. Antibody formation with streptokinase can lead to fever, allergic reactions (3%), therapeutic failure

Answer 179

Heparin (UFH) / enoxaparin (LMWH), warfarin, dabigatran, rivaroxaban 

Answer 180

Aspirin, clopidrogel, GIIB/IIIa inhibitors (as class: abciximab / eptifibatide / tirofiban)

Answer 181

Tissue plasminogen activator (tPA) and variants

Answer 182

``` is coronary blood flow. Factors include. Directly related to perfusion pressure (aortic pressure). Blood flows only during diastole (length of diastole related to heart rate, shortened by tachycardia). Blood flow also decreased by increased end diastolic pressure (LVEDP). Inversely proportional to coronary vascular resistance, determined by: Vascular control by metabolites, i.e., autoregulation (e.g., adenosine vasodilation) is most important; damage to endothelium can alter ability of vasculature to dilate and Neural and humoral control (autonomic activity) of vascular tone has only small effect ```

Answer 183

``` Contractile state (myocardial contractility). Heart rate . Myocardial wall tension (LV pressure) and stress (ventricular volume) ```

Answer 184

Primary cause is imbalance between O2 requirement of heart and oxygen supplied to it by coronary vessels. Angina is most often due to atherosclerotic obstruction of large coronary vessels that results in decreased blood supply.

Answer 185

Risk factor modification and amelioration for hypertension, diabetes, cigarette smoking, post- menopausal state, dyslipidemias. Aspirin (low dose). HMG-CoA reductase inhibitors (“statins”)

Answer 186

The goal of therapy is to restore the balance between oxygen demand and oxygen supply by increasing supply or reducing demand. Improve coronary blood flow (MBF). This primary intervention is accomplished surgically with coronary artery bypass grafts (CABG) or percutaneous transluminal coronary angioplasty (PTCA) or pharmacologically with vasodilators. Reduction of myocardial oxygen requirement (MVO2). Achieved pharmacologically through use of vasodilators and negative inotropic and chronotropic agents. Stable angina (aka classic or exertional angina) results from a fixed stenotic endothelialized atheromatous plaque. Imbalance occurs when myocardial oxygen demand increases and the oxygen supply (coronary blood flow) is unable to increase in response Chronic Pharmacotherapy is aimed at reducing oxygen demand with: nitrates, Ca++ channel blockers, and β-blockers

Answer 187

results from coronary vasospasm with or without atheromatous plaque. Imbalance occurs as oxygen supply decreases due to reversible coronary vasospasm (associated with atheromas), commonly at rest. Chronic Pharmacotherapy aimed at reversing or preventing vasospasm and increasing supply with vasodilators (nitrates and Ca++ channel blockers)

Answer 188

results from ruptured atheromatous plague with subocclusive thrombus (platelet-fibrin clot), myocardial infarction from occlusive thrombus generally imminent. Angina at rest, signaled by change in frequency, character, duration, and precipitating factors in patients with stable angina. Medical emergency (acute coronary syndrome). Acute Pharmacotherapy for clot (aspirin, heparin, GPIIB-IIIA inhibitors, PTCA/CABG, fibrinolytics), arrhythmias (β-blockers), and pain (NTG, morphine). Post-MI Therapy with ACEIs, “statins”, β-blockers, aspirin, clopidrogel (if post-stent).

Answer 189

[Nitroglycerin (Nitrostat, Transderm-Nitro, Nitropaste), Isosorbide mononitrate (Ismo) and Isosorbide dinitrate (Isordil)]. Mechanism of Action: Nitrates are converted to nitric oxide (NO) at or near the plasma membrane of vascular smooth muscle cells via a process that may involve thiol (-SH) compounds and aldehyde dehydrogenase. NO then activates guanylate cyclase, increasing the conversion of GTP to cGMP, causing increased levels of cGMP then lead to relaxation of smooth muscle via an incompletely understood mechanism relating to decreased levels of myosin phosphate. Thiol compounds and aldehyde dehydrogenase may be involved in the tolerance seen with continuous

Answer 190

nitrate administration. NO formation following activation of cholinergic muscarinic, bradykinin, or histamine H1 receptors on endothelial cells mediates the vasodilatory actions of these endogenous molecules

Answer 191

Ca++ entry and binds calmodulin. This activates MLCK leading an increase in myosin-PO4, causing contraction. Calcium channel blockers block Ca++ entry causing an increase in relaxation

Answer 192

triggers an increase in Ca++ causing contraction

Answer 193

triggers an increase in cAMP causing relaxation

Answer 194

this results in reduction of LVEDP (PCWP) and systemic vascular resistance that is associated with decreased wall tension, which decreases myocardial O2 requirement (primary effect). Also improves perfusion of ischemic myocardium (secondary effect).

Answer 195

Low oral bioavailabilty; administered orally (sustained-release), sublingually, transdermally, parenterally. Best route for rapid achievement of therapeutic levels is sublingual. Half-lives of 2-8 min (rapid denitration in liver). Active mononitrate metabolite has half-life of 1-3 hrs. Sublingual administration. Rapid pain relief (45 sec-5 min) lasting < 30 min. May repeat x 3 every 5 min, if no relief seek assistance (strongly indicative of impending MI). Transdermal administration. Once daily dosing initially effective for 24 hours (often removed at night to prevent tolerance development). Oral administration. Higher doses needed (first pass metabolism); duration probably only 4-8 hours (even with sustained release). Exception is isosorbide mononitrate.

Answer 196

Treatment of acute angina (sublingual tablet, translingual spray). Prophylaxis for chronic angina (long-acting oral, topical, transdermal). Control of blood pressure in perioperative hypertension. In congestive heart failure associated with acute myocardial infarction (intravenous nitroglycerin, “unloads” damaged heart).

Answer 197

Side effects are direct extension of therapeutic vasodilation: Throbbing headache (30-60%), orthostatic hypotension (optimal therapeutic doses generally relieve symptoms with no more than a 10- 15 mm drop in blood pressure), reflex tachycardia, facial flushing. Tachyphylaxis (tolerance) can occur with continuous exposure (depletion of nitrosothiol groups required for nitric oxide [NO] formation or inactivation of aldehyde dehydrogenase by free radical formation). Thus, nitrate free interval of 6-14 hours each day is recommended.

Answer 198

[Verapamil (Calan), Diltiazem (Cardizem), Nifedipine (Procardia)]

Answer 199

Block of L-type Ca++ channels in cardiac and smooth muscle (vascular smooth muscle is most sensitive, arterioles > veins). Prevents calcium entry into cell leading to smooth muscle relaxation and vasodilation. Little or no effect on N-type (neurotransmitter release) or T-type (heart and neurons). Agents differ in selectivity for vascular vs heart calcium channels. Dihydropyridines (prototype is nifedipine) have a greater ratio of vascular (relaxation) to cardiac (contractility, SA node impulse generation, AV nodal conduction) effects. Verapamil and diltiazem, each at a distinct site, have prominent effects at cardiac nodal tissue (phase 0 at SA and AV node) and on cardiac muscle (phase 2)

Answer 200

Short-acting dihydropyridines (nifedipine) may rapidly lower blood pressure with reflex activation of the SNS, tachycardia, exacerbation of angina and increased risk for angina. AVOID USE. Longer acting dihydropyridines (amlodipine [Norvasc], felodipine [Plendil]) and extended-release formulations (nifedipine [Procardia XL], diltiazem [Cardizem CD], verapamil [Calan XR]) result in fewer symptomatic side effects and reduced likelihood of angina if the medication is suddenly withdrawn. Oral bioavailability varies widely (10-90%). Most agents are extensively protein bound (> 90%) and extensively metabolized by cytochrome P450, so plasma levels may fluctuate unexpectedly if administered with inhibitors or inducers of these enzymes.

Answer 201

Use in angina results in a long-lasting decrease in peripheral vascular resistance reducing heart O2 requirement and coronary arterial tone (aiding in spasm-induced angina). Other uses include: arrhythmias (cardiac tissue), hypertension (vascular tissue), subarachnoid hemorrhage (cerebral vasculature) [esp., Nimodipine (Nimotop)], inhibition of premature labor (uterine smooth muscle) [nifedipine]

Answer 202

Direct extention of therapeutic actions. Cardiac depression (cardiac arrest, bradycardia, AV block, congestive heart failure); more likely with verapamil or diltiazem. Minor toxicities: Flushing / edema / dizziness (esp. with the dihydropyridine [nifedipine] class), nausea, constipation (more common with verapamil), gingival hyperplasia possible.

Answer 203

unique action with no effect on heart rate or blood pressure. Failure of late Na+ current to inactivate is seen in a number of cardiovascular disease states, including ischemia and hypertrophy. In ischemia, this persistent late Na+ current can lead to intracellular Na+ overload which in turn leads to reversal of the Na+-Ca++ exchanger and subsequent intracellular Ca++ overload. Ca++ overload can result in both mechanical dysfunction (increased diastolic tension) and further imbalance between O2 demand and supply. Ranolazine inhibits this late Na+ current, thus preventing the deleterious events described above

Answer 204

Absorption: Highly variable (bioavailability 35-55%); substrate of p-glycoprotein efflux transporters, so administration with inhibitors may increase plasma levels. Elimination: Primarily hepatic via CYP3A4 (use should be avoided with strong inhibitors). Administered twice daily

Answer 205

Add-on to standard anti-anginal therapy - reduces symptoms of chronic stable angina and increases exercise capacity. Can substitute for beta-blockers if they are not tolerated or contraindicated

Answer 206

Can prolong the QT interval (inhibition of HERG channel - IKr) in dose-dependent manner. Torsades has not been observed, but use cautiously with QT-prolonging drugs. Cardiovascular effects (∼ 5%) include bradycardia, hypotension, palpitations, edema

Answer 207

Useful in stable angina due to hemodynamic effects that result in decreased heart rate, blood pressure, and contractility with a subsequent decrease in O2 requirements (during rest and exercise). Can block the reflex tachycardia associated with use of nitrate vasodilators in chronic stable angina. NOT vasodilators, thus no role in variant (vasospastic) angina

Answer 208

Indicated in angina patients with concomitant hypertension or arrhythmias that are responsive to β- blockers.

Answer 209

Asthma (relative), peripheral vascular disorders, abrupt withdrawal that precipitates sympathetic overactivity.

Answer 210

Target is block of beta-1 adrenergic receptors in the heart, reducing rate and contractility, leading to a reduction in myocardial oxygen demand

Answer 211

Primary target is relaxation of venous capacitance vessels leading to a reduction in preload and a reduction in myocardial oxygen demand. The action to dilate coronary artery vessels, resulting in an increase in myocardial oxygen supply, plays a greater role in variant angina.

Answer 212

Primary target is block of L-type calcium channels to reduce vasoconstriction in both coronary and noncoronary vessels, increasing coronary blood flow and reducing cardiac afterload (all classes). Diltiazem and verapamil also have secondary action in the heart to decrease rate and contractility, reducing myocardial oxygen demand.

Answer 213

ALL drug groups decrease O2 requirement (demand) by decreasing peripheral vascular resistance and / or decreasing cardiac output. Nitrates and Ca++-channel blockers can reverse arterial spasm which would tend to increase blood flow / O2 supply.

Answer 214

The M-mode echo, which provides a 1D view, is used for fine measurements. Temporal and spatial resolutions are higher because the focus is on only one of the lines from the 2D trace

Answer 215

LDL infiltrates into the subendothelial space. The LDL is modified (oxidized, glycosylated). Release of proinflammatory cytokines (TNFα, Il-1, Il-6, IFN), increase expression of cell adhesion molecules (CAMS), monocyte chemotactic protein-1 (MCP-1), and IL-8. Monocytes are recruited to clean up the oxidized LDL. Phagocytosis of LDL leads to foam cell formation. Foam cells and T-lymphocytes within the plaque cause matric metalloproteinase (MMP) secretion and activation of tissue factors. Plaque rupture occurs in “unstable” lesions, leading to vessel thrombosis and acute coronary events.

Answer 216

used for synthesis and repair of cell membranes and organelles. precursor of steroid hormones

Answer 217

fuel source for muscle use and adipose tissue storage

Answer 218

The role of lipoprotein particles is to transport triacylglycerols (a.k.a. triglycerides) and cholesterol in the blood between all the tissues of the body. The lipoprotein particles have hydrophilic groups of phospholipids, cholesterol, and apoproteins directed outward. Such characteristics make them soluble in the salt water-based blood pool. Triglyceride-fats and cholesteryl esters are carried internally, shielded from the water by the phospholipid monolayer and the apoproteins.

Answer 219

are lipoprotein particles that consist of triglycerides (85–92%), phospholipids (6–12%), cholesterol (1–3%), and proteins (1–2%). They transport dietary lipids from the intestines to other locations in the body. Chylomicrons are one of the five major groups of lipoproteins (chylomicrons, VLDL, IDL, LDL, HDL) that enable fats and cholesterol to move within the water-based solution of the bloodstream.

Answer 220

the calcification occurring in degenerated or necrotic tissue, as in hyalinized scars, degenerated foci in leiomyomas, and caseous nodules. This occurs as a reaction to tissue damage, including as a consequence of medical device implantation. Dystrophic calcification can occur even if the amount of calcium in the blood is not elevated. (A systemic mineral imbalance would elevate calcium levels in the blood and all tissues and cause metastatic calcification.) Basophilic calcium salt deposits aggregate, first in the mitochondria, and progressively throughout the cell. These calcifications are an indication of previous microscopic cell injury. It occurs in areas of cell necrosis in which activated phosphatases bind calcium ions to phospholipids in the membrane.

Answer 221

deposition of calcium salts in otherwise normal tissue, because of elevated serum levels of calcium, which can occur because of deranged metabolism as well as increased absorption or decreased excretion of calcium and related minerals, as seen in hyperparathyroidism. In contrast, dystrophic calcification is caused by abnormalities or degeneration of tissues resulting in mineral deposition, though blood levels of calcium remain normal. These differences in pathology also mean that metastatic calcification is often found in many tissues throughout a person or animal, whereas dystrophic calcification is localized.

Answer 222

a type of lipoprotein made by the liver. VLDL transports endogenous triglycerides, phospholipids, cholesterol, and cholesteryl esters. It functions as the body's internal transport mechanism for lipids. In addition it serves for long-range transport of hydrophobic intercellular messengers, like the morphogen Indian hedgehog (protein).

Answer 223

Biologic Plausibility: LDL cholesterol elevations lead to atherosclerosis. Epidemiology: LDL cholesterol elevations are associated with an increased risk of coronary heart disease. Randomized Trials: LDL cholesterol lowering reduces heart disease related events and deaths. Atherogenic lipoproteins (LDL, VLDL, IDL, remnants) are central to the initiation and progression of atherosclerosis. This process is slow and progressive and likely starts at a young age. Acute events occur in unstable plaques. Cholesterol lowering stablizes plaque and reduces ASCVD-related events

Answer 224

Reduction in lipid content of atheromatous plaque core. Decrease in inflammatory cells (macrophages and T-lymphocytes). Decreased MMP and tissue factor activation. Decreased propensity for plaque rupture. Decrease in thrombogenesis. Regression of atherosclerosis

Answer 225

Adults 20 y/o and older should have a fasting lipid panel done at least every 5 years. Obtain complete lipoprotein profile after 8-12 hour fast. LDL is primary lipoprotein of “interest”. Measure: Total Cholesterol, HDL, and Triglycerides. Calculate LDL using Friedewald formula:In fasted state: Total-C = LDL + HDL + VLDL. VLDL = TG÷5 when TG are < 400 mg/dl. Therefore: LDL = Total Cholesterol – HDL – (TG/5)

Answer 226

Based on population curves: Average LDL-C in the US is 130 mg/dl. Based on “biology”: Other mammalian species have LDL-C ~60-70 mg/dl. Hunter gatherer populations have LDL-C ~60-70 mg/dl. We’re born with LDL-C ~30 mg/dl. Based on morbidity: Majority of CHD occurs with “average” cholesterol. CHD can/does occur with “low” cholesterol. Is there a threshold at which point no atherosclerosis occurs?

Answer 227

a type of accidental cell death typically caused by ischemia or infarction. In coagulative necrosis the architecture of dead tissue is preserved for at least a couple of days.[1] It is believed that the injury denatures structural proteins as well as lysosomal enzymes thus blocking the proteolysis of the damaged cells. The lack of lysosomal enzymes allows it to maintain a "coagulated" morphology for some time. Like most types of necrosis if enough viable cells are present around the affected area regeneration can occur.

Answer 228

(or colliquative necrosis) is a type of necrosis which results in a transformation of the tissue into a liquid viscous mass.[1] Often it is associated with focal bacterial or fungal infections. In liquefactive necrosis, the affected cell is completely digested by hydrolytic enzymes, resulting in a soft, circumscribed lesion consisting of pus and the fluid remains of necrotic tissue. Dead leukocytes will remain as a creamy yellow pus.[1] After the removal of cell debris by white blood cells, a fluid filled space is left. It is generally associated with abscess formation and is commonly found in the central nervous system.

Answer 229

a form of cell death in which the tissue maintains a cheese-like appearance. The dead tissue appears as a soft and white proteinaceous dead cell mass.

Answer 230

Contraction band necrosis is a type of uncontrolled cell death (necrosis) unique to cardiac myocytes and thought to arise in reperfusion from hypercontraction, which results in sarcolemmal rupture. Can occur as early as 2-4 hours.

Answer 231

occur due to edema after 4-12 hours.

Answer 232

are nodules found in the hearts of individuals with rheumatic fever. They result from inflammation in the heart muscle and are characteristic of rheumatic heart disease. collections of plump, reactive-looking mononuclear cells, lymphocytes and macrophages

Answer 233

While definitely thickened, the leaflet commissures are not clearly fused (you can still distinguish the two leaflets from each other). Fusion is seen in Rheumatic Heart Disease. Medicine often has lots of names to describe the same disease process. Ballooning / tenting / hooding / myxomatous degeneration have been used as descriptors of the changes seen in this type of valve. The leaflets are fibrotic / thickened with a vaguely myxoid appearance (myxoid / myxomatous degeneration) on histologic evaluation. Myxoid appearance is prominent on MICROSCOPIC examination The chordae tendinea appear to be slightly thickened, likely in response to stress of prolapse

Answer 234

Tachyarrhythmias, Palpitations, Atrial fibrillation, Chest pain, and Shortness of breath

Answer 235

Atrial thrombus formation due to regurgitation and incomplete emptying / stasis-> emboli. Arrhythmias. Vegetations on damaged leaflets-> emboli. Bacterial endocarditis (consider antibiotics prior to dental work and surgery in patient with known mitral valve prolapse). With persistent regurgitation / insufficiency-> cardiac failure

Answer 236

Etiology: Can be familial / inherited: e.g. can be seen in Marfan and Ehlers-Danlos syndromes. Can be seen sporadically without a known underlying process. Clinical: Can manifest with midsystolic “click” and / or late systolic murmur (regurgitation). Toxic-Metabolic: Increased frequency in patients taking "Fen-Phen" (fenfluramine/phentermine) for weight loss (now off the market; fenfluramine most closely linked to heart valve damage and pulmonary hypertension). Sex Predominance: More common in women, especially with lean / thin habitus

Answer 237

carotid artery atherosclerosis with thrombus formation. Mural thrombus in left atrium due to atrial fibrillation, endocarditis of mitral or aortic valve (infective or non-infective), and mural thrombus in left ventricle due to myocardial infarct.

Answer 238

Previous damage to and fibrotic repair valve-> altered blood flow across valve-> damage to endothelial cells-> thrombosis / vegetation formation. Vegetations: small, lines of closure of the valve leaflets

Answer 239

In lupus – presumed damage to valve surface -> thrombus. There can be underlying damage to valve in context of connective tissue disease, like valvulitis with fibrinoid necrosis, inflammation of the valve leaflet. Vegetations: Small or medium-sized; on either one or both sides of the valve leaflets. Mitral and tricuspid most affected

Answer 240

Either normal valve - or - underlying valve disease, Nonbacterial Thrombotic Endocarditis (NBTE). Along line of closure. Associations: Cancer (especially mucin secreting carcinomas), Sepsis, Hyperestrogenism, and Burns

Answer 241

Normal or Abnormal Valve. Large, irregular aggregates; cusps +/- chordae tendineae. May damage valve. Formation: Damage of valve by bacteria or yeast-> fibrin and platelet deposition-> vegetation or Sterile Vegetation becomes colonized by bacteria or yeast. Acute IE: typically virulent bacteria: e.g. Staph. Aureus. Subacute: typically low virulence bacteria: e.g. Strep. viridans; yeast

Answer 242

Various carcinomas can manifest with hypercoagulability including pancreas, colon, prostate, breast. Procoagulant Process: Tissue factor derived from tumor or mucin itself may be to blame. Thrombosis may be considered a paraneoplastic process

Answer 243

non-tender, small erythematous or haemorrhagic macular or nodular lesions on the palms or soles only a few millimeters in diameter that are indicative of infective endocarditis.

Answer 244

painful, red, raised lesions found on the hands and feet. They are associated with a number of conditions, including infective endocarditis, and are caused by immune complex deposition.

Answer 245

are retinal hemorrhages with white or pale centers. They can be composed of coagulated fibrin including platelets, focal ischemia, inflammatory infiltrate, infectious organisms, or neoplastic cells. They are usually caused by immune complex mediated vasculitis often resulting from bacterial endocarditis. Roth's spots may be observed in leukemia, diabetes, subacute bacterial endocarditis, pernicious anemia, ischemic events, hypertensive retinopathy and rarely in HIV retinopathy.

Answer 246

lesion is concentric and located in the media. Composition is collagen, glycoproteins in diabetes. Risk factors include hypertension and diabetes. Organs producing symptoms include brain, eyes (retinas), kidneys, and nerves).

Answer 247

lesion is eccentric and located in the intima. Composition is lipid debris, inflammatory cells, collagen/ fibroblasts, smooth muscle cells, and calcium salts (dystrophic calcification=mineralization). Risk factors include hypertension, diabetes, and hyperlipidemia. Can create symptoms when located in coronary arteries and aorta and major branches (carotid, renal, and iliac).

Answer 248

Lipid accumulations which have been dissolved out during tissue processing

Answer 249

Accumulation of acellular ("necrotic") material including cholesterol clefts and other debris. Accumulation of excessive extracellular material -- collagen . Mineralization: dystrophic = purple, granular material

Answer 250

often forms after bleeding (hemorrhage). When blood leaves a ruptured blood vessel, the red blood cell dies, and the hemoglobin of the cell is released into the extracellular space. Are located in the cytoplasm of macrophages during atherosclerosis.

Answer 251

after 4-12 hours occasionally dark molting appears. After 12-24 hours dark mottling does appear. After 1-3 days, mottling with yellow tan infarct centers appear. After 3-7 days, hyperemic border with central yellow-tan softening. After 7-10 days, maximally yellow tan and soft with depressed red-tan margins. 10-14 days, red gray depressed infarct borders. 2-8 weeks later, gray-white scar progressive from border toward core of infarct. After more than two months, scarring is complete