PowerPoint Slideshow about 'Atherosclerosis' - phyre
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The term atherosclerosis, which comes from the Greek words atheros (meaning “gruel” or “paste”) and sclerosis (meaning “hardness”), denotes the formation of fibrofatty lesions in the intimal lining of the large and medium-size arteries such as the aorta and its branches, the coronary arteries, and the large vessels that supply the brain.
Atherosclerosis contributes to more mortality and more serious morbidity than any other disorder in the western world.
There are a number of other less well-established risk factors for atherosclerosis, including:
High serum homocysteine levels
Homocysteine is derived from the metabolism of dietary methionine
Homocysteine inhibits elements of the anticoagulant cascade and is associated with endothelial damage.
Elevated serum C-reactive protein
It may increase the likelihood of thrombus formation;
The presence of some organisms (Chlamydia pneumoniae, herpesvirus hominis, cytomegalovirus) in atheromatous lesions has been demonstrated by immunocytochemistry, but no cause-and-effect relationship has been established.
The organisms may play a role in atherosclerotic development by initiating and enhancing the inflammatory response.
The fibrous atheromatous plaque is the basic lesion of clinicalatherosclerosis.
It is characterized by the accumulation of intracellularand extracellular lipids, proliferation of vascularsmooth muscle cells, and formation of scar tissue.
The lesionsbegin as a elevated thickening of the vesselintima with a core of extracellular lipid (mainly cholesterol,which usually is complexed to proteins) covered by a fibrouscap of connective tissue and smooth muscle.
As thelesions increase in size, they encroach on the lumen of the arteryand eventually may occlude the vessel or predispose to thrombusformation, causing a reduction of blood flow.
The LDLis removed from the circulation by either LDL receptors or byscavenger cells such as monocytes or macrophages.
Approximately70% of LDL is removed by way of the LDL receptordependentpathway.Although LDL receptors are widely distributed,approximately 75% are located on hepatocytes; thusthe liver plays an extremely important role in LDL metabolism.
Tissues with LDL receptors can control their cholesterol intakeby adding or removing LDL receptors.
The scavenger cells, such as the monocytes and macrophages,have receptors that bind LDL that has been oxidized orchemically modified.
The amount of LDL that is removed bythe “scavenger pathway” is directly related to the plasma cholesterollevel. When there is a decrease in LDL receptors orwhen LDL levels exceed receptor availability, the amount ofLDL that is removed by scavenger cells is greatly increased.
Theuptake of LDL by macrophages in the arterial wall can result inthe accumulation of insoluble cholesterol esters, the formationof foam cells, and the development of atherosclerosis.
Endothelial disruption leads to platelet adhesionand aggregation and fibrin deposition.
Platelets and activatedmacrophages release various factors that are thought to promotegrowth factors that modulate the proliferation of smoothmuscle cells and deposition of extracellular matrix in the lesions: elastin, collagen, proteoglycans.
Activated macrophages also ingest oxidized LDL to becomefoam cells, which are present in all stages of atheroscleroticplaque formation.
Lipids released from necrotic foamcells accumulate to form the lipid core of unstable plaques.
Connective tissue synthesis determinates stiffness, calcium fixation and further ulceration of atheromatous plaque.
There are two main coronary arteries, the left and the right, which arise from the coronary sinus just above the aortic valve.
Although there are no connections between the large coronary arteries, there are anastomotic channels that join the small arteries.
The primary factor responsible for perfusion of the coronary arteries is the aortic blood pressure.
Changes in aortic pressure produce parallel changes in coronary blood flow.
The contracting heart muscle influences its own blood supply by compressing the intramyocardial and subendocardial blood vessels. As a result, blood flow through the subendocardial vessels occurs mainly during diastole.
Thus, there is increased risk of subendocardial ischemia when a rapid heart rate decreases the time spent in diastole, and when an elevation in diastolic intraventricular pressure is sufficient to compress the vessels in the subendocardial plexus.
Blood flow usually is regulated by the need of the cardiac muscle for oxygen.
Even under normal resting conditions, the heart extracts and uses 60% to 80% of oxygen in blood flowing through the coronary arteries, compared with the 25% to 30% extracted by skeletal muscle.
Because there is little oxygen reserve in the blood, myocardial ischemia develops when the coronary arteries are unable to dilate and increase blood flow during periods of increased activity or stress.
Heart muscle relies primarily on fatty acids and aerobic metabolism to meet its energy needs. Although the heart can engage in anaerobic metabolism, this process relies on the continuous delivery of glucose and results in the formation of large amounts of lactic acid.
Atherosclerosis is by far the mostcommon cause of CHD, and atherosclerotic plaque disruptionthe most frequent cause of myocardial infarction and suddendeath.
More than 90% of persons with CHD have coronary atherosclerosis.
Most, if not all, have one or more lesions causingat least 75% reduction in cross-sectional area, the point atwhich augmented blood flow provided by compensatory vasodilationno longer is able to assure even moderate increasesin metabolic demand.
There are two types of atherosclerotic lesions:
the fixed orstable plaque, which obstructs blood flow
commonly implicated in chronic ischemic heart disease: stable angina, variant or vasospastic angina, and silent myocardial ischemia;
the unstable orvulnerable plaque, which can rupture and cause platelet adhesionand thrombus formation
commonly implicated in unstable anginaand myocardial infarction.
Acute myocardial infarction (AMI), also known as a heartattack, is characterized by the ischemic death of myocardialtissue associated with atherosclerotic disease of the coronaryarteries.
The pain typically is severe and crushing, often described as being constricting, suffocating. It usually is substernal, radiating to the left arm, neck, or jaw, although it may be experienced in other areas of the chest.
Gastrointestinal complaints are common. There may be a sensation of epigastric distress; nausea and vomiting may occur.
Elevation of the ST segment usually indicates acutemyocardial injury.
When the ST segment is elevated withoutassociated Q waves, it is called a non–Q-wave infarction. Anon–Q-wave infarction usually represents a small infarct thatmay evolve into a larger infarct.
Myoglobin is an oxygen-carrying protein, similar to hemoglobin,that is normally present in cardiac and skeletal muscle. Itis a small molecule that is released quickly from infarcted myocardialtissue and becomes elevated within 1 hour after myocardialcell death, with peak levels reached within 4 to 8 hours. It rapidly eliminates through urine (low molecular weight). Because myoglobin is present in both cardiac and skeletalmuscle, it is not cardiac specific.
Creatine kinase (CK), formerly called creatinine phosphokinase,is an intracellular enzyme found in muscle cells. Muscles, includingcardiac muscle, use ATP astheir energy source. Creatine, which serves as a storage formof energy in muscle, uses CK to convert ADP to ATP. CK exceedsnormal range within 4 to 8 hours of myocardial injuryand declines to normal within 2 to 3 days. There are threeisoenzymes of CK, with the MB isoenzyme (CK-MB) beinghighly specific for injury to myocardial tissue.
The troponin complex consists of three subunits (i.e., troponinC, troponin I, and troponin T) that regulate calcium-mediatedcontractile process in striated muscle. These subunits are releasedduring myocardial infarction. Cardiac muscle forms ofboth troponin T and troponin I are used in diagnosis of myocardialinfarction. Troponin I (and troponin T; not shown) risesmore slowly than myoglobin and may be useful for diagnosisof infarction, even up to 3 to 4 days after the event. It isthought that cardiac troponin assays are more capable ofdetecting episodes of myocardial infarction in which celldamage is below that detected by CK-MB level.