Atherosclerosis Flashcards
explain arterioslecrosis, atherosclerosis, & atherogenesis
Arteriosclerosis: Arteriosclerosis is a general term used to describe the thickening and hardening of the arterial walls. It typically involves a loss of elasticity in medium and large arteries. Arteriosclerosis can occur due to various factors, including age, high blood pressure, and other chronic conditions.
Atherosclerosis: Atherosclerosis is a specific type of arteriosclerosis that involves the formation of atherosclerotic plaques within the inner layers of arteries. These plaques are composed of lipids (fats), cholesterol, calcium, and other substances. Over time, they can narrow and block the arteries, leading to reduced blood flow. Atherosclerosis is a common cause of heart disease, stroke, and other cardiovascular problems.
Atherosclerotic Vascular Disease (ASVD): In the United States, atherosclerosis is often referred to as Atherosclerotic Vascular Disease (ASVD). This term is used to emphasize the connection between atherosclerosis and the various vascular diseases it can lead to, including coronary artery disease, peripheral artery disease, and carotid artery disease.
Atherogenesis: Atherogenesis refers to the process of plaque formation in the arteries. It involves the gradual buildup of atheromatous plaques in the arterial walls. This process begins with the accumulation of lipids and other substances, which can trigger inflammation and lead to the development of fatty streaks and eventually more complex atherosclerotic plaques. Atherogenesis is a key component of atherosclerosis.
explain the consequences and effects of atherosclerosis
Causes Stenosis of Arteries: Atherosclerosis can lead to the narrowing or stenosis of various arteries in the body. This narrowing is primarily due to the buildup of atheromatous plaques within the arterial walls. The arteries mentioned include the aorta (the largest artery in the body), coronary arteries (supplying the heart muscle), popliteal arteries (located in the legs), and cerebral arteries (supplying blood to the brain).
Causes Myocardial Infarctions: Atherosclerosis in the coronary arteries can lead to the reduced blood flow to the heart muscle. This can result in myocardial infarctions, commonly known as heart attacks. When a plaque ruptures or completely blocks a coronary artery, it can lead to the death of heart muscle tissue due to lack of oxygen and nutrients.
Causes Cardiac Arrest: In severe cases, when atherosclerosis leads to a complete blockage of a coronary artery, it can result in cardiac arrest. This is a life-threatening condition where the heart stops beating effectively, and it requires immediate medical intervention.
Causes Cerebral Infarctions (Strokes): Atherosclerosis affecting the cerebral arteries can reduce blood flow to the brain, leading to ischemic strokes. Ischemic strokes occur when a blood clot or plaque obstructs a cerebral artery, causing damage to brain tissue.
Less Commonly Causes Other Conditions: While the most common consequences of atherosclerosis are related to the heart and brain, it can also affect other parts of the body. Less commonly, atherosclerosis can lead to peripheral vascular disease (narrowing of arteries in the limbs), aneurysms (weakening and ballooning of arterial walls), ischaemic heart disease (a broader term for coronary artery disease), ischaemic encephalopathy (brain damage due to reduced blood flow), and mesenteric occlusion (blockage of arteries supplying the intestines).
It’s important to note that atherosclerosis is a progressive condition, and its consequences can be severe.
explain the consequences of atherosclerosis, including the mechanisms behind these consequences
Plaques Cause Stenosis: Atherosclerotic plaques can lead to stenosis, which is the narrowing of arteries. When an artery becomes narrowed due to plaque buildup, it can result in hypoperfusion, meaning that the blood flow to the region that artery serves is reduced. This can occur in various arteries, such as the renal artery, leading to conditions like renal artery stenosis.
Plaques Cause Blood Clots: Atherosclerotic plaques can be unstable and prone to rupture. When a plaque ruptures, it can expose the inner layers of the arterial wall, which triggers the formation of blood clots. These clots can partially or completely block the artery and may lead to conditions like coronary thrombosis (clot formation in the coronary arteries) or cerebral thrombosis (clot formation in the cerebral arteries).
Arterial Hardening (Arteriosclerosis): In addition to narrowing arteries, atherosclerosis can lead to the hardening of arterial walls, a condition known as arteriosclerosis. This hardening can reduce the flexibility and elasticity of the arteries. Arteriosclerosis can increase blood pressure, as less elastic arteries are less able to accommodate changes in blood flow. Increased blood pressure can contribute to conditions such as angina (chest pain) and peripheral vascular disease (narrowing of arteries in the limbs).
Aneurysm Formation: In some cases, atherosclerosis can cause arteries to become wider and develop into aneurysms. An aneurysm is a localized, abnormal dilation or ballooning of an artery. If an aneurysm ruptures, it can lead to severe bleeding. In the brain, this can result in a hemorrhagic stroke.
Plaque Rupture Leads to Embolism: When an atherosclerotic plaque ruptures, it can release small particles, known as emboli, into the bloodstream. These emboli can travel through the bloodstream and may become lodged in smaller arteries, causing embolisms. Depending on where the embolism lodges, it can lead to conditions like coronary embolism or cerebral embolism.
outline the key steps in the development of atherosclerosis
Initial Insult to Endothelium: The process begins with some form of damage or insult to the endothelium, the inner lining of blood vessels. This damage can be caused by factors such as high blood pressure, smoking, or inflammation.
Monocytes Adhere to and Attack Endothelium: In response to the endothelial injury, monocytes, a type of white blood cell, adhere to the damaged endothelium and begin to attack it.
Inflammation Initiated: The adhesion and attack of monocytes trigger an inflammatory response in the arterial wall. Inflammation is a key factor in the progression of atherosclerosis.
Monocytes Migrate into Sub-Endothelial Space: Monocytes move from the bloodstream into the sub-endothelial space, which is located just below the endothelium.
Differentiation into Macrophages: Once in the sub-endothelial space, monocytes differentiate into macrophages. Macrophages are immune cells that play a central role in the development of atherosclerotic plaques.
Lipids (LDL) Collect in Fatty Streaks: Low-density lipoprotein (LDL), often referred to as “bad cholesterol,” starts to accumulate within the sub-endothelial space. This leads to the formation of fatty streaks.
Lipids Become Oxidized: Oxidative processes can lead to the oxidation of LDL particles within the fatty streaks.
Endothelium Damaged by LDL-Ox: The oxidized LDL can damage the endothelium further, perpetuating the inflammatory response.
Lesion Visible as Fatty Streak: Over time, the accumulation of oxidized LDL and inflammatory cells creates a visible lesion, referred to as a fatty streak. This is the earliest visible stage of atherosclerosis.
Macrophages Ingest Oxidized LDL: Macrophages actively ingest and attempt to process the oxidized LDL particles, but they may become overwhelmed by the excessive lipids.
Macrophages Turn into Foam Cells: As macrophages ingest more LDL and become laden with lipids, they transform into foam cells. Foam cells are a hallmark of atherosclerotic plaques.
outline the progression of atherosclerosis, specifically detailing the later stages of plaque development and potential complications
Core Forms of Extracellular Lipid: As the atherosclerotic plaque continues to develop, a core of extracellular lipid material forms within the lesion. This core consists of lipids, cellular debris, and other substances.
Smooth Muscle Becomes Less Elastic: The smooth muscle cells in the arterial wall may become less elastic as the plaque enlarges and matures.
Lumen Still Patent, Vessel Widens: While the plaque continues to grow, the lumen (the inner opening) of the artery remains patent, meaning it is still open. However, the vessel itself may widen due to the plaque’s presence.
A Second Layer of Fat May Form: In some cases, an atherosclerotic plaque can develop a second layer of fat or lipid deposits, further contributing to its size.
Fibrotic or Calcified Lid Forms: The plaque may become more stable as it develops a fibrotic cap or calcified covering. This cap can help contain the plaque.
Surface Shows Surface Defect: The surface of the plaque may show irregularities or defects, which can make it more vulnerable to rupture.
Artery Enlarges (Total Width): The artery itself may enlarge, increasing its total width, as it adapts to the presence of the plaque.
Plaque Ruptures or Thrombus Is Formed: Atherosclerotic plaques are prone to rupture. When a plaque ruptures, it exposes the underlying tissue and can trigger the formation of a blood clot or thrombus.
Vessel May Occlude: In some cases, the formation of a thrombus within the artery can lead to complete occlusion or blockage of the vessel. This can significantly reduce or completely cut off blood flow to the affected area.
Thrombus Becomes an Embolus and Causes Blockage Elsewhere: Sometimes, a thrombus can dislodge from the original site, becoming an embolus. This embolus can travel through the bloodstream and block a blood vessel in another location, potentially causing blockage and damage to another organ or tissue.
explain the key terms related to cardiovascular health
Arteriosclerosis: Arteriosclerosis is a broad term that encompasses the hardening and loss of elasticity in medium or large arteries. This condition can result from various factors, including aging, high blood pressure, and other chronic health issues.
Atherosclerosis: Atherosclerosis is a specific type of arteriosclerosis characterized by the narrowing of an artery due to the buildup of atheromatous plaques. These plaques consist of lipids, cholesterol, and other substances that accumulate in the arterial walls.
Atheroma: Atheroma refers to the nodular collection of soft, flaky, yellowish material found at the center of large atherosclerotic plaques. It primarily consists of macrophages (a type of immune cell) and lipids. Atheromas are a key component of atherosclerotic plaques and are often associated with the inflammatory process within the arterial walls.
outline the risk factors for atherosclerosis, categorizing them as non-modifiable and modifiable
Non-Modifiable Risk Factors:
Advancing Age: Atherosclerosis becomes more common as individuals age. Over time, the risk of plaque buildup and arterial damage increases.
Male Gender: Men generally have a higher risk of developing atherosclerosis compared to women. However, the risk in women increases after menopause.
Genetic Predisposition: Family history plays a significant role. If close relatives have had atherosclerosis or related conditions, your risk may be higher.
Inherited Abnormalities: Some rare genetic disorders, like familial hypercholesterolemia, can lead to extremely high levels of LDL cholesterol, significantly increasing the risk of atherosclerosis.
Untreated Infections: Chronic infections or inflammatory conditions can contribute to the inflammation and endothelial damage that are early steps in atherosclerosis.
Modifiable Risk Factors:
Diabetes Mellitus Type 2: People with uncontrolled or poorly managed type 2 diabetes have an increased risk of atherosclerosis. High blood sugar levels can damage blood vessels and accelerate plaque formation.
Dyslipidemia (High LDL + Low HDL): High levels of low-density lipoprotein (LDL) cholesterol, often referred to as “bad cholesterol,” are a primary contributor to atherosclerosis. Low levels of high-density lipoprotein (HDL) cholesterol, known as “good cholesterol,” can also increase the risk.
Smoking: Smoking not only promotes the production of atherosclerotic plaques but also increases the likelihood of plaque rupture due to its pro-inflammatory and pro-thrombotic effects.
Untreated High Blood Pressure: High blood pressure can damage arterial walls and accelerate the progression of atherosclerosis. It’s a significant risk factor for plaque rupture.
Elevated CRP (C-Reactive Protein): Elevated CRP levels are associated with inflammation, which can contribute to plaque formation and rupture.
Inactivity: Physical inactivity can exacerbate atherosclerosis by contributing to obesity, elevated blood pressure
explain the layers of a healthy arterial wall
Endothelial Layer: The innermost layer of a healthy arterial wall is lined by a single layer of endothelial cells. These cells form a smooth, selectively permeable surface that separates the blood in the lumen from the surrounding arterial wall. The endothelium plays a critical role in regulating blood vessel tone, permeability, and the prevention of blood clot formation.
Intima: The next layer, known as the intima, is situated just beneath the endothelial layer. It includes the sub-endothelial layer, which is a part of the intima. This layer primarily consists of connective tissue and a small number of smooth muscle cells.
Media: The media is the middle layer of the arterial wall. It contains a substantial number of smooth muscle cells, which are responsible for regulating the diameter of the artery, thereby controlling blood flow and pressure.
Adventitia: The outermost layer of the arterial wall is the adventitia, which is made up of connective tissue, nerves, and small blood vessels. It provides structural support and nourishment to the artery.
This layered structure of the arterial wall serves to maintain the integrity and function of the blood vessels. However, when atherosclerosis develops, it typically involves changes in the intima and media layers, leading to the accumulation of atherosclerotic plaques and the narrowing of the arterial lumen.
explain role of lipoproteins and their association with atherosclerosis and cardiovascular health
Lipoproteins Carry Fats: Lipoproteins are molecules that transport fats (lipids) in the bloodstream. Fats are hydrophobic, meaning they don’t mix well with water. Lipoproteins provide a way to transport these hydrophobic fats through the watery environment of the blood.
Composition of Lipoprotein Outer Layer: The outer layer of lipoproteins consists of a single layer of phospholipids and cholesterol molecules. These molecules have hydrophilic (water-attracting) and hydrophobic (water-repelling) portions. The hydrophilic portions face the watery blood plasma, while the hydrophobic portions are oriented away from the water.
Low-Density Lipoproteins (LDL): LDLs are a type of lipoprotein that carries a significant amount of cholesterol and fat molecules. High concentrations of LDL in the blood are associated with an increased risk of atherosclerosis. When LDL levels are elevated, these lipoproteins can deposit cholesterol in the arterial walls, contributing to the formation of atherosclerotic plaques.
High-Density Lipoproteins (HDL): HDLs are another type of lipoprotein, often referred to as “good cholesterol.” HDLs have a role in collecting excess cholesterol from the body’s cells, including arterial plaque, and transporting it to the liver for excretion. High levels of HDL are associated with a reduced risk of atherosclerosis or even the regression of existing plaques.
explain the process of oxidative damage to LDL (Low-Density Lipoprotein) in the context of atherosclerosis
Oxidation of Retained LDL: When LDL particles become trapped and retained in the intima (the innermost layer of the arterial wall), they are susceptible to oxidation. Oxidation occurs when these LDL molecules are exposed to free radicals or oxidative stress within the arterial wall.
Formation of Compounds: As a result of this oxidation, various compounds are generated. These compounds include lipid hydroperoxides, lysophospholipids, and carbonyl compounds. These products are oxidative byproducts and are associated with the inflammatory process within the arterial wall.
Inactivation of Nitric Oxide (NO): Nitric oxide (NO) is a crucial signaling molecule in the body. It acts as a vasodilator, helping to relax and widen blood vessels. In the context of the cardiovascular system, NO plays a key role in regulating blood vessel tone and maintaining healthy blood flow.
Inhibition of NO Function: The compounds formed during the oxidation of retained LDL have the ability to rapidly inactivate NO. This inhibits NO from acting as a vasodilator and signaling molecule. As a result, the normal vasodilatory function of NO is impaired.
Impaired NO function is a critical event in the progression of atherosclerosis. Atherosclerosis is associated with inflammation and oxidative stress within the arterial walls, which can lead to endothelial dysfunction and reduced NO bioavailability. This, in turn, contributes to the narrowing and hardening of arteries and is a key factor in the development of cardiovascular diseases like coronary artery disease.
Efforts to reduce oxidative stress, inflammation, and protect NO function can be important in preventing or managing atherosclerosis and related cardiovascular conditions. This often involves lifestyle changes, such as a heart-healthy diet, regular exercise, and medication when necessary.
