Cardiovascular Diseases Notes PDF

**[Atherosclerosis: Development, Progression, Risk Factors, and Consequences]** **Atherosclerosis** is an inflammatory disease process that involves the thickening and hardening of the vessel wall. This process is caused by an accumulation of lipid-laden macrophages within the arterial wall, which...

**[Atherosclerosis: Development, Progression, Risk Factors, and Consequences]** **Atherosclerosis** is an inflammatory disease process that involves the thickening and hardening of the vessel wall. This process is caused by an accumulation of lipid-laden macrophages within the arterial wall, which leads to the formation of a lesion called a plaque. Atherosclerosis can affect vascular systems throughout the body and is the leading cause of peripheral artery disease, coronary artery disease, and cerebrovascular disease. - The development of atherosclerotic plaques begins with endothelial injury and dysfunction, which can be caused by risk factors such as smoking, hypertension, diabetes, increased levels of low-density lipoprotein (LDL), decreased levels of high-density lipoprotein (HDL), and autoimmunity. - Other nontraditional risk factors for endothelial injury include increased serum markers for inflammation and thrombosis, adipokines, infection, and air pollution. - Injured endothelial cells become inflamed and are unable to produce normal amounts of antithrombotic and vasodilating cytokine. - These inflamed cells also express adhesion molecules that attract and bind to macrophages and other inflammatory and immune cells. - Macrophages release inflammatory cytokines, such as tumor necrosis factor-alpha (TNF-α), interferons, interleukins, and C-reactive protein. Macrophages also release enzymes that further injure the vessel wall. - Toxic oxygen free radicals generated by the inflammatory process cause LDL oxidation. - Oxidized LDL stimulates the expression of additional adhesion molecules and the recruitment of monocytes that differentiate into macrophages. - These macrophages engulf oxidized LDL, becoming foam cells. - Foam cells then accumulate in significant amounts, forming a lesion called a fatty streak. - Fatty streaks produce more toxic oxygen free radicals and inflammatory mediators, contributing to progressive vessel wall damage. - Oxidized LDL and foam cells activate macrophage release of inflammatory cytokines and recruit autoreactive T cells. This process leads to autoimmune vascular injury. - Fibrous plaques develop as smooth muscle cells proliferate, produce collagen, and migrate over the fatty streak, forming a fibrous cap. - Fibrous plaques can become unstable and rupture due to the effects of shear forces, inflammation, the secretion of neutrophil- and macrophage-derived degradative enzymes, and apoptosis of cells at the edges of the lesions. **Consequences of Ruptured Plaques** Rupture of unstable plaques occurs due to the degradative effects of inflammatory cytokines and enzymes, wall stress, and neurohumoral changes. When a plaque ruptures, the underlying tissue is exposed, resulting in: - Platelet adhesion - Initiation of the clotting cascade - Rapid thrombus formation The thrombus may occlude the affected vessel, resulting in ischemia and infarction. **[Cellular Injury and Death During Ischemia and Oxidative Stress]** **Ischemia** is the insufficient blood supply to a tissue, which deprives the tissue\'s cells of oxygen and nutrients. This deprivation can lead to cellular injury and death. **Oxidative stress** occurs when there is an imbalance between the production of reactive oxygen species (ROS) and the body\'s ability to detoxify these reactive intermediates or repair the resulting damage. ROS are highly reactive molecules that can damage cellular components such as DNA, proteins, and lipids. **Mechanisms of Cellular Injury During Ischemia and Oxidative Stress** - ATP depletion: Ischemia reduces oxygen supply, leading to a decrease in ATP production. ATP is the primary energy source for cells, and its depletion disrupts vital cellular functions. - Calcium overload: Ischemia can cause an influx of calcium ions into cells. Excessive intracellular calcium activates enzymes that damage cell membranes, proteins, and DNA. - Free radical formation: Ischemia and oxidative stress promote the formation of free radicals, which are highly reactive molecules that can damage cellular components. - Inflammation: Ischemia and oxidative stress trigger an inflammatory response that further damages tissues. **[Necrotic and Apoptotic Cell Death]** **Necrosis** and **apoptosis** are two distinct mechanisms of cell death. **Necrosis** is a passive form of cell death that occurs as a result of acute cellular injury. It is characterized by: - Cell swelling - Rupture of the cell membrane - Release of cellular contents - Inflammation **Apoptosis** is an active, programmed form of cell death that is initiated by specific signals. It is characterized by: - Cell shrinkage - DNA fragmentation - Formation of apoptotic bodies - Absence of inflammation **Key Differences** Feature Necrosis Apoptosis ------------------- ------------------------- ---------------------------------- **Initiation** External injury Internal or external signals **Process** Passive Active **Morphology** Cell swelling and lysis Cell shrinkage and fragmentation **DNA breakdown** Random Specific DNA cleavage **Energy** No energy required Energy-dependent **Inflammation** Yes No **[Myocardial Infarction]** Myocardial infarction (MI), also known as a heart attack, is a serious condition that occurs when blood flow to the heart is suddenly blocked, causing damage to the heart muscle. This blockage is usually caused by a blood clot that forms in a coronary artery that has been narrowed by atherosclerosis. **Pathophysiology** - MI is caused by the rupture of an unstable plaque and subsequent thrombus formation. - The thrombus blocks blood flow to a portion of the heart muscle, leading to prolonged, unrelieved ischemia. - After about 20 minutes of myocardial ischemia, irreversible hypoxic injury leads to cellular death (apoptosis) and tissue necrosis. - The extent of myocardial damage depends on the location and size of the blockage, as well as the time it takes for blood flow to be restored. **Clinical Manifestations** The clinical manifestations of MI can vary depending on the size and location of the infarction. However, common symptoms include: - Chest pain - Shortness of breath - Sweating - Nausea - Vomiting - Light headedness - Anxiety **[Thrombus vs. Embolus]** A thrombus is a blood clot that forms within a blood vessel, obstructing the flow of blood. An embolus is anything that travels through the blood vessels until it reaches a vessel that is too small to let it pass. When this happens, the embolus blocks the flow of blood. An embolus can be: - A blood clot that has broken loose from a thrombus - A clump of bacteria - A piece of foreign material - An air bubble - A piece of fat - A piece of tumor **[Hypertension: Risk Factors and Pathophysiology]** **Hypertension** is a condition characterized by persistently elevated systemic arterial blood pressure. Risk Factors The risk factors for primary hypertension include: - A positive family history - Male sex - Advancing age - Black race - Obesity - High sodium intake - Low magnesium, potassium, or calcium intake - Diabetes mellitus - Cigarette smoking - Heavy alcohol consumption **Pathophysiological Mechanisms** Primary hypertension is the result of a complex interaction between genetics and environmental factors. The following pathophysiological mechanisms are involved in the development of hypertension: - **Increased activity of the sympathetic nervous system (SNS):** The SNS releases norepinephrine, which causes vasoconstriction, increases heart rate, and promotes sodium and water retention by the kidneys. - **Overactivity of the renin-angiotensin-aldosterone system (RAAS):** The RAAS is a hormone system that regulates blood pressure and fluid balance. In hypertension, the RAAS is overactive, leading to vasoconstriction, sodium and water retention, and vascular remodeling. - **Sodium and water retention by the kidneys:** The kidneys play a crucial role in regulating blood pressure by controlling sodium and water excretion. In hypertension, the kidneys retain excess sodium and water, which increases blood volume and contributes to elevated blood pressure. - **Defects in renal sodium excretion:** Genetic factors can contribute to defects in renal sodium excretion, making individuals more susceptible to developing hypertension. - **Insulin resistance:** Insulin resistance is a condition in which the body\'s cells do not respond properly to insulin, a hormone that regulates blood sugar levels. Insulin resistance is associated with decreased endothelial release of nitric oxide and other vasodilators, renal salt and water retention, and overactivity of the SNS and RAAS. - **Obesity:** Obesity is a major risk factor for hypertension. It contributes to adipocyte dysfunction, ectopic fat deposition, and altered adipokine levels. Adipokines are hormones produced by fat cells that can influence blood pressure regulation. Increased leptin and decreased adiponectin levels, which are commonly seen in obesity, are associated with increased SNS and RAAS activity, insulin resistance, decreased renal sodium excretion, inflammation, and myocyte hypertrophy. - **Endothelial dysfunction:** The endothelium, the inner lining of blood vessels, plays a crucial role in regulating vascular tone and blood pressure. Endothelial dysfunction, which can be caused by factors such as smoking, hypertension, and diabetes, impairs the production of vasodilators and promotes vasoconstriction. - **Inflammation:** Inflammation contributes to the development and progression of hypertension. It promotes endothelial dysfunction, vascular remodeling, and renal dysfunction. **[Primary vs. Secondary Hypertension]** **Primary hypertension,** also called essential or idiopathic hypertension, is diagnosed when there is no identifiable secondary cause for the hypertension. It accounts for 90% to 95% of hypertension cases. **Secondary hypertension** is diagnosed when a specific underlying disease process or medication is found to be causing the elevation in blood pressure. This type of hypertension accounts for only 5% to 10% of cases. **[Congenital Heart Diseases]** **Tricuspid Atresia** **Tricuspid atresia** is a heart defect present at birth (congenital) in which the tricuspid heart valve is missing or abnormally developed. - Pathophysiology: In tricuspid atresia, there is no communication between the right atrium and right ventricle because the tricuspid valve, which normally connects these two chambers, is missing. Deoxygenated blood returning to the right atrium flows through an atrial septal defect (ASD) or a patent foramen ovale (PFO) to the left atrium. From there, the blood enters the left ventricle and is either pumped into the systemic circulation through the aorta or flows through a ventricular septal defect (VSD) into the hypoplastic (underdeveloped) right ventricle and then to the lungs. - The mixing of deoxygenated and oxygenated blood in the left side of the heart results in systemic hypoxemia (low blood oxygen) and mild cyanosis (a bluish discoloration of the skin and mucous membranes). - A PDA is often necessary to ensure adequate blood flow to the lungs for oxygenation. **Tetralogy of Fallot** **Tetralogy of Fallot** is a rare condition that is characterized by four specific heart defects: 1. Ventricular septal defect (VSD): A hole in the wall (septum) that separates the two lower chambers (ventricles) of the heart. 2. Pulmonary stenosis: Narrowing of the pulmonary valve, which controls blood flow from the right ventricle to the lungs. 3. Overriding aorta: The aorta, which carries oxygen-rich blood to the body, is shifted slightly to the right and lies directly over the VSD. 4. Right ventricular hypertrophy: Thickening of the muscular wall of the right ventricle. - **Pathophysiology:** In TOF, the pathophysiology varies depending on the degree of pulmonary stenosis, the size of the VSD, and the pulmonary and systemic resistance to blood flow. - In cases with a large VSD, pressures are equal in the right and left ventricles. - The direction of blood flow (shunt) through the VSD depends on the difference between pulmonary vascular resistance and systemic vascular resistance. - If systemic resistance is greater than pulmonary resistance, the shunt is from left to right (acyanotic or \"pink tets\"). - If pulmonary resistance is greater than systemic resistance, the shunt is from right to left, resulting in decreased pulmonary blood flow, hypoxemia, and cyanosis. **Patent Ductus Arteriosus (PDA)** PDA is a condition in which the ductus arteriosus, a blood vessel that connects the aorta and the pulmonary artery in a fetus, fails to close after birth. - **Pathophysiology:** The ductus arteriosus normally closes soon after birth as oxygen levels in the blood rise. If it remains open, blood flows from the aorta (which has higher pressure) to the pulmonary artery, leading to increased blood flow to the lungs. - This can cause the heart to work harder and may lead to heart failure if left untreated. **Ventricular Septal Defect (VSD)** VSD is a congenital heart defect characterized by a hole in the wall (septum) that separates the two lower chambers (ventricles) of the heart. - Pathophysiology: A VSD allows blood to flow from the left ventricle (which has higher pressure) to the right ventricle, leading to increased blood flow to the lungs. - The size of the VSD and the pressure difference between the ventricles determine the amount of shunting. - Small VSDs may cause minimal symptoms, while large VSDs can lead to heart failure. **[Peripheral Artery Disease (PAD)]** **Peripheral artery disease** is a common circulatory problem in which narrowed arteries reduce blood flow to your limbs. Underlying Pathophysiological Changes - PAD is primarily caused by atherosclerosis, the buildup of fatty deposits (plaques) in the arteries. - These plaques can narrow or block the arteries, reducing blood flow to the legs and feet. - Risk factors for PAD are similar to those for other forms of atherosclerosis, including smoking, diabetes, high blood pressure, high cholesterol, and a family history of vascular disease. **Clinical Manifestations** Common symptoms of PAD include: - Intermittent claudication: Pain, cramping, or fatigue in the legs or buttocks that occurs during activity and is relieved by rest. - Numbness or tingling in the feet or toes - Sores or wounds on the feet or legs that heal slowly or not at all - Changes in skin color or temperature - Hair loss on the feet and legs - Weak or absent pulses in the feet and legs **[Deep Venous Thrombosis (DVT)]** Deep venous thrombosis (DVT) is a serious condition that occurs when a blood clot forms in a deep vein, usually in the legs. Three factors promote **venous thrombosis**, also known as the **triad of Virchow**: (1) venous stasis, (2) venous endothelial damage, and (3) hypercoagulable states. - **Venous stasis** occurs when conditions limit blood flow through the veins. For example, immobility prevents the muscular pump from increasing blood flow from the lower extremity to the inferior vena cava and right atrium. Heart failure also causes venous stasis because increased diastolic filling pressures reduce venous return. - **Venous endothelial damage** can occur from trauma, caustic intravenous medications, or invasive venous procedures. The healthy endothelium serves as a barrier between the blood and the prothrombotic subendothelium. It also expresses anticoagulant factors. When damaged, endothelial cells lose their anticoagulant properties and express adhesion molecules that activate inflammatory cells and platelets. - **Hypercoagulable states** can be transient or prolonged. For example, pregnancy is associated with both hypercoagulability and venous stasis. Active cancer is another cause of hypercoagulability because cancer cells produce tissue factor which activates coagulation, fibrin synthesis, and platelet activation. **DVT** is often asymptomatic. However, some cases involve venous inflammation that causes pain and redness. A thrombus that significantly obstructs venous blood flow can increase venous pressure behind the clot, leading to edema of the extremity. - While most thrombi will eventually dissolve without treatment, untreated **DVT** has a high risk of thromboembolization. Persistent venous obstruction may lead to chronic venous insufficiency and postthrombotic syndrome, which is associated with pain, edema, and ulceration of the affected limb **[Left and Right Sided Heart Failure]** Heart failure is a condition that develops when the heart can no longer pump blood effectively. It can affect the left side, the right side, or both sides of the heart. **Left-Sided Heart Failure** Left-sided heart failure occurs when the left ventricle is unable to pump blood effectively to the body. **Pathophysiological Mechanisms:** - Increased preload: Preload is the amount of blood that fills the ventricle before it contracts. Conditions that increase preload, such as kidney failure, can overwork the heart and lead to left-sided heart failure. - Decreased contractility: Contractility is the ability of the heart muscle to contract forcefully. Conditions such as MI can damage the heart muscle, decreasing its contractility and leading to left-sided heart failure. - Increased afterload: Afterload is the pressure that the heart has to pump against to eject blood. Conditions that increase afterload, such as hypertension, can overwork the heart and lead to left-sided heart failure. **Right-Sided Heart Failure** Right-sided heart failure occurs when the right ventricle is unable to pump blood effectively to the lungs. **Pathophysiological Mechanisms:** - Right-sided heart failure often develops as a result of left-sided heart failure. As the left ventricle fails, pressure backs up into the pulmonary circulation, increasing the workload of the right ventricle. - Right-sided heart failure can also be caused by conditions that primarily affect the lungs, such as COPD, cystic fibrosis, and acute respiratory distress syndrome (ARDS). - These conditions lead to pulmonary hypertension, increasing the resistance to blood flow from the right ventricle. **Systolic vs. Diastolic Heart Failure** **Systolic heart failure** (heart failure with reduced ejection fraction) is a type of heart failure in which the left ventricle is unable to contract forcefully enough to eject an adequate amount of blood with each heartbeat. - It is characterized by a reduced ejection fraction, which is a measurement of the percentage of blood pumped out of the ventricle with each heartbeat. **Diastolic heart failure** (heart failure with preserved ejection fraction) is a type of heart failure in which the left ventricle is unable to relax and fill with blood properly. - It is characterized by a preserved ejection fraction, but the ventricle is stiff and unable to accommodate a normal volume of blood during diastole. **FAQ: Cardiovascular Diseases** **What are varicose veins and what causes them?** Varicose veins are distended, tortuous, and palpable vessels caused by blood pooling in the veins. They typically occur in the saphenous veins of the legs. The primary causes include damaged vein valves or prolonged venous distention due to gravity. Factors like prolonged standing, constricting garments, genetics, female sex, and pregnancy contribute to their development. **What is Superior Vena Cava Syndrome (SVCS) and how is it diagnosed and treated?** SVCS arises from a blockage of the superior vena cava, hindering blood return from the head, neck, and upper extremities to the heart. Symptoms include facial swelling, distended neck veins, and difficulty breathing. Diagnosis involves chest x-rays, Doppler studies, CT scans, MRI, and ultrasounds. Treatment varies depending on the cause, ranging from radiation therapy and chemotherapy for malignant disorders to balloon angioplasty and bypass surgery for non-malignant causes. **What is hypertension and how does it develop?** Hypertension, or high blood pressure, is a complex condition with various contributing factors. Genetic predisposition coupled with environmental risks leads to neurohumoral dysfunction (involving the sympathetic nervous system, renin-angiotensin-aldosterone system, and natriuretic hormones) and promotes inflammation and insulin resistance. These factors cause sustained systemic vasoconstriction, increasing peripheral vascular resistance. Additionally, inflammation contributes to renal dysfunction, leading to salt and water retention and increased blood volume. Together, these mechanisms lead to sustained hypertension, increasing the risk of damage to organs like the heart, kidneys, brain, and eyes. **What is the role of the renin-angiotensin-aldosterone system (RAAS) in hypertension?** The RAAS plays a critical role in blood pressure regulation and fluid balance. In hypertension, overactivity of the RAAS contributes to both salt and water retention and increased vascular resistance. This occurs through the production of angiotensin II, which causes vasoconstriction and stimulates aldosterone secretion, leading to increased salt and water retention. Medications that block the RAAS, like ACE inhibitors, ARBs, and aldosterone blockers, are effective in reducing blood pressure and protecting target organs. **What is atherosclerosis and how does it contribute to cardiovascular disease?** Atherosclerosis is a specific form of arteriosclerosis characterized by the build-up of plaque within the arterial wall. This plaque is formed by an accumulation of lipid-laden macrophages, leading to thickening and hardening of the vessel wall. Atherosclerosis is a systemic disease affecting various vascular systems and is the leading cause of peripheral artery disease, coronary artery disease (CAD), and cerebrovascular disease. **What is Peripheral Artery Disease (PAD) and what are its symptoms and treatment options?** PAD is a manifestation of atherosclerosis affecting the arteries supplying blood to the limbs, particularly the lower extremities. Symptoms include pain during walking (intermittent claudication) and, in severe cases, critical limb ischemia, potentially leading to gangrene. Treatment aims to manage risk factors like smoking, diabetes, and hypertension. Medications include vasodilators and antiplatelet drugs. For acute or severe cases, revascularization procedures like angioplasty or bypass surgery may be necessary. **What are the different types of angina and their causes?** Angina, or chest pain, results from reduced blood flow to the heart muscle. Stable angina is the most common type, usually triggered by exertion and relieved by rest. It\'s caused by narrowing of coronary arteries due to atherosclerosis. Unstable angina occurs unpredictably and can signal a higher risk of heart attack. It\'s caused by plaque rupture and thrombus formation, leading to transient blockage of a coronary artery. Vasospastic angina, also known as Prinzmetal\'s angina, results from coronary artery spasm, leading to reduced blood flow. Triggers can include stress, cold, smoking, and certain medications. **What are the main differences between heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF)?** HFrEF, previously known as systolic heart failure, occurs when the heart muscle is weakened and cannot pump blood effectively. This leads to a reduced ejection fraction, the percentage of blood pumped out of the ventricle with each heartbeat. HFpEF, or diastolic heart failure, happens when the heart muscle becomes stiff and cannot relax properly during filling. This leads to increased pressure within the heart chambers, even though the ejection fraction might be normal. While both types of heart failure can cause similar symptoms like shortness of breath and fatigue, their underlying mechanisms and treatment approaches differ.