Atherosclerosis - Mod 3

Atherosclerosis

• Atherosclerosis is an inflammatory disease of blood vessels, causing thickening and hardening of the vessel walls.
• It involves the accumulation of lipid-laden macrophages, forming plaques in the arteries.
• This process can affect vascular systems throughout the body, leading to peripheral artery disease, coronary artery disease, and cerebrovascular disease.
• Plaque development begins with endothelial injury caused by risk factors like smoking, hypertension, diabetes, high LDL, low HDL, and autoimmunity.
• Inflammation and expression of adhesion molecules contribute to macrophage recruitment and further vascular damage.
• Oxidized LDL attracts monocytes to form foam cells and fatty streaks, which contribute to plaque growth and vessel wall damage.
• Fibrous plaques develop as smooth muscle cells proliferate and produce collagen, and migrate across fatty streaks creating a fibrous cap.
• Plaque rupture exposes underlying tissue, stimulating platelet adhesion, clotting cascade, and thrombus formation, possibly leading to ischemia and infarction.

Cellular Injury and Death during Ischemia and Oxidative Stress

• Ischemia: Insufficient blood supply to tissues, depriving cells of oxygen and nutrients.
• Oxidative Stress: Imbalance between reactive oxygen species (ROS) production and the body's ability to detoxify or repair damage from ROS.
• Mechanisms of Cellular Injury: ATP depletion, calcium overload, free radical formation, inflammation.
• Necrosis: Passive cell death due to acute injury, characterized by cell swelling, membrane rupture, and release of cellular contents, triggering inflammation.
• Apoptosis: Active, programmed cell death, initiated by specific signals, characterized by cell shrinkage, DNA fragmentation, and formation of apoptotic bodies (without inflammation).

Myocardial Infarction (MI)

• MI, or heart attack, is caused by sudden blockage of blood flow to the heart muscle.
• Blockages are usually caused by a blood clot formed in a coronary artery.
• Pathophysiology involves plaque rupture, thrombus formation, and prolonged ischemia leading to cellular death (apoptosis) and tissue necrosis.
• Extent of damage depends on location, size of blockage, and restoration time.
• Clinical manifestations can vary, including chest pain, shortness of breath, sweating, nausea, vomiting, lightheadedness, and anxiety.

Thrombus vs Embolus

• Thrombus: A blood clot formed within a blood vessel that obstructs blood flow.
• Embolus: Any substance traveling in the bloodstream that obstructs blood flow when reaching a vessel too small to pass through. Examples include blood clot, air bubble or foreign material.

Hypertension

• Hypertension is persistently elevated systemic arterial blood pressure.
• Risk factors include positive family history, male sex, advancing age, black race, obesity, high sodium intake, low magnesium/potassium/calcium, diabetes, smoking, and heavy alcohol consumption.
• Pathophysiological mechanisms include increased activity of the sympathetic nervous system, overactive renin-angiotensin-aldosterone system (RAAS), sodium and water retention by kidneys, defects in renal sodium excretion, and insulin resistance.

Endothelial Dysfunction

• Endothelial cells line blood vessels and play a role in regulating blood flow.
• Dysfunction impairs the production of vasodilators and promotes vasoconstriction.
• Inflammation contributes to the development and progression of hypertension and endothelial dysfunction.

Congenital Heart Diseases (Tricuspid Atresia)

• Tricuspid atresia is a congenital heart defect wherein the tricuspid valve is missing or abnormally developed.
• Resultant pathophysiology involves lack of communication between the right atrium and right ventricle, leading to blood flow through an ASD or PFO to the left side, and to the lungs.
• Blood mixing on the left side causes hypoxemia and mild cyanosis.

Tetralogy of Fallot

• Tetralogy of Fallot is a congenital heart defect characterized by 4 specific defects.
• Ventricular septal defect (VSD): hole in the wall separating ventricles
• Pulmonary stenosis: narrowing of the pulmonary valve, controlling blood flow from the right ventricle to the lungs
• Overriding aorta: Aorta shifted slightly to the right over the VSD
• Right ventricular hypertrophy.

Patent Ductus Arteriosus (PDA)

• PDA is a condition where the ductus arteriosus (connection between aorta and pulmonary artery in a fetus) fails to close after birth.
• Pathophysiology involves blood flow from the aorta (higher pressure) to the pulmonary artery, increasing blood flow to the lungs, potentially leading to heart failure if untreated.

Ventricular Septal Defect (VSD)

• VSD is a congenital heart defect characterized by a hole in the wall (septum) separating the ventricles of the heart.
• Pathophysiology involves blood flow from the left ventricle (higher pressure) to the right ventricle, increasing blood flow to the lungs.

Peripheral Artery Disease (PAD)

• PAD is a circulatory problem where narrowed arteries reduce blood flow to the limbs, primarily caused by atherosclerosis (plaque buildup in the arteries).
• Risk factors include smoking, diabetes, high blood pressure, high cholesterol, and family history.
• Clinical manifestations include intermittent claudication (pain during activity relieved by rest).

Deep Venous Thrombosis (DVT)

• DVT is a blood clot formation in a deep vein, typically in the legs.
• Three factors (Virchow's triad) promote DVT: venous stasis, endothelial damage, and hypercoagulability.
• Potential symptoms include pain, swelling, redness in affected areas. Can lead to potentially serious thromboembolizations if not treated.

Left and Right Sided Heart Failure

• Left-sided heart failure: Left ventricle struggles to pump blood effectively to the body.
• Right-sided heart failure: Right ventricle struggles to pump blood effectively to the lungs.
• Pathophysiology of both involves reduced cardiac output, increased workload for the affected side, and pressure differences throughout the heart.

This quiz covers the key aspects of atherosclerosis, an inflammatory disease that affects blood vessels by causing thickening and hardening. It details the mechanisms behind plaque formation and the risk factors that contribute to this vascular condition. Understanding the pathology of atherosclerosis is crucial for recognizing its implications in various cardiovascular diseases.