Cardiovascular - Atherosclerosis Midterm Notes PDF

3 1 CARDIOVASCULAR - Atherosclerosis 1. Cause of Atherosclerosis Primary Cause: o Atherosclerosis is a chronic inflammatory disease caused by the accumula9on of lipid-laden macr...

3 1 CARDIOVASCULAR - Atherosclerosis 1. Cause of Atherosclerosis Primary Cause: o Atherosclerosis is a chronic inflammatory disease caused by the accumula9on of lipid-laden macrophages within the arterial wall, leading to the forma8on of a lesion known as a plaque. o The process is ini8ated by endothelial injury due to risk factors like hypertension, dyslipidemia, smoking, and diabetes. o Oxidized low-density lipoprotein (LDL) plays a cri8cal role as it is phagocytosed by macrophages, forming foam cells, which are essen8al in the development of faAy streaks—the earliest stage of atherosclero8c lesions. 2. Pathophysiology of Atherosclerosis The process of atherosclerosis development occurs in four main stages, as follows: 1. Endothelial Dysfunc9on: o Endothelial injury ini8ates the process due to exposure to risk factors such as hypertension, smoking, hyperglycemia (diabetes), and hyperlipidemia. o Injured endothelial cells become inflamed and lose their ability to produce normal amounts of vasodilatory and an8thrombo8c factors (like nitric oxide). o The injured endothelium increases its expression of adhesion molecules, which bind immune cells like monocytes and T-lymphocytes. 2. FaKy Streak Forma9on: o LDL par9cles penetrate the damaged endothelium and are oxidized by reac8ve oxygen species. o Macrophages engulf oxidized LDL, forming foam cells, which cluster to create the first visible lesion, the faKy streak. o FaAy streaks may be rela8vely innocuous but have the poten8al to progress to more severe lesions. 3. Forma9on of a Fibrous Plaque: o Smooth muscle cells migrate from the tunica media to the tunica in8ma (the inner layer of the blood vessel wall). o These smooth muscle cells proliferate and secrete extracellular matrix (ECM) components like collagen and elas9n, forming a fibrous cap over the lipid core. o The fibrous cap stabilizes the plaque, but the core remains lipid-rich, increasing the risk of rupture. 4. Complicated Plaque (Plaque Rupture) and Thrombus Forma9on: o Plaque rupture exposes the thrombogenic lipid core and extracellular matrix proteins to the bloodstream. o This exposure ac8vates platelets, leading to the forma8on of a platelet plug and eventually a thrombus. o If the thrombus is large enough, it can occlude blood flow, leading to ischemia or infarc8on.  2 o Alterna8vely, fragments of the thrombus may break off, forming an embolus, which can occlude smaller downstream vessels. 3. Disease Transmission Transmission: o Atherosclerosis is not a transmissible disease. o However, environmental exposure to risk factors such as secondhand smoke may indirectly contribute to its development. o There is also some evidence of a role for chronic infec8ons (like Chlamydia pneumoniae) in promo8ng chronic vascular inflamma9on, but this remains controversial. 4. Risk Factors for Atherosclerosis Risk factors for atherosclerosis are divided into non-modifiable and modifiable categories, with addi8onal factors influencing disease progression. Non-Modifiable Risk Factors Age: Risk increases with age as endothelial integrity declines. Gender: Men are at higher risk, but postmenopausal women experience an increased risk due to the loss of estrogen. Family History: A family history of early-onset cardiovascular disease is a known risk factor. Ethnicity: Certain ethnic groups, such as African, Asian, and First Na9ons popula9ons, are at greater risk due to gene8c and environmental factors. Modifiable Risk Factors Dyslipidemia: High LDL cholesterol and low HDL cholesterol are key drivers of atherogenesis. Hypertension: Causes endothelial injury, leading to dysfunc8on and promo8ng plaque forma8on. CigareKe Smoking: Promotes the oxida8on of LDL, damages endothelium, and increases thrombogenicity. Diabetes Mellitus: Chronic hyperglycemia damages the endothelium and promotes chronic inflamma8on. Obesity/ Increased Waist Circumference: Linked to metabolic syndrome, which includes insulin resistance, hypertension, and dyslipidemia. Sedentary Lifestyle: Increases risk of metabolic syndrome and obesity, both of which contribute to atherosclerosis. Diet: Diets high in saturated fats, trans fats, and simple sugars increase the risk of atherosclerosis. Addi9onal Risk Factors Markers of Inflamma9on: High levels of C-reac9ve protein (CRP) and other inflammatory cytokines indicate ongoing vascular inflamma8on. Microbiome: Changes in gut microbiota have been linked to increased produc9on of trimethylamine N-oxide (TMAO), which may promote atherogenesis.  3 Chronic Kidney Disease: Associated with vascular calcifica8on and accelerated atherosclerosis. Environmental Factors: Air pollu9on and exposure to environmental toxins are associated with increased oxida8ve stress, which promotes atherogenesis. Medica9ons: Certain medica8ons, like oral contracep8ves, have been linked to increased cloXng risk. Summary Table Criteria Atherosclerosis Chronic inflammatory disease ini8ated by endothelial injury from factors like Cause hypertension, smoking, and diabetes. Accumula8on of oxidized LDL, foam cells, and smooth muscle cells creates plaques. 1. Endothelial dysfunc9on → 2. FaKy streak → 3. Fibrous plaque → 4. Pathophysiology Complicated plaque (rupture and thrombosis). Transmission Not transmissible. It is a non-infec8ous, lifestyle-related disease. Non-Modifiable: Age, sex, ethnicity, family history. Modifiable: Smoking, Risk Factors hypertension, diabetes, dyslipidemia, obesity, sedentary lifestyle, diet.