Pathophysiology of Arterial Vascular Disease Flashcards
atherosclerosis
- Characterized by intimal thickening caused by the accumulation of a plaque, which contains inflammatory cells, smooth muscle cells, connective tissue and lipids
- Dysregulation of efflux and influx of lipids; more lipids coming into the arteries
- Causes an imbalance in blood-oxygen supply and blood-oxygen demand
- Can be symptomatic or asymptomatic
Arterial Vascular Disease
- Abnormality of the structure and/or function of arterial blood cells
- Caused by atherosclerosis plaque
modifiable risk factors for atherosclerosis
- Diabetes Mellitus (DM)
- Hypertension (HTN)
- Obesity: (BMI >30 kg/m2)
- Cigarette Smoking
- Dyslipidemia: Especially atherogenic dyslipidemia (defined as low HDL and high LDL and TG)
- Physical Inactivity
non-modifiable risk factors for atherosclerosis
- Sex: Male > Female (men have higher risk until women are post-menopausal)
- Age: > 45 years in males; > 55 years in females
- Family history of premature CVD: < 55 years for male relative; < 65 years for female relative; First degree relative that has had an MI or stroke
How does cigarette smoking contribute to atherosclerosis?
- Cigarette smoking
- The stuffs in the cigarette sits on the arterial walls and causes a endothelial dysfunction
- Foreign substance -> inflammatory response
- Increase oxidative stress
- Alter lipid metabolism -> increase LDL, decrease HDL
How does HTN contribute to atherosclerosis?
- Chronically vasoconstricted
- Enhanced calcium sensitivity
- Exacerbating the response to vasoconstrictors
How does DM contribute to atherosclerosis?
Hyperglycemia causes tissue damage -> Contributes to endothelial dysfunction
How does dyslipidemia contribute to atherosclerosis?
Provides more LDL-C to be oxidized, which potentiates an inflammatory response
Identify patients who would benefit from aspirin for primary prevention of ASCVD-related events
- Aged 50 to 59 years
- ≥ 10% 10-year CVD risk
- Life expectancy of at least 10 years
- Willing to take low-dose aspirin daily for at least 10 years
- Should not have increased risk for bleeding
initiation of atherosclerosis
- Endothelial dysfunction
- Development of Fatty Streak
Endothelial dysfunction
- Imbalance between vaso-constriction and dilation
- Inflammation via LDL-C
- Ultimately leads to apoptosis of vascular smooth muscle
Development of Fatty Streak
- Accumulation of LDL-C in the arterial intima -> Oxidized LDL-C potentiates cytokine release -> Cytokines induce expression of adhesion molecules for leukocytes -> Cytokines cause monocytes to differentiate to macrophages and express scavenger receptors -> Scavenger receptors allow macrophages to uptake of oxidized LDL-C, which cause macrophages to become foam cells
- Endothelial dysfunction -> artery becomes porous and allows for oxidized LDL to come into the arterial intima -> leukocytes in blood attaches to them
- Comprised mainly of macrophage foam cells
- Precursor to atheroma
- Accumulation of foam cells in intima produce the “fatty streak”
progression of atherosclerosis
Cytokines cause smooth muscle cells to migrate from media of artery into intima (starting to get stenosis of that vessel) -> Smooth muscle cells divide and develop extracellular matrices, contributing to a growing, fibrotic plaque -> Calcification, fibrosis, and apoptosis, yielding a fibrotic capsule, surrounding a lipid-rich core (AKA – “the necrotic core”) -> more macrophages and monocytes are going to come to that area
risk factors for plaque rupture
- High lipid content
- Higher concentration of macrophages
- Thin fibrous cap of plaque
steps involved in atherothrombosis
- Plaque sits on top of endothelial tissues -> damaged endothelial tissues -> exposes tissue factor -> activates coagulation cascade -> potentiates thrombin production via extrinsic pathway
- Platelets roll along exposed collagen via surface glycoproteins and bind to vWF -> after adhesion, activated platelets release molecules that help promote more activation and vasoconstriction: serotonin, adenosine diphosphate (ADP), thromboxane A2 (TxA2)
