Lecture 14: Cardiovascular Disease I Flashcards
Arteriosclerosis
Hardening of arteries
Atherosclerosis
Development of soft, pasty plaques (“atheromas”) in walls of mainly large and medium arteries
Effects of atheroma development
- Obstruct arterial blood flow
- Precipitate thrombosis
- Weaken arterial wall
Monckeberg medial calcific sclerosis
Age-related calcification of arteries; limited clinical importance
Arteriolosclerosis
Microvasculature sclerosis; assoc. w/ hypertension, diabetes
Atheromas
Intimal lesions made of:
- Cells (sm. muscle, mφ, inflam. cells)
- ECM (collagen, elastin, proteoglycan)
- Lipid (cholesterol esters)
Lipid core + fibrous cap, usually in abd. aorta, coronary/popliteal arteries
Complicated atheromas
Atheroma characterized by any of:
- Calcification
- Rupture/erosion
- Internal hemorrhage
- Assoc. thrombosis
- Medial atrophy/replacement
Fatty streak
Potential precursor of atheromatous plaque.
Foam cell accumul. in intima, does not disturb blood flow
“Response to injury” hypothesis
Main hypothesis for atherosclerosis pathogenesis.
1. Endothelial dysfunction
2. Lipid insudation
3. mφ infiltration
4. Myocyte migration
How does hypertension cause endothelial dysfunction in atherosclerosis?
A-II and mechanical stress on vessel wall due to hypertension generates ROS
Atherosclerosis pathogenesis
- Increased luminal endothelial ICAM/VCAM expression
- Increased leukocyte migration/adhesion
- Mφ accumul. + activation -> foam cell formation
- Sm. muscle migration into intima
- Sm. muscle proliferation + collagen/ECM deposition (fibrous cap)
- Accumul. of EC lipid
Modifiable risk factors of atherosclerosis
- Hyperlipidemia
- Hypertension
- Smoking
- Diabetes mellitus
Non-modifiable risk factors of atherosclerosis
- Age
- Male gender
- Family history
- Genes (LDLR, Apo A, Apo E)
Other minor risk factors of atherosclerosis
- Obesity
- Stress
- Carbs
- Homocysteinemia
Metabolic Syndrome
Complex of 3+ risk factors coexisting in a person incl.:
- Central obesity
- Low HDL, high TGs
- High BP
- Insulin resist./glucose intolerance
- Prothrombotic state
- Pro-inflam. state
Ischemia/IHD
Deficiency of blood in part due to stenosis/obstruction of a vessel; imbalance btwn supply/demand
Symptoms of IHD
- Angina pectoris
- MI
- SCD
- Chronic IHD
IHD pathogenesis
- Fixed coronary obstruction
- Acute plaque change
- Vasoconstriction
- Coronary thrombus
Angina pectoris
Symptom complex comprised of recurrent crushing substernal chest pain, radiating to the left arm/jaw
Types of angina
- Stable (fixed)
- Prinzmetal (variant)
- Unstable (crescendo)
Stable (typical) angina
Precipitated by exertion, relief w/ rest/nitro.
Caused by fixed coronary obstruction
Fixed lesions
Causes symptoms w/ exertion
- Significant: >50% diameter reduction, 75% cross-section. area, nutritional demand met at rest
- Critical: >75% diameter reduction, 90% cross-section. area, chronic IHD
Prinzmetal (variant) angina
Pain occurs at rest; unpredictable.
- Caused by coronary artery spasm on/near plaques or in normal vessels
- Responds to vasodilators (nitro., Ca channel blockers)
Unstable (crescendo) angina
Pain occurs w/ increasing freq., w/ less exertion, or at rest
Acute plaque changes
- Erosion
- Rupture (high chance of occlusive thrombosis, thrombogenic core)
- Hemorrhage
- Thrombosis
Acute Coronary Syndrome (ACS)
- UA, MI, SCD
- EKG changes, elevated CRP
Coronary thrombosis pathogenesis
Plaque rupture creating microthrombi/microemboli -> Unstable Angina; creating occlusive thrombosis -> MI
Vasoconstriction may exacerbate thrombosis-assoc. ischemia (damaged endothelium releases vasoconstrictive factors)
Infarction
= ischemic necrosis caused by:
- Occlusive arterial thrombi
- Thromboemboli
- Vasospasm
- Compression
Why does blockage of venous drainage rarely cause infarction?
Collateral vessels (exception: ovary, testis)
Effects of myocardial ischemia
- Anaerobic glycolysis -> increase lactic acid, inadequate ATP/creatine Pi production
- Cell edema/arrhythmia due to rise in IC Na+, fall in K+
- High IC Ca++ activates degradative enzymes
Factors determining extent of MI
- Location, severity, rate of occlusion
- Vascular bed size
- Ischemic episode duration
- Metabolic demands
- Collateral vessels
Infarct evolution
- Necrosis
- Acute inflam.
- Chronic inflam.
- Organization
- Fibrosis
Troponins
Heart myoprotein. Elevated release to plasma after MI
Contraction band necrosis
Accelerated necrosis of irreversibly damaged myocytes after reperfusion
- Hypercontraction due to massive Ca++ influx from membrane dmg
- Occurs at margins of infarcts
Transmural vs subendocardial MI
Transmural:
- Entire wall due to plaque rupture/thrombosis
- Begins in SE region
- Q waves typical
Subendocardial:
- Inner 1/3rd to 1/2 of wall
- Caused by global reduction in coronary blood flow, not limited to branch zone
- non-Q wave
Sudden Cardiac Death
Death within 1 hour of symptom onset. Highly assoc. w/ severe IHD, cardiomyopathy, myocarditis, cocaine
Heart failure
State in which the heart fails to output sufficient for metabolic requirements; compensatory mechanisms are maxed and sometimes contribute to dysfunction
Congestive Heart Failure
Heart failure assoc. w/ congestion of lungs and other organs
Forward heart failure
Decreased output (systolic dysfunction)
- Contractility, output
Backwards heart failure
Increased end diastolic pressure (diastolic dysfunction)
- Compliance, vein congestion
Pulmonary congestion/edema with heart failure effects
- Congested capillaries/veins
- Septa/alveolar edema
- Hemosiderin-laden mφ’s
Renal effects of heart failure
- Prerenal azotemia
- Acute Tub. Necrosis
- Renin activation
