Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
28 Cards in this Set
- Front
- Back
|
Atherosclerosis:
Literal Definition Characterized by x,y |
Literal Def: "hardening of the arteries"
Characterized by: Vascular diseases all char. by rigidity, often thickening of blood vessels, wall (medial) thinning, and loss of elasticity |
|
|
Atherosclerosis: Frequency in descending order of most commonly involved arteries
|
Most commonly found at branch points where = turbulent BF!!
1. Lower abdominal aorta (abdominal > thoracic, high assoc. with smoking, no vasa vasorum below renal arteries) 2. Coronary arteries (also cerebrovascular arteries) 3. Popliteal arteries (lower extremity arteries) 4. Internal carotid arteries 5. Vessels in the circle of Willis Trick: Look, C Plaque in vessels |
|
|
What are the 5 Major and Minor Risk Factors of atherosclerosis?
|
Non-Modifiable: age, gender (male), family history, genetics
Modifiable: Major Risk Factors *Hyperlipidemia *Hypertension *Cigarette Smoking *Diabetes *Diet Minor Risk Factors: Obesity, Physical Activity, Stress, Hyperhomocysteinemia (Folate Deficiency) Infection and Immune Disorders, Post Menopausal Estrogen Deficiency, Alcohol, Chlamydia, Pneumoniae |
|
|
Name vascular complications of atherosclerosis in the cerebrovascular system, heart, lower extremities, along the aorta
|
1. Coronary Artery Disease
--> Heart – Myocardial Infarction and Ischemia 2. Carotid and Cerebrovascular disease --> Brain – Infarction and Stroke and aneurysms (C of W) --> Aorta – aneurysms, thromboembolism, and stenosis of aorta or aortic branches 3. Peripheral Vascular Disease --> Gangrenous changes in Lower Extremities – peripheral vascular disease 4. Kidneys – renal damage and insufficiency |
|
|
Roddick: Pathogenisis of atherosclerosis
|
Response to injury hypothesis: chronic and repetitive injury of endothelial cells leads to
INSUDATION THEORY: intimal proliferation w/ plasma proteins and lipid entering bv wall --> organization and repetitive growth of thrombi lead to plaque formation |
|
|
Describe the hallmark of the atherosclerotic disease process: the "plaque"
(what does it contain?) |
Fibrous plaque (or atheroma)consists of:
1) a CENTRAL CORE of: CH, CH-E, foam cells, Ca++, necrotic debrit - Core is covered by a SUBENDOTHELIAL FIBROUS CAP: of SMCs, foam cells, fibrin, coag factors, EMC, lymphocytes |
|
|
Describe the intimal thickening process of atherosclerosis that leads to occlusion of small and medium-sized BV
|
1. Altered balance between inhibition and stimulation of SMC growth
2. Formation of a neointima from migration, proliferation, deposition of ECM by smooth muscle cells 3. ECM prolif replaces MACs and other cells--> acute endothelial cell loss or chronic endothelial injury 4. Intimal hyperplasia/ thickening leads to occlusion of small and medium-sized bv 5. Plaques increase in size through lipid accumulation, SMC proliferation, collagen deposition |
|
|
What is the earliest recognizable change of atherosclerosis?
|
The deposition of lipid filled MACs into the intima
--> FATTY STREAK or DOT |
|
|
Name the 5 characteristic lesion of atherosclerosis, the "atheroma" or "fibrofatty plaque"
|
1. Present in the Intima
2. Raised plaque (0.3-1.5cm, but may be larger) 3. Fibrous cap (SMCs, MACs, foam cells, lymphocytes, collagen, elastin, proteoglycans, neovascularization) 4. Lipid rich core (necrotic center containing extra-cellular lipid, cholesterol clefts, calcium, foam cells) 5. Adventitial neovascularization at base of plaque |
|
|
Name 6 acute morpholigic changes that characterize the "Complicated Plaque."
|
1. Fragmented elastic fibers
2. SMC loss and increase in collagen deposition 3. Calcification 4. Acute plaque changes by focal rupture, ulceration, plaque fissuring leading to: (1) hemorrhage into atheroma producing and inc. in volume d/t hematoma (2) Exposure of thrombogenic core leading to thrombus formation (tissue factor) (3) Exposure of thrombogenic basement membrane to blood 5. Production of microemboli (atheroemboli or cholesterol emboli) 6. May induce MI, stroke, gangrene --> ischemic atrophy, infarcts, aneurysms, claudication, angina (cardiac or intestinal) |
|
|
Morphology of Atherosclerotic lesion:
Type I |
Type I: (Initial)
--> isolated macrophage --> foam cells *CAN STILL REGRESS *GROWTH MAINLY BY LIPID ACCUMULATION *FROM FIRST DECADE ON *CLINICALLY SILENT |
|
|
Morphology of Atherosclerotic lesion:
Type II |
Type II: (Fatty Streak)
--> High intracellular lipid accumulation *CAN STILL REGRESS *GROWTH MAINLY BY LIPID ACCUMULATION *FROM FIRST DECADE ON *CLINICALLY SILENT |
|
|
Morphology of Atherosclerotic lesion:
Type III |
Type III: (Intermediate)
--> Type II changes plus small extracellular lipid pools *CAN STILL REGRESS *GROWTH MAINLY BY LIPID ACCUMULATION *FROM THIRD DECADE ON *CLINICALLY SILENT |
|
|
Morphology of Atherosclerotic lesion:
Type IV |
Type IV: (Atheroma, or FFP)
--> Type II changes plus core of extracellular lipid *GROWTH MAINLY BY LIPID ACCUMULATION *FROM THIRD DECADE ON *CLINICALLY SILENT OR OVERT |
|
|
Morphology of Atherosclerotic lesion:
Type V |
Type V: (Fibrotheroma)
--> Multiple lipid cores and fibrous tissue layers have been added (some layers may be calcific, but mainly fibrotic) *GROWTH BY ACCELERATED SMOOTH MUSCLE AND COLLAGEN INCREASE *FROM FOURTH DECADE ON *CLINICALLY SILENT OR OVERT |
|
|
Morphology of atherosclerotic lesion:
Type VI, VII, VIII |
Type VI: (complicated)
--> Surface disruption w/ hemorrhage, hematoma or thrombosis *GROWTH BY THROMBOSIS, HEMATOMA *FROM FOURTH DECADE ON *CLINICALLY SILENT OR OVERT Type VII - Calcification Type VIII - Fibrous w/o lipid |
|
|
Describe three alternate theories of atherogenesis to the chronic endothelial injury theory.
|
1. Monoclonal hypothesis - hyperlipidemia incites monoclonal SMC prolif, migration
2. Infec. d/t Chlamydia pneumonia, CMV, or H. Pylori --> altered systemic lipid metabolism --> circulating inflammatory mediators --> MAC activation w/ plaque weakening d/t matrix metalproteases --> Release of acute phase reactants resulting in plaque associated thrombosis (Inc. PDGF) 3. Insudation theory: infiltration of intima w/ lipid and protein is the primary atherogenic event, accelerated by hypercholesterolemia 4. Thrombogenic hypotesis: organization of repeated mural thrombi on the intimal surgace leads to buildup of plaques filled w/ lipid derived from breakdown of platelets and WBCs |
|
|
Main effect of atherosclerosis on the vessel wall
|
MEDIAL ATROPHY:
- Loss of SMC - Loss of elastic tissue - Myxomatous degeneration - Weakness of vessel wall - Aneurysmal dilation - Formation of aneurysm and associated complications (bleeding, rupture, embolism, death) |
|
|
5 strategies to prevent the atherogenic process
Primary Prevention (delay atheroma formation + regression) Secondary prevention: prevent recurrence Prevention should begin in childhood! |
1. Lipid lowering strategies:
EARLY PHASE OF CH REDUCTION: CH reduction will degrade intracellular lipid (in MACS and SMCs) and slowly reduce extracellular lipid in all stages of plaques --> After 6 mths, stage 1-3 plaques will be mostly normal vs. stage 4,5 will show progressive reduction of extracellular lipid, rare foam cells, absent MACs --> FINAL OUTCOME: conversion of stage 4,5 plaques to fibrocalcific lesions (types 7,8) containing minimal or no lipid! 2. Smoking cessation 3. Dietary Interventions 4. Stress reduction 5. Exercise |
|
|
3 Clinical effects of atherosclerotic coronary disease
|
1. Inadequate tissue perfusion
2. Cardiac muscle ischemia 3. MI |
|
|
What is the role of endothelial injury in atherogenesis?
|
EC Activation d/t
1. hemodynamics, infection, cigarette smoke, cytokines, hypercholesterolemia 2. Systemic endothelial dysfunction 3. Usually no associated w/ endothelial denudation in humans 4. Promotes ingress of WBCs, MACs 5. Increase in endothelial permeability 6. Produces endothelial cell gene product alterations |
|
|
What is the role of Hypercholesterolemia and Abnl Lipoproteinemia in EC activation?
|
Hypercholesterolemia:
- Atheromatous plaques contain plasma derived CH and CH-E - Oxidized LDL - Genetic defects in CH metab - Reduction of serum CH helps Lipoproteinemia Abnormalities: - Inc. LDL cholesterol levels - Dec. HDL cholesterol levels - Inc. Lp(a) |
|
|
Role of SMCs in atheroscleroisis pathogenesis
|
1. Migrate from media to intima and proliferate
2. Synthesize and deposit ECM material incl. collagen --> converts fatty streak to fibrofatty streak --> development of fibrous cap |
|
|
Role of Inflammatory Cells in atherogenesis
|
Recruitment of monocytes:
- adheare to endothelium and migrate into intima - transform into MACs (foam cells) T-Lymphocytes (CD4,8) - Inflammatory cytokines (INF-G, TNF-B) -Fibrogenic mediators, SMC replication |
|
|
Clinical significance of small artery atherosclerotic lesions
|
Comprimise blood flow--> ischemic injury
Plaque disruption --> obstructive thrombosis |
|
|
Clinical significance of large artery atherosclerotic lesions
|
- Luminal narrowing
- Damage media - Produce aneurysms - Shed embolic material to distant sites |
|
|
What are the three patterns of arteriosclerosis?
Name all three, including variants, and the vessel size affected in each |
Three patterns:
(1) Arteriolosclerosis (small art. and arterioles) --> Hyaline - hyaline thickening of arteriolar walls. In kidney (benign nephrosclerosis) assoc. with benign hypertension --> Hyperplastic - proliferative changes marked by concentric, laminated "onion skin" thickening of arteriolar walls. Accompanied by necrotizing arteriolitis, intramural deposition of fibrinoid material in arterioles w. vascular necrosis and inflammation. In kidney (malignant neprhrosclerosis) assoc. w/ malig htn (2) Monckeberg arteriosclerosis (medial calcific sclerosis) inv. media of medium-sized muscular arteries, usually radial and ulner. DOES NOT OBSTUCT BLOOD FLOW! (3) Atherosclerosis (most freq) - medium-sized and large elastic arteries |
|
|
Current concept of pathogenesis of atherosclerosis
|
Primary event - injury to (or dysfunction of) arterial endothelium, which may be produced by hypercholesterolemia, mechanical injury, HTN, immune mechanisms, toxins, viruses, or other infectious agents.
Hyperlipidemia may initiate endothelial inury, promote foam cell formation, act as a chemoattractant for monocytes, inhibit MAC motility, or injury smooth muscle cells |
