2-Aterosclerosis Flashcards
(33 cards)
1- Define Atherosclerosis
1
1- Literally means hardening of the arteries
2- Formation of intimal fibrous plaques with lipid core called atheromas
2- Affects of atherosclerosis
location
(1)
1- Elasctic arteries (aorta)
2- Muscular arteries (coronary)
3- Consequences of atherosclerosis
1
1- Myocardial infarction
2- Cerebral infarction
3- Aortic aneurysm
4- Lower limb gangrene
Athers contributes to more mortality and more serious morbidity than any other disorders in the western world.
4- Describe the atheomatous plaque
2
1- Located in the intima
2- lipid core (LDL)
3- Covered with fibrous cap
4- diameter 0.3 to 1.5 cm
5- Components:
1) Cells ( macrophages, smooth muscle cells, T lymphocytes
2) Connective tissue
3) Lipid deposits
5- What are foam cells?
3
1- A peculiar differentioation stage of macrophages
2- Macrophage binds with oxideized LDL (OxLDL), thus trapping the macrophage in the intima
6- Pathology and pathogenesis
Explain the type of lesions associateed with athers
(4)
1- The fatty streak
2- The fibrous atheromatous plaque
3- Complicated lesion
the ;atter 2 are responsible for the clinically significant manifestations of the disease
7- Sequences in progression of atherosclerosis
5
1- Initial lesion 2- Fatty streak 3- Intermediate lesion 4-Atheroma 5- FIbroatheroma 6- Complicated lesion
8- Define fatty streaks
6
1- thin, flat yellow intimal discolorations that progressively enlarge by becoming thicker and slightly elevated as they grown in length
2- Consists of macrophages and smooth muscle cells distended with lipids ( foam cells)
9- Describe the formation of fatty streaks
7
1- Excess LDL-choestrol accumulation between the endothelium and connective tissues.
2- It is oxidized and phagocytosed.
3- The macrophages produce paracrines that attract smooth muscle cells.
10- Define atheromatous plaque
9
1- The basic lesion of clinical atherosclerosis
2- Accumulation of intracellular and extracellular lipids, proliferation of vascular smooth muscle cells, and formation of scar tissue
3- The lesion is an elevated thickening of the intima with a core of extracellular lipid.
4- The lumen increases in size, they cover the lumen ofd the artery
11- Histological appearance of an atheromatous plaque
10
1- Fibrous cap
(smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans, neovascularization)
2- Necrotic centre
(cell debris, cholestrol crystals, foam cells, calcium)
3- Media
12- Define Complicated lesions
11
1- Advanced complicated lesions are characterized by
- Hemorrhage
- Ulceration
- Scar tissue deposits
2- Thrombosis is the most important complication of atheros
3- It is caused by slowing and turbulence of blood flow in the region of the plaque and ulceration of the plaque.
13- Describe plaque evolution
12
1- Stable plaques
2- Vulnerable plaques
formation of calcified scar tissue.
If damaged, platelets from the plaque, stick to damaged area and a blood clot forms (thrombus). consequences, heart attack.
14- Explain the mechanisms that causes atheros
14
1- Endothelial injury with leukocyte ( lymphocyte and monocyte) adhesion and platelet adherence
2- Smooth muscle cell migration and proliferation
3- Lipid engulfment of activated macrophages
4- Subsequent development of an atherosclerotic plaque with lipid core
15- Mechanism: hypothesis of the reaction of injury
16
1- Atheros as a chronic inflammation and healing response to the endothelial injury
2- Inflammation of blood vessels due to endothelial damage caused by:
1) Hemodynamic disturbances (turbulent flow activates endothelium)
2) Hyperlipidemia, particularly LD with its high cholestrol content
3) products associated with smoking, immune mechanisms, mechanical stress (hypertension)
16- Explain the earliest mechanism of elevated cholestrol levels
(17)
- One of the earliest responses to elevated
cholesterol levels is the attachment of monocytes to the endothelium. - The monocytes emigrate through the cell to cell attachments of the endothelial layer intothe subendothelial spaces, where they are transformed into macrophages.
- Activated macrophages release free radical
that oxidize LDL. - Oxidized LDL
It has a chemotacti effect on lymphocytes and monocytes
It has chemotactic effect on smooth muscle cells from the arterial media and stimulates production of GM-CSF, cytokines, adhesion molecules in the endothelium
It stimulates specific immune system (production of antibodies against oxidized LDL)
17- Explain the mechanisms of complicated lesions
19
1- OxLDL is toxic to the endothelium, causing endothelial loss and exposure of the subendotheilal tissue to blood components
2- Endothelial disruption leads to platelet adhesion and aggregation and fibrin deposition
3- Platelets and activated macrophages release various factors that are thought to promote growth factors that modulate proliferation of smooth muscle cells and deposition of ECM in the lesions: elastins, collagen , proteoglycans
4- Activated macrophages also ingest oxidized LDL to become foam cells, which are present in all stages of atherosclerotic plaque fromation
5- Lipids released from necrotic foam cells accumulate to form lipid core of unstable plaques
6- Connective tissue synthesis determines stiffness, calcium fixation and further ulceration of artheromatous plaque.
18- Types of risk factors related to atheros
21
1- Modifiable risk factors
2- Non modifiable risk factors
19-Describe Non Modifiable risk factors
22
1) Age
2) Male gender
- men are at greater risk than premenopausal women due to the protective effects of estrogen
3) Hereditary
- several genetically determined alterations in lipoproteins and cholestrol metabolism have been identified
20- Describe modifiable risk factors
23
1) Hyperlipidemia 20 C)garette smoking 3) Hypertension 4) Diabetes mellitus 5) Insufficient physical activity 6)a stressful lifestyle 7) obesity
21- Complications of atheros
21
1) Calcification
- Renal artery stenosis
- Angina
- Peripheral vascular disease
2) Rupture
- Myocardial infarction
- Thrombotic stroke
3) Hemorrhage
4) Embolization Distal sites
- Embolic stroke
5) Aneurysm
- AAA
23- Cosequences of Atheros plaque
24
Aneurysm and rupture
- Mural thrombosis
- Embolization
- Wall weakening
2) Occlusion by thrombus
- Plaque rupture
- Plaque erosion
- Plaque hemorrhage
- Mural thrombosis
- Embolization
3) Critical stenosis
- Progressive plaque growth
24- Evidences of the role of hypercholestrolemia in atherogenesis
(28)
- Cholesterol and cholesterol esters are the dominant lipids in atheromatous plaques.
- Genetic defects causing hyperlipoproteinemia are associated with accelerated atherosclerosis. Homozygous familial hypercholesterolemia (defective LDL receptors and inadequate hepatic LDL uptake) can lead to myocardial infarction before age 20 years. Similarly, accelerated atherosclerosis occurs in animal models with engineered deficiencies in apolipoproteins or LDL receptors.
- Other genetic or acquired disorders (e.g., diabetes mellitus, hypothyroidism) that cause hypercholesterolemia lead to premature therosclerosis.
- Significant correlation between the severity of atherosclerosis and the levels of total plasma cholesterol or LDL.
• Lowering serum cholesterol by diet or drugs slows the rate of progression of atherosclerosis, causes regression of some plaques, and reduces the risk of
cardiovascular events.
24- Explainthe correlation of inflammation and atheros
29
1- Observations of-the-inflammatory nature-of- therosclerotic plaques made-by- Rudolf-Virchow in-1858
2- Immune-cells dominate-early lesions
3- Inflammation mediators accelerate-the-progression of-the-lesion
4- Activation of-inflammation stimulates acute-coronary syndromes
5-Inflammation present in-all the-aterosclerotic process
