Done By
:
Nurmaganbet Samal
Atherosclerosis
Checked By :
1
Department of
Foreign languages
GM – 043
-2
Normal Blood Vessel
Wall
- Vessel walls are organized into three concentric layers: intima, media, and adventitia
- These are present to some extent in all vessels but
are most apparent in larger arteries
and veins.
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Normal Blood Vessel
Wall
Blood vessel
walls
1. The three
tunics:
a) Tunica intima
(1) Endothelium
(2) Subendothelial layer
b) Tunica
media
(1) Smooth
muscle
(2) Elastin
c) Tunica
adventitia (externa)
(1) CT(Connective
tissue) surrounding TM(Tunica Media)
(2) Arterioles
in larger vessels
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Normal Blood Vessel
Wall
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Normal Blood Vessel
Wall
- Arterial walls are thicker than corresponding veins at the same level
of branching to accommodate pulsatile flow and higher blood pressure.
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Classes of Arteries
Arteries
a) Elastic arteries – large arteries
near heart
b) Muscular (distributing) arteries – thick tunica
media
c) Arterioles- Diameter regulated
by vasoconstriction/dilation
Atherosclerosis
affects mainly elastic and muscular arteries and hypertension affects
small muscular arteries and arterioles.
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Atherosclerosis
- Atherosclerosis is a disease of large and medium-sized
muscular arteries and is characterized by –
- endothelial dysfunction,
- vascular inflammation, and
- the buildup of lipids, cholesterol, calcium, and cellular
debris within the intima of the vessel wall.
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Atherosclerosis
It is characterized
by intimal lesions called atheromas (also called Atheromatous or atherosclerotic
plaques), that protrude into vascular lumina.
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Atheromatous plaque
- An Atheromatous plaque consists of a raised lesion
with a soft, yellow, grumous core of lipid (mainly cholesterol and cholesterol
esters) covered by a firm, white fibrous cap.
- Besides obstructing blood flow, atherosclerotic plaques
weaken the underlying media and can themselves rupture, causing acute
thrombosis.
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Atheromatous plaque
Atherosclerosis or Arteriosclerosis
is a slow and progressive building up of plaque, fatty substances, cholesterol,
cellular waste products, calcium and fibrin in the inner lining of an
artery.
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Atherosclerosis
- Atherosclerosis primarily affects elastic arteries
(e.g., aorta, carotid, and iliac arteries)
- Large and medium-sized muscular arteries (e.g., coronary
and popliteal arteries).
- In small arteries, atheromas can gradually occlude
lumina, compromising blood flow to distal organs and cause ischemic
injury.
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Atherosclerosis
- Atherosclerosis also takes a toll through other consequences
of acutely or chronically diminished arterial perfusion, such as mesenteric occlusion,
sudden cardiac death, chronic IHD, and ischemic encephalopathy.
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Risk Factors for
Atherosclerosis
Major risk factors
(Non Modifiable)-
- Increasing Age
- Male gender
- Family history
- Genetic abnormalities
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Risk Factors for
Atherosclerosis
Lesser, Uncertain,
or Nonquantitated Risks-
- Obesity
- Physical Inactivity
- Postmenopausal estrogen deficiency
- High carbohydrate intake
- Lipoprotein(a)
- Hardened (trans)unsaturated fat intake
- Chlamydia pneumoniae infection
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Risk Factors for
Atherosclerosis
Potentially Controllable-
- Hyperlipidemia
- Hypertension
- Cigarette smoking
- Diabetes
- C-reactive protein
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Age as a risk
factor
- Age is a dominant influence.
- Although the accumulation of atherosclerotic plaque
is typically a progressive process, it does not usually become clinically
manifest until lesions reach a critical threshold and begin to precipitate
organ injury in middle age or later.
- Thus, between ages 40 and 60, the incidence of myocardial
infarction in men increases fivefold
- Death rates from IHD rise with each decade even into
advanced age.
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Gender
- Premenopausal women are relatively protected against
atherosclerosis and its consequences compared with age-matched men
- Myocardial infarction and other complications of atherosclerosis
are uncommon in premenopausal women unless otherwise predisposed by
diabetes, hyperlipidemia, or severe hypertension.
- After menopause, the incidence of atherosclerosis-related
diseases increases and with greater age exceeds that of men.
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Genetics
- The familial predisposition to atherosclerosis and
IHD is multifactorial.
- In some instances it relates to familial clustering
of other risk factors, such as hypertension or diabetes
- In others it involves well-defined genetic derangements
in lipoprotein metabolism, such as familial hypercholesterolemia that
result in excessively high blood lipid levels.
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Hyperlipidemia
- Hyperlipidemia-more specifically, hypercholesterolemia-is a major risk factor for atherosclerosis;
- Even in the absence of other risk
factors, hypercholesterolemia is sufficient to stimulate lesion development.
- The major component of serum cholesterol
associated with increased risk is low-density lipoprotein (LDL) cholesterol
("bad cholesterol")
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Hyperlipidemia
- LDL cholesterol has an essential physiologic role
delivering cholesterol to peripheral tissues.
- In contrast, high-density lipoprotein (HDL, "good
cholesterol") mobilizes cholesterol from developing and existing
atheromas and transports it to the liver for excretion in the bile.
- Consequently, higher levels of HDL correlate with
reduced risk.
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Factors affecting
plasma lipid levels
- High dietary intake of cholesterol and saturated fats
(present in egg yolks, animal fats, and butter, for example) raises
plasma cholesterol levels.
- Diets low in cholesterol and/or with higher ratios
of polyunsaturated fats lower plasma cholesterol levels.
- Omega-3 fatty acids (abundant in fish oils) are beneficial,
whereas (trans)unsaturated fats produced by
artificial hydrogenation of polyunsaturated oils (used in baked goods
and margarine) adversely affect cholesterol profiles.
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Factors affecting
plasma lipid levels
- Exercise and moderate consumption of ethanol both
raise HDL levels, whereas obesity and smoking lower it.
- Statins are a class
of drugs that lower circulating cholesterol levels by inhibiting hydroxy
methylglutaryl coenzyme A reductase, the rate-limiting enzyme in hepatic
cholesterol biosynthesis.
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Hypertension
- On its own, hypertension can increase the risk of
IHD by approximately 60% in comparison with normotensive populations
- Left untreated, roughly half of hypertensive patients
will die of IHD or congestive heart failure, and another third will
die of stroke.
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Cigarette Smoking
- Cigarette smoking is a well-established risk factor in men
- An increase in the number of women
who smoke probably accounts for the increasing incidence and severity
of atherosclerosis in women.
- Prolonged (years) smoking of one
pack of cigarettes or more daily increases the death rate from IHD by
200%.
- Smoking cessation reduces that
risk substantially.
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Diabetes Mellitus
- Diabetes mellitus induces hypercholesterolemia as well as a markedly increased predisposition
to atherosclerosis.
- Other factors being equal, the
incidence of myocardial infarction is twice as high in diabetic as in Nondiabetic individuals.
- There is also an increased risk
of strokes and a 100-fold increased risk of atherosclerosis-induced
gangrene of the lower extremities.
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Additional Risk
Factors
- Despite the identification of hypertension, diabetes,
smoking, and hyperlipidemia as major risk factors, as many as 20% of
all cardiovascular events occur in the absence of any of these.
- other "nontraditional" factors contribute
to risk.
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Lipoprotein a
or Lp(a)
- Lipoprotein a or Lp(a), is an altered form of LDL that
contains the apolipoprotein B-100 portion of LDL linked to apolipoprotein
A;
- Increased Lp(a) levels
are associated with a higher risk of coronary and cerebro vascular
disease, independent of total cholesterol or LDL levels.
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Additional Risk
Factors
- Stressful lifestyle ("type
A" personality);
- Obesity - Due to
- Hypertension
- Diabetes
- Hypertriglyceridemia and
- Decreased HDL.
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Pathogenesis of
Atherosclerosis
- The contemporary view of atherogenesis is expressed
by the response-to-injury hypothesis.
- This model views atherosclerosis as a chronic inflammatory
response of the arterial wall to endothelial injury.
- Lesion progression occurs through interactions of
modified lipoproteins, monocyte-derived macrophages, T lymphocytes,
and the normal cellular constituents of the arterial wall.
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Pathogenesis of
Atherosclerosis
1) Endothelial
Injury
- Initial triggering event in the development of Atherosclerotic
lesions
- Causes ascribed to endothelial injury in include mechanical trauma, hemodynamic forces, immunological
and chemical mechanisms, metabolic agents like chronic hyperlipidemia,
homocystine, circulating toxins from systemic infections, viruses, and
tobacco products.
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Pathogenesis of
Atherosclerosis
- Intimal Smooth Muscle Cell Proliferation
- Endothelial injury causes adherence aggregation and
platelet release reaction at the site of exposed sub endothelial connective
tissue.
- Proliferation of intimal smooth muscle cells is stimulated
by various mitogens released from platelets adherent at the site of
endothelial injury.
- These mitogens include platelet derived growth factor
(PDGF), fibroblast growth factor, TNF-ά.
- Proliferation is also facilitated by nitric oxide
and endothelin released from endothelial cells.
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Pathogenesis of
Atherosclerosis
3) Role of Blood
Monocytes
- Though blood monocytes do not possess receptors
for normal LDL, LDL does appear in the monocyte cytoplasm to form foam
cell.
- Plasma LDL on entry into the intima undergoes oxidation.
- Oxidized LDL formed in the intima is readily taken
up by scavenger receptor on the monocyte to transform it to a lipid
laden foam cell.
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Pathogenesis of
Atherosclerosis
- Oxidized LDL stimulates the release of growth factors,
cytokines, and chemokines by endothelial cells (EC)and macrophages that
increase monocyte recruitment into lesions.
- Oxidized LDL is cytotoxic to ECs and smooth
muscle cells (SMCs )and can induce Endothelial dysfunction.
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Pathogenesis of
Atherosclerosis
4) Role of Hyperlipidemia
- Chronic hyperlipidemia in itself may initiate endothelial
injury and dysfunction by causing increased permeability.
- Increased serum concentration of LDL and VLDL promote
formation of foam cells, while high serum concentration of HDL has anti-atherogenic
effect.