Pathology CVS #5 by Omar BaniErshaid

“Pathology” Lecture #5
Arteriosclerosis and Atherosclerosis

Arteriosclerosis
• Hardening, thickening and loss of elasticity of the arterial wall. “Only arteries”
Three types:
1.Arteriolosclerosis: sclerosis of small arteries and arterioles, may cause
ischemic injury.
2.Monckeberg medial sclerosis:
- Calcific deposits in muscular arteries “tunica media”
- Older than 50, males > females
- No narrowing in the lumen
- Not clinically significant.
3.Atherosclerosis
1. Hyaline arteriolosclerosis:
- Benign hypertension.
- Pink hyaline thickening of the walls, and luminal narrowing
- In the kidneys: narrowing leads to diffuse vascular compromise and
nephrosclerosis (glomerular scarring).
kidneys are the most common site of hyaline arteriosclerosis
- Seen in elderly patients (normo- or hypertensive)
- Common in diabetic microangiopathy
2. Hyperplastic arteriolosclerosis:
- Severe hypertension.
- Onionskin concentric, laminated thickening of walls and luminal narrowing
- The laminations consist of smooth muscle cells and thickened,
reduplicated BM “hyperplastic smooth muscle in media + reduplicated BM
in intima”
- In malignant hypertension: accompanied by fibrinoid deposits and vessel
wall necrosis (necrotizing arteriolitis), prominent in the kidney.
ATHEROSCLEROSIS
• Intimal lesions called atheromas (atheromatous or atherosclerotic plaques)
>> Obstruction and narrowed lumen.
 Atheroma: mass like, subintimal collection of fat, created by deposition of
fat in intima >>> progressively enlarging till obstruction of the lumen.
• Plaques can obstruct vascular lumina.
- Extracellular cholesterol: cholesterol clefts, washed out during routine tissue processing
• Fatty Streaks:
- Minute yellow, flat macules
The main pathologic feature of
- Composed of lipid-filled foamy macrophages
atherosclerosis >>> deposited
- Do not cause any significant flow disturbance.
cholesterol and fats
- Not all progress to atherosclerosis.
0795372799
Constitutional “non-modifiable” Risk Factors
• Genetics: FH, Familial Hypercholesterolemia, multifactorial traits including HTN and DM

• Age >50 yrs
• Gender:
- Males are affected more than females.
- Premenopausal women are relatively protected against atherosclerosis in the absence of other RF, due
to estrogen.
- After menopause, incidence increases (male = female), No benefit of H therapy.
Modifiable Major Risk Factors

• Hyperlipidemia: “cholesterol has the highest risk of developing atherosclerosis”
- low-density lipoprotein (LDL) cholesterol (“bad cholesterol”)
- High-density lipoprotein (HDL) (“good cholesterol”): Higher levels of HDL correlate with reduced risk.
• Hypertension
• Cigarette smoking
• Diabetes mellitus
Additional Risk Factors
• Inflammation: high CRP levels >>> atherosclerosis

• Hyper-homocysteinemia “high homocysteine levels in blood are toxic to endothelial cells”
• Metabolic syndrome:
- Central obesity
- Insulin resistance, hypertension, dyslipidemia (elevated LDL and depressed HDL), hypercoagulability,
and a proinflammatory state
• Lipoprotein(a) levels: LDL-like particle
• Elevated levels of procoagulants
• Lack of exercise and living a competitive, stressful life style (“type A personality”).
PATHOGENESIS
• Endothelial injury leading to increased permeability, leukocyte adhesion, and thrombosis

• Accumulation of lipoproteins
• Platelet adhesion
• Monocyte adhesion to the endothelium, migration into the intima, and differentiation into macrophages and
foam cells
• Lipid accumulation extracellulary and within macrophages
• Smooth muscle cell recruitment due to factors released from activated platelets, macrophages, and vascular
wall cells
• Intimal smooth muscle cell proliferation and ECM production
- Converts fatty streak, into a mature atheroma
0795372799
Most important causes of endothelial dysfunction:
- Hemodynamic disturbances: Plaques occur where there is turbulent blood flow: at ostia of exiting
vessels, at branch points, and along the posterior wall of the abdominal aorta.
- Hypercholesterolemia.
• Lipids:
- The dominant lipids in plaque: cholesterol and cholesterol esters
- Can directly impair endothelial cell function by increasing local oxygen free radical production,
accelerate NO decay, damping its vasodilator activity.
• LDL is oxidized through the action of oxygen free radicals and ingested by macrophages, resulting in foam cell
formation.
• Role of oxidized LDL in atherogenesis
– Stimulates the local release of GF, cytokines, and chemokines
– Increasing monocyte recruitment
– Cytotoxic to endothelial cells and smooth muscle cells
0795372799
Types of Plaque
• Vulnerable plaques: leads to dramatic and acute fatal ischemic complications “highly susceptible for rupture and
hemorrhage, thrombosis”
- Large numbers of foam cells and abundant extracellular lipid
- Thin fibrous caps
- Clusters of inflammatory cells.
• Stable Plaques: leads to chronic ischemia
- Minimal lipid accumulation
- Dense collagen, thick fibrous cap
- Minimal inflammation
Most extensively involved vessels in atherosclerosis:

1. Infrarenal abdominal aorta
2. Coronary arteries
3. Popliteal arteries
4. Internal carotid arteries
5. The vessels of the circle of Willis
Atherosclerotic Stenosis
• At early stages: remodeling of the media “decreased thickness by atrophy or necrosis in smooth muscles” tends
to preserve the luminal diameter by increasing the vessel circumference.
• Critical stenosis: chronic occlusion limits flow so severely that tissue demand exceeds supply.
Acute Plaque Change
• Rupture/fissuring: expose highly thrombogenic plaque constituents

• Erosion/ulceration: Expose the thrombogenic subendothelial BM to blood “platelet and fibrin >>> thrombus
formation >>> micro-emboli”
• Hemorrhage into the atheroma, expanding its volume >>> obstruction >>> sudden infarction
0795372799
Clinical Consequences of Atherosclerotic Disease
• Signs and symptoms related to ischemia in the heart, brain, kidneys, and lower extremities
- Myocardial infarction (heart attack), cerebral infarction (stroke), aortic aneurysms, and peripheral
vascular disease (gangrene of extremities)
• Atheroembolism: Ruptured plaque can discharge debris into the blood, producing microemboli composed of
plaque contents.
• Outcomes depend on: size of the affected vessel, size and stability of the plaques
The End of patho #5
A 66-year-old woman has the sudden loss of movement on part of the left side of her body. She has smoked a pack
of cigarettes a day for the past 45 years. She has vital signs including T 37.1 C, P 80/minute, RR 16/minute, and BP
160/100 mm Hg. A cerebral angiogram reveals occlusion of a branch of her middle cerebral artery. Laboratory
findings include a hemoglobin A1C of 9%.
Which of the following components of blood lipids is most important in contributing to her disease?
A. Chylomicrons
B. Lipoprotein lipase
C. Oxidized LDL
D. VLDL
E. HDL cholesterol
0795372799

Pathology CVS #5 by Omar BaniErshaid

Uploaded by

Copyright:

Available Formats

Pathology CVS #5 by Omar BaniErshaid

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Pathology CVS #5 by Omar BaniErshaid

Uploaded by

Copyright:

Available Formats

“Pathology” Lecture #5

Arteriosclerosis and Atherosclerosis

• Genetics: FH, Familial Hypercholesterolemia, multifactorial traits including HTN and DM

Modifiable Major Risk Factors

Additional Risk Factors

• Inflammation: high CRP levels >>> atherosclerosis

• Endothelial injury leading to increased permeability, leukocyte adhesion, and thrombosis

Most extensively involved vessels in atherosclerosis:

Acute Plaque Change

• Rupture/fissuring: expose highly thrombogenic plaque constituents

The End of patho #5

You might also like