Atherosclerotic process and the

risk factors

Dr. Budiana Tanurahardja.,Sp.PA

dr. Lisnawati SpPA

Department of Anatomical Pathology

Faculty of medicine University of Indonesia
Center of Anatomic Pathology Studies
 Normal blood vessels
• Arteries : - large/elastic
- medium size/muscular/distribute
- small arteries ( < 2 mm ).
• Arterioles : 20 - 100 u .
• Capillaries: 7 - 8 u.
• Postcapillary venules.
• Collecting venule.
 Normal blood vessels
• Veins : - small.
• - medium.
• - large.
• Lymphatic.
• The main components : - endothelial cells.
• - smooth muscles.
• Tn. intima, tn.media, tn.adventitia.
Normal blood vessels
Normal blood vessels
 Normal blood vessels
• Main cellular components : endothelial cells, smooth
muscle cells
• Endothel : - Weibel- Palade bodies 0,1x0,3u
• storage organelle for vWF.
• - IHC : antibody to vWF (factor VIII related Ag) ;
CD31
• Vascular abnormalities caused by 2 mecha :
• - narrowing/complete obstruction
• - weakening of the walls : dilatation/rupture
 Atherosclerosis
• ARTERIOSCLEROSIS: hardening of the
arteries, 3 patterns :
• 1. ATHEROSLEROSIS : Fibrofatty plaque.
• 2. MONCKEBERG MEDIAL CALCIFIC
SCLEROSIS: calcific deposits in tn. Media.
• 3. ARTERIOLOSCLEROSIS : hyaline and
hyperplastic.
 Atherosclerosis
• Intimal lesion: ATHEROMA/fibrofatty plaques.
• Small arteries: obstruction--> ischemia.
• Large arteries: destruction -->weakening of the
vessel --> aneurysm/ rupture.
• Morphology: fatty streaks --> atheromatous
plaques ( core of lipid -cholesterol/ cholesterol
ester- with fibrous cap).
• Location: aorta abdominalis, a. coronaria,
a.poplitea, aorta thoracica descendens, a.
carotis interna, cycle of Willis etc.
 Atherosclerosis
• Three main components :
• 1. Cells: smooth muscle cells,
macrophag,leukocytes.
• 2. Connective tissue extracellular matrix
including collagen, elastic fibre and
proteoglycans.
• 3. Intracellular and extracellular lipid
deposits.
Atheromatous plaque
Aortic atherosclerosis
Fatty streak
Atheromatous plaque
 Atherosclerotic plaques
1. Stable plaques
2. Unstable plaques
stable plaques un stable when
dynamic alterations occur that lead, to
abrupt luminal narrowing.
The 4 most frequently : plaque
rupture, plaque hemorraghe,
thrombosis medial spasm.
Atheromatous plaque
Nomenclature of atherosclerotic lesions
Atherosclerosis: complications
• Calcification.
• Focal rupture/ gross ulceration
-->thrombus formation -->
microemboli(cholesterol emboli).
• Hemorrhage into plaque --> hematome
--> plaque rupture.
• Superimposed thrombosis --> occlusive--
>organization.
• Weakening of wall--> aneurysmal
dilatation.
Plaque rupture
Atherosclerotic plaque: natural
history
Natural history
 Atherosclerosis: pathogenesis
• Imbibition theory : Virchow 1856 --> modified :
insudation /infiltration hypothesis.
• Encrustation theory : Rokitansky.
• Reaction to injury hypothesis : Ross and Glomset
1976, modified 1986.
• Others : monoclonal hypothesis, intimal cell mass
hypothesis, hemodynamic hypothesis.
• Unifying hypothesis.
 Imbibition theory
• By Virchow in 1856.
• Cellular proliferation in the intima was a
form of low grade inflammation as a
reation to increased filtration of plasma
proteins and lipids from the blood.
• Undergone modification  lipid,
insudation, infiltration hypothesis.
 Encrustation theory
• By Rokitansky.
• Small thrombi composed of platelets,
fibrin and leukocytes collected over foci
of endothelial injury. Organization and
gradual growth of thrombi resulted in
plaque formation.
 Reaction to injury theory
• By Ross and Glomset in 1976, modified in
1986.
• The lesions of atherosclerosis are initiated
as a response to some form of injury to
arterial endothelium.
• The injury may be subtle or desquamation
of endothelal cells.
Reaction to injury theory
Reaction to injury theory
 Other theories/factors
• Monoclonal/oligoclonal hypothesis
• Intimal cell proliferation
• By Benditt and Benditt.
• The plaques may be equivalent to benign
monoconal neoplastic growth ( such as
leiomyomas) and may be initiated by
mutation. This concept based on the idea
that smooth muscle proliferation was the
initial event and the endothelial injury may
be the secondary phenomenon.
 Other theories/factors.
• The mutagenic effects ,from : exogenous
chemical ( hydrocarbons) and/or
endogenous metabolite ( cholesterol ) and/
or virus ( herpes virus m RNA ).
• Infection : Chlamydia pneumoniae and
cytomegalovirus, can infect blood vessel
wall  exhibit persistent ,latent and
recurrent infection. Strongest evidence of
participation : C.pneumoniae
Risk factors
Estimated 10-yr risk of coronary
heart disease
Pathway of lipoprotein metabolism
Pathway of lipoprotein metabolism