ATHEROSCLEROSIS

THICKENING AND
==
ARTERIOSCLEROSIS LOSS OF
ELASTICITY

ARTERIOLOSCLEROSIS
ATHEROSCLEROSIS (AFFECTS SMALARTERIOLES
IN HYPERTENSION )
(AFFECTS LARGE & MEDIUM SIZED
BLOOD VESSELS).

MONCKEBERG’S MEDIAL CALCIFICATION.

(AFFECTS SMALL AND MEDIUM SIZED ARTERIES)
Endothelial Cell Properties and Functions

1. Maintenance of Permeability Barrier .

2. Elaboration of Anticoagulant, Antithrombotic, Fibrinolytic
Regulators.Prostacyclin, Thrombomodulin , Heparin-like molecules
Plasminogen activator .
3. Elaboration of Prothrombotic Molecules Von Willebrand factor ,Tissue
factor ,Plasminogen activator inhibitor .
4. Extracellular matrixProduction(CollagenProteoglycans).
5. Modulation of Blood Flow and Vascular Reactivity Vasconstrictors:
endothelin, ACE
Vasodilators: NO, prostacyclin
6. Regulation of Inflammation and Immunity IL-1, IL-6, chemokines
Adhesion molecules: VCAM-1, ICAM, E-selectin P-selectin Histocompatibility
antigens
7. Regulation of Cell Growth Growth stimulators: PDGF, CSF, FGF,Growth
inhibitors: heparin, TGF-β.
8. Oxidation of LDL
ATHEROSCLEROSIS
IT IS THE DISEASE OF THE LARGE OR
MEDIUM SIZED MUSCULAR ARTERIES AND
AORTA.
IN THIS THERE IS SUBINTIMAL DEPOSITION
OF LIPID, SLOWLY LEADING TO NARROWING
OF THE VESSEL LUMEN AND WEAKENING OF
THE VESSEL WALL.
THESE CHANGES LEAD TO OBSTRUCTION TO
BLOOD FLOW.
 ↓BLOOD FLOW AND COMPLICATIONS OF
ATHEROSCLEROSIS PRODUCES DISEASES LIKE
MYOCARDIAL INFARCTION,CEREBRAL
INFARCTION.
Table 1: Fractions of Lipoproteins in Serum
Class Sites of Normal Role in
synthesis serum levels Atherosclerosi
s
1. HDL cholesterol Liver, intestine > 40 mg/dl Protective
2. LDL cholesterol Liver < 130 mg/dl Maximum
3. VLDL Intestine, liver < 160 mg/dl Less marked
triglycerides
4. Chylomicrons Liver, intestine, - Indirect
macrophage
Theories explaining Atherosclerosis
1.Insudation Hypothesis :"Lipid infiltration "
lipids from plasma infiltrate and accumulate in vessel wall .(Virchow1886)
 
2.Encrustation Hypothesis:
small initial mural thrombi are the initial event in atherosclerosis.
(Rokitansky1852)
 
3.Monoclonal Hypothesis:
Smooth muscle proliferation starting with one or two cells like in tumours.
 ( Benditt 1973)
 
4.Reaction to injury hypothesis:
Smooth muscle proliferation due to release of growth factors from platelets and
monocytes. (Russel,Ross and John Glomset 1976,1986&1993)
 
5.Intimal cell mass Hypothesis :
Another smooth muscle cell Theory.
Low-density lipoprotein (LDL) is richest in cholesterol
and has the maximum association with
atherosclerosis.

Very-low-density lipoprotein (VLDL) carries much of

the triglycerides and has less marked effect than LDL.

High-density lipoprotein (HDL) is protective against

atherosclerosis.
Many studies have demonstrated the harmful effect of
diet containing larger quantities of saturated fats (e.g.
in eggs, meat, milk etc) which raise the plasma
cholesterol level. On the contrary, a diet low in
saturated fats and high in poly-unsaturated fats (e.g. in
fish, fish oils etc) lowers the plasma cholesterol levels.
Hypertension, increases the risk through mechanical
injury to intimate cells.
Diabetes mellitus, D.M. has greater effect on men
than in women.
Cigarette smoking, smoking 20 cigarettes a day
increases the risk of IHD three times over the non-
smokers.
Obesity, increases the risk due to the associated
hyperlipidaemia and hypercholesterolemia.
Sedentary life style & Lack of physical exercise.
RISK FACTORS FOR ATHEROSCLEROSIS

I. CONSTITUTIONAL FACTORS:
A. AGE: ADVANCING AGE.MOST CASES SEEN
BETWEEN 40-70 YRS.
B. SEX: MALES ARE MORE COMMONLY AFFECTED.
BUT AFTER 70 YRS OF AGE MALES AND FEMALES
ARE EQUALLY AFFECTED.
C. GENETICS: FAMILIAL PREDISPOSITION DUE TO
FAMILIAL CLUSTERING OF OTHER RISK FACTORS.
II. PREVENTABLE MAJOR RISK FACTORS:
A. DIABETES MELLITUS
B. HYPERTENSION
C. CIGARETTE SMOKING
D. HYPERCHOLESTEROLEMIA
E. C-REACTIVE PROTEIN
III. MINOR,UNCERTAIN RISK FACTORS:
-TYPE ‘A’ PERSONALITY, ALCOHOLISM, 0BESITY
LACK OF EXERCISE,HOMOCYSTEINEMIA,
CHLAMYDIA PNEUMONIAE INFECTION,POST
MENOPAUSAL OESTROGEN DEFICIENCY.
Schematic diagram of the mechanism of intimal thickening, emphasizing
smooth muscle cell migration to, and proliferation and extracellular matrix
elaboration in, the intima
PATHOGENESIS
‘RESPONSE TO INJURY’ HYPOTHESIS.
THE MECHANISM IS THE CHRONIC INFLAMMATORY
RESPONSE OF THE ARTERIAL WALL INITIATED BY
INJURY TO THE ENDOTHELIUM.
 THESE CHANGES PROGRESS DUE TO SUSTAINED
INTERACTION BETWEEN LIPIDS, MACROPHAGES
T-LYMPHOCYTES AND SMOOTH MUSCLE CELLS OF
THE ARTERIAL WALL
Histologic features of
atheromatous plaque in the
coronary artery. A, Overall
architecture demonstrating
fibrous cap (F) and a central
necrotic (largely lipid) core (C).
The
lumen (L) has been moderately
narrowed. Note that a segment
of the wall is plaque free
(arrow). In this section, collagen
has been stained blue (Masson's
trichrome stain).
 Higher-power
photograph of a section of the
plaque shown in A, stained for
elastin (black), demonstrating
that the internal and external
elastic membranes are destroyed
and the media of the artery is
thinned under the most advanced
plaque (arrow).
Higher-magnification
photomicrograph at the
junction of the fibrous cap
and core, showing
scattered inflammatory
cells, calcification
(broad arrow), and
neovascularization (small
arrows).
 MORPHOLOGY
3 FORMS:
1.FATTY STREAKS
2.FIBROLIPID PLAQUE
3.FIBROUS PLAQUE.
COMPLICATIONS:
- FISSURING AND ULCERATION
- HEMORRHAGE INTO THE PLAQUE
- SUPERIMPOSED THROMBOSIS
- RUPTURE WITH EMBOLIZATION
- ANEURYSM FORMATION
LOCATION FOR ATHEROSCLEROSIS
 
1. Lower abdominal aorta.
2. Coronary arteries
3. Popliteal arteries.
4. Descending thoracic aorta.
5. Internal carotid arteries
6. Circle of Willis in the brain.
American Heart Association classification of human atherosclerotic lesions from the fatty
dot (type I) to the complicated type VI lesion. The diagram also includes growth
mechanisms and clinical correlations
CLINICAL MANIFESTATIONS OF
ATHEROSCLEROSIS &COMPLICATIONS
1. Cerebral infarction.
2. Myocardial infarction.
3. Carotid atheroma – emboli causing transient
ischemic attacks.
4. Aortic aneurysm which may rupture and cause sudden
death.
5. Peripheral vascular insufficiency with intermittent
claudications.
6. Gangrene of parts affected by atherosclerosis.
PREVENTION OF ATHEROSCLEROTIC VASCULAR DISEASE
PRIMARY PREVENTION
PROGRAMS AIMED AT DELAYING ATHEROMA
FORMATION OR REGRESSION OF ESTABLISHED
LESIONS.
SECONDARY PREVENTION
PROGRAMS INTENDED TO PREVENT
RECURRENCE OF EVENTS LIKE MYOCARDIAL
INFARCTION OR STROKE IN SYMPTOMATIC
PATIENTS