Atherosclerosis

Prof Mary Leader 2017

 Learning Objectives
Define Atherosclerosis
Describe the risk factors and
pathogenesis of Atherosclerosis
Describe the clinical presentation
and consequences of Atherosclerosis
 Normal Vasculature

Arteries
Elastic, muscular/distributing, small
Arterioles
Capillaries
Venules
Veins
 Vascular Endothelial Cells
Serve as semipermeable membrane.
Maintain blood tissue interface.
Modulate vascular tone and blood flow.
Regulate immune and inflammatory
reactions ?? Altering flow and leakage
permeability
Modify lipoproteins atheroma in
arterial wall.
Regulate growth of other cell types,
esp smooth fibrous ?? muscle cells.
 Atherosclerosis

Hardening of the arteries

Deposition of atheroma on larger
elastic or muscular arteries
Definition
Atheroma is a fibrolipid plaque in the
intima
 Consequences of
Atherosclerosis
1. Infarction cell necrosis due to
blood flow
2. Ischaemia
3. Source for emboli to break of
4. Vessel wall dilatation (aneurysm)
 Atherosclerosis
What are the clinical consequences of
atherosclerosis?
Myocardial infarction / ischaemic heart disease.
Cerebral infarction (stroke).
Peripheral vascular disease.
Aortic aneurysms.
Mesenteric occlusion ischaemic bowel
Tubular necrosis due to acute renal failure
Liver failure due to infarction(white)
Atherosclerosis - Pathogenesis

A chronic inflammatory response of

the arterial wall initiated by injury to
the endothelium
 Atherosclerosis
Pathogenesis
Chronic endothelial injury thrombotic
potential
Accumulation of lipoprotein (LDL with high
cholesterol) in vessel wall
Monocytes and leukocytes intima of blood
vessel transform to macrophages
Factors from platelets and macrophages cause
migration of smooth muscle cells from media
of artery to intima.
Smooth muscle cells collagen accumulation
giving a fibrolipid plaque i.e. atheroma
 Response to injury
hypothesis
CHRONIC ENDOTHELIAL INJURY

ACCUMULATION OF LIPOPROTEINS[LDL]IN VESSEL WALLS

MODIFICATION OF LESIONAL LIPOPROTEINS BY OXIDATION

ADHESION OF MONOCYTES TO ENDOTHELIUM AND

TRANSFORMATION INTO MACROPHAGES AND FOAM CELLS

ADHESION OF PLATLETS - MIGRATION OF SMC TO INTIMA AND

PROLIFERATION

ENHANCED ACCUMULATION OF LIPIDS IN CELLS AND EXTRA

CELLULARLY
 Microscopic appearance
Fibrous Cap smooth muscle cell
(SMC), elastin, macrophage, foam
cells, lymphocyte, collagen
Monocyte
Smooth muscle cell

Cholesterol cleft
Foam cell

Necrotic center cell debris,

cholesterol crystals, foam Neovascularisation
cells, calcium
 Key components of Atheromatous
plaque
Smooth muscle cell,
macrophage,leukocytes
Collagen, elastic fibers, proteoglycans
Intracellular and extra cellular lipid
deposits
Atheroma Aorta
Atheroma Coronary Artery
Flow diagram in center column indicates pathways in evolution and progression of human
atherosclerotic lesions.

Stary H C et al. Circulation. 1995;92:1355-1374 Copyright American Heart Association, Inc. All rights reserved.
 Atherosclerosis Consequences:
Occlusion, thrombus of plaque, embolus,
aneurysm
Complete occlusion of artery infarction
Partial occlusion of artery ischaemia e.g.
Angina
Thrombus formation
size of plaque occlusion
Embolisation of
Thrombus
Cholesterol
Platelet
Aneurysm formation
Dissection e.g. Aorta
Calcification
 Risk Factors for
Atheroma***
Major Lesser, Uncertain, or
Nonquantitated

Nonmodifiable
Age Postmenopausal oestrogen deficiency
Gender Stress ("type A" personality)
Genetic abnormalities
Potentially Controllable
Hyperlipidaemia Obesity
Hypertension Physical inactivity
Cigarette smoking Hardened (trans)unsaturated fat intake
Diabetes Alcohol
Chlamydia pneumoniae
 Does atheroma occur in veins?
Why not?
 Risk Factors
Age.
Death rates from IHD rise with each decade
Between ages 40 and 60 the incidence of
myocardial infarction increases fivefold
Gender.
Other factors being equal, males are more
prone to atherosclerosis why? ?? smoking
After menopause, the incidence of
atherosclerosis-related diseases increases,
probably owing to a decrease in natural
oestrogen levels.
 Risk Factors
Genetics
Familial predisposition to atherosclerosis
is most likely polygenic.
Relates to familial clustering of other
risk factors, such as hypertension or
diabetes.
Less commonly it involves well-defined
hereditary genetic derangements in
lipoprotein metabolism.
 Risk Factors
Hyperlipidaemia, predominantly
hypercholesterolaemia.
Low-density lipoprotein (LDL) delivers
cholesterol to peripheral tissues.
High-density lipoprotein (HDL) mobilizes
cholesterol, transporting it to the liver
for excretion in the bile.
High dietary intake of cholesterol and
saturated fats, (egg yolk & animal fats)
raises the plasma cholesterol level.
 Risk Factors
Hypertension around branches.
Men between ages 45 and 62 whose
blood pressure exceeds 169/95 mm Hg
have a more than fivefold greater risk of
IHD than those with blood pressures of
140/90 mm Hg or lower. Why?
Both systolic and diastolic levels are
important.
Cigarette smoking.
Smoking one or more packs of cigarettes
per day for several years increases the
death rate from IHD by up to 200%.
 Risk Factors
Diabetes mellitus.
Induces hypercholesterolemia and a
markedly increased predisposition to
atherosclerosis.
Incidence of myocardial infarction is twice
as high in diabetics as in non-diabetics.
100-fold increased risk of atherosclerosis-
induced gangrene of the lower
extremities.
 Distribution of Atheroma
Abdominal aorta, esp around ostia of
its major branches. Why around ostia?
Coronary arteries.
Popliteal arteries.
Descending thoracic aorta.
Internal carotid and vessels of Circle of
Willis.
Often widespread within an individual.
Atheropath
 Symptoms
Gradual narrowing of a vessel will
result in ischaemia of the supplied
tissue.
Sudden occlusion of a vessel will
result in infarction.
Erosion of a vessel wall and
aneurysmal change +/- rupture
 Ischaemia
Coronary arteries ischaemic heart
disease
Lower limbs intermittent
claudication
Mesenteric artery postprandial angina
Understand significance of end artery
occlusion with/without collateral
circulation
 Occlusion - Infarction
Coronary arteries Myocardial
infarction
Circle of Willis Cerebral infarction
Mesenteric artery Infarcted bowel
Lower limb arteries Gangrene
 Summary
Atherosclerosis (fibro lipid plaque)
commonest arterial cause of ischaemia and
infarction
Leading cause of death
Related to endothelial damage
Must know pathogenesis and risk factors
Often complicated by thrombus formation on
plaque +- subsequent systemic embolization
(Platelets, cholesterol, thrombus, plaque)
May cause aneurysm and rupture
 Aneurysm
A localised abnormal dilation of a blood
vessel.
True or false.
True congenital(by birth)bounded by
arterial wall components or the attenuated
wall of the heart.
False - a breach in the vascular wall leading
to an extravascular hematoma that freely
communicates with the intravascular space
e.g. Following trauma
 Aneurysm - Causes

Atherosclerosis
Congenital defects berry aneurysm
in Circle of Willis
Infections (mycotic aneurysm)
Syphilitic (luetic)
Trauma
Cystic medial degeneration
Systemic diseases, e.g. vasculitis
 Atherosclerotic Aneurysms
Most frequently in the abdominal
aorta (AAA).
Common iliac arteries, the arch, and
descending parts of the thoracic
aorta can be involved.
Abdominal Aortic Aneurysm
Usually positioned below the renal
arteries and above the bifurcation of
the aorta. pulsation
Saccular or fusiform.
Can be up to 15 cm in greatest
diameter and of variable length.
The risk of rupture is directly related
to the size of the aneurysm > 5 cms.
Important clinical factor afecting
aneurysm growth is blood pressure.
 Abdominal Aortic
Aneurysms
Clinical Consequences
Rupture into the peritoneal cavity or
retroperitoneal tissues with massive,
potentially fatal, haemorrhage.
Obstruction of a vessel (iliac, renal,
mesenteric, or vertebral branches that supply
the spinal cord) leading to ischemic tissue
injury.
Embolism from atheroma or mural thrombus
Impingement on an adjacent structure, such as
compression of a ureter or erosion of vertebrae
Presentation as an abdominal mass (often
Aneurysm with blood
clot
Blood clot
What might it
do?
Tear and
rupture
 How do we manage atheroma
lifestyle vegetarian non smoker
 Aortic dissection
Not related to atheroma
Tear in the intima allows dissection of blood between and
along the laminar planes of the media, resulting in the
formation of a blood-filled channel within the aortic wall.
Can rupture outward, causing massive haemorrhage.
May or may not be associated with dilatation/aneurysm of
the aorta (Avoid term dissecting aneurysm).
 Aortic dissection - Causes
More than 90% of dissections occur
in men between the ages of 40 and
60 with antecedent hypertension.
Systemic or localised abnormality
of connective tissue that afects
the aorta (eg. Marfan syndrome).
Latrogenic, as a complication of
arterial cannulation.
 Aortic dissection

Clinical symptoms
Sudden onset of excruciating pain, usually
beginning in the anterior chest, radiating to the
back, and moving downward as the dissection
progresses
Complications depend on the level of the
aorta afected
Most serious complications occurring from the
aortic valve to the arch haemopericardium
Main cause of death is rupture of the dissection
outward.
 Aortic dissection
Prognosis has improved.
Development of techniques for surgical
repair of the aortic wall.
Early institution of intensive
antihypertensive therapy.
 Other causes of Aortitis
Giant cell arteritis
Other arteritis
Rheumatoid arthritis
Syphilis
 Clinical Situation
Male 70
Admitted with central chest pain
Infarct evidence on ECG
troponins
Commonest cause of this infarct?
 What is the diference
between atherosclerosis and
arteriolosclerosis?