CHAPTER 11: BLOOD VESSELS

PRINCIPAL MECHANISMS OF VASCULAR

PATHOLOGY
1. Narrowing (Stenosis) or Complete
obstruction of vessel lumen
Progressively (atherosclerosis)
Precipitously (thrombosis or embolism)
2. Weakening of vessel walls dilation
or rupture

STRUCTURE AND FUNCTION OF BLOOD

VESSELS
General architecture and cellular
composition of blood vessels are same
throughout the CVS.
Certain features vary with and reflect
distinct functional requirements at
different locations,
Arterial walls are thicker than veins : to
withstand the pulsatile flow and higher
blood pressure
Arterial wall thickness gradually
diminishes as vessels become smaller; but
ratio of wall thickness to lumen diameter
becomes greater

BASIC CONSTITUENTS OF THE WALLS OF

BLOOD VESSELS:
Endothelial cells
Smooth muscle cells
Extracellular Matrix (ECM) : elastin,
collagen, glycosaminoglycans
3 CONCENTRIC LAYERS most clearly
defined in larger vessels (arteries)
1. Intima consists of a single layer of
endothelial cells with minimal
underlying subendothelial connective
tissue
2. Media smooth muscle cell layers
near the vessel lumen receive O2 and
nutrients by direct diffusion via holes
in the internal elastic membrane
3. Adventitia external to the media;
consists of connective tissue with
nerve fibers and vasa vasorum

Internal Elastic Lamina dense elastic

membrane which separates intima from
media
External Elastic Lamina outer limit of
the media of most arteries
Vasa vasorum / Vessels of the
vessels

small arterioles arising from the

outside vessel
nourishes the outer portions of large
and medium sized arteries

ARTERIES
a. Large or Elastic Arteries
- includes the aorta, its large branches
(innominate, subclavian, common
carotid, iliac) and pulmonary arteries
- media is rich in elastic fibers: allows
aorta to expand (systole) and recoil
(diastole)
**With aging, the aorta loses elasticity and
large vessels expand less readily (increased
BP)
**In older individuals, arteries are tortuous
and dilated (ectatic)
b. Medium-sized or Muscular Arteries
- comprise other branches of the aorta
(coronary and renal arteries)
- media is composed predominantly of
circularly and spirally arranged smooth
muscle cells
- Regional blood flow and pressure is
controlled by changes in lumen size
through vasoconstriction and
vasodilation, ANS and local metabolic
factors and cellular interactions
**Resistance of a tube to fluid flow is
inversely proportional to the fourth power of
the diameter
(eg. diameter = 16 fold increase in
resistance)
c. Small Arteries
- less than approx. 2mm in diameter and
d. Arterioles
- (20-100micrometer in diameter) within
the substance of tissue and organ
- Principal points of physiologic
resistance to blood flow

CAPILLARIES
approx. Same diameter of RBC (7-8
micrometers)
with endothelial cell lining

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NO media
very large total cross sectional area
thin walls only
slow flow
ideally suited in the rapid exchange of
diffusible substances between blood and
tissues

**In solid tissues with distances > approx 100

micrometers, O2 diffusion is inefficient rich
capillary network
**Myocardium has the highest density of
capillaries

VEINS
have larger diameters, larger lumens and
thinner, less well organized walls than
arteries
predisposed to irregular dilation,
compression, easy penetration by tumors
and inflammatory processes due to poor
support
has large capacity; 2/3 of all blood is in
veins
reverse flow prevented by venous valves
in extremeties, where blood flow against
gravity
LYMPHATICS
thin walled, endothelium-lined channels
drainage system for returning interstitial
tissue fluid and inflammatory cells to
blood
pathway for disease dissemination
(transport of bacteria and tumor cells)

Blood Flow:
Capillary beds post capillary venules
collecting venules and small, medium and
large veins
**Post capillary Venules where vascular
leakage and leukocyte exudation occur during
inflammation

Atherosclerosis affects Elastic and

Muscular arteries
Hypertension affects Small muscular
arteries and Arterioles
Vasculitis involves various Vascular
segments

VESSEL DEVELOPMENT, GROWTH AND

REMODELING
1. Vasculogenesis
- de novo formation of blood vessels
during embryogenesis
- Hemangioblast angiogenic precursor
migrate to sites of vascularisation
differentiate to endothelial cells form
primitive vascular plexus remodels
into definitive vascular system
(influenced by local genetic, metabolic
and hemodynamic factors)
- VEGF primary growth factor involved
- Subsequent stabilization of endothelial
tubes require pericytes and smooth
muscle cells recruitment; involves
Angiopoietin 1 binding to endothelial
cell Tie2 receptors
2. Angiogenesis or Neovascularization
- process of new vessel formation in the
mature organism

3. Arteriogenesis
- remodelling of existing arteries in
response to chronic changes in
pressure/flow
- results from interplay of endothelial
cell and smooth muscle cell derived
factors
CONGENITAL ANOMALIES
Developmental or Berry Aneurysms
- Occur in cerebral vessels
- Causes of fatal intracerebral
hemorrhage
Arteriovenous Fistulas
- Abnormal, small, direct connections
between arteries and veins that
bypass intervening capillaries
- Occur most commonly as
developmental defects
- Result from rupture of arterial
aneurysm into and adjacent vein (by
penetrating injuries, inflammatory
necrosis)
- Intentionally created AV fistulas
provide vascular access for chronic
hemodialysis
- Can also cause intracerebral
hemorrhage

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-

Large/extensive AV fistulas may cause

high output cardiac failure

Fibromuscular Dysplasia
- Focal irregular thickening of the walls
of medium and large muscular arteries
(renal, carotid, splanchnic and
vertebral vessels)
- Increased risk if first degree relative is
affected
- Segments of vessel wall are focally
thickened by combination of irregular
medial and intimal hyperplasia and
fibrosis luminal stenosis and
renovascular hypertension (renal
arteries)

of adjacent tissues by electrolytes and

protein; leukocytes (during inflammation)

Endothelial cells vary on phenotype

depending on specific anatomic site:
o Fenestrated with holes for
facilitated diffusion; found in
liver sinusoids or in renal
glomeruli
o Impermeable blood brain
barrier of the CNS (perivascular
cells)

Endothelial activation structurally

intact endothelial cells respond to
pathophysiologic stimuli by adjusting
their usual functions and expressing
newly acquired properties
Inducers of Endothelial activation:
o Cytokines and bacterial
products inflammation and
shock
o Hemodynamic stress and lipid
products (atherosclerosis)
o Advanced glycosylation end
products
o Viruses
o Complement components
o Hypoxia

Activated endothelial cells express

adhesion molecules; produce
cytokines, chemokines, growth factors,
vasoactive molecules (vasoconstriction
OR vasodilation), MHC molecules,
procoagulant, anticoagulant moieties
and biologically active products

Endothelial dysfunction
- altered phenotype that impairs
vasoreactivity or induces a surface
that is thrombogenic or abnormally
adhesive to inflammatory cells
- responsible for the initiation of
thrombus formation,
atherosclerosis, vascular lesions of
hypertension
- may be rapid in onset (within
minutes); reversible; independent
of protein synthesis
- others may involve alterations in
gene expression and protein
synthesis; require hours/days to
develop

VASCULAR WALL CELLS AND INJURY

RESPONSE

ENDOTHELIAL CELLS
Endothelium critical for maintaining
vessel wall homeostasis and circulatory
function
contain Weibel Palade bodies
intracellular membrane bound storage
organelles for von Willebrands factor
Antibodies to vWF and/or PECAM-1 or
CD31 (protein localized to interendothelial
junctions) used to identify EC
immunohistochemically
Vascular Endothelium multifunctional
tissue with a wealth of synthetic and
metabolic properties; has several
constitutive activities critical for normal
vessel homeostasis
Functions of Endothelial Cells:
Maintain a nonthrombogenic bloodtissue interface
Modulate vascular resistance
Metabolize hormones
Regulate inflammation
Affect the growth of other cell types
(smooth muscle)
Influence vasoreactivity of the
underlying smooth muscles through
production of relaxing (NO) and
contracting factors (endothelin)
**Tight endothelial cell junctions can
loosen under the influence of
hemodynamic factors (high BP) and/or
vasoactive agents (histamine) flooding

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VASCULAR SMOOTH MUSCLE CELLS

predominant cellular element of the
vascular media
involved in vascular repair and pathologic
processes (atherosclerosis)
synthesize ECM collagen, elastin,
proteoglycans
elaborate growth factors and cytokines
responsible for the vasoconstriction or
dilation that occurs in response to
physiologic or pharmacologic stimuli
promoters and inhibitors regulate
migratory and proliferative activities

PROMOTERS

PDGF

Endothelin
1

Thrombin

Fibroblast
growth
factor
(FGF)

Interferon
gamma

IL 1

INHIBITORS
Heparan
Sulfate

Nitric
Oxide

TGF beta

OTHERS
RAAS
(angiotensi
n II)
Catechola
mines
Estrogen
receptor
Osteoponti
n (ECM
component
)

no consequence because a compensatory

outward remodelling of vessel little net
change in luminal diameter
NEOINTIMAL SMC
Does not contract
(+) capacity to divide

INTIMAL THICKENING STEREOTYPIC

RESPONSE TO VASCULAR INJURY
Vascular Injury stimulates smooth
muscle cell growth and associated with
matrix synthesis that thickens the intima
Healing of injured vessels forms
neointima (typically completely covered
by endothelial cells)
During the healing process, endothelial
cells that fill areas of denudation may
migrate from circulating precursors
medial SM cells or SM precursor cells
migrate into the intima proliferate
synthesize ECM
Neointimal response occurs with any form
of vascular damage or dysfunction
Healing response results in permanent
intimal thickening
Persistent/recurrent insults, excessive
thickening narrowing of small and
medium sized vessels impeding
downstream tissue perfusion
Maturation and aging may also cause
intimal thickening and may typically show

MEDIAL SMC
Contracts
Does not divide

Intimal Smooth Muscles

o At least in part derived from
circulating precursor cells
o Regulated by products derived
from platelets, endothelial cells,
macrophages, activated
coagulation, and complement
factors
o PDGF, Endothelin1, Thrombin,
Fibroblast growth factor (FGF),
Interferon gamma, IL 1 (+)
neointimal SMC
o Heparan sulphates, nitric oxide,
TGF beta (-) neointimal SMC
growth
HYPERTENSIVE VASCULAR DISEASE
Hypotension result in inadequate organ
perfusion dysfunction or tissue death
Hypertension cause vessel and endorgan damage
Sustained diastolic pressure >
89mmHg OR sustained systolic
pressure > 139mmHg increased risk
of atherosclerosis

HYPERTENSION
Essential Htn multifactorial, resulting
from combined effects of multiple genetic
polymorphisms and interacting
environmental factors
Prevalence increases with age
Higher in African Americans
Can cause: heart failure (Hypertensive
heart dse.), multi-infarct dementia, aortic
dissection, renal failure
Typically remains asymptomatic until in its
late course; silent for years
If untreated death due to ischemic
heart dse. (IHD), CHF and stroke
Prophylactic BP reduction incidence
and death rates
** Types and Causes of HTN: See Table 11-2
page 493

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ESSENTIAL OR IDIOPATHIC
HYPERTENSION
95%
Generally does not cause short term
problems
If controlled compatible with long life,
asymptomatic unless if with presence of
MI, CVA, other complications
ACCELERATED OR MALIGNANT
HYPERTENSION
5%
Rapidly rising BP
May develop in previously normotensive
but most often in individuals with preexisting benign htn (essential or
secondary)
If untreated death within a year or 2
Manifestations:
o severe htn (systolic >200mmHg;
diastolic >120mmHg)
o renal failure
o retinal haemorrhages and exudates
with or w/o papilledema

pH, hypoxia, alpha and beta

adrenergic system influence heart
rate, cardiac contraction, vascular tone;
ensures adequate perfusion of all tissues,
despite regional differences in demand

Kidneys
a. Influences both peripheral resistance
and sodium homeostasis (RAAS):
BP renin release by
juxtaglomerular cells
angiotensinogen to angiotensin
I angiotensin II by ACE
angiotensin II both peripheral
resistance (direct action on
smooth muscle cell) and blood
volume (stimulation of
aldosterone and distal
tubular reabsorption of sodium)
b. Produces vascular
relaxing/antihypertensive substances
(prostaglandin, NO) counterbalance
vasopressor effects of angiotensin
c. blood volume GFR
reabsorption of Na by proximal tubules
Na conservation and blood volume
expansion
d. Volume expansion natriuretic
peptide secretion by atrial and
ventricular myocardium inhibit Na
reabsorption in distal tubules and
induce vasodilation Na excretion
and diuresis

REGULATION OF NORMAL BP
Blood Pressure function of cardiac
output and peripheral vascular resistance;
influenced by multiple genetic factors,
environmental and demographic factors

Major Factors that Determine BP:

o Age
o Gender
o BMI
o Diet (sodium intake)

Cardiac Output highly dependent on

blood volume and greatly influenced by
sodium homeostasis
Peripheral Vascular Resistance
determined mainly at the levels of the
arterioles; affected by neural and
hormonal factors
Normal Vascular Tone balance
between humoral vasoconstricting
influences (angiotensin II, catecholamines,
endothelin) and vasodilators (kinins,
prostaglandins, NO)
Autoregulation exhibited by resistance
vessels; blood flow induces
vasoconstriction to protect against tissue
hyperperfusion

MECHANISMS OF ESSENTIAL
HYPERTENSION
Genetic factors play a definite role in
determining BP
Single gene d/o cause relatively rare forms
of hypertension and hypotension by
altering net Na reabsorption in the kidney:
Gene defects affecting enzymes:
eg. aldosterone synthase, 11betahydroxylase, 17alpha-hydroxylase
aldosterone secretion, salt and water
resorption, plasma volume expansion
hypertension
Mutations affecting proteins that
influence Na reabsorption: eg.
Liddle Syndrome (mod, severe form
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of salt sensitive htn) caused by

mutations in Na channel protein
distal tubular reabsorption of Na
induced by aldosterone
Predisposition to essential hypertension
associated with gene variations of RAAS
(hypertension: polymorphisms in both
angiotensinogen locus and angiotensin
receptor locus)
Reduced renal excretion key initiating
event in essential hypertension; final
common pathway for hypertension
pathogenesis
o Na excretion fluid volume,
CO and peripheral vasoconstriction
BP
o At higher BP additional Na would
be excreted to equal intake and
prevent further fluid retention
steady Na excretion (resetting of
pressure natriuresis)
Vasoconstrictive influences
o increase peripheral resistance; play
a role in primary htn
o Chronic or repeated influences
thickening and rigidity of vessels
Environmental factors modify impact
of genetic factors; stress, obesity,
smoking, physical inactivity and heavy salt
consumption

VASCULAR PATHOLOGY IN
HYPERTENSION
Associated with 2 forms of small blood vessel
disease:
1. Hyaline Arteriosclerosis
Chronic hemodynamic stress
plasma protein leakage across
injured endothelial cells and
increased smooth muscle cell
matrix synthesis arterioles show
homogenous, pink hyaline
thickening with associated luminal
narrowing
Also seen in:
o Diabetic Microangiography:
due to hyperglycemiainduced endothelial cell
dysfunction
o Nephrosclerosis: due to
chronic hypertension
diffuse impairment of renal
blood supply and glomerular
scarring
2. Hyperplastic Arteriolosclerosis
occurs in severe(malignant)
hypertension
onion-skin lesions concentric,
laminated thickening of the walls
and luminal narrowing
laminations consist of smooth
muscle cells with thickened,
reduplicated basement membranes
In malignant htn, they are
accompanied by fibrinoid deposits
and vessel wall necrosis
(necrotizing arteriolitis)
particularly in the kidney

Essential hypertension results from

interactions of mutations of polymorphisms of
several loci
Sustained hypertension requires participation
of the kidney by salt and water elimination.
In established hypertension, both blood
volume and peripheral resistance contribute
to pressure.

PATHOGENESIS OF SECONDARY
HYPERTENSION
Renovascular hypertension renal artery
stenosis glomerular flow and pressure
in afferent arteriole (a.) renin secretion
vasoconstriction and peripheral
resistance; (b.) Na reabsorption and
blood volume
Primary Hyperaldosteronism one of
the most common causes of secondary
htn

ARTERIOSCLEROSIS
hardening of the arteries
Arterial wall thickening and loss of
elasticity
3 General Patterns:
1. Arteriosclerosis affects small
arteries and arterioles; cause
downstream ischemic injury
2. Monckeberg medial sclerosis
- calcific deposits in muscular
arteries in persons older than 50
- deposits may undergo metaplastic
change into bone

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3. Atherosclerosis from Greek word
gruel and hardening; most
frequent and clinically important

ATHEROSCLEROSIS
characterized by intimal lesions called
atheromas/ atheromatous or
atherosclerotic plaques
Atheromatous plaque
o consists of a raised lesion with a
soft, yellow, grumous core of lipid
(cholesterol and cholesterol esters)
covered by a white fibrous cap
o Mechanically obstructs blood flow;
can rupture catastrophic vessel
thrombosis; weaken underlying
media aneurysm formation
EPIDEMIOLOGY
ubiquitous among most developed
nations; less prevalent in Central and
South America, Africa and parts of Asia
IHD 2nd leading cause of death in Japan
risk factors have multiplicative effect: 2
risk factors increase risk 4fold; 3 risk
factors MI risk increased 7 times

CONSTITUTIONAL RISK FACTORS IN IHD

1. Age
Dominant influence
Atherosclerosis does not clinically
manifest until middle age or later
Ages 40-60 MI increases fivefold
2. Gender
Premenopausal women are protected
against atherosclerosis
After menopause, incidence increases
at older ages
In younger postmenopausal women,
coronary atherosclerosis is reduced
with estrogen therapy
Women show differences in
hemostasis, infarct healing and
myocardial remodelling
3. Genetics
Most significant independent risk
factor for atherosclerosis
MODIFIABLE RISK FACTORS IN IHD
1. Hyperlipidemia specifically
Hypercholesterolemia
Major risk factor for atherosclerosis

Sufficient to stimulate lesion

development
LDL or bad cholesterol (cholesterol
delivered to peripheral tissues) =
risk
HDL or good cholesterol (mobilizes
cholesterol from tissue to the liver for
excretion) = risk
cholesterol and saturated fats intake
plasma cholesterol levels
Polyunsaturated fats plasma
cholesterol levels
Omega 3 FA are beneficial
Trans-unsaturated fats adversely affect
cholesterol profiles
Exercise, moderate alcohol
consumption raise HDL
Obesity, smoking lower HDL
Statins cholesterol lowering drugs;
inhibit hydroxymethylglutaryl
coenzyme A (HMG-CoA) reductase,
rate limiting enzyme in hepatic
cholesterol biosynthesis
2. Hypertension
Increases risk of IHD by 60%
Most important cause of left
ventricular hypertrophy
3. Cigarette Smoking
Well established risk factor in men
Prolonged smoking of one pack or
more doubles IHD death rate
4. Diabetes Mellitus
Induces hypercholesterolemia
MI is twice as high in diabetics as in
nondiabetics
Increased risk of strokes and 100 fold
increased risk of atherosclerosisinduced gangrene of the lower
extremities
ADDITIONAL RISK FACTORS
1. Inflammation
Present during all stages of
atherogenesis; intimately linked with
atherosclerotic plaque formation and
rupture
C-reactive protein (CRP)
o one of the simplest and most
sensitive markers of
inflammation
o Acute phase reactant
synthesized by the liver

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Plays a role in innate immune
response by bacterial
opsonization and complement
activation
o Activate local endothelial cells
o Induce prothrombotic state
o Increase adhesiveness of
endothelium for leukocytes
o Predicts risk of MI, stroke,
peripheral arterial disease and
sudden cardiac death
Hyperhomocystinemia
Caused by low folate and vitamin B12
Homocystinuria due to rare inborn
errors of metabolism elevated
homocysteine (>100 micromol/L) and
premature vascular disease
Metabolic Syndrome
associated with a number of
abnormalities associated with insulin
resistance
due to abnormal adipose tissue
signaling
glucose intolerance
hypertension
central obesity
Dyslipidemia endothelial cell
dysfunction secondary to oxidative
stress
Systemic proinflammatory state
vascular thrombosis
Lipoprotein (a)
altered form of LDL that contains
apolipoprotein B-100 linked to
apolipoprotein A
Factors affecting hemostasis
thrombin (procoagulant and
proinflammatory) local vascular
pathology
Other factors
lack of exercise
competitive, stressful lifestyle (type A
personality)
obesity
o

2.

3.

4.

5.

6.

PATHOGENESIS OF ATHEROSCLEROSIS
2 Dominant Hypotheses:
o Intimal cellular proliferation

Repetitive formation and

organization of thrombi

RESPONSE-TO-INJURY HYPOTHESIS
views atherosclerosis as a chronic
inflammatory and healing response of
arterial wall to endothelial injury; lesion
progression occurs through the interaction
of modified lipoproteins, monocytederived macrophages and T lymphocytes
PATHOGENIC EVENTS:
Endothelial Injury
Accumulation of lipoproteins
Monocyte adhesion to the
endothelium
Platelet adhesion
Factor release
Smooth muscle proliferation and
ECM production
Lipid accumulation

o
o

o
o

Endothelial Injury
Cornerstone of the response-toinjury hypothesis
Show increased endothelial
permeability, enhanced leukocyte
adhesion and altered gene
expression
Etiologic culprits: hypertension,
hyperlipidemia, toxins from
cigarette smoke, homocysteine and
infectious agents
Inflammatory cytokines stimulate
pro-atherogenic patterns of
endothelial cell gene expression
2 Important causes of
Endothelial Dysfunction:
(hemodynamic disturbances
and hypercholesterolemia)
Hemodynamic
Disturbances plaques
occur at ostia of exiting
vessels, branch points,
along the posterior wall of
the abdominal aorta, where
there are disturbed flow
patterns
Lipids
- Dyslipoproteinemia result
from mutations that alter
apoproteins or lipoproteins
receptors on cells
- Common lipoprotein
abnormalities: LDL,

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HDL, abnormal lipoprotein
(a)
Evidence implicating
hypercholesterolemia in
atherogenesis:
- Dominant lipids in atheroma
are cholesterol and
cholesterol esters
- Genetic defects associated
with accelerated
atherosclerosis;
homozygous familial
hypercholesterolemia
caused by defective LDL
receptors and inadequate
hepatic LDL reuptake MI
before age 20
- Genetic/acquired d/o (DM,
Hypothyroidism)
premature atherosclerosis
- serum cholesterol or
drugs slows progression of
atherosclerosis
Mechanisms by which
hyperlipidemia contribute to
atherogenesis:
- Hypercholesterolemia
directly impair endothelial
cell function by increasing
O2 free radical which injures
tissues and accelerate NO
decay reducing its
vasodilating activity
- Lipoproteins accumulate
within the intima lipids
are oxidized through the O2
free radicals oxidized
LDL ingested by
macrophages
accumulates in phagocytes
(foam cells); stimulates
relaease of growth factors,
cytokines and chemokines
increase monocyte
recruitment into lesions
induce endothelial cell
dysfunction

Inflammation
Contribute to the initiation,
progression and
complications of
atherosclerotic lesions

Dysfunctional arterial
endothelial cells express
adhesion molecules that
encourage leukocyte
adhesion; vascular cell
adhesion molecule 1 (VCAM1) binds monocytes and T
cells migrate into the
intima

Infection
Herpesvirus,
cytomegalovirus, Chlamydia
pneumonia has been
detected in atherosclerotic
plaques but NOT in normal
arteries
Increased antibody titers to
C. pneumonia in patients
with more severe
atherosclerosis
Such organisms could infect
sites of early atheroma
formation
Foreign antigens potentiate
atherogenesis
Infectious agents contribute
to local prothrombotic state

Smooth Muscle Proliferation

o Intimal SMC proliferation and
ECM deposition convert a fatty
streak (earliest lesion)
mature atheroma and
contribute to progressive
growth of atherosclerotic lesion
o PDGF, FGF, TGF alpha
implicated in the SMC
proliferation and ECM synthesis
o Activated inflammatory cells
cause apoptosis and increase
ECM catabolism unstable
plaques
MORPHOLOGY OF ATHEROSCLEROSIS
Fatty Streaks
o Earliest lesions
o Composed of lipid filled foamy
macrophages
o Begins as multiple minute yellow
spots coalesce into elongated
streaks 1 cm or more in length

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o
o

o
o

Not raised and not cause any flow

disturbance
Aortas of infants < 1 y/o can
exhibit fatty streaks and older than
10 yrs. Regardless of race, gender,
geography, environment
Not all fatty streaks develop into
advanced lesions
Coronary fatty streaks begin to
form in adolescence tend to
develop plaques

Atherosclerotic Plaque
o Key processes are: intimal
thickening and lipid
accumulation
o Impinge on the lumen of the artery
and grossly appear white-yellow
o Vary from 0.3-1.5cm in diameter
o Patchy; usually involves a portion
of arterial wall; rarely
circumferential; eccentric
o Local flow disturbances
increased susceptibility of certain
portions of vessel wall to plaque
formation
o Lesions can become numerous and
diffuse with time
o Abdominal aorta involved to a
much greater degree than thoracic
aorta
o Most extensively involved vessels
(descending order):
Lower abdominal aorta
Coronary arteries

o
o

o
o

Popliteal arteries
Internal carotid arteries
Vessels of circle of Willis
Vessels of upper ext., mesenteric
and renal arteries are usually
spared except at their ostia
3 principal components of
atherosclerotic plaque:
Cells (SMC, macrophage, T
cells)
ECM (collagen, elastic
fibers, proteoglycan)
Intracellular and
extracellular lipid
Superficial fibrous cap
composed of SMC and dense
collagen; beneath and to the side
of the cap is a more cellular area
with macrophages, T cells and SMC
Necrotic core deep to the
fibrous cap; contains lipids (primary
cholesterol and cholesterol esters),
debris, foam cells, , fibrin, variably
organized thrombus, plasma
proteins
Cholesterol frequently present as
crystalline aggregates washed out
during tissue processing leaving
behind empty clefts
Neovascularization at the periphery
Fibrous plaque composed
almost exclusively of SMC and
fibrous tissue
Atheromas often undergo
calcification

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