Blood Vessels
Dr. Nabila Hamdi
MD, PhD
ILOs
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Understand the structure and function of blood vessels.
Discuss the different mechanisms of blood pressure regulation.
Compare and contrast the following types of hypertension: benign, malignant,
essential and secondary.
Discuss the morphologic effects of hypertension on different organs and
enumerate their clinical consequences.
Compare and contrast between hyaline and hyperplastic arteriosclerosis in terms
of pathogenesis, morphology and clinical significance.
Differentiate between arteriosclerosis, atherosclerosis and Mönckeberg medial
sclerosis.
Be aware of the risk factors of atherosclerosis
Outline the development of the atherosclerotic lesion with respect to:
pathogenic mechanisms
morphology
clinical manifestations
complications
Outline
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IV.
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STRUCTURE AND FUNCTION OF BLOOD VESSELS
VASCULAR WALL RESPONSE TO INJURY
BLOOD PRESSURE REGULATION
ARTERIOSCLEROSIS
HYPERTENSIVE VASCULAR DISEASE
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Pathogenesis of Hypertension
Vascular Pathology in Hypertension
 MONCKEBERG MEDIAL SCLEROSIS
 ATHEROSCLEROSIS
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Epidemiology
Pathogenesis
Morphology
Clinical Consequences
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STRUCTURE AND FUNCTION OF BLOOD VESSELS
 Regional vascular specializations
Elastic arteries
Iliac, pulmonary
Expansion/recoiling
Coronary, renal
Vasoconstriction/
Vasodilation
Arterioles are where blood
flow resistance is regulated
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STRUCTURE AND FUNCTION OF BLOOD VESSELS
 Endothelial Cell Properties and Functions
Injury or exposure to certain mediators results in endothelial
activation, a state in which endothelial cells have adhesive,
procoagulant surfaces and release factors that lead to smooth
muscle contraction and/or proliferation and matrix synthesis.
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STRUCTURE AND FUNCTION OF BLOOD VESSELS
 Vascular Smooth Muscle Cells
 Participate in both normal vascular repair and pathologic processes such
as atherosclerosis.
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When stimulated by various factors, SMC can:
proliferate
upregulate ECM collagen, elastin, and proteoglycan production
elaborate growth factors and cytokines.
 SMC also mediate the vasoconstriction or vasodilation that occurs in
response to physiologic or pharmacologic stimuli.
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VASCULAR WALL RESPONSE TO INJURY
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Thrombosis
Atherosclerosis
Hypertensive vascular
disease
Intimal Thickening: A stereotypical response
of the vessel wall to any insult.
Infection, inflammation, immune injury, physical trauma (e.g., from a balloon
catheter or hypertension), or toxic exposure (e.g. oxidized lipids or cigarette smoke)
 Neointimal smooth muscle cells lack the capacity to contract like medial smooth muscle cells, but do have the
capacity to divide and have a considerably greater synthetic capacity than their medial colleagues.
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ARTERIOSCLEROSIS
 Arteriosclerosis literally means “hardening of the arteries”
 It is a generic term reflecting arterial wall thickening and loss of elasticity.
 Three distinct types are recognized, each with different clinical and pathologic
consequences:
 Hypertensive vascular disease: affects small arteries and arterioles and may
cause downstream ischemic injury. Two variants, hyaline and hyperplastic
arteriolosclerosis are described in relation to hypertension.
 Mönckeberg medial sclerosis is characterized by the presence of calcific deposits
in muscular arteries, typically in persons older than 50. The lesions do not
encroach on the vessel lumen and usually are not clinically significant.
 Atherosclerosis is the most frequent and clinically important pattern.
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BLOOD PRESSURE REGULATION
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BLOOD PRESSURE REGULATION
Renin-producing tumors
Aldosterone-secreting adrenal
tumors (adrenal cortex)
Natremia/Kalemia??
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HYPERTENSIVE VASCULAR DISEASE
• “Essential hypertension” results from the interplay of genetic
polymorphisms and environmental factors.
• Sustained diastolic pressures greater than 90 mmHg, or sustained
systolic pressures greater than 140 mmHg are used as cutoffs in
diagnosing hypertension in clinical practice.
• Without appropriate treatment, 50% of hypertensive patients die of
ischemic heart disease (IHD) or congestive heart failure, and another
third succumb to stroke.
• Detection and treatment of asymptomatic hypertension constitute one
of the few instances in which “preventive medicine” has a major
demonstrated health benefit.
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HYPERTENSIVE VASCULAR DISEASE
 Pathogenesis:
 The mechanisms leading to hypertension in the vast majority of affected
persons remain unknown.
 Essential hypertension (idiopathic) (95%).
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Secondary hypertension: most cases are due to
Primary renal disease (acute glomerulonephritis, chronic renal disease)
Renal artery narrowing (Renal artery stenosis) (renovascular hypertension)
Renin-producing tumors
Adrenocortical hyperfunction (primary aldosteronism, Cushing syndrome)
Pheochromocytoma
 Single-gene disorders (rare) cause hypertension by affecting renal sodium
resorption (enzymes involved in aldosterone metabolism or proteins that
affect sodium resorption)
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HYPERTENSIVE VASCULAR DISEASE
Reduced renal sodium excretion
Increase in fluid volume
Vasoconstriction/Structural changes
In vessel walls
Increased cardiac output
Increased vascular resistance
Essential Hypertension
Genetic factors
Angiotensinogen polymorphisms
and angiotensin II receptor variants
Environmental factors
Stress, obesity, smoking, physical inactivity,
and high levels of salt consumption 13
HYPERTENSIVE VASCULAR DISEASE
 Although it occasionally manifests in an acute aggressive form, high
blood pressure is much more often asymptomatic for many years
(Benign hypertension).
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Hypertension increases the risk of:
Stroke
Multi-infarct dementia
Atherosclerotic coronary heart disease
Cardiac hypertrophy and heart failure (hypertensive heart disease)
Aortic dissection
Renal failure
 Malignant hypertension (5%): rapidly rising blood pressure (systolic
over 200 mm Hg or diastolic over 120 mm Hg). It is associated with
renal failure and retinal hemorrhages and, if untreated, leads to death
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in within 1 to 2 years.
HYPERTENSIVE VASCULAR DISEASE
Morphology:
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Hypertension accelerates atherogenesis and causes degenerative changes in the walls of
large and medium sized arteries that can lead to aortic dissection and cerebrovascular
hemorrhage.
Two forms of small blood vessel disease are hypertension-related:
 Hyaline arteriolosclerosis is associated with benign hypertension
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The lesions stem from leakage of plasma components across injured endothelial cells,
into vessel walls and increased ECM production by smooth muscle cells in response to
chronic hemodynamic stress.
Ex: Nephrosclerosis in the kidneys (glomerular scarring).
The same changes occur in elderly patients (normo- or hypertensive) and in diabetic
microangiopathy (hyperglycemia-associated endothelial cell dysfunction)
 Hyperplastic arteriolosclerosis
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is
more
typical
of
severe
(malignant)
hypertension.
The laminations consist of smooth muscle cells and thickened, and reduplicated
basement membrane.
In malignant hypertension these changes are accompanied by fibrinoid deposits and
vessel wall necrosis (necrotizing arteriolitis), which are particularly prominent in the
kidney.
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HYPERTENSIVE VASCULAR DISEASE
Morphology:
Hyaline arteriolosclerosis
Homogeneous, pink hyaline thickening of
the arteriolar walls, with loss of underlying
structural detail, and luminal narrowing.
Hyperplastic arteriolosclerosis
“Onionskin,” concentric, laminated thickening
of arteriolar walls and luminal narrowing.
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ATHEROSCLEROSIS
 Atherosclerosis is characterized by the presence of intimal lesions called
atheromas (or atheromatous or atherosclerotic plaques).
The basic structure of an atheromatous plaque
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ATHEROSCLEROSIS
Epidemiology:
 Atherosclerosis is virtually ubiquitous among most developed nations but is much
less prevalent in Central and South America, Africa, and parts of Asia.
 In the Western world, roughly half of all deaths are attributed to atherosclerosis.
 Epidemiologic data related to atherosclerosis mortality typically reflect deaths
caused by ischemic heart diseases (IHD) (one fourth of all deaths in the US).
 The mortality rate for IHD in the United States is among the highest in the world,
approximately five times higher than that in Japan.
 The prevalence and severity of atherosclerosis and IHD have been correlated with
a number of risk factors.
 The risk factors have roughly multiplicative effects. Thus, two factors increase the
risk of myocardial infarction approximately four-fold, and three (hyperlipidemia,
hypertension, and smoking), increase the rate by a factor of 7.
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ATHEROSCLEROSIS
Epidemiology:
Risk factors
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ATHEROSCLEROSIS
Pathogenesis:
Endothelial injury
Intimal cellular proliferation
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Repeated formation and
organization of thrombi
Risk factors
Response-to-injury hypothesis
Atherosclerosis is a chronic inflammatory response of the
arterial wall to endothelial injury
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Pathogenesis:
Fatty streaks are composed of
lipid-filled foamy macrophages
but are only minimally raised
and do not cause any significant
flow disturbance
oxLDL
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ATHEROSCLEROSIS
Morphology:
Atherosclerotic plaques have three principal
components:
(1) Cells, including smooth muscle cells,
macrophages, and T cells
(2) Extracellular matrix, including collagen,
elastic fibers, and proteoglycans
(3) Intracellular and extracellular lipids
Atherosclerotic plaque in the coronary artery
(F): fibrous cap
(C): central necrotic core (largely lipid)
(L): lumen is moderately narrowed by this eccentric lesion,
which leaves part of the vessel wall unaffected (arrow).
Collagen is stained blue
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ATHEROSCLEROSIS
Clinical Consequences:
 Large elastic arteries (e.g., aorta, carotid, and iliac arteries) and large and
medium-sized muscular arteries (e.g., coronary, renal, and popliteal arteries) are
the vessels most commonly involved by atherosclerosis.
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The major clinical consequences of atherosclerosis are:
Myocardial infarction
Cerebral infarction (stroke)
Aortic aneurysms
Renal artery narrowing
Peripheral vascular disease (Intermittent claudication, gangrene of extremities)
Intermittent claudication: An aching, crampy, tired and sometimes burning pain in the legs that
comes and goes. It typically occurs with walking and disappears with rest, due to poor blood
circulation in the arteries of the legs.
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ATHEROSCLEROSIS
Clinical Consequences:
Unstable plaques can cause dramatic and
potentially fatal ischemic complications related to
acute plaque rupture, thrombosis, or embolization
Stable plaques can produce symptoms related
to chronic ischemia by narrowing vessels
Vulnerable and stable atherosclerotic plaque.
Stable plaques have densely collagenized and thickened fibrous caps with minimal inflammation and
negligible underlying atheromatous cores, whereas vulnerable plaques have thin fibrous caps, large
lipid cores, and increased inflammation.
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(Adapted from Libby P: Circulation 91:2844, 1995.)
ATHEROSCLEROSIS
Clinical Consequences:
Plaque erosion or rupture typically triggers thrombosis, leading to partial or
complete vascular obstruction and often tissue infarction.
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ATHEROSCLEROSIS
Clinical Consequences:
 Atherosclerotic stenosis:
Critical stenosis occurs when chronic occlusion limits blood flow
so severely that tissue demand exceeds supply (70% fixed
occlusion).
Ex: Bowel ischemia, sudden cardiac death, ischemic heart
disease, ischemic encephalopathy,
and
intermittent
claudication (ischemic leg pain).
 Acute Plaque Changes:
• Rupture/fissuring, exposing highly thrombogenic plaque
constituents.
• Erosion/ulceration, exposing the thrombogenic subendothelial
basement membrane to blood.
• Hemorrhage into the atheroma, expanding its volume.
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ATHEROSCLEROSIS
Plaque Changes:
 Rupture, ulceration, or erosion of the luminal surface of atheromatous
plaques exposes highly thrombogenic substances and induces thrombus
formation. Thrombi may partially or completely occlude the lumen,
leading to tissue ischemia (e.g., in the heart). If the patient survives,
thrombi become organized and incorporated into the growing plaque.
 Hemorrhage into a plaque: Rupture of the overlying fibrous cap or of
the thin-walled vessels in the areas of neovascularization can cause
intra-plaque hemorrhage; the resulting hematoma may cause rapid
plaque expansion or plaque rupture.
 Atheroembolism: Ruptured plaque can discharge debris into the blood,
producing microemboli composed of plaque contents.
 Aneurysm formation: Atherosclerosis-induced pressure or ischemic
atrophy of the underlying media, with loss of elastic tissue, causes
structural weakening that can lead to aneurysmal dilation and rupture.
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References
ROBBINS Basic Pathology 9th Edition
Source of the cover: http://www.123rf.com/photo_26711342_cloggedartery-and-atherosclerosis-disease-medical-concept-with-a-three-dimensional-human-arterywit.html
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Thank you…
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