Vascular pathology

 Vascular disorders are responsible for more

morbidity and mortality than any other
category of human disease.
 Vascular pathology results in disease via two
principal mechanisms:
(1) Narrowing (stenosis) or complete
obstruction of vessel lumens
(2) weakening of vessel walls, leading to
dilation or rupture.
 Diseases involve the blood vessels are:
 Vasculitis
 Degenerative disease: arteriosclerosis
 Hypertension
 Aneurysms
Hypertensive Vascular Disease
 Definition: an elevated blood pressure leading to end organ damage, or sustained
diastolic pressure >90 mm Hg and /or systolic blood pressure > 140 mm Hg.
 Incidence: 25% of population.

Classification (JNC) Systolic blood pr. Diastolic blood pr.

Mm Hg Mm Hg
Normal < 120 < 80
Prehypertension 120-139 80-89
Stage I hypertension 140-159 90-99
Stage II hypertension ≥ 160 ≥ 100
 Types and Causes of Hypertension (Systolic
and Diastolic)

 ESSENIAL THYPERTENSION (90% TO 95% OF CASES)

 SECONDARY HYPERTENSION:
 Renal : Acute glomerulonephritis; Chronic renal disease; Polycystic
disease; Renal artery stenosis
 Endocrine: Adrenocortical hyperfunction (Cushing syndrome);
Pheochromocytoma; Hyperthyroidism (thyrotoxicosis); Pregnancy-induced
 Cardiovascular: Coarctation of aorta; Increased cardiac output;
Rigidity of the aorta.
 Neurologic: Sleep apnea; Psychogenic; Acute stress, including surgery
Regulation of Normal Blood
Pressure
 Blood pressure is a function of cardiac
output and peripheral vascular
resistance.
 These two hemodynamic variables are
influenced by multiple genetic,
environmental, and demographic factors.
 The major factors that determine blood
pressure variation within and between
populations include age, gender, body
mass index, and diet, particularly sodium
 With benign hypertension there is gradual
elevation of blood pressure over many years,
with accelerated hypertension (malignant
hypertension) blood pressure elevation is severe
and becomes worse over a short period.
 The pathological changes seen in blood vessels
differ between benign and accelerated
hypertension.
Benign hypertension
 95% of hypertension cases.
 Mild to moderate elevation in blood pressure causing end organ
damage.
 Asymptomatic
 No organ is spared
 Micro: hyaline arteriosclerosis
 Late manifestations: left ventricular hypertrophy
congestive heart failure
myocardial infarction
Aneurysm formation, rupture, dissection
Intracerebral hemorrhage
chronic renal failure
Malignant ( accelerated)
hypertension
 5% of hypertension cases
 Markedly elevated blood pressures ( systolic > 180, and
/or diastolic > 120) causing end organ damage.
 Effect on eye: funduscopic exam : retinal hemorrhage , papilledema.
 Effect on kidney: gross : petechial hemorrhage
 Micro: hyperplastic arteriolosclerosis ( onion skin); necrotizing
arteriolitis ( fibrinoid necrosis of vessel wall)
 Complications: if untreated most patient die within 2 years from renal
failure, intracerebral hemorrhage, congestive heart failure.
Hypertension is associated with two forms of small blood vessel
disease: hyaline arteriolosclerosis and hyperplastic arteriolosclerosis.

 Hyaline Arteriolosclerosis:  Hyperplastic Arteriolosclerosis.

Arterioles show homogeneous,
pink hyaline thickening with
associated luminal narrowing .
 of the walls and luminal
These changes stem from plasma
protein leakage across injured
endothelial cells, and increased
smooth muscle cell matrix
synthesis in response to chronic
hemodynamic stress.
The vessels exhibit “onion-skin
lesions,” characterized by
concentric, laminated thickening
narrowing .
 The laminations consist of
smooth muscle cells with
thickened, reduplicated
basement membranes; in
malignant hypertension they are
accompanied by fibrinoid
deposits and vessel wall necrosis
(necrotizing arteriolitis),
particularly in the kidney.
Hypertension mainly affect the heart, brain, kidneys and aorta
The pathological consequences of hypertension are seen in four
main tissues:
• Heart.With Increasing Pressure,the left ventricular myocardium
undergoes hypertrophy. Continued remodeling of the heart leads to
dilatation and left ventricular failure.
• Brain. Hypertensive patients are prone to develop intracerebral
hemorrhage due to rupture of intracerebral blood vessels
• Kidney. Arteriolosclerosis leads to progressive ischemia of the
nephron, with eventual destruction of glomeruli.
Aorta:Hypertension predisposes to the development of severe
atheroma, abdominal aortic anyersms, and dissections
Aneurysms and Dissection

 An aneurysm is a localized abnormal dilation of a

blood vessel or the heart
 it can be congenital or acquired.
 an aneurysm involves an intact attenuated arterial
wall or thinned ventricular wall of the heart :
Atherosclerotic, syphilitic, and congenital vascular
aneurysms, and ventricular aneurysms that follow
transmural myocardial infarctions .

 An arterial dissection arises when blood enters the

arterial wall itself, as a hematoma dissecting between
its layers.
 The two most important disorders that
predispose to aortic aneurysms are
atherosclerosis and hypertension.
 Atherosclerosis is a main cause of abdominal
aortic aneurysms.

 Other conditions that weaken vessel walls and

lead to aneurysms include: trauma, vasculitis,
congenital defects (e.g., berry aneurysms
typically in the circle of Willis, and infections
(mycotic aneurysms).
Complication:

 Rupture with massive, potentially fatal

hemorrhage.
 Embolism from atheroma or mural
thrombus
 Compression on an adjacent structure,
e.g., compression of a ureter or erosion
of vertebrae
Aortic dissection
 Aortic dissection occurs principally in two
groups:
(1) men aged 40 to 60, with hypertension (more
than 90% of cases of dissection)
(2) younger patients with systemic or localized
abnormalities of connective tissue affecting the
aorta (e.g., Marfan syndrome).
 Dissections can also be iatrogenic (e.g.,
complicating arterial cannulations during
diagnostic catheterization or cardiopulmonary
bypass).
Arteriosclerosis “hardening of the arteries”

 it is a generic term reflecting arterial wall thickening and loss of

elasticity.
 There are three general patterns, with differing clinical and
pathologic consequences:
o Arteriolosclerosis affects small arteries and arterioles, and may
cause downstream ischemic injury ( hyaline and hyperplastic).
o Atherosclerosis, from Greek root words for “gruel” and
“hardening,” is the most frequent and clinically important
pattern.
o Mönckeberg medial sclerosis is characterized by calcific deposits
in muscular arteries in persons typically older than age 50. The
deposits may undergo metaplastic change into bone. the lesions
are usually not clinically significant.
Atherosclerosis

 Atherosclerosis is a major cause of morbidity

and mortality (roughly half of all deaths) in the
Western world than any other disorder.
 Lipid deposition and intimal thickening of large and
medium sized ( elastic / muscular arteries) resulting in
fatty streaks & atheromatous plaques over a period of
decades ( type of chronic inflammatory condition).
Atherosclerosis
 Atherosclerosis is characterized by intimal lesions
called atheromas (also called atheromatous or
atherosclerotic plaques) that protrude into vessel
lumens.
 An atheromatous plaque consists of a raised lesion
with a soft, yellow, core of lipid (mainly cholesterol
and cholesterol esters) covered by a white fibrous
cap .
 Atherosclerotic plaques can mechanically obstructing
blood flow, rupture, leading to catastrophic vessel
thrombosis; plaques also weaken the underlying
media and thereby lead to aneurysm formation.
 Distribution of disease: aorta, coronary, carotid,
cerebral, iliac, popliteal.
 Major Risk Factors for
Atherosclerosis
 MODIFIABLE
 NONMODIFIABLE
 Hyperlipidemia
 Increasing age
 Hypertension
 Family history
 Diabetes
 Male gender
 Cigarette smoking
 Genetic abnormalities

Minor risk factors: sedentary life style, stress ( type A personality), contraceptiv
PATHOGENESIS OF ATHEROSCLEROSIS

 Response-to-injury hypothesis: the model views atherosclerosis as a chronic

inflammatory and healing response of the arterial wall to endothelial injury:
 Endothelial injury: causes increased vascular permeability, leukocyte
adhesion, and thrombosis.
 Accumulation of lipoproteins (mainly LDL and its oxidized forms) in the
vessel wall.
 Monocyte adhesion to the endothelium, followed by migration into the
intima and transformation into macrophages and foam cells.
 Platelet adhesion
 Factor release from activated platelets, macrophages, and vascular wall
cells, inducing smooth muscle cell recruitment, either from the media or
from circulating precursors
 Smooth muscle cell proliferation and ECM production
 Lipid accumulation both extracellularly and within cells (macrophages and
smooth muscle cells)
Morphology
• Fatty streaks are the earliest lesions in
atherosclerosis.
• They are composed of lipid-filled foamy
macrophages.
• Beginning as multiple minute flat yellow spots,
they eventually coalesce into elongated
streaks 1 cm or more in length.
• These lesions are not significantly raised and
do not cause any flow disturbance
Atherosclerotic Plaque
• The key processes in
atherosclerosis are intimal
thickening and lipid accumulation
• Atherosclerotic lesions are patchy,
grossly appear white to yellow;
superimposed thrombus over
ulcerated plaques is red-brown.
• Atherosclerotic plaques have three
principal components:
 (1) cells, including smooth muscle
cells, macrophages, and T cells.
 (2) ECM, including collagen, elastic
fibers, and proteoglycans.
 (3) intracellular and extracellular
lipid
• atheromas often undergo
calcification .
 Complication to atheromatous
plaque:

 Rupture, ulceration, or
erosion.
 Hemorrhage into a plaque
 Atheroembolism
 Aneurysm formation
Vasculitis
 Vasculitis syndromes are a mixed group of diseases, affecting blood
vessels of all types

 Vasculitis: is inflammation of vessel wall.

 The clinical features of the various vasculitides are diverse and largely
depend on the vascular bed affected (central nervous system vs. heart
vs. small bowel)
 A pathological classification divides vasculitis into three groups
depending on the size of vessel predominantly involved.

 Vessels of any type in virtually any organ can be affected; most

vasculitides involve small vessels, from arterioles to capillaries to
venules.
Polyarteritis nodosa (PAN}

 Is a systemic disease that affects small and medium-sized arteries

 Polyarteritis nodosa is a systemic disease characterized by inflammatory necrosis of

medium-small -sized arteries , but can also affect small vessels.
 The clinical effects of the disease are the result of vessel occlusion leading to small areas
o f infarction, and the tissues most seriously affected are the kidneys, heart:; alimentary
tract, liver, central nervous system, peripheral nerves, skeletal muscle, and skin.
 Although the disease is systemic, it is patchy and focal, only parts o f some arteries
being involved. Affected vessels show necrotizing vasculitis
 The cause of the disease is unknown, but it is may be immune-complex mediated. There is
an association with chronic hepatitis B virus antigenemia.