VASCULAR PATHOLOGY

V. N. Karazin Kharkiv National University

School of Medicine
General and Clinical Pathology Department
Ass. Tkachenko N.A.

2022
 There are three major vessel types:
• arteries (carry blood from the heart to the systemic

circulation);
• capillaries (responsible for exchange of water and

chemicals between the blood and tissues);

• and veins (carry blood from capillaries back towards

the heart)
 The arteries and veins have a similar structure with three layers, from inside to outside:

1. Tunica intima (thinnest layer): It is composed of a single layer of flattened

cells (lining endothelium) held together by a polysaccharide matrix composed
of collagen, proteoglycans and elastin. Outside this is present a thin layer of
connective tissue (subendothelial connective tissue) and circularly arranged
elastic bands called internal elastic lamina, which separates the intima from the
media.
2. Tunica media (thickest layer): This is limited on the inside by the internal
elastic lamina and on the outside by another thick elastic band called external
elastic lamina (the latter separates the media from adventitia). Tunica media is
constituted by connective tissue and polysaccharide substances and is rich in
vascular smooth muscle (especially arteries), which controls the calibre of the
vessel.
3. Tunica adventitia: It is made of loose connective tissue and
elastic fibres and contains nerves that supply the vessel as well as
nutrient capillaries (vasa vasorum). The inner part of the tunica
media receives nourishment by direct diffusion of nutrients and
oxygen from the lumen whereas the outer part of the media is
nourished by the vasa vasorum.
 Vascular pathology
Vascular disease is responsible for more morbidity and
mortality than any other category of human disease. Although
the most clinically significant lesions involve arteries, venous
pathology can also cause clinical disorders.

 narrowing or complete obstruction of vessel lumina, either

progressively (e.g., by atherosclerosis) or precipitously (e.g.,
by thrombosis, embolism)
 weakening of vessel walls, causing dilatation and/or rupture
 ATHEROSCLEROSIS
In atherosclerosis, inflammatory and immune cells, smooth
muscle cells, lipid and connective tissue progressively accumulate in
the intima of large and medium-sized elastic and muscular arteries.
The classic atherosclerotic lesion is best described as a
fibroinflammatory lipid plaque (atheroma).
An atheromatous plaque consist of a raised lesion with a soft,
yellow, grumous core of lipid (mainly cholesterol and cholesterol
esters) covered by a firm, white fibrous cap. Besides obstruction
blood flow, atherosclerotic plaques weaken the underlying media and
can themselves rupture, causing acute catastrophic vessel thrombosis.
 MORPHOLOGY OF ATHEROSCLEROSIS

Grossly recognizable atherosclerosis begins as a fatty streak and

progresses to an atherosclerotic plaque.
Fatty streak are cd-filled foam cells but are not significantly raised and
thus do not cause any disturbance in blood flow. They begin as multiple
minute yellow, flat spots that can coalesce into elongated streaks, 1 cm
long on longer.
Atherosclerotic plaque – also called fibrous or fibrofatty plaques impinge
on the lumen of the artery and grossly appear white to yellow; thrombosis
superimposed over the surface of ulcerated plaques is red-brown in color.
Plaque vary from 0.3 to 1.5 cm in diameter but can coalesce to form larger
masses. There are three main components of a atherosclerotic plaque:
• Fibrous cap –a thick fibrous cap is more stable
and less likely to develop complication. The fibrous
cap is composed of smooth muscle cells and
extracellular matrix (e.g., collagen)
• Atheromatous core – contains extracellular lipid
macrophages with intracellular lipid and necrotic
tissue
• Shoulder of plaque - (the side of the cap): Has
macrophages leukocytes and blood vessels.
 Complications
Acute occlusion: Thrombosis on an atherosclerotic plaque may
abruptly occlude the lumen of a muscular artery. The result is
ischemic necrosis (infarction) of the tissue supplied by that vessel,
manifested clinically as myocardial infarction, stroke or gangrene
of the intestine or lower extremities. Some occlusive thrombi can
be dissolved by enzymes that activate plasma fibrinolytic activity,
including streptokinase and tissue plasminogen activator.
Chronic narrowing of the vessel lumen: As an
atherosclerotic plaque grows, it may impinge on the lumen,
progressively reducing blood flow to the tissue served by that
artery. Chronic ischemia of the affected tissue causes atrophy
of the organ, as exemplified by unilateral renal artery stenosis
leading to renal atrophy, mesenteric artery atherosclerosis
causing intestinal stricture or ischemic atrophy of the skin
occurring in a diabetic with severe peripheral vascular
disease.
 Aneurysm formation: The complicated lesions of atherosclerosis may
extend into the media of elastic arteries and weaken their walls, so as to
allow aneurysm formation, typically in the abdominal aorta. Sudden
rupture of these aneurysms may precipitate a vascular catastrophe.
 Embolism: A thrombus formed over an atherosclerotic plaque may
detach and lodge in a distal vessel. For example, embolization from a
thrombus in an abdominal aortic aneurysm may acutely occlude the
popliteal artery, with subsequent gangrene of the leg. Ulceration of an
atherosclerotic plaque may also dislodge atheromatous debris and
produce so-called “cholesterol crystal emboli,” which appear as needle-
shaped spaces in affected tissues, most commonly in the kidney.
SYSTEMIC HYPERTENSION
 Systemic hypertension
• Benign – has a slow clinical course. Patients can survive
with the diseases for 10-20byears or more. Note, that despite
the designation of “benign’’, all forms of hypertension are
associated with increased morbidity and mortality
• Malignant – has a rapid clinical course. Death occur within
1 to 3 years. Patients have retinal hemorrhage, papilledema
and renal failure. Malignant hypertension can arise in the
background of “benign” hypertension, or it can arise de
novo.
 Morphology of hypertension
Gross morphology:
 Microscopic morphology
• Hyaline arteriolosclerosis: associated with benign hypertension.
This vascular lesion consists of a homogeneous pink hyaline
thickening of the walls of arterioles with loss of underlying structural
detail and with narrowing of the lumen.
• Hyperplastic arteriolosclerosis: associated with malignant
hypertension. Hyperplastic arteriolosclerosis is associated with
“onion-scin”, concentric, laminated thickening of the walls of
arterioles with luminal narrowing .
 ANEURYSMS AND AORTIC DISSECTION
Aneurysm
An aneurysm (“true” aneurysm) is a localized abnormal
dilation of the wall of a blood vessel involving all layers.

A “false” aneurysm (pseudoaneurysm) is a defect in the

wall allows blood to escape the vessel or organ and
accumulate outside the wall. False aneurysms can result
from trauma or rupture of a vessel.
Causes of aneurysms
Acquired disease of vessel wall (atherosclerosis, arteritis)
Congenital weakness of the wall of a blood vessel
Hypertension
Trauma
Infections
Types of aneurysm
 Saccular aneurysm: saccular outpouching from one side of
the affected vessel
Fusiform aneurysm: generalized dilation of the entire
circumference of the affected vessel
 Pathogenesis of aneurysms
• Blood pressure (hypertension is important in all types of
aneurysma)
• Resistance to distension of the vessel wall (weakness of the
vessel wall potentiates the form which the aneurysm assumes)
Atherosclerotic aneurysm
Atherosclerosis is the most common cause of aneurysms and such
aneurysms most commonly occur in the abdominal aorta.
Contributing factors are matrix metalloproteinases that are secreted
by macrophages and contribute to damage of the wall. Aneurysms
have a decreased level of tissue inhibitors of metalloproteinases
(TIMP).
 Syphilitic Aneurysms
Syphilis causes obliterative endarteritis of the vasa vasorum (aorta root and arch), which
results in ischemia of the vessel’s media. The ischemia of the media leads to scarring and loss
of elastic recoil so the vessel dilates.
“Berry” Aneurysm
Occurs in medium-sized vessels at the base of the brain, e.g. Circle of Willis. Associated
with congenital deficiency of apterial media. Rupture causes subarachnoid hemorrhage.
 Mycotic aneurysm
Mycotic aneurysm are the result of weakening of the
arterial wall, secondary to bacterial or fungal infection.
The organism are throught to reach the arterial wall via
the vasa vasorum.
Lessions are commonest in
the cerebral arteries but almost any
area can be affected. Bacterial
endocarditis is the commonest
underlying infection.
 Capillary micro-aneurysm
Capillary micro-aneurysm (Charcot-Bouchard aneurysms) are
associated with both hypertension and diabetic vascular disease. In
hypertension, they are common in branches of the middle cerebral
artery, particularly the lenticulo-striate. They are throught to be the
precursors of primary
hypertensive
intracerebral hemorrhage,
which characteristically occurs in
the basal ganglia, cerebellum
or brainstem.
 MORPHOLOGY OF ANEURYSM
Abdominal aortic aneurysm (AAA) – usually
positioned below the renal arteries and above the
bifurcation of the aorta, AAA can be saccular or
fusiform, as large as 15 cm in diameter and as
long as 25 cm. The aneurysm frequently contains
a bland, laminated, poorly organized mural
thrombus that may fill some of or all of the
dilated segment.
Syphilitic Aneurysm – tr. pallidum has a predilection to involve
small blood vessels, the vasa vasorum, in the aortic adventitia.
These vessels develop so-called obliterative endarteritis. The
affected vessels wall, and a dense surrounding rim of lymphocytes
and plasma cells that may extend into the media (syphilitic aortis).
The narrowing of the lumina of the vasa vasorum causes ischemic
injury of the aortic media, with patchy loss of the medical elastic
fibers and muscle cells, followed by inflammation and scarring.
With destruction of the media, the aorta loses its elastic recoil and
may become dilated, producing an aneurysm. Contraction of
fibrous scars may lead to wrinkling of intervening segments of
aortic intima, grossly reminiscent of “tree bark”.
A case of a syphilitic aneurysm quite similar to that described by Morgagni in a
man in the anatomomedical letter XXIV. Note on the left the penetrated sternum
and on the right the huge aneurysm of the aortic arch (University of Padua,
Museum of Pathological Anatomy)
 Complications of aneurysm
• Emboli from atherosclerotic plagues that form within the
aneurysm.
• Thrombosis: aneurysm allows for stagnation of blood and
formation of thrombi, with or without resultant emboli.
• Rupture of aneurysm with resultant hemorrhage. Triad:
abdominal pain, hypotension and pulsatile abdominal
mass.
• Obstruction od branch vessels.
• Impingement on neighboring structures
 AORTIC DISSECTION
Aortic dissection is separation of the aortic media by blood entering
the wall through an intimal tear. In contracts to atherosclerotic and
syphilitic aneurysms, aortic dissection may or may not be associated
with aortic dilation. Consequently, the older term “dissecting
aneurysm” is discouraged.
The sudden onset of tearing chest pain may be the initial presentation of an acute
aortic dissection. A small tear in the aortic intima can quickly split the aortic wall and
create a rapidly expanding false lumen (yellow arrow), which may be rapidly fatal
even with prompt medical treatment.
In the United States, aortic dissection occurs most frequently in hypertensive patients. The true
prevalence is difficult to estimate, with most estimates based on autopsy studies (as shown), in
which aortic dissection is found in 1%-3% of cadavers. The incidence is estimated to be 5-30 cases
per 1 million people per year. Aortic dissection occurs once per 10,000 patients admitted to the
hospital; approximately 2000 new cases are reported each year in the United States.
Dissecting aneurysm (HE staining)
 Complications of aortic dissection
• if the second tear is in the intima in another location: results in a “double-
barrel” aorta, the most benign complication of an aortic dissection.
• if the second tear is in the pericardial sac: results in hemopericardium
and possible cardiac tamponade.
• with involvement of the aortic valve ring: disrupts stability of the valve,
leading to aortic insufficiency.
• if the second tear is into the pleural cavity: results in hemothorax.
• if the second tear is into the retroperitoneum: results in retroperitoneal
hemorrhage.
• with involvement of the coronary arteries: as blood dissects through the
media, branch vessels can be compressed or the vessels themselves may
dissect, resulting in infarction of the downstream organ.
 VASCULITIS
Vasculitis is inflammation of the vessels,
which most commonly has an infectious or
immune-mediated cause. In most forms of
vasculitis.
In the most forms of vasculitis the
pathological changes in the vessels are broadly
similar.
 Giant cells arteritis
• Vessels affected: aorta and branches of the carotid arteries
(ophthalmic, temporal).
• Clinical manifestation: includes visual disturbances (diplopia
and visual loss) and unilateral temporal headache and jaw
claudication. Patients can have an elevated erythrocyte
sedimentation rate.
• Microscopic morphology: granulomatous inflammation of vessel
wall with disruption of elastic lamellae.
• Complications: thoracic aortic aneurysms.
 Takayasu arteritis
• Vessels affected: aorta, branches vessels to upper extremities and
pulmonary arteries. The condition is also called “pulseless disease”
• Clinical manifestation: weak pulses in upper extremities; arthralgias,
myalgias, night sweats, visual disturbances and fever. Patients can
have an elevated erythrocyte sedimentation rate.
• Morphology: cross: vessel wall with near occlusion of lumen by thick
intima. Microscopic: varies from a mononuclear inflammatory
infiltrate to granulomatous inflammation. Intimal proliferation and
fibrosis is present.
• Complications: thoracic aortic aneurysms.
 Polyarteritis nodosa
• Vessels affected: small or medium-sized muscular arteries.
Polyarteritis nodosa does not involve the smaller vessels (venules,
capillaries, arterioles) or pulmonary arteries. Commonly involved
vessels are the renal and visceral arteries.
• Clinical manifestation: Polyarteritis nodosa presents a challenging
clinical diagnosis since a multitude of symptoms are possible.
Hypertension and abdominal pain are common. Arthritis and
myalgias are present in more than 60% of cases. Polyarteritis
nodosa is not associated with glomerulonephritis.
• Microscopic morphology: transmural inflammation of vessels in
combination with fibrinoid necrosis (smudgy, pink degeneration of
wall), which leads to scarring.
Polyarteritis nodosa (PAN), acute phase. High-
power view of skin biopsy from a 4-year-old
boy with PAN. Biopsy shows a neutrophilic
vasculitis affecting medium and small arteries
in the deep dermis and subcutis.
 Wegener granulomatosis
• Vessels affected: small vessels in upper and lower respiratory
tract and kidney.
• Clinical manifestation: Wegener granulomatosis is a
necrotizing vasculitis characterized by a triad: a) acute
necrotizing granulomas of the upper upper extremities; and
lower respiratory tract, causing chronic sinusitis; b)
necrotizing and granulomatous vasculitis of organs: most
prominently involve the lungs, forming nodules and
infiltrates and causing pneumonitis; c) focal necrotizing or
crescentic gromerulonephritis, causing renal disease.
• Microscopic morphology: granulomatous inflammation.
 Kawasaki arteritis
• Vessels affected: most important is involvement of the coronary
arteries.
• Clinical manifestation: Kawasaki disease classically presents in
children younger than 5 years of age who present with a high fever (up
to 400 C, or 104 F) for more than 5 days; with conjunctivitis,
strawberry tongue, cervical lymphadenopathy; and with peeling
erythematous rash of lips, palms and soles of feet.
• Microscopic morphology: similar to polyarteritis nodosa but with less
prominent fibrinoid necrosis.
• Complications: includes aneurysms of the coronary arteries and
myocardial infarction. These are late complications occurring many
years after acute disease.
 Buerger disease (thromboangiitis obliterans)
• Vessels affected: small and medium-sized arteries, most
commonly radial and tibial artries.
• Clinical manifestation: severe pain with activity or rest,
most likely due to neural involvement and digital
ulceration.
• Microscopic morphology:. segmental acute and chronic
vasculitis; can have thrombosis of the lumen; thrombus
can contain microabscesses.
• Complications: ulcers of toes, feet or fingers.
 RAYNAUD DISEASE (PHENOMENON)

There are spasmodic attacks of pallor or cyanosis of

the fingers (the toes, ears and nose may also be
affected) due to intense constriction of the small
arteries and arterioles in response to cold. The cause is
not known.
This condition may continue for many years and no
permanent damage results.
 Primary Raynaud phenomenon
Raynaud’s disease is a relatively rare phenomenon, affecting 5–
10% of the population worldwide. The aberration of blood flow
caused by the sudden vasospasm of small vessels is not severe
enough to cause necrosis or other trophic lesions due to limited
blood supply. As Raynaud’s disease is only a functional disorder,
no structural changes of the vessel wall are present. Comparing
with the secondary Raynaud’s syndrome, the vasospasm in
Raynaud’s disease is relatively rare, less severe and patients
usually lack anti-nuclear antibodies ANA (or the ANA titer may be
very low).
 Secondary Raynaud phenomenon
Secondary Raynaud’s phenomenon, in contrast to the
primary one, is not an isolated symptom, but an integral
part of a spectrum of different symptoms of chronic
connective tissue diseases. Disorders, most often
heralded by RP are: systemic sclerosis (SSc), mixed
connective tissue disease (MCTD), systemic lupus
erythematosus (SLE), dermatomyositis (DM), Sjögren
syndrome (SS) and rheumatic arthritis
 DISEASE OF VEINS
Like arteries, veins have an intima, media and adventitia.
There is no definite internal elastic lamina and as in arteries
the thickness of the intima increase with age
(phlebosclerosis).
Small veins have only a thin muscular wall but in larger
channels, such as the saphenous vein and the inferior vena
cava, there are coarse bundles of irregular muscle, partially
organized into longitudinal and circular layers.
 Venous thrombosis
The veins of the lower limbs are very common sites of acute
thrombosis, especially after surgical operations and during
illnesses with enforced bed rest.
Common predisposing causes include:
Immobility (in severe cardiac failure, bed rest, leg fractures)
In patients with cancer
Pregnancy and childbirth
Estrogen therapy
Hematological disorders
Intravenous cannulae
 Pulmonary embolism
Is a common and serious clinical complication of deep venous
thrombosis, resulting from fragmentation or detachment of the venous
thrombus. In many cases, the first manifestation of thrombophlebitis is
a pulmonary embolus. Depending on the size and number of emboli,
the outcome can range from no symptoms at all to death.
 Varicose veins
A varix is a localized bulge in a vein analogous to a saccular aneurysm in an artery. It is
almost always associated with more generalized varicosity of the vein.
Causes and pathogenesis
acting on the vein wall
Hereditary
Obesity
Age
Periods of prolonged standing
Increasing the intraluminal pressure
Pregnency, tumor, thrombosis of veins, constructional pressure
Special communicating veins between deep and superficial systems, if valves not competent,
cause backflow into superficial veins greatly increasing the pressure within them
Gravitation pressure of a long column of blood
 Clinical manifestation

Varicose dilatation renders the venous valves

incompetent and leads to
- Stasis, Congestion, Edema, Pain, Thrombosis.
The most disabling sequelae include persistent edema
in the extremity and secondary
ischemic skin changes including stasis dermatitis and
ulcerations; poor wound healing and superimposed
infections can became chronic varicose ulcers
 Varicosities also occur in two
other sites that deserve mention:
 Esophageal varices. Liver cirrhosis (less frequently, portal

vein obstruction or hepatic vein thrombosis) causes portal

vein hypertension. Portal hypertension leads to the opening
of porto-systemic shuts, increasing blood flow into veins at
the gastroesophageal junction (forming esophageal varices),
the rectum (forming hemorrhoids), and periumbilical veins of
the abdominal wall (forming a caput medusa). Esophageal
varices are the most important, since their rupture can lead to
massive (even fatal) upper GI hemorrhage.
Caput medusa
Esophageal varices
 Hemorrhoids can also result from primary dilatation of the
venous plexus at the anorectal junction ( through prolonged pelvic
vascular congestion due to pregnancy or straining to defecate).
Hemorrhoids are uncomfortable and may be a source of bleeding;
they can also thrombose and are prone to painful ulceration.
Morphology varicose veins show wall thinning at the points of
maximal dilatation with smooth muscle hypertrophy and intimal
fibrosis in adjacent segments; elastic tissue degeneration and spotty
medial calcifications (phlebosclerosis) also occur. Focal
intraluminal thrombosis (due to stasis) and venous valve
deformities (rolling and shortening) are common.
 VASCULAR TUMORS
Benign tumors
Hemangiomas – are common benign tumors of small capillaries.
Microscopic morphology:
- Capillary (small, back to back, capillary-like vessels)
- Cavernous (large, blood-filled spaces).
 Malignant tumors
• Angiosarcoma - lesions most commonly develop in the soft tissues of
the lower limbs, the head and neck of elderly individuals.
• Kaposi’s sarcoma – develop in patients with acquired immune
deficiency following HIV infection.
Morphology gross- patches progress to raisedplaques, which progress to
nodules. Microscopic –
spindled cells, extravasated
red blood cells.
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