Blood Vessels

Part III
Aneurysms are
congenital or
acquired dilations of
blood vessels or the
heart

It can be
•Congenital
•acquired.
A false aneurysm results when a wall defect
leads to the formation of an extravascular
hematoma that communicates with the
intravascular space (“pulsating hematoma”)

pseudo-aneurysm

a leak at the suture site of a

vascular graft with a natural artery
may also be a cause
True Aneurysm
True aneurysm involves an intact attenuated
arterial wall or thinned ventricular wall of the
heart
Predisposing Factors
Aortic Aneurysms:
Atherosclerosis (abdominal)
hypertension (ascending aorta)
Tertiary syphilis (now rare) (ascending
aorta)
Ventricular – Post Transmural MI
Other conditions include
trauma, vasculitis,
congenital defects (Berry)
infections (mycotic)
Types of Aneurysms
Saccular aneurysms: Eccentric
spherical outpouchings; 5 to 20 cm in
diameter & often contain thrombus.
Fusiform aneurysms: diffuse,
circumferential dilation of a long
segment; vary in diameter (up to 20 cm)
& length, involve the aortic arch,
abdominal aorta, or the iliac arteries.

Pathogenesis
•Inadequate or abnormal connective tissue synthesis.
•Excessive connective tissue degradation.
•loss of smooth muscle/inappropriate synthesis of ECM.
Inadequate or abnormal connective
tissue synthesis.
PATHOGENESIS
•Marfan syndrome: defective fibrillin
synthesis leads to aberrant TGF-β activity
& elastic tissue weakening
•Loeys-Dietz syndrome: mutations in
TGF-β receptors lead to abnormalities in
elastin & collagen I/III.
•Ehlers- Danlos syndrome: Weak vessel
walls due to defective type III collagen
synthesis
•vitamin C deficiency altered collagen
cross-linking
Excessive connective tissue degradation.
•By inflammatory infiltrates & increased MMP production, by
macrophages in atherosclerotic plaque or in vasculitis.
•Decreased tissue inhibitor of metalloproteinase (TIMP)
expression can contribute to the ECM degradation. Predisposition to
aneurysm formation may be related to polymorphisms of MMP &/or
TIMP genes & Local inflammation

Adventitial inflammatory
infiltrate and thickening of the
vasa-vasorum (HE staining)
Weakened vascular wall due to loss of smooth
muscle/inappropriate synthesis of ECM.

Ischemia due to atherosclerosis (the

inner media) or hypertension (outer
media vaso-vasorum) leads to
• smooth muscle cell loss & “degenerative
changes,” (fibrosis, loss of elastic fibres,
inadequate ECM synthesis, and
production of excessive amorphous
ground substance - glycosaminoglycan)
• Histologically these nonspecific changes
are collectively called cystic medial
degeneration (also seen in Marfan disease
and scurvy)
 ABDOMINAL
AORTIC ANEURYSM
• Atherosclerosis is a major cause.
• More frequently in men and smokers,
and rare before 50 years of age
• Usually positioned below the renal
arteries and above the bifurcation of the
up to 15 cm in diameter, and up to
aorta, can be saccular or fusiform,
25 cm in length
– Inflammatory AAAs frequently contains a bland, laminated,
• Mycotic AAAs occur when circulating mural thrombus
microorganisms (as in bacteremia from a
Salmonella gastroenteritis) seed the
aneurysm wall or the associated thrombus;
 The Clinical Consequences Of AAA

• Rupture into the peritoneal cavity or retroperitoneal tissues

with massive, potentially fatal haemorrhage
• Obstruction of a branch vessel resulting in ischemic injury
of downstream tissues: iliac (leg), renal, mesenteric (GIT) or
vertebral arteries
• Embolism from atheroma or mural thrombus
• Compression of an adjacent structure, e.g., of a ureter or
erosion of vertebrae
• Simulates an abdominal tumor (often pulsating)
• Most commonly with hypertension, Thoracic Aortic
Marfan, Loeys -Dietz syndromes
Aneurysms
• Signs & symptoms referable to
encroachment
– on mediastinal structures,
– On lungs & airways with respiratory
difficulties
– On oesophagus with difficulty in
swallowing
– On recurrent laryngeal nerve with
persistent cough
– On ribs and vertebrae with erosion &
bone pain
• Aortic valve dilation (syphilitic) with
valvular insufficiency or narrowing of the
coronary ostia
 arterial
dissection
• Occurs when blood enters the
arterial wall itself, as a
hematoma dissecting between
its layers. Dissections are
often but not always
aneurysmal.
• Dissections can rupture, often
with catastrophic
consequences.
 Aortic Dissection
Occurs principally in two groups:
• men aged 40 to 60, with antecedent hypertension (more than
90% of cases of dissection);
• younger patients with connective tissue abnormalities of
affecting the aorta (Marfan’s)
Iatrogenic: complicating arterial cannulations during
catheterization or cardiopulmonary bypass
Rarely, for unknown reasons, during or after pregnancy.
• Dissection is unusual in the presence of substantial
atherosclerosis or other cause of medial scarring
 Aortic Dissection
• starts with an intimal tear.
• In majority of cases the tear is
in the ascending aorta,
usually within 10 cm of the
aortic valve, transverse or
oblique, 1 to 5 cm in length.
• The dissecting hematoma
spreads usually between the
middle & outer thirds of
laminar planes
Aortic Dissection

Proximal lesions (type A

dissections) (More common
and dangerous), involving the
ascending aorta with or without
descending aorta (types I and
II of the DeBakey)
Distal lesions beginning distal
to the subclavian artery (type B
dissections or DeBakey type
III)
 Symptoms & Outcome of Aortic
Dissection

• Sudden onset of excruciating pain, mimicking MI

• The most common cause of death is rupture of the
dissection outward into the pericardial (cardiac tamponade),
pleural, or peritoneal cavities. Retrograde dissection into the
aortic root aortic insufficiency.
• Rapid diagnosis and institution of intensive antihypertensive
therapy, coupled with surgical procedures involving plication
of the aortic wall, permit 65% to 75% survival
 •The Chapel Hill Consensus System
–Large-vessel vasculitis: the aorta and its
larger branches
Vasculitis –Medium-sized vessel vasculitis:
–Small-vessel vasculitis:
Inflammatory Disorders of Blood Vessels
Large Vessel Vasculitis Giant cell arteritis
(granulomatous) Takayasu arteritis
Medium-Sized Vessel Polyarteritis nodosa (IC)
Vasculitis Kawasaki disease (Anti-EC-Ab)
Small Vessel Vasculitis Henoch-Schonlein purpura
(With Immune Complexes) Cryoglobulinemic vasculitis
Small Vessel Vasculitis Microscopic polyangiitis (MPO-ANCA)
(Pauci -Immune) often with Churg -Strauss syndrome (MPO-ANCA)
ANCA
Wegener Granulomatosis (PR3-ANCA)
IC = Immune complex; Anti-EC-Ab = Anti-endothelial cell antibody;
PR3-ANCA- = antineutrophil cytoplasmic antibody - Antiproteinase-3
(c-ANCA); MPO-ANCA- antineutrophil cytoplasmic antibody –
antimyeloperoxidase (p-ANCA)
 Immunological Basis
1. Immune complex deposition: SLE, PAN, Drug
hypersensitivity, Virus infection associated
2. antineutrophil cytoplasmic antibodies:
– Anti-myeloperoxidase (MPO-ANCA)(p-ANCA):
microscopic polyangiitis, Churg Strauss syndrome
– Anti-proteinase-3 (PR3-ANCA)(c-ANCA): Wegener
granulomatosis
3. anti–endothelial cell antibodies: Antibodies to endothelial
cells may predispose to certain vasculitides, for example,
Kawasaki disease
 Giant Cell Arteritis (Temporal
Arteritis, Granulomatous Arteritis)
• A focal, granulomatous
inflammation
• Rare before the age of 50
• Possible T cell–mediated immune
response against an unknown Ag
• fever, fatigue, weight loss, facial
pain or headache
• Abrupt ocular symptoms in ~ 50%
of patients; may lead to loss of
vision
• Steroids are effective

Classic lesions exhibit medial granuloma with

an infiltrate of T cells (CD4+> CD8+) &
macrophages. Giant cells are found in >75%
of specimens
Takayasu Arteritis • Classically granulomatous vasculitis of
(Pulseless disease) Aortic arch & great vessels; affects
pulmonary in 50%; others in < 1/3rd
• Unknown cause, may be immune
• Affects young women (<30y); ocular
disturbances, retinal haemorrhages, total
blindness; and neurologic deficits; weak or
absent pulse; intermittent claudication;
• Intimal thickening with obliteration of
lumen; Histology is similar to giant cell
arteritis
• Respond to steroids in early stages
 Kawasaki Disease
(Mucocutaneous Lymph Node
Syndrome)
• Acute febrile, self-limited
vasculitis of infancy &
childhood
• Unknown cause; May be T
cell mediated response
• Fever, skin rash, oral &,
conjunctival lesions,
lymphadenopathy
• Coronary artery aneurysms
cause death in 1% to 2% of
cases.
• Histology resembles PAN
 Polyarteritis • a disease of young adults but can occur in
nodosa (PAN) all age groups.
• Segmental transmural necrotizing
inflammation of small to medium-sized
arteries of the kidneys, heart, liver, and
GIT
• 30% association with Hepatitis B
• presentation is varied: hypertension due to
renal artery involvement; abdominal pain,
peripheral neuritis; Renal arterial
involvement is often a major cause of
Fibrinoid necrosis
death.
(arrow), acute • Untreated, the disease is fatal
inflammation, eosinophils • Remissions or cures with Steroids and
cyclophosphamide (90%)
 Allergic Granulomatosis And Angiitis
(Churg-Strauss Syndrome)
• Small-vessel necrotizing
vasculitis with asthma,
allergic rhinitis, lung
infiltrates, eosinophilia, &
granulomas.
• ANCAs (mostly MPO-
ANCAs) present in < half
the cases
• The heart is involved in
60% of patients & accounts
for 50% of death
 Wegener • Necrotizing vasculitis
granulomatosis • Granulomatous lesions of the nose,
sinuses, and lungs
• focal necrotizing, often crescentic,
glomerulonephritis
• PR3-ANCAs are present in up to 95% of
cases;
• Untreated, the disease is fatal
• steroids, cyclophosphamide, TNF-
antagonists are useful

ORGANS MOST
FREQUENTLY AFFECTED
• Affects capillaries, arterioles & Microscopic Polyangiitis
venules (hypersensitivity vasculitis;
• skin, mucosa, lungs, brain, heart, GIT, leukocytoclastic vasculitis)
kidneys, & muscle may be involved
• necrotizing glomerulonephritis (90%
of patients) and pulmonary capillaritis
are particularly common
• In some cases, antibody responses to
Ag such as drugs (e.g., penicillin),
microorganisms (streptococci),
heterologous proteins, or tumor
proteins have been implicated. MPO-
ANCAs are causally im-plicated.
• cyclophosphamide and steroid induces
remission

necrotizing glomerulonephritis
Thromboangiitis obliterans
(Buerger disease)
• segmental, thrombosing, acute and
chronic inflammation of medium-sized
&small arteries, (the tibial and radial
arteries)
• occurs almost exclusively in heavy
cigarette smokers, usually before the
age of 35.
• Pain in the instep of the foot induced by
exercise (instep claudication)
• cold sensitivity of the Raynaud type
 Haemangioma
• Very common tumors/malformation of normal or abnormal
vessels
• Difficult to distinguish from vascular malformations.
• Constitute 7% of all benign tumors of infancy and
childhood; most are present from birth and many of the
capillary lesions regress spontaneously.
• Some hemangiomas involve large portions of the body
(angiomatosis), most are localized.
• The majority are superficial lesions, often in head or neck, but
nearly one third being found in the liver.
Capillary Haemangioma
This lesion is composed of vascular
channels with the size and structure of
normal capillaries. In the skin they are
known as birthmarks or ruby spots.
"Infantile haemangioma”
"Strawberry nevus” usually appear
between one and four weeks after
birth. Some regress by the age of 2 ,
about 60% by 5 years, and 90–95%
by 9 years.[5]
 Cavernous Haemangioma
Port-wine stains
• Usually present at birth and
They do not involute but
persist.
• Sturge-Weber syndrome:
congenital ocular & CNS
vascular malformations that
may lead to vision loss,
glaucoma, seizures, mental
retardation, and hemiplegia.
 Kaposi sarcoma
• Appears in epidemic form in
association with AIDS & in
mmunosuppressed patients.
• HHV 8, (KSHV) is thought to be
responsible for this tumor
• begins as painful purple or brown
cutaneous nodules, most often on
the hands or feet but occur
anywhere.
• 4 types: Lymphadenopathic,
Classic, Transplant and AIDS
associated
Angiosarcoma

• Affects Older adults with equal

gender predilections;
• most often involve skin, soft
tissue, breast, and liver. Liver
tumours are associated with
PVC, arsenic, Thorotrast
• aggressive tumors with current 5-
year survival rates approaching
30%.