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DISEASES OF THE BLOOD VESSELS
Clinical manifestations of blood vessel diseases.
-pathologic changes in blood vessels have one or more basic
consequencies
 narrowing of the lumen of the vessel (vascular atrophy), occlusion of
vessel (tissue ischemia), and potential infarction in tissues supplied
by the vessel
 damage to the intima with thrombosis
 weakening of the wall with dilatation (aneurysm) and/or potential
rupture of the blood vessel
Congenital anomalies of blood vessels.
1- berry aneurysm- caused by congenital focal weakness of the
blood vessel wall results in outpouching
-occur in cerebral vessels- weakening of the wall may lead to fatal
rupture- resulting in subarachnoidal hemorrhage
2- arterio-venous fistula- is an abnormal communication
between vein and artery
-may be congenital or caused by trauma
-fistulas may cause left-to right shunt with an increase of venous
return - possible right heart failure
-may cause fatal hemorhage
ACQUIRED DEGENERATIVE DISEASES OF BLOOD VESSELS.
ARTERIOSCLEROSIS
-is slowly progressive disease of arteries, characterized by
thickening and loss of elasticity of arterial walls
atherosclerosis
- is a slowly progressive d. of arteries characterized by elevated intimal
fibrofatty plaques, formed by lipid deposition, smooth muscle
proliferation and synthesis of extracellular matrix
- large to medium-sized muscular arteries and large elastic arteries
are involved, particularly the aorta, and its branches, coronary
arteries, and arteries of the circle of Willis
arteriolosclerosis
-affects small arteries and arterioles
-occurs in two variants, as hyaline and hyperplastic, both cause
thickening of the vessel wall with luminal narrowing
 hyaline arteriolosclerosis- is characterized by diffuse pink hyaline
thickening of the aretriolar wall
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-occurs typically in older pateints
- affects the kidney- causes benign nephrosclerosis - grossly:
- the kidneys are symmetrically atrophic, finely granular surface
microscopically:
- hyaline thickening of the walls of the small arteries and arterioles
(homogenous, pink) with narrowing of the lumena
- decrease of the blood flow through affected vessels- causes ischemia
and ischemic atrophy of the kidney
- in younger patients- associated with arterial hypertension and DMfrequency and severity of the lesions is increased
 hyperplastic
arteriolosclerosis
-characteristic
of
malignant
hypertension- microscopically- concentric lamellar „onion-skin“
arteriolar thickening with reduplication of basement membrane and
smooth muscle cell proliferation- fibrin deposition and vessel wall
necrosis
 ATHEROSCLEROSIS
- is the most important pattern in arteriosclerosis
 pathogenesis and epidemiology:
multifactorial, idiopathic, not completely understood
risk of development of atherosclerosis increases with
-age, cigarette smoking, positive family
hypertension, diabetes mellitus, and hypercholesterolemia
history,
-major acquired risk factors:
1) acquired hyperlipemia
2) hypertension
3) cigarette smoking
4) diabetes mellitus
-the risk is correlated with elevated serum levels of low-density
lipoprotein (LDL)
-the higher total cholesterol level, the greater risk of AS
pathogenesis:
- most theories invoke some damage to endothelium or underlying
smooth muscle with subsequent proliferation of smooth muscle cells
"response-to-injury-hypothesis"
- according to this idea- atherosclerosis is a reaction to chronic
repeated endothelial cell injury, caused by such insults as
hyperlipidemia,
hypertension,
cigarette
smoking,
diabetic
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microangiopathy, circulating endotoxins, anoxia, hypoxic changes,
viruses, turbulent blood flow,etc.
-endothelial injuries induce metabolic and structural changes
accompanied by increased permeability to plasma constituents, such
as lipids, lipoproteins, mainly cholesterol - these substances may
accumulate within the intima at these sites of endothelial injurybecause of local increase of endothelial cell permeability
-subsequent cellular events include imigration of macrophages
into the intima- these change to foamy cells
-endothelial injury also result in adhesion of platelets and
monocytes and release of factors from activated platelets and
monocytes, such as PDGF- platelet-derived growth factor, induce
smooth muscle proliferation and their migration to the intima,
-smooth muscle cell produce large amounts of extracelular
matrix components, such as collagen, elastic fibres, proteoglycans
-smooth muscle cells accumulate lipid (cholosterol) to become
foam cells
 MORPHOLOGY OF ATHEROSCLEROTIC LESIONS
1) FATTY STREAKS
-are thin flat yellow streaks in the intima- caused by lipid
depositions in the cytoplasm of intimal mesenchymal cells and in
macrophages- aggregates of foamy cells
-they may occur in the aorta very early in life- are harmless and
reversible in early stage- there is not a obvious relation to AS- some of
them disappear, some may progress to atheromatous plaques- many
believe however that fatty streaks are precursors of AS plaques
2) ATHEROMATOUS PLAQUES- fibrofatty atheroma - fibrous plaques
-early changes- monocytes adhere to endothelial cells close to the site of injurymigrate between endothelial cells to get to the subendothelial spacethan change to foamy cells
- in addition- smooth muscle cells from the media layer- become
larger and proliferate- these cells also take up lipids to form foam
cells- aggregates of foam cells within the intima = fatty streaks
-later
plaque)
stage-MATURE
FIBROFATTY
ATHEROMAS
(intimal
-is composed of aggregates of foam cells and macrophages and SMCs,
extracellular lipids, cellular debris, fibroblasts and collagenous matrix
-with proggresion of the disease- fibrofatty atheroma is modified by
further deposition of collagen, elastin, proteoglycans. Atheromas
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undergo considerable cellular proliferation and formation of fibrous
connective tissue = FIBROUS PLAQUES
-secondary changes in atheromatous plaque-dystrophic calcification-very common
-severely affected vessels- can be changed into completely calcified
rigid tubes
-ulceration of the overlying endothelium - thrombosis of the
plaque- most common complication
-thrombosis- often associated with ulceration -parts of atherothrombotic masses- may be discharged to the blood stream as emboli
-vascularisation of the plaques- may lead to the hemorrhage in
the plaques- occlude the lumen (coronary vessels)
-aneurysms may develop in vessels weakened by extensive
plaque formation- the abdominal aorta is a favourite site
HYPERTENSIVE VASCULAR DISEASE
-hypertension is the single most important risk factor in both
coronary heart disease and cerebro-vascular accidents
-it may also lead directly to congestive heart failure (hypertensive
heart disease), to renal failure and aortic dissection
-90% of hypertension is primary and idiopathic- essential
hypertension-10% of hypertension is secondary-mostly related to renal
disease, endocrine abnormalities, vascular malformation
blood pressure- is a complex trait that is determined by the
interaction of multiple genetic and environmental factors that regulate
the relatioship between cardiac output and total arteriolar resistence
pathogenetic mechanisms leading to essential hypertension-essential hypertension is either related to a primary increase in
cardiac output (retention of natrium)
-or to an increase in peripheral resistence- release of
vasoconstrictive factors, neurogenic causes, increased sensitivity of
smooth muscle cells, etc.
 Inflammatory Diseases of Blood Vessels.
1) POLYARTERIITIS NODOSA
=systemic disease characterized by necrotizing inflammation of
medium- and small-sized arteries throughout the body sparing the
pulmonary circulation
-most often - in middle aged adults, more often in males
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-disease is characterized by fibrinoid necrosis of the intima, and heavy
mixed inflammatory infiltration in and about the vessel- infiltrates
composed of lymphocytes, plasma cells and leukocytes
-vasculitis in acute phase is characterized by transmural
inflammation composed of neutrophils, eosinophils frequently
associated with fibrinoid necrosis of the inner half of the vessel wall
-lumen becomes thrombosed- results in acute tissue ischemia and
infarction
- in later stage- nodular fibroblast proliferation and irregular
aneurysmal dilatation of blood vessels
 Clinical course:
virtually all organs may be affected with exception of the lungs,
most commonly affected- are kidney, heart, liver, GIT
- variety of clinical symptoms including malaise= vague feeling
of physical discomfort, fever, weakness, weight loss
-renal involvement- possible cause of death
- vascular lesions of the GIT- abdominal pains, diarrhea, melena
- peripheral neuropathy
2) WEGENER'S GRANULOMATOSIS
= is characterized by complex of three major symptoms 1) necrotizing
granulomas of the upper respiratory tract and 2) necrotizing or
granulomatous vasculitis of small arteries and veins most commonly
in the lungs and 3) necrotizing glomerulonephritis
pathogenesis: no etiological agent has been identified
-immune complexes are occasionally present in vessell walls and
glomeruli, most patients have antineutrophilic cytoplasmic
autoantibodies ANCA
clinical symptoms: the course of untreated disease - is progressive
diagnosis: - biopsy of upper respiratory tract lesions
appropriate therapy: prednisone+ antibiotics
3 ) THROMBANGIITIS OBLITERANS ( BUERGER'S DISEASE)
=is a chronic relapsing inflammatory vascular disease characterized
by acute and chronic vasculitis of medium-sized and small arteries
followed by thrombosis of affected vessels and severe vascular
insufficiency
-mostly affected- arteries of lower extremities- may lead to gangrene
pathogenesis: unknown, but closely related to the use of tobacco
products -tobacco smoking (clear mechanism is not established yet)
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leads to endothelial damage- either direct toxicity or it initiates
immune reaction
morphology:
-arterial walls are infiltrated by mixed inflammatory cells, mostly
lymphocytes, the lumen is closed by thrombosis
-thrombus typically contains small microabscesses- inflammatory
reaction may extend to acompanying veins and nerves (organization of
thrombi)
clinical symptoms: claudications, color and temperature changes in
lower extremities
-chronic ulcerations of the toes, feet, fingers- gangrene, severe pain
even at rest
-stop of cigarette smoking-relief from further attacks
4 ) RAYNAUD'S DISEASE
=paroxysmal pallor or cyanosis of acral parts (fingers, tip of nose,
ears) caused by intense spasm of small arteries and arterioles
-idiopathic disease in young women
-in contrast, Raynaud syndrome refers to arterial insufficiency of acral
parts caused by some other disorders, such as atherosclerosis,
Buerger disease, vascular disease in lupus erythematodes
in later stage- trophic changes, ulcerations in the skin, areas of
gangrene in finger tips
5) LEUKOCLASTIC ANGIITIS
-disease involves small vessels than PAN, lesions are
characterized by fibrinoid necrosis and rich lekocytic infiltration
within the affected blood vessel wall
-pathogenesis: immune complexes in previously sensitized
person, intiated by drugs, microorganisms, heterologous protein, etc
 ANEURYSMS
= abnormal focal dilatation of arteries or veins
-develop wherever there is marked weakening of the wall of the vessel
most common causes of aortic aneurysms
-atherosclerosis, cystic medionecrosis
other causes
-inflammatory-syphilis
-congenital (intracranial arteries)accidents
may lead to cerebrovascular
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-traumatic
-mycotic- due to local inflammation
1) atheroclerotic aneurysms- is by far the most common, mostly
affected- abdominal aorta
-AS aneurysms take form of saccular or cyllindroid swelling
-mural thrombus is frequently found within the aneurysmal sac
clinically:
-parts of thrombus from the aneurysm may embolize
-occlusion of renal, mesenteric or other arteries may result from the
pressure in the aneurysmal sac
-rupture- rare in smaller, very often in larger than 6 and more cm in
diameter
dissecting aneurysm
= special type of aneurysm, characterized by the intima defects that
allows the blood to penetrate into the aortic wall with propagation of
hemorhage along the vessel
clinically:
- severe chest pain, abdominal pain due to compresion of mesenteric
arteries, and sudden decrease of blood pressure
treatment:
- immediate administration of antihypertensive drugs
-replacement of the affected part of the aorta by the graft
morphology:
-longitudinal tears in the intima of the aorta (sharp, irregular edges)
-blood enters through the intimal defect into the media- hematoma
-typically devides the outer and middle thirds of the aorta
-the hemorhage may dissect in proximal direction to the heart or to
the periphery
-in about 20%- focal areas of degenerative changes in the media
known as cystic medionecrosis Erdheim (may be a part of Marfan
syndrome)
 VENOUS DISEASES
two most important diseases- varicose veins and phlebothrombosis
1) VARICOSE VEINS - abnormally dilated tortuous veins
-varicose change is caused by higher pressure in the venous lumen
-most commonly affected- superficial veins of the leg
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causes:
-degenerative changes in vessel walls, muscle atrophy,
intraluminal pressure
-higher
-familial tendency
morphology:
-affected veins are dilated, tortuous and elongated, focal thickening of
the blood vessel wall
-common complication- phlebothrombosis
special types of venous varicosities:
1) hemorrhoids- result from varicose dilatation of the
hemorhoidal plexus of the vein at the anorectal junction- bleeding to
GI- melena
2) varicose veins in the esophagus- in patients with portal
hypertension- due to liver cirhosis- rupture may cause death
clinically:
-lower extremities varicose veins- usually asymptomatic, rarely pain,
but often followed by thrombosis of the venous plexuses
 Thromboembolic disease:
-thrombi most common- in deep veins of the lower extremitiessource of pulmonary embolism
TUMORS OF BLOOD AND LYMPHATIC VESSELS

benign-benign vascular tumors
frequently are seen in skin
are
very
common-most
1) capillary hemangioma
-most common sites - skin,
membranes of oral cavity and lips,
subcutaneous
tissue,
mucous
less common sites- spleen, liver, salivary glands, etc.
-grossly: bright red or bluish lesions, may level with the surface or
may be elevated
-usually present at birth, may regress spontaneously
-morphology:- composed of capillary-like
endothelial cells and filled by blood or lymph,
channels
lined
by
-these channels are separated one from another by a scant connective
tissue stroma
-thrombosis or fibrous organisation in the lumina- common
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2) cavernous hemangioma
-occurence - skin, subcutaneous tissue, internal organs, such as
spleen, liver, pancreas
3) multiple vascular tumors in cerebellum, brain stem and internal
organs- associate in clinical syndrome called von HIPPEL-LINDAU
DISEASE (VHL gene mutated)
borderline malignancy 1) epithelioid hemangioendothelioma
-is an angiocentric vascular tumor with metastatic potential,
composed of epithelioid endothelial cells arranged in short cords and
nests in myxohyaline stroma
Sites of involvement: the tumor develops in deep soft tissue of
extremities, less commonly in bone, liver and lungs
Clinical features: the tumor develops painful nodule-behaviour is
intermediate with an uncertain clinical course-it is locally aggressive,
recurrence rate is 10-15%, metastatic rate about 25%
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malignant
1) Angiosarcoma- is a rare malignant tumor the cells of which
recapitulate the features of endothelium
- cutaneous tumors in old patients, affect the skin of head and neck
region, less commonly soft tissues are affected
clinically- are highly aggressive tumours- local recurrences develop in
30%, one half of patients are expected to die of tumour within one
year after diagnosis with metastases in the lungs, bone, lymph nodes,
soft tissues, etc.
2) KAPOSI SARCOMA
KS is a locally aggressive endothelial tumour that typically presents
with cutaneous lesions in the form of plaques, nodules, pathes but
may also involve mucosal sites, lymph nodes and visceral organs,
earlier- it was a rare tumor, now more common- in immunosupressed
patients and particularly important- in AIDS