Fung > Vascular Path Flashcards
what is ECM made of?
elastin
collagen
glycosaminoglycans
what are the 3 components of the vasculature?
endothelial cells
smooth muscle cells
ECM
what are the 5 fxns of the endothelial cells?
maintain non-thrombogenic blood-tissue interface modulate vascular resistance metabolize hormones regulate inflammation regulate cell growth
which component of the vasculature proliferates when stimulated?
smooth muscle cells
what do smooth muscle cells synthesize?
collagen
elastin
proteoglycans
what do smooth muscle cells elaborate?
growth factors
cytokines
what are the 3 layers of the vasculature?
intima
media
adventitia
what are the 2 specialized layers in muscular arteries?
internal elastic lamina
external elastic lamina
T/F: arteries have valves
false
veins do
where do berry aneurysms occur?
cerebral vessels
T/F: the majority of berry aneurysms occur sporadically
TRUE
what are 4 possible genetic causes of berry aneurysms?
AD polycystic kidney disease
Ehlers-Danlos syndrome
NF1
Marfan
what are 2 risk factors for developing berry aneurysms?
cigarette smoking & HTN
are berry aneurysms present at birth?
no
they develop over time
(they’re still inexplicably called congenital though)
what are atriovenous fistulas?
small direct connections btwn arteries & veins that bypass capillaries
can inflammatory necrosis of adjacent vessels cause AV fistulas?
yes
can developmental defects cause AV fistulas?
yes
can penetrating injuries that pierce arteries & veins cause AV fistulas?
yes
can rupture of an arterial aneurysm into an adjacent vein cause an AV fistula?
yes
can AV fistulas be iatrogenic?
yes
what is fibromuscular dysplasia?
focal irregular thickening of the walls of medium & large muscular arteries
what does fibromuscular dysplasia result in?
luminal stenosis
at what age does fibromuscular dysplasia occur?
any
in what group is fibromuscular dysplasia most common?
young women
what is an aneurysm?
localized abnormal dilation of a blood vessel or the heart
T/F: aneurysms are always acquired
false
they can also be congenital
what are the 2 types of aneurysms?
true
false
what are the 2 forms of true aneurysms?
saccular
fusiform
what is a true aneurysm?
involves an intact attenuated arterial wall or thinned ventricular wall
what are 4 examples of true aneurysms?
atherosclerotic
syphilitic
congenital
ventricular following transmural infarction
what is another name for a false aneurysm?
pseudo-aneurysm
what is a false aneurysm?
a defect in the vascular wall leading to an extravascular hematoma that freely communicates w/ the intravascular space
what is an example of a false aneurysm?
ventricular rupture w/ pericardial adhesion
what is a saccular true aneurysm?
spherical outpouchings involving only a portion of the vessel
how big are saccular true aneurysms?
5-20 cm diameter
what is a fusiform true aneurysm?
diffuse circumferential dilation of a long vascular segment
how big are fusiform true aneurysms?
up to 20 cm diameter
where can you find fusiform true aneurysms?
extensive portions of the aortic arch
abdominal aorta
iliac arteries
what can cause an aneurysm to form (generally)?
any process that causes weakening of the vessel wall
what are the 2 main general causes of aneurysms?
sporadic
OR
connective tissue disease
what is Marfan syndrome?
a defect of fibrillin
what is Ehlers-Danlos?
a defect in the synthesis or structure of fibrillar collagen
what is Vitamin C deficiency?
altered collagen cross-linking
what is Loeys-Dietz syndrome?
a defect in elastin, collagen I, & collagen III
how can inflammation cause an aneurysm?
alters the balance of synthesis & destruction of collagen
increased matrix metalloproteases (MMP) degrade the ECM
what causes a thickening of the intima and cystic medial degeneration?
loss of smooth muscle cells
OR
proliferation of non-collagenous/non-elastic ECM
what is the consequence of a thickened intima?
decreased diffusion of oxygen and nutrients to the media
what are the 2 most important predisposing factors for aneurysms?
HTN & atherosclerosis
what does atherosclerosis cause particularly?
AAA
abdominal aortic aneurysm
what does HTN cause particularly?
ascending aortic aneurysm
can infection cause an aneurysm?
yes d/t embolization, direct extension, or organism circulation
can aneurysms be congenital?
yes (developmental berry aneurysms)
what is the most common location of atherosclerotic aneurysms?
abdominal aorta
how do AAAs form?
cystic medial degeneration results in thinning & weakness
what is a major influence for developing AAA?
increased MMP (matrix metalloproteases)
T/F: AAAs are always saccular
false
they can be saccular or fusiform
what is an inflammatory type AAA?
dense periaortic fibrosis containing abundant lymphocytes, plasma cells, & macrophages
what is a mycotic type AAA?
d/t circulating microorganisms that destroys the media
what are the 4 clinical consequences of a AAA?
rupture w/ potential fatal hemorrhage
obstruction of branch vessel
embolism from atheroma or mural thrombus
impingement on adjacent structures
what is a thoracic aneurysm most commonly assoc w?
HTN
what are the sx of a thoracic aneurysm?
bone pain
cough (pressure on recurrent laryngeal nerve)
aortic valve dilation w/ insufficiency
what can a TAA encroach on?
mediastinal structures
lungs & airways
esophagus
what is a dissection?
blood splays apart the laminar planes of the media to form a blood filled channel w/i the vessel wall
T/F: dissection is always assoc w/ vessel dilation
FALSE (may or may not be assoc w/ it)
who gets dissections?
men 40-60 yo w/ HTN
younger pts w/ systemic & localized abnormalities of the aorta
why don’t you usually see dissection w/ atherosclerosis?
bc of medial fibrosis
what is the major risk factor for dissection?
HTN
what is the pathophysiology of dissection?
medial hypertrophy of the vasa vasorum w/ degenerative changes of the media
i.e. injury d/t diminished flow
what 3 tissue disorders can lead to dissection?
Marfan
Ehlers-danlos
Vitamin C deficiency
what is the most frequent histologically detectable lesion w/ dissection?
cystic medial degeneration
what is a Type A dissection?
a proximal lesion involving either the ascending aorta only or in conjunction w/ the descending aorta
what DeBakey types are assoc w/ Type A dissection?
I & II
what is a Type B dissection?
distal lesion beginning distal to the subclavian artery & NOT involving the ascending aorta
what DeBakey types are assoc w/ Type B dissection?
type III
what is DeBakey type I?
involves ascending AND descending aorta
type A
what is DeBakey type II?
involves ascending aorta only
type A
what is DeBakey type III?
involves the descending aorta only (distal to subclavian)
type B
what is vasculitis?
general term for vessel wall inflammation
what do the clinical features of vasculitis depend on?
which vascular bed is affected
T/F: vasculitis affects only small vessels
false
affects any vessels of any organ or any size
what are the 2 most common pathogenic mechanisms of vasculitis?
immune-mediated inflammation
direct invasion of vascular walls by infectious pathogens
T/F: infectious pathogens can initiate both infectious AND non-infectious vasculitis
true
idk why
what vessels does large vessel vasculitis affect?
aorta
large branches to extremities/head/neck
what are 2 types of large vessel vasculitis?
Giant cell (temporal) arteritis Takayasu arteritis
what vessels does medium vessel vasculitis affect?
main visceral arteries & their branches
what are 2 types of medium vessel vasculitis?
Polyarteritis nodosa
Kawasaki disease
what vessels does small vessel vasculitis affect?
arterioles
venules
capillaries
small arteries
what vessels does variable vessel vasculitis affect?
no predominant type
what are 2 types of variable vessel vasculitis?
Behcet’s disease
Cogan’s syndrome
what is the mechanism for large vessel vasculitis?
granulomatous disease
what is the mechanism for medium vessel vasculitis?
immune-complex mediated
OR
anti-endothelial cell ab
what are the mechanisms for small vessel vasculitis?
immune complex mediated
OR
paucity of immune complexes (often w/ ANCA)
what are the 4 types of immune-complex mediated small vessel vasculitis?
SLE
IgA
Cryoglobin
OTHER
what are the 3 types of “paucity of immune complexes” small vessel vasculitis?
vasculitis w/o asthma or granulomas
granulomas, no asthma
eosinophils, asthma, & granulomas
what are the 8 types of small vessel vasculitis?
SLE vasculitis IgA vasculitis cryoglobinemic vasculitis Wegener granulomatosis Churg-Strauss syndrome Microscopic polyantitis anti-GBM disease hypocomplementemic urticarial vasculitis
what are 3 other types of vasculitis?
single organ
vasculitis assoc w/ systemic disease
vasculitis assoc w/ probable etiology
does non-infectious vasculitis predispose you to vasculitis?
yes
Kawasaki disease
what 3 things happen in non-infectious vasculitis?
immune complex deposition
anti-neutrophil cytoplasmic ab
anti-endothelial cell ab
what are 3 examples of immune-complex associated vasculitis?
SLE
polyarteritis nodosa
drug hypersensitivity vasculitis
what 3 things are detected in immune complex assoc vasculitis?
ab
complement
ag-ab complexes
what does ANCA stand for?
antineutrophil cytoplasmic antibodies
what is ANCA?
circulating abs react w/ neutrophil cytoplasmic ag
what are the abs directed against in ANCA?
they're heterogeneous directed against: neutrophil primary granules monocyte lysosomes endothelial cells
what are the 2 types of antineutrophil cytoplasmic antibodies?
anti-myeloperoxidase (MPO-ANCA)
&
anti-proteinase-3 (PR3-ANCA)
what is MPO?
a lysosomal granule constituent
what conditions is MPO-ANCA seen in?
therapeutic agents (propylthiouracil)
microscopic polyangitis
Churg-Strauss syndrome
what is p-ANCA?
perinuclear
what is c-ANCA?
cytoplasmic
what is PR3?
a neutrophil azurophilic granule constituent
what does PR3 share homology with?
microbial peptides
when do you see PR3-ANCA?
in Wegener granulomatosis
what are the 2 mechanisms for vasculitis with ANCA?
drugs or cross-reactive microbe (ag) induce ANCA formation
OR
neutrophils release MPO/PR3 & cause ANCA formation in a susceptible host
what happens when the host releases cytokines?
causes expression of MPO/PR3 on neutrophils or other cell types
what happens when ANCA reacts?
directly induces endothelial injury OR activates other neutrophils
what do ANCA-activated neutrophils do?
degranulate, release ROS > further injure endothelial cells
what is the process for vasculitis with ANCA (4 steps)?
- induced ANCA formation via drugs (or ag) OR neutrophil release of MPO/PR3
- cytokine release > MPO/PR3 expression on neutrophils
- ANCA react > endothelial injury or activation of neutrophils
- ANCA-activated neutrophils degranulate > ROS > injure endothelial cells
what is the most common vasculitis among elderly pts over 50 yo?
giant cell arteritis
what is giant cell arteritis?
chronic granulomatous inflammation of large to small-sized arteries
what does giant cell arteritis affect?
arteries of the head: temporal artery, vertebral artery, ophthalmic artery, aorta
is giant cell arteritis a medical emergency?
YES
ophthalmic artery involvement can cause blindness
what is the mechanism of giant cell arteritis?
T cell lymphocytic immune response to an unknown ag
what 2 things may also contribute to giant cell arteritis?
TNF & anti-endothelial cell humoral immune responses
what is the histology of giant cell arteritis?
discontinuous involvement of the vessel
intimal thickening
medial granulomatous inflammation with giant cells
elastic lamina fragmentation
what is the clinical consequence of having discontinuous involvement of the vessel?
multiple biopsies
what is takayasu arteritis?
granulomatous arteritis of medium or large arteries
what characterizes takayasu arteritis?
ocular disturbances
marked weakening of pulses in upper extremities (pulseless disease)
what happens to the aorta in takayasu arteritis?
fibrous thickening of the aortic arch & great vessels
what does takayasu arteritis share features with?
giant cell arteritis
BUT W/ TAKAYASU THE PTS ARE LESS THAN 50 YO!!!!!
what is polyarteritis nodosa?
systemic vasculitis of small or medium-sized muscular arteries
what arteries does polyarteritis nodosa affect?
renal vessels visceral vessels (heart, liver, GI tract)
what arteries does polyarteritis nodosa NOT affect?
pulmonary circulation
arterioles, capillaries, venules
what disease is polyarteritis nodosa assoc w/?
chronic hep B
what complexes in vessels w/ hep B & polyarteritis nodosa?
HBsAg-HBsAb
immune complex mediated
what is the cause of polyarteritis nodosa?
unknown in most cases
what is polyartertitis nodosa?
segmental transmural necrotizing inflammation (neutrophils, eosinophils, & lymphocytes)
how does polyarteritis nodosa affect the vessel?
circumferentially
what region does polyarteritis nodosa prefer?
vessel branch points
what are some complications of polyarteritis nodosa?
weakened vessels
aneurysms
what replaces the acute inflammatory infiltrate in polyarteritis nodosa?
fibrous thickening of the vessel wall
what are the lesions like in polyarteritis nodosa?
coexist in different stages > recurrent & ongoing insults
what is kawasaki disease?
acute febrile self-limited illness of infancy/childhood
what vessels does kawasaki affect?
large to medium to small vessels
what kind of syndrome is kawasaki?
mucocutaneous lymph node syndrome
what are the sx of kawasaki?
conjunctival & oral erythema & erosion edema of hands & feet erythema of palms & soles desquamative rash cervical lymph node enlargement
why is kawasaki clinically significant?
coronary artery involvement
what can cause MI in kawasaki?
aneurysms that rupture & thrombose
why is there vasculitis in kawasaki?
from delayed hypersensitivity rxn of T cells to uncharacterized ag (possibly infectious agents)
what is the auto-ab process in kawasaki?
cytokines produced
B cell activation
auto-ab produced against endothelial & smooth muscle cells
what part of the vessel do kawasaki inflammatory lesions affect?
entire thickness of the vessel wall
does kawasaki have more or less fibrinoid necrosis than polyarteritis nodosa?
less
what happens w/ healed lesions in kawasaki?
may have obstructive intimal thickening
what is microscopic polyangitis?
segmental fibrinoid necrotizing vasculitis
what vessels does microscopic polyangitis affect?
capillaries, arterioles, and venules
what disease does microscopic polyangitis resemble?
polyarteritis nodosa
but microscopic polyangitis affects SMALLER VESSELS
T/F: all lesions in microscopic polyangitis are at the same stage at the same time
TRUE
which ANCA is microscopic polyangitis assoc w/?
MPO-ANCA
what is another name for microscopic polyangitis?
leukocytoclastic vasculitis
what does microscopic polyangitis affect?
skin > palpable cutaneous purpura mucous membranes lungs > hemoptysis brain heart GI tract > bowel pain & bleeding kidney > hematuria, proteinuria muscle > pain, weakness
what can microscopic polyangitis occur w/?
henoch-schonlein purpura
essential mixed cryoglobinemia
vasculitis assoc w/ CT disorders
what is Churg-Strauss syndrome?
small vessel necrotizing vasculitis
what is churg-strauss assoc w/?
asthma allergic rhinitis lung infiltrates peripheral hypereosinophilia extravascular necrotizing granulomas
what is churg-strauss also called?
allergic granulomatosis
what does churg-strauss histologically resemble?
PAN or microscopic polyangitis
BUT churg-strauss has granulomas & eosinophils
what ANCA is present sometimes w/ Churg-Strauss?
MPO-ANCA
what are the clinical manifestations of churg-strauss?
palpable purpura
GI tract bleeding
focal & segmental glomerulosclerosis
what 3 things characterize the necrotizing vasculitis assoc w/ Wegener granulomatosis?
acute necrotizing granulomas in upper &/or lower respiratory tract
necrotizing granulomatous vasculitis affecting small-med sized vessels
focal necrotizing crescentic glomerulonephritis
what does Wegener granulomatosis resemble?
polyarteritis nodosa
BUT Wegener has respiratory involvement
what is Wegener granulomatosis?
a T-cell mediated hypersensitivity rxn to an inhaled infectious agent
what ab it present in 95% of wegener pts?
anti-PR3 c-ANCA
what is another name from thromboangiitis obliterans?
buerger disease
what is thromboangiitis obliterans?
segmental thrombosing acute & chronic inflammation of medium & small arteries
what does thromboangiitis obliterans lead to?
vascular insufficiency principally in the tibial & radial arteries (sometimes veins & nerves)
who gets thromboangiitis obliterans?
almost exclusively seen in heavy smokers before 35 yo
why do cigarettes cause vascular damage?
directly toxic to endothelial cells
OR
an immune response to cigarettes
what are the clinical features of thromboangiitis obliterans?
superficial nodular phlebitis
Raynaud-type cold sensitivity
instep claudication
severe pain at rest in extremities
what is infectious vasculitis?
direct invasion of infectious agents (bacteria or fungus)
how can infectious vasculitis spread hematogenously?
seeding during sepsis or embolization
what can infectious vasculitis lead to?
mycotic aneurysms
what is Raynaud phenomenon a result of?
exaggerated vasoconstriction of digital arteries & arterioles
what are the sx of Raynaud phenomenon?
paroxysmal pallor
cyanosis of digits of hands & feet
what is primary raynaud phenomenon?
exaggeration of central & local vasomotor responses to cold or emotional stress
what is secondary raynaud phenomenon?
vascular insufficiency of the extremities secondary to arterial disease caused by... SLE Scleroderma Buerger disease Atherosclerosis
what are varicose veins?
abnormally dilated tortuous veins
how are varicose veins produced?
prolonged increased intraluminal pressure & loss of vessel support
where can you get varicose veins?
superficial veins of upper & lower leg
esophageal varices
hemorrhoids
how can varicose veins cause esophageal varices?
d/t portal vein HTN
what can esophageal varices do?
rupture > fatal hemorrhage
what are thrombophlebitis & phlebothrombosis?
interchangeable names for venous thrombosis & inflammation
where do you get thrombophlebitis?
deep leg veins periprostatic venous plexus pelvic venous plexus large skull veins dural sinuses
where does MOST thrombophlebitis occur?
deep leg veins
90%
why do pts get thrombophlebitis in their deep leg veins?
prolonged immobilization predisposes you
what can deep leg vein thrombophlebitis lead to?
PE
what predisposes you to thrombophlebitis?
systemic hypercoagulability
when can you get migratory thrombophlebitis?
paraneoplastic syndromes
what causes SVC syndrome?
neoplasms that compress or invade the SVC (bronchogenic ca or mediastinal lymphoma)
what are the complications of SVC syndrome?
dilation of the veins of the head
neck & arm cyanosis
what causes IVC syndrome?
neoplasms that invade or compress the IVC (HCC, RCC)
OR
thrombus from hepatic, renal, or LE veins
what is lymphangitis?
acute inflammation d/t bacteria
which bacteria cause lymphangitis?
group A beta-hemolytic streptococci
what causes primary lymphedema?
congenital defects
OR
familial agenesis or hypoplasia
what causes secondary lymphedema?
tumors lymph node dissection post-irradiation fibrosis filariasis post-inflammatory thrombosis & scarring
T/F: primary tumors of large vessels are common
FALSE
they’re rare!
what is the neoplasm you get in the vessels?
soft tissue sarcoma
from what can vessel neoplasms be derived?
endothelium
OR
cells that support blood vessels
what do benign vessel tumors produce?
well-formed vascular channels lined by normal endothelium
what do malignant vessel tumors look like?
NO well-formed vascular channels cytologic atypia (duh)
what are hemangiomas/pyogenic granulomas?
common tumors w/ increased #s of BVs filled w/ blood
what is a capillary hemangioma?
closely packed thin walled capillaries
what is a cavernous hemangioma?
large dilated vascular channels
what is a pyogenic granuloma a form of?
capillary hemangioma
what is lymphangioma?
benign lymphatic analogues of BV hemangioma
what is simple capillary lymphangioma?
small lymphatic channels
what is cavernous lymphangioma?
massively dilated lymphatic channels w/ lymphocytes in the CT
what is another name for cavernous lymphangioma?
cystic hygroma
what is the cause of Kaposi sarcoma?
HHV-8
who gets chronic Kaposi sarcoma?
older Eastern European/Mediterranean men
how does Kaposi sarcoma present?
skin lesions
who gets lymphadenopathic KS?
people in areas of Africa
how does lymphadenopathic KS present?
lymphadenopathy (duh)
what is transplant associated KS?
occurs in organ transplant & immunosuppressed setting
how does transplant associated KS present?
nodal, mucosal, visceral involvement
v aggressive
who gets AIDS-assoc KS?
pts w/ AIDS
what is the most prevalent malignancy in AIDS pts?
AIDS assoc KS
how does AIDS assoc KS present?
lymph node & visceral involvement
what is angiosarcoma?
malignant endothelial neoplasms that range from well-differentiated to anaplastic
what settings give you hepatic angiosarcoma?
arsenic, thorotrast, polyvinyl chloride, lymphedema, post-radiation
what is a glomus tumor?
benign tumor arising from modified smooth muscle cells of the glomus body
what is the glomus body involved w/?
thermoregulation
what is vascular ectasia?
common lesions but NOT true neoplasms
local dilation of pre-existing vessels
what are the types of vascular ectasia?
nevus flammeus
spider telangiectasia
hereditary hemorrhagic telangiectasia
what are some examples of nevus flammeus?
birthmarks
port-wine stain
Sturge-Weber syndrome
what is another name for hereditary hemorrhagic telangiectasia?
Osler-Weber-Rendu disease
what is bacillary angiomatosis?
vascular proliferation arising from an opportunistic infection in immunocompromised pts
what bacteria causes bacillary angiomatosis?
Bartonella
what is hemangioendothelioma?
intermediate neoplasm eg epithelioid hemangioendothelioma
what is hemangiopericytoma?
rare tumors derived from pericytes
i am so sorry this is a fucking million cards
at least it’s over! :)
