Fung: Vascular Pathology Flashcards
Occur in cerebral vessels
Majority occur sporadically
Some are genetic
AD polycystic kidney disease, Ehler-Danlos syndrome, NF1, Marfan syndrome
developmental (berry) aneurysms
What diseases are associated with berry aneurysms?
polycystic kidney disease
Ehler-Danlos syndrome
Marfan syndrome
What are two major risk factors for berry aneurysms?
cigarette smoking
hypertension
Are berry aneurysms really congenital?
no, they are referred to as congenital but they actually develop over time
Small direct connections between arteries and veins that bypass capillaries
atriovenous fistulas
Why do atriovenous fistulas occur?
developmental defects
rupture of arterial aneurysm into an adjacent vein
penetrating injuries that pierce arteries and veins
inflammatory necrosis of adjacent vessels
iatrogenic (consequence of medical treatment)
Focal irregular thickening of the walls of medium and large muscular arteries
Results in luminal stenosis
fibromuscular dysplasia
**occurs most frequently in young women
Localized abnormal dilation of a blood vessel or the heart
Congenital or acquired
Aneurysms
Involves an intact attenuated arterial wall or thinned ventricular wall
True aneurysm
**ex: Atherosclerotic
Syphilitic
Congenital
Ventricular following transmural infarction
Defect in the vascular wall leading to an extravascular hematoma that freely communicates with the intravascular space
False aneurysm, or pseudo-aneurysm
**Ex: ventricular rupture with pericardial adhesion
Differentiate between a saccular and fusiform true aneurysm
a saccular aneurysm is going to involve spherical outpouchings of only a portion of the vessel (usu 5-20cm in diameter)
a fusiform aneurysm is a diffuse, circumferential dilation along a vascular segment (can be up to 20cm in diameter); these aneurysms often involve extensive portions of the aortic arch, abdominal aorta, and iliac arteries
T/F: Any process that causes weakening of the vessel wall can cause aneurysm formation
true!
**aneurysms can be sporadic or due to connective tissue disease
Defect in fibrillin which can lead to aneurysm formation
Marfan syndrome
Defect in the synthesis or structure of fibrillar collagen; can lead to aneurysm formation
Ehlers-Danlos syndrome
Altered collagen cross-linking; can lead to aneurysm formation
Vit C deficiency
Defect in elastin, collagen I, and III; can lead to aneurysm formation
Loeys-Dietz syndrome
How do aneurysms form?
inflammation alters the balance of synthesis and destruction of collagen
increased matrix metalloproteases degrade the ECM
or
loss of smooth muscle cells or proliferation of non-collagenous/non-elastic extracellular matrix
**thickening of the intima decreases diffusion of oxygen and nutrients to the media causing the media to degrade
Two of the most important predisposing factors for aneurysm formation?
atherosclerosis
hypertension
Other causes of aneurysm formation?
congenital defects
infections due to embolization, direct extension or circulation of organisms
Where are atherosclerotic aneurysms most likely to occur?
abdominal aorta
**seen in male smokers >60 yo with HTN
What is one major influence in the formation of an abdominal aneurysm?
increased matrix metalloproteinase
**also, athersclerosis increases the diffusion barrier to the media, resulting in atrophy and weakening of the vessel wall
Name these two flavors of aneurysms:
- dense periaortic fibrosis containing abundant lymphocytes, plasma cells and macrophages
- due to circulating microorganisms that destroys the media
- inflammatory type
2. mycotic type
What are some clinical consequences if you have an abdominal aortic aneurysm?
rupture w potentially fatal hemorrhage (hypotension, pulsatile abdominal mass, flank pain)
impinging on adjacent structures
obstruction of some branch vessel
embolism from atheroma or a thrombus
This type of aneurysm is most commonly associated with hypertension; classically seen in tertiary syphilis
thoracic aneurysm
**tree bark appearance of the aorta
List 4 signs and symptoms of a thoracic aneurysm
- cough due to pressure on recurrent laryngeal nerve
- bone pain
- aortic valve dilation with insufficiency
- encroachment on lungs/airways, esophagus, and mediastinal structures
What is this?
Blood splays apart the laminar planes of the media to form a blood filled channel within the vessel wall
May or may not be associated with vessel dilation
dissection
Who gets dissections?
men 40-60 yo with hypertension
younger pts with abnormalities of the aorta
iatrogenic (complication of medical procedure)
Are dissections usu seen in cases of athersclerosis?
no, because in atherosclerosis there is fibrosis of the media, which would make it less likely for blood to splay apart the media
What is the major risk factor for dissection?
hypertension!!
**hyaline arteriosclerosis of the vasa vasorum –>cystic medial degeneration
In which inherited/acquired tissue disorders is dissection more common?
Marfan syndrome
Ehler-danlos syndrome
Vit C deficiency
**cystic medial necrosis due to connective tissue dysfunction
What is the most frequent histologically detectable lesion in patients with dissection?
cystic medial degeneration
Type A dissections are proximal lesions, and involve which parts of the aorta?
the ascending aorta only (DeBakey II)
or
both the ascending and descending aorta (Debakey I)
Type B dissections are distal lesions and involve which part of the aorta?
They begin distal to the subclavian artery and don’t involve the ascending aorta (DeBakey III)
General term for vessel wall inflammation
Clinical features depends on the vascular bed affected and can affect vessels of any organ or any size
vasculitis
What are the two most common pathogenic mechanisms for vasculitis?
- immune-mediated inflammation
2. direct invasion of the vascular walls by infectious agents
Which vessels are affected in large vessel vasculitis?
aorta
large branches to extremities, head, and neck
Which vessels are affected in medium vessel vasculitis?
main muscular/visceral arteries and their branches
Which vessels are affected in small vessel vasculitis?
arterioles, capillaries, venules
List two types of large vessel vasculitis
- giant cell arteritis
2. Takayasu arteritis
List three types of medium vessel vasculitis
- Polyarteritis nodosa (immune complex mediated)
- Kawasaki disease (anti-endothelial cell antibodies)
- Buerger disease
List 4 types of small vessel vasculitis
- Microscopic polyangitis (vasculitis w/ no asthma or granulomas)
- Wegener granulomatosis (granulomas, but no asthma)
- Chrug-Strauss syndrome (eosinophilia, asthma, and granulomas)
- Henoch-Schonlein Purpura
3 causes of non-infectious vasculitis
immune-complex deposition
anti-neutrophil cytoplasmic antibodies
anti-endothelial cell antibodies
This antineutrophil cytoplasmic antibody is perinuclear; it is seen in therapeutic agents (propylthiouracil), microscopic polyangiitis and Churg-Strauss syndrome
P-ANCA (Anti-myeloperoxidase antibody)
**Ab against a lysosomal granule constituent
This antineutrophil cytoplasmic antibody is cytoplasmic; it shares homology with microbial peptides, and is seen in Wegener granulomatosis
c-ANCA (anti-proteinase-3 antibody)
**PT2 is a neutrophil granule constituent
How do antineutrophilic cytoplasmic antibodies cause vasculitis?
drugs or cross-reactive microbes induce formation of the antibodies
or
neutrophils produce MPO/PR3 and cause antibody formation in a susceptible host
then
the host releases cytokines that causes expression of MPO and PR3 on neutrophils and other cells
the antibodies react with these cells and directly induce endothelial cell injury or activate other neutrophils
ANCA activated neutrophils degranulate and release ROS which further damage endothelial cells
Most common vasculitis among elderly individuals (50 years and older); usually affects females
Chronic, granulomatous inflammation of large arteries, usually involving branches of the carotid artery
temporal giant cell arteritis
Which arteries are primarily affected by giant cell arteritis? So how does it present?
arteries of the head (temporal, vertebral, ophthalmic and aorta)
temporal: headache
ophthalmic: visual disturbances
jaw claudication
flu-like symptoms w joint/muscle pain
Why is giant cell arteritis a medical emergency?!
if it affects the ophthalmic artery, it can lead to blindness
What might you see histologically in giant cell arteritis?
granulomatous, inflamed vessel wall with giant cells and intimal fibrosis/thickening
discontinuous involvement of the vessel **need to biopsy a long segment
elastic lamina fragmentation
Granulomatous arteritis of medium or larger arteries characterized by
Visual disturbances
Marked weakening of the pulses in the upper extremities (pulseless disease)
Fibrous thickening of the AORTIC ARCH
Shares many attributes with GCA (clinical features and histology)
Patients are less that 50 years old
Takayasu arteritis
What are two clinical features of Takayasu arteritis?
visual disturbances
weakening of the pulses in the upper extremities (pulseless disease)
**very similar to giant cell arteritis
Necrotizing systemic vasculitis of small or medium-sized muscular arteries
Renal vessels
Visceral vessels (heart, liver, GI tract)
Spares pulmonary circulation
Does not involve arterioles, capillaries or venules
Associated with chronic hepatitis B
HBsAg-HBsAb complexes in vessels (immune complex mediated)
Cause is unknown in the majority of cases
Polyarteritis nodosa
What disease is associated with polyarteritis nodosa (PAN)?
Chronic hepatitis B
**HBsAg in serum
Which vessels are affected in polyarteritis nodosa?
renal vessels (hypertension)
visceral vessels (abdominal pain)
NO pulmonary vessels
NO arterioles, capillaries, or venules
Describe the inflammatory process in polyarteritis nodosa
lesions of varying stages are present
early lesions have transmural inflammation with fibrinoid necrosis
eventually these early lesions will heal with fibrosis, and produce a string-of-pearls appearance on imaging
Acute febrile, self-limited illness of Asian children affecting large to medium sized and small vessels
Mucocutaneous lymph node syndrome
Conjuntival and oral erythema and erosion
Edema of hands and feet
Erythema of palms and soles
Desquamative rash
Cervical lymph node enlargement
Kawasaki disease
**think of an Asian kid riding a Kawasaki bike with rashes on their hands and feet and the risk of an MI (involves coronary artery)
Why is Kawasaki disease clinically significant?!
involves coronary artery
**aneurysms can rupture and thrombose resulting in MI in these kids :(
What is going on pathologically in Kawasaki disease?
vasculitis is caused by a delayed hypersensitivity T cell reaction to an unknown antigen; produces cytokines which activate B cells leading to antibody formation; auto-antibodies are formed to endothelial cells and smooth muscle cells
Describe the lesions in Kawasaki disease
lesions show marked inflammation which affects the full thickness of the vessel wall; less fibrinoid necrosis than PAN; healed lesions may have obstructive intimal thickening
Segmental fibrinoid necrotizing vasculitis that affects capillaries, arterioles and venules (like PAN but affects smaller vessels)
Effects multiple organs, esp kidney and lungs
Hypersensitivity vasculitis (leukocytoclastic vasculitis)
All lesions are in the same stage at the same time
serum pANCA (anti-MPO) levels correlated with disease activity
microscopic polyangitis
Which vessels are affected in microscopic polyangitis?
capillaries, arterioles, venules of multiple organs
**esp lung and kidney
Which organs are affected by microscopic polyangiitis?
nearly all organs!
Skin (palpable cutaneous purpura) Mucous membranes Lungs (hemoptysis) Brain Heart Gastrointestinal tract (bowel pain, bleeding) Kidney (hematuria, proteinuria) Muscle (muscle pain, weakness)
Small vessel necrotizing vasculitis associated with Asthma Allergic rhinitis Lung infiltrates Peripheral hypereosinophilia Extravascular necrotizing granulomas Also called allergic granulomatosis
Churg-Strauss syndrome
What does Churg-Strauss syndrome look like histologically?
granulomas and eosinophils
**sometime MPO-ANCAs are present
Clinical manifestations of Henoch Schlonlein Purpura, a vasculitis due to IgA immune complex deposition
palpable purpura
GI tract bleeding
focal and segmental glomerulosclerosis
Necrotizing vasculitis characterized by
Acute necrotizing granulomas of the upper respiratory tract and/or lower respiratory tract
Necrotizing granulomatous vasculitis affecting small to medium sized vessels
Focal necrotizing, crescentic glomerulonephritis
Clinically resembles polyarteritis nodosa except has respiratory involvement
Wegener granulomatosis
What antibody is present in 95% of cases or Wegener’s granulomatosis?
Anti-PR3 (c-ANCA) is present in 95%
Segmental thrombosing acute and chronic inflammation of medium and small sized arteries
Leads to vascular insufficiency principally in the TIBIAL and RADIAL arteries
Almost exclusively seen in heavy smokers before 35
Cigarettes are directly toxic to endothelial cells or an immune response to cigarettes
Buerger disease or
thromboangiitis obliterans
Who gets Buerger disease (thromboangiitis obliterans)?
heavy smokers before 35
What are some clinical features of thromboangiitis obliterans?
superficial nodular phlebitis raynaud type cold sensitivity instep claudication severe pain at rest in extremities ulceration gangrene autoamputation of digits
Direct invasion of infectious agents Bacteria Fungus (Mucor, Aspergillus) Hematogenous seeding during sepsis or embolization May lead to mycotic aneurysms
infectious vasculitis
Results from exaggerated vasoconstriction of digital arteries and arterioles
Symptoms include paroxysmal pallor and cyanosis of digits of hands and feet
Raynaud phenomenon
Exaggeration of the central and local vasomotor responses to cold or emotional stress
Primary Raynaud Phenomenon
Vascular insufficiency of the extremities secondary to arterial disease caused by SLE Scleroderma Buerger disease Atherosclerosis
Secondary Raynaud Phenomenon
Abnormally dilated, tortuous veins produced by prolonged increased intraluminal pressure and loss of vessel support Superficial veins of upper and lower leg Esophageal varices Due to portal vein hypertension Can rupture and cause fatal hemorrhage Hemorrhoids
varicose veins
Another name for venous thrombosis and inflammation Deep leg veins (90%) Prolonged immobilization predisposes Pulmonary embolism Periprostatic venous plexus Pelvic venous plexus Large veins of the skull Dural sinuses
thrombophlebitis
phlebothrombosis
Where does venous thrombosis and inflammation most often occur?
in the deep leg veins
What are two conditions that may predispose you to thrombophlebitis (venous thrombosis)
systemic hypercoagulability
paraneoplastic syndromes with migratory thrombophlebitis
caused by neoplasms (bronchogenic CA, mediastinal lymphoma) that compress or invade the SVC
Dilation of veins of the head
Neck and arm cyanosis
superior vena cava syndrome
Neoplasms that compress or invade the IVC (HCC, RCC)
Thrombus from hepatic, renal or LE veins
IVC syndrome
Acute inflammation of the lymphatic vessels due to bacteria (group A βhemolytic streptococci)
lymphangitis
What can cause primary lymphedema?
congenital defects
familial agenesis or hypoplasia
What can cause secondary lymphedema?
Tumors Dissection of lymph nodes Post-irradiation fibrosis Filariasis Post-inflammatory thrombosis and scarring
Where can primary tumors of large vessels arise from?
endothelium of vessels
or
cells that support the blood vessels
How do benign vascular tumors differ from malignant vascular tumors?
benign vascular tumors form well formed vascular channels that are lined by normal endothelium; malignant tumors don’t produce the well formed vascular channels and show cytologic atypia
common tumor with closely packed thin walled capillaries
capillary hemangioma
common tumor with large dilated vascular channels
cavernous hemangioma
common tumor that is a form of capillary hemangioma
pyogenic granuloma
Benign lymphatic analogues of blood vessel hemangioma
lymphangioma
Compare a simple capillary lymphangioma to a cavernous lymphangioma
simple: small lymphatic channels
cavernous: massively dilated lymphatic channels with lymphocytes in the connective tissue
Human herpes virus 8 (HHV-8) is causative
Chronic forms occur in older men eastern Europe/ Mediterranean. Presents as skin lesions
Lympadenopathic forms occur in areas of Africa. Presents as lymphadenopathy
Transplant forms occur in the setting of organ transplantation and immunosuppression. Presents with nodal, mucosal and visceral involvement. Aggressive.
AIDS- associated forms occur in the setting of HIV/AIDS. Most prevalent malignancy in AIDS patients. Presents with lymph node and visceral involvement.
Kaposi sarcoma
Malignant endothelial neoplasms that range from well differentiated to anaplastic
Hepatic form arises in the setting of arsenic, thorotrast and polyvinyl chloride
Also arises in the setting of lymphedema and post-radiation
angiosarcoma
**common in skin, breast, and liver
benign tumors arising from modified smooth muscle cells of the glomus body (thermoregulation)
glomus tumor
common lesions, not true neoplasms. Local dilation of pre-existing vessels
Nevus flammeus: birthmarks, port-wine stain, Sturge-Weber syndrome
Spider telangiectasia
Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease)
vascular ectasia
vascular proliferation arising from an opportunisitc infection in immunocompromised individuals. Caused by Bartonella bacteria
bacillary angiomatosis
rare tumors derived of pericytes
hemangiopericytoma
