Name these two flavors of aneurysms: 1. dense periaortic fibrosis containing abundant lymphocytes, plasma cells and macrophages 2. due to circulating microorganisms that destroys the media

1. inflammatory type 2. mycotic type

Fung: Vascular Pathology Flashcards by Megan Foggia

Occur in cerebral vessels
Majority occur sporadically
Some are genetic
AD polycystic kidney disease, Ehler-Danlos syndrome, NF1, Marfan syndrome

developmental (berry) aneurysms

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What diseases are associated with berry aneurysms?

polycystic kidney disease
Ehler-Danlos syndrome
Marfan syndrome

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What are two major risk factors for berry aneurysms?

cigarette smoking

hypertension

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Are berry aneurysms really congenital?

no, they are referred to as congenital but they actually develop over time

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Small direct connections between arteries and veins that bypass capillaries

atriovenous fistulas

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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)

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Focal irregular thickening of the walls of medium and large muscular arteries
Results in luminal stenosis

fibromuscular dysplasia

**occurs most frequently in young women

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Localized abnormal dilation of a blood vessel or the heart

Congenital or acquired

Aneurysms

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Involves an intact attenuated arterial wall or thinned ventricular wall

True aneurysm

**ex: Atherosclerotic
Syphilitic
Congenital
Ventricular following transmural infarction

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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

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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

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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

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Defect in fibrillin which can lead to aneurysm formation

Marfan syndrome

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Defect in the synthesis or structure of fibrillar collagen; can lead to aneurysm formation

Ehlers-Danlos syndrome

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Altered collagen cross-linking; can lead to aneurysm formation

Vit C deficiency

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Defect in elastin, collagen I, and III; can lead to aneurysm formation

Loeys-Dietz syndrome

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How do aneurysms form?

inflammation alters the balance of synthesis and destruction of collagen

increased matrix metalloproteases degrade the ECM

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

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Two of the most important predisposing factors for aneurysm formation?

atherosclerosis

hypertension

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Other causes of aneurysm formation?

congenital defects

infections due to embolization, direct extension or circulation of organisms

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Where are atherosclerotic aneurysms most likely to occur?

abdominal aorta

**seen in male smokers >60 yo with HTN

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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

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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

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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

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This type of aneurysm is most commonly associated with hypertension; classically seen in tertiary syphilis

thoracic aneurysm

**tree bark appearance of the aorta

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List 4 signs and symptoms of a thoracic aneurysm

1. cough due to pressure on recurrent laryngeal nerve 2. bone pain 3. aortic valve dilation with insufficiency 4. 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?

1. 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

1. giant cell arteritis | 2. Takayasu arteritis

List three types of medium vessel vasculitis

1. Polyarteritis nodosa (immune complex mediated) 2. Kawasaki disease (anti-endothelial cell antibodies) 3. Buerger disease

List 4 types of small vessel vasculitis

1. Microscopic polyangitis (vasculitis w/ no asthma or granulomas) 2. Wegener granulomatosis (granulomas, but no asthma) 3. Chrug-Strauss syndrome (eosinophilia, asthma, and granulomas) 4. 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

Fung: Vascular Pathology Flashcards

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