Vascular Pathology-Fung Flashcards
WHat is an aneurysm?
localized abnormal dilation of the blood vessel or the heart
What are the different types of aneurysms?
Congenital or acquired
True aneurysm or false aneurysm
Saccular or fusiform
What is a true aneurysm?
Involves an intact attenuated arterial wall or thinned ventricular wall
could be saccular or fusiform
What are some examples of true aneurysm?
Atherosclerotic
Syphilitic
Congenital
Ventricular following transmural infarction
What’s the deal with atherosclerotic true aneurysms?
atheromas increase distance of diffusion of nutrients to the media of the bv.
necrosis of the media leaves it vulnerable to rupture–aneurysm.
What is a false aneurysm?
Also called pseudo-aneurysm
Defect in the vascular wall leading to an extravascular hematoma that freely communicates with the intravascular space
What is an example of a false aneurysm?
Ventricular rupture with pericardial adhesion
what is a saccular true aneurysm?
Spherical outpouchings involving only a portion of the vessel
5-20 cm in diameter
What is a fusiform true aneurysm?
Diffuse, circumferential dilation of a long vascular segment
Up to 20 cm in diameter
Involve extensive portions of the aortic arch, abdominal aorta, iliac arteries
WHat is the function of endothelial cells in the vascular structure?
Maintain non-thrombogenic blood-tissue interface Modulate vascular resistance Metabolize hormones Regulate inflammation Regulate cell growth
What is the function of smooth muscle cells in the vascular structure?
Proliferate when stimulated Synthesize: ECM--> Collagen Elastin Proteoglycans Growth factors Cytokines
What is the ECM of the vascular structure composed of?
Elastin
Collagen
Glycosoaminoglycans
What is the order of the layers of a muscular artery?
endothelium internal elastic lamina tunica media external elastic lamina adventitia
What is a developmental berry aneurysm?
Occur in cerebral vessels
Majority occur sporadically
Some are genetic
Referred as congenital but not present at birth; develop over time
What are some genetic disease that can lead to the development of berry aneurysms?
AD polycystic kidney disease, Ehler-Danlos syndrome, NF1, Marfan syndrome
What are some risk factors for the development of berry aneurysms?
cigarettes
HTN
What are atriovenous fistulas?
Small direct connections between arteries and veins that bypass capillaries
AV fistulas occur due to….?
Developmental defects
Rupture of arterial aneurysm into an adjacent vein
Penetrating injuries that pierce arteries and veins
Inflammatory necrosis of adjacent vessels
Iatrogenic
What is fibromuscular dysplasia?
Focal irregular thickening of the walls of medium and large muscular arteries
Results in luminal stenosis
Fibromuscular dysplasia is most frequently found in which demographic?
young women
Can CT diseases cause aneurysms?
yes, anything that weakens the vascular wall can cause an aneurysm
Marfan syndrome: defect of fibrillin
Ehlers-Danlos syndrome: defect in the synthesis or structure of fibrillar collagen
Vitamin C deficiency: altered collagen cross-linking
Loeys-Dietz syndrome: defect in elastin, collagen I and III
Why is inflammation extra bad with aneurysms?
Inflammation that alters the balance of synthesis and destruction of collagen
Increased matrix metalloproteases (MMP) that degrade the extracellular matrix
What are the 2 most important predisposing risk factors for aneurysms?
HTN–Ascending Aortic Aneurysm
Atherosclerosis–AAA
What’s the deal with the abdominal aortic aneurysm?
Remember-the most common location for an atherosclerotic aneurysm
caused by cystic medial degeneration & MMP
There are the inflammatory & mycotic types.
Can be saccular or fusiform.
Describe the details of the inflammatory AAA.
Inflammatory type: dense periaortic fibrosis containing abundant lymphocytes, plasma cells and macrophages
Describe the mycotic type of AAA.
Mycotic type: caused by circulating microorganisms that destroys the media
What are the consequences of AAA?
Rupture with potential fatal hemorrhage
Obstruction of branch vessel
Embolism from atheroma or mural thrombus
Impingement on adjacent structures
Thoracic aortic aneurysm is most associated with which risk factor? What are some of its symptoms?
HTN
bone pain
cough–b/c of pressure on the recurrent laryngeal nerve
Thoracic aneurysms cause encroachment on which structures? What is a possible outcome?
Mediastinal structures
Lungs and airways
Esophagus
**TAA leads to aortic valve dilation with insufficiency
WHat is the major risk factor for aortic dissection? What are some conditions that can increase the risk of having it?
HTN
Marfan
Ehler Danlos
Vit C deficiency
How can HTN contribute to a dissection of an artery?
Medial hypertrophy of the vasa vasorum with degenerative changes of the media suggest injury due to diminished flow
What is the most frequently detectable histological lesion for dissections?
cystic medial degeneration
What is Type A dissection?
proximal lesions
involving the ascending & possibly involving the descending aorta
Debakey Types 1 & 2
What is a Type B dissection?
distal lesions
just involving the descending aorta
Debakey Type 3
**begins distal to the subclavian artery
What is Debakey Type 1 & 2?
Type 1: involves the ascending & descending aorta
Type 2: involves just the ascending aorta
What is vasculitis? What are 2 of the main mechanisms that cause it?
General term for vessel wall inflammation
**Immune-mediated inflammation
**Direct invasion of vascular walls by infectious pathogens
Can also initiate a non-infectious vasculitis
Which types of vasculitis affect larger vessels?
Granulomatous disease:
Giant cell (temporal) arteritis
Takayasu arteritis
Which types of vasculitis affect medium sized vessels?
Polyarteritis nodosa (immune complex mediated) Kawasaki disease (anti-endothelial cell antibodies)
Which forms of vasculitis can affect variable sized vessels?
Behcet’s disease
Cogan’s syndrome
Which forms of vasculitis can affect small vessels?
Wegener granulomatosis Churg-Strauss syndrome Microscopic polyangiitis Immune complex vasculitis Anti-GBM disease Cryoglobulinemic vasculitis IgA vasculitis Hypocomplementemic urticarial vasculitis
What are some forms of noninfectious vasculitis?
Immune-complex deposition
Anti-neutrophil cytoplasmic antibodies
Anti-endothelial cell antibodies–Kawasaki Disease
What are some examples of immune complex mediated vasculitis?
Systemic lupus erythematosus
Polyarteritis nodosa
Drug hypersensitivity vasculitis
**here antigen, antibody, and antigen-antibody complexes detected
What is ANCA?
Antineutrophil cytoplasmic antibodies (ANCA)
Circulating antibodies that react with neutrophil cytoplasmic antigen
Heterogeneous group of antibodies directed against:
Neutrophil primary granules
Monocyte lysosomes
Endothelial cells
What are 2 types of ANCA?
MPO-ANCA
PR3-ANCA
What is MPO-ANCA?
anti-myeloperoxidase
p-ANCA (perinuclear)
MPO is a lysosomal granule constituent
Which drug is MPO-ANCA found in? Which conditions?
Seen in therapeutic agents (propylthiouracil)
Seen in microscopic polyangiitis and Churg-Strauss syndrome
What’s the deal with PR3-ANCA? Which condition is it seen in?
Anti-proteinase-3 (PR3-ANCA) c-ANCA (cytoplasmic) PR3 is a neutrophil azurophilic granule constituent Shares homology with microbial peptides Seen in Wegener granulomatosis
Explain how ANCA formation happens.
Drugs or cross-reactive microbe (antigens) induce ANCA formation or
Neutrophil release MPO/PR3 and cause ANCA formation in a susceptible host
How can ANCA cause vasculitis?
Exposed to bacteria or something.
Host release cytokines (TNF) that causes expression of MPO/PR3 on neutrophils or other cell types
ANCA react and directly induce endothelial cell injury or activation of other neutrophils
ANCA-activated neutrophils degranulate and release reactive oxygen species further injuring endothelial cells
What is the usual presentation for giant cell arteritis?
men over the age of 50 with pulsing throbbing temporal arteries
also have vague symptoms, such as fever, fatigue, weight loss
What is giant cell arteritis? Which arteries does it affect?
Chronic, granulomatous inflammation of large to small-sized arteries
Affects principally arteries of the head: temporal artery, vertebral artery, ophthalmic artery and aorta
Medical emergency (ophthalmic artery blindness)
What is the mechanism of giant cell arteritis?
T-cell lymphocytic immune response against an unknown antigen
TNF and anti-endothelial cell humoral immune responses also contribute
What does the histo show for a patient with giant cell arteritis?
Discontinuous involvement of the vessel (multiple biopsies)
Intimal thickening
Medial granulomatous inflammation with giant cells
Elastic lamina fragmentation
What is the usual presentation of Takayasu arteritis?
young patients (less than 50) presenting with vague symptoms, including fever, weight loss, fatigue
What is Takayasu arteritis?
Granulomatous arteritis of medium or larger arteries characterized by
Ocular disturbances-diplopia or blindness
Marked weakening of the pulses in the upper extremities (pulseless disease)
Fibrous thickening of the aorta (aortic arch & great vessels)
What is polyarteritis nodosa & which vessels does it affect?
affects medium sized vessels
NOT pulm circulation
Includes renal vessels, visceral vessels
Follows Chronic Hep B, immune complex mediated
What happens to the affected vessels in polyarteritis nodosa?
transmural necrotizing inflammation, includes neutrophils, eosinophils, lymphocytes
affects the vessels circumferentially-can cause aneurysms
prefer vessel branch points
eventually you get fibrosis
Lesions in different stages coexist – recurrent and ongoing insults
What is Kawasaki Disease?
Acute febrile, self-limited illness of infancy and childhood affecting large to MEDIUM sized and small vessels
Mucocutaneous lymph node syndrome seen
Lesions show marked inflammation affecting the entire thickness of the vessel wall
Healed lesions may have obstructive intimal thickening
What is involved in mucocutaneous lymph node syndrome, the presentation of Kawasaki disease?
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
Which shows more fibrinoid necrosis:
polyarteritis nodosa
Kawasaki disease
PAN
Describe the coronary artery involvement of Kawasaki disease.
The vasculitis produced can cause aneurysms that can thrombose & cause an MI.
Vasculitis caused by delayed hypersensitivity reaction of T cells. Get cytokines, B cells, autoantibodies that attack the smooth muscle cells & endothelial cells of the blood vessels.
What is the vasculitis that is kinda like PAN but affects smaller vessels, including the capillaries?
microscopic polyangitis
Segmental fibrinoid necrotizing vasculitis that affects capillaries, arterioles and venules
Hypersensitivity vasculitis (leukocytoclastic vasculitis)
T/F Like PAN, microscopic polyangitis can have multiple lesions present at different stages.
False. PAN-multiple lesions @ different stages
Microscopic Polyangitis–all lesions are at the same stage @ the same time.
Which ANCA is found in microscopic polyangitis?
MPO-ANCA
What are the important symptoms of microscopic polyangitis?
Skin (palpable cutaneous purpura) Mucous membranes Lungs (hemoptysis) Brain Heart Gastrointestinal tract (bowel pain, bleeding) Kidney (hematuria, proteinuria) Muscle (muscle pain, weakness)
Which conditions does microscopic polyangitis occur with?
Henoch-Schonlein purpura
Essential mixed cryoglobulinemia
Vasculitis associated with connective tissue disorders
Which type of vasculitis is like PAN, but affects small vessels like capillaries & has granulomas & eosinophils present?
Churg-Strauss Syndrome
resembles microscopic polyangitis, except for the presence of granulomas & eosinophils
What are the clinical manifestations of Churg-Strauss Syndrome? Which ANCAs are sometimes present?
MPO-ANCA sometimes present
Palpable purpura
GI tract bleeding
Focal and segmental glomerulosclerosis
What should you associate with Churg-Strauss Syndrome? What is it aka?
aka allergic granulomatosis
think LUNG
Asthma
Allergic rhinitis
Lung infiltrates
Where do you find the eosinophils & granulomas in Churg-Strauss?
Peripheral hypereosinophilia
Extravascular necrotizing granulomas
What is Wegener Granulomatosis? Which size vessels does it involve?
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
PAN + Resp involvement
What type of reaction occurs with Wegener Granulomatosis? Which ANCA is found?
PR3-ANCA
T cell mediated hypersensitivity to inhaled infectious agent
What is thromboangitis obliterans? aka?
aka Buerger disease
Segmental thrombosing acute and chronic inflammation of medium and small sized arteries
Leads to vascular insufficiency
What do cigarettes do to vessels?
Hurt them! Directly toxic to endothelial cells or can be hurtful via an immune response to the cigarettes.
Which arteries are primarily affected by thromboangitis obliterans? What is the usual presentation?
principally the tibial and radial arteries (sometimes veins and nerves)
Almost exclusively seen in heavy smokers before 35
What are the clinical features of thromboangitis obliterans?
Superficial nodular phlebitis
Raynaud type cold sensitivity
Instep claudication
Severe pain at rest in the extremities
What’s the deal with infectious vasculitis?
could be bacterial or fungal (mycotic aneurysms)
affects vessels when it is spreading throughout the body via sepsis or embolus
What is Raynaud phenomenon?
Results from exaggerated vasoconstriction of digital arteries and arterioles
Symptoms include paroxysmal pallor and cyanosis of digits of hands and feet
can be primary or secondary
What is primary Raynaud?
Exaggeration of the central and local vasomotor responses to cold or emotional stress
What is secondary Raynaud?
Vascular insufficiency of the extremities secondary to arterial disease caused by SLE Scleroderma Buerger disease Atherosclerosis
What are varicose veins? What are 3 examples?
Abnormally dilated, tortuous veins produced by prolonged increased intraluminal pressure and loss of vessel support
superficial vessels of legs
esophageal varicose from portal HTN, can be fatal if they rupture
hemorrhoids
Thrombophlebitis means what? Where can it be seen?
venous thrombosis w/ inflammation deep leg veins Periprostatic venous plexus Pelvic venous plexus Large veins of the skull Dural sinuses
Paraneoplastic syndromes can have migratory _____.
thrombophlebitis
What are 2 types of vena caval syndromes?
SVC syndrome: neoplasms that compress the SVC (bronchogenic cancer, mediastinal lymphoma)
IVC syndrome: neoplasms that compress the IVC or from thrombus from renal or hepatic veins
WHat is lymphangitis? What causes it?
inflammation of the lymph vessels Group A (beta hemolytic) strep
WHat are causes of primary lymphedema?
Congenital defects
Familial agenesis or hypoplasia
What are causes of secondary lymphedema?
Tumors Dissection of lymph nodes Post-irradiation fibrosis Filariasis Post-inflammatory thrombosis and scarring
T/F Primary tumors of large vessels are relatively common.
False. Rare. Called soft tissue sarcoma & can be endothelial derived or derived from supporting cells.
Describe the vascular supply of benign tumors. Of malignant tumors.
Benign: well vascularized
Malignant: not well vascularized. cytologic atypia.
What is a Hemangioma/ Pyogenic granuloma?
Common tumors with increased numbers of blood vessels filled with blood
- *Capillary hemangioma: closely packed thin walled capillaries
- -subtype:pyogenic granuloma
- *Cavernous hemangioma: large dilated vascular channels
What is a lymphangioma? Different types?
Benign lymphatic analogues of blood vessel hemangioma
Simple capillary lymphangioma: small lymphatic channels
Cavernous lymphangioma (cystic hygroma): massively dilated lymphatic channels with lymphocytes in the connective tissue
Which virus causes Kaposi’s sarcoma?
Herpes VIrus 8
GIve 4 different types of Kaposi’s sarcoma.
Chronic KS: occurs in older men eastern Europe/ Mediterranean. Presents as skin lesions
Lympadenopathic KS: occurs in areas of Africa. Presents as lymphadenopathy
Immunocompromised Patients
Which types of immunocompromised patients experience Kaposi’s sarcoma?
Transplant associated KS: occurs in the setting of organ transplantation and immunosuppression. Presents with Nodal, MUCOSAL and Visceral involvement. Aggressive.
AIDS- associated KS: occurs in the setting of HIV/AIDS. Most prevalent malignancy in AIDS patients. Presents with Lymph node and Visceral involvement.
What is angiosarcoma?
Malignant endothelial neoplasms that range from well differentiated to anaplastic
What are 2 settings for angiosarcoma?
Hepatic angiosarcoma in the setting of certain substances: arsenic, thorotrast, polyvinyl chloride
Can arise with lymphedema, post-irradiation
What is a glomus tumor?
tumor of the glomus body involved in thermoregulation
it is benign & arises from smooth muscle cells
What is vascular ectasia?
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)
What is bacillary angiomatosis?
vascular proliferation arising from an opportunisitc infection in immunocompromised individuals. Caused by Bartonella bacteria
