Pathology of Non-Atherosclerotic Vascular Disease Flashcards
What is Monckeberg disease? When is it seen?
Calcific medial sclerosis
- > a type of calcification of the media of medium-sized muscular arteries (arteriosclerosis)
- > seen as incidental finding of X-ray or mammogram
What is a true vs false aneurysm?
True - dilatation of entire wall of cardiovascular system
False - more like a hematoma, communicates with vascular lumen but has ripped through and is walled off by adjacent connective tissue
What type of aneurysm is a berry aneurysm?
Saccular aneurysm - focal, spherical outpouching
What is it called when an aneurysm is large and linearly dilates along the entire circumference of the vessel?
Fusiform aneurysm
What things can cause aneurysm? Include what a mycotic aneurysm is.
Significant weakening of vascular wall
- > atherosclerosis is most common
- > cystic medial degeneration
- > congenital abnormalities (i.e. berry aneurysms in ADPKD)
- > Vasculitides
- > Mycotic aneurysm - aneurysm due to infective embolus
Who usually gets an abdominal aortic aneurysm, and what is the typical etiology? What type of aneurysm is it?
Men with a genetic predisposition
Etiology - atherosclerosis since there is little vasa vasorum in abdominal aorta -> thinning and destruction of media
-> Fusiform aneurysm
What are the complications of abdominal aortic aneurysm?
- Rupture - proportional to size
- Vascular occlusion - due to aneurysm itself or mural thrombosis caused by turbulent flow
- Embolism - atheromatous or thrombotic debris
- Compression of neighboring structures - i.e. vertebral bodies
What is the pathogenesis of Syphilitic aneurysm and where does it occur?
It is an obliterative endarteritis of tertiary syphilis due to destruction of vasa vasorum in the adventitia -> ischemic damage of the media
Occurs in thoracic aorta, where vasa vasorum is more important
How will syphilitic aneurysm appear grossly?
Grossly - fusiform dilatation of aortic arch / thoracic aorta with white, folded appearance on inside, due to contracture of fibrosis “tree-barking”**
How will syphilitic aneurysm appear microscopically?
Intima - undamaged, will have ribbon-like effect w/alternating bulges into lumen
Media - scattered patches of smooth muscle cell loss with inflammation & subsequent fibrosis (ischemia)
Adventitia - Vasa vasorum surrounding by plasma cells and lymphocytes -> destruction via syphilis
What are the possible complications of syphilitic aneurysm? What is notably absent?
- Aortic insufficiency - aneurysm increases aortic annulus size -> regurgitation and LV volume overload
- Superimposed atherosclerosis / ischemic heart disease - from tubulence
- Compression / erosion of adjacent structures (absent = bronchi, esophagus, recurrent laryngeal nerves, vertebrae)
Absent = Rupture -> media / adventitia is scarred so rupture is unlikely
What is the most common, and two uncommon causes of aortic dissection?
Most common - hypertension
Uncommon - inherited connective tissue disorder (i.e. Marfan), or peripartum (due to volume shifts in pregnancy)
Where does aortic dissection occur within the wall, and what are the two types?
A tear in the intima allows blood to enter media. Blood begins dissecting between inner 2/3 and outer 1/3 of media
Type A: proximal dissection - involves ascending aorta +/- descending
Type B: distal dissection - involves descending aorta only
What is a double-barreled aorta?
When the aorta dissects both proximally and distally, leading to channel of blood flowing through both the aorta and the aortic dissection
What is seen microscopically in the elastic media of aortic dissection?
“cystic” medial degeneration -> loss of layers of elastic connective tissue which are replaced by loose, pale, amorphous extracellular matrix
What are the major symptoms of aortic dissection?
Severe chest pain radiating to the back and extending downward
What are the complications of aortic dissection and why?
- Rupture into body cavity -> most often pericardial sac if proximal dissection, leading to tamponade
- Aortic insufficiency - valve becomes flopping when unanchored from wall
- External compression of aortic branches (i.e. renal)
What is the most common result of infectious vasculitis?
Mycotic aneurysm -> usually due to bacterial or fungal pathogen (i.e. aspergillus)
What are the two types of antineutrophil cytoplasmic antibodies (ANCAs) and their targets?
cytoplasmic, c-ANCA - proteinase-3
perinuclear, p-ANCA - myeloperoxidase
p doesn’t go with p
What are the three types of immune-mediated, noninfectious vasculitis?
- Immune-complex mediated
- ANCA-mediated
- Anti-endothelial antibody mediated
How are ANCAs originally generated and what is their pathogenesis?
Initial insult -> neutrophil activation -> sensitization of immune system against neutrophil antigens PR3 and MPO -> antibodies bind neutrophils and cause degranulation + vascular injury
What are the three broad possible outcomes of vascular inflammation and injury which can lead to a wide variety of sequellae in vasculitis?
- Luminal narrowing -> ischemia
- Thrombosis -> embolic events
- Aneurysm -> wall weakening and risk or rupture
What vessels are involved in temporal arteritis, and what type of inflammation dominates?
Temporal and ophthalmic arteries
Inflammation: Granulomatous inflammation with giant cells lined up on internal elastic lamina, with focal destruction and fibrosis of vessel -> narrowed lumen + ischemia
How tends to get temporal arteritis, and what are the symptoms? Should it be treated?
Older adults, present with constitutional symptoms as well as painful and nodular temporal artery, with headache and visual impairment
YES - it needs to be treated very rapidly with systemic corticosteroids if suspected before bilateral vision loss occurs
What disease is associated with temporal arteritis and what are its symptoms?
Polymyalgia rheumatica
-Chronic inflammatory condition characterized by joint / muscle pain and stiffness
- > hips and shoulders most affected, with worse symptoms in morning (rheumatica = like rheumatoid arthritis)
- > synovitis of proximal joints / structures
What is Takayasu arteritis also called and why? What vessels does it involve?
Pulseless disease - involves aortic arch and its major branches
Associated with weak upper extremity pulses due to degeneration of aortic arch branches
What is the vascular pathology of pulseless disease?
Granulomatous inflammation very similar to temporal arteritis, except it involves aorta + branches so giant cells will span the entire thickness of the vessel wall, with luminal narrowing
Who does Takayasu arteritis typically affect and what are the symptoms?
Young women - symptoms include neurologic / visual deficits from poor perfusion and strokes / TIAs from thromboembolism.
Can cause myocardial ischemia due to coronary artery involvement or hypertension if it affects kidneys (increased RAA system)
What is granulomatosis with polyangiitis also called, and what is the clinical triad?
Wegener’s granulomatosis
Triad:
1. Necrotizing granulomatous inflammation of upper / lower respiratory tract
- Necrotizing granulomatous vasculitis of small vessels of upper / lower respiratory tract
- Necrotizing, proliferative glomerulonephritis -> hematuria / proteinuria
Who is Wegener’s typically found in, and what marker correlates with disease activity?
Typically middle-aged men
c-ANCA levels (Proteinase-3) correlate with disease activity
What vessels are involved in polyarteritis nodosa? Treatment?
Small to medium-sized arteries of kidneys, GI tract, and heart
Notably - LUNGS are spared
Treatment = immunosuppressive therapy - cyclophosphamide + corticosteroids
What does polyarteritis nodosa look like under the microscope?
Type III hypersensitivity - patchy, transmural acute / chronic inflammation and fibrinoid necrosis / thrombosis.
Notable: alternating regions of fibrosis and necrosis (lesions of varying stages present)
Who typically gets polyarteritis nodosa and what symptoms do they present with?
Young adults - especially following hepatitis B infection
Symptoms - constitutional symptoms, signs of multifocal vascular injury -> hypertension (kidneys), abdominal pain w/melena, skin lesions (nodules)
What is Kawasaki disease? What disease is it similar to under the microscope? Who tends to get it?
Mucocutaneous lymph node syndrome
Similar to polyarteritis nodosa, young children tend to get it.
What vessels are affected in Kawasaki disease, and what are the clinical symptoms?
Vessels affected are coronary arteries
Symptoms: Erythematous rash of palms / soles (mucosa), peripheral edema (lymph involvement), cervical adenopathy (lymph node syndrome), and cardiovascular complications
What are the cardiovascular complications of Kawasaki disease and what is the treatment?
Myocardial infarction or coronary artery aneurysms with possible rupture
Treatment - Aspirin and IV immunoglobulin (aspirin normally contraindicated in children)
What vessels does microscopic polyangiitis affect, and what marker correlates with severity?
Smallest vessels, multi-organ involvement, includes arterioles, capillaries, and venules
p-ANCA correlates -> microscopic Polyangiitis
What vascular pathology predominates microscopic polyangiitis?
Looks alot like polyarteritis nodosa, except the lesions will be the same age, smaller vessels are affected, and there will be the presence of fragmented neutrophils due to anti-p-ANCA
(also called leukocytoclastic vasculitis. Leukocytoclastic = destruction of WBCs)
When does microscopic polyangiitis typically develop and what does it look like clinically?
Frequently following a drug exposure or malignancy
Involves small vessels of kidney, lung, and skin the most:
Palpable purpura on skin, hematuria, and hemoptysis
What vasculitis is caused by deposition of IgA immune complexes, especially following an upper respiratory infection in children? What vessels does it preferentially involve?
Henoch-Schonlein purpura
= skin + GI + IgA nephropathy + kids
- > small blood vessels, especially skin and GI tract
- > glomeruli - mesangial deposits of IgA immune complexes, similar to IgA nephropathy
What are the symptoms of HSP?
Palpable purpura on buttocks, dorsal legs, and arms
Arthralgias / abdominal pain / intestinal bleeding / renal abnormalities (hematuria, proteinuria, HTN)
What is thromboangiitis obliterans also called and what vessels are affected?
Buerger disease
-> small to medium-sized arterties of distal extremities
What is the clinical presentation of Buerger disease and how is it treated?
Occurs in young adult smokers
Thrombosis and microabscesses in distal exremities, can include veins and nerves, very PAINFUL and may lead to autoamputation
-> treated with smoking cessation
What is Churg-Strauss syndrome and what marker might is be associated with? What disease is associated?
Allergic granulomatous angiitis
- > vasculitis with eosinophil predominance
- > heavily associated with asthma
Is Churg-Strauss syndrome focal or widespread? What do lesions look like?
In its most severe phase, it is very widespread, affecting almost any small vessels in any tissue in the body
Lesions are necrotizing granulomatous inflammation with eosinophils
What causes varicose veins and what are the most common sites?
Long-standing increased intravenous pressure with poor wall support -> dilated veins with wall abnormalities
Sites:
- Superficial on lower extremities
- Submucosal veins - i.e. distal esophagus / rectum due to portal HTN
What are the potential complications of varicose veins?
Usually just thrombosis (NOT thromboembolism) and worsening congestion / edema
Submucosal varicosities may hemorrhage
What are thrombophlebitis and phlebothrombosis and what usually causes them? Major complication?
Deep vein thrombosis
Usually caused by stasis, occurring in lower extremities
Complication: Pulmonary thromboembolism
What typically causes lymphangitis / lymphadenitis?
Bacterial infection spreading thru lymphatic vessels with acute inflammation til it reaches lymph nodes
What causes lymphedema?
Obstruction of lymphatic vessels (i.e. filariasis) or s/p surgery / radiation (i.e. breast cancer removal of axillary nodes)
What are nevus simplex and port wine stains examples of?
Nevus simplex = salmon patch on skin
Port wine stain - large collection of ruby capillaries
Examples of capillary malformations, the most common type of simple vascular malformation
Are nervus simplexes and port wine stains flat or raised? What are they made of?
Flat - patches of discoloration (pink to reddish-purple macules)
Consist of dilated capillaries and/or postcapillary venules
Do vascular malformations usually regress? What types of lesions do these include?
No
Includes capillary malformations and lymphatic malformations
What would a cystic hygroma be called now and what is it?
Macrocystic lymphatic malformation
Lesion composed of variably-sized, dilated lymphatic channels
Tend to develop under skin of neck / axillary region, may also be microcystic or mixed
What is the most common type of benign vascular tumor? What does it look like under the microscope?
Infantile hemangioma - most common tumor of infancy
Looks like plump endothelial cells (with unique markers and pericytes) that form densely packed vascular spaces
When do infantile hemangiomas appear and do they regress? Where do they appear?
Tend to be in subcutaneous skin / face, appearing within first few weeks of life
Gradually regress over 5-9 years
How does a congenital hemangioma differ from an infantile hemangioma, and do they regress?
Congenital must be present at birth, and may involve other locations like soft tissue / viscera. May also involve lympatic vessels / larger, dilated vessels.
Wide variability in regression -> some regress rapidly, others never do
What causes Kaposi sarcoma and where do they tend to appear?
STI with HHV-8 in combination with immunosuppression
Appear in reddish-purple plaques on skin (esp. nose), mucous membranes, lymph nodes, and visceral organs (esp. GI tract)
What does Kaposi sarcoma look like under the microscope?
Irregular vascular spaces, plump spindle cells, and mononuclear infiltrate (chronic inflammation to fight virus) with hemorrhage
What is the classic form of Kaposi sarcoma and where does it tend to be?
Indolent form affecting distal extremities of lower limb preferentially of Eastern European (Russia) / Mediterranean men
What are the features of endemic Kaposi sarcoma?
Aggressive -> found in Africa, primarily involves lymph nodes
What are the features of immunosuppression-associated Kaposi sarcoma?
In AIDS / transplant patients
Multi-organ systemic disease with visceral involvement
-> treat with immunosupportive therapy + antineoplastics
What are the common sites for angiosarcoma and what is it?
Highly aggressive malignancy of endothelial cells
Common sites include skin, breast, and liver
What carcinogens is angiosarcoma associated with?
polyvinyl chloride (PVC), Thorotrast (radiocontrast agent), arsenic (pesticides)
