Flashcards in Module 6 CVS continued: Vasculitis Deck (50):
A good portion of this set of flashcards will cover the different vasculitis's, so what is vasculitis?
Inflammation and necrosis of the blood vessels , including arteries, veins and capillaries
can be classified based on:
type of vessel involved
What disease are associated with large vessel vasculitis (Aorta)?
---giant cell arteritis (temporal)
Which diseases are associated with medium vessel vasculitis (arteries)?
Immune complex mediated (polyartertitis nodosa)
Anti-endothelial cell antibodies (kawasaki disease)
Which diseases are associated with small vessel vasculitis (arterioles, capillaries, venules and veins)?
Vasculitis without asthma or granulomas: microscopic polyangiitis
Vasculitis, Granulomas without asthma (Wegener granulomatosis)
Eosinophilia, Asthma, and granulomas (Churg-Strauss Syndrome)
The etiology of vasculitis can either be direct infection,unknown or immunological. What are the associated vasculitis diseases?
Direct Infection: bacterial (Rickettsia, Spirochete) or fungal
Unknown: Giant cell (Temporal) arteritis, Takayasu arteritis and polyarteritis nodosa
Immunological: Immune complex = Hep B/C, SLE and RA and Drug induced. Direct Ab attack = Goodpasture and Kawasaki disease. Anti-neutrophil cytoplasmic Ab (ANCA) = Wegener's Granulomatosis and Churg-Strauss Syndrome
What are ANCA anti-neutrophil antibodies?
Heterogenous group of auto antibodies against enzymes found with in:
primary granules of neutrophils
lysosomes of monocytes
Detected as a blood test for autoimmune disorders and vasculitis
What are c-ANCA and p-ANCA?
c-ANCA (cytoplasmic)- PR3 (proteinase 3)
--neutrophil granule that shares homology with several microbial peptides
p-ANCA (peripheral)- MPO (myeloperoxidase)
--lysosomal granules involved in free radical production
---churg straus: granulomas, vasculitis, asthma and eosinophils
The first type of vasculitis talked about in class is Giant Cell (Temporal) Arteritis and it is the most common vasculitis , what is the pathogenesis for this disease?
Medium to large arteries affected --> temporal, ophthalmic and vertebral arteries --> forms a granuloma via CD4+ mediated T cells
How does Giant cell (temporal) arteritis present?
Men and Women over 50
Jaw claudication and facial pain (this pain because the temporal artery is affected)
polymyalgia rheumatica (muscle and joint pain)
What layer/s of the blood vessel does Giant Cell arteritis affect?
Intima and Inner Media
so NOT TRANSMURAL
Once you realize the patient has Giant cell arteritis, what do you do next??
Treat with IV steroids to prevent blindness/reduce inflammation on ophthalmic artery
Once you treat the patient, what is the next step in Giant cell arteritis?
Biopsy of the temporal artery---- called a segmental temporal artery biopsy ---- inflammation has it is focal so therefore need to segment so you dont miss it
What marker will be elevated in the blood for giant cell arteritis?
Elevated- ESR (non specific marker for inflammation) this marker is super sensitive for inflammation though
So what is the main complication in giant cell arteritis
Blindness (Again due to the inflammation of the temporal artery)
On histological slide, what do you see on temporal/giant arteritis?
On elastic trichrome stain:
---focal, nodular thickening with reduction of lumen
--intimal thickening and medial involvement and scarring
--focal destruction/fragmentation of internal elastic lamina
On H and E
--granulomatous inflammation of intima and inner media
--giant cells, mononuclear cells centered on internal elastic membrane
---additionally considered having a tree-bark appearance because of intima wrinkling ---- inflammation is in intima and inner media and there is scarring (note compare this to syphilis)
Takayasu arteritis presents with the same pathogenesis and symptoms as giant cell (temporal arteritis) however what is the difference between the two??
Asian women less then 40 and affects the arch of aorta (vs. temporal and ophthalmic in giant cell)
Notes: also called pulseless disease
The next vasculitis that affects medium vessels is called Polyarteritis Nodosa (PAN), what is the pathogenesis for this?
Transmural and again affected medium vessels
(capillaries, venules and arterioles are unaffected)
Necrotizing, systemic vasculitis
SPARES PULMONARY CIRCULATION
who gets polyarteritis nodosa and what the etiology of hep B?
Young ppl get this
Idiopathic but a strong correlation in 1/3rd of ppl with Hep B (so for investigation of hep B do surface antigen)
In what order of vessels does polyarteritis nodosa affect?
Renal, coronary, liver (hepatic) and GI
cerebral arteries (Stroke)
arteries of lower extremities (ulcers and gangrene)
Arteries feed off peripheral nerves called vaso navorum--affects the common fibular nerve ---foot drop
For the different arteries affected by polyarteritis nodosa, each card will go through the different pathogenesis for the organs. 1. Kidney
Kidney --- renal artery thrombosis (but doesnt cause glomerular nephritis so no hematuria because it doesnt touch the capillaries) ----- ischemia ---- hypoxia ---acute tubular necrosis ------ coagulative necrosis due to pale infarct --renal failure
patients have HTN because the HTN stimulates JG cells due to hypoxia so RAS is activated
In the coronary artery what occurs in polyarteritis nodosa?
Coronary ----- aneurysms ---- transmural MI ---- pale infarct
In the liver what occurs in polyarteritis nodosa?
Liver ---- occludes artery and therefore pale infarct ---- chronic hep B (leads to cirrhosis and HCC)
In the GI what occurs in polyarteritis nodosa?
GI ----- watershed area splenic flexure where most infarcts are and its red --- bloody diarrhea, fever and abdominal pain
What investigation is done for polyarteritis nodosa?
Angiogram and on there you see string of pearls and those are due to aneurysms
What is the best investigation for polyarteritis nodosa?
Arteriole biopsy: shows displaced temporal heterogeneity old (fibrosis) and new (neutrophils and fibrnoid necrosis) inflammatory changes
Microscopic Polyangiitis is a necrotizing vasculitis similar to PAN but what differences?
Smaller vessels are affected as well as GN so therefore hematuria
Lungs are affected via pulmonary capillaries therefore hemoptysis
Lesions of same stage/age vessels
NOT associated with HBV
Kawasaki syndrome (mucocutaneous lymph nodes syndrome) is what?
Arteries affecting large, medium and small arteries
favorite is the coronary artery so you get thrombus of the coronary artery and therefore a transmural MI (pale infarct)
Also children can get coronary artery aneurysms again because its transmural
leading cause of acquired heart disease in children in the US
What age group does kawasaki syndrome affect?
What are the symptoms associated with kawasaki syndrome?
Cervical lymph node swelling
Erythema of conjunctiva and oral pharynx
Edema of hands and feet
Peeling or exfoliating rash (Desqamous rash of upper and lower extremities)
What is the treatment for kawasaki syndrome?
Aspirin (to suppress the inflammation)
If the doctor did a biopsy of the coronary artery in a patient with kawaskai syndrome, what is seen?
Segmental fibrinoid necrosis and lumen with thrombus
dense infiltration of inflammatory cells
In Kawaskai syndrome what leads to acute vasculitis?
auto antibodies against endothelium and smooth muscle cells
The next vasculitis disease discussed was Buerger Disease (aka thromboangitis Obliterans), what is the pathogenesis for this disease?
Segmental, thrombosis, acute and chronic transmural inflammation of small and medium arteries
(basically a thrombotic obliteration of lumen)
Granulomatous vasculitis with microabscesses - type IV
What is a unique feature of Buerger disease?
Only one that eventually extends to veins and nerves and involves the entire neurovascular bundle
Which arteries are favored in Buerger disease?
Tibial and radial arteries (distal peripheral arteries) this explains why there is gangrene in the fingers and toes
What population is affected by Buerger disease ? Also what is the most important risk factor???
Young less then 35 male smokers of Japanese, indian or jewish descent
If the patient stops smoking does this reverse Buerger disease???
Nope just stops the progression
What is the best investigation for Buerger disease?
Best: arteriole biopsy (Thrombus completely obliterate the lumen of the artery) with microabscesses (necrotic debrie and PMNs) that spread to the nerve bundle (therefore this spread means you will have pain at rest)
Usual: angiogram ----- cork screw appearance
What are the symptoms of Buerger Disease?
Intermittent claudication ---- pain on walking and relieved by rest
Reynaud's Phenomenon -- white, blue, red
Phlebitis (acute inflammation of superficial veins --- medium cubital vein is red, warm, swollen)
Pain at rest ( once the nerves are affected)
In Buerger disease are collateral arteries made?
Yep because the lumen in occluded
The next vasculitis is Churg Strauss, what are some features?
Vasculitis of small to medium arteries (therefore affects the capillaries) so it damages the lungs and kidneys so you get hemoptysis and hematuria
What is the difference in Churg Strauss compared to wagners?
Churg Strauss has no URT involvement
usually patients have a history of bronchial asthma and peripheral eosinophilia
What enzymes do you look for in the blood for Churg Strauss?
what else has P-ANCA? microscopic polyangiitis
What is the etiology of Wegener's disease and who usually presents with this?
More common in males about 40
Describe the pathogenesis for wegener's disease in the URT and LRT
URT: ulceration of nasal mucosa and sinusitis
LRT: Necrotizing pneumonia that leads to granulomatous vasculitis that leads to a lung abscess and this leads to aspergilloma and patient presents with hemoptysis
patient has develops pneumonia that does not respond to abx..
Why does the pneumonia in Wegener's disease not respond to abx???
possible to get pneumonia without organism ---- so inflammation in this cause due to autoimmune damage to artery and patient forms a thrombus this leads to acute ischemia that leads to red infarct and coagulative necrosis --- leads to inflammation ---- pneumonia (so this only responds to steroids not abx)
Describe the pathogenesis for Wegener's disease in the kidney?
Nephritic syndrome: due to the renal infarcts affecting glomeruli capillaries: hematuria, oliguria, proteinuria, azotemia (elevated BUN/CREA) and HTN)
Renal failure is possible due to glomerular nephritis
What is the difference between Wegener's and Limited Wegener's?
Limited Wegener's does not affect the kidneys
still involves URT and LRT
What is the investigation done vs best investigation for Wegeners disease?
Investigation: PR3 antibodies in the blood (protease 3)
Best: lung biopsy with giant cells and lots of CD4 T cells, macrophages, PMNs