Module 6 CVS continued: Vasculitis

Question 1

A good portion of this set of flashcards will cover the different vasculitis’s, so what is vasculitis?

Answer 1

Inflammation and necrosis of the blood vessels , including arteries, veins and capillaries
can be classified based on:
type of vessel involved
etiology

Question 2

What disease are associated with large vessel vasculitis (Aorta)?

Answer 2

Granulomatous Disease

• –giant cell arteritis (temporal)
• –takayasu arteritis

Question 3

Which diseases are associated with medium vessel vasculitis (arteries)?

Answer 3

Immune complex mediated (polyartertitis nodosa)

Anti-endothelial cell antibodies (kawasaki disease)

Question 4

Which diseases are associated with small vessel vasculitis (arterioles, capillaries, venules and veins)?

Answer 4

Vasculitis without asthma or granulomas: microscopic polyangiitis
Vasculitis, Granulomas without asthma (Wegener granulomatosis)
Eosinophilia, Asthma, and granulomas (Churg-Strauss Syndrome)

Question 5

The etiology of vasculitis can either be direct infection,unknown or immunological. What are the associated vasculitis diseases?

Answer 5

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

Question 6

What are ANCA anti-neutrophil antibodies?

Answer 6

Heterogenous group of auto antibodies against enzymes found with in:
primary granules of neutrophils
lysosomes of monocytes
endothelial cells
Detected as a blood test for autoimmune disorders and vasculitis

Question 7

What are c-ANCA and p-ANCA?

Answer 7

c-ANCA (cytoplasmic)- PR3 (proteinase 3)
–neutrophil granule that shares homology with several microbial peptides
–Wegener’s Granulomatosis
p-ANCA (peripheral)- MPO (myeloperoxidase)
–lysosomal granules involved in free radical production
—rheumatoid arthritis
–polyarderitis nodos
—churg straus: granulomas, vasculitis, asthma and eosinophils

Question 8

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?

Answer 8

Medium to large arteries affected –> temporal, ophthalmic and vertebral arteries –> forms a granuloma via CD4+ mediated T cells
idiopathic

Question 9

How does Giant cell (temporal) arteritis present?

Answer 9

Men and Women over 50
Jaw claudication and facial pain (this pain because the temporal artery is affected)
polymyalgia rheumatica (muscle and joint pain)
Headache
Blurred Vision

Question 10

What layer/s of the blood vessel does Giant Cell arteritis affect?

Answer 10

Intima and Inner Media

so NOT TRANSMURAL

Question 11

Once you realize the patient has Giant cell arteritis, what do you do next??

Answer 11

Treat with IV steroids to prevent blindness/reduce inflammation on ophthalmic artery

Question 12

Once you treat the patient, what is the next step in Giant cell arteritis?

Answer 12

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

Question 13

What marker will be elevated in the blood for giant cell arteritis?

Answer 13

Elevated- ESR (non specific marker for inflammation) this marker is super sensitive for inflammation though

Question 14

So what is the main complication in giant cell arteritis

Answer 14

Blindness (Again due to the inflammation of the temporal artery)

Question 15

On histological slide, what do you see on temporal/giant arteritis?

Answer 15

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)

Question 16

Takayasu arteritis presents with the same pathogenesis and symptoms as giant cell (temporal arteritis) however what is the difference between the two??

Answer 16

Asian women less then 40 and affects the arch of aorta (vs. temporal and ophthalmic in giant cell)
Notes: also called pulseless disease

Question 17

The next vasculitis that affects medium vessels is called Polyarteritis Nodosa (PAN), what is the pathogenesis for this?

Answer 17

Transmural and again affected medium vessels
(capillaries, venules and arterioles are unaffected)
Necrotizing, systemic vasculitis
SPARES PULMONARY CIRCULATION
NO GRANULOMATOUS

Question 18

who gets polyarteritis nodosa and what the etiology of hep B?

Answer 18

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)

Question 19

In what order of vessels does polyarteritis nodosa affect?

Answer 19

Renal, coronary, liver (hepatic) and GI
also affects:
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

Question 20

For the different arteries affected by polyarteritis nodosa, each card will go through the different pathogenesis for the organs. 1. Kidney

Answer 20

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

Question 21

In the coronary artery what occurs in polyarteritis nodosa?

Answer 21

Coronary —– aneurysms —- transmural MI —- pale infarct

Question 22

In the liver what occurs in polyarteritis nodosa?

Answer 22

Liver —- occludes artery and therefore pale infarct —- chronic hep B (leads to cirrhosis and HCC)

Question 23

In the GI what occurs in polyarteritis nodosa?

Answer 23

GI —– watershed area splenic flexure where most infarcts are and its red — bloody diarrhea, fever and abdominal pain

Question 24

What investigation is done for polyarteritis nodosa?

Answer 24

Angiogram and on there you see string of pearls and those are due to aneurysms

Question 25

What is the best investigation for polyarteritis nodosa?

Answer 25

Arteriole biopsy: shows displaced temporal heterogeneity old (fibrosis) and new (neutrophils and fibrnoid necrosis) inflammatory changes

Question 26

Microscopic Polyangiitis is a necrotizing vasculitis similar to PAN but what differences?

Answer 26

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
Involves P-ANCA

Question 27

Kawasaki syndrome (mucocutaneous lymph nodes syndrome) is what?

Answer 27

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

Question 28

What age group does kawasaki syndrome affect?

Answer 28

Japanese children

Question 29

What are the symptoms associated with kawasaki syndrome?

Answer 29

Fever
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)

Question 30

What is the treatment for kawasaki syndrome?

Answer 30

Aspirin (to suppress the inflammation)

Question 31

If the doctor did a biopsy of the coronary artery in a patient with kawaskai syndrome, what is seen?

Answer 31

Segmental fibrinoid necrosis and lumen with thrombus

dense infiltration of inflammatory cells

Question 32

In Kawaskai syndrome what leads to acute vasculitis?

Answer 32

auto antibodies against endothelium and smooth muscle cells

Question 33

The next vasculitis disease discussed was Buerger Disease (aka thromboangitis Obliterans), what is the pathogenesis for this disease?

Answer 33

Segmental, thrombosis, acute and chronic transmural inflammation of small and medium arteries
(basically a thrombotic obliteration of lumen)
Granulomatous vasculitis with microabscesses - type IV

Question 34

What is a unique feature of Buerger disease?

Answer 34

Only one that eventually extends to veins and nerves and involves the entire neurovascular bundle

Question 35

Which arteries are favored in Buerger disease?

Answer 35

Tibial and radial arteries (distal peripheral arteries) this explains why there is gangrene in the fingers and toes

Question 36

What population is affected by Buerger disease ? Also what is the most important risk factor???

Answer 36

Young less then 35 male smokers of Japanese, indian or jewish descent

Question 37

If the patient stops smoking does this reverse Buerger disease???

Answer 37

Nope just stops the progression

Question 38

What is the best investigation for Buerger disease?

Answer 38

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

Question 39

What are the symptoms of Buerger Disease?

Answer 39

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)
Ulcers
Gangrene
Pain at rest ( once the nerves are affected)

Question 40

In Buerger disease are collateral arteries made?

Answer 40

Yep because the lumen in occluded

Question 41

The next vasculitis is Churg Strauss, what are some features?

Answer 41

Vasculitis of small to medium arteries (therefore affects the capillaries) so it damages the lungs and kidneys so you get hemoptysis and hematuria

Question 42

What is the difference in Churg Strauss compared to wagners?

Answer 42

Churg Strauss has no URT involvement

usually patients have a history of bronchial asthma and peripheral eosinophilia

Question 43

What enzymes do you look for in the blood for Churg Strauss?

Answer 43

P-ANCA

what else has P-ANCA? microscopic polyangiitis

Question 44

What is the etiology of Wegener’s disease and who usually presents with this?

Answer 44

Etiology: idiopathic

More common in males about 40

Question 45

Describe the pathogenesis for wegener’s disease in the URT and LRT

Answer 45

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..

Question 46

Why does the pneumonia in Wegener’s disease not respond to abx???

Answer 46

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)

Question 47

Describe the pathogenesis for Wegener’s disease in the kidney?

Answer 47

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

Question 48

What is the difference between Wegener’s and Limited Wegener’s?

Answer 48

Limited Wegener’s does not affect the kidneys

still involves URT and LRT

Question 49

What is the investigation done vs best investigation for Wegeners disease?

Answer 49

Investigation: PR3 antibodies in the blood (protease 3)
Best: lung biopsy with giant cells and lots of CD4 T cells, macrophages, PMNs

Question 50

What is the difference between Wegener’s disease and Polyarteritis Nodosa?

Answer 50

Hematuria Pulmonary Involvement (none of this in polyarteritis)