Vasculitis Flashcards Preview

MDTI > Vasculitis > Flashcards

Flashcards in Vasculitis Deck (53):
1

vasculitis definition

a heterogenous group of immune mediated disorders that causes inflammation and damage to blood vessel walls leading to tissue ischemia and organ failure

2

pathogenesis of vasculitis

starts with infiltration of blood vessel walls by leukocytes or immune complex deposition on the vessel walls, which triggers leukocyte infiltration. This triggers an inflammatory cascade that damages the vessel, causes lumenal occlusion and ischemia/inflammation, ultimately leading to organ failure

3

which vessels are targeted in vasculitis?

all arteries, microcirculation, and venues & small veins (medium and large veins are spared)

4

large vessel vasculitis

any inflammatory disease that affects the aorta and or its major branches to the head, neck, and extremities

5

medium vessel vasculitis

everything else on the arterial side (not aorta and main branches). Includes not only medium, but small muscular arteries as well

6

small vessel vasculitis

largest group of vasculitis. microcirculation, intraparenchymal arteries and veins.

7

two subtypes of small vessel vasculitis

ANCA associated vasculitides (pauci-immune) & Immune complex mediated

8

ANCA associated vasculitis (AAV)

serum antibody in blood (ANCA) causes disease. Immune complexes aren't found in vessel walls (pauci-immune)

9

Immune complex mediated vasculitis

immune complex deposition in vessel walls. no ANCAs

10

primary diagnostic procedure for vasculitis

biopsy of affected tissue

11

if you can't get a tissue biopsy, how can you diagnose vasculitis?

angiogram

12

cardinal features of vasculitis

leukocyte infiltration (inflammation) of vessel wall
damage to vessel wall
possibly deposition of immune complex in vessel wall for IC mediated small vessel vasculitis

13

what is the damage to the vessel wall in vasculitis?

lumenal narrowing, fibrinoid necrosis, disruption of the internal and external elastic laminae

14

polyarteritis nodosum (PAN)

medium (occasionally small) artery vasculitis that targets the gut, kidneys, nervous system, heart, muscles, joints, testes, and skin.

15

what organs are specifically spared in PAN?

lungs and glomeruli (doesn't affect microcirculation)

16

diagnostic test for PAN

angiogram

17

cardinal features of PAN

narrowing, dilation, aneurysm

18

a case where PAN affects small muscular arteries

digital gangrene

19

test for digital gangrene

MRI angiogram

20

3 cellular layers of artery (luminal to outer)

intima (single lining of epithelial cells)
Media (smooth muscle cells)
Adventitia (outer layer of connective tissue)

21

2 membranes of arteries

internal elastic lamina (between intima and media)
external elastic lamina (between media and adventitia)

22

how does nutrition reach small arteries?

diffusion

23

how does nutrition reach larger arteries?

vasa vasorum (vessels of the vessel) in adventitia.

24

pathology of PAN

mixed transmural inflammatory cell infiltrate (intima, media, adventitia). fibrinoid necrosis, lumen obliteration

25

specific details of vessel damage in PAN

destruction of internal and external elastic laminae, intimal proliferation that causes lumen narrowing, fibrosis

26

renal involvement in PAN

narrowing of renal arteries causes decreased blood supply, which causes the kidney to activate renin and angiotensin hormonal system, which causes increased salt/H2O retention, which leads to hypertension

27

where do aneurysms and inflammation occur in PAN?

branch points of arteries (sites of increased shear stress)

28

how is shear stress associated with inflammation in PAN?

induces expression of endothelial cell adhesion molecules like ICAM and increases the expression of pro inflammatory transcription factors (NFkB)

29

what does ANCA stand for?

Antineutrophil cytoplasm antibodies

30

what are ANCAs?

serum autoantibodies that bind neutrophil cytoplasmic granules

31

how do we detect ANCAs?

indirect immunofluorescence. add patients serum to slides coated with neutrophils that have been fixed with ethanol and have disrupted membranes. if ANCAs are present, they will bind to granules. Wash away unbound antibody and add anti human IgG that is conjugated with fluorescein

32

ANCA fluorescent patterns

C-ANCA and P-ANCA

33

C-ANCA

cytoplasmic staining, most specific for AAV, least common, recognizes proteinase-3, must be confirmed via ELISA

34

P-ANCA

perinuclear staining, least specific for AAV, most common, recognizes MPO, must be confirmed by ELISA

35

tropism for AAV

microcirculation in respiratory tract and kidneys (commonly causes pulmonary hemorrhage and acute renal failure)

36

sign of kidney involvement in AAV

cresentic glomerulonephritis

37

pathogenesis of crescentic glomerulonephritis

injury to glomerular capillary wall causes leakage of plasma proteins into bowman's space. This triggers the influx of inflammatory cells that release pro inflammatory cytokines (IL-1, TNFa), fibroblasts are triggered to secrete collagen that forms crescents.

38

consequence of glomerulonephritis

hematurua, proteinuria, anasarca

39

anasarca

whole body edema due to renal involvement from AAV

40

role of ANCAs in AAV

markers of the disease and bind to/activate neutrophil granule antigens, which makes them more adherent to endothelium and then they release lytic enzymes that cause free radical endothelial damage in vessels

41

how can infection be linked to AAV?

proinflammatory cytokines from infection primes the neutrophils, which causes migration of the ANCA antigens to the cell surface.

42

immune complex mediated small vessel vasculitis

most common and most benign, usually presents as a skin rash.

43

tropism for IC mediated SVV

dermal vessels, especially venules

44

what determines immungenicity of IC mediated SSV?

IC size and solubility, which is determined by Ab:Ag ratio. Equal=large ICs=removed by RES, Excess Ab=small ICs=soluble, Excess Ag=ICs precipitate and deposit

45

common clinical manifestation of IC mediated SSV

palpable purpura

46

most common pattern of IC mediated SSV

leukocytoclasis (WBC fragmentation, predominantly PMNs)

47

name of nuclear debris from fragmentation in leukocytoclastic vasculitis

karyorrhexis

48

how can we test for IC deposition?

immunofluorescent staining of biopsy

49

pathogenesis of IC mediated SVV

antigen excess causes IC deposition in vessel walls. complement binds IC and is cleaved in C3/5a that then attracts other inflammatory cells. Neutrophils try to phagocytose ICs and become activated to start causing damage via lysosomal enzyme release

50

endothelial cell activation in IC-SVV

activated in response to various stimuli to up regulate adhesion proteins which allow for further neutrophil containment

51

role of C3a and C5a in IC-SVV

attract inflammatory cells and trigger histamine release which widens the EC junctions, allowing plasma/cells/fluid to leak out causing palpable purpura

52

what infection is PAN commonly associated with?

Heo B

53

ANCA priming

migration of ANCA antigens to neutrophil surface