PATH: Kidney in Systemic Disease I Flashcards
Microscopic polyangitis is associated with what?
P-ANCA (antibodies against myeloperoxidase)
Small vessel vasculitis usually causes what type of glomerulonephritis?
pauci-immune crescentic (have few Abs or ICs but lots of ANCAs)
What are the thrombotic microangiopathies?
HUS
TTP
Before ANCA-associated glomerulonephritis occurs, what sort of symptoms can occur?
extrarenal symptoms: joint pains, muscle aches, flu-like symptoms
Where do ANCAs act in the glomerulus?
cause ENDOTHELIAL injury in glomeruli and blood vessels
What normally happens when neutrophils release proteinase 3?
circulating alpha-1 antitrypsin rapidly breaks it down
What can increase the surface expression of proteinase 3 and MPO on the surface of the neutrophil?
TNF-alpha and IL-8 (synergistic inflammatory event)
If C-ANCA is present, what happens to neutrophils coated with proteinase 3?
the ANCA “coats” the proteinase 3 and “hides” it from alpha-1 antitrypsin
What happens when ANCAs bind to neutrophils?
they are activated and adhere to endothelial cells by beta-2 integrins, MAC-1, and Fc-Gamma
What type of complement pathway is activated by ANCA/neutrophil binding to endothelium?
alternative pathway
What is the overall result of the ANCA/neurtophil binding to the endothelium?
endothelial surface damage, ADCC, internalization of MPO adn proteinase 3 –> apoptosis
What else can ANCAs bind to in the glomerulus?
monocytes –> activates them to become macrophages in the crescents of Bowman’s space (release chemotactic mediators and toxic oxygen metabolites)
Wht type of ANCAs are seen in granulomatosis with polyangiitis?
C-ANCA (diffuse cytoplasmic)- directed at proteinase 3
What is the triad seen in granulomatosis with polyangitis patients?
Kidney problems
Lung problems
Pharynx problems (ulcers)
Who gets HUS?
children under 5 (sometimes connected with inherited factor H mutation 10%)