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%)
What is the clinical triad of HUS?
Microangiopathic hemolytic anemia, thrombocytopenia, acute kidney injury
What is the underlying cause of HUS?
Complication of an intestinal infection with E Coli (H7:O157) that produces Shiga Toxin and changes ednothelium to a pro-coagulant state
What is the main form of treatment for HUS?
blood transfusion (80%), dialysis (60%), Eculizumab (10%)
What causes TTP?
deficiency (or antibody formed during pregnancy, infection, malignancy) against ADAMTS13
What does ADAMTS13 do?
von-Willegrand factor-cleaving protease that cleaves and inactivates it to prevent interaction with platelets
What does a mutation in ADAMTS13 do?
allows vWF to uncontrollably activate platelet aggregation and causes systemic microvascular thrombosis
What are the symptoms of TTP?
FAT RN
What is the treatment for TTP?
plasmapheresis
What is the most severe form of lupus?
type IV (diffuse proliferative)
What is the most common form of lupus?
type IV (diffuse proliferative)
What Abs are postiive in Lupus?
Anti-DNA, Anti-Sm
What does IF look like of a lupus glomerulus?
“Full House” where IgG, IgM, IgA, C3, and C4 are all positive
What is scleroderma?
systemic sclerosis (CT and microvascular disease with fibrosis and vascular occlusion)
What are the symptoms of limited cutaneous SS?
severe Raynaud’s, ulcers, gangrene, NO renal involvement
What type of SS has renal involvement?
Diffuse cutaneous SS
What are the s/s of diffuse cutenaous systemic sclerosis?
fatigue/weight loss, skin tight and thick, renal mainfestations, myalgia
What is a scleroderma renal crisis?
new-onset of accelerated HTN and/or rapidly progressive oliguric renal failure
How do you treat a scleroderma renal crisis?
ACE inhibitors
What is the pathology of SS?
Arcuate arteries have intimal/medial proliferation and luminal narrowing (onion skinning of interlobar arteries)
- Get fibrinoid necrosis and thrombosis
- Vascular changes–> poor outcome
