PATH: Kidney in Systemic Disease I

Question 1

Microscopic polyangitis is associated with what?

Answer 1

P-ANCA (antibodies against myeloperoxidase)

Question 2

Small vessel vasculitis usually causes what type of glomerulonephritis?

Answer 2

pauci-immune crescentic (have few Abs or ICs but lots of ANCAs)

Question 3

What are the thrombotic microangiopathies?

Answer 3

HUS

TTP

Question 4

Before ANCA-associated glomerulonephritis occurs, what sort of symptoms can occur?

Answer 4

extrarenal symptoms: joint pains, muscle aches, flu-like symptoms

Question 5

Where do ANCAs act in the glomerulus?

Answer 5

cause ENDOTHELIAL injury in glomeruli and blood vessels

Question 6

What normally happens when neutrophils release proteinase 3?

Answer 6

circulating alpha-1 antitrypsin rapidly breaks it down

Question 7

What can increase the surface expression of proteinase 3 and MPO on the surface of the neutrophil?

Answer 7

TNF-alpha and IL-8 (synergistic inflammatory event)

Question 8

If C-ANCA is present, what happens to neutrophils coated with proteinase 3?

Answer 8

the ANCA “coats” the proteinase 3 and “hides” it from alpha-1 antitrypsin

Question 9

What happens when ANCAs bind to neutrophils?

Answer 9

they are activated and adhere to endothelial cells by beta-2 integrins, MAC-1, and Fc-Gamma

Question 10

What type of complement pathway is activated by ANCA/neutrophil binding to endothelium?

Answer 10

alternative pathway

Question 11

What is the overall result of the ANCA/neurtophil binding to the endothelium?

Answer 11

endothelial surface damage, ADCC, internalization of MPO adn proteinase 3 –> apoptosis

Question 12

What else can ANCAs bind to in the glomerulus?

Answer 12

monocytes –> activates them to become macrophages in the crescents of Bowman’s space (release chemotactic mediators and toxic oxygen metabolites)

Question 13

Wht type of ANCAs are seen in granulomatosis with polyangiitis?

Answer 13

C-ANCA (diffuse cytoplasmic)- directed at proteinase 3

Question 14

What is the triad seen in granulomatosis with polyangitis patients?

Answer 14

Kidney problems
Lung problems
Pharynx problems (ulcers)

Question 15

Who gets HUS?

Answer 15

children under 5 (sometimes connected with inherited factor H mutation 10%)

Question 16

What is the clinical triad of HUS?

Answer 16

Microangiopathic hemolytic anemia, thrombocytopenia, acute kidney injury

Question 17

What is the underlying cause of HUS?

Answer 17

Complication of an intestinal infection with E Coli (H7:O157) that produces Shiga Toxin and changes ednothelium to a pro-coagulant state

Question 18

What is the main form of treatment for HUS?

Answer 18

blood transfusion (80%), dialysis (60%), Eculizumab (10%)

Question 19

What causes TTP?

Answer 19

deficiency (or antibody formed during pregnancy, infection, malignancy) against ADAMTS13

Question 20

What does ADAMTS13 do?

Answer 20

von-Willegrand factor-cleaving protease that cleaves and inactivates it to prevent interaction with platelets

Question 21

What does a mutation in ADAMTS13 do?

Answer 21

allows vWF to uncontrollably activate platelet aggregation and causes systemic microvascular thrombosis

Question 22

What are the symptoms of TTP?

Answer 22

FAT RN

Question 23

What is the treatment for TTP?

Answer 23

plasmapheresis

Question 24

What is the most severe form of lupus?

Answer 24

type IV (diffuse proliferative)

Question 25

What is the most common form of lupus?

Answer 25

type IV (diffuse proliferative)

Question 26

What Abs are postiive in Lupus?

Answer 26

Anti-DNA, Anti-Sm

Question 27

What does IF look like of a lupus glomerulus?

Answer 27

"Full House" where IgG, IgM, IgA, C3, and C4 are all positive

Question 28

What is scleroderma?

Answer 28

systemic sclerosis (CT and microvascular disease with fibrosis and vascular occlusion)

Question 29

What are the symptoms of limited cutaneous SS?

Answer 29

severe Raynaud's, ulcers, gangrene, NO renal involvement

Question 30

What type of SS has renal involvement?

Answer 30

Diffuse cutaneous SS

Question 31

What are the s/s of diffuse cutenaous systemic sclerosis?

Answer 31

fatigue/weight loss, skin tight and thick, renal mainfestations, myalgia

Question 32

What is a scleroderma renal crisis?

Answer 32

new-onset of accelerated HTN and/or rapidly progressive oliguric renal failure

Question 33

How do you treat a scleroderma renal crisis?

Answer 33

ACE inhibitors

Question 34

What is the pathology of SS?

Answer 34

Arcuate arteries have intimal/medial proliferation and luminal narrowing (onion skinning of interlobar arteries) - Get fibrinoid necrosis and thrombosis - Vascular changes--> poor outcome