The Kidney in Systemic Disease I

Question 1

What are the vascular injury syndromes involving the kidney.

Answer 1

1. Vasculitis
2. Thrombotic Microangiopathy
3. SLE
4. Sclerosis

Question 2

What are the causes of these vascular injuries?

Answer 2

1. Inflammation

2. Loss of Thromboresistance

Question 3

What is the most common cause of vasculitis?

Answer 3

Auto-immune

Question 4

What do vasculitis normally result in?

Answer 4

Renal infarcts and distal glomerular ischemia.

Question 5

What is the result of Distal glomerular ischemia?

Answer 5

DECLINE IN GFR NOT ASSOCIATED WITH GLOMERULAR INFLAMMATION OR RBC CASTS

Question 6

What do Wegner’s, Churg-Strauss, microscopic polyangiitis cause?

Answer 6

Focal Necrotizing lesions with crescent formation, active urinary settlement and rapid progression of urinary failure.

Question 7

Are small vessel vasculitis ANCA positive?

Answer 7

Yes.

Question 8

Is PAN ANCA positive?

Answer 8

No

Question 9

Does PAN cause glomerulonephritis?

Answer 9

No

Question 10

What does PAN produce?

Answer 10

1. Segmental Transmural necrotizing inflammation

2. Thrombosis that results in renal ischemia or infarction

Question 11

What is anothe common finding in PAN?

Answer 11

Arterial aneurysms (May thrombose or rupture)

Question 12

What is Microscopic polyangiitis associated with?

Answer 12

1. P-ANCA
2. Antibodies against myeloperoxidase (lysosomal enzyme)
3. Involved with the small blood vessels an
4. Causes inflammation in the Kidney

Question 13

What is the difference between Microscopic polyangitis and polyarteritis nodosa?

Answer 13

Microscopic polyangiitis commonly involves kidneys, causing glomerulonephritis whereas polyarteritis nodosa causes macroscopic areas of ischemia and infarction.

Question 14

What are some of the accompanying symptoms of Pauci-immune crescentic glomerulonephritis?

Answer 14

1. Athralgias (joint pain)
2. Arthritis (joint inflammation)
3. Myalgias (muscle pain)
4. Fatigue
5. Flu-like symptoms usually preceed ANCA associated vasculitis (crescentic glomerulonephritis)

Question 15

How are ANCA diagnosed?

Answer 15

By indirect immunofluorescence microscopy on alcohol-fixed neutrophils incubated with patient serum and then reacted with fluorescein-labeled polyspecific anti-human immunoglobulin

Question 16

What is the most specific test for C-ANCA?

Answer 16

Enzyme-linked immunosorbant assays for detecting autoantibodies against protinase 3 (a serine protease in neutrophil cytoplasmic granules)

Question 17

What is the test for P-ANCA?

Answer 17

Enzyme-linked immunosorbant assays for detecting antibodies against myeloperoxidase.

Question 18

Whaen both P-ANCA and anti-myeloperoxidase antibodies are detected what does that suggest?

Answer 18

Microscopic polyangiitis.

Question 19

What is the pathology behind P-ANCA?

Answer 19

Antibodies bind to proteinase 3 preventing its degradation/inactivation by Alpha-1-trypsin while retaining protease activity at different molecular sites.

Question 20

What happens when ANCAs bind to neutrophils?

Answer 20

Neutrophils become activated and adhere to endothelialcells by Beta-2-integrin, Mac-1 and Fc-gamma, these immune complexes are injurious to endothelial cells

Question 21

What role does protinase 3 play in endothelial injury?

Answer 21

Digests endothelial surface components resulting in endothelial lysis

Question 22

Through what pathway do neutrophils activated by ANCA activate the complement pathway?

Answer 22

Alternative pathway

Question 23

What other cells do ANCAs activate?

Answer 23

Monocytes.

Question 24

Where do ANCAs do their damage?

Answer 24

ANCAs are pathogenic and cause endothelial cell injury in glomeruli and blood vessels.