The Kidney in Systemic Disease I Flashcards
What are the vascular injury syndromes involving the kidney.
- Vasculitis
- Thrombotic Microangiopathy
- SLE
- Sclerosis
What are the causes of these vascular injuries?
- Inflammation
2. Loss of Thromboresistance
What is the most common cause of vasculitis?
Auto-immune
What do vasculitis normally result in?
Renal infarcts and distal glomerular ischemia.
What is the result of Distal glomerular ischemia?
DECLINE IN GFR NOT ASSOCIATED WITH GLOMERULAR INFLAMMATION OR RBC CASTS
What do Wegner’s, Churg-Strauss, microscopic polyangiitis cause?
Focal Necrotizing lesions with crescent formation, active urinary settlement and rapid progression of urinary failure.
Are small vessel vasculitis ANCA positive?
Yes.
Is PAN ANCA positive?
No
Does PAN cause glomerulonephritis?
No
What does PAN produce?
- Segmental Transmural necrotizing inflammation
2. Thrombosis that results in renal ischemia or infarction
What is anothe common finding in PAN?
Arterial aneurysms (May thrombose or rupture)
What is Microscopic polyangiitis associated with?
- P-ANCA
- Antibodies against myeloperoxidase (lysosomal enzyme)
- Involved with the small blood vessels an
- Causes inflammation in the Kidney
What is the difference between Microscopic polyangitis and polyarteritis nodosa?
Microscopic polyangiitis commonly involves kidneys, causing glomerulonephritis whereas polyarteritis nodosa causes macroscopic areas of ischemia and infarction.
What are some of the accompanying symptoms of Pauci-immune crescentic glomerulonephritis?
- Athralgias (joint pain)
- Arthritis (joint inflammation)
- Myalgias (muscle pain)
- Fatigue
- Flu-like symptoms usually preceed ANCA associated vasculitis (crescentic glomerulonephritis)
How are ANCA diagnosed?
By indirect immunofluorescence microscopy on alcohol-fixed neutrophils incubated with patient serum and then reacted with fluorescein-labeled polyspecific anti-human immunoglobulin
What is the most specific test for C-ANCA?
Enzyme-linked immunosorbant assays for detecting autoantibodies against protinase 3 (a serine protease in neutrophil cytoplasmic granules)
What is the test for P-ANCA?
Enzyme-linked immunosorbant assays for detecting antibodies against myeloperoxidase.
Whaen both P-ANCA and anti-myeloperoxidase antibodies are detected what does that suggest?
Microscopic polyangiitis.
What is the pathology behind P-ANCA?
Antibodies bind to proteinase 3 preventing its degradation/inactivation by Alpha-1-trypsin while retaining protease activity at different molecular sites.
What happens when ANCAs bind to neutrophils?
Neutrophils become activated and adhere to endothelialcells by Beta-2-integrin, Mac-1 and Fc-gamma, these immune complexes are injurious to endothelial cells
What role does protinase 3 play in endothelial injury?
Digests endothelial surface components resulting in endothelial lysis
Through what pathway do neutrophils activated by ANCA activate the complement pathway?
Alternative pathway
What other cells do ANCAs activate?
Monocytes.
Where do ANCAs do their damage?
ANCAs are pathogenic and cause endothelial cell injury in glomeruli and blood vessels.
