Renal (Glomerular Disease Ii)

Front 1

what are the two types of primary glomerular diseases?

name causes in each group.

Back 1

Nephritic: "PIC"
Post Infectious GN
IgA Nephropathy
Crescentic (Rapidly
Progressive) GN

Nephrotic: "MFMM"
Minimal Change Disease
Focal Segmental
Glomerulosclerosis
Membranous GN
Membranoproliferative GN

Front 2

what is post-infectious GN and what is its pathophysiology?

Back 2

type of GN that occurs after streptococal (usually Group A) infection (though other infections can cause it too); usually occurs in children.

pathophysiology =
Antibody response to certain streptococcal antigens --> Circulating immune complexes Localization in glomeruli --> Activate the complement system

Front 3

what are the two major antigens implicated in post-infectious GN?

Back 3

exotoxin B and endostreptosin

Front 4

what is the dx triad of post-infectious GN

Back 4

nephritic syndrome + positive streptozyme test + low C3 levels

(don't usually do renal biopsy, unless severe/persisitent case)

Front 5

what is the prognosis of post-infectious GN?

Back 5

usually reversible after offending antigen subsides; self-limited dz and pts usually get better spontaneously without specific therapy (95%)

Front 6

what is IgA nephropathy?

Back 6

proliferative glomerulonephritis with constant presence of IgA immune depositis and C3 in mesangium; requires renal biopsy

Front 7

what is the pathogenesis of IgA nephropathy?

Back 7

IgA containing immune complexes deposit in mesangium --> activation of mesangial cells via Fc alpha receptos --> cell proliferation and matrix expansion

Increased mucosal IgA immune response to oral antigen challenge --> Antigens gaining access to the circulation --> Profound bone marrow IgA response --> IgA containing circulating immune complexes.

also, the clearance of these IgA containing immune complexes bc there is an abnormality (IgA molecule lacks galactose)--> Poor clearance via the sialoglycoprotein receptors for IgA in the liver --> High levels of circulating complexes --> Glomerular deposition

Front 8

on EM, you see deposits primarily in the mesangial areas, what condition do you think of?

Back 8

IgA nephropathy

Front 9

what is the most common type of acute GN world wide?

Back 9

IgA nephropathy

Front 10

what's the clinical presentation of IgA nephropathy?

Back 10

asymptomatic hyematuria, non-nephrotic proteinuria, mildly reduced renal fxn (so mild glomerular changes)

if more severe glomerular changes, will have gross hematuria with red cell casts

Front 11

what is the only nephritis that needs a renal biopsy to make a diagnosis?

Back 11

IgA nephropathy

Front 12

what is crescentic GN?
what are the 3 major subtypes?
Which one typically does NOT have crescent formation?

Back 12

proliferation of parietal epithelial cells (leading to histologic feature -- crescent formation) with a common clinical presentations, i.e. severe nephritic syndrome, acute renal failure, rapid development of end-stage renal disease (Rapidly progressive GN).


types:
-Immune mediated crescentic GN
-Anti-GBM antibody mediated crescentic GN
-ANCA mediated crescentic GN


crescents rarely develop in immune mediated crescentic GN

Front 13

what is Anti-GBM nephritis?

Back 13

auto-Ab develops to NC1 domain of collagen type IV of glomerular BM (this activates complement, inflammatory cell infiltration, leading to glomerular injury); usually appear as crescentic GN, associated with sever, rapidly progresive renal failure

this disease may be renal-limited or may be accompanied by pulmonary hemorrhage (Goodpasture's syndrome)

Goodpasture = this is bc the auto-Abs can also be directed against alveolar BM....

Front 14

T or F. ANCA-mediated crescentic glomerulonephritis is a type of immune-mediated type.

Back 14

F it is "idiopathic" -- no one knows why ANCA is released

Front 15

in ANCA-mediated crescentic GN, what 2 molecules inside the cytoplasm of neutrophils?

Back 15

-proteinase 3 (C-ANCA)
-myeloperoxidase (P-ANCA)

during infection, somehow these cytoplastic molecules are exported onto surface of neutrophils and now the Abs can bind to them

Front 16

what is minimal change dz?

Back 16

T cell- derived circulating permeability factor that directly damage the podocytes and the permeability barrier --> effacement of podocyte foot processes

one etiology may be mutation of nephrin (slit diaphragms)

Front 17

is renal biopsy needed for children with minimal change dz? in adults?

Back 17

no, if a child has NS, it's usually due to minimal change dz (90%)

yes in adults, bc there are so many other causes of nephrotic syndrome (and MCD is just 10%)

Front 18

why is important to dx the etiology of MCD?

Back 18

bc it's importatnt to tx the etiology and can lead to reverse of MCD

Front 19

what is the most common cause of nephrotic syndrome in adults?

Back 19

focal segmental glomerulosclerosis (FSGS) -- this is sclerosis of some, but not all glomeruli (focal) and in only a portion of these glomeruli are involved (segmental)

note: proteinuria is global and diffuse and involves all glomerular capillaries (this is what actually happens, compared to what you see on LM)

Front 20

what is primary "idiopathic" FSGS caused by?

Back 20

circulating factor that causes direct injury to podocytes

when FSGS is assoc with other conditions, these conditions may induce podocytic injury (ie. HIV, obesity inc glom blood flow and stretches podocytes)

Front 21

most common cause of nephrotic syndrome in Blacks and young adults (20-40 y/o)

Back 21

focal segmental glomerulosclerosis (it can also develop from MCD in children who are steroid resistant)

Front 22

unlike MCD, pts with FSGS have what clinical features?

Back 22

FSGS shows both nephrotic and nephritic sx's (HTN, microhematuria, decreased renal function)

Front 23

what is the antigen that creates electron dense deposits in Membranous nephropathy?

Back 23

The molecule responsible is (in the rat) MEGALIN.

recent = Phospholipase A2 receptor on podocyte cell membrane are now recognized as the target antigen for membranous nephropathy. Someday, you won’t need to take renal biopsy.

Front 24

what kind of cell proliferation characterizes crescentic GN?

3 kinds of crescentic GN?

which one(s) will show immune deposits on EM?

Back 24

parietal epithelial cell proliferation (exocapillary cell proliferation)

- immune-mediated, anti GBM, and ANCA-mediated

- only immune mediated will show immune deposits on EM

Front 25

T or F. crescents often form in immune-mediated GN

if true (or false), what does crescent represent in immune-mediated GN?

Back 25

false

if crescent develops, represents rapidly progressing dz

Front 26

tx:
- post-infectious
- IgA nephropathy
-crescentic GN

Back 26

post-infectious --> underlying infection
IgA nephropathy --> no specific Tx
crescentic GN ---> immunosuppression (cyclophosphamide + steroids)

Front 27

why is early diagnosis important in anti-GBM mediated crescentic GN?

Back 27

if you tx aggressively with steroids, immunosuppressive agents and plasma exchange increases chance of renal survival

Front 28

what do you have to deal with before kidney transplant to severe anti-GBM patients?

Back 28

tx with immunosuppressives to get rid of all the anti-GBM Ab's (otherwise youll get recurrence of the dz even with transplant)

Front 29

T or F. most cases of minimal change dz are primary and "idiopathic."

Back 29

true (this means they are not associated with any other dz's)

Front 30

what is the antigen implicated in membranous nephropathy? hint: found in rats

Back 30

-megalins!

Front 31

what is the histologic pattern found in membranoproliferative GN?

how does it show up clinically?

Back 31

MPGN =
- glomerular cell proliferation (usually mesangial)
- leukocyte infiltration
- GBM thickening due to circumferencial mesangial interposition

clinically show up with nephrotic syndrome (some with nephritic syndrome)

Front 32

which glomerular dz is characterized clinically by both nephrotic and nephritic sx's?

Back 32

focal segmental glomerulosclerosis (FSGS)

nephrotic syndrome + nephritis (HTN, microhematuria, decreased renal fxn)

Front 33

what is membranous nephropathy?

Back 33

an immune mediated glomerular disease associated with immune complex deposits in the subepithelial space (between the podocytes and GBM).

most cases are primary "idiopathic" and this is autoimmune mediated by an Ab directed against an antigen (megalin --- in rats) on the podocytes themselves

Front 34

immune complexes form in membranous nephropathy b/w auto-Ab's and megalin in subepithelial space.

do these complexes activate complement system?

what about inflammatory cell infiltrates?

Back 34

yes (Glomerular capillary injury probably due to a direct toxic effect of the membrane attack complex C5b-C9 --> Direct injury to the podocytes Release from these cells mediators (proteases and oxygen-free radicals) to further damage the glomerular basement membrane)

No inflammatory cell infiltrates

Front 35

what is the most common cause of nephrotic syndrome in older adults?

Back 35

membranous nephropathy (presents most commonly with nephrotic syndrome + edema)

Front 36

what are the 2 types of MPGN, explain a little.

Back 36

1) MPGN type I (associated with immune complex deposits, common)

2) MPGN type II ("dense deposit disease" assoc with complement activation in the absence of immune deposits, very rare)

so most MPGN is type I!!

Front 37

what is the most frequent dz associated with membranoproliferative GN?

Back 37

hepatitis C (pt will have HCV and RNA present in circulation, so you can test for it)

- if pts have hep C-associated MPGN, they may respond well to anti-viral therapy with alpha interferon +/- ribavirin