10. Path of Glomerular Disease Flashcards
which cells of the glom filter particles by both size and charge?
podocytes, via the diaphragm across the filtration slit. Basement membrane also filters by charge and size. Endothelial cells (capillary) only filter by size.
which cells in the glomerulus have negative charges?
both epithelial/podocytes and the endothelial capillary wall
Type IV collagen is impt to which component of the glomerulus?
major component of the basement membrane. triple helical alpha molecules, in dimers or tetramer formations
hereditary mutation in alpha chains of Type IV collagen leads to what disease?
Alport syndrome
Filtration governed by what 4 factors?
size, charge, shape/flexibility of cells, hemodynamic forces
most cases of glomerulonephritis involve what kind of mechanisms?
immune. deposits of immunoglobulins found in 70% of all GN patients
what are the 2 major forms of Ab-associated injury?
-in situ -circulating immune complex nephritis
what kind of injury is anti-GBM nephritis?
in situ, ab-associated injury
what kind of injury is membranous GN?
in situ, ab-associated injury
anti-GBM nephritis: antibodies are directed against what?
antigens intrinsic to the GBM
Anti-GBM nephritis: where do immune complexes form and congregate?
in the GBM
Anti-GBM: what kind of staining on IF?
linear
Goodpasture’s is associated with which nephritis? mechanism?
associated with Anti-GBM nephritis. the Anti-GBM antibodies cross-react with alveolar BMs in lung and can lead to hemorrhage
membranous GN: where do immune complexes form and deposit?
on the foot process: deposit on the sub epithelial (podocyte) side of the BM
circulating immune complex nephritis: what is seen on EM?
deposits in mesangium and/or sub epithelium.
circulating immune complex nephritis: what is pattern of complex deposition?
granular
what is EM good to look for?
immune complex deposits, podocyte changes (effacement), GBM changes (microfibrils, thinning)
4 characteristics of nephrotic disease?
proteinuria, hypoalbuminemia, edema, hypercholesterolemia
if a child has nephrotic sx, what is it likely to be?
minimal change disease
minimal change disease: appearance on light microscopy?
normal
minimal change disease: appearance on IF?
normal/negative
minimal change disease: appearance on EM?
widespread effacement of podocytes
minimal change disease: severity? treatment?
benign. responds to steroids
FSGS: how to differentiate from minimal change?
10% of glomeruli will have segmental sclerosis (areas of cap collapse, expanded mesangium)
FSGS: appearance on light micro?
focal, segmental cap collapse and sclerosis
FSGS: appearance on IF?
normal/negative
FSGS: appearance on EM?
moderately widespread effacement of podocytes
if a child is thought to have MCD and does not respond to steroids, what is the likely disease?
FSGS
membranous GN: where are immune deposits?
subepithelial deposits in capillary wall, which evolve over time as body tries to re-sorb them
membranous GN: appearance of GBM?
may see spikes and holes of GBM
membranous GN: appearance on EM?
subepi deposits with spike/fringe projections, eventual incorporation into BM (4 stages)
membranous GN: appearance on IF?
granular pattern along the GBM (IgG and C3)
membranous GN: what are 4 stages?
-small numerous deposits on BM -BM sends out projections between deposits -individual spikes surround deposits -deposits incorporated into thickened BM
diabetic nephrosis: appearance on light micro?
early on: glomerular hypertrophy, thickened GBM, mesangial sclerosis later: advancement of the above, K-W nodules, micro aneurisms, hyalinization
diabetic nephrosis: appearance on IF?
negative (no immune complexes) may have linear IgG and albumin in GBM??
diabetic nephrosis: appearance on EM?
thickened GBM, mesangial sclerosis
amyloidosis: nephrotic or nephritic?
nephrotic
memory trick for the nephrotic diseases?
DAM Fine Man: Diabetes, Amyloid, MembranousGN, FSGS, MCD (all cause proteinuria)
memory trick for the nephritic diseases?
Peeing blood Means Lupus: Postinfectious, Membranoproliferative, Lupus (all cause hematuria)
memory trick for the hematuric diseases?
hemATurIa Alport, Thin bm disease, IgA nephropathy
what unique stains are used to dx amyloidosis?
congo red, polarized light
amyloidosis: appearance with congo red?
salmon-colored glomeruli, nodular
amyloidosis: appearance with polarized light?
apple green birefringence
amyloidosis: appearance with IF?
positive for kappa or lambda light chain
amyloidosis: appearance with EM?
random thin fibrils
amyloidosis: appearance with light micro?
thickened mesangium, thickened cap walls
post-infectious GN: prototypical disease?
post-strep
post-infectious GN: appearance on IF?
granular deposits along GBM, especially C3
post-infectious GN: appearance on EM?
classic sub epithelial hump deposits: almost round
post-infectious GN: cellularity on light micro?
inflammatory cells (PMNs), swollen, hypercellular
Membranoproliferative GN: most common GN associated with what?
Hep C and Hep B
Membranoproliferative GN: appearance on light micro?
proliferative, hypercellular glomeruli with leukocytes gloms often hyperlobulated, with separation between lobules
Membranoproliferative GN: appearance on EM or silver stain?
train track appearance due to duplicated BM, large subendo deposits
Membranoproliferative GN: appearance on IF?
smudgy appearance due to bulky deposits, positive for C3 can be granular or globular
lupus: appearance on EM?
extensive mesangial and peripheral deposits
lupus: appearance on IF?
Full House staining! positive for many different reactants (IgG, IgA, IgM, C3, light chains)
lupus: what is the spectrum of the disease?
6 different classes encompassing wide disease spectrum
Alport disease: appearance on EM?
basket weave pattern on GBM due to fragmentation, splitting
Alport disease: clinical presentation?
hematuria, nerve deafness, ocular abnormalities
Alport: cause of disease?
X linked recessive mutations to collagen type IV
Thin Basement Membrane Disease: Appearance on EM?
generalized thinning of BM, some areas more than others
Alport: progression of disease?
often progresses to ESRD
Thin Basement Membrane Dz: progression?
benign, non progressive
IgA nephropathy: appearance on IF?
positive for IgA staining in the paramesangial area
IgA nephropathy: appearance on EM?
mesangial deposits (mesangial areas have more than 3 nuclei)
most common cause of GN worldwide?
IgA nephropathy. particularly common in asians
Crescentic GN: sign of what?
severe glomerular injury
Crescentic GN: appearance on light micro?
cellular proliferation along inside of Bowman’s capsule, fills part of Bowman’s space
Crescentic GN: what are the three types? what tests distinguish them?
Anti-GBM disease, immune complex mediated disease, Pauci-immune test: IF staining pattern
Crescentic GN with Positive Linear IF: what disease?
Anti-GBM
Crescentic GN with Positive Granular IF: what disease?
Immune complex mediated disease lumpy-bumpy on IF
Crescentic GN with Negative IF: what disease?
Pauci-immune
If Pauci-immune disease, what should I test for? what will results tell me?
test for ANCA (anti-neutrophilic circulating antibodies) if Positive, there is association with systemic vascular disease
Dx?
Amyloid
Dx?
Crescentic GN
dx?
crescentic GN
dx?
DM
dx?
DM
Dx?
DM
dx?
FSGS
dx?
IgA nephropathy
dx?
minimal change disease
dx?
MGN
dx?
MPGN
dx?
MPGN
dx?
PIGN
dx?
PIGN
dx
lupus
