Summary Slides and Pics Nephritis Flashcards
Membranoproliferative Glomerulonephritis
- Presentation?
- Cause
- Laboratory Marker?
Membranoproliferative glomerulonephritis
Presentation
• may present with Hematuria
• non-nephrotic Range Proteinuria
• Nephrotic Syndome
• Acute Nephritic Syndrome
• RPGN
Cause
• Often associated with HEPITITIS C in adults (sometime hep B)
• Ideopathic
Laboratory
• Associated with low C3
Membranoproliferative Glomerulonephritis
• Changes on LM, IF, and EM
LM:
• Hypercellularity duplication of the GBM with double contour appearance
IF:
• Complement Deposition in a rim pattern outlining the glomerular capillary wall
EM:
• Type I Thickening of the Glomerular capillary wall
• DDD (type II membranoproliferative) = Ribbon-like appearance of subendothelial and intramembranous material
IgA Nephropathy
• Prevlance
• Pathogensis
• part of glomerulus affected
IgA Nephropathy
Prevalence:
• Most common glomerulonephritis worldwide
Location:
• MESANGIUM
Pathogenesis:
• Aberrent Glycosylation of IgA hinge region leading to auto-antibody formation against IgA
IgA Nephropathy
• what would you expect to see on LM, IF, and EM?
LM:
• Variable, may see mesangial Expansion
IF:
• Dominant or Co-dominant deposition of IgA
EM:
• Mesangial Deposits
Anti-GBM disease (Goodpasture’s)
• pathogenesis
• Key finding on biopsy?
• Rapid Development of Renal Failure due to AUTOANTIBODIES binding to the noncollagenous portion of the alpha-3 subunit of type IV collagen
• IF = LINEAR PATTERN
Hereditary Nephritis (Alport’s syndrome)
• pathogenesis
• key finding on biopsy
Alport’s
• Defects in alpha-5 type IV collagen
Biopsy = EM = Abnormally thin basement membranes with splintering of the lamina desna causing a Basket Weave Appearance
What nephritic disease affects the tissue in blue?
• nephritic disease that affects tissue in green?
Blue:
• IgA nephropathy
Green:
• Membranoproliferative glomerulonephritis
What nephritic disease(s) is this image indicative of?
• Key features?
• Membranoproliferative Glomerulonephritis and Dense Deposit Disease
Key Features:
- The glomeruli are large and lobular
- Cell proliferation – mesangial, endothelial and leukocytes.
- The GBM is thickened
What changes can be observed between the glomeruli shown here? (normal on the left)
- GBM thickenening
- Increased Cellularity
- If this were zoomed out you would also see that these glomeruli are large and lobular
Diagnosis?
• explain the appearance of the glomerulus shown here.
• This disease may be secondary to what other disease?
• Key lab Findings?
Membranoproliferative Glomerulonephritis TYPE I
- Glomerular appearance = TRAM TRACKS, this is due to mesangial cells trying to eat immune complexes in the SUBENDOTHELIUM
- May be secondary to Hepatitis C infection
- C3 levels are often LOW/Depleted in these patients
What is happening here?
• what would you expect to see on immunofluorscence of this biopsy?
Mesangial Cell has penetrated into Subendothelium to scavenge immune deposits
This is TYPE 1 Glomerulonephritis so patient will have Immunofluorescence for C3 in a GRANULAR PATTERN
What key marker can be used to help differentiate between Type I and Type II (aka Dense deposit disease) MembranoPROLIFERATIVE Glomerulonepthris?
- C3 nephritic factor that STABILIZES C3 convertase = key finding
- Shown here is dense deposit disease, notice more of a ribbon appearance on the EM
Is Membranoproliferative GN Type I or Type II shown here?
This is MPGN type II aka Dense Deposit Disease - notice bright specs.
Below is a picture of MPGN type I - more evenly granular appearance
Describe the major differences between the appearance of the disease shown on the right and the one shown on the left.
Left: MPGN type I, you can see splitting of the subendothelium
Right: Dense Deposit Disease, you can see deposits in the subendothelium, but they do not evenly split the membrane like in type I
What disease may have lead to this appearance on H and E considering the patient had low serum C4.
• Mediating antibody type?
Hepatitis C may have caused Membranoproliferative Glomerulonephritis. MPGN is associated with high MONOCLONAL IgM levels.
CHRONIC high levels of monoclonal IgM may lead to MULTIPLE MYELOMA
Other than looking for C3 nehpritic factor, how could you differentiate MPGN type I and type II on the basis of complement?
Type I - associated with CLASSICAL COMPLEMENT so you would expect C4 depletion
Type II - is associated with alternative complment so you would see a more rapid depletion of C3
What disease is shown here? KEY features?
• would you expect there to be elevated levels of inflammatory proteins in the serum? if so which ones?
IgA Nephropathy
IgA may or MAY NOT be elevated in the serum so don’t bank on that (its 50% chance)
Key feature here is proliferation of the MESANGIUM this is shown by increased black color on the Silver Stain
Shown below is what a normal silver stain looks like
T or F: immune mediated diseases of the glomeruli most often lead to Nephritis rather than nephrotic syndrome.
True, INFLAMMATION means its a nephritic condition
T or F: increased cellularity is a feature you should look for in all immune mediated nephropathies.
True, these will be inflammatory processes so you should definetly see increased cell numbers
What is the ONLY antibody that could be mediating that this immunofluorescent dye could be oriented against? why?
IgA - the dye is concentrated in the mesangium, IgA nephropathy is the only one where you see Mesangial Antibody deposits
What is shown here?
• Risk factor for this pathology?
Electron Dense Deposits in the mesangium indicative of IgA nephropathy aka Berger’s disease (associated with smoking)
What disease is shown here?
• what antibodies might you look for in this person?
• is this primarily a kidney disease?
This is a Rapidly Progressing Glomerulonephritis resulting from Goodpasture’s Syndrome. This is PRIMARILY a kidney disease with some respiratory involvement. In contrast Wegner’s is a respiratory disease with some kidney involvment.
****NOTE: you know that this is a rapidly progressing glomerulonephritis because CRESENT proliferation is pushing down on the glomerulus
What is seen here?
• disease most commonly associated with this pattern?
- wire loops are seen here
- Lupus associated, but you also see cresents starting to form which is suggestive of RPGN
What disease PROCESS is shown here?
This is how crescent formation looks on Silver stain
How is this disease aqcuired?
• Key EM features?
• KEY clinical features to pick up on?
Here you see basket weaving indicative of ALPORT syndrome which is acquired via X-LINKED inheritance
KEY clinical features: ASSOCIATED WITH HEARING LOSS and OCULAR DISTURBANCES
