modified glomerular pathology-2 nephritic syndrome€¦ · 1- membranoproliferative...
TRANSCRIPT
![Page 1: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/1.jpg)
Glomerular pathology-2Nephritic syndrome
Dr. Nisreen Abu Shahin
1
Modified by Nour Hussein
![Page 2: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/2.jpg)
2
The Nephritic Syndrome• Pathogenesis: inflammation• proliferation of the cells in glomeruli &
leukocytic infiltrate → • Injured capillary walls Æ escape of RBCs
into urine →↓ GFR → • oliguria, fluid retention, and azotemia. • Hypertension (a result of both the fluid
retention and some augmented renin release from kidneys).
mm of glomeruluscontentsendothelial mesangio epithelial
Decrease run acreatinine9Blood Unea
Higherlevelof damage will effect majorfunctionsof glomermulus Glomerulo
filtrationRateGER
![Page 3: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/3.jpg)
3
NotsereneNephrotic73.5
Presentingsymptom
clumpsi durineoutputEdema
![Page 4: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/4.jpg)
Glomerular diseases mostly presenting with Nephritic
syndrome
4
![Page 5: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/5.jpg)
5
1- Membranoproliferative Glomerulonephritis (MPGN )
• Abnormal proliferation of glomerular cells• Usually nephritic syndrome; others have a
combined nephrotic-nephritic picture. • Types of MPGN:
1-type I (80% of cases)Æ immune complex disease (The inciting antigen is not known)
2-type II Æ excessive complement activation
Type 111 also exist but will not be included in our material
![Page 6: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/6.jpg)
6
Type I MPGN• circulating immune complexes• Many associations :hepatitis B and
C; SLE; infected A-V shunts.
reach the kidney and cause deposition in the membrane but
will cause elicit in the reaction causing activation of immuneresponses inside glomeruli leading to Nephritic syndrome cascade
![Page 7: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/7.jpg)
7
Type II MPGN (dense-deposit disease)• Cause: excessive complement
activation• autoantibody against C3 convertase
called C3 nephritic factor (it stabilizes the enzyme and lead to uncontrolled cleavage of C3 and activation of the alternative complement pathway).
• Result: Hypocomplementemia
DDD
AC3 Tactivation Tcleavage
1 Less of complement from the blood2 Accumulation of complement in glomeruli
![Page 8: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/8.jpg)
8
• Morphology• LM • both types of MPGN are similar by LM. • glomeruli are large with accentuated lobular
appearance and show proliferation of mesangial and endothelial cells as well as infiltrating leukocytes
• GBM is thickened (double contour or "tram track" )
• The tram track appearance is caused by "splitting" of the GBM
![Page 9: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/9.jpg)
9
silver stain -double contour of the basement membranes("tram-track" ) that is characteristic of (MPGN)(arrows).
Appear as two
silver stainGBM Black
![Page 10: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/10.jpg)
10
• IF• Type I MPGNÆsubendothelial electron-
dense deposits (IgG and complement C1q and C4)
• Type II MPGNÆ C3 alone in GBM
Positive
![Page 11: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/11.jpg)
11
EM- dense deposits in the basement membrane of MPGN type II in a ribbon-like mass (arrows)
![Page 12: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/12.jpg)
12
• Clinical Course• prognosis poor. • No remission.• 40% progress to end-stage renal failure. • 30% had variable degrees of renal insufficiency.• Dense-deposit disease (type II) has a worse
prognosis.• It tends to recur in renal transplant recipients
mm mmTreatmentProblem is
with theimmunesystem notwithkidney
![Page 13: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/13.jpg)
13
2- Acute Postinfectious (Poststreptococcal) Glomerulonephritis (PSGN)
• deposition of immune complexes + proliferation of glomerular cells and leukocytes ( neutrophils).
• Not direct infection of the kidney
• Causes: infection of pharynx or skin• poststreptococcal GN (most common).• Infections by other organisms as pneumococci
and staphylococci
Ab against strep kidney inflammation abnormal
![Page 14: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/14.jpg)
14
Poststreptococcal GN
• 1-4 wks after recovery from a group A streptococcal infection (pharynx or skin).
• Afew strains (3%)of β-hemolytic streptococci are capable of this
• Mechanism: binding of immune complexes or antibodies to bacterial antigens “planted” in the GBM
![Page 15: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/15.jpg)
• LM• proliferation of endothelial and mesangial
cells and neutrophilic infiltrate.• IF• deposits of IgG and complement within
the capillary walls • EM• immune complexes “subepithelial
"humps" in GBM.
15
![Page 16: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/16.jpg)
16
PSGN: increased epithelial, endothelial, and mesangial cells as
well as neutrophils in and around the capillary loops (arrows)
![Page 17: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/17.jpg)
17
g preferable Location
![Page 18: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/18.jpg)
18
PSGN- Clinical Course• acute onset .• fever, nausea, and nephritic syndrome. • gross hematuria.• Mild proteinuria. • Serum complement levels are low
during the active phase of the disease.• ↑serum anti-streptolysin O antibody
titers.• Recovery occurs in most children.
CBC
Treveri though infection is over Post Ab take time tobe lost from the circulation
![Page 19: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/19.jpg)
19
3- IgA Nephropathy
• one of the most common causes of recurrent microscopic or gross hematuria
• children and young adults.• hematuria 1 or 2 days after nonspecific
upper respiratory tract infection. • hematuria lasts several days and then
subsides and recur every few months.
Most common on mucosal surfaces
![Page 20: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/20.jpg)
20
Pathogenesis• abnormality in IgA production and clearance.
• LM: variable• IF: mesangial deposition of IgA with C3• EM: deposits in the mesangium
extra slaysLonger d
![Page 21: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/21.jpg)
21
IF : IgA mesangial staining. Positive
![Page 22: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/22.jpg)
22
Rapidly Progressive (Crescentic) Glomerulonephritis
Dr Stopped here in the video
![Page 23: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/23.jpg)
23
• characterized by the presence of crescents(crescentic GN).
• proliferation of the parietal epithelial cells of Bowman's capsule in response to injury and infiltration of monocytes and macrophages
• nephritic syndrome rapidly progresses to oliguria and azotemia.
Rapidly Progressive (Crescentic) Glomerulonephritis
![Page 24: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/24.jpg)
24
Crescentic GN (PAS stain). the collapsed glomerular tufts and the crescent-shaped mass of proliferating cells and leukocytes internal to Bowman's capsule.
![Page 25: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/25.jpg)
25
• a group of hereditary glomerular diseases caused by mutations in GBM proteins (most common X-linked).
• Most important type: Alport syndrome
Hereditary Nephritis
![Page 26: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/26.jpg)
26
• Alport syndrome nephritis + nerve deafness + eye disorders (lens dislocation, posterior cataracts,corneal dystrophy).
• Pathogenesis:• Mutation of any one of the α chains of type IV collagen• renal failure occurs between 20- 50 yrs of age
• EM• GBM thin and attenuated• GBM later develops splitting and lamination "basket-
weave" appearance
![Page 27: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/27.jpg)
27
Basket weave GBM in Alport syndrome
![Page 28: Modified Glomerular pathology-2 Nephritic syndrome€¦ · 1- Membranoproliferative Glomerulonephritis (MPGN) Abnormal proliferation of glomerular cells Usually nephritic syndrome;](https://reader036.vdocument.in/reader036/viewer/2022082803/605c609129d2c7668c2351b7/html5/thumbnails/28.jpg)
28
Disease Presentation
Age LM IF EM Prognosis
MCD nephrotic Children none negative Effaced foot processes
good
FSGS nephrotic adults Segmental sclerosis negative Effaced foot processes
Poor?
MNP nephrotic adults Thickened GBM IgG+ C3+ Sub-epithelial spikes and domes
Poor?
MPGN-type1 Nephritic/ nephrotic
adults Tram track Ig s Subendothelial deposits
poor
MPGN-type2 Nephritic/ nephrotic
adults Tram track C3+ Dense deposits poor
IgA nephropth nephritic Children, young adults
variable IgA+ Mesangial deposits variable
PSGN nephritic children hypercellularity IgG+ C3+ Subepithelialdeposits (humps)
good
Alport syndrome
hematuria, hearing loss
children variable negative Basket weave GBM poor