Light micrograph ofa normal glomerulus.There are only 1 or 2 cells
per capillary tuft, the capillary lumens are open, the thickness of the
glomerular capillary wall (long arrow) is similar to that of the tubular
basement membranes (short arrow), and the mesangial cells and
mesangial matrix are located in the central or stalk regions of the tuft
(arrows).
Glomerular diseases associatedwith
nephritic syndrome
Primary
◦ Postinfectious / Diffuse proliferative GN
◦ Membranoproliferative GN
◦ IgA nephropathy
◦ Crescentic GN
Secondary
◦ Systemic vasculitis
◦ SLE
◦ Systemic sclerosis
9.
Classification of glomerulardisease
How many glomeruli?
◦ Focal = only some glomeruli
◦ Diffuse = all glomeruli affected
How much of a single glomerulus?
◦ Segmental = only part of the glomerulus
◦ Global = the entire glomerulus
Primary vs Secondary
◦ primarily renal disease vs renal complication of
systemic disease
Focal nephritic
◦Associated with inflammatory to less than half of
the glomeruli on light microscopy
◦ Red cells – often dysmorphic
◦ Occasional red cell casts
◦ Mild proteinuria (<1.5g/day)
14.
Diffuse nephritic
◦Damage to all or almost all of the glomeruli
◦ Similar to focal disease but may also have
heavy proteinuria (even nephrotic range),
oedema, hypertension and/or renal
insufficiency
- ‘full house’ urinary sediment – red cells, white
cells, red cell casts, white cell casts, hyaline
casts
15.
Nephrotic
◦ Heavyproteinuria
◦ Lipiduria – refractile fat bodies that look like a maltese
cross under polarised light
◦ Few cells
◦ Few casts – but those present are hyaline and granular
Phase contrast microscopy showing
dysmorphic red cells in a patient with
glomerular bleeding.Acanthocytes can be
recognized as ring forms with vesicle-
shaped protrusions (arrows).
16.
Minimal change disease
(Synonyms:MCD, Lipoid Nephrosis, Foot Process
Disease, Nil Deposit Disease)
Diffuse effacement of foot processes of epithelial cells in glomeruli
that appear virtually normal by light microscopy
Commonest cause of nephrotic syndrome in children
Can occur in adults
Causes : Children = Follows a respiratory infection, routine
prophylactic immunization, ingestion of heavy metals, food allergies
Adult =NSAIDs (fenoprofen), Hodgkin lymphoma
Characterised by
◦ Lack of glomerular changes on light microscopy
◦ Lack of immune deposits
◦ Good response to steroids
Pathogenesis
◦ Circulating factor causing damage to podocytes (glomerular epithelial cells)
17.
Glomerulus stained withPAS. Note
normal basement membrane and
absence of proliferation.
Effacement of foot processes
(double arrows), absence of deposits
18.
Diagrammatic representation ofultrastructure of a portion of
glomerular lobule showing diffuse fusion or flattening of foot
processes of visceral epithelial cells (podocytes).The GBM is
normal and there are no deposits
19.
Membranous GN
Commonestcause of nephrotic syndrome in adults
Diffuse thickening of the glomerular capillary wall and
the accumulation of electrondense, immunoglobulin-
containing deposits along the subepithelial side of the
basement membrane
Idiopathic (75%) or secondary (25%) to:
◦ Neoplasms (lung, colon, melanoma)
◦ Autoimmune disease (SLE, thyroiditis)
◦ Infections (Hep B, Hep C, syphilis, malaria)
◦ Drugs (Penicillamine, gold)
• Most common causes worldwide are malaria and
schistosomiasis.
• Age: > 30 yr Sex: male> female
40% progress to chronic renal failure (CRF)
20.
Endogenous antigen:
SLE- self nuclear protein and autoantibodies
Neonatal membranous nephropathy- nutral
endopeptidase antigen and placentally transferred
maternal autoantibodies
Exogenous antigen:
antigen – hep B and treponema pallidum
• Pathogenesis
It is a form of chronic immune complex mediated
disease.
Antigens may be endogenous or exogenous
21.
PAS stain. Notethe marked diffuse
thickening of the capillary wall without
an increase in the number of cells.
Membranous GN, light microscopic
appearance. Glomeruli are
normocellular but the capillary walls
are diffusely thickened due to
duplication of the GBM
22.
Membranous glomerulonephritis,
stageI.The basement membrane
is normal in thickness. Small
sparse subepithelial deposits
(arrows) are separated from the
basement membrane by a thin
clear zone (inset).The epithelial
foot processes are obliterated.
Membranous glomerulonephritis, stage
II. Subepithelial deposits are separated
by projections of the basement
membrane.
23.
Membranous glomerulonephritis, stage
III.The basement membrane is markedly
thickened and the deposits appear
surrounded by a newly formed basement
membrane (arrows).
Membranous glomerulonephritis, stage
IV. The basement membrane is
markedly irregular and most of the
deposits have been reabsorbed, leaving
large electron-lucent areas
24.
Granular immunofluorescent
deposits ofIgG along GBM.
Diagrammatic representation of
ultrastructure of a portion of glomerular
lobule showing subepithelial deposits
of electron-dense material so that the
basement membrane material protrudes
between these deposits
25.
FSGS
Idiopathic orsecondary to:
◦ Other glomerular disease (IgA)
◦ Other renal disease (chronic reflux / pyelonephritis /
interstitial nephritis)
◦ Systemic disorder (HIV)
◦ Drugs (Heroin)
Primary FSGN is the most common cause of nephrotic
syndrome in adults in the US.
Characterised by:
◦ Sclerosis of portions of some, not all glomeruli
◦ Often progresses to chronic renal failure (CRF)
◦ Recurs in 25-50% renal transplants
26.
Light microscopy(LM)
◦ Focal segmental sclerosis
◦ Some normal glomeruli
Immunofluorescence (IF)
◦ IgM and C3 deposition in sclerotic
areas/mesangium
Electron microscopy (EM)
◦ Fusion of podocyte foot processes
27.
Low-power view showingsegmental
sclerosis in one of three glomeruli (at
3 o'clock).
High-power view showing hyaline
insudation and lipid (small vacuoles) in
sclerotic area.
28.
Diabetic Nephropathy
Diabetesmellitus is a major cause of renal
morbidity and mortality
Advanced or end-stage kidney disease occurs in as
many as 40% of both insulin-dependent type 1
diabetics and type 2 diabetics.
Most common lesions involve the glomeruli
The morphologic changes in the glomeruli include
(1) capillary basement membrane thickening,
(2) diffuse mesangial sclerosis, and
(3) nodular glomerulosclerosis.
29.
Pathogenesis
(1) insulindeficiency hyperglycemia biochemical
alterations in
diabetic GBM
increased amount and synthesis of
collagen type IV and fibronectin and
decreased synthesis of the heparan
sulfate proteoglycan.
(2) Nonenzymatic glycosylation of proteins, which is known to occur
in diabetics and gives rise to advanced glycosylation end products,
may contribute to the glomerulopathy.
30.
The characteristic featuresare diffuse involvement of the glomeruli showing
thickening of the GBM and diffuse increase in the mesangial matrix with mild
proliferation of mesangial cells and exudative lesions (fibrin caps and capsular drops).
Capsular drop is an eosinophilic hyaline thickening of the parietal layer of Bowman’s capsule
and bulges into the glomerular space
Fibrin cap is homogeneous, brightly eosinophilic material appearing on the wall of a
peripheral capillary of a lobule.
31.
Nodular lesion (Kimmelstiel-WilsonLesion).There are one or more hyaline
nodules within the lobules of glomeruli, surrounded peripherally by glomerular
capillaries with thickened walls
specific for type 1 diabetes (juvenile onset diabetes)
Amyloidosis
Most commonlyrenal amyloid is of light-chain (AL) or AA
type.
Congo red amyloid-positive fibrillary deposits are present
within the mesangium and capillary walls
AL amyloidosis (formerly known as ‘primary’ or ‘associated
with multiple myeloma’) is the most common.
AA amyloidosis (formerly known as secondary amyloidosis)
is a rare complication of persistent inflammation that may
develop in patients affected by chronic rheumatic diseases.
Dialysis-related amyloidosis, a serious complication in
patients undergoing long-term dialysis that is caused by the
deposition of fibrillar ß2-microglobulin (amyloid ß2M)
35.
Glomerulus with
prominent mesangialand
vascular deposition of
amyloid
Deposits of amyloid
exhibiting birefringence
under polarized light
(Congo red stain).
Fluorescence of amyloid
under ultraviolet light
(thioflavinT stain).
36.
Post infectious /Diffuse proliferative GN
Diffuse proliferation of glomerular cells associated with
influx of leukocytes
Lesion are typically caused by immune complexes
Characterised by
◦ Onset 1 – 4 weeks after upper respiratory / cutaneous infection
with Group A -haemolytic streptococci
◦ Can occur after a number of other bacterial, viral and parasitic
infections
◦ Elevated antistreptococcal antibody and decreased C3
◦ Secondary to anti-strep antibodies binding to glomerular
components
◦ Usually resolves within 6 weeks
Membranoproliferative GN
TypeI:
◦ Subendothelial Immune complex disease
◦ Idiopathic or secondary to Neoplasm,Autoimmune disease, Infections,
Drugs
Type II: (dense deposit disease)
◦ Complement activation
◦ BM deposits
50% progress to chronic renal failure (CRF)
High recurrence rate in renal transplants
Characterised by
◦ Thickened capillary loops
◦ Glomerular hypercellularity due to mesangial proliferation
41.
Membranoproliferative GN
Lightmicroscopy (LM)
◦ Mesangial proliferation
◦ Thickened capillary BM
Immunofluorescence (IF)
◦ Type I: Granular BM and mesangial IgG, IgM, C3
◦ Type II: Granular BM C3
Electron microscopy (EM)
◦ Type I: Subendothelial deposits and mesangial
interposition
◦ Type II: Dense deposits in GBM
42.
Mesangial cell proliferation,increased
mesangial matrix (staining black with
silver stain), basement membrane
thickening and focal splitting,
accentuation of lobula rarchitecture,
swelling of cells lining peripheral
capillaries, and influx of leukocytes
The glomerular tufts show lobulation and
mesangial hypercellularity.
There is increase in the mesangial matrix
between the capillaries.There is
widespread thickening of the GBM.
43.
Membranoproliferative
glomerulonephritis, type I.Note the
large subendothelial deposit (arrow)
incorporated into mesangial matrix
Type II membranoproliferative
glomerulonephritis, dense-deposit
disease.There are markedly dense
homogeneous deposits within the
basement membrane proper.
44.
Type I thereare subendothelial
deposits; type II is characterized by
intramembranous dense deposits
(dense-deposit disease). In both,
mesangial interposition gives the
appearance of split basement
membranes when viewed in the light
microscope.
Type I (left half) and type II (right half)
MPGN.Type I (classic form) shows the
characteristic
subendothelial electron-dense deposits,
while type II (dense deposit disease) is
characterised by intramembranous dense
deposits
45.
Granular BM andmesangial IgG, IgM, C3
C3 showing weak linear staining along
glomerular capillary and tubular
basement membranes (right lower
corner) and bright granular deposits
in the mesangium, some of which
have a ring-like pattern.
Type I Type II
46.
IgA Nephropathy
Characterisedby episodic haematuria following
respiratory tract infections
Pathogenesis
◦ Increased mucosal IgA secretion in response to
inhaled/ingested antigens
◦ Glomerular (mesangial) deposition of IgA
50% progress to chronic renal failure (CRF)
Recurs in 20-60% of transplants
Light microscopy showing
mesangialproliferation and matrix
increase.
Characteristic deposition of IgA,
principally in mesangial regions,
detected by immunofluorescence.
49.
Crescentic GN
Rapidly progressiveGN
Characterised by
◦ Glomerular crescents
Accumulation of cells in Bowman’s space
Inflammatory cells, fibrin and epithelial cell proliferation
Compression of glomerulus
◦ Rapidly progressive clinical course
Pathogenesis
◦ Damage to glomerular vessels
◦ Egress of inflammatory cells and fibrin into Bowman’s space
◦ Proliferation of epithelial cells
50.
Pathogenesis
◦ TypeI – anti-GBM antibodies
linear deposition of IgG
May bind to alveolar BM in lung = Goodpasture’s disease
◦ Type II – immune complexes
Idiopathic or secondary to autoimmune disease or other GN
SLE
HSP
IgA nephropathy
Postinfectious GN
◦ Type III – pauci-immune
Idiopathic or secondary to systemic vasculitis
Wegeners
51.
collapsed glomerular tuftsand the
crescent shaped mass of proliferating
cells and leukocytes internal to
Bowman capsule.
There are crescents in Bowman’s space
forming adhesions between the
glomerular tuft and Bowman’s capsule.The
tuft shows hypercellularity and leucocytic
infiltration
52.
Electron micrograph showing
characteristicwrinkling of GBM with
focal disruptions in its continuity
(arrows).
RPGN, diagrammatic representation of
ultrastructure of a portion of glomerular
lobule showing epithelial crescent
formation and subepithelial granular
deposits
53.
Continuous linear IgGreactivity along
the capillary walls in a case of anti-GBM
glomerulonephritis.The tuft is compressed
by an epithelial crescent.
The glomerular tuft is compressed by an
epithelial crescent. Coarse granular
deposits of IgG are prominent along the
capillary walls.
Type I: linear IgG Type II: granular IgG
54.
Systemic sclerosis
Connectivetissue disorder of unknown etiology
F > M
Raynaud syndrome, skin thickening, digital pulp atrophy, and
telangiectasia are the primary clinical manifestations of systemic
sclerosis.
Two types of systemic sclerosis or scleroderma –
1) localised form called morphea
2) generalised form called progressive systemic sclerosis.
CREST syndrome. (C = calcinosis, R = Raynaud’s phenomenon, E =
esophageal dismotility, S = sclerodactyly and T = telangiectasia)
By electron microscopy - basement membrane wrinkling with focal
widening of the subendothelial area
Immunofluorescence studies often demonstrate reactivity for
fibrinogen
55.
Systemic vasculitis
Largevessel vasculitis's, such as giant cell (temporal)
arteritis andTakayasu disease, can produce narrowing of
the renal arteries, resulting in renal ischemia and
hypertension.
Medium-sized vessel vasculitis's, such as
polyarteritis nodosa and Kawasaki disease, can affect
intrarenal arteries and cause infarction and hemorrhage.
Small vessel vasculitis's, such as microscopic
polyangiitis (microscopic polyarteritis),Wegener
granulomatosis, Henoch–Schönlein purpura, and
cryoglobulinemic vasculitis, the renal involvement is often
manifested by glomerulonephritis.
56.
Henoch-Schönlein Purpura
Purpuricskin lesions characteristically involving the
extensor surfaces of arms and legs as well as buttocks.
Abdominal manifestations including pain, vomiting, and
intestinal bleeding, non migratory arthralgia; and renal
abnormalities.
Most common in children 3 to 8 years old, but it also
occurs in adults, in whom the renal manifestations are
usually more severe.
IgA is deposited in the glomerular mesangium.
poorer prognosis
57.
Chronic GN
A Massontrichrome preparation
shows complete replacement of
virtually all glomeruli by blue-staining
collagen.
59.
References
1) Robbinsand Cotran PATHOLOGIC
BASIS OF DISEASE
2) Rosai and Ackerman's Surgical
Pathology
