GLOMERULAR DISEASES

Ass.prof. Rihab Al-Mudhaffer

Kufa university
department of pathology and forensic medicine
The glomerulus

 is a sophisticated filter.
 Filters can clog
Renal failure
 Filters can leak
Proteinuria
Haematuria
 Why? How? To whom? With what effect?
 How can we stop it?
Normally, the glomerulus consists of an
anastomosing network of capillaries lined by
fenestrated endothelium invested by two layers of
epithelium.
The glomerular capillary wall is the filtering
membrane and consists of the following structures:
• A thin layer of fenestrated endothelial cells.
• A glomerular basement membrane (GBM)
• The visceral epithelial cells (podocytes)
• The entire glomerular tuft is supported by
mesangial cells lying between the capillaries.
Pathogenesis of glomerular diseases

Two forms of antibody associated injury:-

 Injury resulting from deposition of soluble
antigen antibody complexes in the
glomerulus.
 Injury by antibodies reacting in situ within the
glomerulus, either with:
 Insoluble fixed (intrinsic) glomerular antigens, or
 With molecules planted within the glomerulus.
Sites of glomerular injury

 Subepithelial.
 Within glomerular basement
membrane.
 Subendothelial.
 Mesangial and paramesangial
 Primary Glomerulopathies
1.Acute diffuse proliferative GN
2.Rapidly progressive (crescentic) GN
3.Membranous glomerulopathy (idiopathic)
4.Minimal change disease
5.Focal segmental glomerulosclerosis
6.Membranoproliferative GN (mesangiocapillary GN)
7.IgA nephropathy (Focal GN)
8.Chronic GN
 Acute diffuse proliferative Glomerulonephritis
Poststreptococcal GN

 Any age
 Presents with acute oliguric renal failure and
haematuria – Nephritic syndrome
 Two weeks after a streptococcal infection
 Usually gets better
 Morphology.
The classic diagnostic picture is one of enlarged,
hypercellular glomeruli, which may be due to:
(1) infiltration by both neutrophils and monocytes;
(2) proliferation of endothelial and mesangial cells;
(3) in severe cases crescent formation.
The proliferation and infiltration by leukocyte are
diffuse, that is, involving all lobules of all glomeruli.
There is also swelling of endothelial cells, and the
combination of proliferation, swelling, and leukocyte
infiltration obliterates the capillary lumens. There
may be interstitial edema and inflammation, and the
tubules often contain red cell casts.
Acute proliferative glomerulonephritis. A, Normal
glomerulus. B, Glomerular hypercellularity is due to
intracapillary leukocytes and proliferation of intrinsic
glomerular cells. C, Typical electron-dense subepithelial
"hump" and a neutrophil in the lumen.
RAPIDLY PROGRESSIVE (CRESCENTIC) GN

The histologic picture, however, is dominated by the formation

of distinctive crescents. Crescents are formed by
proliferation of parietal cells and by migration of monocytes
and macrophages into the urinary space. Neutrophils and
lymphocytes may be present. The crescents eventually
obliterate Bowman space and compress the glomerular tuft.
Fibrin strands are prominent between the cellular layers in
the crescents; indeed, the escape of fibrin into Bowman
space is an important contributor to crescent formation.
Electron microscopy may reveal subepithelial deposits in some
cases, but in many cases, it shows distinct ruptures in the
GBM, the severe injury that allows leukocytes, proteins, and
inflammatory mediators into the urinary space, where they
trigger the crescent formation.
Crescentic glomerulonephritis (PAS stain). Collapsed
glomerular tufts and the crescent-shaped mass of
proliferating cells and leukocytes internal to Bowman
capsule
MEMBRANOUS GLOMERULOPATHY (MEMBRANOUS
NEPHROPATHY)

 Commonest cause of nephrotic syndrome in adults

 One third remit, one third continue, one third progress to
renal failure.
 Treatment?
 May be secondary - SLE, infections, cancer, drugs…
 Probably autoimmune.
 By LM, the glomeruli either appear normal in the early
stages of the disease or exhibit uniform, diffuse
thickening of the glomerular capillary wall.
By EM, the thickening is seen to be caused by irregular
dense deposits between the basement membrane
and the overlying epithelial cells, the latter having
effaced foot processes. Basement membrane
material is laid down between these deposits,
appearing as irregular spikes protruding from the
GBM. These spikes are best seen by silver stains,
which color the basement membrane black. In time,
these spikes thicken to produce dome-like protrusions
and eventually close over the immune deposits,
Membranous GN
PAS stain. Note the marked diffuse thickening of the capillary wall
without an increase in the number of cells.
light microscopic appearance of membranous glomerulonephritis in
which the capillary loops are thickened and prominent, but the
.cellularity is not increased
MINIMAL CHANGE DISEASE (LIPOID NEPHROSIS
 Children
 Nephrotic range proteinuria
 Responds to steroids (Usually).

The glomeruli are normal by light microscopy. By EM, the

basement membrane appears normal, and no electron-dense
material is deposited. The principal lesion is in the visceral
epithelial cells, which show a uniform and diffuse effacement of
foot processes.
The cells of the proximal tubules are often laden with lipid and
protein, reflecting tubular reabsorption of lipoproteins passing
through diseased glomeruli (thus, the historical term lipoid
nephrosis)
Minimal change disease. Glomerulus stained with PAS. Note normal
basement membrane and absence of proliferation. Compare with
.membranous glomerulopathy
A, Ultrastructural characteristics of minimal change disease:
effacement of foot processes (double arrows), absence of
deposits, vacuoles (V), and microvilli in visceral epithelial
cells (single arrow). B, Schematic representation of minimal
change disease, showing diffuse effacement of foot processes.
FOCAL SEGMENTAL GLOMERULOSCLEROSIS

By light microscopy, the segmental lesions may involve only a minority of

the glomeruli and may be missed if the biopsy specimen contains an
insufficient number of glomeruli .
In the sclerotic segments, there is collapse of basement membranes,
increase in matrix, and segmental insudation of plasma proteins along
the capillary wall (hyalinosis), which may extend to aggregates within
glomerular capillaries that occlude the lumina.
Glomeruli that do not exhibit segmental lesions either appear normal on
light microscopy or may show increased mesangial matrix and mesangial
proliferation.
On electron microscopy, both sclerotic and nonsclerotic areas show the
diffuse effacement of foot processes characteristic of minimal change
disease.
Focal segmental glomerulosclerosis, PAS stain. segmental sclerosis in
.one of three glomeruli
Focal segmental glomerulosclerosis PAS stain. High-power view
.showing hyaline insudation and lipid (small vacuoles) in sclerotic area
MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS
By light microscopy, both types are similar. The glomeruli are
large and hypercellular. The hypercellularity is produced both
by proliferation of cells in the mesangium and so-called
endocapillary cell proliferation involving capillary
endothelium and infiltrating leukocytes.
The glomeruli have a "lobular" appearance accentuated by the
proliferating mesangial cells and increased mesangial
matrix.
The GBM is clearly thickened, often focally; this is most evident
in the peripheral capillary loops. The glomerular capillary
wall often shows a "double-contour" or "tram-track"
appearance, especially evident in silver or PAS stains. This is
caused by "duplication" of the basement membrane, usually
as the result of new basement membrane synthesis. Within
the besement membrane there is inclusion or interposition
of cellular elements, which can be of mesangial, endothelial,
or leukocytic origin. Such interposition gives rise to the
appearance of "split" basement membranes.
Membranoproliferative GN, showing mesangial cell proliferation,
increased mesangial matrix (staining black with silver stain),
basement membrane thickening and focal splitting, accentuation of
lobular architecture, swelling of cells lining peripheral
capillaries, and influx of leukocytes.
A silver stain of the glomerulus highlights the proteinaceous basement
membranes in black. There are characteristic "spikes" seen with
membranous glomerulonephritis seen here in which the black
basement membrane material appears as projections around the
.capillary loops
IgA NEPHROPATHY (BERGER DISEAS)

 Any age
 Presents with haematuria
 May get worse at time of mucosal Infections
 Significant proportion progress to renal failure.
 Very variable glomerular changes – mesangial proliferation
 Deposits of IgA-containing immune complexes in mesangium

 failure On histologic examination, the lesions vary considerably.

The glomeruli may be normal or may show mesangioproliferative
glomerulonephritis, focal proliferative glomerulonephritis, or
rarely, overt crescentic glomerulonephritis.
 Healing of the focal proliferative lesion may lead to focal
segmental sclerosis.
 IgA nephropathy. A, mesangial proliferation and matrix
increase.
primary glomerular diseases leading to chronic glomerulonephritis
(GN). The thickness of the arrows reflects the approximate
proportion of patients in each group who progress to chronic
glomerulonephritis: poststreptococcal (1% to 2%); rapidly
progressive (crescentic) (90%), membranous (30% to 50%), focal
glomerulosclerosis (50% to 80%), membranoproliferative
glomerulonephritis (50%), IgA nephropathy (30% to 50%).
The microscopic appearance of the "end stage kidney" is similar regardless of cause,
which is why a biopsy in a patient with chronic renal failure yields little useful
information. The cortex is fibrotic, the glomeruli are sclerotic, there are scattered
chronic inflammatory cell infiltrates, and the arteries are thickened. Tubules are often
"..dilated and filled with pink casts
 Goodpasture syndrome
 Catastrophic nephritic presentation
 With haemoptysis if a smoker
 Autoimmune:
 Antibody against GBM
 Eminently treatable if caught early
Systemic lupus erythematosis

 Systemic, multi-organ disorder

 Kidney involvement – bad prognostic sign
 Produces almost any pattern of glomerular
damage
 Usually massive immune complex deposition
Vasculitis

 Systemic disorders
 No antibody deposition
 Associated with Anti Neutrophil Cytoplasmic
Antibodies
 Nephritic presentation
 Eminently treatable IF caught early
Diabetes mellitus

 Mainly ‘microvascular’ problems

 Basement membrane thickening
 Mesangial sclerosis – may become nodular
 (‘Kimmelsteil-Wilson’ nodules)
 Arteriolar hyalinosis
 Progressive proteinuria
 Progressive renal failure
 Amyloidosis

 Multi-organ deposition, several types

 In the glomerulus, a little bit of amyloid can
cause a lot of proteinuria
THANK YOU