histology and gross aspect of the inflammatory disease associated with renal system and urinary bladder.

1. INFLAMMATORY
DISEASES OF
THE URINARY
SYSTEM
-KIDNEYS AND BLADDER-
• STUDENT NAMES: AKEBAT ALI BIN ILAMI; ATRASH
SHAMS; COHEN YISHAI; PETCU IOANA; PREGO TOM;
VENETIS ALEXANDRA.
• SUBJECT: MORPHOPATHOLOGY
• UNIVERSITY: TITU MAIORESCU UNIVERSITY
• PROGRAM: GENERAL MEDICINE IN ENGLISH
• YEAR: 3RD YEAR
• DATE: 10/06/2020

2. ABSTRACT
The urinary system is an important part of the body, functioning as a gate
mechanism in order to help regulate the internal environment and maintain
homeostasis through its subunits. The kidneys are in charge or secreting,
excreting, and reabsorbing water, waste products, minerals and ions. The
bladder is the reservoir, collecting the formed urine and allowing for control
over discharge. The aim and outcome of this project is to better understand the
morphological changes of the kidney and bladder brought forward by
inflammatory disorders. In order to accomplish this, an introduction on the
normal histological aspects of the kidney and the bladder was given along with
examples of different stains that are used for these structures. Furthermore, in
the main body of the project, various inflammatory disorders will be discussed
from a morphological point of view. For an easier approach of the subject, the
qualitative research method in a thematic pattern was used for reviewing first
the organs of importance, then for listing and expanding on the pathologies
relevant to each of them. In the ending of the project, a list of conclusions was
provided along with references for the sources that have been used throughout

3. 1. INTRODUCTION

4. THE URINARY SYSTEM
GENERALITIES
• The urinary system consists of the:
Kidneys
Ureters
Urinary bladder
Urethra
• The main function of the urinary system is to eliminate the waste products of metabolism
from the body by forming and excreting urine.
• The main waste products are urea (by-product of protein catabolism) and uric acid, (by-
product of nucleic acid catabolism) along with excess water and mineral ions.
• Other vital functions of the system include:
 maintaining homeostasis of mineral ions in the extracellular fluid – they can be excreted in
urine or returned to the blood.
regulating acid-base balance in the body
controlling the volume of extracellular fluids, including the blood, which helps maintain blood
pressure.
the kidneys release hormones to regulate blood pressure and control production of RBCs
by releasing erythropoietin.

5. KIDNEYS – NORMAL MACROSCOPIC ASPECT
Gross anatomy in cross-section: this is a cross
section of a normal adult kidney. The outer layer
represented by the cortex which is lighter, while
the inner layer, represented by the medulla is
slightly darker in colour. Within the medulla, the
renal pyramids can be observed into which the
collecting ducts coalesce and drain into the
calyces and into the central renal pelvis.
Gross anatomy of a normal kidney:
as it can be seen in this image, the
kidney has a smooth shiny outer
cortex, which represents an
indication of the health of a kidney,
together with its size and weight
(121-201g for men and 96-204g for
females)

6. KIDNEY PARENCHYMA - NORMAL MICROSCOPIC ASPECT
• The renal cortex:
-darker than the
medulla because it
receives over 90% of
the kidney blood
supply.
- presents a grainy
appearance, as it
mostly contains renal
corpuscles (ovoid) and
convoluted tubules of
the nephrons.
• The renal medulla:
- appears striped, as it
contains vertical
nephron structures
(tubules, collecting
ducts).

7. A light microscopy (PAS stain)
showing normal renal tubules
KIDNEY - NORMAL MICROSCOPIC ASPECT

8. SPECIMEN SECTIONS
• Very thin sections (2-3µm or less):
– are recommended especially for the definition of
glomerular pathologies, especially regarding cellularity.
- for enhanced detectiontion of subtle pathologic
abnormalities
• Electron microscopy – is essential for demonstrating
functional details like capillary and podocyte filtration
slits.

9. STAINS
• Silver stain accentuates (BLACK) collagenous
structures (I.e. in the glomerulus, the
mesangual matrix, the glomerular basement
membrane and tubular basement
• PAS stain also accentuates (RED) matrix and
basement membrane constituents.
• Trichrome also accentuates (BLUE) matrix and
basement membrane constituents
• In certain circumstances, the trichrome stain
demonstrates granular immune (not linear)
deposits as bright fuchsinophilic (orange,
red-orange) smooth homogenous structures.
• Congo red, elastic tissue and other stains are
employed when indicated.

11. URINARY BLADDER-
ANATOMY AND HISTOLOGY
 The wall of the bladder contains folds called rugae,
and a layer of smooth muscle called the detrusor
muscle.
 As urine fills the bladder, the rugae smooth out to
accommodate the volume.
 The detrusor relaxes to hold the urine, then
contracts for urination.
 The bladder has three layers of smooth muscle, and
a transitional epithelium. It is harder to make out the
three layers, because the bladder is sac like in
aspect, not tubular.
 The mucosa is heavily folded - this helps to
accommodate for large volume changes.
 The transitional epithelial lining can stretch until it
looks like stratified squamous epithelium.

12. URINARY BLADDER-
ANATOMY AND HISTOLOGY

13. INFLAMMATION
• Inflammation represents a process intimately linked to renal disease and can be defined as a complex
network of interactions between renal parenchymal cells and resident immune cells, such as
macrophages and dendritic cells, coupled with recruitment of circulating monocytes, lymphocytes, and
neutrophils.
• Once stimulated, these cells activate specialized structures such as Toll-like receptor (TLR) and Nod-
like receptor (NLR).
• By detecting danger-associated molecules, these receptors can set in motion major innate immunity
pathways such as nuclear factor ĸB (NF-ĸB) and NLRP3 inflammasome, causing metabolic
reprogramming and phenotype changes of immune and parenchymal cells and triggering the
secretion of a number of inflammatory mediators that can cause irreversible tissue damage and
functional loss.
• Inflammatory conditions involving the urinary tract are among the most common infectious disorders
affecting humans. In most cases, the infection is confined to the lower urinary tract, and the diagnosis
is established by clinical or laboratory studies.
• Imaging studies are not required when there is prompt resolution after appropriate therapy. However,
when the kidney is involved by the inflammatory process, or when the precise diagnosis is not known,
renal imaging studies may play an important role in the diagnosis and management.

14. 2. MATERIAL AND METHODS
 In order to investigate the different inflammatory pathologies of the urinary system, a qualitative research
method was used since there is a need for smaller but focused samples rather than large random samples.
 Furthermore, qualitative analysis involves categorizing data into patterns as the primary basis for organizing
and reporting results. Therefore, the method chosen to undertake this feat was that of analysis of primary
research and medical educational materials, which may be found either in a physical or virtual format.
 The analysis techniques chosen was a thematic and systematic one as the project approaches first an
introductory section to the subjects and then moves to discuss the two structures of interest, separately,
providing data on the various disorders that can affect them, including their macroscopic and microscopic
aspects.
 The aim and outcome of this project is to better understand the morphological changes of the kidney and
bladder brought forward by inflammatory disorders.

15. 3 . K I D N E Y S
I N F L A M M A T O R Y
P A T H O L O G I E S
I. Glomerulonephritis
II. Tubulointerstitial nephritis
III. Lupus nephritis
IV. Other pathologies

16.  Nephritis is defined as the inflammation of the kidney.
 The two most common causes of nephritis are represented by
infection or an auto-immune process.
 Nephritis has the effect of damaging and closing up the
microscopic filters in the kidney which results, in addition to
various toxic waste products, in the excretion by the inflamed
kidney filters of important proteins from the blood.
 Therefore the characteristic symptom of nephritis is proteinuria -
meaning the excessive removal of protein from the blood and its
excretion in urine.

17. I.

18. NON-PROLIFERATIVE GLOMERULONEPHRITIS
1. Focal segmental glomerulosclerosis
2. Membranous glomerulonephritis
3. Minimal change disease

19. 1. FOCAL SEGMENTAL GLOMERULOESCLEROSIS
 Mainly a nephrotic disease .
 As a primary disease, the cause is idiopathic, but can also be
secondary to (HIV, parvovirus, drugs, sickle cell anemia,
hypertension and obesity..)
 Predilection by masculine sex, 7% to 15% in children and 10%
to 20% in adults. ( most seen in black people)
 Glomerular hypertrophy and hyper filtration have been,
associated to segmental glomerular lesions.
 Injury of podocytes is another mechanism in some forms of
FSGS and it has been associated mainly in intravenous drug
abusers and HIV infection.
Light Microscopy: segmental glomerular scarring can be seen
as hyaline material once the process of sclerosis advances,
therefore, starting to affect the healthy glomeruli as well. The
sclerosing segments are positive with PAS and silver-
methenamine stains, lipid droplets and foam cells are often
present.
Immunofluorescence: very frequently, deposits of IgM and C3,
weak deposits of IgG in segments with lesions.
Electron microscopy: hyaline material can be seen in areas with
sclerosis; the epithelial cell may become detached from the
glomerular basement membrane leaving clear areas, thickening
of the basal membrane; both sclerotic and non-sclerotic areas
show diffuse effacement of foot processes.
Electron microscopy showed glomerular
capillary loop with diffuse podocyte foot
process effacement .

20. 2. MEMBRANOUS GLOMERULONEPHRITIS
 Nephrotic syndrome is characterized by
subepithelial immune deposits and
formation of perpendicular projections of
material similar to the glomerular basement
membrane.
 idiopathic disease, or secondary to cancer,
lupus, NSAIDS,HBV, Hepatitis B, syphilis,
antibody against anti-phospholipid A2
receptor.
 *30% in adults (in Caucasian adults with a
male/female relation of 2:1)
 Light microscopy: capillary walls appear
thickened
 Immunofluorescence: granular parietal IgG
positivity, accompanied by C3 deposits
 Electron microscopy: subepithelial granular
deposits which are usually diffuse and
homogenously distributed; Spikes are
demonstrated as irregular projections of the
GBM among the subepithelial deposits.
** The deposits are amorphous; the presence
of organized deposits must alert of a possible
see as the material that appears in
the external part of the GBM forms
circles or ring that completely
surrounds the immune deposits.
(Methenamine-silver)
Masson’s
trichrome

21. 3. MINIMAL CHANGE DISEASE
 Nephrotic syndrome associated to minimal
glomerular changes, predominantly affects
children(70-90%)
 Primarily idiopathic but can be caused due to
treatment with NSAIDS, Hodgkin’s disease, clinical
association with respiratory infections and
prophylactic immunization, atopic disorders
(eczema, rhinitis)..
 occur more frequently in Caucasians than in Afro-
American.
 referred to as “asthma of the nephron”.
 Response to steroids is high in children ( as
treatment) .
 Light microscopy: little changes, looks normal
(Cellularity is normal in most of cases)
Immunofluorescence: There are neither
immunoglobulins nor complement fractions
deposition in renal tissue.
Electron microscopy:The principal lesion is in the
podocytes, which show a uniform and diffuse
effacement of foot processes, these being replaced by
a rim of cytoplasm often showing vacuolization
swelling, and hyperplasia of villi.
** The cells of the proximal tubules are often laden
with lipid and protein, reflecting tubular reabsorption

22. PROLIFERATIVE GLOMERULONEPHRITIS
1.MEMBRANOPROLIFERATIVE
2.POST-INFECTIOUS
3.IgA NEPHROPATHY
4.RAPIDLY PROGRESSIVE
A.GOODPASTURES SYNDROME
B.VASCULITIC DISORDERS:
-WEGENER GRANULOMATOSIS
-MICROSCOPIC POLYANGITIS

23. * have a combined nephrotic-nephritic picture.
*accounts for 10% to 20% of cases of nephrotic syndrome in children and young adults.
* Primary MPGN is divided into two major types on the basis of distinct ultrastructural, immunofluorescent, and
pathologic findings: type I and type II MPGN (dense-deposit disease).
* idiopathic, associated with malignancy, hepatitis c , bacterial infection, complement dysregulation.
 light microscopy: both types of MPGN are similar, The glomeruli are large and hypercellular. The
hypercellularity by proliferation of cells in the mesangium and endocapillary proliferation involving capillary
endothelium and infiltrating leukocytes,(Crescents are present in many cases),The glomeruli have an
accentuated “lobular” appearance due to the proliferating mesangial cells and increased mesangial matrix, The
GBM is thickened.
 Electron microscopy:
Type I MPGN - is characterized by the presence of discrete subendothelial electron-dense deposits. Mesangial
and occasional subepithelial deposits may also be present.
Type II MPGN - the lamina densa of the GBM is transformed into an irregular, ribbon-like, extremely electron-
dense structure due to the deposition of dense material
 Immunofluorescence:
Type I MPGN C3 is deposited in a granular pattern, and IgG and early complement components (C1q and C4)
are often also present.
Type II MPGN C3 is present in irregular granular or linear foci in the basement membranes on either side but
not within the dense deposits. C3 is also present in the mesangium in characteristic circular aggregates
(mesangial rings), gG is usually absent,.
1. MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS

24. MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS
aDDD case, capillary walls
thickening Glomerulus increased of size, with
mesangial hypercellularity and lobulated
aspect
Direct immunofluorescence for
C3 in a case of dense deposits
disease
Subendothelial electron-dense
deposits. In this case they proved to
be positive for IgG and C3
subendothelial deposits with the trichrome
stain

25. 2. ACUTE PROLIFERATIVE GLOMERULONEPHRITIS (POSTSTREPTOCOCCAL,
POSTINFECTIOUS)
 Nephritic disease that is characterized histologically by diffuse proliferation of
glomerular cells, associated with influx of leukocytes, These lesions are typically
caused by immune complexes (Glomerular lesions are not associated to direct
infection by the microorganism, but, to the formation of immune
 The most common underlying infections are streptococcal, but the disorder also
has been associated with other infections.
 Other infectious agents have been associated with acute GN: Streptococcus
pneumoniae, Staphylococcus, gram negative bacilli, Treponema, mycobacterium,
Plasmodium, etc.
Light microscopy: loss of capillary lumens with enlarged, hyper cellular glomeruli
caused by:
(1) infiltration by both neutrophils and monocytes
(2) proliferation of endothelial and mesangial cells
(3)There is also swelling of endothelial cells
well-defined rounded deposits in the external aspect of the capillary peripheral
walls: “humps”, The presence of humps strongly suggests postinfectious.
**There may be interstitial edema and inflammation, and the tubules often contain
red cell casts.
 Immunofluorescence: Heavy, granular,deposits of IgG and C3 are
demonstrated.
 Electron microscopy: diminution of capillary lumens, cellular edema, and
electron-dense immune deposits in the epithelial side of the capillary walls
(humps)
humps, pointed by the arrows
global cellular
proliferation that
obstructs capillaries

26. 3. IgA NEPHROPATHY (BERGER DISEASE)& HENOCH-SCHÖNLEIN PURPURA
Mesangial
hypercellularity
diffuse mesangial
immunostaining for IgA in
 Nephritic disease is defined by the presence of diffuse dominant or
codominant mesangial deposits of IgA (only IgA1 forms the
nephritogenic deposits of IgA).
 may be primary or secondary to other diseases, mainly hepatobiliary ,
celiac disease, Crohn’s disease, ulcerative colitis, Sjögren’s syndrome,
chronic infectious or inflammatory mucosal diseases (specially of lung),
autoimmune diseases, lymphoproliferative diseases, carcinoma of
colon, stomach, breast, and lung
 similar IgA deposits are present in a systemic disorder of children,
Henoch-Schönlein purpura, is characterized by purpuric skin lesions
(mainly on the lower extremities and buttocks), is considered a form of
IgA Nephropathy with prominent extra-renal involvement: systemic
vasculitis mediated by IgA rich immune complexes.
 occurs in all ages but is most frequent in the second or third decades
of the life; the mean age of diagnosis is 28-years-old.
 Light microscopy: normal appearing glomeruli to any type of
proliferative or sclerosing lesion, including extracapillary proliferation,
predominant glomerular changes are mesangial proliferation
 immunofluorescent:mesangial deposition of IgA , often with C3 and
properdin and lesser amounts of IgG or IgM (the diagnosis is made only
by immunocytochemical techniques)
Electron microscopy: mesangial deposits that correlate with the
immune deposit, located in the interphase between mesangium and
capillary lumen.
**In Henoch-Schönlein purpura immunofluorescence and electron
microscopy the findings may be similar to those of IgAN.
Schönlein-Henoch
syndrome are usually
similar to those of IgAN

27. 4. ANTI-BGM DISEASE, “GOODPASTURE DISEASE”
 This disease frequently appears like a pulmonary-
renal syndrome
 characterized by linear deposits of IgG and, in
many cases, C3 in the GBM that are visualized by
immunofluorescence
 “Goodpasture disease” it is used to denominate
the pulmonary-renal syndrome produced by anti-
GBM antibodies.
 Caused by AutoAb to glomerular basement
membrane
Antibodies recruit complement and lymphocytes
damages to capillaries  proliferation and
accumulation in Bowman’s space crescent
Light microscopy: crescent formation
Immunofluorescence: positive for IgG in linear
pattern
Electron microscopy: normal aspect

28. 4. GRANULOMATOSIS WITH POLYANGITIS (WEGENER GRANULOMATOSIS)
 Rare autoimmune disease of unknown etiology with
triad of :
(a) necrotizing granulomatous inflammation of upper
respiratory tract or lungs,
(b) necrotizing pauci-immune vasculitis of vessels in
lungs, upper airways and other sites
(c) focal necrotizing glomerulonephritis.
 Occurs at any age but more common at ages 30 - 49
years
 Light microscopy: Focal necrotizing
glomerulonephritis, often with cellular crescents and
usually with glomerular thrombosis ,Interstitial
inflammation common, renal papillary necrosis in 20%
of cases.
Immunofluorescence: Usually no immune complex
deposits, but fibrinogen in glomeruli and vessel walls,
small amounts of IgM, IgG or C3 in glomeruli and
vessels (pauci-immune)
Electron microscopy: Rarely sparse electron dense
deposits in glomeruli
Glomerulonephrit
focal necrotizing,
sclerosing, early
crescent
Positive c-ANCA (immunofluorescence
pattern produced by binding of ANCA to
ethanol-fixed neutrophils)

29. 4. MICROSCOPIC POLYANGITIS
*systemic, pauci-immune, small vessel necrotizing vasculitis
associated with antineutrophil cytoplasmic antibodies (ANCA),
often targeting myeloperoxidase (MPO), but without immune
complex deposition or granulomas.
*occurs at any age but more common at age 50+ years, About
80% of patients with MPA have serum ANCA , usually pANCA.
**In microscopic polyangiitis (MPA), the vascular changes are
very similar to those seen in Wegener Granulomatosis but
granulomatous inflammation is absent.
 Light Microscopic: focal and segmental to severe diffuse
crescentic, Arterial lesions usually all at same stage, Usually
tubulointerstitial infiltrate, Sausage shaped microaneurysms of
interlobular arteries.
 Immunofluorescence: pauci- immune, not much light up
 Electron microscopy: looks normal
Mild mesangial cellular
proliferation
and expansion; mesangial and
diffuse IgA deposits were

30. II. TUBULOINTERSTITIAL NEPHRITIS
Group of renal diseases
characterized by histological and
functional alteration
predominantly of the tubules and
of the interstitium.

31. ACUTE INTERSTITIAL NEPHRITIS
(AIN)
 Lesion with interstitial edema with a mononuclear cell
infiltrate invading the interstitium and tubules,
composed mostly of T lymphocytes and monocytes.
The classic lesion of "tubulitis" is found when
inflammatory cells invade the tubular basement
membrane (TBM).
 There are scattered plasma cells and macrophages,
occasionally with non-necrotizing granulomas, and
variable presence of eosinophils.
 Clinical manifestation: acute kidney injury, rapid
decline in glomerular filtration rate, with fever,
eosinophilia, hematuria, sterile pyuria, and non-
nephrotic proteinuria.
 Gross:
 Light microscopy: patchy edema and mononuclear
cell infiltrate, with mostly T lymphocytes, variable
plasma cells, and macrophages. Tubulitis is typically
present with concomitant variable acute tubular injury.
Non-necrotizing granulomas are often ill-defined.
Eosinophils are variably present.
 Immunofluorescence microscopy: No specific
staining.
 Electron microscopy: Typically there are no specific
findings. In some cases with NSAIDs-induced AIN,
LM of severe acute interstitial nephritis showing diffuse
interstitial inflammatory infiltrate. One normal glomerulus is
present at the top of the slide.
LM of interstitial nephritis
showing diffuse interstitial
infiltrate of mononuclear
cells, many of which are
actively invading the tubules
leading to disruption of the
tubular basement
membranes (arrows). A
white cell cast is present in
the tubule in the upper right
corner.

32. ACUTE INTERSTITIAL NEPHRITIS
(AIN)
“Kidney in a condition of acute interstitial nephritis” by
Godart, Thomas

33. CHRONIC INTERSTITIAL NEPHRITIS
(CIN)
 Nonspecific diagnosis of a pattern of kidney
injury - infiltrating lymphoplasmacytic infiltrate
with occasional tubulitis, without evident
specific cause
 May occur due to any of many conditions that
initially cause an acute interstitial nephritis.
 Light microscopy: CIN with a
lymphoplasmacytic infiltrate out of proportion
to the degree of interstitial fibrosis and tubular
atrophy. The infiltrate consists of CD4/CD8 T-
cells, B-cells, and plasma cells, with scattered
tubulitis. Glomeruli are initially unremarkable,
but may show periglomerular fibrosis and
ischemic wrinkling of glomerular basement
membranes and even sclerosis in advanced
cases. Vascular sclerosis and hyalinosis may be
present.
 Immunofluorescence microscopy: No specific
staining.
 Electron microscopy: No specific changes.
CIN with interstitial lymphocytic infiltrate with eosinophils
associated with tubulitis, interstitial fibrosis, and tubular
atrophy (hematoxylin and eosin stain).

34. ACUTE
PYELONEPHRITIS
• Acute suppurative inflammation of
the kidney caused by bacterial and
viral infections, histologically
characterized by interstitial edema
and leukocytic infiltration of the
interstitium and tubules causing
necrosis.
• Gross: Cortical surface shows grayish
grayish white areas of inflammation
and abscess formation.
• Light microscopy: patchy
suppurative inflammation;
intratubular aggregates of
neurtophils; tubular necrosis;
collecting tubules in cortex and
medulla are filled with neutrophils;
glomeruli are spared.
 Early stages- Neutrophilic infiltration
limited to the interstitial tissues.
 Later stages- Involvement of tubules
and produces abscess with
destruction of engulfed tubules.
Papillary necrosis- Arrows shows grey-yellow necrosis in the pyramids.
Mainly seen in diabetics and urinary tract obstruction. On microscopic
picture we will expect coagulative necrosis
Discrete, yellowish,
raised abscesses
are grossly
apparent on the
Acute neutrophilic
exudate with
tubules and in the
renal substance.

35. CHRONIC PYELONEPHRITIS
• Chronic pyleonephritis predominantly consist of
mononuclear leukocytic infiltration, fibrosis and
atrophy of tubules.
• Can be divided in two forms: chronic reflux-
associated and chronic obstructive.
• Chronic reflux nephropathy is more common and
may occurs in early childhood due to severe UTI or
congenital reflux.
• Chronic obstructiv - predisposes the kidney to
infections; recurrent infections due to obstruction
lead to recurrent bouts of renal inflammation and
scarring
• Gross: irregular scarring of the kidney; in cross
section, dilatation and blunting of calyces are visible.
The ureter shows dilatation and thickening.
• Light microscopy: interstitium and tubules with
atrophy or dilatation and hypertrophy in others.
Dilated calyx and corticomedullary scar
tissue. In cortex thyroidization (colloid
casts filled) of tubules is visible

36. CHRONIC PYELONEPHRITIS
The cystic appearing structures
are actually dilated calyces,
reflecting hydronephrosis. The
renal parenchyma between the
dilated calyces show reduction in
tissue when compared to the
more normal renal parenchyma
of the lower pole.

37. III. LUPUS NEPHRITIS It is a type of kidney disease caused by systemic lupus erythematosus, Lupus nephritis is more common in men than in women.
 Hystological classification:
Class I - Minimal mesangial lupus nephritis. Normal glomeruli by LM, but mesangial immune deposits by IF
Class II - Mesangial proliferative lupus nephritis. Purely mesangial hypercellularity of any degree or mesangial expansion by LM,
with mesangial immune deposits
Class III - Focal lupus nephritis. Active or inactive focal, segmental or global, endo- or extracapillary GN involving <50% of all
glomeruli, typically with focal subendothelial immune deposits, with or without mesangial alterations. Further divided into class III
A, A/C and C.
Class IV - Diffuse lupus nephritis. Active or inactive diffuse, segmental or global endo or extracapillary GN involving >/= 50% of
of all glomeruli, typically with diffuse subendothelial immune deposits, with or without mesangial alterations. This class is divided
in diffuse segmental (IV-S) when >/= 50% of the involved glomeruli have segmental lesions, and diffuse global (IV-G) when >/=
50% of the involved glomeruli have global lesions.
Class V - Membranous lupus nephritis. Global or segmental subepithelial immune deposits immune or their morphologic
sequelae by LM and by IF or EM, with or without mesangial alterations. Class V lupus nephritis may occur in combination with
class III or IV.
Class VI - Advanced sclerosing lupus nephritis. >/= 90% of glomeruli globally sclerosed without residual activity.

38. Electron microscopy: some deposits can have an organization in “fingerprint”, seen like parallel, regularly curved and spaced
deposits with wavy aspect and intersections. We can see effacement of podocyte foot processes, similar to the changes seen in
other glomerulopathies with nephrotic syndrome.
Immunofluorescence: In classes I and II we can see mesangial deposits of IgS and complement, occasional subendothelial
deposits. In class III there are mesangial and capillary wall deposits with a segmental distribution. In class IV there are invariably
present intense, global and diffuse subendothelial deposits, usually accompanied by mesangial deposits. In class V there are
diffuse subepithelial granular deposits of IgG and C3, usually accompanied by C1q. Mesangial and some small subendothelial
deposits can be seen in class V.
Class IV lupus nephritis. Subendothelial immune deposits. Left: deposits
thickening capillary walls and hyaline thrombi (blue arrows) that correspond to
immune aggregates in capillary lumina; Right. Extensive immune subendothelial
deposits, fuchsinophilic (red), in almost all the capillary walls (green arrows).
Class III lupus nephritis. There are visible several segments with
endocapillary proliferation (green arrow) and two small segments
with fibrinoid necrosis in which fuchsinophilic material is
identified (red arrows)
Class III lupus nephritis. There are visible several segments with
endocapillary proliferation (green arrow) and two small segments
with fibrinoid necrosis in which fuchsinophilic material is
identified (red arrows)

39. IV. OTHER PATHOLOGIES
- Diabetic nephropathy
- Fibrillary glomerulonephritis
- Immunotactoid glomerulopathy
- Chronic glomerulonephritis
- Amyloidosis
- Polycystic kidney disease
- Renal abscesses
- Nephrolithiasis
- Tuberculosis of the kidney

40. DIABETIC NEPHROPATHY
 Developes in approximately 1/3 of patients with type 1 and type 2 diabetes
 Pathologic hallmark: glomerulo sclerosis, it result from a progresive increase in extracelullar matrix
 Genotype can be an important determinant of incidence and severity
 Classification based on glomerular lesions:
Class I - glomerular basement membrane thikening, only mild, nonspecific changes by light microscopy.
Class II - mesangial expansion, mild (IIa) or severe (IIb). Difference between mild and severe is based on whether the expanded
expanded masangial area is smaller or larger then the mean area of capillary lumen (>25% of capillaries affected = IIb, <25% of
capillaries affected = IIa).
Class III - nodular sclerosis (Kimmelstiel-Wilson lesion). In the early stage 2 processes take place: mesangiolysis and detachment
of endothelial cells from the GBM. Dissociation of endothelial cells may disrupt the connection betweenthe mesangial area and
GBM leading to expansion of the kimmelstiel-Wilson lesion.
Class IV - advanced diabetic glomerulosclerosis, more then 50% global glomerulosclerosis plus other pathological evidences.
 Clinical manifestation is similar in type 1 and type 2 diabetes. However, the renal lesions may differ.
Electron microscopy: we can se mesangial expansion caused by increased extracelullar matrix. GBM is seen diffusely
thickened, with fibrillary aspect and can appear laminated. GBM thickening is a consequence of extracellular matrix accumulation,
with increased deposition of normal extracellular matrix components such as collagen types IV and VI, laminin, and fibronectin.
Immunofluorescence: presence of linear deposits of IgG and albumin in walls of glomerular capillaries. Hyaline lesions can
have IgM and C3 as in other focal and segmental changes. Linear positivity for kappa and lambda can also be detected.

41. DIABETIC NEPHROPATHY
Glomeruli with Kimmelstiel-Wilson nodules. The
smallest nodules can be more cellular and the
greatest nodules tend to be acellular Mesangial thickening (global or segmental)
and diffuse thickening of the capillary walls
The larger nodules usually have a laminated aspect
more evident with silver stain
Deposits of IgG that are
accompanied by
albumin and adopt a
linear parietal pattern
Mesangial widening by
expansion of the matrix;
arteriolar hyalinosis (blue
arrows); two capsular
drops, one in each
glomerulus (red thin
arrows); and
microaneurisms (green
arrows)

42. FIBRILLARY GLOMERULO NEPHRITIS AND IMMUNOTACTOID GLOMERULOPATHY
Fibrillary glomerulo nephritis
 Glomerular disease characterized by deposition of
IgG (usually polytypic) and infiltrative fibrils.
 It has an unknown etiology. It is associated with
malignancy, usually carcinoma, dysproteinemia,
infectious diseases like hepatitis C virus and
autoimmune diseases.
 Electron microscopy: we can see randomly
fibrils deposits in mesangial and capillary walls.
 Immunofluorescence: mesangial and variable
capillary wall staining for polyclonal IgG and C3.
Immunotactoid glomerulopathy
 Extracellular glomerular deposition of nonamyloid fibrils.
Very rare, <1% of biopsies.
 Patients have monoclonal immunoglobulin deposition in
glomeruli and may have circulating paraproteins.
 More common in white people and females.
 Electron microscopy: we can see large extracellular
nonamyloid deposits, focally arranged in parallel arrays
and with a visible lumen (microtubules).
 Immunofluorescence: variable IgG, C3 and occasional
IgM, IgA.
Microtubular
deposits showing a
parallel, packed
arrangement. Thick
wallswith
prominent lumens

43. CHRONIC GLOMERULONEPHRITIS
 This general (glomerular, vascular and interstitial)
affection represents the end-stage of all
glomerulonephritis with unfavorable evolution.
 In most cases it is associated with systemic
hypertension.
 The cause is not known. Sometimes it is hereditary.
Some forms are caused by changes in the immune
system.
 It shows up in young men who may also have
hearing loss and vision loss.
Gross: symmetrical small kidneys, thin granular
cortex and increased peripelvic fat.
 Microscopic: depending on the stage of the disease
different degrees of hyalinization can be pressent,
causing hyalinosclerosis (total replacement of
glomeruli and Bowmans’s space with hyaline tissue).
Totally hyalinised glomeruli are atrophic (smaller),
lacking capillaries, hence these glomeruli are non-
functional. Obstruction of blood flow will produce
secondary tubular atrophy, interstitial fibrosis and
thickening of the arterial wall due to hyaline deposits.
In the interstitium is present an abundant inflammatory
infiltrate, mostly with lymphocytes. Still functional
nephrons have dillated tubules with hyaline casts inside
their lumen.

44. AMYLOIDOSIS
 Pathogenic extracelullar deposition of proteins,The pathologic mechanism is
still unclear
 Amyloid composition: 95% fibrillary proteins and 5% p component and other
glycoproteins
 *This proteins are resistent to digestion
 Biochemical forms:
1. AL type (primary): Most common cause of renal amyloidosis, Related to
monoclonal plasma cell disorders, especially multiple myeloma or other B cell
related disorders
2. AA type (secondary): Associated with chronic inflammations, neoplasm,
rheumatoid arthritis, osteomyelitis, tuberculosis, Crohn’s disease,Related to
hereditaru amyloidosis caused by familial mediterranean fever (aotosomal
recessive pattern)
3. Beta 2 microglobulin type: Associated with long-term hemodialysis
4. ATTR type: Associated with familial amyloidosis
5. AH type: Very rare, associated with plasma cell disorders
Electron microscopy: liner, rigid-appearing, nonbranchinf fibrils can be seen
in mesangium and subenthelium, randomly dispersed.
Immunofluorescence: staining for Kappa or Lambda chains.
Gross: the kidney is firm, pale and waxy. Size can vary between large, normal
normal and small. If amyloid deposits in the arteries or arterioles and causes
ischemia, the kidney becomes small.
Pale amyloid
deposits in
enlarged kidney

45. POLYCYSTIC KIDNEY DISEASE
 PKD is a genetic disease in which the kidneys become filled with
hundreds of cysts, causing them to be larger than normal and to
quit functioning over time.
 The blood vessels that feed neighboring healthy nephrons can
get compressed by growing cysts, which prevents them from
receiving oxygen.
 Poorly perfused kidneys respond by activating the renin-
angiotensin-aldosterone system, which facilitates fluid retention
and leads to hypertension.
 Over time, as enough nephrons are affected, it leads to renal
insufficiency and eventually renal failure.
 Also, expanding cysts can compress the collecting system,
causing urinary stasis,
 and in some cases this can lead to kidney stones.
 PKD can be either autosomal dominant (adult PKD) or autosomal
recessive (infantile PKD).

46. AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
 ADPKD is characterized by numerous cysts in the cortex and
medulla causing bilateral enlarged kidneys ultimately
destroying the kidney parenchyma.
 Can be caused by the mutation in the PKD1 gene on
chromosome 16 (85% of cases) or by a mutation to the PKD2
gene on chromosome 4 (15% of cases)
Gross:
- Enlarged kidneys with lumpy surface composed of subcapsular
cysts up to 4 cm.
Cysts contain clear-brown fluid
Microscopically:
- Saccular expansions of all portions of renal tubule and
glomerular capsule that later become disconnected and filled
with fluid
- Cysts are lined with cuboidal or flattened epithelium and may
have papillary projections or polyps
- Functional nephrons exist between cysts with areas of global
sclerosis, tubular atrophy, interstitial fibrosis and chronic
inflammation
- Infants may show primarily cystic dilatation of Bowman's space
- 20% mat have renal adenomas
ADPKD

47. AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
A. Cyst lined by low cuboidal to flat epithelial cells (H&E ×
40). Inset showing high power image of the cystic wall lined
cuboidal epithelium (H&E × 400). B. Aneurysmal, thin dilated
vessels lined by horizontally oriented endothelial cells (H&E ×
200). C. Thick, dilated vessels with excessive surrounding
matrix and edema (H&E × 100). D. Extravasation of red blood
cells and edema surrounding a vessel lined by horizontally
oriented endothelial cells (H&E × 400).
Very rarely, dominant polycystic kidney
disease (DPKD) can manifest at birth,
and microscopically the distinctive
feature in the kidneys is a glomerular
cyst in which a glomerulus is involved
with the cystic change, as shown here.

48. AUTOSOMAL RECESSIVE POLYCYSTIC KIDNEY DISEASE
 ARPKD is characterized by a cystic dilation of the
collecting ducts.
 It often presents in infancy and is associated with
congenital hepatic fibrosis
 Gross:
- Enlarged kidneys with smooth surface
- Small cysts can be seen in the cortex and medulla
- Dilated channels are perpendicular to cortical surface
- Cysts are present in medulla (collecting ducts)
 Microscopically:
- Radially arranged, elongated cysts that form as
dilations of all collecting tubules with fluid accumulation
- Cysts are lined by cuboidal or flattened cells from
collecting tubules
- Normal nephrons without cystic change / interstitial
fibrosis are present in between the cysts
- The liver shows portal fibrosis with complex bile
ductular profiles
- All portal tracts are involved
Macroscopically, the organ
displays multiple small cysts on
its surface and is severely
enlarged.
dilation of collecting ducts

49. SIMPLE AND MESOTHELIAL CYSTS
 Simple cysts are filled with ultrafilatrate. They are very
common and account for the majority of all renal masses.
 Gross:
- Thin walled cortical cysts, measuring up to 10 cm, filled with clear
yellow fluid
 Microscopically:
- Single layer of cuboidal, flattened or atrophic epithelium
- May have thickened walls with hemosiderin laden macrophages
and atrophic epithelium
 Mesothelial cysts are more rare and are lined by mesothelial
cells in the vicinity of the kidney that may present as renal
masses. It is Also called primary retroperitoneal cysts of
mesothelial origin
 Gross:
- Thin walled, unilocular cyst filled with clear fluid. May be
hemorrhagic
 Microscopically:
- Thin walled cyst lined by a single cell lining of nonpleomorphic
with abundant eosinophilic cytoplasm, vesicular nuclei and small
nucleoli. May have small gland-like spaces
Large simple renal cyst of the upper pole.
Other smaller cysts are also scattered around
the kidney. Such simple cysts are unlikely to
compromise renal function.
A: bisected tumor consisting of
a unilocular cyst with
hemorrhage.
B: bisected cyst showing a

50. RENAL ABSCESSES
• An abscess is a collection of pus,
resulting from an infection, most
commonly from bacteria, and the
immune cells that arrive to
eliminate it. The ensuing battle
creates a zone of liquefactive
necrosis, or pus.
• The most common cause of renal
abscess are: infection with
Staphylococcus aureus, UTI, kidney
stones, kidney inflammation.
– Conditions that contribute to
abscess formation form UTI are:
diabetes mellites, pregnancy,
and stone disease.
• The abscesses can be classified by
their anatomical position i.e.-
perinephric, renal cortical, and
• The symptoms of renal
abscesses are fever, chills,
feeling of discomfort, and
abdominal pain. These are very
general symptoms, which
together with the fact that this
pathology is not very common
leads to a high number of
misdiagnosis.
• Diagnosis is done by imaging
techniques such as x-ray or
preferably ultrasound or CT.
• Treatment of renal abscesses is
done by IV antibiotics, and
drainage of the abscess through
a catheter (percutaneous
drainage).

51. RENAL ABSCESSES
In the lower pole of this kidney is a
1 cm pale yellow abscess. Infections
can reach the kidney either by
ascending up the urinary tract
(from a bladder infection, for
example) or by hematogenous
spread with sepsis. This lone
abscess was probably
hematogenous in origin.
The cut surface of the
kidney reveals many small
yellowish microabscesses in
both cortex and medulla.

52. KIDNEY STONES
NEPHROLITHIASIS:
• Kidney stones are crystalized mineral and salts, that can
form in a several locations in the kidney, mainly the calyxes
and renal-pelvis.
• There are several types of stones that can form as a result of
differing pathologies.
• The stone starts small but get bigger over time, as more
minerals and slats aggregate onto it.
• the main causes of kidney stones are, low volume urine due
to dehydration, and an abundance of acid in the urine.
– These can come about due to several different habits
and or pathologies such as: not drinking enough water,
eating too much calcium, salt or animal proteins. Bowel
conditions (diarrhea), obesity, hyperparathyroidism,
family history.
• The main symptom of kidney stones is a sharp, cramping
pain in the lumbar region, that is a result of the body trying
to expel the stone from the ureter.
– Other symptoms of kidney stones are the need to
urinate frequently, dysuria, haematuria, nausea, and
vomiting.
• Diagnosis of kidney stones is done through imaging
techniques such as ultrasound and X-ray which allow the
doctors to measure the size and location of the stone.

53. TYPES OF
KIDNEY
STONES:
There are several types of stones that can form as a result of
differing pathologies.
• These are the most common type (about 80%), and they comes in two
forms, calcium oxalate, and calcium phosphate.
Calcium
stones:
• Represent 5-10% of stones.
• Uric acid is a waste product of purine metabolism, when
there is excess amounts of it it can lead to gout and kidney
stones.
Uric acid
stones:
• Represent 10% of stones.
• Also called infection stones, they form mostly in people with
frequent UTIs, or poor bladder emptying.
Struvite
stones:
• A rare pathology, the cause of which is cystinuria, an inherited
disorder the leads to leakage of cystine into the collecting
ducts.
• These stones tend to be the largest and often need to be
surgically removed.
Cystine
stones:

54. A large staghorn
calculus is seen
obstructing the renal
pelvi-calyceal system.
The lower pole of the
kidney shows areas of
hemorrhage and
necrosis with collapse
of cortical areas

55. Calcium Oxalate
Calcium Phosphate
Uric Acid Struvite
Cystine

56. • Calcium oxalate kidney stones examined
using scanning electron microscopy.
a | outer nodular appearance of a calcium
oxalate (CaOx) monohydrate stone.
b | The fractured surface showing CaOx
monohydrate crystals organized in concentric
laminations and radial striations.
c | Bipyramidal CaOx dihydrate crystals
protruding on the surface are shown (arrows)
and are powdered with tiny calcium phosphate
crystals.
d | The surface of a CaOx monohydrate
stone.

57. RENAL TUBERCULOSIS
 Mycobacterium tuberculosis, a slow
dividing aerobic bacillus bacteria is
the pathogen that causes this
pathology.
 TB infection starts at the lungs, and
can spread throughout the body
through the blood stream.
 The arrival of the bacteria in the
kidneys induces the formation of
granulomas which envelopes them
and starts the process of caseous
necrosis.
 The growing granulomas can either
reach the renal pelvis, burst and
leak the infection to the ureter, or
destroy the cortex and medulla
leading to chronic renal failure.

58. RENAL TUBERCULOSIS
 Microscopic aspect: the
granulomas are infiltrates of
immune cells that envelope and
isolate the bacteria, creating a wall
and inside it the process of
necrosis can be evident.
 Macroscopic aspect: when the
infection grows and the
granulomas burst the normal
parenchyma is replaced with
calcified caseous material
in cyst like formation.

59. 4 . B L A D D E R
I N F L A M M AT O R Y
PAT H O L O G I E S
1. Interstitial Cystitis (Chronic pelvic pain Syndrome)
2. Malacoplakia
3. Polypoid cystitis

60. 1. INTERSTITIAL CYSTITIS OR CHRONIC PELVIC PAIN SYNDROME
 Also called Hunner’s ulcer, painful bladder syndrome.
 Chronic condition most frequently middle-aged white women .
 Etiology – unknown – It may mimic carcinom and therefore very
important to take a biposy to rule out cancerious etiology.
 Characterized by severe intermittent pain in suprapubic area with
symptoms such as frequent and urgent micturation, hematuria and
dysuria.
 Gross : reddened mucosal areas with small vessels radiating towards
towards a central scar, fibrin deposit or coagulum; site may rupture
with oozing of blood and can have bullous edema or normal
appearing urothelium or can have multiple glomerulations.
 Microscopic: may have normal histology ,may have mucosal
ulceration with overlying fibrinous exudates and necrotic
debris ,Lamina propria contains chronic inflammatory cells,
prominent mast cells and fibrosis ,Usually no bacteria
identified.
**Mast cells and fibrosis are common but there is no
specificity and uniformity about this disease in
Inflamed mucosa and massive thickening
of the bladder wall.
Eosinophils and mast cells
within the detrusor muscleSuperficial ulcer and dense
submucosal inflammatory infiltrate
involving the adjacent muscle.

61. 2. MALACOPLAKIA
 Related to bacterial infection by Escherichia coli
and Proteus
 May occur in immunosuppresive transplant
recipients.
 It appears as the macrophage and giant
phagosomes has defect in phagycytosis and
becomes overloaded with undigestied products.
 Gross- Affected kidney has small, discrete,
yellowish-brown nodules or patches; vesical
inflammatory reaction characterized
macroscopically by soft, yellow, slightly raised
mucosal plaques 3-4cm in diameter
 Microscopical – Stained with PAS- shows
infiltration with large, foamy macrophages mixed
with multinucleated giant cells and interspersed
lymphocytes The macrophages shows abundant
granular cytoplasm due to phagosomes and
membranous debris of bacterial origin.
Deposition of calcium in enlarged lysosomes
known as Michaelis-Gutmann bodies are
Accumulation of histiocytes with pale pink foamy cytoplasm (von Hansemann
histiocytes). Diagnostic feature is the presence of intracytoplasmic round
concentric basophilic inclusions (Michaelis-Guttman bodies). – black arrow.

62. 3. POLYPOID-PAPILLARY CYSTITIS
• Non-specific inflammatory lesion characterized by
lamina propria edema and mucosal polypoid or
papillary projections.
• Although indwelling catheters are the most
commonly cited culprits, any injurious agent may
give rise to this lesion.
• Gross :The urothelium is thrown into broad
bulbous polypoid nodules as a result of marked
submucosal edema.
• Microscopy: thin, finger - like papillae or broad
based polypoid lesions with congestion and
edema of lamina propria; mild chronic
inflammatory infiltrate; may have reactive
epithelial atypia or reactive fibroblasts that appear
bizarre; covered by normal appearing or
metaplastic urothelium with orderly maturation
and surface umbrella cells; fronds with fibrosis can
mimic papillary urothelial neoplasms; however,
the fibrovascular cores tend to be simple, non-
branching and broad-based; no hyperchromasia,
no coarse chromatin, no abnormal mitotic figures.
***This condition may be and has been reported to
be confused with papillary urothelial papilloma both
clinically and histologically.
This is a reactive
lesion seen in
response to any
agent that inflames
or injures urothelial
mucosa. The
urothelial lining may
form broad-based
polypoid or slender
papillary structures
that may at first
glance mimic
urothelial neoplasia.
In-dwelling catheters
and colovesical
fistulas are some of
the common causes.
This bladder biopsy
shows several
polypoid and
papillary areas. The
lamina propria
contains dense
friable
edematous
irregular mucosa
with multiple
small polypoid
(<5 mm)
nodules

63. 5. CONCLUSIONS
 A variety of histologic patterns can produce diverse clinical syndromes; thus, for example,
nephritic syndrome and hematuria can be produced by membranoproliferative
glomerulonephritis (GN),, IgA nephropathy (or Berger’s disease), and so on.
 A nephrotic syndrome (NS) can be produced by several diseases: membranous GN, focal and
segmental glomerulosclerosis, minimal change disease, amyloidosis, diabetic nephropathy,
and others.
 In a disease, different patterns of pathologic changes can be seen; for example, in lupus may
appear only mesangial changes, diffuse endocapillary proliferation, membranoproliferative-
like lesions, membranous pattern, or focal segmental (chronic) lesions. This variability in the
morphologic expression has given origin to the classification of lupus nephritis.
 A type of pathologic change can be caused by several diseases: for example, a
membranoproliferative pattern can be seen in lupus, infections, hepatitis and
cryoglobulinemia.
 The changes found in a renal biopsy rarely are specific of a disease, therefore the renal
diagnosis is a process that integrates the clinical information, laboratory data, morphology
and immunopathology to reach the “better diagnosis”.
 Different diseases can have the same pathogenic mechanism; for example, crescentic GN can
be seen in lupus, acute GN, IgA nephropathy, and in all these conditions the formation
mechanism of crescents is related to rupture of glomerular capillary walls with protein
passage to the Bowman’s space.

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66. THANK YOU!