pathology of renal syatem

The kidneys:
An Excretory organ or a Regulatory
organ?!!!

• The main purpose of the kidney is to
separate urea, mineral salts, toxins, and
other waste products from the blood.
• They also do the job of conserving water,
salts, and electrolytes.
• At least one kidney must function properly
for life to be maintained.
The Kidneys- function

GLOMERULUS:
• Glomerular capillary wall:
1. Fenestrated endothelium –70 – 100 nm,
2. Glomerular Basement Membrane
.. Lamina rara interna,
.. Lamina densa,
.. Lamina rara externa
3. Visceral epithelial cells (podocytes)
4. Mesangial cells – contract, proliferate,
collagen & matrix, secretion;
THE KIDNEY

Three-dimensional schematic drawing of the glomerulus
Afferent arteriole
Efferent arteriole
Bowman’s
Capsule
Basement membrane
Visceral
Epithelium(Podocyte)
Parietal Epithelium
Capillary
loops
Bowman’s Space
Endothelial cells
Stucture of renal
glomerulus
Mesangial matrix
and cell

Ultramicroscopic
Stucture of
glomerullar
Capillaries
Filtration Mem

Light microphotograph of glomerulus
•Normal
celluarity
;
•Patent
capillary
lumens

• DISEASES OF GLOMERULI
• DISEASES OF TUBULES
• DISEASES OF INTERSTITIUM
• DISEASES OF BLOOD VESSELS
DISEASES OF THE KIDNEY

• AZOTEMIA – BUN, Creatinine
--- GFR
• UREMIA – Azotemia + Clinical signs and
symptoms + Biochemical abnormalities +
Involvement of G I tract, Peripheral nerves
.. and heart;
Clinical manifestations of
renal diseases

• DEFINITION
Abnormalites of glomerular funtion can
be caused by damage to the major components
of the glomerulus: Epithelium (podocytes),
Basement membrane, capillary endothelium,
mesangium.
• Damage manifested by an inflammatory
process.
GLOMERULAR DISEASES

Clinical manifestation of glomerular injury

Histologic alterations
a) hypercellularity:
i) cell proliferation of mesangial cells or
endothelial cells
ii) leukocyte infiltration (neutrophils,
monocytes and sometimes lymphocytes)
iii) formation of crescents
- epithelial cell proliferation (from
immune/inflammatory injury)
- fibrin thought to elicit this injury
(TNF, IL-1, IFN- are others)
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b) basement membrane thickening
- thickening of capillary wall
c) hyalinization (hyalinosis) and sclerosis
-accumulation of material that is
eosinophilic and homogeneous
- obliterates capillary lumen of glomerulus
(sclerotic feature)

classification is based on histology.
Subdivided:
a) diffuse (all glomeruli)
b) global (entire glomerulus)
c) focal (portion of glomeruli)
d) segmental (part of each glomerulus)
e) mesangial (affecting mesangial region)

What causes
glomerular disease ?
Most are of
immunologic origin, and
caused by immune
complexes !
• metabolic stress: DN
• mechanical stress:
• hypertension

 Antibody mediated injury
 In situ immune complex deposition
Fixed intrinsic tissue antigens
collagen type4 antigen [anti GBM-nephritis]
Heymann antigen [membranous nephropaty
Mesangial antigens
Circulating immune complex deposition
Endogenous antigen[DNA,Nuclear
proteins,immunoglobulins,igA]
Exogenous antigen [infectiousagents,drugs]
Cytotoxic antibodies
Cell mediated immune injury
Activation of alternative complement pathway
Pathogenesis of glomerular injury

Pathogenesis of Glomerular Disease
Immune mechanisms underlie most cases of
primary GN and many of the secondary cases
a) 2 forms of Ab-associated injury
i) injury resulting from soluble Ag-Ab
deposits in glomerulus
ii) injury from Ab reacting in-situ with
glomerulus

• In Situ Immune Complex Deposition
a) Ab act directly with intrinsic tissue Ag
“planted” in the glomerulus from the
circulation
b) 2 forms of Ab-mediated glomerular
injury
i) anti-GBM Ab-induced nephritis
- Ab directed against fixed Ag in
ii) Heymann nephritis
- a form of membranous GN
- Ab bind along GBM in “granular
pattern”

Antibody mediated GN -
Circulating Immune complex
Location: Mesangial and sub-endothelial

Antibody mediated GN -
In-situ Immune complex
Location: GBM sub-epithelial
• circulating auto antibodies with intrinsic autoantigens
(component of normal parenchyma)

Antibody mediated GN - In-situ Immune
complex (trapped Ag)
Location: GBM sub-epithelial
Extrinsic antigens planted within the glomerulus

Pathogenesis
In situ immune
complex
Circulating immune
complex
Activation of T
lymphocytes
Acitvation of complements
cytokines
C5b-9 C5a,C3a
Epithelial, mesangial,
Endothelial cells
Macrophagepolynuclear
leucocyte, platelets
Mesangial
cells
oxidative stress, protease, matrix accumulations
Glomerular Disease

Glomerular Diseases
PRIMARY GLOMERULOPATHIES
Acute proliferative glomerulonephritis Post-infectious
Rapidly progressive (crescentic) glomerulonephritis
Membranous glomerulopathy
Minimal-change disease
Focal segmental glomerulosclerosis
Membranoproliferative glomerulonephritis
IgA nephropathy
Chronic glomerulonephritis
SYSTEMIC DISEASES WITH GLOMERULAR INVOLVEMENT
Systemic lupus erythematosus
Diabetes mellitus
Amyloidosis
Goodpasture syndrome
Microscopic polyarteritis/polyangiitis
Wegener granulomatosis
Henoch-Schönlein purpura
Bacterial endocarditis
HEREDITARY DISORDERS
Alport syndrome
Thin basement membrane disease
Fabry disease

Various types of glomerulopathies are
characterized by one or more of four basic
tissue reactions:
1. Hypercellularity
2. Basement membrane thickening
3. Hyalinosis
4. Sclerosis
HISTOLOGIC ALTERATIONS

ACUTE PROLIFERATIVE
(Poststreptococcal, Postinfectious)
GLOMERULONEPHRITIS

• Common form of GN in developing countries.
• 6 to 10yrs of age
• 1 - 4 weeks after a streptococcal infection of pharynx
or skin (Impetigo)
• Group A β-haemolytic streptococci - types 12, 4, 1
• Immunologically mediated disease
• Immune Complex mediated
• Anti - endostreptosin & other cationic antigens .
• Serum – C
Poststreptococcal Glomerulonephritis

Glomeruli-
• Enlarged , hypercellular glomeruli
- infiltration by leukocytes
- proliferation of endothelial &
mesangial cells,
- crescent formation (severe cases)
- obliteration of capillary lumen
• Fibrin deposition in capillary lumen & mesangium.
• Interstitial edema and leucocytic infiltration
• Tubules contain red cell cast.
Microscopy
Diffuse

Immunofluorescence:
- granular deposits of IgG , IgM , C3 in
mesangium , along BM

Electron microscopy:
• Discrete , amorphous , electron dense deposits
on epithelial side of BM often having the
appearance of “humps

• Sudden onset in a young child - malaise,
fever , nausea , oliguria , hematuria,
• Edema , mild - moderate hypertension ,
elevation of BUN
• Urine - RBC casts, proteinuria
• Lab - antistreptococcal antibody titre ,
C3
Clinical Course

• 95% -- children recover,
• < 1% - rapidly progressive GN
• 1-2% - slow progression to chronic GN,
• Persistent proteinuria,
• Abnormal GFR
• Adults
Prognosis
Poor
prognosis

CRESCENTIC
GLOMERULONEPHRITIS
(Rapidly Progressive Glomerulonephritis)
[RPGN]

• Severe glomerular injury
• Does not denote a specific etiologic form of GN
• Clinically - rapid & progressive loss of renal
function & death within weeks to months
• Crescents in most glomeruli – parietal
epithelial cells proliferation;
RPGN
(Crescentic Glomerulonephritis)

• Type - I RPGN ( Anti-GBM antibody induced
disease)
.. Idiopathic,
.. Goodpasture syndrome;
• Type - II RPGN (immune Complex)
.. Idiopathic, postinfecious, SLE, Henoch-
Schonlein purpura (IgA), others;
• Type - III RPGN ( Pauci-immune )
.. ANCA associated, Idiopathic, Wagener
granulomatosis, PAN;
Classification & Pathogenesis

• Linear deposits of IgG , C3 in GBM
• Cross reaction with pulmonary alveolar BM
• Good - Pasture’s antigen located in
noncollagenous portion of α3 domain of
collagen type - IV
Type I - RPGN ( Crescentic GN )

• Immune complex mediated disease
• Complication of immune complex nephritides
- Post infectious GN , SLE , IgA nephropathy
• Granular deposit of immune complexess of
IgG and C3 along glomerular capillary walls.
• IF - lumpy bumpy granular pattern
Type - II RPGN

• Lack of anti GBM antibody , immune
complexes by IF , EM
• ANCA present- defect in humoral immunity.
• Usually a component of systemic vasculitis -
Wegeners Granulomatosis , Polyarteritis
• Idiopathic
Type III RPGN
( Pauci - immune )

• Gross :
Kidneys enlarged , pale ,smooth outer
surface.
C/S petechial hemorrhages on cortical
surface
Morphology

• Crescents
proliferation of parietal cells migration of
monocytes ,macrophages into Bowmans space
• Crescents obliterate Bowman’s space ,
compress glomerular tuft
• Fibrin strands are prominent between cellular
layers in the cresents.
Microscopy

• Crescents Sclerosis
• EM : subepithelial deposits
ruptures in GBM
• IF : Postinfectious cases - granular
Good Pastures syndrome - linear
Idiopathic - granular / linear
Microscopy of RPGN (cont. )

Electron micrograph showing characteristic wrinkling of GBM with focal
disruptions (arrows).

CRESCENTIC
GLOMERULONEPHRITIS
(Rapidly Progressive
Glomerulonephritis)
[RPGN]

RPGN
(Crescentic Glomerulonephritis)
• Severe glomerular injury
• Does not denote a specific etiologic form of GN
• Clinically - rapid & progressive loss of renal
function & death within weeks to months
• Crescents in most glomeruli – parietal
epithelial cells proliferation;

Idiopathic crescentic GN(RPGN) ：
• Type I : with linear deposits of Ig anti－GBM
antibody＋
• Type II: with granular deposits of Ig immune
complex-mediated
• Type III: with few or no immune deposits of Ig
Pauci-immne ,ANCA＋
• Type IV: anti－GBM antibody＋& ANCA＋
• Type V: Pauci-immne，ANCA－
RPGN…..

Type I - RPGN ( Crescentic GN )
• Linear deposits of IgG , C3 in GBM
• Cross reaction with pulmonary alveolar BM
• Good - Pasture’s antigen located in
noncollagenous portion of α3 domain of
collagen type - IV

Type - II RPGN
• Immune complex mediated disease
• Complication of immune complex nephritides
- Post infectious GN , SLE , IgA nephropathy
• Granular deposit of immune complexes of IgG
and C3 along glomerular capillary walls.
• IF - lumpy bumpy granular pattern

Type III RPGN
( Pauci - immune )
• Lack of anti GBM antibody , immune
complexes by IF , EM
• ANCA present- defect in humoral immunity.
• Usually a component of systemic vasculitis -
Wegeners Granulomatosis , Polyarteritis
• Idiopathic

Morphology
• Gross :
Kidneys enlarged , pale ,smooth outer
surface.
C/S petechial hemorrhages on cortical
surface

Microscopy
• Crescents
proliferation of parietal cells migration of
monocytes ,macrophages into Bowmans space
• Crescents obliterate Bowman’s space ,
compress glomerular tuft
• Fibrin strands are prominent between cellular
layers in the cresents.

Microscopy of RPGN (cont. )
• Crescents Sclerosis
• EM : subepithelial deposits
ruptures in GBM
• IF : Postinfectious cases - granular
Good Pastures syndrome - linear
Idiopathic - granular / linear

Clinical Course
• Hematuria , RBC casts , proteinuria
• Hypertension , Edema
• Good - Pastures syndrome -
Hemoptysis
• Anti - GBM , antinuclear , ANCA
• Renal involvement - progressive

Definition
• Manifestation of glomerular disease,
characterized by nephrotic range proteinuria and
a triad of clinical findings associated with large
urinary losses of protein : hypoalbuminaemia ,
edema and hyperlipidemia
- Nelson Textbook of Paediatrics, Vol 2, 19th Edition, page 1801

Why ‘nephrotic range’
• Defined as
– protein excretion of > 3gm/24hr
– First morning protein : creatinine ratio of > 2-3 : 1
Other causes of proteinuria

Proteinuria
• Selective - Low molecular weight proteins
Albumin - 70 kDa
Transferrin – 76 kDa,
• Poorly selective - High molecular weight
globulins

Hyperlipidaemia
Increase in cholesterol , LDL , VLDL ,
Lipoprotein , apoprotein
Decrease in HDL
CAUSES:
• Increased synthesis of lipoproteins in liver
• abnormal transport of lipids
• decreased catabolism

Lipiduria
Leakage across glomerular
capillary wall

Incidence ( paediatric ) ?
• 2 – 7 cases per 100,000 children per year
• Higher in underdeveloped countries ( South
east Asia )
• Occurs at all ages but is most prevalent in
children between the ages 1.5-6 years.
• It affects more boys than girls, 2:1 ratio
http://www.kidney.org/site/107/pdf/NephroticSyndrome.pdf

Etiology
• Genetic
• Secondary
• Idiopathic or Primary

Causes of Nephrotic Syndrome
PRIMARY
• Lipoid nephrosis – ch. 65% - ad. 10%
• Membranous glomerulonephritis – 5%, 30%
• FSGN - 10%, 35%,
• Membranoproliferative GN
SECONDARY
• Diabetes mellitus,
• Amyloidosis,
• SLE,
• Drugs, infections, malignant diseases;

Complex disturbances
immune system
Genetic Mutations /
Mutations in proteins
Extensive effacement of podocyte foot processes
Increased permeability of the glomerular capillary wall
Massive proteinuria
Hypoalbuminaemia
Edema

• Edema
– Mild to start with – peri orbital puffiness, lower extremities
– Progression to generalized edema, ascites, pleural
effusion, genital edema
• Decreased urine output
• Anorexia, Irritability, Abdominal pain and diarrhoea
• Absence of
– Hypertension
– Gross hematuria

Lab Investigations
• Urine Examination
• Complete Blood Count & Blood picture
• Renal parameters :
– Spot Urine Protein : Creatinine ratio
– Urinary protein excretion
– protein selectivity ratio
• Liver Function Test
• Renal Biopsy ???

• Urinalysis - 3+ to 4+ proteinuria
• Renal Function
–Spot UPC ratio > 2.0
–UPE > 3gm/24hr
• Serum Creatinine – normal or elevated
• Serum albumin - < 2.5 gm/dl
• Serum Cholesterol/ TGA levels – elevated
• Serum Complement levels – Normal or low

Additional Tests
• C3 and antistreptolysin O
• Chest X ray and tuberculin test
• ANA
• Hepatitis B surface antigen
Ghai Essential Paediatrics,8th edition, page 478
Indications for Biopsy
• Age below 12 months
• Gross or persistent microscopic hematuria
• Low blood C3
• Hypertension
• Impaired renal Function
• Failure of steroid therapy

MINIMAL CHANGE DISEASE
(Lipoid Nephrosis)

Minimal change disease …
Clinical Course
• Despite massive proteinuria renal function remains
good,
• Proteinuria - highly selective,
• > 90 % children respond to corticosteroid therapy,
• Adults: - slower to respond,
- long term prognosis excellent;

Lipoid Nephrosis
Minimal change Glomerulonephritis
• Most frequent cause of NS in children,
• Peak incidence in children = 2 - 6 yrs
• Sometimes follows respiratory infection /
immunization, HD & atopic disorders.
• characteristic feature : responds to
corticosteroid therapy

Pathogenesis
Immune dysfunction of T cells
cytokine like circulating substance
affects visceral epithelial cells & increases
glomerular permeability

Morphology
• Light microscopy : Glomeruli - Normal,
… Cells of PCT laden with lipid
• Electron Microscopy :
… BM - Normal ,
… No electron dense deposits
Visceral epithelial cells - effacement
of foot processes
• IF: No immune / complement deposits;

Minimal change
Disease:
• Normal BM,
• Absence of
proliferation

Minimal Change Disease
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or.com

Complications
• Edema
• Infections
• Thrombotic complications
• Hypovolaemia and Acute renal Failure
• Steroid Toxicity
Ghai Essential Paediatrics,8th edition, page 480, 481

Prognosis
• Steroid Responsive NS : Good prognosis
( MCNS )
• Steroid Resistant NS : Poor prognosis
( FSGS )

Membranous Glomerulonephritis
• Most common cause of NEPHROTIC SYNDROME
in adults
• Characterised by
- diffuse thickening of the glomerular
capillary wall
- electron dense immunoglobin deposits
along subepithelial side of BM

• Idiopathic - 85%
• Secondary
- Drugs : captopril , penicillamine ,
gold , NSAID,
- Tumors : lung , colon , melanoma
- SLE
- Infections : Hepatitis B,C, Malaria
- Thyroiditis
Causes……

• Chronic immune complex-mediated disease,
• Autoimmune
• Direct damage to glomerulus by C5b - C9
• C5b- C9 induce epithelial & mesangial cells to
secrete proteases & oxidants
Pathogenesis………..

Light Microscopy
Uniform , diffuse thickening of
glomerular capillary wall
Membranous Glomerulonephritis
-- Morphology

Electron Microscopy
• Irregular electron dense deposits between
Basement Membrane & overlying epithelial
cells.
• Basement Membrane laid down between
deposits -SPIKES
• Thickening of spikes -- dome like protrusions --
close over deposits

Immunofluorescence
The granular deposits contain both
immunoglobulins & complement

Clinical Features
• Nephrotic Syndrome
• Nonnephrotic Proteinuria - 15 %
Proteinuria is non-selective & non-
responsive to corticosteroids
• Haematuria & mild Hypertension -15 to 35%

Membranoproliferative
Glomerulonephritis
(Mesangiocapillary Glomerulonephritis)

Definition
• Is a group of disorder # histologically by
alterations in the BM and proliferation of
glomerular cells.
• Proliferation is predominantly in mesangium -
Mesangiocapillary

Classification
• Primary
Type - I MPGN
Type - II MPGN
• Secondary

Type I or classic form ( 70 %)
• Ex of immune complex disease
• # by immune deposits in SUBENDOTHELIAL
position
• I/F/M/ - granular pattern
Ig G +C 3 early
complement components.

Type II or dense deposit disease(30%)
• Alternate complement pathway dis
• Capillary wall thickening is due to the deposition of electron dense
material in lamina densa of GBM. INTRAMEMBRANOUS DEPOSITS
• I/F/M/C3 granular linear foci on either side of BM,
• C3 in circular aggregates (mesangial rings)
• Ig – absent
• Early complement components absent
• Serum C3 reduced

PATHOGENESIS
• Type I : immune complexes
• Type II : Activation of alternate pathway
C3 nephritic factor present in serum

Secondary Glomerulonephritis
-causes
• Malignant epithelial tumors,
ex., ca lung,ca colon,melanoma
• SLE
• Exposure to inorganic salts,Hg.
• Drugs (penicillamine,captopril)
• Infections- HBs,syphilis,MP,schistosomiasis
• Metabolic disorders, DM,Thyroiditis.

Light Microscopy
• Glomeruli large & hypercellular
Proliferation of cells in mesangium
infiltrating leukocytes
Parietal epithelial crescents
• Glomeruli - lobular appearance
• Capillary wall - double contour / tram track appearance-
mesangial interposition.

Tubules- vacuolation and
hyaline droplets.
Interstitium- scattered
chronic inflammatory
cells.
Hypertensive vascular
changes.

Electron Microscopy & IF
• Type - I : sub endothelial deposits
IF - C3 , early complement components (
C1q -C4) , IgG in granular pattern
• Type - II : ( Dense deposit disease )
GBM contains electron dense material in a
ribbon like fashion. C3 is present but no early
complement components

Type - II : ( Dense deposit disease )

Clinical Course
• 50 % develop chronic renal failure in 10 years
• High recurrence rate in transplant patients
especially in Type II disease

IgA NEPHROPATHY
(BERGER DISEASE)

IgA Nephropathy
• Most common type of Glomerulopathy
worldwide
• Prominent IgA deposits in the mesangial
regions

• Genetically determined abnormality of immune
system.
• Mucosal infection---mucosal secretion of IgA.
• IgA complexes entrapped in mesangium.
• Activation of alternate complement pathway – C3
and properdin. absence of early components.
IgA Nephropathy - Pathogenesis

IgA Nephropathy - Morphology
LIGHT MICROSCOPY:
• Glomeruli may be normal.
• Mesangial widening & proliferation
(mesangioproliferative)
• Focal proliferative Glomerulonephritis
Focal segmental sclerosis
• Crescentic Glomerulonephritis

IgA Nephropathy -Immunofluorescence
• Mesangial deposition of IgA
• C3 and properdin
• Lesser amounts of IgG / IgM

IgA Nephropathy - Electron Microscopy
• Electron dense
deposits in the
mesangium
• Prominent
thickening of the
arterioles

IgA Nephropathy - Clinical course
• Affects children & young adults
• Gross haematuria after an infection of
respiratory , gastrointestinal , urinary tract
• Microscopic haematuria with or without
proteinuria : 30 - 40 %
• Acute Nephritic syndrome : 5 - 10 %

CHRONIC GLOMERULONEPHRITIS
Final stage of glomerular disease caused by specific types
of glomerulonephritis:
• Poststreptococcal glomerulonephritis in adults.
• Crescentic glomerulonephritis,
• Membranous nephropathy,
• MPGN,
• IgA nephropathy,
• FSGS

Morphology
• The kidneys are symmetrically
contracted and have diffusely
granular cortical surfaces.
• On section, the cortex is
thinned, and there is an
increase in peripelvic fat.

Microscopy
• obliteration of glomeruli,
transforming them into
acellular eosinophilic masses.
• Arterial and arteriolar sclerosis
• Marked atrophy of associated
tubules
• Iirregular interstitial fibrosis
• Mononuclear leukocytic
infiltration of the interstitium

Chronic glomerulonephritis
• Clinical presentations:
Proteinuria(<3.5g/d);Hematuria;
Hypertension;Edema;Azotema(BUN/Cr↑)
• Pathological manifestations of all of major
glomerulopathies.
• Exclusion of secondary cause :SLE etc.
• To correct the reversible factors:
hypertension, infection, drug toxicity

Cause Light
microscopy
Immunoflorescence Electron Microscopy
Minimal Change
Nephrotic
Syndrome
Normal Negative Foot process fusion
Focal Segmental
Glomerulosclerosis
Focal
sclerotic
lesions
IgM, C3 in lesions Foot process fusion
Membranous
Nephropathy
Thickened
GBM
Fine Granular IgG Sub epithelial deposits
Membranoprolifera
tive
Glomerulonephritis
Type I Thickened
GBM,
proliferation
Granular IgG, C3 Mesangial and
subendothelial deposits
Type II Lobulation C3 only Dense deposits
- Nelson Textbook of Paediatrics, Vol 2 : page 1803, table 521-2

Idiopathic Lab Findings
Minimal Change Nephrotic Syndrome Raised BUN in 15 – 30 %
Highly Selective proteinuria
Focal Segmental Glomerulosclerosis Raised BUN in 20 – 40 %
Membranoproliferative
Glomerulonephritis
Type I Low C1, C4 , C3 – C9
Type II Normal C1, C4 , Low C3 – C9
- Nelson Textbook of Paediatrics, Vol 2 : page 1803, table 521-2

• 14 year-old, male, high-school student
• History: No significant medical history
Fatigue x 3 weeks
– Edema x 1 week
• Physical: Mild generalized edema
• Urinalysis: 4 protein
– Many hyaline casts
– Few granular casts
No RBCs or RBC casts
• Lab Data: proteinuria 4g/d , alb 20g/l,normal renal
function, Hepatitis (-), Auto-immunity Ab (-)
• Renal biopsy
CASE I

Electron Microscopy: effacement and fusion of foot processes

The patient has
Minimal change
disease!

CASE I
• 11 year-old male
• History: Intermittent hematuria x 1 year
Hx of recurrent pharyngitis
• Physical: tonsillitis
• Urinalysis: 15 RBC/HPF
1  protein
RBC casts
• Lab Data: dysmorphic RBC
red blood cells per high-
power field

H&E
Light
microscopy:
diffuse
mesangial
hypercellularity

PAS
mesangial hypercellularity

IgA
Immunofluorescence microscopy: diffuse
mesangial IgA

Electron microscopy: mesangial
electron-dense deposits.

The
Patient Has
IgA nephropathy!

CASE III
• 65 year-old, male, Smoke for 40 years
• History: Fatigue x 3 months
Cough and chest pain x 2 months
Facial edema x 1 week
• Physical: edema,
• Urinalysis: protein ++++
• Lab Data: proteinuria 8g/d ,
alb 24g/l, normal renal function,
Hepatitis (-),
Auto-immunity Ab (-)

Why is a thorough
Clinical evaluation
important in patients
with the nephrotic
syndrome !
Many such
patients have
an occult
malignancy !

CASE III
LM-PASM:”spikes” along the GBM

CASE III
IF: IgG deposition along GBM

CASE III
EM: subepithelial electron dense material

It’s Clearly a case Of
carcinoma related
Membrano proliferative
nephropathy !

Clinical syndromes and presentation
Latent GN
(asymptomatic
urinary
abnormalities)
Nephrotic
syndrome
Acute GN RPGN Chronic GN
microscopic or
Macroscopic
hematuria
Proteinuria
Dysmorphic
Glomerular
erythrocytes
Proteinuria>3.5g/d
Hypoalbuminemia
Hyperlipidemia
Edema
Hematuria
Proteinuria
(1-3g/d)
ARF
Edema
Hypertension
Red cell casts
•Rapidly
deterioration of
renal function
•Hematuria,
Proteinuria
• oliguria or anuria
Red cell casts
•With or without
systemic symptom
•Hematuria,
Proteinuria
•Hypertensio
n
•Reduced GFR

Lupus nephritis
• Renal involvement tends to occur within the first 2 years
of SLE .
• Almost half of patients present with asymptomatic urine
abnormalities, such as hematuria and proteinuria.
• Lupus nephritis reduces survival 88% at 10 years.

Immune complex formation
deposition in the kidney
intraglomerular inflammation
activation and proliferation of resident renal
cells
necrosis or apoptosis

International Society of Nephrology/ Renal Pathology Society (ISN/RPS)
classification of lupus nephritis (2003)
Class I Minimal mesangial lupus nephritis
Class II Mesangial proliferative lupus nephritis
Class III Focal lupus nephritis
Class IV Diffuse segmental (IV-S) or global (IV-G) lupus nephritis
Class V Membranous lupus nephritis
Class VI Advanced sclerosing lupus nephritis

• Class I: Minimal Mesangial Lupus Nephritis
Normal glomeruli by light microscopy, but
mesangial immune deposits by IF.
• Class II: Mesangial Proliferative Lupus
Nephritis
Purely mesangial hypercellularity of any degree
or mesangial matrix expansion by light
microscopy, with mesangial immune deposits.

Class III: Focal Lupus Nephritis
focal segmental endo- or extracapillary
glomerulonephritis involving <50% of all glomeruli,
typically with focal subendothelial immune deposits, with
or without mesangial alterations.

• Class IV: Diffuse Lupus Nephritis
(most common & most severe form)
diffuse subendothelial immune deposits, with or without mesangial
alterations.
This class is divided into diffuse segmental (IV-S) lupus nephritis when
50% of the involved glomeruli have segmental lesions, and diffuse
global (IV-G) lupus nephritis when 50% of the involved glomeruli have
global lesions.

• Class V: Membranous Lupus Nephritis
Global or segmental subendothelial immune deposits with
or without mesangial alterations.
Class V lupus nephritis may show advanced sclerosis.
• Class VI: Advanced Sclerotic Lupus Nephritis
90% of glomeruli globally sclerosed without residual
activity.

Types of renal lesions
• Diabetic glomerulosclerosis
 Diffuse glomerulosclerosis
 Nodular glomerulosclerosis
• Vascular lesions
• Diabetic pyelonephritis
• Tubular lesions

“DIFFUSE GLOMERULOSCLEROSIS”
• refers to enlarged glomeruli .
• Glomerular basement membrane thickening.
• Mesangial expansion with predominance of
increased mesangial matrix.

Diabetic
glomerulosclerosis

2) Glomerular capillary subendothelial hyaline (hyaline caps).
Green Arrow
Glomerular
hyalinosis is
formed by plasma
components that
are accumulated
in peripheral
segments of the
tuft, also it is
called hyaline
cap or fibrin cap
(Masson’s
trichrome, X400).

3) Capsular drops along the parietal surface of the Bowman
capsule
• Homogenous, hyaline deposit, in the
Bowman’s capsule.
• Usually it is rounded or elongated and it is
highly suggestive of DN.
• Although non-pathognomonic (it can be
occasionally seen in hypertension and other
idiopathic nodular glomerular lesions).

The arrow indicates a
beautiful capsular drop.
In this image we see the
capsular drop red, but in
other cases we can see
it with a green or blue
tone;
(Masson’s trichrome,
X400).

Hyalinematerial is seen in
capillary
loops, including in a
globally sclerosed
glomerulus, and there is a
large capsular drop on the
inside
of Bowman’s capsule of
the surviving glomerulus

Nodular glomerulosclerosis
• Kimmelstiel-Wilson nodules (nodular
glomerulosclerosis
• Spherical, eosinophilic, with a central acellular area,
and they can be surrounded by a ring of cells.
• They stain blue or green with the trichrome stain and
they are positive with PAS and methenamine-silver
stains.

Nodular lesion as well as
mesangial expansion;
There is a typical
Kimmelstiel-
Wilson nodule at the top of
the glomerulus (arrow)
(periodic acid–Schiff).

The larger nodules
usually have a
laminated aspect
(arrow)
Notice the variability
in the size of nodules
in this glomerulus,
something that usually
does not happen in
amyloidosis nor in light
chain deposits disease
(Masson’s trichrome,
X400).

The prominent
concentric lamination
with the silver stain
(arrow).
This finding is very
characteristic of
nodular diabetic
glomerulosclerosis.
(Methenamine-
Silver, X400)

1) Afferent and efferent glomerular arteriolar hyalinosis within 3 to 5
years after onset of diabetes
Afferent and Efferent arteriolar
hyalinosis. Diffuse and nodular
mesangial expansion
Glomerular arteriole showing
complete replacement of the
smooth muscle wall by hyaline
material and lumeral narrowing
(PAS stain)

Renal biopsy specimen from
the woman of 58 with
diabetic glomerulopathy.
Arterioles have severe
hyalinosis

Tubular changes in DNP
In tubules there are Nonspecific changes:
Armani-Ebstein change (or Armani-Ebstein cells)
Deposits of glycogen in the tubular epithelial cells.
It is very rare to see it at the present time; it appears in
decompensated diabetics with glycemia superior to
500 mg/dL and severe glycosuria.

DEFINITION
• Nephrolithiasis refers to renal stone
disease
• urolithiasis refers to the presence of
stones in the urinary system.
• Stones, or calculi are formed in the
urinary tract from the kidney to bladder
by the crystallization of substances
excreted in the urine
•

ETIOLOGY
METABOLIC
LIFESTYLE
GENETIC FACTORS
DRUGS
OTHERS

Kidney Stone Formation
• Causes:
– Highly concentrated urine, urine stasis
– Imbalance of pH in urine
• Acidic: Uric and Cystine Stones
• Alkaline: Calcium Stones
– Gout
– Hyperparathyroidism
– UTI
– Medications
• Lasix, Topamax, Crixivan
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RISK FACTORS
IMMOBILITY
SEDENTARY LIFE
STYLE
DEHYDRATION
METABOLIC
DISTURBANCES
HISTORY OF
RENAL
CALCULI

PATHOPHYSIOLOGY
Slow urine flow
supersaturation of urine
with the particular element
crystallized
stone

PATHOPHYSIOLOGY
• Damage to the lining of the urinary
tract

PATHOPHYSIOLOGY
Decreased inhibitor substances
supersaturation and crystalline
aggregation

Types of Stones
• Calcium Oxalate
– Most common
• Calcium Phosphate
• Struvite- mag+ammo+ca phos
– More common in woman than men.
– Commonly a result of UTI.
• Uric Acid
– Caused by high protein diet and gout.
• Cystine
– Fairly uncommon; generally linked to a hereditary disorder.

Calcium stone
Imbalance
supersaturation &
inhibitors of urine
Crystal
stone

Mixed stone (struvite)
UTI
Urea splitting
organism (proteus)
Urease
Production of stones

Uric acid stone
Acidic urine
Solubility of uric acid
Ppt of uric acid crystals
Uric acid stone

CLINICAL MANIFESTSTIONS
• Severe
abdominal or
flank pain
• Frequency and
dysuria
• Oliguria and
anuria in
obstruction

CLINICAL MANIFESTSTIONS
• Hematuria
• Renal colic
• Nausea
• hydronephrosis

Treatment
• Two Focuses of Treatment:
– Treatment of acute problems, such as pain, n/v, etc
– Identify cause and prevent kidney stones from reoccurring
• Acute Treatment:
– Pain Medication!!!
– Strain urine for stones
– Keep Hydrated
– Ambulation
– Diet Restrictions
– Emotional Support
– Invasive Procedure (may be necessary)
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Definition
• Hydronephrosis is the aseptic dilatation of the
renal pelvis or calyces.
• It may be associated with obstruction but may
be present in the absence of obstruction.
• There is accompanied destruction of kidney
parenchyma.
6/3/2015 Hydronephrosis - Intro 210

Etiology
• It can be Unilateral or bilateral.
• Unilateral maybe extramural, intramural or
Intraluminal
• Bilateral causes are either congenital or
acquired

Unilateral hydronephrosis
• By some form of ureteric
obstruction, with the ureter
above the obstruction being
dilated.
Causes
A. Extramural obstruction
B. Intramural (in the walls)
C. Intraluminal

Causes of Unilateral hydronephrosis
A. Extramural
1. Obstruction by Aberrant renal vessels (vein or
artery). It is common on left side.
2. Compression by growth ( CA cervix, carcinoma
rectum)
3. Retroperitoneal fibrosis (Ormond disease)

B. Intramural
1. Congenital PUJ obstruction
2. Ureterocele
3. Neoplasm of ureter
4. Narrow ureteric orifice
5. Stricture ureter following removal of stone, pelvic
surgeries or tuberculosis of ureter.

C. Intraluminal
1. Stone in the renal pelvis
2. Sloughed papilla in papillary necrosis

Bilateral Hydronephrosis
• Result of urethral obstruction ; but may also
be caused by one of the lesions described
above occurring on both sides

Causes of Bilateral hydronephrosis
A. Congenital
• Congenital stricture of external urethral meatus, pin-hole
meatus.
• Congenital posterior urethral valve.
B. Acquired
• BPH
• Carcinoma prostate
• Postoperative bladder neck scarring
• Inflammatory / traumatic urethral stricture
• Phimosis
• Carcinoma cervix
• Bladder carcinoma

Gross
• Moderate to marked
enlargement of kidney.
• Extra renal
hydronephrosis
• Intra renal
hydronephrosis

Microscopy
• Atrophy of tubules and
glomeruli
• Thickened sac
• Chronic inflammatory
cell infiltrate
• Interstitial fibrosis.

Tubular & TUBULOINTERSTITIAL
diseases

TUBULOINTERSTITIAL DISEASES
• Primary tubulointerstitial disease of the
kidney characterized by histologic and
functional abnormalities that involve the
tubules and interstitium to a greater degree
than glomeruli and renal vasculature.
• Primary tubular disease- Acute tubular
necrosis
• Tubulointerstitial disease- pyelonephritis

Acute Renal Failure
Classification
• Destruction of tubular epithelial cells
• Acute suppression of renal function
• Pre-renal (functional/hypoperfusion)
• Renal (structural/intrinsic)
• Post-renal (obstructive)

Problems affecting the flow of blood before it
reaches the kidneys
• Dehydration
• Blockage or narrowing of a blood vessel carrying
blood to the kidneys.
• Heart failure or heart attacks causing low blood
flow.
Pre-renal causes

Acute Tubular Necrosis
• Acute tubular necrosis
showing focal loss of
tubular epithelial cells
(arrows) and partial
occlusion of tubular
lumens by cellular
debris (D) (H&E stain).

Acute Tubular Necrosis
• Tubular epithelial degeneration and
hyaline amphophilic casts

TUBULOINTERSTITIAL NEPHRITIS
1. Infective
.. Acute Bacterial pyelonephritis
.. Chronic pyelonephritis
.. Tuberculous pyelonephritis
.. Other Infections ( Viruses, parasites)

2. Toxins
.. Acute hypersensitivity interstitial
nephritis
.. Analgesic nephropathy

3. Metabolic Diseases
.. Urate nephropathy
.. Nephrocalcinosis
.. Hypokalamic nephropathy
.. Oxalate nephropathy

4. Physical Factors
.. Chronic Urinary Tract Obstruction
.. Radiation nephropathy
5. Neoplasms
.. Multiple myeloma

6. Immunologic Reactions
.. Transplant Rejection
.. Sjogren syndrome
.. Sarcoidosis

7. Vascular Diseases
8. Miscellaneous
.. Balkan nephropathy
.. Nephronophthisis-medullary cystic
disease
.. “Idiopathic” Interstitial nephritis;

Pyelonephritis
Affects :
• Tubules
• Interstitium
• Renal pelvis
TYPES:
• Acute
• Chronic

Etiology & Pathogenesis
• Gram negative bacilli - > 85%,
.. Escherichia coli,
.. Proteus,
.. Klebsiella,
.. Enterobacter
.. Streptococcus faecalis,
.. Staphylococci
.. Others

Pathways of
Renal Infection
HAEMATOGENOUS ROUTE
•Septicemia
•Infective endocarditis
•Debilitation
•On immunosuppressive therapy
•Nonenteric organisms;

Pathways of
Renal Infection
ASCENDING INFECTION:
1. Colonisation of distal
urethra

Pathways of
Renal Infection
ASCENDING INFECTION
2. Common in females:
- Short urethra,
- Lack of defensive fluids
- Hormonal changes –
- Urethral trauma – sexual
intercourse;

Pathways of
Renal Infection
ASCENDING INFECTION
3. Multiplication in bladder:
- Outflow obstruction,
- Bladder dysfunction
Residual volume of urine
(Bacterial Growth)

Pathways of
Renal Infection
ASCENDING INFECTION
4. Vesicoureteral Reflux
Incompetence of
vesicoureteral valve

Pathways of
Renal Infection
ASCENDING INFECTION
5. Intrarenal Reflux

Clinical features
• Fever
• Chills
• Loin pain
• Lumbar tenderness
• Dysuria
• Frequency of micturition

Ac. Pyelonephritis –
Multiple abscesses

• Yellow-white abscess with
haemorrhagic rim.

Ac. Pyelonephritis - Neutrophilic infiltration

Acute Pyelonephritis
COMPLICATIONS:
• Papillary necrosis
… Diabetes mellitus,
… UT obstruction
• Pyonephrosis
… Complete obstruction
• Perinephric abscess
… Extension through the renal capsule

Acute Pyelonephritis – Clinical Course
• Uncomplicated cases with
appropriate antibiotic treatment
recovery is complete

Chronic Pyelonephritis
And Reflux Nephropathy

Chronic pyelonephritis
• Chronic tubulointerstitial renal disorder in
which repeated interstitial inflammation is
associated renal scarring and pelvicalyceal
damage.
TYPES OF CHRONIC PYELONEPHRITIS:
• Chronic Reflux-associated
• Obstructive pyelonephritis

Reflux nephropathy
• Common in childhood
• Unilateral or bilateral
• Congenital absence or shortening of
intravesical portion of ureter.
• Sterile reflux - no infection
• UTI + congenital vesicoureteral reflux +
intrarenal reflux

Chronic obstructive pyelonephritis
• Infection + obstructive lesions
• Recurrent bouts of renal inflammation- renal
damage and scarring
• Bilateral – posterior urethral valve,
• Unilateral
- urolithiasis, ureteric anomalies;

MORPHOLOGY:
Gross-
• Small and contracted, unequal reduction.
• Surface is irregularly scarred, capsule is adhered.
• Blunting and dilation of calyces.
• Dilated pelvis.

Chronic
Pyelonephritis:
-Coarse polar
scars with
underlying
-Blunted calyces

microscopy
• Tubular atrophy
• Dilated tubules filled with colloid casts
(Thyroidisation)
• Interstitial inflammation and fibrosis
• Wall of renal pelvis and calyces- ch.inflammation
• Hyaline arteriosclerosis if hypertension is
present;
• Periglomerular fibrosis;
• Xanthogranulomatous variant –
(foamy macrophages, pl. Cells, lymphocytes,
neutrophils, giant cells)
-- proteus infection + obstruction;

Diseases Involving
Blood Vessels of the Kidneys

• Nearly all renal diseases of the
kidney involve the renal blood
vessels secondarily.
• However the main diseases affecting
blood vessels of the kidney are
1. Benign nephrosclerosis ,
2. Malignant nephrosclerosis
3. Thrombotic microangiopathies.

I- Benign nephrosclerosis
• This lesion describe the renal changes in benign
hypertension.
Morphology:
• The kidneys are symmetrically atrophic with diffuse
fine granularity.
• Capsule is adherant to cortical surface.
• V shaped scar.

• Benign nephrosclerosis. The smaller arteries in the kidney have become thickened and
narrowed. (Hyaline arteriolosclerosis.) This leads to patchy ischemic atrophy with focal loss
of parenchyma that gives the surface of the kidney the characteristic granular appearance
(symmetrical)

61
 Patchy ischemic atrophy with focal loss of parenchyma that gives
the surface of the kidney the characteristic granular appearance (symmetrical)

Microscopically
hyaline arteriolosclerosis
• Homogenous pink hyaline thickening of
vessel wall & narrowing of lumen.
• Proliferation of smooth muscle cells in
intima.
• Parenchyma- ischemic atrophy of
kidney includes-
• glomerular shrinkage, collagen in
bowmans space, periglomerular fibrosis,
tubular atrophy and interstitial fibrosis.

62
Benign nephrosclerosis.
High power view of two arterioles with hyaline
deposition, marked thickening of the walls, and
narrow lumen.
hyaline deposition, marked thickening of the walls
narrow lumen

Malignant Nephrosclerosis
Malignant hypertension may occasionally
develop in previously normotensive
individuals
but often is superimposed on
• Preexisting essential benign hypertension
• Secondary forms of hypertension, or
• An underlying chronic renal disease,
particularly glomerulonephritis or
reflux nephropathy

Gross-
• The kidney is enlarged, edematous.
• Small pinpoint hemorrhage may appear on
cortical surface due to rupture of arterioles .
• It has flea bitten appearance.
Morphology

• In malignant nephrosclerosis.
• The kidney demonstrates focal small pinpoint hemorrhages. Giving a flee
bitten appearance

Microscopically:
• Hyperplastic arteriolosclerosis- It show onion-skin
concentric laminated thickening of the wall of
arterioles with progressive narrowing of the lumen.
• Necrotising arteriolitis- fibrinoid necrosis.
• Tubular loss,interstitial fibrosis and foci of necrosis.

• Thickening of the arterial wall with malignant hypertension also produces
a hyperplastic arteriolitis The arteriole has an "onion skin" appearance.

• Malignant hypertension leads to fibrinoid necrosis of small arteries as
shown here. The damage to the arteries leads to formation of pink fibrin--
hence the term "fibrinoid

Malignant hypertension
• Clinical picture:
It is characterized by
• Marked elevation of blood pressure (diastolic
pressure more than 120 mm/Hg)
• Papilledema
• Encephalopathy
• Renal failure
• Cardiac abnormalities.

Malignant hypertension
• Malignant hypertension require immediate
treatment .
• Death may occur particularly in those without
treatment, due to
• Renal failure
• Cerebrovascular accident
• Cardiac failure.

• Benign
.. Cortical adenoma,
.. Renal fibroma
.. Angiomyolipoma
.. Oncocytoma
• Malignant
.. Renal cell carcinoma,
.. Wilms tumour
TUMOURS OF THE KIDNEY

RENAL CELL CARCINOMA
Adenocarcinoma of kidney,
Hypernephroma

• 1 to 3% of visceral cancers,
• 85% of renal cancers in adults
• 6th and 7th decades of life,
• M : F = 2 to 3 : 1
• Histogenesis – Tubular epithelium
Renal cell carcinoma

Lack of physical activity
Drugs
smoking
High caloric diet

RISK FACTORS:
• Tobacco smokers
• Obesity - (women)
• Hypertension
• Estrogen therapy
• Exposure to asbestos, heavy metals, petroleum
products
• CRF, acquired cystic diseases.
• Tuberous sclerosis
• Mostly sporadic
Renal cell carcinoma - Epidemiology

Genetic and hereditary conditions
Von Hippel-Lindau (VHL) Disease
Hereditary Papillary Renal Cell Carcinoma
Hereditary Leiomyomatosis Renal Cell Carcinoma Syndrome
Hereditary Renal Oncocytoma
Polycystic Kidney Disease

HISTOLOGIC TYPES
Clear cell RCC .
Papillary RCC .
Chromophobe RCC .
Collecting duct RCC .
Unclassified RCC .
RENAL CELL CARCINOMA

Three classic diagnostic features of renal cell carcinoma
Hematuria (50%), costovertebral pain, mass
• Asymptomatic/incidental finding
• Constitutional symptoms (fever, malaise, weakness, and
weight loss)
• Present with metastasis (lungs and bones )
• Paraneoplastic syndromes
Clinical features of RCC

Paraneoplastic syndromes
– Polycythemia 5-10%
– Hypercalcemia
– Cushing’s syndrome
– Hypertension
– Feminization or masculinization
– Eosinophilia, leukemoid reactions, and amyloidosis
Clinical features of RCC

• Grossly: Mainly polar, spherical yellow variegated tumor
with hemorrhagic, necrotic & cystic areas. May extend
into renal vein.
• Microscopically:
– Clear cell carcinoma: (70-80%)
– Papillary carcinoma: (10-15%)
– Chromophobe renal carcinoma (5%)
– Sarcomatoid carcinoma
RENAL CELL CARCINOMA (RCC)

Clear Cell
Renal Cell Carcinoma
Total nephrectomy
(gross)
(Most common renal tumor in adults)

Renal cell carcinoma arising in the middle pole of the kidney. Fairly circumscribed, The cut surface demonstrates
a yellowish areas, white areas, brown areas, and hemorrhagic red areas.
RCC

RENAL CELL CARCINOMA (RCC)
Clear cell carcinoma solid to trabecular or
tubular growth pattern
rounded or polygonal
shape and abundant
clear or granular
cytoplasm, which
contains glycogen and
lipids

Renal Cell Carcinoma, Clear Cell, Type
(microscopic)

Chromophobe renal carcinoma
• 5% of all RCC
• Arise from cortical collecting ducts or their intercalated
cells
• composed of cells with prominent cell membranes and
pale eosinophilic cytoplasm, usually with a halo around
the nucleus
• General good prognosis

Prognosis: 5 yr survival is around 70% in the absence of
distant metastases
With renal vein invasion or extension into the
perinephric fat, the figure is reduced to
approximately 15% to 20%
Renal cell Carcinoma

Wilms Tumor
• 1 in every 10,000 children in the United States
• most common primary renal tumor of childhood
• peak incidence for Wilms tumor is between 2 and 5
years of age
• 5% to 10% of Wilms tumors involve both kidneys

• Congenital anomalies related:
• WAGR syndrome: WT1 (11p13)
• DENYS-DRASH syndrome: similar path.
• BECKWITH-WIEDEMANN syndrome: WT2
Wilms Tumor

Wilms Tumor
Clinical
• Tumor has tendency to easily metastasize
• major complaint is associated with large size of
the tumor - readily palpable mass
• Good outcome with early diagnosis.

Wilms Tumor
• less common complaints include
– a) fever
– b) abdominal pain
– c) hematuria
– d) intestinal obstruction (uncommon)

NEPHROBLASTOMA (WILM’S TUMOR)
GROSSLY:
• Large well-circumbscribed soft tan-gray homogenous
tumor.
• Solitary & unilateral.
• C/S- variegated appearance- soft, fish-flesh like tumor,
foci of necrosis and haemorrhage , cartilaginous
element.

MICRO:
• Mixture of primitive epithelial and
mesenchymal elements.
• Small, round to spindled anaplastic tumor
cells.
• Abortive tubules and poorly formed glomeruli.
• Mesenchymal elements- muscle, cartilage and
bone, fat cells & fibrous tissue.
• Blastemal, stromal and epithelial elements
• Prognosis: Currently 90% long term survival

MICRO: Blastemal, stromal and epithelial elements

• 2 to 5 yrs common
• Palpable abdominal mass
• Hematuria,
• Pain,
• Intestinal obstruction,
• Hypertension
• Pulmonary metastases
Wilms tumour – Clinical Course

PROGNOSIS
• Very good,
• Nephrectomy + chemotherapy,
• 2 yrs survival – 90%
Wilms tumour – Clinical Course

Urinary bladder tumors
• Exophytic papilloma
• Inverted papilloma
• Papillary urothelial neoplasms of low malignant potential
• Low grade and high grade papillary urothelial cancers
• Carcinoma in situ (CIS, or flat non-invasive urothelial carcinoma)
• Mixed carcinoma
• Adenocarcinoma
• Small-cell carcinoma
• Sarcomas

Bladder Carcinoma
• Derived from transitional epithelium
• Present with painless hematuria
• Prognosis depends on grade and depth of
invasion.
• 5th decade. M>F
• Overall 5y survival = 50%
Things you must know

Etiology
• Cigarette Smoking
• Industrial Chemicals :
Dye workers, Dry Cleaners, Hair Dyes
o-aminophenol is the carcinogen
Slow acetylators have more risk
• Schistosoma hematobium
• Chronic Bladder infection

Etiology
• Bladder calculi
• Long term indwelling catheter
• Past history of upper urothelial cancers
• Chlorinated municipal water
• Radiation Exposure
• Use of Cyclophosphamide
• Mutation of p53, Rb gene and p21 gene

Pathology
• Most Common Type is Transitional Cell
Carcinoma 93%
Papillary Flat
Benign Dyspalsia
Malignant Cis
Invasive Cancer

Pathology
• Squamous Cell Carcinoma
• Adenocarcinoma
• Small Cell Cancer
• Rhabdomyosarcoma
• Lymphoma
• Melanoma
• Secondaries frm other sites
• Primary UB Pheochromocytoma

Clinical Features
• Painless gross hematuria 75%
• Symptoms of Bladder irritation
• Advanced disease : pelvic pain, ureteral
obstruction, HUN, Rectal obstruction

Bladder Carcinoma
Morphology
The gross patterns of urothelial tumors vary from
purely papillary to nodular or flat
Papillary lesions appear as red, elevated
excrescences varying in size from less than 1 cm
in diameter to large masses up to 5 cm in
diameter
Multicentric origins
Trigone

Urinary bladder tumors
large papillary tumor
multifocal smaller papillary neoplasms

Bladder Carcinoma
Grading of Urothelial (Transitional Cell Ca)
WHO/ISUP Grades
Urothelial papilloma
Urothelial neoplasm of low malignant
potential
Papillary urothelial carcinoma low grade
Papillary urothelial carcinoma, high grade

Low-grade papillary urothelial carcinoma with an overall orderly
appearance, with a thicker lining than papilloma and scattered
hyperchromatic nuclei and mitotic figures (arrows)

High-grade papillary urothelial carcinoma with marked cytologic
atypia

Cystic Diseases of the Kidney
Cystic diseases of the kidney are
heterogeneous, comprising
Hereditary
Developmental
acquired disorders

Classification of renal cysts
1. Multicystic renal dysplasia
2. Polycystic kidney disease
a. Autosomal-dominant (adult) polycystic disease
b. Autosomal-recessive (childhood) polycystic
disease

3. Medullary cystic disease
a.Medullary sponge kidney
b. Nephronophthisis
4. Acquired (dialysis-associated) cystic disease
5. Localized (simple) renal cysts

6. Renal cysts in hereditary malformation
syndromes (e.g., tuberous sclerosis)
7. Glomerulocystic disease
8. Extraparenchymal renal cysts
(pyelocalyceal cysts, hilar lymphangitic
cysts)

Is a genetic disorder
characterized by the growth
of numerous cysts in the
kidneys
• Adult type- Autosomal
dominant .
• Infantile type- autosomal
recessive.

Adult polycystic kidney disease
Inheritance
Autosomal dominant- PKD gene
mutations in genes located on chromosome
16p13.3 (PKD1) & 4q21 (PKD2)
Pathologic Features
 Large multicystic kidneys, liver cysts, berry
aneurysms

Clinical Features or Complications
Hematuria, flank pain, urinary tract infection,
renal stones, hypertension
Chronic renal failure beginning at age 40–60
years

Morphology (Gross)
kidneys are usually bilaterally enlarged
external surface appears to be composed solely of a
mass of cysts, up to 3 to 4 cm in diameter, with
no intervening parenchyma

Microscopic examination
functioning nephrons dispersed between the cysts
The cysts may be filled with a clear, serous fluid or, more
usually, with turbid, red to brown, sometimes hemorrhagic
fluid
The cysts arise from the tubules throughout the nephron and
therefore have variable lining epithelia
Bowman capsules are occasionally involved in cyst formation,
and glomerular tufts may be seen within the cystic space

Microscopy
• cysts to be markedly
dilated tubules that
contain granular
eosinophilic material
(probably protein) and in
some cases, red blood
cells.
• The glomeruli are
compressed.

A hereditary disorder characterized by
multiple expanding cysts of both kidneys
that ultimately destroy the renal
parenchyma and cause renal failure

Childhood polycystic kidney disease
Inheritance
Autosomal recessive
Genes – ARPKD1
Pathologic Features
 Enlarged, cystic kidneys at birth

Subcategories
depending on the time of presentation
1. Perinatal
2. Neonatal
3. Infantile
4. juvenile
Chidhood polycystic kidney disease

Clinical Features or Complications
Hepatic fibrosis
Variable, death in infancy or childhood

Morphology
The kidneys are enlarged and have a smooth external
appearance
On cut section, numerous small cysts in the cortex and
medulla give the kidney a spongelike appearance
Dilated elongated channels are present at right angles to
the cortical surface, completely replacing the medulla
and cortex

Morphology

Childhood polycystic kidney disease
microscopic examination
there is cylindrical or, less commonly, saccular
dilation of all collecting tubules
The cysts have a uniform lining of cuboidal
cells, reflecting their origin from the
collecting ducts.

Microscopy
• sub-capsular
nephrogenic zone with
glomeruli (arrow).
• Lower cortex and
medulla shows numerous
cysts of varying sizes
lined by cuboidal
epithelium (arrowheads).
• Interstitium shows foci of
mild lymphocytic
infiltrate.

Medullary Sponge Kidney
• Characterized by multiple cystic dilatations of
collecting ducts in medulla.
• Generally clinically benign, but recurrent
nephrolithiasis and UTI may lead to renal
insufficiency
• Sometimes autosomal dominant, but usually
sporadic mutations

• Prevalence unknown, but seen in 10-20% of
patients who form calcium stones
• Diagnosis usually incidental - made by IVP,
with dilation of cystic ducts showing “brush”
appearance radiating outward from calyces
• U/S and CT less specific – show
nephrocalcinosis

Gross
• Enlarged kidney.
• c/s- several, small,
cystically dilated
papillary ducts, which
may contain spherical
calculi.
• Cysts are lined by
cuboidal epithelium/
transitional
epithelium.

Clinical Characteristics
• Usually asymptomatic - incidental
• Recurrent calcium phosphate or calcium
oxalate stones – concretions within cysts act
as nidus for stone formation
• UTI (secondary to stones, stasis)
• Hematuria

Aplasia/agenesis
 Bilateral – fatal
 Unilateral –
compatable with
normal life,
contralateral kidney
hypertrophed
 Failure of
mesonephric duct to
bud

Crossed Ectopia /
Crossed Dystopia
• Both kidneys lie in one loin
• May be fused with each
other or separate
• Ureter of lower crosses
midline to open into
bladder on its normal side
30-march, 2010, tuesday 382

pathology of renal syatem

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