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‫واسع كرمك وقت الحاجة‬

‫‪GU Pathology‬‬
‫‪L1-4‬‬
‫‪Done by :Roaa Mohammad‬‬
 Diseases Affect Glomerular
Nephrotic Syndrome
Massive proteinurea(3.5 gm/ day in adult )
hypoalbuminemia <= 3gm/dl
generalized edema (Periorbital)
hyperlipidemia and lipid urea
No azotemia, hematurea or hypertention

Primary Diseases

Minimal Change Disease (MCD) Lecture 1

Most frequent (65%) in Children 1-7 years but occur in all ages
Normal Light Microscope
EM: effacement of podocyte foot processes & without Ab deposits
IF: Negative
No Hypertention
Selective proteinurea (albumin)
Treatment : Corticosteroid 90% of cases
5% developed chronic renal failure after 25 years
In adult the response is smaller and relapse is common

Focal and Segmental Glomerulosclerosis (FSGS) Lecture 2

Scelerosis affect some not all G
Causes :
1) assosiated with other condition
2) As secondary of other GN
3) Maladaptation after nephron loss
4) Inhereted or congenital (Mutation : Cytoskeleton or related protein expressed in podocyte (nephrin)
Nephrin : transmembrane glycoprotein component of slit diaphragm of foot processes
5) As primary or Ideopathic (20-30%)
The most common Cause of Nephrotic Stndrome in Adults
adult increase to 35% and children remain frequent cause
Unlike MCD , FSGS :
Non selective proteinurea , Higher Hematurea and Hypertention
poor response to corticosteroid with 50% develop RF within 10 years
Adult feel less well than children
Permiability Increasing factor by Lymphocyte in MCD & FSGS (pathogenesis)
Hyaline masses , IgM & complement protein
Morphology :
Increase mesangial trixal
Deposit of Hyaline masses , lipid droplet and endocapillary foam cell
obliteration of the capillary lumen
In EM , effacement if foot processes
Progression of FSGS lead to global scelerosis of G , with progression to RF in 50% after 10 year
Collapsing glomerulopathy" Aggressive type of FSGS“ has worse prognosis
Membranous GN (MGN) - Membranous nephropathy MN
Diffuse thickining of the capillary wall
Subepithelial immunoglobulin containing deposit
most common 30-50 years old
Is a form of chronic immune complex nephritis
Types:
1) Ideopathic : (85%) > insidious development of the nephrotic syndrome
Sexond most common cause of nephrotic syndrome in non diabetic after FSGS
Diffuse subepithelial immune complex deposition
Thickening of glomerular basement membrane and subepithelial deposition of immune complexes
(silver stain, spike)
Anti-PLA2R autoantibodies
immune complex formation that activates the lectin complement pathway and causes podocyte injury
and proteinuria
Two target Ag : PLA2R /THSD7A
2) Secondary membranous nephropathy : Drug / malignant tumer / infection / autoimmune D
LM : Diffuse thickining of the GBM
IF :deposits of immunoglobulins and complement along the GBM (IgG) > Glanular staining
EM :
1)effacement of Foot processes
2)diffuse thickening of the GBM is caused in part by subepithelial dome deposits (Spikes / Dome pattern)
Unlike to MCD :
Non selective proteinurea / Not response to Conticosteroid
Poor prognosis : 60% proteinurea / 30% complete remission / 40% progressive D & RF 2 to 20 y
Membranoprliferative GN (Nephritic And nephrotic)
hypocomplementemic,lobular or mesangiocapillary GN
LM : hypercellularity and thickening of GBM (Similar in both type)
MPGN should be diagnosis with specific etiology , Idiopathic MPGN is diagnosis of exclusion
Essential feature : endocapillary and mesangial hypercellularity, mesangial and subendothelial deposits
and duplicating of glomerular basement membrane.
Clinical Feature :
Either immunoglobulin mediated (Infection , Autoimmune and paraproteinemias )or complement
mediated.( genetic or aquited abnormality in regulatory , Autoimmune and paraproteinemias )or
complement mediated.( genetic or aquited abnormality in regulatory factor) factor)
Traditional classification based on electron microscopy findings:
MPGN type I (subendothelial and mesangial deposits),
MPGN II (intramembranous dense ribbon-like deposits) and
MPGN III (subendothelial and subepithelial deposits)
Type I MPGN:
- Mostly immune complex deposition indicating activation of classic complement pathway
and some alternative complement pathway
C3 is deposited in an irregular granular pattern &IgG
>=50% Nephrotic Stndrome
10-20% Acute nephritis syndrome
~50% low C3
Can be peimary ir Secondary
50% Renal survival at 10 y
Recurs in ~30% of children 6 - 12 months after transplantation
Type 2 MPGN :(Dense deposit D)
- Essential diagnostic feature based on the presence of highly electron dense ribbon-like deposits of the
glomerular basement membrane
Now categorized under C3 glomerulopathies
autoantibody against C3 convertase called C3 nephritic factor
IgG & the early components of the classical complement pathway (C1q & C4) are usually absent.
Result: Hypocomplementemia
Av age of diagnosis 14y
Typically present with renal insufficiency, nearly all with hematuria and 33% with nephrotic syndrome
Also deposits in basement membranes of spleen, choroid and retina
Poorer prognosis than type l; 50% have renal failure in 10 years;
80 - 100%recur after renal transplant
Morphology:
Both types of MPGN are similar by LM.
(Mesangial and endocapillary hypercellularity with lobular accentuation), Irregular
thickening of glomerular basement membrane
double contour / tram track appearance (PAS or silver stain)
splitting" of the GBM
Crescents in ~20% cases

Clinical Course :
50% of MPGN are nephrotic syndrome
prognosis is poor
No remission
40% progress to end stage renal failuer
It tends to recur in renal transplant recipients
 Nephritic Syndrome Lecture 3
proteinurea(<3.5 m2/ day )
RBCs Cast
oligurea
Azotemia (Increase creatinine and urea), hematurea hypertention

Acute Post infectious (Post streptococcal) Glomerulonephritis(PSGN)

No direct effect on the kindney
Immune complex > Ag Exogenous or endogenous
Exogenous >post streptococcal similar proliferative of GN of infection causes by
other organism
Endogenous > SLE
Developed in Children 1-4 y after they recover from a group A,
"nephritogenic"strains or p-hemolytic streptococcal infection.
Initial infection in the pharynx or skin
Pathogenesis
Is immune complex deposition :
Granular deposits of IgG & complement on the GBM
Hypocomplementemia
LM:
proliferation of endothelial and mesangial cells and neutrophilic infiltrate.
In post infectious GN, the most characteristic change by light microscopy is a
Diffuse (affecting nearly all glomeruli), uniform increased cellularity of the G tufts
(caused both by swelling & proliferation of EC & mesangial cells & by a
neutrophilic & monocytic infiltrate)
Necrosis and some times crescents in response to severe inflammatory injury (Both
finding are ominous)
IF
Granular deposit of IgG (Clear in a period about 2 moths)
EM
•immune complexes "subepithelial" humps"in GBM
Clinical Course:
•Acute onset .
•Fever, nausea, and nephritic syndrome.
•Gross hematuria with smoky brown rather than bright red urine
• Mild proteinuria. ~» Periorbital edema azsio alue arellerogyall
•Serum complement levels are low during the active phase of the disease.
• inc serum anti-streptolysin O antibody titers.
•Recovery occurs in most children.
IgA Nephropathy (Berger Disease)
It is the most common causes of current microscopic or gross hematuria
is the most common G disease revealed by renal biopsies worldwide
Depositin of IgA if the mesangium
Children & young Adult
More than 50% present with gross Hematurea 1-2 day of a non specific Uper RTI less
commonly GIT or UT infection , last for several day and return every few months with loin
pain
40% Microscopic Hematurea with or without proteinurea
Up to 10% develop Acute nephritic syndrome
Pathogenesis :
IgA Normaly is low , It is inc in 50% of patients due to inc production of BM
Genetic influence occurs in families and HLA idintical siblings
Studies suggest that inc IgA synthesis in response to respiratory or GIT exposure to
environmental agents> deposition of IgA > activate alternative complement pathway& initiate
G injury
Some viruses and bacteria express N-acetylgalactosamine on their cell surfaces so that
infection may promote anti-glycan antibody formation
Some of these patients proaress slowly to chronic renal failure.
So pathogenesis : abnormality in IgA production and clearance.,
LM: Variable , The G may be normal or mesangeal widening , segmental inflammation and
mesangioproliferative or rarely G crescentic
IF: mesangial deposition of IgA with C3
EM: deposits in the mesangium

Rapidly Progressive (Crescentic) Glomerulonephritis

clinical syndrome(Not specific etiology) characterized by rapid & progressive loss of renal function
with features of the nephritic syndrome,with severe oligurea ,azotemia and death from RF
Pathogenesis :
The G injury is immunologically mediated.
caused by different diseases, some restricted to the kidney & others systemic
Divided into Three groups : A B C on the basis of immunologic findings; all have severe G injury
The disease may be idiopathic or caused by known well difined renal or extra renal D
Morphology:(All 3 group)
Grossly enlarged & pale kidneys, often with cortical petechial hemorrhages
Histology :
Segmental necrosis
GBM breaks
crescents produced by :
1) proliferation of the parietal epithelial cells of Bowman's capsule in response to injury & exudation
of plasma proteins, including fibrin, into Bowman's space
2)migration & infiltration of monocytes /macrophages into Bowman's
space
Group A (12%) Anti (GBM Antibody Crescentic GN)

Characterized by linear deposits of IgG & C3 along the GBM (which can be seen by IF M
Anti-GBM Abs are present in the serum of all patients& are helpful in their diagnosis &
patients benefit from plasmapheresis or immunoadsorption,which removes pathogenic Abs
from their circulation
The disease is either:
idiopathic Anti-GBM Ab GN cases, in which the anti-GBM Abs bind to renal GBM only,
without pulmonary lesions, or
Goodpasture syndrome cases of Anti-GBM Ab GN,in which the anti-GBM Abs bind to GBM as
well as to pulmonary alveolar capillary, BM, causing pulmonary hemorrhages,

Group B: (44%) Immune Complex-Mediated Crescentic GN

Are immune complex-mediated disorders.
This can be a complication of any of the immune complex nephritis, including post
streptococcal GN, SLE, lgA nephropathy, & Henoch-Schönlein purpura.
In some cases, immune complexes can be demonstrated but the underlying cause is
undetermined (Idiopathic).
In all these cases, immunofluorescence studies reveal the characteristic granular ("lumpy
bumpy") pattern of staining of the GBM &/or mesangium for immunoglobulin &/or
complement, demonstrates positivity with antibody to fibrinogen.
These individuals cannot usually be helped by plasmapheresis
Capillary lobe thickened "wire loop” lesion of lupus nephritis (SLE)

Group C: (44%) Pauci-Immune Crescentic GN

Defined by the lack of anti-GBM Abs or significant immune complex deposition detectable by
immunofluorescence & EM.
Most of these individuals have anti-neutrophil cytoplasmic Abs in the serum,which have a role in some
vasculitis.
Therefore,
(I) in some cases group C CrGN is a component of a systemic vasculitis such as microscopic polyangiitis or
Wegener granulomatosis, while
(II) in many cases, however, pauci-immune CrGN is limited to the kidney & is thus called idiopathic.
immunofluorescence M shows NO immunoglobulin or complement, & NO EM detectable deposits.
Clinical Course of all RPGN (CrGN)
RPGN present as nephritic syndrome with severe oliguria & azotemia, & a proteinuria sometimes
approaching nephrotic range. Some patients become anuric & require long-term dialysis or transplantation.
Hereditary Nephritis
Are a group of hereditary G diseases caused by mutations in GBM proteins, the
best-studied one is, Alport syndrome in which nephritis is accompanied by nerve deafness, & eye
disorders including lens dislocation & cataracts
Normally, the GBM is largely composed of type IV collagen, also crucial for normal function
of the lens & cochlea.
The disease is NOT immunologically mediated disease.
Morphology
the G in hereditary nephritis appear unremarkable until late in the course, when secondary
sclerosis may occur. In some kidneys, interstitial cells take on a foamy appearance as a result
of accumulation of neutral fats (foam cells)as a reaction to marked proteinuria.
With progression, there is glomerulosclerosis, vascular sclerosis, tubular atrophy,&
interstitial fibrosis.
Pathogenesis:
Mutation of any one of the a chains of type IV collagen
renal failure occurs between 20-50 yrs of age
EM
GBM thin and attenuated.
GBM later develops splitting and lamination "basket-weave" appearance
Clinically: The inheritance is heterogeneous, being most commonly X linked as a result of
mutation of the gene encoding a5 type IV collagen. Males therefore tend to be affected more
frequently & more severely &are more likely to develop RF than females
Patients present at the age 5 to 20 years with gross or microscopic hematuria & proteinuria, &
overt RF occurs between 20 & 50 years of age.

Chronic Glomerulonephritis Lecture 4

Chronic GN is the final outcome of various forms of G disease, irrespective of whether there has been
preceding G inflammatory injury.
When it is discovered, the G changes are so far advanced that it is difficult to ascertain the original
lesion.
It represents the end stage of a variety of entities, including Cr GN, FSGS, MN, MPGN & lgA
nephropathy.
Although it may develop at any age, it is usually first noted in young & middle-aged adults.
It is a common & important cause of CRF, e.g,
It has been estimated that 20% of chronic GN cases arise with no history of symptomatic renal disease!
Grossly, both kidneys are symmetrically contracted& their surfaces are red-brown & diffusely granular.
Histopathology showing:(Masson trichrome stain)
Advanced scarring & obliteration of the G, sometimes to the point of complete sclerosis.
Atrophy of the tubules in the cortex
Interstitial fibrosis, with marked lymphocytic cell infiltrates.
the small & medium-sized arteries are frequently thick walled& narrowed, due to hypertension
secondary to the chronic GN
Such markedly damaged kidneys are designated "end-stage kidneys"!
Causes and symptoms Vary
Urinalysis : protein urea , urinary cast
C-xray reveal cardiac enlargement & pulmonary edema
ECG- normal or indicate Left ventricular hypertrophy
CT/MRI reveal reduced size of renal cortex
DISEASES AFFECTING TUBULES (T) & INTERSTITIUM L

Tubulointerstitial Nephritis
Causes :
1. bacterial infection.
2. drugs!
3. metabolic disorders
4. physical injury (irradiation).
5. immune reactions.
Reffer a group of inflammatory D
G may be spare or affected only late
pyelonephritis caused by bacteria infection
interstitial nephritis are nonbacterial in origin
It can be divided into
acute
chronic categories on the basis of clinical features & the character of the
inflammatory exudate,

Urinary Tract Infection

Infectious : Acute Pyelonephritis(Upper UTI)

Acute Pyelonephritis is a common suppurative inflammation of the kidney & the renal
pelvis caused by bacterial infection
The great majority of cases of upper UTI are associated with lower UTI.
Gram negative rod (E coli)
Bacteria reach kidney by two routes:
1. Rarest is hematogenous route, through the bloodstream, septicemia or infective
endocarditis
2. Commonest& most important is ascending route from lower UT
UTI most commonly affects females , due to:
close proximity of the urethra to the rectum,
the short urethra
trauma to the urethra during sexual intercourse facilitate the bacterial entry into the
bladder.
Normally, bladder urine is sterile, as a result of the:
Antimicrobial properties of the bladder mucosa
flushing action associated with periodic voiding of urine.
The bladder outflow obstruction or bladder dysfunction predispose to UTI.
Bladder obstruction results incomplete emptying & increase residual volume (urine).
In the presence of stasis ,bacteria introduced into the bladder can multiply undisturbed,
without being flushed out or destroyed by the bladder wall.
Cont.
UTI is common among individuals with UT obstruction, as may occur with benign prostatic
hyperplasia & uterine prolapse, &stones.
UTI also in DM
incompetence of the vesicoureteral orifice that allows bacteria to ascend the ureter into the pelvis
and allows the reflux of bladder urine into the ureters (vesicoureteral reflux)
1-VUR is present in 20% to 40% of young children with UTI, in which VUR is a congenital defect
that results in incompetence of the ureter vesical valve.
2-VUR can also be acquired in individuals with a flaccid bladder resulting from spinal cord
injury& with neurogenic bladder & dysfunction secondary to DM.
Morphology
Grossly, in acute PN,one or both kidneys may be involved. The affected kidney may be normal in
size or enlarged.
Characteristically, multiple abscesses, raised, discrete, & yellowish, are grossly apparent on the
renal surface
The cortical surface is studded with multiple, focal, pale abscesses, Between the abscesses there is
dark congestion of the renal surface
Microscopically
Early, the suppuration is limited to the interstitial tissue, but later the abscesses rupture into
tubules, & the masses of intratubular neutrophils extend into the collecting ducts, giving rise to
the characteristic WBC (granular) casts found in the urine
G not affected
second infrequent form of pyelonephritis is necrosis of the renal papillae, known as Papillary
Necrosis. Which is combination of (I) ischemic + (11) suppurative necrosis of the tips of the renal
pyramids (renal papillae).
1. This is particularly common among diabetics who develop acute pyelonephritis.!
2. May complicate acute pyelonephritis when there is significant UT obstruction.
3. It is also seen with the chronic interstitial nephritis associated with analgesic abuse
gross feature of papillary necrosis is sharply defined, gray-white to yellow necrosis of the apical
2/3 of 1,2 or all,the pyramids papillae
Microscopically , the papillary tips show ischemic coagulative necrosis,
Symptoms
Back pain (loin pain)
Cloudy urine
Tissue pieces (in urine)
Fever
Painful/frequent urination
Urinary incontinence
In terms of cause, almost any condition that involves ischemia can lead to renal papillary necrosis
Analgesic nephronathy is a common cause of renal papillary necrosis(NSAID)
The interstitial tissue are infiltrated with polymorphs, lymphocytes & plasma cells
some tubules show severe cloudy swelling,others, tubular cells are necrotic & contain large number
of bacteria
some tubules are full of pus & lost most of its epithelial lining
Clinically : sudden, with pain at the costovertebral angle ,systemic evidence of infection (chills,
fever, & malaise), & indications of bladder & urethral irritation (dysuria, frequency, & urgency).
Diagnosis : pyuria& bacteriuria by urinalysis & urine culture.
The disease is usually unilateran,In cases with predisposing influences, the disease may become
recurrent or chronic, particularly when it is bilateral The development of papillary necrosis is
associated with very poor prognosis
 Malakoplakia (Very Important)
Malakoplakia is an uncommon chronic granulomatous inflammatory condition, It usually
involves gram-negative bacteria.
It makes its presence known as a papule, plaque or ulceration that usually affects the
genitourinary tract.
It may also be associated with other bodily organs.
Malakoplakia is thought to result from the insufficient killing of bacteria by macrophages.
Therefore, the partially digested bacteria accumulate in macrophages and leads to a
deposition of iron and calcium.
Foamy macrophages with PAS+ granular cytoplasm due to phagosomes stuffed with bacterial
debris and Michaelis-Gutmann bodies (laminated mineralized concretions) Calcium and iron

Drug-Induced Interstitial Nephritis

Two forms:
Acute Drug-Induced Interstitial Nephritis
chronic (Analgesic) Nephropathy
Acute TIN (Tubularintestitial nephritis)
Most common: synthetic penicillins (methicillin, ampicillin)
Others: synthetic antibiotics; diuretics; NSAIDs; other drugs
Pathogenesis
immune mechanism.
Type I hypersensitivity.(any type of drug can cause it)
Cell-mediated (type IV) hypersensitivity reaction.
The drugs act as haptens (small molecule that stimulates the production of antibody
molecules only when conjugated to a larger molecule) So during secretion of the drug by
tubules, covalently bind to some cytoplasmic or extracellular component of tubular cells
&become immunogenic.
The resultant tubulointerstitial injury is then caused by immunological, either IgE-(Type I) or
cell-mediated immune (Type IV) reactions to tubular cells or their BMs.
Morphology
The interstitium shows pronounced (I) edema & (II) infiltration by large numbers of lymphocytes,
macrophages ,eosinophils &neutrophils.
Glomeruli are normal, except in some cases caused by NSAID, when the hypersensitivity
reaction also leads to podocyte foot process effacement & the development of nephrotic
syndrome
With some drugs (e.g., methicillin, thiazides, rifampin), interstitial non-necrotizing
granulomas with giant cells may be seen
Clinically
The disease begins 2 to 40 days (average 15 days) after exposure to the drug
is characterized by fever & rash & eosinophilia in about 25% of persons, & renal abnormalities
including hematuria, mild proteinuria, & leukocyturia.
A rising serum creatinine or, acute RF with oliguria, develops in about 50% of cases,
particularly in older patients.
withdrawal of the offending drug is followed by recovery