‫بسم هللا الرحمن الرحيم‬

After hours, or maybe days, of working hard, WE “THE

PATHOLOGY TEAM” are proud to present
“PATHOLOGY OF THE RENAL SYSTEM”, I hope you guys
like it . Plz give us your prayers.

Credits:
1st part = written by Assem “ THe AWesOme” Kalantan revised by
A.Z.K

2nd part = written by TMA revised by A.Z.K

3rd part = written by Abo Malik revised by ‫خالد القرني‬.‫د‬

4th part = written by A.Z.K revised by Assem “ THe AWesOme”

Kalantan

5th part = written by The Dude revised by TMA

figures were provided by A.Z.K

Page styling and figure embedding by:

If u find any error, or u want to share any idea

then plz, feel free to msg me 
[email protected]

Table of Contents

2
 Topic page

THE NEPHROTIC SYNDROME 4

Minimal Change Disease 5

MEMBRANOUS GLOMERULONEPHRITIS 7

FOCAL SEGMENTAL GLOMERULOSCLEROSIS 9

MEMBRANOPROLIFERATIVE 11
GLOMERULONEPHRITIS

Nephritic Syndrome 16

Acute Postinfectious GN 17

IgA Nephropathy (Berger Disease) 18

Crescentic GN 20

Chronic GN 21

Urinary Tract OBSTRUCTION, 23

RENAL STONES 23

HYDRONEPHROSIS 25

ACUTE POLYNEPHRITIS 27

CHRONIC PYELONEPHRITIS 30

DRUG-INDUCED Interstitial Nephritis 32

Tumors of the kidney and urinary 33

bladder
Benign tumors 33

Clear Cell Carcinomas 34

Papillary Renal Cell Carcinoma 34

Chromophope Renal Carcinomas 35

Wilms'Tumor 37

WAGR syndrome, Denys-Darsh syndrome 37

Beckwith-Wiedemann syndrome 38

Tumors of the Urinary Bladder and Collecting 40

System

3
 part 1
THE NEPHROTIC SYNDROME

refers to a clinical complex that includes the following:

(1) massive proteinuria - daily loss of 3.5 or more in the urine

(2) hypoalbuminemia - plasma albumin levels less than 3 g/dL
(3) generalized edema - the most obvious clinical manifestation
(4) hyperlipidemia and lipiduria

 The initial event is a derangement in the capillary walls of the glomeruli,

resulting in increased permeability to the plasma proteins

 In the normal kidney - the glomerular capillary wall, with its endothelium,
basement membrane (GBM), and podocytes , acts as a barrier through which
the glomerular filtrate must pass.

 Any increased in permeability allows protein to escape from the plasma into
the glomerular filtrate.  Massive pruteinuria

 Long standing proteinuria  hypoalbuminemia drop in osmotic pressure

 generalized edema  drop in plasma volume

 Compensatory to the drop of plasma volum, secretion of aldosterone, along

with the reduced GFR and reduction of secretion of natriuretic peptides,
promotes retention of salt and water by the kidneys  worsening the edema

 Repeating of this chain of events  accumulation of massive edematous fluid

(anasarca)
 Hyperlipidemia may occur but its not really understood, most likely (but not
certainly) because hypoalbuminemia triggers increased synthesis, abnormal
transport and impairment of breakdown of lipoproteins.

 The lipiduria, reflects the increased GBM permeability to lipoproteins.

Causes of nephrotic syndrome :

- < 15 years old  almost always caused by a lesion primary to the kidney
- Adults  often associated with a systemic disease

Table. Cuases of Nephrotic Syndrom

4
 MINIMAL CHANGE DISEASE (LIPOID NEPHROSIS)

 A benign disorder that is the most frequent cause of the nephrotic syndrome
in children

 It is characterized by:
- normal appearance of glomeruli under the light microscope
- diffuse effacement of podocyte foot processes when viewed with the
electron microscope

 It may develop at any age, but it is most common between ages 1 and 7 years.

5
 Pathogenesis :

Based on some experimental studies, the proteinuria has been attributed to a T-

cell derived factor that causes podocyte damage and effacement of foot
processes. However, this is not established in the human disease. (they don`t
realy know ^^)

Morphology :

 The cells of the proximal convoluted tubules are often heavily laden with
lipids, but this is secondary to tubular reabsorption of the lipoproteins ( this
appearance of the proximal convoluted tubules is the basis for the older term
for this disease, lipoid nephrosis )

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  Even with the electron microscope, the glomerular capillary wall appears
normal.

 The only obvious glomerular abnormality is the uniform and diffuse

effacement of the foot processes of the podocytes  The cytoplasm of the
podocytes appears smeared

 The changes in the podocytes are reversible after remission of the

proteinuria.

 There are also epithelial cell vacuolization, microvillus formation, and

occasional focal detachments.

Clinical Course :

 There is no hypertension.

 Renal function is preserved.

 Selective proteinuria (mainly albumin loss)

 Prognosis is good  90% of cases respond to a short course of corticosteroid

therapy

 Proteinuria recurs in more than two thirds of the responders

 5% develop chronic renal failure after 25 years

 Adults also respond to steroid therapy, but the response is slower and
relapses are more common.

MEMBRANOUS GLOMERULONEPHRITIS (MEMBRANOUS NEPHROPATHY)

 Slowly progressive & common between ages 30 and 50 years

 Secondary MGN occurs in association with :

(1) infections (chronic hepatitis B, syphilis, schistosomiasis, malaria)

(2) malignant tumors (carcinoma of the lung and colon and melanoma)

(3) SLE and other autoimmune conditions

(4) exposure to inorganic salts (gold, mercury)

(5) drugs (penicillamine, captopril, nonsteroidal anti-inflammatory agents)

 85% of PRIMARY MGN are idiopathic

7
 Pathogenesis :

 Non-idiopathic MGN is caused by exogenous (e.g., hepatitis B virus) or

endogenous (DNA in SLE) antigen

 Idiopathic forms of MGN are thought to be induced by antibodies reacting in

situ to endogenous or planted glomerular antigens.

 The lesions is similar to those of experimental Heymann nephritis (simply a

MGN induced in rats).

 How does the glomerular capillary wall become leaky?

Absence of neutrophils, monocytes, or platelets and the presence of
complement (C5b – C9)  direct action of complements on the glomerular
epithelial cell  activation of glomerular mesangial and epithelial cells 
liberation of proteases and oxidants that can damage capillary walls

 The epithelial mediators also seem to reduce nephrin synthesis and

distribution.

Morphology : (see fig. below)

 By light microscopy  diffuse thickening of the GBM (normal in early stages)

 By electron microscopy  the thickening is caused in part by subepithelial

immunoglobulin-containing deposits that lie against the GBM

 Spike and dome pattern:

Small, spikelike protrusions of GBM matrix that separate the deposits from
each others

 As the disease progresses, these spikes incorporate the deposits into the GBM

 The podocytes lose their foot processes

 Later in the disease, the incorporated deposits are catabolized and eventually
disappear, leaving cavities within the GBM. These cavities are later filled in by
deposition of GBM-like material

 With further progression, the glomeruli become sclerosed and hyalinized.

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 Clinical course :

 Non-Selective proteinuria (in contrast to minimal change disease)

 proteinuria persists in over 60% of patients

 40% of patients suffer progressive disease  renal failure in 2 to 20 years

 10% to 30% have benign course with partial or complete remission of

proteinuria.

FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSG)

Can be
(1) in association with HIV infection or heroin addiction
(2) as a secondary event in other forms of GN
(3) as a component of glomerular ablation nephropathy
(4) in an inherited congenital form (Abnormal podocytes)
(5) as a primary disease. (10% of all cases of the nephrotic syndrome)

9
 Pathogenesis :

 Pathogenesis of primary FSG is unknown.

 Injury to the visceral epithelial cells and the resultant disruption of visceral
epithelial cells is thought to represent the hallmark of FSG

 Entrapment of plasma proteins and lipids in foci and reaction of the

mesangial cell to such proteins and to fibrin deposits (hyalinosis & sclerosis)

 IgM and complement proteins are present

Morphology :

 At first, it affects only some of the glomeruli (hence the term “focal”) and only
the juxtamedullary glomeruli, eventually all levels of the cortex are affected

 Lesions occurring in some tufts within a glomerulus and sparing of the others
(hence the term “segmental”)

 Increased mesangial matrix & Collapsed basement membranes

 Deposition of hyaline and lipid

 Immunofluorescence microscopy  immunoglobulins, usually IgM, and

complement in the areas of hyalinosis

 Electron microscopy  effacement of foot processes and detachment of

podocytes (greater than lipoid nephrosis)

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 Clinical course :

 Hematuria and Hypertension (higher incidence than lipoid nephrosis)

 Non–selevtive proteinuria

 Poor response to corticosteroid (50% develop renal failure within 10 years)

MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS (MPGN)

 MPGN is manifested by
- alterations in the basement membrane and mesangium
- proliferation of glomerular cells

 5% to 10% of cases of idiopathic nephrotic syndrome

 Some patients present only with hematuria or proteinuria

 Two major types of MPGN (I and II)

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 Pathogenesis :

 Type I :
Circulating immune complexes, akin to chronic serum sickness
The inciting antigen is not known
occurs in association with:
- hepatitis B and C antigenemia
- SLE
- infected atrioventricular shunts
- secondary infections with antigenemia

 Type II :
C3 nephritic factor (C3NeF)  activate the alternative complement pathway
 elaboration of biologically active complement fragments

Morphology :

By light microscopy : (Both types are similar)

- glomeruli are large and show proliferation of mesangial cells

- infiltrating leukocytes

- The GBM is thickened

- the glomerular capillary wall often shows a double contour or "tram

track" appearance (evident in silver & PAS stains) caused by “splitting”
of the GPM due to the inclusion within it of processes of mesangial and
inflammatory cells extending into the peripheral capillary loops.

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 By electron microscopy :

(1) Type I (2/3 of cases)

- Subendothelial electron-dense deposits

- C3 is deposited

- IgG

- complement components (C1q and C4)

(2) Type II

- IgG is usually absent

- complement components (C1q and C4) are also absent

- C3 is present

- irregular lamina densa and subendothelial space of the GBM

- deposition of material of unknown composition (Dense Deposit

Disease)

Clinical course :

 Poor prognosis (worse in type II)

- 40% develops renal failure

- 30% develops renal insufficiency

- 30% persistent nephrotic syndrome without renal failure

(so, all are screwed :P)

 MPGN, usually type I, may occur in association with other known disorders
(secondary MPGN)

- SLE

- Hepatitis B & C

- Chronic liver disease

- Chronic bacterial infection

 Idiopathic cases are believed to be associated with hepatitis C .

End of Part 1

by Assem “ THE AWESOME” Kalantan

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 ____________________________________________________________________________________________

Additional figures :

14
15
 2nd part
Nephritic Syndrome
By TMA

Outline
1. General Characteristics of the Nephritic Syndrome

2. Primary Causes

a. The Nephritides

i. Acute Postinfectious Glomerulonephritis (Poststreptococcal

GN)

ii. IgA Nephropathy (Berger Disease)

b. Rapidly Progressive GN (RPGN or Crescentic Glomerulonephritis-CrGN)

3 immune causes:

i. Type I (Anti-Glomerular basement membrane or Anti-GBM)

ii. Type II (Immune Complex-Mediated)

iii. Type III (Pauci-immune)

iv. Summary of RPGN

c. Chronic GN

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 General Characteristics of the Nephritic Syndrome
1. Hematuria
a. Gross (may be a smoky brown urine)
b. Microscopic
2. Oliguria
3. Azotemia
a. Increased blood nitrogen
b. Increased creatinine
c. Decreased GFR
4. Some proteinuria (not as much as in nephrotic syndrome, but may come close)
5. Hypertension (b/c of decreased GFR and/or rennin released by ischemic kidney)

Some things you need to know:

 Primary glomerular disease affects the glomeruli first and last and rarely
affects anything else

 Some systemic diseases (SLE-systemic lupus erythematosus) may be

primary causes of the nephritic syndrome

Note: Secondary causes of Nephritic syndrome will not be discussed.

Almost all primary causes are autoimmune.

Acute Postinfectious GN (Poststreptococcal)

It is an immune complex disorder. Diffuse proliferation and swelling of

resident glomerular cells (Proliferative GN) is a strong characteristic. When the
glomerular basement membrane (GBM) is also affected by this proliferation and
swelling it becomes membranoproliferative GN (commonly seen when SLE is the
primary cause).

Exogenous causative antigens include streptococcus, staphylococcus,

pneumococcus, mumps, measles, chicken pox and hepatitis B and C. This is
usually associated with a leukocyte infiltrate (commonly neutrophils).

Endogenous antigens show GBM thickening and are best exemplified by

SLE.

During the active stage, look for IgG and complement deposits on the GBM
(the excess deposit of complements results in hypocomplementemia).

17
 Morphology:

The most characteristic change in postinfectious GN is a fairly uniformly

increased cellularity of the glomerular tufts that affects nearly all glomeruli,
hence the term "diffuse" (see figure). Increased cellularity of glomeruli because
of proliferation and swelling of the endothelial and mesangial cells as well as a
leukocytic infiltrate of monocytes and (mostly) neutrophils in the capillary walls.
This may lead to capillary wall necrosis and a characteristic “crescent” formation
in the urinary space in response to the inflammatory injury.

Immune complexes may be seen as subendothelial, intramembranous,

occasionally mesangial but mostly subepithelial “humps” on the GBM. These
usually clear over the next two months.

Clinical course:

Clinically, there is malaise, slight fever, nausea and a mild nephritic

syndrome. Proteinuria may be severe enough to reach the level of that in the
nephrotic syndrome (this doesn`t mean it will transform to nephritic syndrome).
Gross hematuria with smoky brown urine (instead of being bright red) is one of
the reasons the patient goes to see the doctor. Recall that strep. releases
antistreptolysin-O. Antibodies (from now on I will use “Ab’s”) are raised against
this and may be used in diagnosis. Recall that complements are low in the active
phase. RPGN (part 2c) with the characteristic “crescents” or chronic renal
disease may develop in some children. Note that chronicity is far more common
in adults (again, uncommon in children). 15-50% of all patients develop end-
stage renal failure.

IgA Nephropathy (Berger Disease)

It affects children and young adults. An episode of gross hematuria (which

last for a few days and recurs every few months) will develop within 1 or 2 days
of a nonspecific upper respiratory tract infection. It is THE MOST COMMON
GLOMERULAR DISEASE REVEALED BY BIOPSY and THE MOST COMMON CAUSE
OF GROSS AND MICROSCOPIC HEMATURIA.

Some believe it to be a localized variant of Henoch-Schonlein purpura

(this is systemic and characterized by a purpuric rash over-skin, abdominal pain-
GIT, and arthritis-joints). Both, however, have the main feature of IgA deposition
in the mesangium.

It may be a result of abnormal production of IgA from the marrow (recall

that IgA is usually associated with secretion from the mucosa) or clearance.
Celiac disease (intestinal mucosal defects) or liver disease (decreased
hepatobiliary IgA clearance) patients are at an increased risk of Berger’s Disease,
especially when the respiratory or GI tracts are exposed to environmental
antigens. In half of all patients (with Berger’s) there is increased serum IgA and

18
 an absence of complements C1q and C4 complements (suggesting activation of
the alternative complement pathway). There may be a genetic predisposition.

Morphology:

Mesangial widening and inflammation of segments of some glomeruli

(segmental or focal proliferative GN) or diffuse mesangial proliferation or, rarely,
crescentic GN may be seen microscopically. The characteristic
immunofluorescence picture is of mesangial deposition of igA, often with C3
and properdin (see figure)

Clinical course:

More than half of patients have episodes of gross hematuria (after

respiratory or GI or urinary infection). 30-40% have microscopic hematuria with
or without proteinuria. Remember that the episodes last a few days and recur
every few months. 25-50% of patients may eventually develop chronic renal
failure.

19
 Rapidly Progressive GN (Crescentic GN or CrGN)

It is a nephritic syndrome with rapid and progressive loss of renal

function. Renal failure and death result in weeks to months.

Parietal cells of Bowman’s capsule proliferate and, along with a

monocyte/macrophage infiltrate, takes on a crescentic appearance. Remember,
in poststrep GN the infiltrate is in the capillary wall and is mostly neutrophils.

The autoimmune cause can be divided into three types:

Type I CrGN (Anti-GBM)

Deposits of IgG, often with C3, on the GBM. In some these also bind to
pulmonary capillaries producing pulmonary hemorrhages associated with renal
failure. When this occurs the condition is preferably called Goodpasture
Syndrome (if there is no pulmonary involvement it is a pure type I CrGN and is
considered idiopathic).

Diagnose through the identification of Anti-GBM Ab’s. Plasmapheresis is

very beneficial to these patients as it removes the harmful Ab’s.

Morphology:

The kidneys are enlarged and pale with petechial hemorrhages.

Segmental glomerular necrosis and GBM breaks result. This, as well as the
infiltrate (mostly monocytes/macrophages) causes the parietal cells of
Bowman’s capsule to proliferate giving rise to the crescents. These crescents
may scar as they obliterate the capsule and compress the glomeruli.

Immunoflourescence reveals IgG and C3 by linear staining.

20
 Type II CrGN (Immune Complex-Mediated)

This could complicate any immune complex nephritide. Segmental

necrosis, GBM breaks and crescent formation may be seen, but the factor that
differentiates it from type I is that the healthy segments in glomeruli show signs
of complex deposition (diffuse proliferation and leukocyte exudates in SLE or
postinfectious GN, and mesangial proliferation in IgA nephropathy or Henoch-
Schonlein Purpura). The granular appearance of the GBM or mesangium is
described as being “lumpy bumpy” in immunoflourescence because of the Ig or
complement deposition. Plasmapheresis does not help.

Type III CrGN (Pauci-Immune)

Pauci- refers to few or some. From the name you can imagine that there is
not as much immune interaction. There are no anti-GBM Ab’s or immune
complexes to be found. The causative agent is the Antineutrophil Cytoplasmic Ab
discussed in the vasculitides. So, type III CrGN may be a complication of
microscopic polyangiitis or Wegener granulomatosis, but in most cases it is
idiopathic (when its limited to the kidney).

Morphology:

As in the previous two, there is segmental necrosis, GBM breaks and

crescent formation. Healthy segments are normal and immunoflourescence is
almost normal (God knows what this means, probably the ANCA).

Summary of RPGN

It is a classic nephritic syndrome with pronounced oliguria and azotemia.

Proteinuria may approach nephrotic levels. Patients may require long-term
dialysis or kidney transplantation. In general, the lower the number of crescents
(best if <80%) the better the prognosis.

Plasmapheresis may benefit some patients, especially those with type I

RPGN.

Chronic GN

This is not always a result of preceding glomerular inflammatory injury,

but it is an important cause of end-stage renal failure (presenting as chronic
renal failure). About a third to half of all patients on long-term renal dialysis or
waiting for transplantation have chronic GN. 20% of all cases may arise with no

21
 prior history of symptomatic renal disease, and are usually young or middle aged
adults.

Morphology:

Kidneys are symmetrically contracted, red-brown and diffusely granular.

Advanced scarring of glomeruli sometimes leads to complete sclerosis and
obliteration of glomeruli (see figure). There is marked interstitial fibrosis,
atrophy and loss of many cortical renal tubules. Hypertension causes small and
medium sized arteries to thicken with narrowing of the lumina.

The infiltrate seen here is lypho but very rarely plasma cells may also be
found in the fibrotic tissues. In most cases by the time the condition is discovered
it is impossible to tell where the lesion began in the kidney, lending the name of
“end-stage kidneys”.

Clinical course:

Its onset is insidious and discovery is usually late by routine check-up.

Transient nephritic or nephrotic syndromes may be seen, but what brings the
patient is usually the edema that results from proteinuria. Sclerosis slowly limits
the proteinuria, but never stops it completely. Hypertension may also bring the
patient to do a check-up. Microscopic hematuria is usually present, but at this
stage “grossly bloody urine is infrequent.”

22
 Renal dialysis and transplantation prevent the inevitable progression to
uremia and death.

End of 2nd part

By TMA

Part 3

Urinary Tract OBSTRUCTION

URINARY TRACT OBSTRUCTION

RENAL STONES (UROLITHIASIS)
 Calculus formation at any level of urinary collecting system

PATHOGENESIS
 Composition

o 80% of renal stones are composed of

either:

 Calcium oxalate

 or calcium oxalate mixed with

calcium phosphate.

o 10% are composed of magnesium

A large kidney stone that obstructed
ammonium phosphate and; the calyces of the lower pole of this
kidney, leading to a focal
hydronephrosis (dilation of the
collecting system).
o 69% are either uric acid or cystine stones.

 Causes of stone formation (often obscure):-

o Supersaturation ( urine conc. Of stone constitutes)

o 50% of the patients who develop calcium stones have

hypercalciuria (absorptive hypercalciuria)

23
 o 5% to 10% of patients, there is hypercalcemia (due to
hyperparathyroidism, vitamin D intoxication or sarcoidosis) and
consequent hypercalciuria .

o 5% hyperoxaluria or hypercitraturia and the remainder are

unknown cause.

o A high PH favor crystallization of calcium and formation of Mg

ammonium phosphate stones .(NOT uric acid or cystine stone
formation which favored by  PH)

o Excessive Uric acid excretion in urine favors Calcium stone

formation.

o Magnesium ammonium phosphate (struvite) stones almost

always occur in patients with a persistently alkaline urine due to
UTIs

o Bacteria may serve as nidi for the formation of any kind of stone.

o In avitaminosis A, desquamated squamous from the metaplastic

epithelium of the collecting system act as nidi

o Gout and diseases involving rapid cell turnover, such as

leukemias, lead to high uric acid levels in the urine and the
possibility of uric acid stone.

o Cystine stones, genetically determined defect in the renal

transport of certain amino acids.

o Lack of inhibitors of crystal formation in urine (including

Tamm-horsefall protein pyrophosphate, mucopoly-saccharides,
diphosphonates and a glycoprotein called nephrocalcin)

MORPHOLOGY
 Unilateral in about 80%.

 Common sites of formation are renal pelvis, calyces and bladder.

 Tend to be small

 May be smooth or jagged.

 Staghorn calculi.

CLININCAL COURSE

24
  Large stones may be present without producing symptoms or
significant renal damage.

 Smaller stones may pass into the ureter, producing a typical intense
pain known as renal or ureteral colic.

 Gross hematuria.

 Predispose the patient to bacterial infection.

HYDRONEPHROSIS
 Dilatation to the renal pelvis and calyces with accompanying atrophy of
the parenchyma, caused by obstruction to the outflow of urine.

 May be sudden or insidious.

 Any level of the urinary tract.

 Bilateral hydronephrosis occurs only when the obstruction is below

the level of ureters.

 Even with complete obstruction, glomerular filtration persists for some

time.

 Affected calyces and pelvis become dilated.

 Compression of the renal vasculature.

 The most sever effects are seen in papillae , because they are subject to
the greatest increase in pressure.

 Initial functional disturbances are largely tubular, manifested primarily

by impaired concentrating ability.

 Serious irreversible damage occurs in

o about 3 weeks with complete obstruction

o in 3 months with incomplete obstruction.

 Causes:

Congenital Acquired

Atresia of the urethra Foreign bodies: calculi, necrotic papillae.

Valve formations Foreign bodies: calculi, necrotic papillae.

Renal ptosis with torsion or Tumors and Hypertrophy:

kiniking of the ureter
 Prostatic hypertrophy

25
  Carcinoma of the prostate

 Bladder tumors

 Contiguous malignant disease

(retroperitoneal lymphoma,
carcinoma of cervix or uterus)

Aberrant renat artery Inflammation:

 Prostatitis

 Ureteritis

 Urethritis

 Retroperitoneal fibrosis

Neurogenic: Spinal cord damage with

paralysis of the bladder

Normal pregnancy: mild and reversible

 Morphology (macroscopically):

o Bilateral or Unilateral hydronephrosis.

26
 o Kidney may be massively enlarged and greatly distended
pelvicalyceal system.

o Renal parenchyma is atrophied, obliteration of the papillae

and flattening of the pyramids.

o When obstruction is sudden and complete, glomerular filtration

is compromised relatively early, and renal function may cease
while dilation is still comparatively slight

o Hydroureter (dilated of the ureter).

 Morphology (microscopically):

o Tubular dilation, followed by atrophy and fibrous replacement of the

tubular epithelium with relative sparing of the glomeruli.

o Glomeruli also become atrophic and disappear(in sever cases).

 Clinical course:

o Bilateral:

 complete obstruction produces anuria(non-passage of urine)

which is soon brought to medical attention.

 Incomplete obstruction causes polyuria(passage of large

volumes of urine) rather than oliguria.

o Unilateral hydronephrosis:

 May remain completely silent for long periods unless the other
kidney is for some reason not functioning.

o Symptoms due to underlying cause such as renal calculi or an

obstructing tumor draw attention to the hydronephrosis.

INFECTIONS OF THE KIDNEY

1.ACUTE POLYNEPHRITIS

DEFINITION
It is Suppurative inflammation of the kidney and renal pelvis (UTI) involving
upper and lower tracts (majority).

PATHOGENESIS
 Organisms:

o Common: Gram negative Ecoli( the commonest ), proteus,

klebsiella, pseudomonas, enterobacteria.

27
 o Rare: Strep. Feacalis & staph.

 Routes of infection:

o Hematogenous (less common than acending infection)

o Ascending infection from Lower urinary tract common in

female

28
  Predisponsing factors:

o Outflow obstruction(with age esp. in males because of prostatic

hyperplasia and frequent Instrumentation)

o Bladder dysfunction (diabetic pateint)

o Pregnancy (4% -6% of pregnant develop bacteriuria and 20%-40%

of these develop symptomatic urinary infection if not treated)

o Immunosuppression & immunodeficiency are

 Urine stasis in bladder.

 Reflux of urine into ureter (Vesicoureteral reflux, VUR) & into tip of
papillae (intrarenal reflux)

 Diabetes tends to increase risk of complication (because of

susceptibility to infection & neurologic bladder dysfunctionurine
stasis  Ascending infection )

 Morphology:

29
  Macroscopically:

o Multiple, Discrete ,Yellowish and Raised abscesses

 Microscopically:

o Suppurative necrosis with abscess formation within renal

parenchyma(early stage: limited to interstitial tissue , later:
abscess rupture into tubules)

o Large masses of intratubular neutrophil

o Involvement of renal pelvis and calyces

o Papillary necrosis.

o Acute or chronic cystitis.

COMPLICATIONS
 Necrotizing papillitis

 Pyonephrosis

 Perinephric abscess

CLINICAL FEATURES:
 Sudden onset of pain, fever, malaise.

 Pyuria & bacteriuria.

 Painful urination (dysuria)

 Recurrent UTI (esp. in bilateral condition)

 Necrotizing papillitis has poor prognosis with sepsis and renal

failure.

CHRONIC PYELONEPHRITIS (PN)

DEFINITION & FACTS

 Interstitial inflammation with scarring of renal parenchyma and
deformity of pelvic calyces.

 Important cause of chronic renal failure.

 Two forms :

- Chronic obstructive pyelonephritis

-chronic reflux pyelonephritis (Reflux Nephropathy) -more common-

30
 MORPHOLOGY

 Macroscopically

o Unilateral or bilateral

o Patchy or diffuse scar involve pelvis &calyces.

o Asymmetrical scar

 Microscopically:

o Uneven interstitial fibrosis & chronic inflammatory cells.

o Dilation or contraction of tubule (thyroidization)

o fibrosis of calyceal mucosa.

o Vascular change.

o Glomeruli normal OR focal sclerosis

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 CLINICAL COURSE :
 Gradual onset of:

o Renal insufficiency.

o Hypertension

o Polyuria, proteinuria, chronic renal failure.

DRUG-INDUCED INTERSTITIAL NEPHRITIS

 Acute drug induced interstitial nephritis:

 Pathogenesis : Hypersensitivity type I & Hypersensitivity type type IV

o Drugs include: Antibiotics, diuretics, NSAID.

o Signs & Symptoms:

 Fever

 Eosinophilia (may be transient )

 rash

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  renal abnormalities

o withdrawal of the drug is followed with recovery.

 Analgesic (pain relief drugs) Nephropathy:

o mixture of many medications for long time e.g. (aspirin,
acetaminophen and codeine)
 papillary necrosis.
o Complication of analgesic abuse is increased incidence of
transitional cell carcinoma of the renal pelvis or bladder .

End of part 3
Done by Abo Malik

Part 4

Tumors of the kidney and urinary bladder

By A.Z.K
Introduction:

The most common malignant tumor of the kidney is renal cell carcinoma,
followed in frequency by nephroblastoma (wilms tumor). Tumors of the lower
urinary tract are about twice as common as renal cell carcinoma.
Benign tumors:
1) Renal papillary adenoma:
small, discrete (usually yellow) tumors are seen in 7% to 22% of autopsies.
Histologically, consist of vacuolated epithelial cells forming tubules and
branching papillary structures.

2) Angiomyolipoma:
often associated with tuberous sclerosis (25% - 50% of patients), these
tumors are considered to be hamartomas.

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 Malignant tumors:

Renal Cell Carcinoma:

Most common from the sixth to seventh decades, and men are affected about
twice as commonly as women. Renal cell carcinoma represent 85% of all primary
malignant tumors of the kidney. It arises from the renal tubular epithelium, and
hence they are located in the cortex. About 40% of the patients die of the disease.

Risk factors:

-smocking

-hypertension

-obesity

-exposure to cadmium

-acquired polycystic disease (30-fold increased risk)

Based on the molecular origins of these tumors, the three most common forms
are as follows:

1) Clear Cell Carcinomas:

The most common type (80% of renal cell cancers). They are made up of cells
with clear or granular cytoplasm. The majority of them are sporadic, but they
also occur in familial forms or in association with von Hippel-Lindau (VHL)
disease. VHL disease is autosomal dominant and is characterized by
predisposition to a variety of neoplasms , particularly to hemangioblastomas of
the cerebellum and retina. Those with VHL syndrome inherit a germ-line
mutation of the VHL gene on the short arm of chromosome 3 (3p25).

2)Papillary Renal Cell Carcinoma:

Comprises 10-15% of all renal cancers. They show a papillary growth pattern. These
tumors are frequently multifocal and bilateral and appear as early-stage tumors. As
clear cell carcinoma, the occur in familial and sporadic forms. The gene involved is
MET proto-oncogene, located on the long arm of chromosome 7. This MET gene,
which is a tyrosine kinase receptor for hepatocyte growth factor, is expressed in an
increased amount, which will result in an abnormal growth in the proximal tubular
epithelial cells giving precursors of papillary carcinomas.

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 3)Chromophope Renal Carcinomas:
These are the least common, representing 5% of all renal cell carcinomas. They arise
from intercalated cells of collecting ducts. These tumors are unique in having
multiple losses of entire chromosomes including chromosomes 1, 2, 6, 10, 13, 17, 21.
In general, chromophope renal cancers have a good prognosis.

Morphology:
Clear cell cancers (the most common
form) are usually solitary and large when
symptomatic (spherical masses 3-15 cm
in diameter). They may arise anywhere in
the cortex. The cut surface is yellow to
orange to gray-white, with prominent
areas of cystic softening or of
hemorrhage, either fresh or old. The
margins of the tumor are well defined.
Frequently, the tumor invades the renal
vein and grows as a solid column within
this vessel, sometimes extending in
serpentine fashion as far as the inferior
vena cava and even into the right side of
the heart.

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 The tumor cells of clear cell renal cell carcinoma may appear almost vacuolated
(full of lipid and glycogen) or may be solid. The classic vacuolated (lipid-laden), or
clear cells are demarcated only by their cell membranes. The nuclei are usually small
and round (see the figure). At the other extreme (i.e. solid) are granular cells,
resembling the tubular epithelium, which have small, round, regular nuclei enclosed
within granular pink cytoplasm. Between the extremes of clear cells and solid,
granular cells, all intergradations may be found. The stroma is usually scant but
highly vascularized.
Papillary renal cell carcinomas tend to be bilateral and multiple. They may also show
gross evidence of necrosis, hemorrhage, and cystic degeneration. The cells can have
clear or, more commonly, pink cytoplasm.
Chromophobe-type renal cell carcinoma tends to be grossly tan-brown. Having very
prominent, distinct cell membranes. The nuclei are surrounded by halos of cleared
cytoplasm.

Clinical course:

 The most frequent presenting manifestation is hematuria, occurring in

more than 50% of cases.

 Extra-renal effects are fever and polycythemia, both may be associated

with a renal cell carcinoma.

 Polycythemia result from elaboration of erythropoietin by the renal

tumor.

 Uncommonly, these tumor can result in paraneoplastic syndroms, some of

these are hypercalcemia, hypertension, cushing syndrome, feminization
or masculinization.

 The prevalent locations for metastases are the lungs and the bones.

 The following triad is characteristic for renal cell carcinoma:

1) painless hematuria
2)palpable abdominal mass
3) dull flank pain.

End of Part 4

Done by: AZK

36
 Part 5
Wilms' Tumor

Wilm's tumor (nephroblastoma) :

Wilm's tumor is the most common primary kidney tumor in children. Most
cases occur between the ages of 2 to 5 years. Wilm's tumor illustrates three
important concepts of childhood tumors :

 the relationship between congenital malformation and increased risk of

tumors
o an increased risk of tumors in the presence of congenital
malformation
 histologic similarity between the tumor and the developing organ
 the remarkable success in the treatment of childhood tumors

Each of these will be discussed next

As mentioned above, children that are born with congenital malformations

are at high risk of developing Wilm's tumor. Three malformation syndromes will
be discussed , WAGR syndrome ,Denys-Drash syndrome (DDS) , and Beckwith-
Weidmann syndrome (BWS) .

1- WAGR syndrome

This syndrome is characterized by Anridia (absence of the colored part of

the eye, the iris), Genital malformations, and mental Retardation. Patients
with this syndrome have a 33% chance of developing Wilm's tumor.

WAGR syndrome is associated with abnormalities in the WT1 gene, the

abnormality is loss of genetic material ( deletion ).

NOTE : WAGR stands for Wilms tumor, Anridia, Genital malformation and
Retardation .

2- Denys-Darsh syndrome (DDS)

This syndrome is characterized by Gonadal Dysgenesis and Renal
malformation.
Patients with this syndrome are at an extremely high risk of developing
Wilms’ tumor (~90%)

DDS is also associated with abnormalities in WT1 gene, but here the
abnormality is a mutation.

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 NOTE: DDS is a DOMINANT NEGATIVE syndrome. This means that a
mutation in one gene (allele) will block the function of the other.

NOTE: WAGR syndrome and DDS both show abnormalities in the WT1
Gene but
in WAGR it is deletion while in DDS it is mutation.

3- Beckwith-Wiedemann syndrome :
This syndrome is characterized by enlargement of individual body organs
(e.g., tongue, kidneys, or liver) or entire body segments
(hemihypertrophy); enlargement of adrenal cortical cells (adrenal
cytomegaly) is a characteristic microscopic feature

The genetic locus that is involved in these patients is called "WT2" for
the second Wilms' tumor locus.

In addition to Wilms' tumors, patients with BWS are also at increased risk
for developing hepatoblastoma, adrenocortical tumors,
rhabdomyosarcomas, and pancreatic tumors

Morphology:

Grossly:

Externally: Wilm's tumor

tends to present as a large,
solitary, Well-circumscribed
mass. 10 % are bilateral or
multicentric at Diagnosis.

Cut section : the tumor is soft,

homogeneous, and tan to gray,
With occasional foci of
hemorrhage, cystic
degeneration, and necrosis.

Microscopically:

Wilms' tumors are

characterized by recognizable
attempts to recapitulate
different stages of
nephrogenesis (the stages of
development may be repeated
or different stages may be

38
 mixed). The classic triphasic combination of blastemal, stromal, and epithelial
cell types is observed in most lesions, although the percentage of each
component is variable.

The three types of cells that are present are:

1) Blastemal : appear as Sheets of small blue cells, with few

distinctive features.
2) Epithelial : usually takes the form of abortive tubules or
glomeruli.
3) Stromal : are usually fibrocytic or myxoid in nature, although
skeletal muscle "differentiation" is not uncommon.

Rarely, other heterologous elements are identified, including squamous or

mucinous epithelium, smooth muscle, adipose tissue, cartilage, and osteoid and
neurogenic tissue.

Approximately 5% of tumors contain foci of anaplasia. The presence of

anaplasia correlates with underlying p53 mutations, and the emergence of
resistance to chemotherapy. The pattern of distribution of anaplastic cells within
the primary tumor (focal versus diffuse) has important implications for
prognosis.

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 (Morphology continued)

Nephrogenic rests:

Are precursor lesions of Wilms' tumors and are sometimes present in the renal
parenchyma adjacent to the tumor. Nephrogenic rests have a spectrum of
histologic appearances, from expansile masses that resemble Wilms' tumors
(hyperplastic rests) to sclerotic rests consisting mostly of fibrous tissue with
occasional admixed immature tubules or glomeruli. It is important to document
the presence of nephrogenic rests in the resected specimen, since these
patients are at an increased risk of developing Wilms' tumors in the
contralateral kidney.

Clinical Course:
1. Paitent complaints
 Commonly :
Palpable abdominal mass that may extend to the pelvis
 Rarely:
Abdominal pain
Fever
Hematuria
Intestinal obstruction (due to tumor's large size)

2. Progonosis
 generally very good, and excellent results are obtained with a
combination of nephrectomy and chemotherapy.
 Anaplasia is a harbinger of adverse prognosis :
It could be either diffuse or focal
Focal: good prognosis
Diffuse: bad prognosis

Tumors of the Urinary Bladder and Collecting System:

The entire urinary collecting system from renal pelvis to urethra is lined with
transitional epithelium. so its epithelial tumors assume similar morphologic
patterns. Tumors in the collecting system above the bladder are relatively
uncommon; those in the bladder, however, are an even more frequent cause of
death than are kidney tumors.

Classification:
1) Benign papillomas ( rare )
2) Urothelial carcinomas

40
 Morphology:

1) Benign papillomas :
The very rare benign papillomas are 0.2- to 1.0-cm frondlike
structures having a delicate fibrovascular core covered by
multilayered, well-differentiated transitional epithelium

2) Urothelial carcinoma :
they range from papillary to flat, noninvasive to invasive, and low
grade to high grade.

Low grade High grade

Always papillary Can be papillary or flat

Rarely Invasive Invasive

May recur after Covers large area of

removal mucosa

Occasionally, these cancers show foci of squamous cell

differentiation, but only 5% of bladder cancers are true squamous
cell carcinomas.

41
 Clinical course:
Painless hematuria is the dominant clinical presentation of all these tumors.
But since tumors of the bladder are more common than those of the collecting
system , they are discusssed first
1) Urinary bladder tumors:
 They affect men about three times as frequently as women
 usually develop between the ages of 50 and 70 years
 mutations involving several genes on chromosome 9 have
been documented, p53 is the most common
 bladder tumors are 50 times more common in those exposed
to :
o B-Napthylamine
o Ciggarette smoking
o Chronic cystits
o Schistosomiasis of the bladder
o Certain drugs ( eg Cyclophosphamide )

The clinical significance of bladder tumors depends on their histologic grade and
differentiation and, most importantly, on the depth of invasion of the lesion. Except
for the benign papillomas, all tend to recur. Lesions that invade the ureteral or
urethral orifices cause urinary tract obstruction.
As for the prognosis :

 low-grade shallow lesions : the prognosis is good after removal

 high-grade with deep penetration of the bladder wall: the prognosis
is bad , the 5-year survival rate is less than 20%.

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 The over all 5-year survival rate for both types together is 57%.

2) Collecting System (Renal Calyces, Renal Pelvis, Ureter, and

Urethra):
 Present with :
o Painless hematuria
o pain in the costovertebral angle as hydronephrosis
develops (if the tumor blocks the ureter).

 Infiltration of the walls of the pelvis, calyces, and renal vein

worsens the prognosis
 Despite removal of the tumor by nephrectomy, fewer than
50% of patients survive for 5 years
 Cancer of the ureter is fortunately the rarest of the tumors of
the collecting system. The 5-year survival rate is less than
10%.

End Of Part 5
Done by: The DuDe

‫ فرده لي عند‬،‫اللهم اني استىدعك ما قرأت وما حفظت وما تعلمت‬

‫حاجتي إليو‬
.‫ وحسبنا هللا ونعم الىكيل‬،‫انك على كل شيء قدير‬

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