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NEPHROLOGI

• PWM Olly Indrajani

• 18-3-2015
3 Functions of the Urinary System

1. Excretion:
– removal of organic wastes from body fluids
2. Elimination:
– discharge of waste products
3. Homeostatic regulation:
– of blood plasma volume and solute
concentration
Urinary organs

Organs:
1. Ren
2. Ureter
3. Vesica urinaria
4. Urethra
Kidneys
• Organs that excrete urine

Urinary Tract
► Organs that eliminate urine:
 ureters (paired tubes)
 urinary bladder (muscular sac)
 urethra (exit tube)
Kidneys
• Feature like soya bean; 11 X 6 X 3 cm, weight=±150
gr (♂) and ±135 gr (♀); smooth surface
(fetuslobulated); lower pole is palpable in full
inspiration (thin individu)
• Position:
– Regio abdomen posterior.
– Lateral columna vertebra
– Retroperitoneal.
– Between Vertebra T.XII – Vertebra L.III
– Ren dextra usually slightly inferior than sinistra (why?)
Position of the kidneys
Renal projection
Renal relations syntopi
Renal protection
1. Renal projection
• Anterior:
– Hilum: 5cm from midline,
medial from the tip costae
9th
• Dex: under transpyloricum
plane
• Sin: over transpyloricum
plane
• Posterior:
– Hilum: lower border of
processus spinosus
vertebrae lumbalis 1st &
±5 cm from midline.
3. Renal protection
1. Capsula renalis
– Collagen fibers covers outer surface organ
2. corpus adiposum perirenalis/capsula
adiposa/perirenal fat
– Adipose tissue surround renal capsule (
connected by trabeculae, >>ren inferior)
3. Fascia renalis
– fibrous outer layer anchors kidney to
surrounding structures
4. Corpus adiposum pararenalis/pararenal fat
– Adipose tissue posterior to fascia renalis
Renal Blood Vessels
Arteri Renalis
• A. renalis gives:
– a. suprarenalis inferior
• note: a. supraneralis superior and media from a. phrenica
inferior and aorta abdominalis
– Branches to the perinephric tissue, renal capsule, pelvis
and proximal part of the ureter
• Near the hilum a. renalis divides into divisi anterior and
divisi posterior  a. segmentalis
Variation:
– A. renalis accesorius arise from aorta (30%) and rarely from a.
colica, a. mesenterica superior, or a. iliaca communis
• A. renalis  a. segmentalis
– Renal vascular segmentation (by Graves 1956)
1. Apical
2. Superior (anterior)
3. Inferior
4. Middle (anterior)
5. Posterior
• A. lobaris (one for each pyramid)  divides into 2-3
a. interlobaris  a. arcuata
•  a. interlobularis
– diverge radially into the cortex
– Some perforate surface as perforating artery  rami
capsulares
•  a. afferent  a. efferent
–  peritubular capillary plexus (around PCT & DCT in the
cortical nephron)
–  vasa recta (arteriolae rectae in the juxtamedullary
nephron)
•  v. interlobularis
Renal structures
1. Hilus renalis
2. Sinus renalis
3. Capsula renalis
4. Cortex renalis
5. Medulla renalis
a. Pyramida renalis
 Papilla renalis (ductus Bellini)
b. Columna renalis (columna Bertini)
6. Lobus renalis
7. Calyx minor  Calyx major
8. Pelvis renalis
Fig. Renal structures
Left-right orientation (dorsal view)

Anterior:
V.renalis  but branch of
vein exit for hilum
posterior of pelvis renalis

Medial:
A.renalis  but branch of
artery entry for hilum
posterior pelvis renalis

Posterior:
pelvis renalis
Nephron
(functional subunit of the kidney

Where urine production


begin located on cortex
and columna renalis (±1-
2jt /ren)
Consists of:
1. corpusculus renalis
2. tubulus renalis
Corpusculus renalis (Malpighian)

• Consists of:
1. capsula glomerulus
(Bowman)
2. glomerulus (capillary
network)
3. capsular space
• Diameter 150–250
µm
Fig. Glomerullar capillaries (electron micrograph)

Filtration membrane
• Capillary endothelium
(fenestrated capillaries)
• Lamina basalis
• Modified of visceral
epithelium (podocyte) 
proc. Primer  proc.
Secondary (pedicels) 
filtration slits
Tubulus renalis
Consists of:
1. Tubulus contortus
proximal (PCT)
2. Loop of Henle
• Descending limb
• Ascending limb
3. Tubulus contortus distal
(DCT)
Located on:
• Cortex: PCT & DCT
• Medulla: Loop of Henle
JUXTA GLOMERULAR APPARATUS (JGA)

Location:
Near each renal
corpuscel’s vascular
pole, at the point of
contact between a distal
convoluted tubule and
an afferent arteriole.
JUXTA GLOMERULAR APPARATUS (JGA)

Consists of:
– Juxta glomerular (JG cell)
• Modified smooth muscle cell in the afferent arteriole’s
wall
• Function: secrete renin
– A macula densa
• Modified from DCT
• Function: homeostasis
– Polkissen cells (extraglomerular mesangeal
cells)
• Function: maybe phagocyte
Mesangeal cell
• Located between 2 glomerulus, where they have 1
basement membrane (membrana basalis)
• The function maybe as a phagocyt
• concentrated between capillaries at the vascular pole of the
corpuscle
URETER
P
a
rs
a
b
d
o
m
in
al

Pars pelvica
Ureter
• Pars abdominal
– Posterior to the peritoneum
– Medial to anterior of m. psoas major
– Crosses anterior n. genitofemoralis
– Obliquelly crossed by a/v. testicularis (ovarica)
• Pars pelvica
– Posterolaterally on the lateral wall of pelvis minor,
along anterior border of incisura ischiadica major
until spina ischiadica and turns anteromedially into
fibrous adipose tissue above m. levator ani to reach
base of vesica urinaria.
NOTE:

• Male ureter:
– Crossed anterosuperiorly from
lateral to medial by ductus deferens
– Anterior to the upper pole of
vesicula seminalis
URINARY BLADDER (Vesica urinaria)
• Empty: tetrahedral / pyramid in shape
– Apex: anterior, connected by urachus to the umbilicus.
– Basis/fundus (posterior surface):
• Male: related to the rectum separated by rectovesical pouch
• Female: related to the anterior wall of vagina & cervix of uterus
separated by vesicouterine pouch
– Superior surface: covered by peritoneum, in female
posteriorly related to the cervix & corpus uteri.
– Inferolateral surface: separated by the adipose retropubic
pad from pubis and lig. puboprostatic/pubovesical.
• Fills: ovoid
–  above umbilicus
The Trigone of the Urinary Bladder
(trigonum vesicae Lieutaudi)

► Is a triangular area bounded by:


 openings of ureters (ostium ureteris dex-sin)
 entrance to urethra (ostium urethrae internum)
► Acts as a funnel:
 channels urine from bladder into urethra
The Urethral Entrance
• Lies at apex of trigone:
– at most inferior point in urinary bladder
The Neck of the Urinary Bladder
(cervic vesicae)
• Is the region
surrounding urethral
opening
• Contains a musculus
sphincter urethrae
interna (sphincter
vesicae- Smooth
muscle of sphincter
provide involuntary
control of urine
discharge)
Blood supply of VU
A. vesicalis superior & inferior

Nerve supply of VU
Plexus vesicalis:
T10-L2  sympathetic
S2-S4  parasympathetic
Urethrae

►Male urethrae
►Female urethrae
The Urethra
• Extends from neck of urinary bladder
• To the exterior of the body

The Male Urethra


► Extends from neck of urinary bladder
► To tip of penis (18–20 cm)
3 Parts of the Male Urethra
1. Prostatic urethra (pars prostatica):
 passes through center of prostate gland
 Epithel: transitional
2. Membranous urethra (pars membranacea):
 short segment that penetrates the
 urogenital diaphragm
 Epithel: pseudo-stratified columnar / stratified
columnar
3. Spongy urethra/penile urethra (pars spongiosa):
– extends from urogenital diaphragm
– to external urethral orifice (ostium urethrae
externum)
– Epithel: stratified squamous
Pars membranacea
Pars prostatica

Pars spongiosa
Anatomy of prostate gland
• Basis (pierced centrally by urethrae); apex; facies anterior
(convex); facies posterior (concave); 2 of facies infero-lateral

• Colliculus seminalis
(verumontanum) is
used to determine
the position of
prostate gland
during TURP
The Female Urethra
• Is very short (3–5 cm)
• Extends from bladder to vestibule
• External urethral orifice (ostium urethrae
externum) is near anterior wall of vagina
• Epithel: transitional  stratified-squamous
The External Urethral Sphincter
(M. sphincter urethrae externa)

• In both sexes:
– is a circular band of skeletal muscle
– where urethra passes through urogenital diaphragm
• Acts as a valve
• Is under voluntary control:
– via perineal branch of pudendal nerve
• Has resting muscle tone
• Voluntarily relaxation permits micturition
TOPICS :
1. Renal Failure
2. Glomerular diseases
3. Diseases affecting tubules and interstitium
* Acute tubular necrosis
* Pyelonephritis
4. Tumor
* Tumor of the kidney :
- Wilm’s tumor, Grawitz tumor
* Tumor of the bladder :
- Urothelial Tumor
5. Prostate
* BPH
* Ca of the Prostate
RENAL FAILURE :
# Diminution or loss of renal function
* GFR ↓  BUN  , creatinine  (azotemia)  
clinical manifestation (+)  uremia

# Depend on its cause, azotemia can divided as:


* Prerenal azotemia : in hypoperfusion of the kidneys
- Congestive heart failure
- Shock, volume depletion, hemorrhage
* Renal azotemia
* Postrenal azotemia :
- Obstruction of urine flow below the level
of the kidney

# Uremia : azotemia associated with a constellation of


clinical signs and symptoms and biochemical
abnormalities
ACUTE KIDNEY INJURY

* Acute diminution or loss of renal function


* Urine production < / = 400 ml / day
•Caused by :
1. Ischemia, due to decreased or interrupted blood flow :
* Polyarteritis nodosa, malignant hypertension,
decreased effective circulating blood volume
2. Severe glomerular diseases (RPGN)
3. Severe infection (Pyelonephritis)
4. Disseminated intravascular coagulation (DIC)
5. Urinary obstruction : tumor, BPH
6. Acute Tubular Necrosis (ATN)
CHRONIC KIDNEY DISEASE
* The end result of a variety of renal diseases
* The evolution from N function to CRF through 4 stages :
1. Diminished renal reserve
- Asymptomatic, GFR ± 50% N, BUN/SC N
2. Renal insufficiency
- GFR 20-50%
- Azotemia, + anemia, hypertension, polyuria, nocturia
3. Renal failure
- GFR < 20-25%
- edema, metabolic acidosis, hypocalcemia,
- uremia
4. End-stage renal disease
- GFR < 5%, this is the terminal stage of uremia
Systemic Manifestations of CKD and Uremia :
1. Fluid and Electrolytes :
- Dehydration, edema, hyperkalemia, metabolic asidosis
2. Calcium Phosphate and Bone :
-Hiperphosphatemia, hypocalcemia,
secondary hyperparathyroidism, osteodystrophy
3. Hematologic :
-Anemia, bleeding diathesis
4. Cardiopulmonary :
-Hypertension, congestive heart failure,
pulmonary edema, uremic pericarditis
5. Gastrointestinal :
-Nausea, vomiting, esophagitis, gastritis, colitis
6. Neuromuscular :
-Myopathy, peripheral neuropathy, encephalopathy
7. Dermatologic :
-Sallow color, pruritus,dermatitis
Glomerular Diseases
• Some of the major problems encountered
in nephrology
• Chronic glomerulonephritis (GN) is one of
the most common causes of chronic
kidney disease (CKD)

• Glomerulus consists of 4 major element :


endothelial cells, glomerular basement
membrane (GBM), visceral epithelial cells
(podocytes), and mesangial cells
PATOGENESIS of GLOMERULAR DISEASES

1. Immunologic mechanism :
a. Trapped of circulating Ag – Ab complexes within
glomerulus
b. In situ, as react of Ab with :
* intrinsic antigens (GBM  Anti GBM nephritis)
* extrinsic antigens that planted within glomerulus
2 Non immunologic mechanism :
• Any renal disease that destroys functioning
nephrons
 GFR↓ to ± 30 – 50% of N 
capillary hypertrophy & hypertension
(+systemic)
 * epithelial & endothelial damage 
proteinuria
* proliferation of mesangial cells & increased
accumulation of extracellular matrix 
glomerulosclerosis
CLINICAL MANIFESTATION OF GLOMERULAR
DISEASES
1. Acute nephritic syndrome
2. Nephrotic syndrome
3. Rapidly progressive GN (Acute nephritis, proteinuria,
ARF)
4. Chronic renal failure
5. Asymptomatic hematuria or proteinuria

HISTOLOGIC ALTERATION in GLOMERULUS


1. Proliferation of epithelial, endothelial & mesangial
cells
2. Neutrophils & monocytes infiltrates
3. GBM thickening
4. Hyalinization / sclerosis
BMG THICKENING
1. Thickening of GBM itself
* diabetic glomerulosclerosis
2. Thickening of GBM caused by immune complex
deposits

THE HISTOLOGIC CHANGES CAN BE DIVIDED


INTO :
1. Diffuse : involving all glomeruli
2. Focal : involving only a proportion of the glomeruli
3. Segmental : affecting a part of each glomerulus
4. Global : involving the entire glomerulus
5. Mesangial : affecting predominantly the mesangial
region
Schematic diagram of a lobe of a normal glomerulus
Kumar et al, 2007
INJURY GLOMERULAR DISEASE
immune/autoimmune
I. Microscopic :
1. Inflammatory infiltrate
Clinical manifestation
2. Proliferation of Epithel
•Nephritic Syndrome
Endothel
• RPGN
Mesangial
Glomerular •Nephrotic Syndrome
alteration 3. GBM thickening
• CGN
4. Hyalinization / Sclerosis

II. Terms of histologic changes :


* Diffuse
* Focal
* Segmental
* Global
* Mesangial
GLOMERULUS
Ag-Ab
damage of GBM

Nephrotic RPGN
Asymptomatic Nephritic
Hematuria / syndrome
syndrome
Proteinuria
End stage
Diminished Renal Late stage
Reserve RF

Renal Early
Insufficiency stage RF
Uremia (P+ abnormalities):
Pre Uremia (P) *Cardiopulmonary
Mild Azotemia (A) (A)+ Acidosis *Hematologic
Hypocalcemia *Gastrointestinal
Hyperkalemia *Dermatologic
*Neuromuscular
Clinical manifestation of glomerular disease
Nephritic Syndrome
a clinical complex, usually of acute onset, characterized by
1. hematuria with dysmorphic red cells and red blood cell
casts (silinder) in the urine,
2. some degree of oliguria and azotemia, and
3. Hypertension
lesions characteristic: proliferative changes and
leukocyte infiltration
produced by : systemic disorders such as SLE,
primary glomerular disease (as Acute
Postinfectious /Poststreptococcal
Glomerulonephritis )
ACUTE NEPHRITIC SYNDROME :

* Oliguria
* Hematuria
* Erythrocyte cast
* Proteinuria
* Azotemia
* Mild to moderate hypertension
* Mild edema
Post Streptococcal GN
# 1 – 4 weeks after a streptococcal infection
of the pharynx or skin (impetigo)
# AS0 titer ↑
# Serum complement level ↓
# Morphology :
* Diffuse enlarged & hypercellular glomeruli, caused by :
- proliferation of endothelial & mesangial cells
- Infiltration by neutrophils and monocytes
- Crescent formation (in severe cases)
- IF : granular deposits of IgG, IgM and C3
- ME : electron dense deposits (subepithelial)
# Prognosis : - 95% total recovery
- others :  RPGN / CGN  CRF
Rapidly Progressive (Crescentic) GN
# Etiology :
* Anti GBM disease  IF : linear dep.of IgG, C3
* Immune complex disease  IF : granuler
(complication of PSGN, SLE etc)
* Pauci-immune : Wegener granulomatosis, idiopathic
# Morphology :
- The kidneys are enlarged & pale
- Petechiae on the cortical surfaces
- Glomeruli :
- Focal necrosis
- Diffuse/focal endothelial & mesangial
proliferation
- Proliferation of parietal cells & migration of
monocytes, macrophages, neutrophils,
lymphocytes  crescent 
obliterate Bowman space
Nephrotic Syndrome
a clinical complex that includes :

(1) massive proteinuria, ≥ 3.5 gm/d in adults


(2) hypoalbuminemia, < 3 gm/dL
(3) generalized edema (the most obvious clinical
manifestation)
(4) hyperlipidemia and lipiduria

At the onset there is little or no azotemia,


hematuria, or hypertension.
Ag-Ab Reaction
Glomerular inflammation

Permeability of GBM 

Proteinuria

Hypoalbuminemia

Capillary osmotic
pressure ↓ Serum lipid 

Interstitial transudation Hypovolemia

ADH  GFR ↓
Aldosteron 
RPF ↓
Na++ H2o
retention

Scheme : Pathogenesis of nephrotic edema EDEMA


Minimal-Change Disease (Lipoid Nephrosis)
 The most frequent cause of the nephrotic syndrome in
children.

 Characteristic:
- glomeruli have a normal appearance
(light microscope)
- diffuse effacement of podocyte foot processes
(electron microscope)
Age: any age , most common 1 -7 yo

 Pathogenesis
involves some immune dysfunction → resulting in the
elaboration of a cytokine that damages visceral
epithelial cells and causes proteinuria.
Focal Segmental Glomerulosclerosis

# Sclerosis of some glomeruli (focal), and only a portion of


the capillary tuft is involved (segmental)
# Etiology :
* Idiopathic
* In association with other known condition, such as :
- HIV (HIV nephropathy), heroin (heroin nephropathy),
- glomerular scarring in focal glomerulonephritis
- the adaptive resp. to loss of renal tissue (renal ablation,
advanced stages of other renal disorders, agenesis)
# Morphology :
-MC : glomeruli N / prolif. mesangial & matriks mes. 
- ME : diffuse effacement of foot processes
- IF : IgM & C3 in sclerotic area &/or in the mesangium
Membranous Glomerulopathy
* Immune complex disease
* Accumulation of Ig containing deposits along the
subepithelial site of GBM
* Diffuse thickening of the glomerular capillary wall
* Etiology :
- 85% idiopathic
- Others :
- Malignancy, particularly Ca of the lung, colon &
MM
- SLE
- Drugs (penicillamine, captopryl, NSAID, gold)
- Infections(hepatitis B&C, syphilis,schistosomiasis,
malaria)
- Other autoimmune disorders eg. thyroiditis
Morphology :
- The Kidneys are enlarged, pale
- Thickening of the cortex, medulla N
- Diffuse thickening of the glomerular capillary wall
- Proliferation of capillary endothelial cells and
mesangial
-Tubuli : hyalin droplets within epithelial cells
- EM : - Irregular dense deposits between the BM
and the overlying epithelial cells
- The BM thicken to produce dome-like
protrusions and eventually close over the
immune deposits  irregular thickened
- Advance stage  sclerosis of the mesangium
 Glomeruli become totally sclerosed
Membranous nephropathy. A, Diffuse thickening of the glomerular
basement membrane. B, Schematic diagram illustrating subepithelial
deposits,effacement of foot processes, and the presence of "spikes" of
basement membrane material between the immune deposits.
CHRONIC GLOMERULONEPHRITIS
* A pool of end-stage glomerular disease
- Post Streptococcal GN 1 – 2%
- RPGN 90%
- Membranous Gpathy 30 – 50%
- Focal Segmental GS 50 – 80%
- Membranoproliferative GN 50%
- Ig A Nephropathy 30 – 50%
* Morphology :
- The Kidneys are symmetrically contracted
- Diffuse granular of the cortical surfaces
- On section : the cortex is thinned
- Boundary between cortex & medulla unclear
- Microscopic : depend on underlying diseases
Clinical Course
 develops insidiously and slowly progresses
to renal insufficiency or death from uremia
during a span of years or possibly decades
 nonspecific complaints: as loss of appetite,
anemia, vomiting, or weakness.
 Renal disease is suspected: discovery of
proteinuria, hypertension, or azotemia on
routine medical examination.
 Underlying renal disorder is discovered in
the course of investigation of edema.
 Most patients are hypertensive
GLOMERULAR LESION CAUSED BY
SYSTEMIC DISEASES
1. DIABETIC NEPHROPATHY
* One of the leading causes of CRF in USA
* The most common lesion of DM involve the glomeruli
(glomerulopati), with 3 glomerular syndrome :
- non-nephrotic proteinuria, nephrotic syndrome
and CRF
* Others : hyalinizing arteriolar sclerosis, pyelonephritis
(particularly papillary necrosis), and causes
a variety of tubular lesion (deposit glycogen and
fat within the cells)
Morphology :
a. Capillary BM thickening
b. Diffuse mesangial sclerosis
- mesangial matrix >, proliferation of mesangial cells
c. Nodular glomerulosclerosis
(Kimmelstiel- Wilson disease; intercapillary glomeruloscl.)
* ovoid/spherical nodules of matrix, situated in the periphery
of the glomerulus, surrounded by patent peripheral capillary
loop.
* Advance, nodules>, compress & engulf capillaries,
obliterating glomerulus
* Often, + accumulation of hyalin material in capillary loop /
Bowman capsules  renal ischemia, tubular atrophy,
interstitial fibrosis  contraction in size
2. SYSTEMIC LUPUS ERYTHEMATOSUS
Clinical manifestation :
- Recurrent microscopic/gross hematuria
- Acute Nephritis
- Nephrotic Syndrome
- Hypertension
Diseases Affecting Tubules and Interstitium
1. Acute Tubular Necrosis (ATN)
1. Nephrotoxic ATN
2. Ischemic / Tubulorrhectic ATN
2. Tubulointerstitial Nephritis
1. Acute Pyelonephritis
2. Chronic Pyelonephritis
ATN :
* The most common cause of ARF (± 50%)
* Reversible

Pathogenesis of ARF in ATN :


1. Persistent preglomerular vasoconstriction
2. Tubular obstruction, caused by interstitial edema /
intratubular cast
3. Tubular damage  tubular back-leak
 interstitial edema
4. Alterations of intrinsic glomerular function
 glomerular filtration 
ISCHEMIC TUBULAR
ATN DAMAGE
NEPHROTOXIC

(1) (2)
VASO CONSTRICTION OBSTRUCTION (3)
RENIN – ANGIOTENSIN BY CAST S TUBULAR
BACK-LEAK

INTRA TUBULAR Tubular Fluid


PRESSURE  Flow 

(4)
DIRECT GLOMERU GFR  OLIGURIA
LAR - EFFECT

PATHOGENESIS Of ARF in ATN


1. Nephrotoxic ATN
* Caused by nephrotoxic substance :
- Poisons including heavy metals (eg:Hg)
- organic solvents (e.g., CCl4)
- antibiotics
- radiographic contrast agents
* Morphology :
- Necrosis of tubular cells most obvious in
proximal convoluted tubuli,
- tubular BM intact
- distal convoluted tubuli intact
2. Ischemic ATN
(Shock kidney; Hemoglobinuric Nephrosis)
* Caused by persistent and severe disturbances
in blood flow / shock :
- Severe bacterial Infection
- Severe burns
- Conditions that cause peripheral circulation
insuffisiency
- Massive bleeding caused by rupture of
large arteries / aneurysm
- Mismatched blood transfusion and other hemolytic
crisis causing hemoglobinuria
Morphology :
- Focal tubular epithelial necrosis at multiple point along the
nephron accompanied by rupture of BM (tubulorrhexis) and
occlusion of tubular lumen by cast.
- Others : in distal tub. & collect. ducts
- eosinophilic hyalin cast
- pigmented granular cast
PYELONEPHRITIS
* Renal disorder affecting the tubule,
interstitium and renal pelvis
* One of the most common diseases of the
kidney
* Etiology and pathogenesis :
# > 85 % : Gram-negative bacilli
(normal inhabitants of the intestinal tract)
- E. Coli (the most common)
- Proteus
- Klebsiella
- Enterobacter
Route of Infection :
1. Hematogen
- septicaemia; inf. endocarditis pyelonephritis
- the most common etiology : Staphylococci and
E. coli
2. Ascending
- urethritis  cystitis  ureteritis 
pyelonephritis
3. Vesicoureteral reflux
Most often caused by :
- Children : congenital anomalies
- Adults : bladder tumor, stones, BPH, persistent
bladder atony
ACUTE PYELONEPHRITIS

* An acute suppurative inflammation


of the kidney caused by bacterial,
sometimes viral infection, whether
hematogenous or ascending and
associated with vesicoureteral
reflux.
* Morphology :

- The Kidneys are enlarged / N (depend on


severity of infection)
- Patchy interstitial suppurative
inflammation,
intratubular aggregates of neutrophils
and tubular necrosis
- Focal / diffuse; unilateral / bilateral
- Abscesses can extend through the renal
capsule  perirenal tissue
(perinephric abscess)
Complication :
1. Papillary necrosis
- Coagulation necrosis at 2/3 distal pyramids
- Mainly in diabetics / urinary obstruction
2. Pyonephrosis
- In total / almost complete obstruction
Pus is unable to drain  fills the renal pelvis,
calyces and ureter
3. Perinephric Abscess
- Abscesses can extend through the renal
capsule  perinephric tissue
Predisposing conditions :
1. Urinary tract obstruction
2. Instrumentation of the urinary tract
3. Vesicoureteral reflux
4. Pregnancy
5. Patient’s sex and age
6. Preexisting renal lesion, causing intrarenal
scarring and obstruction
7. Diabetes mellitus
8. Immunosupression and immunodeficiency
* Clinical course :
- Pain at the costovertebral angle
- Fever, malaise
- Dysuria, frequency and urgency
- Lab. : urine  leuco >> (pyuria),
leuco cast (+)
* Diagnosis of infection : by urine culture
CHRONIC PYELONEPHRITIS

* Chronic tubulointerstitial renal disorder


in which chronic tubulointerstitial
inflammation and renal scarring are
associated with pathologic involvement
of the calyces and pelvis.

* An important cause of “End-Stage Kidney”


(up to 10-20% of patients in renal
transplants or dialysis units).
* Diagnostic criterion of
Chronic Pyelonephritis :
- Irregular scarr formation
- Inflammation
- Calyceal deformity
Morphology :
- The Kidneys usually are irregularly scarred
If bilateral, the involvement is asymmetric
- Deformity of the calyces and renal pelvis
- The tubules show atrophy in some areas, and
hypertrophy and dilation in others
- Dilated tubules may filled with colloid cast
(thyroidization)
- Chronic interstitial inflammation
 fibrosis in the cortex & medulla
- Periglomerular fibrosis
Types of Chronic Pyelonephritis
1. Chronic Obstructive PN
- Obstruction predisposes to infection
- Recurrent infections superimposed on diffuse
or localized obstructive lesion  scarring 
picture of CPN
- Obstruction  parenchymal atrophy
- Bilateral / unilateral

2. Refluks Nephropathy
- Infection from VU  reflux  the kidney
- Bilateral / unilateral.
Types of Chronic Pyelonephritis
1. Chronic Obstructive PN
- Obstruction predisposes to infection
- Recurrent infections superimposed on diffuse
or localized obstructive lesion  scarring 
picture of CPN
- Obstruction  parenchymal atrophy
- Bilateral / unilateral

2. Refluks Nephropathy
- Infection from VU  reflux  the kidney
- Bilateral / unilateral.
Clinical course :
- Insidious in onset / acute recurrent with back
pain, fever, pyuria and bacteriuria
- Loss of tubular function  polyuria & nocturia
- CPN is a result of superimposed bacterial
infection in obstructive urine or vesicoureteral
reflux (CPN rarely caused by
bacterial infection alone)

Tx. and prevention :


* to correct reflux & obsrtuctive lesion,
and eliminate infection
TUMORS OF THE KIDNEY :
Malignant tumors : 1. Wilm’s tumor
2. Renal Cell Ca

1. WILM’S TUMOR (Nephroblastoma)


* Incidence : - Most often in children,
1-4 years old
- Rarely in adults
* Origin : - Mesonephric (mesodermal)
* Clinical course :
- Pain (-)
- Hematuria
- Dysuria
MACROS :
- Solitary mass, well circumscribe
- 10 % bilateral or multicentric
- Soft, homogen, greyish, sometimes with
hemorrhage foci, necrosis and cyst
formation
MICROS :
* There are 3 types of cells :
blastema, epithelial and stromal
- Epithelial differentiation : tubuli &
glomeruli abortive
- Stromal cells : fibrocytic / myxoid, often
with skeletal muscle differentiation
- Rarely : squamous cells, mucinous
epithelium, smooth muscle,
lipid, cartilage, osteoid,
nerve tissue
* 5% : foci of anaplastic cells
2. RENAL CELL CA
(Grawitz tumor / Hypernephroma / Renal Adeno Ca)
- Represent ± 1-3 % of all visceral cancer
- Account for 85-90 % of renal cancer in adult
- Arise from tubular epithelium
* Etiology / Pathogenesis :
- Tobacco incidence in smokers 2x non
smokers
- Viral and chemical carcinogen
- Genetic  translocation of Cr 3 & 8  cancer
- Renal adenoma  carcinoma
MACROS :
- Commonly affects the poles, particularly
the upper one
- Spherical masses  3 – 15 cm
- Bright yellow-gray-white,
foci of hemorrhage, cystic
- Sometimes : satelite nodule (+)
MICROS :
* 3 types :
# Clear Cell Ca (70-80%)
# Papillary Ca (10-15%)
# Chromophobe Ca (5%)

Clear Cell Ca :
- Tumor cells : rounded / polygonal
- Abundant clear / granular cytoplasm
- Tubular / solid / trabecular
- Most tumor : well differentiated
- Some tumors show marked nuclear atypia,
bizzare nuclei and giant cells
Clinical course :
* Classic diagnostic features :
- Costovertebral pain, palpable mass & hematuria
* Others :
- Fever, malaise, weight loss
- Paraneoplastic syndrome (abN hormone
production)
- polycytemia, hypercalcemia, hypertension,
feminization/masculinization, Cushing syndrome,
eosinophilia, leukemoid reactions, amyloidosis
- Tendency to metastasize widely before giving rise
to any local symptoms or signs
* The most common locations of metastasis :
- lung (50%), bone (23%), lmn, adrenal,
liver, brain

* Prognosis : 5 ysr ± 45%


TUMOR OF THE BLADDER :
Exophitic papilloma
Inverted papilloma
Papillary urothelial neoplasm of low malignant
potential
Low grade and high grade papillary urothelial ca
Ca in situ (flat non invasive urothelial ca)
Mixed ca
Adeno ca
Small-cell ca
Sarcoma
# Etiology and Pathogenesis :
* Cigarette smoking (risk : 3-7x)
* Carcinogen (industrial)
- 2 Naphtylamine,
* Schistosoma Hematobium
- inflammation / local irritation
 mucosal squamous metaplasia
 dysplasia  neoplastic changes
* Long-term use of analgesics
* Heavy long-term use of cyclophosphamide
* Irradiation
UROTHELIAL (TRANSITIONAL CELL) CA
# ± 90% bladder tumor
Grading of Urothelial (Transitional Cell ) Tumor
WHO/ISUP grades ( 1998 )
 Urothelial Papilloma
 Urothelial Neoplasm of Low Malignant Potential
 Papillary urothelial ca, Low Grade
 Papillary urothelial ca, High Grade

WHO grades ( 2004)


 Urothelial Papilloma
 Urothelial Neoplasm of Low Malignant Potential
 Papillary urothelial ca, grade 1
 Papillary urothelial ca, grade 2
 Papillary urothelial ca, grade 3
MACROS :
- solitary / multiple
- papillary / nodular / flat / mixed papillary-nodular
- red elevated

MICROS :
* Grade I : - close resemble N transitional cells
- mitosis ±, number of layer >, slight loss of
polarity
* Grade II : - mitosis >, layers >>, greater loss of polarity
* Grade III :- mitosis>>, layers >>>, polarity (-)
- anaplastic, giant cells (+)
PROSTATE
• Retroperitoneal organ
• Encircling the neck of the bladder & urethra
• Pear-shaped
• Weight (normal adult male) : ± 20 gr
• Divided into 5 lobes :
- posterior, middle, anterior, lateral (2)
• 2 component :
- tubuloalveolar gland
- fibromuscular stroma
BENIGN PROSTATIC HYPERTROPHY /
HYPERPLASIA
• >>50 y.o
• Hyperplasia : stromal & epithelial
 discrete nodule in the periurethral region
 compress & narrow the urethral canal
 obstruction (partial / complete)

• Insidence :
- 40 y.o : ± 20%
- 60 y.o : ± 70%
- 70 y.o : ± 90%
Pathogenesis Testosteron
Stromal Cell Epithelial Cell

T
T
5-reductase tipe 2

DHT
Androgen
receptors

Nukleus

Growth
factor
Growth
factor

Growth factor
receptors
Clinical Course
1. Compression of the urethra
 difficulty in urination
2. Retention of urine in the bladder
 distention, hypertophy, infection
 cystitis & pyelonephritis
3. Frequency, nocturia, difficulty in starting &
stopping the stream of urine, overflow dribbling &
dysuria
4. Acute urinary retention  catheterization
5. Residual urine → infection → pyelonephritis
6. Hydronephrosis, azotemia, uremia
Treatment
• Trans Urethral Resection (TUR)
• Open Prostatectomy
TUR
BPH
CARCINOMA of the PROSTATE
Insidence :
• Disease of men  50 y.o;  50 y.o : 1%
• > 300.000 new cases / yr, 41.000 lethal
• << in Asians, age-adjusted insidence :
- Japanese : 3-4 / 100.000
- Hong Kong : 1 / 100.000
- USA (whites) : 50-60 /100.000
Etiology : ?
Risk Factors :
• age, race, family history, genetics, hormonal
(androgens/testosterone), environmental (fat
intake)
Clinical Staging
Stage A : No palpable lesion
A1 : Focal
A2 : Diffuse
Stage B : Confined to prostate
B1 : Small, discrete nodule
B2 : Large or multiple nodules or areas
Stage C : Localized to periprostatic area
C1 : No involvement of seminal vesicles, tumor ≤ 70 g
C2 : Involvement of seminal vesicles, tumor > 70 g
Stage D : Metastatic disease
D1 : Pelvic lymph node metastasis or urethral
obstruction causing hydronephrosis
D2 : Bone or distant lymph node or organ
or soft tissue metastases
Clinical Course

• Stage A : asymptomatic, discovered incidentally


at autopsy / tissue remove for BPH
• Difficulty in starting/stopping the stream
• Dysuria, frequency, hematuria
• Pain (late finding)  involvement of capsular
perineural space
• Back pain  vertebral metastasis
(osteoblastic)
Diagnosis :
• Clinical symptoms
• Rectal toucher
• Transrectal USG
• Transrectal / transperineal biopsy
• Biochemical markers :
Prostatic Acid Phosphatase (PAP)
Prostate-spesific Antigen (PSA)
# organ spesific, not cancer specific,
also ↑ in non neoplastic condition
(BPH, prostatitis)
- 25-30% BPH : PSA > 4.0 ng/ml
- 80% Prostate Ca : PSA > 4.0 ng/ml
- 20-40% Prostate Ca : PSA ≤ 4.0 ng/ml
 gray zone 4-10 ng/ml
Treatment
• Surgery
• Radiotherapy
• Hormonal manipulation
- orchiectomy
- estrogen therapy
- agonist of luteinizing hormon-releasing hormon

Surgery & Radiotherapy :


- Most suited for localized cases (stage A/B)
- > 90% : expect to live for 15 years
Endocrine therapy : mainstay for advanced cases
Thank You
For
Your Attention