Urinary System

Kidney
Ureter
Bladder
Urethra

1
 Structure and Function
The Urinary System Bladder Kidneys
•Also called the
excretory system

•Maintains water Urinary System

balance

•Removes waste
products from the Urethra Ureters
blood by excreting
them in the urine
Meatus
2
 Kidneys
Kidneys
The kidneys are bean-shaped organs located in the
retroperitoneal portion of the abdominal cavity on
either side of the vertebral column.

Two Primary Functions

•To form urine for excretion

•To retain essential substances the body needs in

the process called reabsorption

3
 Parts of the
Kidneys filter about 1700
Kidney
kidney
liters of blood daily in the
average adult. medulla
Parts of the kidneys

•Cortex hilum
-outer protective portion
•Medulla
-inner soft portion
•Hilum
-a depression located in the middle of the
concave side of the kidney where blood
vessels, nerves, and the ureters enter and cortex
exit the kidneys
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 Urine Production
Urine is produced by filtration of:
•water •sugar •creatine
•salts •urea •uric acid
Each kidney contains more than 1 million nephrons
which are the functional units of the kidneys.
Blood Flow through the Kidneys
Blood enters through the renal artery arterioles
Each arteriole leads to a nephron renal corpuscle
(which has a group of capillaries called the glomerulus)

The glomerulus filters fluid from the blood, and

is the first place where urine is formed in the
kidneys.
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 Blood
Structure and Function
Flow •Blood flows through the
Glomeruli glomerulus at a constant
rate.

•Each glomerulus is
Urine surrounded by a capsule
Flow known as Bowman’s
capsule.

•Blood then passes into

the renal tubules where
some substances are
reabsorbed and the
remaining become urine.
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Flow of Urine Flow of Urine
Nephron
glomerulus

Renal artery
renal tubules
Renal vein

renal pelvis Ureter

Renal medulla
Renal capsule
Renal cortex
renal calices
Filtered blood exits the kidneys via the
renal vein.
ureters The renal tubules carry urine to ducts in
the renal cortex. 7
 Abnormal Findings in Urine
Glucose
Casts Albumin

Abnormal Findings Ketones

Blood
in the Urine

Phenylketones (PKU) Bilirubin

8
 Inflammatory & Infectious
Urinary Tract Infection Glomerulonephritis
Disorders

Inflammatory
Nephritis & Nephrosis
Infectious Disorders

Hydronephrosis Polycystic kidney disease

Cystitis
Nephroblastoma 9
 Pathological Terms
Terms Used to Describe Difficulties in Urination

anuresis polyuria

•No urinary output •Excessive urination

dysuria incontinence

•Involuntary discharge of
•Painful urination
urine or feces
enuresis oliguria
•Lack of bladder •Scanty urination
control

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 Glomerular diseases

• nephritic syndrome
• nephrotic syndrome
• in systemic disease
 Major renal syndromes
• Nephritic syndrome: hematuria, azotemia, variable
proteinuria, oliguria, edema, hypertension.
• Nephrotic syndrome: >3,5 gr proteinuria,
hypoalbuminemia, hyperlipidemia, lipiduria.
• Asymptomatic hematuria or non nephrotic
proteinuria: glomerular hematuria, subnephrotic
proteinuria.
• Rapidly progresive gn’is: acute nephritis,
proteinuria ,acute renal failure.
 Major renal syndrome
• Acute kidney injury: oliguria/anuria 
glomerular injury, interstiial injury, vscular
injury, acute tubular injury.
• Chronic kidney disease: symptom and sign
of uremia.
• Urinary tract infection: bacteria, pyuria.
• Nephrolithiasis (renal stone): renal colic,
hematuria, recurrent stone.
Mechanisms of glomerular injury
• GN (glomerulonephritis) can be induced by
antibodies, deposits of immunoglobulin,
complements, cell-mediated immune mechanisms.
• 2 forms of antibody-associated injury:
1. deposition of soluble circulating Ag-Ab
complexes.
2. antibodies reacting in situ with insoluble fixed
(intrinsic) glomerular Ag or with molecules
planted in glomerulus.
 Acute nephritic syndrome
• Acute proliferative glomerulonephritis:
+ post streptococcal
+ non streptococcal

• Component of crescentic /rapidly

progressive glomerulonephritis
 Acute proliferative (post
streptococcal) glomerulonephritis
• 1 to 4 weeks after group A beta-hemolytic
streptococcal infection type 12, 4 & 1 of the
pharynx or skin ( nephritogenic strain).
• Occurs mostly in children 6 to 10 yrs old, but
adults/ any age can be affected.
• Morphology: - enlarge, hypercellular
glomeruli  caused by : infiltration of
neutrophils and monocytes, proliferation of
endothelial and mesangial cells, and in severe
cases by crescent formation.
Postinfectious glomerulonephritis

• Non streptococcal:
• Caused by other bacteries: staphyloccocal
endocarditis, pneumoccocal pneumonia,
meningococemia.
• Viral : hepatitis B, C, mumps, HIV,
varicella, infectious mononucleosis.
• Parasitic inf: malaria, toxoplasmosis.
 Rapidly progressive glomerulonephritis
(RPGN)
• Acute nephritis, proteinuria and acute renal
failure.
• Rapid and progressive loss of renal function
associated with severe oliguria and death
from renal failure within weeks to months.
• The classic histologic picture: the presence
of crescents in most of the glomeruli
(cresentic glomerulonephritis)
 Nephrotic syndrome
• Massive proteinuria (> 3,5 gr / day).
• Hypoalbuminemia.
• Generalized edema (anasarca)
• Hyperlipidemia.
• lipiduria  free or oval fat bodies.
 Causes of nephrotic syndrome
 Primary glomerular disease:
• minimal change disease
• focal segmental glomerulosclerosis
• membranoproliferative glomerulonephritis
• membranous glomerulopathy
• other proliferative glomerulonephritis (focal,
pure mesangial, Ig A nephropathy)
 Systemic disease:
DM, SLE, amyloidosis, drugs (nsaid,
penicillamine, street heroin), infections
(malaria,syphilis,hepatitis B,C,AIDS),
malignant disease(carcinoma, lymphoma),
miscellaneous (bee-sting allergy, hereditary
npis)
Minimal change nephrotic syndrome
• Most frequent cause of NS in children.
• Diffuse effacement of foot processes of
epithelial cells in glomeruli that appear
normal by light microscopy. These being
replaces by rim of cytoplasm often showing
vacuolization, swelling and hyperplasia of
villi mistermed : fusion of foot processes.
• Cells of proximal tubule are often laden
with lipid and protein  reabsorption of
lipoprotein  lipoid nephrosis.
 Etiology of Minimal change nephrotic
syndrome
 Respiratory infections and prophylactic
immunization.
 Response to corticosteroids and other
immunosupressive th/.
 Association with other atopic disorder
(eczema/rhinitis).
 Increased prevalence of certain HLA haplotypes
in patients with mc dis. ass.with atopy.
 Increased incidence in patients with hodkin
disease.
 Reports of proteinuria-inducing factors in
plasma or lymphocyte supernatant.
 Focal segmental glomerulosclerosis
• Sclerosis of some glomeruli ( thus,it is focal) and only a
portion of capillary tuft is involved ( thus,it is segmental).
• Occurs in the following:
 HIV infection (HIV nephropathy), heroin addiction (heroin
nephropathy), sickle cell disease, massive obesity.
 glomerular scarring /e.g. IgA nephropat.
 in renal ablation, reflux nephropathy, hypertensive
nephropathy, unilateral renal agenesis.
 in certain inherited form of NS  mutations in genes
encoding nephrin, podocin or alpha- actinin 4.
 as a primary disease (idiopathic focal segmental
glomerulosclerosis) 10 – 35 % of NS in child & adult.
Membranoproliferative glomerulonephritis

• Alteration of the basement membrane,

proliferation of glomerular cells and
leukocyte infiltration. Because proliferation
predominantly in mesangium 
mesangiocapillary glomerulonephritis.
• 10 to 20 % NS in children and adults.
• MPGN may be primary (idiopathic) or
secondary ( ass. with sistemic dis and
known etiologic agent)
 Membranous nephropathy
• Most common in adults.
• Diffuse thickening of glomerular capilary wall and
accumulation of Ig containing deposits along the
subepithelial side of basement membrane.
• Occurs at:
 drugs (penicillamine, captopril, gold,NSAID).
 malignant tumor : Ca of the lung, colon and
melanoma.
 SLE : 15 % of glomerulonephritis in SLE.
 Infection ( chronic hepatitis B, C, syphilis,
schistosomiasis,malaria)
 other autoimmune disorder: thyroiditis.
 IgA nephropathy
• Berger disease.
• Presence of prominent IgA deposits in the
mesangial regions detected by immuno
fluorescence microscopy.
• a frequent cause of recurrent gross or
microscopic hematuria.
• Characterized picture : IgA deposit in
mesangial region, often with C3 and lesser
amount of IgG or IgM.
Diabetic nephropathy (glomerulopathy)

• Capillary basement membrane thickening.

• Diffuse mesangial sclerosis.
• Nodular glomerulosclerosis ( Kimmelstiel-
Wilson disease/lesion).
• Prominent accumulation of hyaline material
in capillary loops (fibrin caps) or adherent
to Bowman’s capsule (capsular drops).
 Diabetic nephropathy
• Vasculopathy:
+ hyaline changes in vas afferens and efferens.
+ arteriosclerosis and atherosclerosis.
• Tubulus:
+ Armanni-Ebstein lesion: glycogen vacuoles
in epithelial cells of proximal tubulus.
+ osmotic nephrosis and fatty degeneration
• Interstitium:
+ pyelonephritis.
+ papillary necroticans.
 Lupus nephritis
• Kidney is a frequent target of injury in SLE
• Immune complex deposition in renal structure :
glomerulus, tubular and peritubular capillary
basement membane, and larger blood vessels.
• Morphologic classification: WHO version: 5
patterns (1974): class I: minimal/no detectable
abnormality; class II: mesangial proliferative GN;
class III: focal proliferative GN; class IV: diffuse
proliferative GN; class V : membranous GN.
• Class VI (1982): advanced sclerosing
glomerulonephritis.
 Lupus nephritis
• Morphology: pathognomonic feature :
hematoxylin bodies.
• Others: proliferation lesion, fibrinoid
necrosis and karyorrhexis.
• Thickening of basement membrane  wire-
loop lesion.
• Intracapillary hyaline thrombus.
• Crescent formation.
• Scarring.
 Renal amyloidosis
• Deposition of amyloid in :
+ glomerulus  subendothelial
+ arteriole.
+ peritubular ( tubulus recti)
 Renal amyloidosis
• Morphology: eosinophylic mass.
• Histochemical staining : congo red ,
Birefringent in polarized light, methyl violet
• A kind of immunoglobulin : light chain
(AL) and AA type.
• Glomerular amyloidosis : nephrotic
syndrome  renal failure  uremia.
Diseases of tubules and
interstitium of kidney
ACUTE TUBULAR NECROSIS
• Acute tubular necrosis ( ATN)
– Severe, Reversibel
– Clinicopathologic entity
– Destruction of epithelial cells of tubules
– Acute decrease renal function – cause
acute renal failure
• Pathogenesis :
– Ischemic ATN
• Result from reduced renal perfusion –
hypotension
• Tubular epithelial cells – high rate of
energy-consuming metabolic activity and
numerous organelles – sensitive to hypoxia
and anoxia – cause rapid depletion of
intracellular adenosine triphosphate (ATP)
in tubular epithelium
• Tubular epithelium –simplified (flattened),
some time not necrotic
• Nephrotoxic ATN :
– Chemically induce injury of epithelial
cells
– Tubular epithelial cells are preferred
targets for certain toxins because they
absorb and concentrate toxins.
– Myoglobin and hemoglobin –
endogenous nephrotoxin
• Recovery phase of ATN :
– Tubular epithelium regenerates
– Mitosis
– Increased size of cells and nuclei – cell
crowding
• Clinical features :
– Cause acute renal failure
– Rapidly rising serum creatinin level
– Oliguria
– Urinalysis : degenerating epithelial cells
and dirty brown granular casts
– Duration of renal failure with ATN
depends on many factors : nature and
reversibility of the cause
 TUBULOINTERSTITIAL
NEPHRITIS
• Tubulointerstitial nephritis
– Inflammatory reaction of the tubules and
interstitium
– Histologic and functional alterations that
involve predominantly the tubules and
interstitium
– Chronic tubulointerstitial injury – occur in
disease that primarily affect the glomerulus
– The secondary tubulointerstitial nephritis –
present in a variety of vascular, polycistic,
metabolic, etc
• Tubulointerstitial nephritis (cont)
– Acute and chronic
– Acute tubulointerstitial nephritis :
• Rapid clinical onset
• Histologic : interstitial edema, leukocytic
infiltration of the interstitium and tubules,
focal tubular necrosis
– Chronic tubulointerstitial nephritis
• Mononuclear leukocyte infiltration
• Interstitial fibrosis, widespread tubular
atrophy
Tubulointerstitial nephritis induced by
drugs and toxin
• Drugs and toxin can produce renal injury :
– Trigger an interstitial immunologic reaction-
acute hypersensitivity nephritis induced by
such drugs as methicillin
– Cause acute renal failure
– Cause subtle but cumulative injury to tubules
that takes years to become manifest, resulting
in chronic renal insufficiency – analgesic
abuse nephropathy
• Acute drug-induced interstitial nephritis
– Reported after use of sulfonamided, synthetic penicillins
(methicillin, ampicillin), synthetics antibiotic (rifampicin),
diuretics, NSAIDs
– 15 days ( 2- 40 days) after exposure
– Morphology :
• Edematous interstitium
• Infiltration by mononuclear cells (lymphocyte and
macrophages
– Eosinophils and neutrophils may be present
• Interstitial granulomatous with giant cells (methicillin,
thiazides)
• Tubulitis : infiltration of tubules by lymphocyte
• Glomeruli usually normal, except in some cases caused
by NSAIDs
• Analgesic nephropathy
– Chronic renal disease caused by exessive
intake of analgesic and characterized
morphologically by chronic tubulointerstitial
nephritis with renal papillary necrosis
– The renal damage was first ascribed to
phenacetin, and mixtures with aspirin,
caffeine, acetaminophen and codein
– Patient – usually ingest large quantities of
mixtures of at least two antipyretic analgesic.
– Woman > man
– Pathogenesis :
• Papillary necrosis – induce by mixture of
aspirin and phenacetin, usually combine
with water depletion
• The sequence of events leading to renal
damage, papillary necrosis occurs first, and
cortical tubulointerstitial nephritis is a
second phenomenon.
• The phenacetin metabolite
acetaminophen injures cells by both
covalent binding and oxidative damage
– Morphology :
• Kidneys – normal or slightly reduce
• The cortical changes consist of loss and
atrophy of tubules and interstitial fibrosis
and inflammation.
• These changes are mainly due to
obstructive atrophy caused by the tubular
damage in the papillae.
• Nephropathy associated with
NSAIDs
– NSAIDs associated renal syndrome
include :
• Hemodynamically induce acute renal
failure
• Acute hypersensitivity interstitial nephritis,
resulting in acute renal failure
• Acute interstitial nephritis and minimal
change disease
• Membranous glomerulonephritis, with
nephrotic syndrome
 Pyelonephritis
• Renal disorder affecting the tubules,
interstitium and renal pelvis
• One of the most common disease of the
kidney
• ACUTE : bacterial infection associated
with UTI
• CHRONIC : bacterial infection,
vesicoureteral reflux and obstruction
• Lower UTI :carries the potential of spread
to the kidney
• Etiologi :
– Gram –negative bacilli (85%) : E. Coli, Proteus,
Klebsiella, Enterobacter, Streptococcus
faecalis etc
– Virus : Polyoma virus, cytomegalovirus,
adenovirus
• Route – bacteria can reach the kidneys :
– Blood stream (hematogenous infection)- less
common
– Lower urinary tract (ascending infection)
• Step for renal infection (ascending infection) :
– Colonization of the distal urethrae and introitus(female) by
coliform bacteria
– Urethra to the bladder
• Urethral catheterization
– Multiplication in the bladder
• Outflow obstruction or bladder dysfunction result in incomplete
emptying and increased residual urin – bacteria introduce into
the bladder can multiply unhindered without being flush out or
destroyed in the bladder wall
• UTI frequent occur in lower urinary tract obstruction such as BPH ,
tumor, calculi, neurogenic bladder dysfunction
– Vesicoureteral reflux
• Incompetent of the vesicoureteral valve
• Normal : one-way valve – prevent retrograde flow of urin,
especially during micturition
• Incompetent : reflux of bladder urine into ureters
• Step for renal infection (ascending
infection) : (cont)
– Intrarenal reflux
• Most common in upper and lower poles of
the kidney, where papillae tend to have
flattened or concave tips
Acute pyelonephritis

• Acute suppurative inflammation of the

kidney caused by bacteria or virus.
• Morphology :
– Patchy interstitial suppurative inflammation,
intratubular aggregates of neutrophils and
tubular necrosis.
– Early stage: neutrophils infiltration is limited in
the interstitial tissue, and then reaction involve
tubules and produce abscess with destruction
of the engulfed tubules
– Glomeruli resistant to infection, but large area
of severe necrosis, eventually destroy the
glomeruli. Fungal pyelonephritis often affect
glomeruli
Renal cortical necrosis
Chronic pyelonephritis
• Chronic tubulointerstitial renal disorder in which
chronic tubulointerstitial inflammation and renal
scarring are associated with pathologic
involvement of the calyces and pelvis
• Divide 2 forms : Chronic reflux –associated and
chronic obstructive
• Reflux nephropathy :
– More common
– Renal involvement in reflux nephropathy occurs in
childhood as a result of superimposed of a urinary
infection on congenital vesicoureteral reflux and
intrarenal reflux
• Chronic obstructive pyelonephritis
– The effect of obstruction contribute to parenchymal
atrophy
• Morphology :
– The kidney usually irregular scarred
– The hallmark of chronic pyelonephritis is the
coarse, discrete, cortico medullary scar
overlying a dilated, blunted or deformed
calyx
– Microscopic :
• Tubules show atrophy in some area and
hyperthropy or dilation in others
• Dilated tubulus with flattened epithelium filled with
coloid casts (thyroidization)
Chronic pyelonephritis
 Urinary tract obstruction

• Urinary obstruction – increased

susceptibility to infection and to stone
formation
• Obstruction : sudden/insidious,
partial/complete, unilateral/ bilateral, it
may occur any level of the urinary tract
• Common cause :
– Congenital anomalies : ureteral strictures
– Urinary calculi
– BPH
– Tumor
– Inflammation
– Slough
 Hydronephrosis
• Dilation of the renal pelvis and
calyces associated with progressive
athropy the kidney due to
obstruction to the outflow of urine
• Gross examination : kidney have
slight to massive enlargement
 Urolithiasis
• Most arise in kidney
• Man > woman, 20 – 30 y.o
• Types of calculi :
– Stone (70%) : calcium containing – calcium
oxalat, calcium oxalat mix with calcium
phosphat
– Triple stone or struvite stones, consist of
magnesium amonium phosphat
– Uric acid stone (5%- 10%)
– Cystein (1% -2 %)
 Renal cell carcinoma

• Clear cell RCC ( classical/convensional) 70-80%.

• Papillary RCC  10-15 %.
• Chromophobe  5 %
• Collecting duct Ca  1%
• Medullary Ca.
• Mucinous tubular and spindle cell Ca.
• Carcinoma associated with Xp 11 chromosomal
abberation.
• RCC unclassified.
 Renal cell carcinoma
• Clinical course:
- costovertebral pain
- palpable mass.
- hematuria.
only 10 % of cases.
- fever and paraneoplastic syndrome :
+ polycythemia, hypercalcemia, hypertension, hepatic
dysfunction, feminization/masculinization, cushing
syndrome, eosinophilia, leukomoid reaction and
amyloidosis.
 Renal cell carcinoma
• Tendency to metastasize widely before
giving rise to any local symptoms or signs.
• The common site of metastasis are:
- lungs (> 50%).
- bones (33%).
- regional lymphnode
- liver and adrenal.
- brain.
 Renal cell carcinoma.
• Prognosis:
- 5-year survival rate : 45 – up to 70 %  in the
absence of distant metastases.
- with renal vein invasion or axtension to
perirenal fat  reduced approx : 15 – 20 %.

• Nephrectomy
RENAL CELL
CARCINOMA
 Renal cell carcinoma

-
Urothelial carcinoma
Renal metastases
 Urothelial Carcinoma
• Synonim : Transitional Cell Carcinoma
• Origin : urothelial cell /transitional cell of
tractus urinarius (urethra, vesica urinaria,
ureter, pelviocalyses of the kidney)
• The 7 th most common cancer in the world
• 3,2 % of all cancer in the world
• Men > women = 3,5 : 1
 Etiology
Risk factor :
Cigarette smoking  2-6 x non-smoking
Occupational exposure :
Aniline dye industries
Chronic abuse of analgesics containing phenacetin
Cytostatic agent : Cyclophosphamide,
chlornapazine
Chronic cystitis : Schistosoma Haematobium
 Clinical sign
• Microscopic hematuria
• Painless gross hematuria  most common
• Clotting and painful micturation
• Irritative symptoms (bladder neck or large
area of bladder): dysuria, urgency, frequency
 Diagnosis
• Imaging/Radiology
• Cystoscopy
• Urine cytology
• Histopathology
Urinary bladder
Urothelial carcinoma
Urothelial carcinoma/transitional
cell carcinoma
Urothelial carcinoma
Urothelial carcinoma