Urinary System

Dr. Ika Kartika, SpPA

 Functional Anatomy of Kidney
Structure and Function of Nephrons
Renal Blood Flow and its Regulation
 Kidneys
 Kidneys are a pair of excretory organs situated on the
posterior abdominal wall, extending from upper border of
T12 to L3 vertebra
 Right kidney is slightly lower than the left
 Each kidney is 11 cm long, 6 cm broad and 3 cm thick,
weight 150 g in males and 135 g in females
 Capsules or coverings of kidneys - Fibrous capsule, Peri-
renal fat, Renal fascia and Para-renal fat
 Coronal segment – cortex; medulla; renal sinus
Renal cortex
 Cortical lobules - which
form caps over the
bases of the pyramids
 Renal columns - which
dip in between the
pyramids
Renal medulla
 has 10 conical masses
called renal pyramids,
their apices form renal
papillae
Renal sinus
 Space that extends into kidney from hilus
 Contains branches of renal artery and renal vein
 Renal pelvis divides into 2-3 major calices and these in turn divide into 7-
13 minor calices, each minor calyx (cup of flower) ends in an expansion
which is indented by 1-3 renal papillae
Kidney Location

Lateral to vertebral
column high on body wall,
under floating ribs
in retro-peritoneal
position
 Sectional Anatomy

Cortex: outer layer, light reddish

brown, granular appearance
(due to many capillaries)
Medulla: darker striped
appearance (due to tubules)
Subdivided into distinct renal
pyramids, terminating with a
papilla. Separated by renal
columns from the cortex.

Fig 26-3
 Urine collection:
Ducts within each renal
papilla release urine
into minor calyx

major calyx

renal pelvis

ureter
 Histologically, each kidney is composed 1-3 million
uriniferous tubules. Each consists of
 Secretory part - which forms urine is called nephron, functional
unit of kidney
 Nephrons open into collecting tubules. Many such tubules unite to
form the ducts of Bellini which open into minor calices
Arterial Supply
 One renal artery on each side arising from abdominal aorta
 At or near hilus, renal artery divides into anterior and
posterior branches giving rise to segmental arteries
Lymphatics
 Lateral aortic nodes

Nerve Supply
 Renal plexus (an off shoot of coeliac plexus, T10-L1)
 Circulation of renal blood flow

Renal artery divides serially into – interlobar artery  arcuate  interlobular arteries 
afferent arterioles  capillary tufts of renal glomeruli into outer cortex  efferent arterioles
 in juxtamedullary zone  arterioles become vasa recta (closely applied to loop of henle)
Venous drainage: Stelate veins  interlobular veins  arcuate veins  interlobar veins
Two types of nephrons are present
 Cortical nephrons with short loop of Henle
 Juxtamedullary nephrons with long loops of Henle
 Glomerulus - Five components
 Capillary endothelium – 70-100
nm fenestrations – restricts
Filtration barrier

passage of cells
 Glomerular basement membrane
– filters plasma proteins
 Visceral epithelium – podocytes
with foot processes with 25-60
nm gaps, permeability altered by
contraction of foot processes
 Parietal epithelium (Bowman’s
capsule)
 Mesangium (interstitial cells) –
pericytes, structural support,
phagocytosis, restricts blood flow
in response to angiotensin-II
Filtration barrier Size and charge selective
 Charge: all 3 layers contain negatively charged
glycoproteins  restricts passage of other negatively
charge proteins
 Size: Molecules with radius <1.8 nm  water, sodium,
urea, glucose, inulin  freely filtered
 >3.6 nm  hemoglobin and albumin  not filtered
 Between 1.8-3.6  cations filtered, anions not
 Glomerulonephritis  negatively charged glycoproteins
destroyed polyanionic proteins filtered  proteinuria
Glomerular Filtration Rate (GFR)
 Normal GFR: in men = 125 ml/min, 10% lower in females
 Depends on permeability of filtration barrier
 Difference between hydrostatic process pushing fluid into
Bowman’s space and osmotic forces keeping fluid in
plasma
GFR = Kuf [(Pgc – Pbs) – (gc – bs)
Pgc & Pbs = Hydrostatic pressure in glomerular capillary
and basement membrane
gc & bs = plasma oncotic pressure in glomerular
capillary and basement membrane
Kuf = Ultrafiltration coefficient reflects capillary permeability
and glomerular surface area
Juxtaglomerular apparatus
 Macula densa – modified portion of thick ascending limb
which is applied to glomerulus at the vascular pole between
the afferent and efferent arterioles containing
chemoreceptor cells which sense tubular concentration of
NaCl
 Granular cells – Produce renin, which catalyses the
formation of angiotensin  modulates efferent and afferent
arterial tone and GFR
Juxtaglomerular Apparatus

Macula densa
+
Juxtaglomerular cells
(smooth muscle fibers from
afferent arteriole)
= Juxtaglomerular
Apparatus

= Endocrine system
structure (renin and
EPO)
Functions
Nephron regulates
 Intravascular volume, osmolality, acid base balance,
excrete the end product of metabolism and drugs
 Urine is formed by combination of glomerular
ultrafiltration + tubular reabsorption and secretion
Nephron produces hormones
 Fluid homeostasis (renin, prostaglandins, kinins)

 Bone metabolism (1,25-dihydroxycholecalciferol)

 Hematopoiesis (erythropoietin) – produced by interstitial
cells in peritubular capillary bed (85%  stimulus
hypoxia
 Tubuloglomerular feedback
 GFR

 delivery of NaCl to distal tubule

 Cl- sensed by macular Densa cells

Release of renin (from afferent arterioles)

Angiotensin

Arteriolar constriction
 GFR and RBF
 Hormonal Regulation

 Normally, a balance is present between systems promoting

renal vasoconstriction and sodium retention versus systems
promoting renal vasodilation and sodium excretion.
 Surgical stress, ischemia, and sepsis tip the balance in favor of
vasoconstriction and sodium retention.
 On the other hand, hypervolemia (or induction of atrial stretch)
tips the balance in favor of vasodilation and sodium excretion.
 Epinephrine & norepinephrine

 Afferent arterial tone (directly & preferentially)

Marked  in GFR prevented indirectly by release of renin and
angiotensin-II
Renin angiotensin and Atrial natriuretic peptide (ANP)
 Hypotension or hypovolemia  renin  afferent arteriole 
angiotensin II  release of aldosterone from the adrenal cortex
 Volume reexpansion causes atrial distention  release of ANP
 ANP inhibits the release of renin, renin's action on
angiotensinogen to form angiotensin II, angiotensin-induced
vasoconstriction, stimulation of aldosterone secretion by
angiotensin II, and action of aldosterone on collecting duct
 Prostaglandins
Systemic hypotension and renal ischemia

Angiotensin induced prostaglandin synthesis (PGD2, PGE2 & PGI2)


Vasodilation (protective mechanism)
 Neuronal Regulation
Sympathetic outflow from spinal cord Dopamine dilates afferent and
 efferent arterioles
(via D1 receptor activation)
Celiac & renal plexus


Low dose dopamine partially
1 receptors  sodium reabsorption
reverses norepinephrine induced
in PCT
renal vasoconstriction


2 receptors  Na+ reabsorption and
Dopamine  PCT Na+ reabsorption
 water excretion
Aldosterone
 Enhances Na+ K+ ATPase activity by  number of open Na+
& K+ channels in luminal membrane
 Enhances H+ secreting ATPase on the luminal border od
intercalated cells
 Because principal cells reabsorb Na+ via an electrogenic
pump
 Either Cl- must be reabsorbed
 K+ must be secreted to maintain electroneutrality
  intracellular K+ favours K+ secretion
nMedullary collecting tubule
 Site of action of ADH or AVP (arginine vasopressin) 
activates adenylate cyclase
 Dehydration   ADH secretion  luminal membrane
becomes permeable to water  water is osmotically drawn
out of tubular fluid passing through the medulla 
concentrated urine (upto 1400 mos)
 Adequate hydration – suppressed ADH secretion  fluid in
collecting tubule passes through medulla unchanged and
remains hypotonic (100-200 msom/l)
 Hydrogen ion secreted are excreted in the form of titrable
acids (phosphates) and ammonium ions
Pathology of Kidney
Clinical manifestations of
Renal Diseases
CLINICAL MANIFESTATIONS OF
RENAL DISEASES

 The clinical manifestations of renal

disease can be grouped into
reasonably well-defined syndromes.

 Some are peculiar to glomerular

diseases; others are present in
diseases that affect any one of the
components.
 Terminology
 Azotemia refers to an elevation of blood urea nitrogen and creatinine
levels and is largely related to a decreased glomerular filtration rate
(GFR).
 Azotemia is produced by many renal disorders, but it also arises from
extrarenal disorders.
 Prerenal azotemia is encountered when there is hypoperfusion of the
kidneys, which decreases GFR in the absence of parenchymal damage.
 Postrenal azotemia can result when urine flow is obstructed below the
level of the kidney. Relief of the obstruction is followed by correction of
the azotemia
 When azotemia progresses to clinical
manifestations and systemic biochemical
abnormalities, it is termed uremia.
 Uremia is characterized not only by failure of renal
excretory function but also by a host of metabolic
and endocrine alterations incident to renal damage.
 Secondary gastrointestinal involvement (e.g.,
uremic gastroenteritis), neuromuscular (e.g.,
peripheral neuropathy), and cardiovascular (e.g.,
uremic fibrinous pericarditis) which is necessary for
the diagnosis of uremia
 The major renal syndromes :
 Acute nephritic syndrome is a glomerular
syndrome dominated by the acute onset of usually
grossly visible hematuria (red blood cells in
urine), mild to moderate proteinuria, azotemia,
edema, and hypertension; it is the classic
presentation of acute poststreptococcal
glomerulonephritis.
 The nephrotic syndrome due to glomerular
disease characterized by heavy proteinuria
(excretion of >3.5 gm of protein/day in adults),
hypoalbuminemia, severe edema,
hyperlipidemia, and lipiduria (lipid in the urine).
 Asymptomatic hematuria or proteinuria, or a
combination of these two, is usually a
manifestation of subtle or mild glomerular
abnormalities.
 Rapidly progressive glomerulonephritis
results in loss of renal function in a few
days or weeks and is manifested by
microscopic hematuria, dysmorphic red
blood cells and red blood cell casts in the
urine sediment, and mild-to-
moderateproteinuria
 Acute renal failure is dominated by oliguria or anuria (no
urine flow), with recent onset of azotemia. It can result from
glomerular injury (such as crescentic glomerulonephritis),
interstitial injury, vascular injury (such as thrombotic
microangiopathy), or acute tubular necrosis

 Chronic renal failure, characterized by prolonged

symptoms and signs of uremia, is the end result of all chronic
renal diseases
 Urinary tract infection is characterized by
bacteriuria and pyuria (bacteria and leukocytes
in the urine).
 The infection may be symptomatic or
asymptomatic, and it may affect the kidney
(pyelonephritis) or the bladder (cystitis) only
 Nephrolithiasis (renal stones) is manifested by
renal colic, hematuria,and recurrent stone
formation.
 urinary tract obstruction and renal tumors,
represent specific anatomic lesions that often have
varied manifestations.
Congenital Disorder
 AGENESIS
 HYPOPLASIA
 ECTOPIC
 HORSESHOE
AGENESIS
HYPOPLASIA
ECTOPIC (usually PELVIC)
HORSESHOE
 CYSTIC DISEASES
1. CYSTIC RENAL “DYSPLASIA”
2. Polycystic Kidney Disease
› Autosomal DOMINANT (AD-ULTS)
› Autosomal RECESSIVE (CHILDREN)
3. MEDULLARY
› Medullary Sponge Kidney (MSK)
› Nephronopthisis-Medullary
4. ACQUIRED (Dialysis-associated) cystic disease
5. Localized (SIMPLE) Renal cysts
6. Renal Cysts in hereditary malformation
syndromes (e.g tuberous sclerosis)
7. Glomerulocystic disease
8. Extraparenchymal renal cysts
 CYSTIC RENAL “DYSPLASIA”
 ENLARGED
 UNILATERAL or BILATERAL
 CYSTIC vary in size, multicystic
 islands of undifferentiated
mesenchym, often with cartilage &
immature collecting duct
 NEWBORNS
 AUTOSOMAL DOMINANT
 HEREDITARY, PKD1, PKD2
 FOLLOWS AUTOSOMAL
DOMINANT PEDIGREE
 COMPLEX GENETICS
 RENAL FAILURE in 50’s
 Autosomal dominant polycystic kidney
disease affects up to 1 in 1000 people.

 A definite diagnosis of ADPKD relies on

imaging or molecular genetic testing.
 AUTOSOMAL RECESSIVE
 CHILDHOOD
 KIDNEYS LOOK EXACTLY
LIKE THE ADULT TYPE
 PKHD1
 PATIENTS WHO SURVIVE
CHILDHOOD OFTEN DEVELOP
HEPATIC FIBROSIS
AUTOSOMAL RECESSIVE
(CHILDHOOD) POLYCYSTIC

 Rare developmental anomaly

 Mutations in an unidentified gene localized to chromosome 6p
 Subcategories: perinatal, neonatal, infantile, juvenile
 Perinatal & neonatal : most common, Manifestation : present at birth,
young infants may die quickly from pulmonary or renal failure.
 Kidney : numerous small cysts in cortex & medulla, spongelike
appearance affect both kidney.
 Most cases : + multiple epithelium lined cysts in liver & proliferation of
portal bile ducts
 Patients who survive infancy will develop liver cirrhosis (congenital
hepatic fibrosis)
 MEDULLARY CYSTS
 MEDULLARY SPONGE KIDNEY (MSK),
usually an incidental finding on CT or US

 NEPHRONOPTHISIS, cysts at corticomedullary

junction, hereditary , progressive
ACQUIRED (Dialysis-associated)
Cystic Disease
Kidney from patients with end-stage renal disease who have
undergone prolonged dialysis sometimes exhibit numerous
cortical & medullary cysts
 “SIMPLE” CYSTS
 Usually Cortical
 Multiple or sinngle
 Also called “retention” cysts
 Also “acquired”
 Incidental, asymptomatic
 VERY common
Occasionally, a simple renal cyst can reach a large size and mimic a tumor mass, though
the difference is usually obvious with radiographic procedures. Such a large cyst can be
complicated by hemorrhage or rupture.
Glomerular Disease
Schematic diagram of a lobe of a normal glomerulus
 GLOMERULUS

 Glomerulus consists of an anastomosing network

of capillaries invested by two layers of epithelium
 The visceral epithelium becomes an intrinsic
capillary walls
 The parietal epithelium lines Bowman’s space
(urinary space)
 The glomerular capillary wall is the filtering
membrane
 GLOMERULUS

 The glomerular capillary wall is consist of :

 Endothelial cell
 Glomerular basement mambrane
 Visceral epithelial cells (podocytes)
 Mesangial cells lying between capillaries
GLOMERULAR STRUCTURE
GLOMERULAR DISEASES

A. Primary Glomerulonefritis B. Secondary (systemic) Diseases

 Diffuse proliferative  Systemic Lupus Erythematosus
glomerulonephritis(GN)  Diabetes Mellitus
 Crescentic GN  Amyloidosis
 Membranous GN  Goodpasture syndrome
 Lipoid Nephrosis (MCD)  Polyarteritis nodosa
 Focal segmental  Wagener Granulomatosis
glomerulosclerosis  Henoch-Schonlein Purpura
 Membranoproliferative GN  Bacterial Endocarditis
 Ig A Nephropathy
 Chronic GN

C. Hereditary Disorders
 Alport syndrome
 Fabry Disease
GLOMERULONEFRITIS
PROLIFERATIF DIFUS (PGN)

• Kelainan Glomerulus yang disebabkan oleh postinfeksi.

• Kelainan ini biasanya berupa lesi akut setelah terjadi infeksi.
• Beberapa organisme yang menyebabkan PGN, yaitu :
- Streptococcus ß-hemolitikus
- Virus
- Stafilokokus
- Malaria
- Meningokokus
-Toksoplasmosis
- Pneumokokus
-Skistosomiasis
• Morfologi : Pada umumnya, ginjal dapat normal atau sedikit membesar,
permukaan korteks halus dan bebas jaringan parut.
• Mikroskop cahaya : glomerulus membesar, hiperseluler,disebabkan karena
infiltrasi sel lekosit, proliferasi sel endothel dan mesangial
 GLOMERULONEFRITIS
PROLIFERATIF DIFUS (PGN)

 Pada stadium awal penyakit, mikroskop elektron menunjukkan kompleks

immun tersusun sebagai “punuk-punuk” subepitelial yang bersarang pada
GBM.
 Keadaan klinik : cenderung mendadak ditandai oleh malaise, demam ringan,
nausea, oliguri, azotemia, hypertensi ringan sampai sedang, proteinuria dan
hematuria (urine tampak coklat seperti asap tidak merah terang)
Dengan menggunakan mikroskop cahaya dapat dilihat adanya hiperseluler
anyaman glomerulus yang seragam mengenai hampir semua glomeruli.
 GLOMERULONEFRITIS
PROGRESIF CEPAT (RPGN)

 Glomerulonefritis progresif cepat (RPGN) adalah suatu sindrom yang berhubungan

dengan jejas glomerulus berat dan bukan suatu bentuk etiologik spesifik dari
glomerulonefritis.
 Secara klinik, ditandai khas oleh :
• Oligouria berat.
• Berkurangnya fungsi ginjal dengan cepat dan progresif.
• Kematian karena gagal ginjal dalam beberapa minggu – bulan.
 Kondisi sindrom RPGN dapat terjadi dan dikelompokan kedalam tiga kategori :
• RPGN pasca-infeksi.
Pasca infeksi streptokokus (1 sampai 2 % dari semua kasus) .

• GN disertai dengan penyakit sistemik.

-SLE (Systemic Lupus Erimatosus)
-Poliarteritis
-Sindrom goodpasture
-Granulomatosis wegener
-Purpura Henoch-schohlein

• RPGN Primer atau idiopatik.

  Morfologi :
• Ginjal tampak membesar dan pucat.
• Sering disertai pendarahan petekia pada permukaan korteks.

 Keadaan Klinik :
• Mula gejala RPGN sangat mirip dengan sindrom nefritik
• Tetapi oligouria dan azotemia lebih menonjol.
• 90% penderita menjadi anefritik dan membutuhkan dialisis
kronis/transplantasi.
• Prognosis lebih baik dari pada mereka dengan presentase kresen
yang lebih tinggi.
• Penggantian plasma berguna pada beberapapenderita, terutama
pasien dengan sindrom goodpasture.
GLOMERULONEFRITIS
PROGRESIVE CEPAT

Gambaran histologik ditandai secara khas oleh bentuk

bulan sabit pada kebanyakan glomeruli (GN kresentik).
 GLOMERULONEFRITIS
MEMBRANOSA

• Merupakan kelainan kronis yang diperantarai oleh kompleks immun.

• Penderita dengan SLE merupakan kelompok lain yg penting;sekitar
10% menderita MGN. Lebih dari 85% kasus, penyebabnya tidak
diketahui (glomerulonefritis membranosa idiopatik).
• Pada sebagian kasus mempunyai etiologi yang dapat diidentifikasikan
sebagai berikut :
 infektif : sifilis, malaria, hepatitis B.
 obat : penisilamin, emas, air raksa, heroin.
Keadaan klinis dan prognosis :

 Pria lebih sering terkena dibandingkan wanita.

 Biasanya menunjukan gejala sindroma nefrotik atau adanya
proteinuria.
 Mengenai seluruh kelompok umur tetapi lebih sering pada
dewasa.
 Hipertensi ditemukan kadang- kadang saja pada pemeriksaan
klinik.
 Kira-kira 25% pasien mengalami penyakit progresif yang berakhir
dengan gagal ginjal.
Morfologi :

• Dilihat dengan mikroskop cahaya, perubahan dasar tampak sebagai penebalan

difus GBM.
• Dengan mikroskop elektron, dapat terlihat penebalan yang tampak disebabkan
sebagian oleh pengendapan sub-epitelial yang bersarang pada GBM dan
dipisahkan satu dengan lain oleh penonjolan kecil matriks GBM berbentuk
ujung yang runcing (“gambaran paku dan kubah”).
• Mikroskopik fluoresen menunjukkan imunoglobulin yang tipikal granuler dan
komplemen sepanjang GBM.
• Pemeriksaan imunopatologis menunjukkan adanya deposit granuler dari IgG
dan C3 pada dinding kapiler yang menebal.
• Sesuai dengan berkembangnya penyakit, dinding menjadi lebih tebal akibat
deposit
Ini adalah gambaran glomerulonephritis membranosa yang diambil melalui mikroskop cahaya.
Dalam gambar ini dapat dilihat bahwa lingkaran kapiler mengalami penebalan dan menonjol
tetapi selularitas tidak mengalami pertambahan. Membranous GN adalah penyebab utama
sindrom nefrotik pada orang dewasa.
 Nefrosis Lipoid (MCD)

 Minimal Change Disease juga dikenal sebagai lipoid nephrosis,

nama yang merefleksikan ada lemak di dalam sel epitel tubulus
ginjal.
 Kelainan yang relatif jinak ini adalah penyebab sindrom nefrotik
yang paling sering pada anakanak.
 Pada lipoid nephrosis, terjadi reduksi muatan negatif GBM karena
hilangnya polianion glomerulus; yang selanjutnya memungkinkan
aliran transmembran albumin serum, sehingga terjadi albuminuria.
 Ditandai secara khas oleh glomeruli yang tampaknya normal
dibawah mikroskop cahaya, tetapi tampak adanya kehilangan difus
epitel taju kaki apabila dilihat dengan mikroskop elektron.
Glomerulus tampak normal di bawah mikroskop cahaya. Apabila dilihat dibawah
mikroskopelektron, maka dapat dilihat tidak adanya taju kaki epitel
 FOCAL SEGMENTAL
GLOMERULOSCLEROSIS
(FSGS)
 Menyebabkan terjadinya sindroma nefrotik pada 10% anak-
anak dan 15% dewasa.
 Patogenesisnya belum diketahui
 Gambaran klinis :
* Ditemukan bersama dengan sindroma nefrotik atau
proteinuria yang hebat
* Focal glomerulosclerosis cenderung kambuh lagi pada
ginjal yang ditransplantasikan.
Gambar diatas adalah glomerulus seorang pasien glomeruloskelerosis segmental dan fokal yang diwarnai dengan
trichrome stain. Pada gambar ini dapat dilihat adanya desposisi kolagen ( yang berwana biru). Sekitar 1/6 dari kasus sindrom
nefrotik pada anak-anak dan orang dewasa disebabkan oleh FSGS.
MEMBRANO PROLIFERATIF
GLOMERULONEPHRITIS (MPGN)

• Suatu bentuk glomerulonefritis proliferatif yang menunjukkan adanya

proliferasi dan penebalan membran.
• Biasanya ditemukan pada anak besar dan orang dewasa muda. Perjalanan
penyakit ini sangat lambat, tanpa remisi, dan berakhir dengan payah ginjal.
Keadaan klinik:
• Gejala utama adalah sindrom nefrotik, namun dalam beberapa kasus dapat
hadir sebagai sindrom nefritik ataupun mempunyai ciri keduannya.
• Prognosis MPGN rata-rata jelek.
MEMBRANO PROLIFERATIF
GLOMERULONEPHRITIS
(MPGN)

MPGN dibagi dalam dua bentuk kategori utama, yaitu :

 Tipe 1 MPGN
Deposit tembus elektron terutama terlihat dalam regio subendotelial.
Interposisi sel mesangial didalam reduplikasi membrana basalis juga
merupakan suatu ciri yang konsisten.
 Tipe II MPGN
Bahan yang tembus elekton tidak teratur diendapkan tepat didalam GBM,
menimbulkan penebalan ireguler yang jelas. Pada tipe II deposit-deposit itu
juga ditemukan dalam kapsula bowman, membrana basalis tubuler, dan
kapiler peritubuler
Dengan mikroskop cahaya, GBM menebal dan terdapat proliferasi difus sel – sel mesangial dan suatu penambahan
matriks mesangial. Perluasan mesangium ( sel – sel dan matriks ) berlanjut ke dalam kumparan kapiler perifer,
menyebabkan reduplikasi membrana basalis.
 NEPHROPATHY Ig A

 Penyakit ginjal yang ditandai oleh adanya darah dalam urin,kadar serum Ig A
yang meningkat,hipertensi,dan proteinuria ringan.
 Disebabkan oleh inflamasi glomerolus dan deposit Ig A di jaringan ginjal.
 Menyerang anak-anak dan dewasa muda.
 Gambaran histologis: Proliferasi mesangial fokal ringan,dijumpai Ig A & C3
pada mesangium,ada bercak deposit paramesangial gelap,adanya gambaran
mesangiokapiler yg kadang disertai nekrosis segmental
GLOMERULONEFRITIS
KRONIK

 Merupakan glomerulonefritis tingkat terakhir (“end stage”) dengan kerusakan

jaringan ginjal akibat proses nefritik dan hipertensi sehingga menimbulkan
gangguan fungsi yang irreversible.
 Dapat terjadi pada setiap usia, tetapi paling banyak pada dekade kedua hingga
kelima. Tidak ada perbedaan pada jenis kelamin kecuali pada membranosa
idiopathica, yang lebih sering ditemukan pada pria.
 Kebanyakan GN kronik timbul secara samar-samar dan ditemukan hanya pada
perjalanan lanjut.
Makroskopik :

Tampak ukuran ginjal biasanya mengecil

(secondarycontracted kidney) dan simpai
melekat sangat erat; bila dikupas terjadi
dekortikasi. Permukaan luar granuler tidak
teratur dan bopeng. Pada penampang kortex
tampak menyempit.

Mikroskopik :
- Kelainan glomerulus dapat terjadi karena proses nefritik dan oleh hipertensi
dan penyempitan vaskuler.
- Tubulus biasanya atrofik atau menghilang (tubular loss) dan diganti oleh
jaringan ikat.
- Interstisium menunjukkan penambahan jaringan ikat dan bersebukan sel
radang menahun. Beberapa kelompok tubulus yang berdilatasi dapat
ditemukan.
- Arteri berukuran sedang dan kecil menunjukkan penebalan hialin pada
intima dan media. Derajat kelainan vaskuler biasanya sesuai dengan
kerasnya hipertensi dan perjalanan klinik.
Dapat dilihat pada gambar ini adalah ginjal yang mengalami atrofi dengan korteks yang menipis.
Kenaikan serum kreatinin dan urea dapat digunakan sebagai tanda. Kebanyakan pasien juga
mengalami hipertensi. Pada gambar diatas juga dapat di lihat kista kecil.
SISTEMIK LUPUS
ERITEMATOSUS (SLE)

 SLE merupakan penyakit sekunder ( sistemik ) yang berkaitan

dengan imunologik.
 SLE merupakan penyakit sistemik yang mengenai berbagai organ
seperti kulit, sendi, membran serosa, jantung dan paru, dimana
ginjal ikut terkena pada 70% kasus
 Sindrom klinik yang berhubungan dengan SLE yaitu :
1. Sindrom Nefrotik
2. Sindrom Nefritis
3. Sindrom Klinikopatologi
4. Glomerulonefritis Kronis ( GN Kronis )
5. Glomerulonefritis Fokal ( Proliferatif )
Umum ditemukan penyakit glomerulus yang berhubungan dengan sistemik lupus erimatosus (SLE). Lupus nephritis mempunyai
banyak manifestasi morfologis yang dapat ditemukan dengan renal biopsi. Umumnya, semakin banyak deposit kompleks imun maka
semakin banyak ditemukan proliferasi seluler dan penyakit bertambah berat. Pada gambar ini dijumpai desposisi kompleks imun
yang berat pada membran kapiler glomerulus yang menebal sehingga disebut gambaranwire-loop.
DIABETES MELITUS

 Nefropati diabetik (komplikasi diabetes) merupakan

komplikasi menahun diabetes.
 Kira-kira setelah 15 tahun menderita diabetes maka 10-30%
penderita akan menunjukan gejala komplikasi ginjal.
 Gejala paling awal adalah ditemukan protein dalam urin
(proteinuria).
 Bila proteinuria terjadi sangat hebat maka penderita dapat
menderita kekurangan protein dalam darah yang
mengakibatkan timbulnya sembab seluruh tubuh (sindroma
nefrotik).
 Bila penyakit terus berlangsung akhirnya timbul gagal ginjal
terminal yang memerlukan pengobatan cuci darah atau
cangkok ginjal.
Gambaran histologis glomeropati diabetikum adalah penebalan dinding kapiler dan
terjadi ekspansi matriks mesangial yang mengenai kapiler
Tubulointerstitial Diseases
 Tubulointerstitial diseases

 Kidney diseases that involve structures in the kidney outside the glomerulus.
 These diseases generally involve tubules and/or the interstitium of the kidney
and spare the glomeruli.
 Tubulointerstitial nephritis (TIN)--is a group of inflammatory diseases of the
kidney that primarily involve the interstitium and tubules.
 Pyelonephritis ( pyelo means pelvis)-- tubulointerstitial nephritis with pelvis and
calyceal involvement.
 Pyelonephritis

Acute - usually suppurative

inflammation involving pelvicalyceal
system and parenchyma.

Chronic - involvement of
pelvicalyceal system and parenchyma with
prominent scarring.
 Aetiology of acute pyelonephritis

 Acute pyelonephritis :
mainly caused by bacterial infectionUrinary tract infection
(Proteus,Klebsiella,Enterobacter, Pseudomonas,Stapylococcus albus).
 Invasive procedure :
eg.cystoscopy,catheterization.
 GENDER--Incidence higher in women due to short urethra ( Ratio 1: 20) AND due
to close proximity of urethra to anus.
 Vesicourethral reflux
 Pregnancy
 DM,immunosuppression,immunodefisiency.
 Pathogenesis

Ascending infection
Bacteria from the LUT KIDNEY
Urethral instrumentation (catheterization, cystoscopy ) act as a
predisposing factor.
Hematogenous spread
Less common
septicemia or infective endocarditis kidney
Obstruction
Outflow obstruction or bladder dysfunction
Causes incomplete emptying and increase residual volume
bacteria multiply without disturbance ascend upwards to infect
the kidney
Non obstructive
Incompetence of Vesicourethral orifice allows bacteria to
ascend the ureter into the pelvis of kidney (vesicourethral
reflux)
Sign and symptoms

 Pain at the costovertebral angle

 Chills,fever and malaise
 Dysuria,frequency,urgency
 Urethral irritation
 Urinary findings from laboratory test
showing pyuria,bacteriuria.
 MORPHOLOGY
(Gross)

Kidney, acute pyelonephritis - Gross, outer and cut surfaces

Note: numerous, punctate, yellow foci over the cortical surface.

Question !! what is foci?? what are this foci composed of histologically??

Chronic pyelonephritis
aetiology

 It is a chronic tubulointerstitial inflammation

involving renal parenchyma, pelvis and
calyces associated with scarring.
 non-obstructive
reflux nephropathy
 Obstructive
posterior urethral valves
Chronic pyelonephritis phatogenesis

Chronic obstructive pyelonephritis

Chronic obstruction Outflow obstruction (congenital /acquired)
recurrent infection renal inflammation and renal scarring
chronic pyelonephritis.

*congenital anomalies eg. Posterior urethral valves.

*acquired eg.benign prostatic hyperplasia,stones.

Chronic reflux-associated pyelonephritis(Reflux nephropathy)

more common cause of chronic pyelonephritis
congenital vesico urethral reflux
reflux maybe bilateral/unilateral

Incompetence of Vesicourethral orifice allows bacteria to

ascend the ureter into the pelvis of kidney chronic reflux
chronic pyelonephritis
 Morphology

1.Kidney, chronic pyelonephritis 2. Kidney, chronic

pyelonephritis - Very low power The cortical surface correlates with the
gross appearance, demonstrating elevations and depressions. The calyx
appears dilated and deformed, and there is too much fibrous tissue in the
interstitium.
 Interstitial fibrosis
 Dilated,cast filled tubules
 Chronic inflammation.
Chronic inflammatory cells
 1.Many dilated "colloid"-filled tubules are present. This phenomenon is known,
appropriately enough, as thyroidization of the kidney. 2.markedly thickened
arterial wall in the lower right of the image.
 Diagnosis

Laboratory test Pyuria and bacteriuria

USG to determine size and shape of
the kidney
Pyelogram is characteristis because it shows
the affected kidney to be assymetrically
 Drug induced interstitial nephritis

 Acute drug induced tubulointerstitial

nephritis
adverse reaction to a drug ,begins abruptly, In
most instances, occurs within days of exposure to
the offending drug. Eg.
* Antibiotics (eg, penicillins, cephalosporins,
sulfa drugs, quinolones) ,
* NSAIDs
* Diuretics (eg, thiazides, furosemide)
* Allopurinol
* Phenytoin
* Rifampin
* Interferon alfa  Chronic tubulointerstitial nephritis
an insidious disease and most probably represents
the common final response pattern of the kidney
to a variety of insults and agents.
eg. Lead,drugs,(cyclosporine, cisplatin, and
lithium) and metabolic disorders (hypercalcemia,
and hyperoxaluria)
Because of its insidious nature, chronic
tubulointerstitial
Pathogenesis
 Sign and symptoms

** A unique feature of allergic interstitial nephritis caused by NSAIDs is that patients may present
with nephrotic syndrome. In such patients, massive proteinuria with hypoalbuminemia and edema
are present in addition to the typical features of acute interstitial nephritis
Morphology
 Abnormality in the interstitium.
- pronounced edema
- infiltration of inflammatory cell.
 Acute tubular necrosis

 Phatologically-destruction of tubular cell

 Clinically-acute suppression of renal failure.
 commonest cause of acute renalfailure
 Can be reversible with proper management.
 develops due to :
- direct poisoning of tubules (nephrotoxic lesions)
- renal ischemia (tubulorrhexic lesions)
 Etiology & Pathogenesis

 Ischemic in origin (Tubulorrhexic lesion)

Prolonged ischemia due to :
1. Shock : postoperative, intra-operative, post-traumatic, septic,
hypotensive
2. Hemorrhage: postpartum hemorrhage, abruptio placentae
3. Other: severe burns, transfusion accidents, dehydration, heat stroke,
crushing injuries, non-traumatic rhabdomyolysis, paroxysmal
hemoglobinuria etc.
Direct effects of toxins (Nephrotoxic lesion)
Therapeutic agents :
 Antibiotics : Aminoglycosides, NSAIDs, chemotherapeutic agents, etc.
 Heavy metals: mercury, lead, gold etc.
 Radio contrast agents
 Multiple bee stings, scorpion bites etc
 Gross pathology

 bilaterally enlarged & swollen kidney due

to edema
 Cut surface bulges and has a flabby
consistency
 widened & pale cortex
 dark & congested medulla
 dilated lumen with flattened epithelial cells
 Greatest change in proximal tubules, varies in two forms
1. loss of brush borders- proximal tubules
2. evidence of regeneration of epithelial cells
 hyaline, granular and pigmented casts
 interstitial edema & inflammation
 Intra-vascular collection of nucleated
 depends upon underlying cause, over all mortality
rate » 50%
 post-traumatic (62%), post-operative (56%),
medical (46 %), obstetric (17%)
 Higher in older debilitated pts. & in pts.with
multiple organ disease
 good for uncomplicated and younger patients
Diseases of Blood Vessels
RENAL
CIRCULATION

 The renal circulation receives

around 20% of the cardiac
output.
 It branches from the
abdominal aorta and returns
blood to the ascending vena
cava.
 It is the blood supply to the
kidney, and contains many
specialized blood vessels.
 Renal artery stenosis-caused by atherosclerosis, fibromuscular dysplasia,
Takayasu's arteritis (inflammatory of aorta and its branches), &
posttransplantation stenosis.
Symptoms :
^ sudden onset of hypertension :
before age 50 fibromuscular dysplasia-related stenosis
after age 50 stenosis caused by atherosclerosis
^ hypertension not responsive to 3/> blood pressure medications
^ increased urea in the blood
^ unexplained kidney failure
^ sudden kidney failure when first taking an angiotensin-converting
enzyme (ACE) inhibitor medication for blood pressure and/or heart
 A renal artery aneurysm- bulging, weakened
area in the wall of an artery to the kidney small (<2cm)
& discovered during diagnostic procedures.
Symptoms :
 generally asymptomatic
 hypertension >90% of persons with a renal artery
aneurysm
 dissecting aneurysms (caused by a tear in the inner layer
of the artery wall) flank pain and blood in the urine
Atheroembolic renal disease- a piece of plaque from the aorta / large
arteries breaks off travels through the bloodstream; blocking small arteries; renal
arteries renal insufficiency in the elderly.
Symptoms :
-) Renal artery thrombosis
b) Renal vein thrombosis
NEPHROSCLEROSIS
BENIGN NEPHROSCLEROSIS

Common in : Patients with end-stage renal disease

Pathogenesis:
Chronic hypertension damages small blood vessels, glomeruli, renal tubules, and
interstitial
Tissues progressive renal failure :
* Atrophic kidney finely granular surface (grain leather or pig skin)
* Ischemic atrophy glomerulosclerosis, tubular atrophy, and interstitial fibrosis

In arteries reduplication of the internal elastic lamina → medial

smooth muscle hyperplasia

Symptoms & Signs:

 kidney function chronic renal failure develop
 protein levels in the urine.
 Signs of hypertension-related end-organ damage vasculature of the eyes,
skin, CNS, and periphery
Benign nephrosclerosis : the smaller arteries Arteriolar hyalinosis; insudation of plasm
become thickened and narrowed proteins & medial thickening
leads to patchy ischemic atrophy focal
loss of parenchyma granular
appearance.
MALIGNANT NEPHROSCLEROSIS
 Common in : blacks than whites.
men during their 40s and 50s
women during their 30s.

 Symptoms :
headaches, nausea, vomiting, visual impairment
(scotomas = spots).
Malignant nephrosclerosis focal small
hemorrhages due to essential hypertension
(>300/150 mm Hg)
CHARACTERISTIC LESIONS
 DIAGNOSIS
 Physical examination :
Benign nephrosclerosis: signs of decreased kidney function and have
elevated protein levels in the urine.
Malignant nephrosclerosis: severe high blood pressure, kidney failure,
and visual disturbances.

 Ophthalmoscope damaged blood vessels in the back of the eye,

including bleeding, swelling, and a build-up of fluid.
 The heart may also be enlarged.
 Urine tests will show high levels of protein and clumps of red blood
cells.
 Blood tests high levels of a protein called renin produced by the
kidneys help control blood pressure.
 Computed tomography (CT) scan rule out other disorders that can
cause similar symptoms.
THROMBOTIC
MICROANGIOPATHIES

Pathogenesis & symptoms :

 Classic (Childhood) Hemolytic Uremic Syndrome :
Verocytotoxin-producing E. Coli Sudden onset after a gastrointestinal or flu-like prodromal
episode of bleeding manifestations (hematemesis and melena) severe oliguria, hematuria,
microangiopathic hemolytic anemia prominent neurological changes.
 Adult Hemolytic Uremic Syndrome:
Associated with infection & pregnancy
Secondary :
a. scleroderma
b. systemic lupus erythematosus
c. malignant hypertension
d. chemotherapeutic and immunosuppressive drugs(mitomycin & cyclosporin)
 Thrombotic Thrombocytopenic Purpura :
1. fever
2. neurologic symptoms
3. hemolytic anemia
4. thrombocytopenia
Urinary Tract Obstruction
 Hydronephrosis

 Dilatasi pelvis renalis dan calyces

 Atrofi progresif dan pembesaran kistik
ginjal
 Pelebaran ureter
 Dapat terjadi bilateral atau unilateral
tergantung tempat obstruksi
 ETIOLOGI

 Umumnya disebabkan obstruksi saluran air

kemih
 Obstruksi dapat terjadi pada setiap tempat
dimulai dari ujung distal uretra sampai pelvis
 Bersifat sebahagian sampai total
 Dapat berupa kelainan bawaan atau didapati
 A)Obstruksi

i) pada saluran kemih: katub kongenital pada uretra posterior, batu dan tumor
pelvis renalis

ii) pada dinding saluran kemih: hipertrofi pada dinding setempat, sriktura ureter

iii) dari luar yang menekan saluran kemih: tumor sekitar saluran kemih,hiperplasia
prostate, ateri renalis menekan ureter
B) Kelainan neuromaskular
- misal nya akibat spina bifida, paraplegi, tabes
dorsalis, sklerosis multipel.

C) Kehamilan
- terutama jelas pada primipara, terjadi pelebaran
fisiologik pada ureter dan pelvis, tekanan mekanik
akibat uterus membesar.

D) Idiopatik
 GAMBARAN MAKROSKOPIK

 Ginjal tampak besar

 Pelvis dan calyces melebar

 Papil-papil mendatar serta membentuk cangkir,kistik

kecil-kecil, multilokuler dan berhubungan dengan
calyces dan pelvis melalui lubang-lubang yang lebar

 Kortex lambat laun menipis dan atrofi, akhir nya

berupa pita tipis
Ultrasonographic picture taken from a patient with left ureteral
stone with hydronephrosis.
 GAMBARAN MIKROSKOPIK

 Tampak dilatasi pada susunan tubulus dengan sel epitel tubulus yang menjadi
gepeng

 Glomerulus tidak terjejas

 Dilatasi mengenai tubuli recti

 Tingkat lebih lanjut tubulus dan glomerulus menjadi atrofi dan diganti dgn
jaringan ikat kemudian menghilang.
SIMPTOM

 Flank pain
 Abdominal mass
 Nausea and vomiting
 Urinary tract infection
 Fever
 Dysuria
 Increased urinary frequency
 Increased urinary
DIAGNOSA
UNILATERAL BILATERAL
 KOMPLIKASI

 Pyelonephritis
 Pyonephrosis
 Pyoureter
 Gagal ginjal
 PENGOBATAN

i) Obstruksi akut pada saluran kemih bagian atas :

- Insersi tuba nephrostomy
ii) Obstruksi kronik pada saluran kemih bagian atas:
- Insersi ureteric stent atau pyeloplasty
iii) Obstruksi saluran kemih bagian bawah :
- Insersi urinary catheter atau suprapubic catheter
RENAL CYST

 Cysts may be solitary or multiple, congenital or

acquired.
 A solitary cyst may stimulate a tumour.
 Congenital polycystic disease may not present
until adult life.
 Acquired cysts may be due to renal scarring.
TCC of renal pelvis
Pelvis, ureter, bladder, and urethra
 Lower urinary tract
 Pelvis, Ureters, Bladder& Urethra
› lined by transitional epithelium (urothelium)
› 2 to 3 cells thick - pelvis
› 3 to 5 cells thick - ureters,
› 3 to 7 cells thick - bladder
› surface layer of flattened "umbrella cells"
› apical plaques composed of specific proteins called uroplakins
› Nests of urothelium or in-budding of the surface epithelium into the
mucosa lamina propria called as Brunn nests
 Ureters
 retroperitoneal position
 Retroperitoneal tumors or fibrosis trap and obstructing ureters
 In female, lie close to the uterine arteries
 3 points of slight narrowing:
› Uretero-pelvic junction
› enter the bladder
› cross the iliac vessels
Renal calculi may become impacted
 Congenital anomalies
 1. Double ureters (derived from a double or split ureteral bud)
 2. Uretero -pelvic junction obstruction
› results in hydronephrosis (MCC)
› presents in infants or children
 More in boys on left side
 3. Diverticula= outpouchings of the ureteral wall & asymptomatic
 4. Dilation (hydroureter)= elongation, and tortuosity
a) Congenital hydroureter
 neurogenic defect in the innervation of the ureteral musculature.
b) Megaloureter = Massive enlargement of the Ureter
 due to a functional defect of ureteral muscle
 Inflammations = Ureteritis
› component of UTI
 Forms of chronic ureteritis = ureteritis cystica ( Mucosa forms fine cysts,
ureteritis follicularis small, grapelike clusters on granular mucosal surface)
Ureteritis cystica
Ureter
OBSTRUCTIVE LESIONS
Intrinsic

Calculi Of renal origin, rarely more than 5 mm

indiameter
  Larger renal stones cannot enter ureters

  Impact at loci of ureteral narrowing-

ureteropelvic junction, where ureters
crossiliac vessels, and where they
enter bladder-and cause excruciating
"renal colic"

Strictures Congenital or acquired (inflammations)

Tumors Transitional cell carcinomas arising in

ureters
  Rarely, benign tumors or fibroepithelial
polyps
Blood clots Massive hematuria from renal calculi,
tumors, orpapillary necrosis
Neurogenic Interruption of the neural pathways to the
bladder
Ureter
OBSTRUCTIVE LESIONS
Extrinsic

Pregnancy Physiologic relaxation of smooth

muscle or pressure on ureters
at pelvic brim from enlarging
fundus

Periureteral inflammation Salpingitis, diverticulitis,

peritonitis, sclerosing
retroperitoneal fibrosis
Endometriosis With pelvic lesions, followed by
scarring

Tumors Cancers of the rectum, bladder,

prostate, ovaries, uterus,
cervix, lymphomas, sarcomas
 Sclerosing Retroperitoneal Fibrosis - URETERS
 uncommon cause of ureteral narrowing or obstruction
 leads to hydronephrosis in middle to late age
 Causes
› primary or idiopathic (Ormond disease)
 70% of cases no obvious cause
 similar fibrotic changes in other sites (referred to as
mediastinal fibrosis, sclerosing cholangitis, and Riedel
fibrosing thyroiditis
› Drugs (ergot derivatives, β-adrenergic blockers)
› Adjacent inflammatory conditions (vasculitis, diverticulitis,
Crohn disease)
› Malignant disease (lymphomas, urinary tract carcinomas).
 Tumors

 Benign tumors
› Mesenchymal origin and most common are
 fibro epithelial polyps and leiomyomas
 more often on Left side
 Primary malignant tumors
› TCC ( 6th – 7th decades of life, similar to those
in renal pelvis calyces, and bladder)
TCC of Ureter

 Same system of
grading and staging.
 Often bleed and see in
urine
Urinary Bladder
 Congenital anomalies
 Diverticula= out pouchings
› Congenital
› Acquired - with Prostatic enlargement
› Complications = Infection, calculi, Rarely- carcinomas
 Exstrophy= developmental failure in the anterior wall of the abdomen and
the bladder
 Increased risk of adenocarcinoma of the colon and bladder adenocarcinoma
 Persistent urachus = connects the bladder with the umbilicus
 Increased risk of cancers resembling colonic adenocarcinomas
 CYSTITIS = inflammation of urinary bladder
o Causes = Infections (MCC): E. coli, Proteus, TB, Candida, Chlamydia
 uncommon - Schistosomiasis
› Radiation & chemotherapy
› Prolonged catheterization
o Morphologic Types:
› Acute or Chronic:
Exstrophy.
 Cystitis Special Forms
 1. Interstitial Cystitis (Hunner’s ulcer)
› Characterized by:
 Painful chronic cystitis = dysuria
 MC seen in women
 Ulcers with inflammation & granulation tissue involving all layers
 no bacterial infection
 Mast cells are prominent
 Unknown cause ( difficult to Rx)
 2. Malacoplakia =Peculiar pattern of Cystitis
 Characterized by = soft, yellow, slightly raised mucosal plaques
 Pathogenesis= acquired defect in phagosome degradation
 Histology = large, foamy macrophages , multinucleate giant cells and
interspersed lymphocytes
 Michaelis - Gutmann bodies = Laminated mineralized concretions
 Related to E.coli & Proteus infections
 3. Squamous Metaplasia = response to injury
› Stone in the bladder causes irritation leading to squamous cell carcinoma
Malacoplakia

macrophages with
PAS positive cytoplasm
Michaelis-Gutmann bodies
Papillary Carcinoma- Bladder

 Papillary carcinoma
of urinary bladder
 grows outward rather
than in
 Muscle layer is
preserved
 Papillary projections
– very diagnostic
Urethra
INFLAMMATIONS
 Gonococcal and nongonococcal urethritis
 often accompanied by
› cystitis in women
› prostatitis in men
 Nongonococcal = Chlamydia & Mycoplasma
 25% to 60% of nongonococcal urethritis in men
 20% in women
 Reiter syndrome- triad of arthritis, conjunctivitis, and
urethritis
 Urethral caruncle = inflammatory lesion at external urethral
meatus in the female
› extremely friable = break and bleed
› cause ulceration of the surface and bleeding.
› Surgical excision - cure
Thank you