Functional Anatomy of Kidney

Structure and Function of Nephrons

Renal Blood Flow and its Regulation
 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
Lateral to vertebral
column high on body
wall, under floating
ribs
in retro-peritoneal
position
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
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 in to 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 s 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
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)
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
Medullary 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
AGENESIS
HYPOPLASIA
ECTOPIC
HORSESHOE
 CYSTIC RENAL “DYSPLASIA”
 Polycystic Kidney Disease
› Autosomal DOMINANT (AD-ULTS)
› Autosomal RECESSIVE (CHILDREN)
 MEDULLARY
› Medullary Sponge Kidney (MSK)
› Nephronopthisis-Medullary
 ACQUIRED (Dialysis-associated) cystic
disease
 Localized (SIMPLE) Renal cysts
 Renal Cysts in hereditary malformation
syndromes (e.g tuberous sclerosis)
 Glomerulocystic disease
 Extraparenchymal renal cysts
 ENLARGED
 UNILATERAL or BILATERAL
 CYSTIC
 Have “MESENCHYME”
 NEWBORNS
 VIRAL, GENETIC (rare)
 HEREDITARY, PKD1, PKD2
 FOLLOWS AUTOSOMAL
DOMINANT PEDIGREE
 COMPLEX GENETICS
 RENAL FAILURE in 50’s
 CHILDHOOD
 KIDNEYS LOOK EXACTLY LIKE
THE ADULT TYPE
 PKHD1
 PATIENTS WHO SURVIVE
CHILDHOOD OFTEN DEVELOP
HEPATIC FIBROSIS
 MEDULLARY SPONGE KIDNEY (MSK),
usually an incidental finding on CT or
US

 NEPHRONOPTHISIS, cysts @ CMJ,

hereditary (AR), progressive
Cortical
Also called “retention”
cysts
Also “acquired”
Incidental, asymptomatic
VERY very very common
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.
 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 (e.g., uremic
gastroenteritis), neuromuscular (e.g.,
peripheral neuropathy), and
cardiovascular (e.g., uremic fibrinous
pericarditis) involvement
 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
urinesediment, 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.
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
 Diffuse proliferative
glomerulonephritis(GN)
 Crescentic GN
 Membranous GN
 Lipoid Nephrosis (MCD)
 Focal segmental
glomerulosclerosis
 Membranoproliferative GN
 Ig A Nephropathy
 Chronic GN
C. Hereditary Disorders
 Alport syndrome
 Fabry Disease
B. Secondary (systemic) Diseases
 Systemic Lupus Erythematosus
 Diabetes Mellitus
 Amyloidosis
 Goodpasture syndrome
 Polyarteritis nodosa
 Wagener Granulomatosis
 Henoch-Schonlein Purpura
 Bacterial Endocarditis
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
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??

 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)  Chronic tubulointerstitial nephritis
* Allopurinol an insidious disease and most probably
* Phenytoin represents the common final response
* Rifampin pattern of the kidney to a variety of insults
* Interferon alfa 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.
 continuation

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
 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
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
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 :
- diarrhea - weight loss
- confusion - fever
- skin lesions; purpura - kidney failure
- abdominal pain - muscle aches
- mottling of the toes and feet
a) 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 leads proteins & medial thickening
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
 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
 Papillary
carcinoma of
urinary bladder
 grows outward
rather than in
 Muscle layer is
preserved
 Papillary projections
– very diagnostic
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.
 Same system of
grading and
staging.
 Often bleed and
see in urine
 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)
 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)
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
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).
 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
 Causes = Infections (MCC): E. coli, Proteus, TB, Candida, Chlamydia
 uncommon - Schistosomiasis
› Radiation & chemotherapy
› Prolonged catheterization
 Morphologic Types:
› Acute or Chronic:
 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
 macrophages with
PAS positive cytoplasm
Michaelis-Gutmann bodies
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
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.
 Cysts in the kidney are classified as :

 Simple renal cysts

 Autosomal dominant polycystic kidney disease
 Autosomal recessive polycystic kidney disease
 Congenital nephrotic syndrome
 Renal dialysis-associated
 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) 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)