DEVELOPMENT OF THE URINARY

SYSTEM

Tefera B.(MSc. Human anatomy )

 Development of Urinary System
• The urinary system begins to develop before the genital
system and consists of:
Kidneys, which produce and excrete urine
Ureters, which convey urine from the kidneys to the urinary
bladder
Urinary bladder, which stores urine temporarily
Urethra, which discharges the urine from the bladder
externally
 Development of Kidneys and Ureters
Three sets of successive kidneys develop in human
embryos.
 Pronephroi is rudimentary and nonfunctional.
 Mesonephroi is well developed and functions briefly
during the early fetal period.
Metanephroi forms the permanent kidneys.
 Pronephroi
These transitory, non-functional structures appear early
in the fourth week in the neck region.
They are represented by a few cell clusters and tubular
structures in the neck region.
The pronephric ducts run caudally and open into the
cloaca.
The pronephroi soon degenerate; however, most parts
of the pronephric ducts persist and are used by the
next set of kidneys.
 Mesonephroi
These large, elongated excretory organs appear late in
the fourth week, caudal to the pronephroi.
The mesonephroi are well developed and function as
interim kidneys for approximately 4 weeks, until the
permanent kidneys develop and function.
The mesonephric kidneys consist of glomeruli (10– 50
per kidney ) and tubules.
 Mesonephroi
The mesonephric tubules open into bilateral mesonephric
ducts, which were originally the pronephric ducts.
The mesonephric ducts open into the cloaca.
The mesonephroi degenerate toward the end of the first
trimester however, their mesonephric tubules become the
efferent ductules of the testes.
The mesonephric ducts have several adult derivatives in
males
 Metanephroi
Metanephroi— primordia of permanent kidneys—begin
to develop in the fifth week and become functional
approximately 4 weeks later.
Urine formation continues throughout fetal life.
It is excreted into the amniotic cavity and mixes with
the amniotic fluid.
 Permanent kidneys
The permanent kidneys develop from two sources:
The ureteric bud (metanephric diverticulum)
The metanephrogenic blastema (metanephric mass of
mesenchyme)
The ureteric bud is a diverticulum (outgrowth) from the
mesonephric duct near its entrance into the cloaca.
The metanephrogenic blastema is derived from the caudal
part of the nephrogenic cord.
As the ureteric bud elongates, it penetrates the
metanephrogenic blastema—a metanephric mass of
mesenchyme
 Permanent kidneys
The stalk of the ureteric bud becomes the ureter.
The cranial part of the bud undergoes repetitive
branching, forming branches which differentiate into the
collecting tubules of the metanephros.
The first four generations of tubules enlarge and become
confluent to form the major calices, and the second four
generations coalesce to form the minor calices.
The end of each arched collecting tubule induces clusters
of mesenchymal cells in the metanephrogenic blastema to
form small metanephric vesicles.
These vesicles elongate and become metanephric tubules
 Permanent kidneys
The proximal ends of these tubules are invaginated by
glomeruli.
The tubules differentiate into proximal and distal
convoluted tubules, and the nephron loop (Henle loop),
together with the glomerulus and its capsule , constitute
a nephron.
Proliferation of the nephron progenitor cells and
formation of the nephrons are dependent on BMP7 and
Wnt-4 (Notch)/ β-catenin signaling.
Each distal convoluted tubule contacts an arched
collecting tubule, and the tubules become confluent.
 Development of nephrons
A uriniferous tubule consists of two embryologically
different parts
A nephron derived from the metanephrogenic blastema
A collecting tubule derived from the ureteric bud
Between the 10th and 18th weeks, the number of
glomeruli increases gradually and then increases rapidly
until the 36th week, when an upper limit is reached.
At term, nephron formation is complete , with each
kidney containing as many as 2 million nephrons
 Fetal kidneys
The fetal kidneys are subdivided into lobes.
The lobulation usually disappears at the end of the first year of
infancy as the nephrons increase and grow.
The increase in kidney size after birth results mainly from the
elongation of the proximal convoluted tubules as well as an
increase of interstitial tissue.
Nephron formation is complete at birth except in premature
infants.
Although glomerular filtration begins at approximately the ninth
fetal week, functional maturation of the kidneys and increasing
rates of filtration occur after birth
 Fetal kidneys
Branching of the ureteric bud is dependent on induction
by the metanephric mesenchyme.
Differentiation of the nephrons depends on induction by
the collecting tubules.
The ureteric bud and the metanephrogenic blastema
interact and induce each other, a process known as
ireciproca induction, to form the permanent kidneys.
 Molecular studies
Molecular studies, especially knockout and transgenic
analyses in the mouse, show that this process involves
two principal signaling systems that use conserved
molecular pathways.
Recent research has provided insight into the complex
interrelated molecular events regulating the
development of the kidneys
Before induction, a transcription factor WT1 is
expressed in the metanephrogenic blastema supporting
the survival of the as yet uninduced mesenchyme.
Expression of Pax2, Eya1, and Sall1 is required for the
expression of glial-derived neurotropic factor (GDNF) in
the metanephric mesenchyme.
The transcription factors vHNF1 (HNF1 beta) and
GDNF plays an essential role in the induction and
branching of the ureteric bud (branching
morphogenesis).
The receptor for GDNF, c-ret, is first expressed in
the mesonephric duct, but later becomes localized
on the tip of the ureteric bud.
Subsequent branching is controlled by transcription
factors, including Emx2 and Pax2 and growth factor
signals of the Wnt, FGF, and BMP families.
Transformation of the metanephric mesenchyme to
the epithelial cells of the nephron— mesenchymal-
epithelial transition—is regulated by mesenchyme
factors including Wnt4.
Recent studies reveal that mutation of the
angiotensin-type 2 receptor gene might account for
kidney and urinary tract abnormalities.
 Positional Changes of Kidneys
Initially the primordial permanent kidneys lie close
to each other in the pelvis, ventral to the sacrum.
As the abdomen and pelvis grow, the kidneys
gradually relocate to the abdomen and move farther
apart.
They attain their adult position by the ninth week.
This “ascent” results mainly from the growth of the
embryo’s body caudal to the kidneys.
In effect, the caudal part of the embryo grows away
from the kidneys so that they progressively occupy
their normal position on either side of the vertebral
column.
Initially the hilum of each kidney, where blood vessels ,
the ureter, and nerves enter and leave, face ventrally;
however, as the kidneys relocate (“ascend”), they rotate
medially almost 90 degrees.
By the ninth week, the hila are directed anteromedially.
Eventually the kidneys become retroperitoneal (external
to the peritoneum) on the posterior abdominal wall
 Changes in Blood Supply of Kidneys
During the changes in the kidneys position, they receive
their blood supply from vessels that are close to them.
Initially, the renal arteries are branches of the common
iliac arteries.
Later, the kidneys receive their blood supply from the
distal end of the aorta.
When they are located at a higher level, they receive new
branches from the aorta.
Normally the caudal branches of the renal vessels
undergo involution and disappear
 Changes in Blood Supply of Kidneys
The position of the kidneys becomes fixed once they
come into contact with the suprarenal glands in the ninth
week.
The kidneys receive their most cranial arterial branches
from the abdominal aorta; these branches become the
permanent renal arteries.
The right renal artery is longer and often more superior.
 Accessory Renal Arteries
The common variations in the blood supply to the kidneys
reflect the manner in which the blood supply continually
changed during embryonic and early fetal life.
Approximately 25% of adult kidneys have two to four
renal arteries.
Accessory (supernumerary) renal arteries usually arise
from the aorta superior or inferior to the main renal artery
and follow it to the hilum of the kidney.
Accessory arteries may also enter the kidneys directly,
usually into the superior or inferior poles
 Accessory Renal Arteries
An accessory artery to the inferior pole (polar renal artery)
may cross anterior to the ureter and obstruct it, causing
hydronephrosis—distention of the renal pelvis and calices
with urine.
(If the artery enters the inferior pole of the right kidney, it
usually crosses anterior to the inferior vena cava and
ureter.)
The accessory renal arteries are end arteries; consequently,
if an accessory artery is damaged or ligated, the part of the
kidney supplied by it will be ischemic (loss of blood
supply).
Accessory arteries are approximately twice as common as
accessory veins.
 Congenital Anomalies of Kidneys and Ureters
Some type of defect of the kidneys and ureters occurs in
3% to 4% of neonates.
Defects in shape and position are most common.
Many fetal urinary tract abnormalities can be detected
before birth by ultrasonography.
Renal Agenesis:
Unilateral renal agenesis (absence) occurs approximately
once in every 1000 neonates.
Males are affected more often than females and the left
kidney is usually the one that is absent
 Malrotated Kidney
If a kidney fails to rotate, the
hilum faces anteriorly; that is, the
fetal kidney retains its embryonic
position
If the hilum faces posteriorly,
rotation of the kidney proceeded
too far; if it faces laterally, lateral
instead of medial rotation
occurred.
Abnormal rotation of the kidneys
is often associated with ectopic
kidneys
 Ectopic Kidneys
One or both kidneys may
be in an abnormal position.
Most ectopic kidneys are
located in the pelvis, but
some lie in the inferior part
of the abdomen.
Pelvic kidneys and other
forms of ectopia result from
failure of the kidneys to
ascend.
 Horseshoe Kidney
In 0.2% of the population, the poles
of the kidneys are fused; usually it is
the inferior poles that fuse .
The large U-shaped kidney usually
lies in the pubic region, anterior to
the inferior lumbar vertebrae.
Normal ascent of the fused kidneys
is prevented because they are held
down by the root of the inferior
mesenteric artery.
Approximately 7% of persons with
Turner syndrome have horseshoe
kidneys.
 Duplications of Urinary Tract
Duplications of the abdominal part of the ureter and the
renal pelvis are common.
These defects result from abnormal division of the
ureteric bud.
Incomplete division of the metanephric diverticulum
results in a divided kidney with a bifid ureter.
Complete division results in a double kidney with a bifid
ureter or separate ureters
 Ectopic Ureter
An ectopic ureter does not enter the urinary bladder.
In males, the ureter usually opens into the neck of the
bladder or the prostatic part of the urethra.
They may also enter the ductus deferens, prostatic
utricle, or seminal gland.
In females, the ureter opens into the neck of the bladder,
or the urethra, vagina, or vestibule of vagina.
Incontinence is the common complaint resulting from an
ectopic ureter because the urine flowing from the orifice
does not enter the bladder; instead it continually dribbles
from the urethra in males and the urethra and/ or vagina
in females.
An ectopic ureter results when the ureter is not
incorporated into the trigone in the posterior part of the
urinary bladder.
Instead it is carried caudally with the mesonephric duct
and is incorporated into the middle pelvic portion of the
vesical part of the urogenital sinus.
Because this part of the sinus becomes the prostatic
urethra in males and the urethra in females, the location of
ectopic ureteric orifices is understandable.
When two ureters form on one side, they usually open into
the urinary bladder
 Cystic Kidney Diseases
In autosomal recessive polycystic kidney disease,
diagnosed at birth or in utero by ultrasonography, both
kidneys contain many small cysts, which result in renal
insufficiency.
Death of the infant usually occurs shortly after birth;
however, an increasing number of these infants are
surviving because of postnatal dialysis and kidney
transplantation.
 Development of Urinary Bladder
For descriptive purposes, the
urogenital sinus is divided into
three parts:
A vesical part that forms most
of the urinary bladder and is
continuous with the allantois
A pelvic part that becomes the
urethra in the neck of the
bladder, the prostatic part of
the urethra in males, and the
entire urethra in females
A phallic part that grows
toward the genital tubercle
(primordium of the penis or
clitoris
Urinary bladder develops
mainly from the vesical part
of the urogenital sinus.
The trigone is derived from
the absorbed caudal ends of
the mesonephric ducts.
The entire epithelium of the
bladder is derived from the
endoderm of the vesical part
of the urogenital sinus.
The other layers of its wall
develop from adjacent
splanchnic mesenchyme.
Initially the bladder is
continuous with the allantois,
then it becomes a thick
fibrous cord urachus that
extends from the apex of the Urachus

bladder to the umbilicus.

In adults, the urachus is
represented by the median
umbilical ligament.
As the bladder enlarges,
distal parts of the
mesonephric ducts are
incorporated into its dorsal
wall.
These ducts contribute to the formation of the
connective tissue in the trigone of the bladder.
As the mesonephric ducts are absorbed, the ureters open
separately into the urinary bladder.
Partly because of traction exerted by the kidneys as they
ascend, the orifices of the ureters move superolateral and
enter obliquely through the base of the bladder.
In males, the orifices of the mesonephric ducts move
close together and enter the prostatic part of the urethra
as the caudal ends of these ducts develop into the
ejaculatory ducts.
In females, the distal ends of the mesonephric ducts
degenerate.
In infants and children, the urinary bladder, even when
empty, is in the abdomen.
It starts to enter the greater pelvis at about 6 years,
but it does not enter the lesser pelvis and becomes a
pelvic organ until after puberty.
The apex of the urinary bladder in adults is continuous
with the median umbilical ligament, which extends
posteriorly along the posterior surface of the anterior
abdominal wall.
 Urachal Anomalies
In infants, a remnant of the urachal lumen may persist in
the inferior part of the urachus.
In approximately 50% of cases, the lumen is continuous
with the cavity of the bladder.
Remnants of the epithelial lining of the urachus may
give rise to urachal cysts, which are not usually detected
except during a postmortem unless the cysts become
infected and enlarge
The patent inferior end of the urachus may dilate to form
a urachal sinus that opens into the bladder.
The lumen in the superior part of the urachus may also
remain patent and form a urachal sinus that opens at the
umbilicus
Very rarely the entire urachus remains patent and forms
a urachal fistula that allows urine to escape from its
umbilical orifice
 Urethra
Indifferent stage ;
 The genital tubercle (mesenchymal
elevation) develops at the cranial end
of the cloacal membrane.
 Two urethral folds, develop on either
side of the urogenital membrane.
 Laterally two labioscrotal folds
develop on either side of the urethral Urogenital
membrane

folds.
 2 urethral folds in male fuse with
each other to close the penile urethra.
 2 urethral folds in female remain
separate to form labia minora.
Female urethera
The entire female urethra is
derived from endoderm of
the pelvic (middle) part of
the urogenital sinus.
The external urethral
orifice opens dorsal to the
glans clitoris.
 Male Urethra
The genital tubercle elongates Genital
tubercle
forming the phallus, which is the
precursor of the penis.
Most of the male urethra :
(prostatic, membranous and
spongy parts) is derived from
endoderm of the pelvic middle
part of urogenital sinus.
The distal part of male penile
urethra in glans penis starts as
ectodermal solid cord that grows
towards the root of penis to meet
the spongy urethra , later it
canalizes.