DEVELOPMENT OF THE UROGENTAL

SYSTEM

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Urogenital system• Functionally the urogenital system can be divided into two

entirely different components: the urinary system and the genital system. Embryologically and anatomically, however, they are intimately interwoven. Both develop from a common mesodermal ridge (intermediate mesoderm) along the posterior wall of the abdominal cavity, and initially the excretory ducts of both systems enter a common cavity, the cloaca.

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…Development of urinary system• A longitudinal elevation of mesoderm forms on each side of the

dorsal aorta – The Urogenital Ridge.

• This ridge gives rise to parts of the urinary system which is the nephrogenic cord or ridge. Medial part of the urogenital ridge forms the gonadal (genital) ridge.

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Urinary System

KIDNEY SYSTEMS

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• Along the nephrogenic cord, three slightly overlapping kidney systems are formed in a cranial to caudal sequence during intrauterine life in humans: the pronephros, mesonephros, and metanephros.

• The first of these systems is rudimentary and nonfunctional; the second may function for a short time during the early fetal period; the third forms the permanent kidney.

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Primitive kidneys

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Pronephros• At the beginning of the fourth week, the pronephros is

represented by 7 to 10 solid cell groups in the cervical region.

• These groups form vestigial excretory units, nephrotomes, that regress before more caudal ones are formed. By the end of the fourth week, all indications of the pronephric system have disappeared. Most of the pronephric ducts persist and are utilized by the next set of the kidneys.

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Pronephros…

Mesonephros

• These large; elongated; excretory organs appear late in the 4th week caudal to the rudimentary pronephroi. They are well developed and function as interim kidneys for about 4 weeks.

• It consists of glomeruli and mesonephric tubules. These tubules open into the mesonephric ducts. The mesonephric ducts open into the cloaca.

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…Mesonephros• While caudal tubules are still differentiating, cranial tubules

and glomeruli show degenerative changes, and by the end of the second month the majority have disappeared.

• In the male a few of the caudal tubules and the mesonephric duct persist and participate in formation of the genital system, but they disappear in the female

• Shortly after the formation of the mesonephric (Wolffian ducts) a second pair of ducts is developed; these are the Müllerian ducts. Each arises on the lateral aspect of the corresponding Wolffian duct as a tubular invagination of the cells lining the abdominal cavity.

• The orifice of the invagination remains open, and undergoes enlargement and modification to form the abdominal ostium of the fallopian tube

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Müllerian ducts

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Metanephros (The Definitive Kidney)

• The primordia of permanent kidneys begin to develop early in the 5th week and start to function about 4 weeks later.

• The permanent kidneys develop from 2 sources, the metanephreic diverticulum (ureteric bud) and the metanephric mass of intermediate mesoderm (metanephrogenic blastema).

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Metanephric diverticulum• Ureteric bud is the primordium of the ureter; renal

pelvis; calices and collecting tubules. As it elongates, it penetrates the metanephric mass of the intermediate mesoderm. The stalk of it becomes the ureter and its expanded cranial end forms the renal pelvis.

• The straight collecting tubules undergo repeated branching, forming generations of tubules. The first 4 generations enlarge and become confluent to form the major calices. The 2nd four generations coalesce to form the minor calices. The remaining generations of tubules form the collecting tubules.

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…Metanephric diverticulum• The end of each arched collecting tubule induces

clusters of mesenchymal cells in the metanephric mass of mesoderm to form metanephric vesicles. These vesicles elongate and become metanephric tubules. The proximal ends of these tubules are invaginated by glomeruli. Between the 10th & 18th weeks of gestation, the number of the glomeruli increases until the 32 week, when an upper limit is reached.

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MOLECULAR REGULATION• As with most organs, differentiation of the kidney involves

epithelial mesenchymal interactions. In this example, epithelium of the ureteric bud from the mesonephros interacts with mesenchyme of the metanephric blastema.

• The mesenchyme expresses WT1, a transcription factor that makes this tissue competent to respond to induction by the ureteric bud. WT1 also regulates production of glial-derived neurotrophic factor (GDNF) and hepatocyte growth factor (HGF, or scatter factor) by the mesenchyme, and these proteins stimulate growth of the ureteric buds.

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molecular regulation…• The tyrosine kinase receptors RET, for GDNF, and

MET, for HGF, are synthesized by the epithelium of the ureteric buds, establishing signaling pathways between the two tissues.

• In turn, the buds induce the mesenchyme via fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-7 (BMP-7). Both of these growth factors block apoptosis and stimulate proliferation in the metanephric mesenchyme while maintaining production of WT1.

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Positional Changes of Kidneys• Initially the metanephric kidneys lie close to each other

in the pelvis ventral to the sacrum.

• As the abdomen and pelvis grow, caudal to the kidneys, so that they occupy more cranial level. They gradually come to lie in the abdomen and move farther apart and attain their adult position by 9th week. Initially the hilum faces ventrally, however, as the kidney ascends it rotates medially 90 degrees. By the 9th week the hilum is directed anteromedially.

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Changes in Blood Supply of kidneys

• Initially, the renal arteries are branches of the common iliac arteries. As they ascend, they receive their blood supply from the distal end of the aorta. Then, they receive new branches from the aorta. When they come into contact with the suprarenal glands in the 9th week their ascend stops.

• Normally, the caudal branches undergo involution and disappear.

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ANOMALIES OF THE URINARY SYSTEM

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ACCESSORY RENAL ARTERIES

• The anatomical variation involving blood supply to the kidneys reflects 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.

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Congenital polycystic kidney• In congenital polycystic kidney, numerous cysts form. It

may be inherited as an autosomal recessive or autosomal dominant disorder or may be caused by other factors. Autosomal recessive polycystic kidney disease, which occurs in 1/5,000 births, is a progressive disorder in which cysts form from collecting ducts. The kidneys become very large, and renal failure occurs in infancy or childhood. Death of the infant usually occurs shortly after birth. These infants may survive by using postnatal dialysis and kidney transplantation.

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RENAL AGENESIS (FAILURE OF KIDNEY DEVELOPMENT)

• Renal agenesis results when the metanephric diverticular fails to develop or primordial of the ureters degenerate.

• There are two types of renal agenesis: Unilateral renal agenesis & Bilateral Renal Agenesis

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Unilateral renal agenesis• It occurs approximately once in every 1000 new born

infants. Males are affected more often than females, and the left kidney is usually the one that is absent.

• Unilateral renal agenesis often causes no symptoms and is usually not discovered during infancy stage because the other kidney usually undergoes compensatory hypertrophy and performs the function of the missing kidney.

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Bilateral renal agenesis• Bilateral Renal Agenesis is the absence of both kidneys

at birth.

• This absence of kidneys causes a deficiency of amniotic fluid (Oligohydramnios) in a pregnant woman and hence pulmonary hypoplasia. These newborns often die of respiratory failure within a few hours of birth.

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ECTOPIC KIDNEYS• An ectopic kidney is a birth defect

in which a kidney is located in an abnormal position. In most cases, people with an ectopic kidney have no complaints.

• In other cases, the ectopic kidney may create urinary problems, such as urine blockage, infection, or urinary stones.

• Researchers estimate that ectopic kidney occurs once in every 1,000 births.

• An ectopic kidney may remain in the pelvis, close to the bladder.

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Horseshoe kidney• Also known as renal fusion, is a congenital disorder affecting

about 1 in 400 people.

• In this disorder, the individual's kidneys fuse together to form a horseshoe-shape during development in the womb.

• The fused part is the isthmus of the horseshoe kidney.

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DOUBLE URETERS• Double ureters is a congenital condition in which the

ureteric bud, the embryological origin of the ureter, splits (or arises twice), resulting in two ureters draining a single kidney.

• It is the most uncommon renal abnormality, occurring in approximately 1% of the population.

• Duplicated ureter is more common in females. However, this may be due to the higher frequency of urinary tract infection in females, leading to a higher rate of diagnosis of duplicated ureter.

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DEVELOPMENT OF THE URINARY BLADDER

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Development of the urinary bladder

• During the fourth to seventh weeks of development the cloaca divides into the urogenital sinus anteriorly and the anal canal posteriorly.

• The urorectal septum is a layer of mesoderm between the primitive anal canal and the urogenital sinus. The tip of the septum will form the perineal body.

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Urorectal fistula

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…urinary bladder

• Three portions of the urogenital sinus can be distinguished:

• The vesical part

• The pelvic part

• The phallic part

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Development of the urinary bladder …

• The bladder develops mainly from the vesical part of the urogenital sinus, but the trigone is derived from the caudal ends of the mesonephric ducts.

• The epithelium of the entire 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

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Development of the urinary bladder…

• Initially the bladder is continuous with the allantois. The allantois become constricted and form a thick fibrous cord, the urachus which extends from the apex of the bladder to the umbilicus. In the adult the urachus is represented by the median umbilical ligament which is attached to the apex of the bladder and extends along the posterior surface of the anterior abdominal wall In the adult, it is known as the median umbilical ligament.

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Development of the ejaculatory ducts

• The caudal ends of mesonephric ducts become the ejaculatory ducts. The orifices of these ducts move close together and enter the prostatic part of the urethra. The distal ends of the mesonephric ducts in females degenerate.

• In infants and children the urinary bladder, is in the abdomen when it is empty. It begins to enter the greater pelvis at about 6 years of age. It enters lesser pelvis and become a pelvic organ at or even after puberty.

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DEVELOPMENT OF URETHRA

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Development of Urethra• The pelvic part of the urogenital sinus is narrow, which in the

male gives rise to the prostatic and membranous parts of the urethra.

• The last part is the phallic part of the urogenital sinus. It is flattened from side to side, and as the genital tubercle grows, this part of the sinus will be pulled ventrally. Development of the phallic part of the urogenital sinus differs greatly between the two sexes.

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Development of Urethra…• The epithelium of most of the male urethra is derived from the

endoderm of the phallic part of the urogenital sinus. The epithelium of the terminal part of the urethra is derived from the surface ectoderm.

• The entire female urethra is derived from endoderm of the urogenital sinus.

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CONGENITAL ANOMALIES OF URINARY BLADDER

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PATENT URACHUS

• Patent urachus represents failure of the entire course of the urachus to close resulting in an open channel between the urinary bladder and the umbilicus.

• A patent urachus is usually diagnosed in the neonate when urine is noted leaking from the umbilicus.

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Urachal cysts• Urachal cyst forms when both the umbilical and vesical

ends of the urachal lumen close while an intervening portion remains patent and fluid filled. Urachal cysts usually remain obscure until complicated by infection or bleeding.

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Urachal Sinus• A remnant of the lumen usually persists in the inferior

part of the urachus and in about 50 % of cases the lumen is continuous with the cavity of the bladder. The lumen in the superior part of the urachus may remain patent and form a urachal sinus that opens at the umbilicus.

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Urachal Fistula

• Very rarely the entire urachus remains patent and form a urachal fistula that allows urine to escape from its umbilical orifice.

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DEVELOPMENT OF GENITAL SYSTEM

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Development of seminal vesicle

• A lateral outgrowth from the caudal end of each mesonephric duct gives rise to seminal vesicle/gland

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Development of prostate gland

• Multiple endodermal outgrowths arising from the prostatic part of urethra grow into the surrounding mesenchyme and differentiate into prostate glandular epithelium; mesenchyme differntiate into prostatic stroma

• Bulbourethral glands develop from paired outhgrowths from the spongy part of urethra

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