1. Development of the Urinary System
Ahmed Abdellatif, MD, PhD

2. Objectives Describe the development of the Urinary System, i.e.
Nephrogenic cord; pronephros, mesonephros, & metanephros.
Collecting System; Ureters, Urinary bladder, Urethera.
Migration of the kidney & its effect on blood supply
Describe the development of Suprarenal glands; Cortex & Medulla.
Congenital Anomalies.

3. Urogenital ridge Urogenital ridge
From intermediate mesenchyme (mesoderm)
Longitudinal elevation on each side of aorta
Nephrogenic cord  urinary system
Gonadal ridge  genital system
Drawing on the board:
During development you end up with an aorta that is almost running the full length of the body at that time
On each side of the aorta a piece of tissue develops – predecessor for the urogenital system
A portion goes to urinary system and a portion goes to the genital system = urogenital ridge
There are two of these, one on each side of the aorta
At one stage, around the beginning of the 4th week  process of differentiation will start with the formation of primitive kidneys
- First one develops in the neck, second one develops in the abdominal and thoracic areas, and the 3rd one develops in the pelvic area

4. Nephrogenic cord 1. Pronephros Bilateral,
Appear early in the 4th week in the neck region.
The pronephric ducts run caudally and open into the cloaca.
The pronephroi degenerate.
The pronephric ducts persist and are used by the next set of kidneys.
This would be somewhere around the 4th week
Pronephros which develops in the neck is gone by the end of the 4th week  it is nonfunctional
The intermediate form will be functional between 4 and 5 weeks  keeps functioning until about the 9th week then gone
You need something that collects urine on one side, and blood supply on the other
Pronephros is useless
However, we end up with a tube = this is what is important and remains

5. Mesonephros 2. Mesonephros.
Appear late in the 4th week, caudal to the pronephroi.
Function as interim kidneys for approximately 4 weeks, until the permanent kidneys develop.
Consist of glomeruli (10-50 per kidney) and tubules.
The mesonephric tubules open into bilateral mesonephric ducts, originally the pronephric ducts.
The mesonephric ducts open into the cloaca.
Degenerates end of 1st trimester.
In the mesonephric stage, there are tubules that are going to be functional
- They have blood vessels on one side, and have a glomulerus and collecting duct on the other side

6. Early in 4th week Late in 4th week 5th week
Cloaca = opening that receives openings from different excretory openings
Mesonephric tubules are opening into the sinus at the same time this happens, a new tube develops = ureteric bud
This ureteric bud is like a little branch on a tree that starts to grow and then branches and branches
You can think of the leaves on all these little branches as a metanephric mesenchyme (aka metanephric blastma)
Blastma means group of cells that are able to grow and differentiate to form an organ
This now starts working on the formation of the kidneys
The branching keeps occuring until there is a stage where we reach collecting tubules
Some branches will mix, blend and merge together to form the renal pelvis
Some branches will mix, blend and merge together to form the major calyces
Some branches will mix, blend and merge together to form the minor calyces
Overall, end up with tiny branches of collecting tubules surrounded by a piece of tissue from that mesenchyme (progenitor for the kidney)
Progenitor area starts to develop it’s own tube system (See slide 11) Ss
Late in 4th week
5th week

7. Table 12-1. Derivatives and Vestigial Remains of Embryonic Urogenital Structures
MALE
EMBRYONIC STRUCTURE
FEMALE
Efferent ductules of testis
Mesonephric tubules
Epoophoron
Paradidymis
Paroophoron
Appendix of epididymis
Mesonephric duct
Appendix vesiculosa
Duct of epididymis
Duct of epoophoron
Ductus deferens
Longitudinal duct; Gartner duct
Ureter, pelvis, calices, and collecting tubules
Ureter; pelvis, calices, and collecting tubules
Ejaculatory duct and seminal gland
Kidneys and ureters develop
During the time the kidneys are developing, other organs are being developed such as the ovaries, testicles, gonads etc
These have tubes (both male and female)
The arrangement of these tubes are different in the male and the female (hormones, etc…. Differentiate this)
Embryological remnants stay around from these tubes
The mesonephric duct stays and becomes the collecting system for the testicles (All the things listed from the appendix of the epididymis down)
In females these stay as the broad ligament and can see in the vicinity of the ovaries
Can get cysts in one of these tubules can be see. Otherwise, if this doesn’t occur, cannot be seen to the naked eye S s

8. Metanephros 3. Metanephros
Metanephroi = primordia of permanent kidneys
Begin to develop in the 5th week.
Become functional 9th weeks.
Urine formation continues throughout fetal life. It is excreted into the amniotic cavity and mixes with the amniotic fluid.
The permanent kidneys develop from two sources
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.
A blastema is a mass of cells capable of growth and regeneration into organs or body parts.
Cloaca = opening that receives openings from different excretory openings
Mesonephric tubules are opening into the sinus at the same time this happens, a new tube develops = ureteric bud
This ureteric bud is like a little branch on a tree that starts to grow and then branches and branches
You can think of the leaves on all these little branches as a metanephric mesenchyme (aka metanephric blastma)
Blastma means group of cells that are able to grow and differentiate to form an organ
This now starts working on the formation of the kidneys

9. Metanephros
The branching keeps occurring until there is a stage where we reach collecting tubules
Some branches will mix, blend and merge together to form the renal pelvis
Some branches will mix, blend and merge together to form the major calyces
Some branches will mix, blend and merge together to form the minor calyces

10. Development of the Collecting System
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.
1st four generations of tubules enlarge and become confluent to form the major calices,
2nd four generations coalesce to form the minor calices.

11. Development of the Collecting System
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 (Fig. 12-7B and C).
The proximal ends of these tubules are invaginated by glomeruli.
Overall, end up with tiny branches of collecting tubules surrounded by a piece of tissue from that mesenchyme (progenitor for the kidney)
Progenitor area starts to develop it’s own tube system (See slide 11)
Collecting tubules stimulates the formation of the vesicles
The piece of tissue that surrounded the collecting tubule is now starting to differentiate and become a vesicle  vesicle elongates and differentiates
End up with proximal and distal convoluted tubules
Have a glomerulus at the end of these tubules  stimulates the formation of a capsule, and blood vessels, and a functional unit is now formed S

12. Development of the Collecting System
The tubules differentiate into
Proximal & Distal convoluted tubules
nephron loop (Henle loop).
Each distal convoluted tubule contacts an arched collecting tubule, and the tubules become confluent. (polycystic kidney??).
A uriniferous tubule consists of 2 embryologically different parts (Figs. 12-6 and 12-7):
A nephron derived from the metanephrogenic blastema.
A collecting tubule derived from the ureteric bud
The sight of contact between two developing systems
One coming from the ureteric bud
One coming from the metanephric mesenchyme
Whenever you have a union between to different embryological origins  potential for something to go wrong
It is very likely to get cysts on kidneys
Theories
Could have happened as a problem in the loop  gets blocked
If you block the tube, you block the drainage, but not the function bc the glomerulus, capsule, and collecting system still there  production of urine happening still (just not drainage)
Collection over years can cause cysts
Can be completely asymptomatic
Or can be massive where millions of units are obstructed  death (usually genetic)
In utero or quickly after birth if genetic
Can develop later in life  function will deteriorate Is S Ss s

13. Fetal Kidneys
At full term, nephron formation is complete, with each kidney containing as many as 2 million nephrons.
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.
Increase in kidney size after birth results mainly from the elongation of the proximal convoluted tubules as well as an increase of interstitial tissue.
Remember you have the urogenital ridge
differentiates into the pronephros  goes away soon (within a week)
Mesonephros  stays around for about 4 weeks then gradually degenerates
This is all because we are waiting for the full kidney to develop
The in utero kidney starts to function  produces urine  starts to collect in the bladder  fetus pees in the amniotic fluid  they swallow the amniotic fluid
There is lots of pee swallowing and excretion HOLY CRAP YOU SWALLOW YOUR OWN PEE!!!!! THIS IS WHY BABIES SCARE ME!!!!!!
The kidneys, when the child is born, are functional
They grow in size and improve in function after delivery
We are all born with a lobulated form of a kidney
As the kidneys start to grow in size and develop more, the lobulations go away in most cases
In some animals, and a few humans, they remain, but have no significant effect on the function

14. Migration of the kidney
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..
Initially the hilum of each kidney face ventrally; kidneys rotate medially almost 90 degrees. By the ninth week, the hila are directed anteromedially.
In adults, can see the kidneys in the posterior abdominal wall of the abdomen
This isn’t true migration I regards to a piece of tissue moving from one area to another to another, it’s just differential growth of the body of the embryo
Some pieces of the body grow faster than other pieces
Pelvis descends further down, the kidneys just kind of lag behind

15. Changes in Blood Supply of Kidneys
Kidneys receive blood supply from:
common iliac arteries
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.
And the transition process of the kidneys moving occurs, blood vessels are growing as well and start moving around too
Renal a. move from the beginning of where the common iliac arteries begin to close to the celiac trunk in the abdomen
Know the renal a will come from the aorta somehow. Can be a long or short path
Usually have just one to either kidney because the others involute and disappear

16. Changes in Blood Supply of Kidneys
ACCESSORY RENAL ARTERIES
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 (Fig A, C, and D). Accessory arteries may also enter the kidneys directly, usually into the superior or inferior poles.
ARA = abnormal renal aorta
AA = abdominal artery
IVC = inferior vena cava
Concern with accessory renal arteries is during surgery
Doc thinks pt only has one, goes to remove kidney, and then gets excessive bleeding everywhere and not sure why = because of these arteries
If not controlled quickly the pt will die

17. Congenital Anomalies of Kidneys
Renal Agenesis, unilateral or bilateral.
Malrotated Kidney, hilum stays posterior.
Horseshoe Kidney.
Supernumerary kidney, additional kidneys.
Ectopic Ureter, opens in an abnormal area.
If lower poles of the kidneys fuse together and move up until the SMA stops it
This will prevent a horseshoe kidney from going to it’s normal location
Function will not be effected, but the location of where the kidney normally sits will be different
The suprarenal glands develop from a different source and context , so it is not necessary for them to be right on top of the kidneys to function
It’s just not called suprarenal anymore
Renal agenesis – bye bye to a kidney = unilateral (can go unnoticed for years), bye bye both kidneys = bilateral
Horseshoe kidney and more than one kidney (Supernumary kidney) = functional
Can be hard to make a diagnosis with this

18. Congenital Anomalies of Kidneys
Duplications of Ureter and/or renal pelvis.
Sometimes has no effect on the system
Can have ureter dumping into another place it shouldn’t (into pelvis, vagina, etc…)

19. Congenital Anomalies of Kidneys
Ectopic Kidneys, Most ectopic kidneys are located in the pelvis, pelvic kidneys.

20. Congenital Anomalies of Kidneys
Cystic Kidney Diseases
autosomal recessive polycystic kidney disease, diagnosed at birth or in utero by ultrasonography, both kidneys contain many small cysts (Fig A), which result in renal insufficiency. Death of the infant usually occurs shortly after birth.
Multicystic dysplastic kidney disease results from dysmorphology during development of the renal system (Fig B). The outcome for most children with multicystic dysplastic kidney disease is generally good because the disease is unilateral in 75% of the cases.

21. Development of Urinary bladder
Urogenital sinus is divided into:
Vesical part that forms most of the urinary bladder and is continuous with the allantois
Pelvic part that becomes the urethra in the neck of the bladder,
Prostatic part of the urethra in males, and the entire urethra in females
Phallic part that grows toward the genital tubercle (primordium of the penis or clitoris).
The bladder develops mainly from the vesical part of the urogenital sinus, but its trigone (triangular area at the base of the bladder between the openings of the ureters) is derived from the 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.
Other layers of UB wall develop from adjacent splanchnic mesenchyme.
Sinus = pouch, sac, collecting system, whatever
One chamber develops into the rectum the other into the urogenital system
An additional septum forms in a female and creates the vaginal opening

22. Development of Urinary bladder
Initially the bladder is continuous with the allantois. The allantois constricts and becomes a thick fibrous cord, the urachus (median umbilical ligament).
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.
One chamber develops into the rectum the other into the urogenital system
An additional septum forms in a female and creates the vaginal opening that seperates it from the urethral and anal canal

23. 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.
Easily fixed with surgery (any of these)

24. Congenital Anomalies of the UB
CONGENITAL MEGACYSTIS
A pathologically large urinary bladder may result from a congenital disorder of the ureteric bud, which may be associated with dilation of the renal pelvis. The large bladder may result from posterior urethral valves. Many infants die from this disorder or suffer from renal failure in early childhood.
Exstrophy of the bladder
Deficiency of the anterior abdominal wall, is caused by incomplete median closure of the inferior part of the wall (Fig ). The defect involves both the abdominal wall and the anterior wall of the urinary bladder; it results from failure of mesoderm to migrate between the ectoderm and endoderm of the abdominal wall
Exstrophy
Failure of both the anterior abdominal wall and the UB
Congenital megacystis
Get hyrdonephrosis – backpressure and expansion of the kidneys in utero
Big bc not emptying

25. Development of Urethra
The epithelium of most of the male urethra and the entire female urethra is derived from endoderm of the urogenital sinus.
In males, the distal part of the urethra in the glans of the penis is derived from a solid cord of ectodermal cells that grows inward from the tip of the glans and joins the rest of the spongy urethra.
Consequently, the epithelium of the terminal part of the urethra is derived from the surface ectoderm.
The connective tissue and smooth muscle of the urethra in both sexes are derived from splanchnic mesenchyme.
You can get issues with this
They cannot come together
It’s too narrow
Hypospagous, epispagous (prev lect)

26. Development of the suprarenal glands
Cortex develops from mesenchyme. 
Medulla from neural crest cells from a sympathetic ganglion.
During the 6th week, the cortex begins as an aggregation of mesenchymal cells on each side of the embryo between the root of the dorsal mesentery and the developing gonad.

27. CONGENITAL ADRENAL HYPERPLASIA & ADRENOGENITAL SYNDROME
Excessive androgen production during the fetal period, due to abnormal increase in the cells of the suprarenal cortex results.
In females, this usually causes masculinization of the external genitalia.
Male infants have normal external genitalia.
Later in childhood in both sexes, androgen excess leads to rapid growth and accelerated skeletal maturation.
Labia fuses like a scrotal sac
Clitoris enlarges
Can be fixed with surgical correction
Fix the problem of the adrenal cortex
Also note that with tumors, whenever you have cells that are able to produce something more there is a potential for tumors
- Neuroblastoma  begins from neural crest cells of the suprarenal gland