14 - Devo of Urinary System

Question 1

What are the precursor tissues for the kidney and urinary tract?

Answer 1

Intermediate mesoderm: kidney, caylecesm pelvix, and ureter

Endoderm: epithelial lining of the urinary bladder and urethra.

• The smooth muscle and connective tissue in the walls of these organs are derived from splanchnic mesoderm.

Question 2

How does the intermediate mesoderm develop? When it is seen?

Answer 2

Seen at days 18-20 and eventually separates from the paraxial mesoderm.

Forms the nephrogenic cord that will later be called the urogenital ridge.

Question 3

What allows for the intermediate mesoderm’s kidney-forming ability? What directs kidney formation?

Answer 3

Kidney forming ability mediated by signals from the paraxial mesoderm

TFs Pax2, Pax8, and Lim1 expresed in intermediate mesoderm direct kidney formation

Question 4

What are the urogenital derivatives from the intermediate mesoderm?

Answer 4

• Kidneys
• Ureters
• Gonads
• Genital ducts

This is why you can get defects that affet both the kidneys and the urogenital system

Question 5

What forms within the nephrogenic cord in the thoracolumbar region of the embryo?

Answer 5

A mesonephric kidney: transient functional structure with two components:

• mesonephric duct
• mesonephric tubules

Question 6

What is the function of the mesonephric duct in the mesonephric kidney? What is the cloaca?

Answer 6

Source of inductive signals for kidney structures

Solid cord which eventually canalizes and extends caudally through the nephrogenic cord to fuse with the cloaca (day 26)

Cloaca is the dilated caudal end of the primitive hindgut; a transient, common outlet for the UG and GI systems

Question 7

What are mesonephric tubules? How are they formed?

Answer 7

Immature nephrons: inductive signals from the duct induces tubule formation; differential occurs cranial to caudal along nephrogenic cord.

All tubules induced are not present at the same time.

Question 8

What does the metanephric (mature) kidney form from? Where does it form?

Answer 8

Forms in the pelvic region from the caudal aspect of the nephrogenic cord.

Forms from the metanephric diverticulum (ureteric bud) and the metanephrogenic mesenchyme (metanephric lastema)

Both of these are derived from intermediate mesoderm.

Question 9

What occurs between the metanephric diverticulum and the metanephrogenic mesenchyme?

Answer 9

Reciprocal inductive interactions occur - the epithelial-mesenchyme interactins between them are mediated by GFs, secreted factors, patterning genes, and ECM changes.

They cause the metanephricdiverticulum to branch and the metanephrognic mesenchyme to differentiate into nephrons.

Question 10

What is seen in Potters syndrome?

Answer 10

• Renal agenesis
• Severe urinary obstruction
• Features of facial compression, growth retardation, limb deformities (contracted limbs)
• Pulmonary hypoplasia because you need amniotic fluid to develop the lung

Fetal urine contributes to amniotic fluid volume, esp in the third trimester. Fetus swallows fluid and excretes urine; provides an environment of protection and mobility; growth factors present, lung development.

Question 11

What is oligohydramnias and polyhydramnios?

Answer 11

Oligohydramnios: too little amniotic fluids, associated with renal agenesis, polycystic kidney disease and urethral obstruction.

Polyhydramnios: excessive amniotic fluid, associated with DB, multiple gestation, anencephaly (without part of brain and/or skull), esophageal atresia

Question 12

Inductive interactions between the ___________ and the _______ result in nephron formation.

Answer 12

Metanephric diverticulum (MD) and the metanephrogenic mesenchyme (MM).

Signals frmo MM such as GDNH and RA induce formation of the MD, and the MD branches (cells express Ret, a GDNF receptor)

Expanded tip of the MD is called the ampulla, a key signaling center for nephron induction.

Question 13

What is the function of the ampulla?

Answer 13

Signals from the ampulla direct the arrangement of nephrons and collecting ducts.

Amupllae begin to disappear at about 32 weeks and no new nephrons are formed after all ampullae diappear.

Question 14

The metanephric diverticulum (MD) signals: ____ and ____ prevent the metanephrogenic mesenchyme cell apoptosis and induce a subset of MM cells to aggregate around the ampulla.

Answer 14

FGF2 and BMP7

Question 15

What occurs in the early stages of nephron formation?

Answer 15

Signals from the apulla cause the metanephrognic mesenchyme to form an epithelial vesicle.

Question 16

Formation of the mature nephron involves differentiation and differentual growth of what? What nephron derivatives are made from each part of this?

Answer 16

The S-shaped tubule:

• proximal part forms the DT and loop of henle
• middle part forms the proximal tubule
• distal part forms the renal corpuscle

Question 17

How does the vasculature form in the kidney?

Answer 17

Vascular spouts from the intersegmental arteries are induced to grow toward the forming kidney.

Only induced mesenchyme secretes angiogenic growth factors (VEGF) that attracts the vascualr sprouts to the forming kidney.

Question 18

What is seen in multicystic dysplatic kidney?

Answer 18

Most often unilateral (this differentiates it from polycystic kidney disease which is bilateral), multiple cysts of varying sizes making the kidney non-functioning.

Primitive ductules and cartilage seen; atretic ureter (uretal atresia)

Contralateral kidney hypertorphies

Bilateral disease is rare and fatal.

Question 19

What is seen clinically with multicystic dysplastic kidney?

Answer 19

Potential for abnormalities of the contralateral kidney, such as vesicoureteral reflux, approximately 28%

HTN potentially

Failure of large MCKD to regress may be indication for nephrectomy (surgical removal)

Non-genetic (polycystic kidney disease is genetic)

Question 20

Remodeling and differental growth of the branchting metanephric diverticulum results in the formation of what? Describe the growth.

Answer 20

Formation of collecting ducts, calyzes, pelvis and ureter.

There’s little growth of early generations of branches, and faster growth of of polar branches.

Exapnsions of the 3rd to 6th generations of branches form the calyces, pelvis, and ureters. Branches distal to the 5th and 6th generations form collecting ducts.

Question 21

What is visible in the fetal kidney but not the adult kidney?

Answer 21

Renal lobes

Each kidney lobe ends in a pyramid shaped renal papilla which empties into a minor caylx.

Question 22

What are some anomalies that result in variations in kidney size, histological organization or number?

Answer 22

Hypoplastic kidneys: may be small and normal or small because of abnormal development

Dysplastic kidneys

Duplications of ureter or kidney (partial or complete)

Horshoe kidney: fusion prevents complete ascent

Question 23

How does the metanephric kidney get where it’s supposed to be in the body?

Answer 23

Develops in the pelvis and “ascends” into the abdomen because of differential growth of the embryonic body.

• pelvic and lumbar kidneys can result from failed or incomplete ascent
• extra renal vessels result from failure to atrophy during ascent

Gonads develop in the abdomen and descend.

Question 24

How do people get polycystic kidney disease?

Answer 24

It’s inherited: either autosomal recessive or autosomal dominant

Question 25

What is a common renal tumor seen in children? Where is the defect?

Answer 25

Nephroblastoma (Wilm's tumor) Gene is located on chromosome 11.

Question 26

What is the clinical presentation of a ureteropelvic junction (UPJ) obstruction in an infant and older child or adult? How would you diagnose it?

Answer 26

**Infant**: flank mass, UTI, failure to thrive, sepsis **Older child/adult**: flank pain, colicky pain, UTI, hematuria Hydronephrosis is usually seen: kidney swells from failure to drain **Diagnose with ultrasound or renal scan.**

Question 27

Division of the cloaco results in what?

Answer 27

Division of the cloaco by the urorectal septum provides separate outlets for the UG and GI systems. The primitive UG sinus is located ventrally and the anorectal canal is located dorsally.

Question 28

What does the cranial or vesicle part of the primary UG sinus form?

Answer 28

It enlarges to form the bladder and urethra. The lining is derived from endoderm. Smooth muscle and CT of the bladder wall is derived from the surrounding splanchnic mesoderm.

Question 29

What does remodeling of the posterior wall of hte bladder result in?

Answer 29

**The formation of the trigone region:** which is associated with the netrance of the ureters and exit of hte urethra. **In males, differential growth results in the mesonephric ducts opening into the urethra rather than the urinary bladder.** * in men, the mesonephric duct distal to the metanepheric diverticulum becomes the vas deferenes (see image)

Question 30

What are two anomalies of the urinary bladder?

Answer 30

**Anomalies of the urachus:** arise from failure of regression of the allantois and urachus (fibrous remnant of the allantois, a canal that drains the urinary bladder of the fetus that joins and runs within the umbilical cord) **Exstrophy of the bladder:** defect of the ventral abdominal wall in which the lining of the bladder and the urethra is open to the surface.

Question 31

What are the risks associated with ureteral reflux?

Answer 31

The higher the grade reflux: * the greater risk for scarring * the more abnormal the anatomy is * spontaneous resolution is less likely * surgical intervention may be necessary.

Question 32

What causes ureteral reflux? How is it treated?

Answer 32

A lateralized ureter leads to reflex, which can lead to recurrent kidney infections and subsequent atrophy or the kidney. Treatment is antibiotic prophylaxis and/or surgical repair.

Question 33

What is bladder exstrophy? How common is it and who gets it?

Answer 33

**When the bladder fuses with the anterior abd. wall. due to a failure of medial mesenchymal migration.** Can occur in makes with epispadius or females with shortened vagina or bifid clitoris. Gonadal structures are norma and babies are typically healthy. 1 per 30,000 live births, male to female 3:1

Question 34

What occurs with bladder exstrophy repair? What are the long term issues?

Answer 34

Surgery performed shortly after birth, babies only hostpitalized for 6-14 days. Incontinence is a long-term issue Upper tracts at risk after repair.

Question 35

What is the extent to which the urethra is formed from the caudal part of the UG sinus differs in males and females?

Answer 35

**Males:** forms the proximal portiopn of the prostatic urethra **Females:** forms most of the urethra

Question 36

How does the fate of the UG sinus differ in males and females?

Answer 36

**Males:** pelvic portion forms the distal prostatic and membranous urethra; phallic portion forms the penil urethra **Female:** pelvic portion forms the lower half of the vagina; phallic portion forms the vestibule

Question 37

What are two anomalies of the urethra?

Answer 37

Agenesis and atresia of the urethra: associated with urinary obstruction and prune belly syndrome Posterior urethral valves: mucosal folds that obstruct the lumen of hte urethra, a common cause of renal failure in boys

Question 38

What results from posterior urethral valves?

Answer 38

Occurs in males only, 1/5000 male births Obstructing valves in the prosthetic urethra just below where the vas deferens enters leads to severe obstruction of urinary tract and irreversible renal dysplasia Most likely cause of

Question 39

What is the pathology of posterior urethral valves? How are they treated?

Answer 39

Obstructing membrane at membranous urethra Small echo-bright kidneys. Valves easily ablated. Outcome largely determined by how bad the kidneys are.

Question 40

The kidney and ureter form from \_\_\_\_\_\_\_. The lining of the urinary bladder and urethra are derived from _____ and the wall from \_\_\_\_\_\_\_\_.

Answer 40

The kidney and ureter form from **intermediate mesoderm.** The lining of the urinary bladder and urethra are derived from **endoderm** and the wall from **splanchnic mesoderm**.

Question 41

What is the source of the metanephric diverticulum?

Answer 41

The mesonephric koidney provides the mesonephric duct, the source of the metanephic diverticulum.

Question 42

When does the metanephric (mature) kidney begin to form? What does it depend on?

Answer 42

Week 5. Depends on inductive interactions between the metanephric diverticulum and the metanephrogenic mesenchyme.

Question 43

What forms from the metanephric diverticulum?

Answer 43

The ureter, pelvis, calyces, and collecting ducts.

Question 44

What do the nephrons derived from? What are the glomeruli derived from?

Answer 44

Nephrons: metanephrogenic mesenchyme Glomeruli: sprouts of intersedmental arteries

Question 45

What does the ventral part of the divided cloaca become? What does this form?

Answer 45

The primitive UG sinus from which the urinary bladder and urethra are formed.

Question 46

What does amniotic fluid in the third trimester of pregnancy reflect? What does oligohydramnios raise concerns for?

Answer 46

Kidney function; therefore, oligohydramnios raises concern for kidney dysfunction A physical exam finding of flank mass on a newborn should raise concerns for kidney pathology, especially if they are otherwise well.

Question 47

A febrile UTI in a child should raise concern for what?

Answer 47

congenital anomalies.

Question 48

Dilated bladder + bilateral renal pelvis dilation + male fetus = ?

Answer 48

Posterior urethral valves until proven otherwise.