Development of the Urinary System

Question 1

Precursor Tissues for the Kidney and Urinary Tract:

1. Intermediate Mesoderm
2. Endoderm

Answer 1

1. Intermediate Mesoderm
   
   • Kidney
   • Caylces
   • Pelvis
   • Ureter
2. Endoderm
   
   • Epithelial Lining of:
     
     • Urinary Bladder
     • Urethra

Question 2

What parts of the urinary system come from the splanchnic mesoderm?

Answer 2

Smooth Muscle & CT in the walls of urinary system organs are derived from Splanchnic Mesoderm

Question 3

Developmental History of the Intermediate Mesoderm

1. Intermediate Mesoderm is observable at …
2. It eventually separates from the …
3. It forms the …

Answer 3

1. Intermediate Mesoderm is Observable at day 18-20
2. It eventually separates from the paraxial mesoderm
3. It forms the Nephrogenic Cord

Question 4

What paraxial mesoderm transcription factors, expressed in intermediate Mesoderm, direct kidney formation?

Answer 4

Pax2, Pax8 & Lim1

Question 5

Urogenital Derivatives from Intermediate Mesoderm:

Answer 5

1. Kidneys
2. Ureters
3. Gonads
4. Genital Ducts

Question 6

A __________ Kidney Forms Within the Nephrogenic Cord in the Thoracolumbar Region of the Embryo

Answer 6

A **Mesonephric **Kidney Forms Within the Nephrogenic Cord in the Thoracolumbar Region of the Embryo

Question 7

What are the 2 components of the mesonephric kidney?

Answer 7

1. Mesonephric Duct
2. Mesonephric Tubules

Question 8

Why is the mesonephric duct important?

Answer 8

Important Source of Inductive Signals for Kidney Structures:

• A solid cell cord which eventually canalizes
• Extends caudally through nephrogenic cord
• Fuses with Cloaca (day 26)

Question 9

What is the cloaca?

Answer 9

• The dilated, caudal end of the primitive hindgut
• A transient, common outlet for the UG & GI systems

Question 10

What are the immature nephrons?

• Describe their differentiation:

Answer 10

Mesonephric Tubules = Immature Nephrons

• Inductive signals from the mesonephric duct induce tubule formation
• Differentiation occurs in a cranial to caudal direction along the nephrogenic cord
• All tubules induced are not present at same time

Question 11

The _________ (Mature) Kidney forms in the Pelvic Region of the Embryo from the Caudal Aspect of the Nephrogenic Cord

• What are the 2 precursors for this structure?

Answer 11

The Metanephric (Mature) Kidney Forms in the Pelvic Region of the Embryo from the Caudal Aspect of the Nephrogenic Cord

• 2 precursors: Both derived from the Intermediate Mesoderm
  
  • Metanephric Diverticuclum (ureteric bud)
  • Metanephrogenic Mesenchyme (metanephric lastema)

Question 12

What are the reciprocal inductive interactions in the metanephric kidney?

Answer 12

Question 13

What can lead to Renal Agenesis?

Answer 13

If the inductive interactions between the metanephric diverticulum and metanephrogenic mesenchyme are altered or absent

Question 14

1. When is Renal Agenesis usually asymptomatic?
2. When is Renal Agenesis symptomatic? What syndrome is this associated with?

Answer 14

1. Unilateral, is usually asymptomatic
2. Bilateral
   
   • Incompatible with extrauterine life
   • Key features include oligohydramnios and pulmonary hypoplasia
   • Compression of the face due to decreased amniotic fluid
   • Characteristic of Potter’s syndrome

Question 15

Oligohydramnios vs. Polyhydramnios

Answer 15

1. Oligohydramnios
   
   • Too little amniotic fluid
     
     • Associated with renal agenesis, polycystic kidney disease, urethral obstruction
     • Chronic amniotic leak
2. Polyhydramnios
   
   • Excessive amniotic fluid
     
     • Associated with diabetes, multiple gestation, anencephaly, esophageal atresia

Question 16

1. What can lead to oligohydramnios?
2. What can oligohyramnios lead to?
3. What can fetal compression lead to?

Answer 16

1. defect of urinary output & chronic leak of amniotic fluid ⇒ oligohydramnios
2. oligohydramnios ⇒ fetal compression, growth deficiency, pulmonary hypoplasia
3. fetal compression ⇒ Potter’s facies, limb positioning defect, growth deficiency, pulmonary hypoplasia

Question 17

Describe the signals that guide formation of the nephron:

What prevents cell apoptosis?

Answer 17

• Signals from the MM [GDNF, RA] induce formation of MD
• MD branches [cells express Ret a GDNF receptor]
• Expanded tips of MD called Ampulla
  
  • ​key signaling center for nephron induction
• Varying nature of signals from the ampulla directs the arrangement of nephrons and collecting ducts
• Ampullae begin to disappear at about 32 weeks
• No new nephrons are formed after all ampullae disappear
• MD signals [Fgf2, Bmp7] prevents MM cell apoptosis
  
  • induces a subset of MM cells to aggregate around ampulla

Question 18

What are the stages of nephron formation?

Answer 18

Signals via the ampulla cause:

Segregation ⇒ Compaction ⇒ Vesicle Fusion ⇒ S-Shaped Tubule

Question 19

Nephron Derivatives of the S-Shaped Tubule Include:

1. From the Proximal Part (P)
2. From the Middle Part (M)
3. From the Distal Part (D)

Answer 19

1. From the Proximal Part (P)
   
   • Distal Tubule & loop of Henle
2. From the Middle Part (M)
   
   • Proximal Tubule
3. From the Distal Part (D)
   
   • Renal Corpuscle

Question 20

Vascular Spouts From ___________ _______ are Induced to Grow Toward the Forming Kidney

Answer 20

Vascular Spouts From Intersegmental Arteries are Induced to Grow Toward the Forming Kidney

• They form the vasculature of the kidney
• Only induced mesenchyme secretes angiogenic growth factors [VEGF] that attracts the vascular sprouts to the forming kidney

Question 21

1. What is hydronephrosis?
2. What are two types of cystic kidney disease?

Answer 21

1. Hydronephrosis
   
   • Obstruction of the urinary tract
2. Cystic Kidney disease
   
   • Polycystic kidney disease
   • Multicystic dysplastic kidney disease

Question 22

What are the characteristics of Multicystic Dysplastic Kidney?

Answer 22

• Most often unilateral (polycystic kidney disease is bilateral)
• Multiple cysts of varying sizes
• Non-functioning
• Pathology—primitive ductules and cartilage seen; atretic ureter
• Contralateral kidney hypertrophies
  
  • potential abnormalities of the contralateral kidney
• Bilateral disease is rare; fatal
• Hypertension is potential complication
• Failure of a large MCKD to regress may be indication for nephrectomy
• Non-genetic (Polycystic kidney disease is genetic)

Question 23

Remodeling & Differential Growth of the Branching Metanephric Diverticulum results in ….

Answer 23

Formation of the Collecting Ducts, Calyces, Pelvis and Ureter

• Little growth of early generations
• Faster growth of polar branches
• Expansion of the 3rd-6th generations of branches to form the Calyces, Pelvis and Ureters
• Branches distal to the 5th & 6th generations form Collecting Ducts

Question 24

• In the kidney, Nephrons and Collecting Ducts are organized into larger structures called _____ _____
• Each kidney lobe ends in a pyramid shaped _____ ______ which empties into a _____ _____

Answer 24

• In the kidney, Nephrons and Collecting Ducts are organized into larger structures called Renal Lobes
• Each kidney lobe ends in a pyramid shaped Renal Papilla which empties into a Minor Caylx

Question 25

Anomalies That Result in Variations in Kidney Size, Histological Organization or Number:

Answer 25

* **Hypoplastic Kidneys** * May be small & normal * May be small because of abnormal development * **Dysplastic Kidneys** * **Duplications** * Of the Ureter or Kidney which may be partial or complete * **Horseshoe Kidney** * Fusion prevents complete ascent

Question 26

Pelvic or Lumbar Kidneys are due to...

Answer 26

**Failed or incomplete ascent** * Ectopic location * Extra renal vessels result from failure to atrophy during kidney ascent

Question 27

Polycystic Disease of the Kidneys is an \_\_\_\_\_\_\_ Disorder

Answer 27

Polycystic Disease of the Kidneys is an **Inherited** Disorder 1. Autosomal Recessive Polycystic Kidney Disease 2. Autosomal Dominant Polycystic Kidney Disease

Question 28

What are the characteristics of **Nephroblastoma (Wilm’s Tumor)**?

Answer 28

* A _common neoplasm in children_ * The gene is located on **chromosome 11**

Question 29

What will enhance a **Ureteropelvic Junction (UPJ) Obstruction**?

Answer 29

Diuresis (increased water excretion) enhances obstruction of the urinary tract

Question 30

**UPJ Obstruction:** * Clinical Presentation: * Diagnostic Studies:

Answer 30

* Clinical Presentation: * **Infant:** flank mass, UTI, failure to thrive, sepsis * **Older child or adult:** flank pain, colicky pain, UTI, hematuria * _Prenatal diagnosis_ * **Diagnostic studies:** ultrasound (anatomy) or renal scan, intravenous pyelogram (functional studies)

Question 31

What Provides for Separate Outlets for the UG & GI Systems?

Answer 31

**Division of the Cloaca** * The **Primary (Primitive) UG Sinus** is located _ventrally_ * The **Anorectal Canal** is located _dorsally_

Question 32

What does remodeling of the posterior wall of the bladder result in? * In males, what happens in this region?

Answer 32

Formation of the **Trigone Region** * The trigone is associated with _entrance of the ureters & exit of the urethra_ * In males, _differential growth results in the mesonephric ducts_\*\* _opening into urethra_ rather than urinary bladder * \*\*the mesonephric duct distal to the metanephric diverticulum becomes the vas deferens

Question 33

How can **anomalies of the urinary bladder** occur?

Answer 33

* **Anomalies of the Urachus** [allantois & urachus] * Arise from failure of regression of these structures * **Exstrophy of the Bladder** * A defect of the ventral abdominal wall * The lining of the bladder and the urethra is open to the surface * Associated with UG & skeletal anomalies

Question 34

Ureteral Reflux * The higher the grade of reflux ...

Answer 34

1. the greater the risk for scarring 2. the more abnormal the anatomy is 3. spontaneous resolution is less likely 4. surgical intervention may be necessary

Question 35

* What is the consequence of a lateralized ureter? * How is it treated?

Answer 35

* A lateralized ureter leads to _reflux_, which can lead to _recurrent kidney infections_ and subsequent _atrophy_ of the kidney. * Treatment is _antibiotic prophylaxis_ and/or _surgical repair_

Question 36

* **What causes bladder exstrophy**? * What is the difference in presentation between males and females? * How healthy are infants at birth?

Answer 36

* **Failure of medial mesenchymal migration ** * 1 per 30,000 live births * 1 per hundred if positive FH * **Male:Female 3:1** * Males with _epispadius_ * Females with _shortened vagina_; _bifid clitoris_ * Gonadal structures normal * **Babies typically healthy**

Question 37

* What should be done to treat bladder exstrophy? * What are the major long term complications?

Answer 37

* _Surgery performed shortly after birth_ * Babies hospitalized for 10-14 days * _Incontinence is a major long term issue_ * Upper tracts at risk after repair

Question 38

The Extent of the Urethra Formed from the Caudal Part of UG Sinus Differs in Males & Females. What is the difference?

Answer 38

* **Male** * Proximal Portion of Prostatic Urethra * **Female** * Most of It

Question 39

How does the fate of the **definitive UG sinus** differ between males and females?

Answer 39

* **_​Male_** * **Pelvic portion:** * Distal Prostatic & Membranous Urethra * **​Phallic portion** * **​**Penile urethra * **_Female_** * **Pelvic portion:** * ​lower half of the Vagina * **Phallic portion:** * **​**Vestibule

Question 40

How can **anomalies of the urethra** occur?

Answer 40

* **Agenesis & Atresia of the Urethra** * **Atresia** is associated with _urinary obstruction_ & _Prune Belly Syndrome_ * **Posterior Urethral Valves** * _Mucosal folds which obstruct the lumen of the urethra_ * A common cause of renal failure in boys

Question 41

What are the characteristics of **Posterior Urethral Valves**?

Answer 41

* Occurs only in _males_ * 1/5000 male births * **Obstructing valves leads to severe obstruction of urinary tract and irreversible renal dysplasia**