Embryology

Question 1

What do the ureters/kidneys come from?

Answer 1

Intermediate mesoderm

Question 2

3 Kidney Systems

Answer 2

• 1- Propnephric (cervical) - 4th wk/non-functional
• 2- Mesonephric (thoracolumbar) 2nd mo/ functional
• 3- Metanephric (sacral) - becomes adult kidney; about 10 wks/ functional

Question 3

What are the 2 components that ea kidney is derived from?

Answer 3

• 1- Ureteric Bud - off metanephric duct; becomes collecting system by proliferating and branching
• 2- Metanephric mesenchyme - loose collection of cells that becomes nephron epithelium –> tubules

Question 4

Genetics of Ureter/Kidney Formation

Answer 4

• GDNF prod by mesenchyme binds RET of bud –> bud proliferation/branching
• Wnt expressed by bud –> regulates transition of mesenchyme to nephron epithelium

Question 5

What 3 transcription factors regulate GDNF-RET system?

Answer 5

EYA1, PAX2, SALL1

Question 6

What limits ureteric bud to caudal area?

Answer 6

• BMP4 inhibits RET
• SLIT2 binds ROBO2 –> inhibit GDNF
• Hox also leads to specific metanephric identity

Question 7

Wilms Tumor Gene 1

Answer 7

if less WT1 exp –> pause in proliferation of metanephric mesenchyme progenitors –> Wilms tumor

Question 8

Potter’s Syndrome

Answer 8

• Bilateral renal agenesis - ureteric bud doesn’t form or degenerates –> oligohydramnios (insufficient amniotic fluid volume)
• Also… clubbed feet, limb position defects, craniofacial abnormalities, pulmonary hypoplasia

Question 9

7 Possible Kidney/Ureter Malformations

Answer 9

1– Renal agenesis

2- Obstructions/ Reflux - can lead to dilation of ureter or renal pelvis; can cause pediatric kidney disease or multiple UTIs

3- Duplex Ureter - premature bifurcation or formation of 2 ureteric buds; may have improper bladder connection or reflux in duplicate

4- Dysplasia - Undifferentiated kidney tissue or cysts

5- Accessory Renal Arteries - if early segmental inferior arteries do not regress when kidney ascends

6- Pelvic kidney- kidney does not ascend

7- Horseshoe kidney - fusion of inferior poles of 2 kidneys; may not be able to ascend b/c blocked by inferior mesenteric artery

Question 10

Polycystic Kidney Disease

Answer 10

• Can occur as an adult or in utero
• Can be due to mutations in proteins of non-motile cilia involved in mechanosensation and signaling in growth/development
  
  • These cilia regulate cell polarity, cell cycle and Wnt signaling
• Can be part of BBS (Bardet-Beidl Syndrome) - mutations in BBS proteins normalling regulate trafficking of proteins to cilia
• Can be mutation in HFN-1B (transcription factor for cystic genes - PKD1/PKD2)

Question 11

What does the bladder/urethra come from?

Answer 11

Cloaca; caudal end of the hindgut (endoderm)

Question 12

What is the main gene that influences bladder/urethra formation?

Answer 12

Sonic hedgehog

Question 13

5 Possible Bladder/Urethra Malformations

Answer 13

1- Urorectal Atresia/Fistula - connection b/n rectum and urethra/vagina/bladder

2- Cloaca Malformation - single common channel in females only

3- Urachal fistula/cyst/sinus - if allantois or urachus persists

4- Exstrophy of Bladder - bladder open at anterior wall; may be due to enlarged cloaca membrane

5- Posterior Urethral Valve - extra membrane in males that can lead to obstruction/hydro-ureter