Embryology: Urogenital Ridge & Urinary System

• Fiona Cronin presented embryology of the urogenital ridge, kidneys, ureters, and bladder for RGU on 24/02/2025

Learning Outcomes

• Describe development of the urinary system within the embryo, including pro-, meso-, and metanephros
• Compare development of the mesonephric and paramesonephric ducts in males and females
• Describe how common developmental abnormalities of the urinary system may occur (i.e. horseshoe kidney, vesicoureteric reflux, duplex ureter, hydronephrosis)

Urogenital Ridge

• A longitudinal elevation of the mesenchyme forms on each side of the dorsal aorta
• The urogenital ridge gives rise to the urinary system which is the nephrogenic cord

Development of Urinary System

• Three excretory organs develop: pronephros, mesonephros, metanephros

Pronephros

• First set of kidneys appear in the fourth week of development
• The cluster of cells is in the neck region
• They are rudimentary and non-functional and degenerate, contributing to the next set of kidneys (mesonephros)

Mesonephros

• Mesonephric ducts appear late in the fourth week as rods, caudal to pronephros
• Ducts induce mesonephric buds, forming the mesonephroi
• Mesonephroi consist of approximately 40 glomeruli with mesonephric tubules
  • Tubules open into mesonephric ducts that open into the cloaca
• They create urine between weeks 6 and 10, and degenerate at the end of the first trimester
• In females, they regress; in males, the mesonephric tubules become efferent ductules of testis
  • Mesonephric ducts become the appendix of epididymis, duct of epididymis, vas deferens, and ejaculatory duct and seminal gland

Metanephros

• Primordium of the permanent kidney which appears in the fifth week and functions ~4 weeks later
• Urine is excreted into amniotic cavity and mixes with amniotic fluid
• Develops from two sources
  • The ureteric bud (metanephric diverticulum) forms the collecting portion
  • The metanephrogenic blastema forms the excretory portion
• Structures composing the collecting and excretory portions of the metanephros:
  • Collecting Portion (Ureteric Bud): ureter, renal pelvis, major and minor calyces, collecting ducts
  • Excretory Portion (or Nephron) (Metanephric Mesenchyme): Bowman's capsule, proximal convoluted tubule, loop of Henle, distal convoluted tubule

Ureteric Bud (Metanephric Diverticulum)

• Metanephric diverticulum elongates and penetrates metanephrogenic blastema
• Forms the ureter, renal pelvis, major and minor calyces and collecting tubules
  • The stalk of the bud becomes the ureter and collecting tubules undergo repeated branching: first four generations of tubules enlarge and coalesce to form the major calices; second four generations coalesce to form the minor calices

Metanephrogenic Blastema

• End of each newly formed collecting tubule induces meschymal cells of metanephrogenic blastema to form metanephric vesicles
• Vesicles elongate and become metanephric tubules
• Tubules with their glomeruli form nephrons: proximal ends of tubules invaginated by glomeruli; the distal end becomes confluent with a collecting tubule, which together forms a uriniferous tubule
• Nephron = glomerulus and glomerular capsule + proximal convoluted tubule + nephron loop (Henle) + distal convoluted tubule

Positional Changes of the Kidneys

• Kidneys initially lie close to each other in the pelvis and gradually come to lie in abdomen and move further apart, rotating medially almost 90 degrees
• Ascent of kidney results from straightening of the vertebral curvature and growth of the thorax and abdomen, attaining adult position ~ week 9

Blood Supply

• Renal arteries are initially branches of the common iliac arteries
• As kidneys ascend, receive blood supply from distal aorta; receive new branches from aorta as ascend further; caudal branches usually disappear
• Ascent stops when kidneys reach the level of suprarenal glands and receive their most cranial branches from abdominal aorta, which become the permanent renal arteries

Accessory Renal Arteries

• Persistence of embryonic vessels
• Approx 25% of adult kidneys have 2-4 renal arteries, usually arising from aorta and may enter kidney directly
  • A polar renal artery (enters inferior pole) may obstruct ureter causing hydronephrosis
• Are "end arteries," so if damaged/ligated, the area supplied may become ischaemic

Renal Agenesis

• Absence of one or both kidneys because the ureteric bud(s) fail to develop due to faulty tissue-tissue interactions
  • No nephrons are induced by collecting tubules

Unilateral Renal Agenesis

• Occurs in approximately 1/1000 births
• More prevalent in males, remaining kidney undergoes hypertrophy

Bilateral Renal Agenesis

• Occurs in approximately 1/3000 births and is more common in males
• Leads to oligohydramnios and is incompatible with postnatal life

Abnormal Position (Ectopic Kidney)

• Failure to ascend remaining usually in the pelvis
• Pancake (discoid) kidney is fusion of the kidneys in the pelvis

Horseshoe Kidney

• Poles of kidneys fuse (usually the inferior pole) anterior to the inferior lumbar vertebrae
• Normal ascent is prevented by the inferior mesenteric artery
• It is functional, with normal ureter and blood supply, and may produce no symptoms, but kidneys are prone to increased occurrence of renal stones and infection

Duplications

• Supernumerary kidney is rare
• Early division of ureteric bud: duplication of the Y shaped bifid ureter
• Caudal end of ureter attaches to the bladder with one branch ending blindly, and infections of the ureter more common because of asynchronous contractions leading to reflux and stagnation of urine

Ectopic Ureter

• Ureter carried caudally with mesonephric duct and is incorporated into the caudal portion of the vesical part of the urogenital sinus
• In males, may open into the neck of the bladder, the prostatic part of the urethra, the ductus deferens, prostatic utricle, or seminal gland
• In females, may enter the neck of the bladder, urethra, vagina, or vestibule of the vagina

Vesico-ureteric Reflux

• Intramural region of the ureter is too short, increasing the risk of backflow
• Congenital (primary reflux) is most common; secondary causes are high pressure voiding states or duplex collecting systems, bladder exstrophy
• Associated with recurrent UTIs
• Imaging of Choice: Micturation Cystourethrogram (MCUG) (Girls); Fluoroscopy (Boys)
• Management can be conservative, antibiotic prophylaxis, or surgical

Polycystic Kidney Disease

• Numerous cysts form within the kidney and may be inherited as autosomal dominant or autosomal recessive (mutations in genes that encode proteins important for function of cilia)
• Autosomal recessive polycystic kidney disease (ARPKD): progressive disorder with cysts forming from collecting ducts, kidneys enlarge, renal failure occurs in childhood, diagnosed in utero or at birth by ultrasonography
• Autosomal dominant polycystic kidney disease (ADPKD): formation of cysts from all parts of the nephron and usually not causing renal failure until adulthood

Development of the Bladder

• Cloacal region of hindgut is divided into urogenital sinus anteriorly and anorectal canal posteriorly
• Urogenital sinus is divided into 3 parts: vesicle/bladder part becomes the bladder, pelvic part becomes the urethra (membranous and prostatic urethra in males, entire urethra in females), and the phallic part contributes to penile urethra or vestibule of vagina

Formation of Trigone

• Bladder develops mainly from vesicular part of urogenital sinus
• Trigone is derived from caudal ends of mesonephric ducts
  • Distal parts of the mesonephric ducts are incorporated into dorsal wall which contribute to connective tissue of trigone of the bladder, with ureters opening separately into bladder
  • Remodeling and expansion of the bladder wall leads to the ureteric openings shifting laterally and superiorly while the mesonephric duct in males shifts inferiorly to empty into the developing prostatic urethra

Urachal Defects

• Lumen of allantois obliterates and becomes a thick fibrous cord, the urachus
• The median umbilical ligament is the fibrous remnant of urachus in adults
• A remnant of the lumen may persist -Urachal cysts are patent areas of the urachus
  • Urachal sinus is a patent end of the urachus which open in the umbilicus (or at the bladder)
  • Urachal fistula-- the entire urachus remains as a patent opening, allowing urine to escape

Ventral Body Wall Defects

• Bladder exstrophy
• Incomplete closure of the anterior abdominal wall
• Exposure and protrusion of the mucosal surface of the bladder
• Epispadias-urethra opens on the dorsum of the penis
• Exstrophy of the cloaca
  • Severe body wall defect: lumens of both the bladder and the anorectal canal are exposed

Development of Genital Ducts

• Male and female embryos have two pairs of genital ducts (initially)
  • Mesonephric (Wolffian) ducts
  • Paramesonephric (Müllerian) ducts
• Mesonephric ducts -Drain urine from mesonephric kidneys -Essential role in the development of the male reproductive system -Form epididymis, vas deferens, and ejaculatory duct -(Mostly) degenerate in females
• Paramesonephric ducts -Essential role in the development of the female reproductive system -form the uterine tubes, uterus, and uper vagina -Degenerate in males