Embryology of the Urinary System PDF

Embryology of the Urinary System Dr Nerissa Naidoo mbru.ac.ae Objectives:  Describe role & fate of three main developmental stages of kidney  Enumerate adult derivatives of mesonephric components  Briefly explain relocation process of kidneys  List factors involved in molecular reg...

Embryology of the Urinary System Dr Nerissa Naidoo mbru.ac.ae Objectives:  Describe role & fate of three main developmental stages of kidney  Enumerate adult derivatives of mesonephric components  Briefly explain relocation process of kidneys  List factors involved in molecular regulation of kidney development  Highlight abnormal conditions associated with defects in development of urinary system (e.g., oligohydramnios, mal-rotated and ectopic kidneys, ectopic ureter, renal agenesis, horse-shoe kidney, malposition)  Describe how urine is formed & excreted into amniotic fluid during fetal period (SDL) Basic concepts  Appearance of urogenital ridge After folding of embryonic disc: Bulge of intermediate mesoderm along post wall of abdominal cavity = urogenital ridge Extends from cervical  sacral region of embryo Kidney Systems Kidney develops bilaterally in 3 successive stages from cranial  caudal sequence (aligned adjacent to mesonephric/Wolffian duct) 1. Pronephros 2. Mesonephros 3. Metanephros Urogenital ridge Mesoderm Genital Nephrogenic cord component Medial Lateral Pronephros: Forekidney Beginning of week 4: Develops from cranial-most part of nephrogenic cord within urogenital ridge Appears as series of tubules (viz. Nephrotomes/pronephros tubules) connected to pronephric duct (contained within embryo  no excretion) Pronephric duct will give rise to mesonephric duct (Overlap) Nephrotomes Pronephros tubules Pronephric duct End of week 4: Non-functional & regresses completely  Mesonephros: Transitory kidney Weeks 4 - 10: Caudal to pronephros Develops from 3 structures: nephrogenic cord, mesonephric duct & glomerular capillary network Development of solid cord: Solid cord of cells forms on dorsal side of nephrogenic cord Differentiation of cord into Mesonephric tubules (BMP4): Releases from nephrogenic cord & localizes under ectoderm Develops caudally from pronephric duct (Fibronectin) canalizes  ends in cloaca = Mesonephric/Wolffian duct Gives off lateral branch  forms ureteric bud  Mesonephros: First excretory organ Formed from 2 main sources: 1. Mesenchymal-epithelial interaction: renal tubule 2. Glomerular capillary network: renal corpuscle 1. Mesenchymal-epithelial interaction  Nephrogenic cord gives rise to Mesonephric vesicles ~ adult nephron Laterally: Connect to mesonephric duct via mesonephric tubules Medially: Forms funnel ~ Bowman’s capsule Key: 1 - Nephrogenic cord; 2 - Mesonephric duct; 1&2 – Mesonephros; 3 – Intestine; 4 – Cloaca; 5 – Atrophied pronephros; 6 - Yolk sac; 7 – Allantois; 8 - Outflow of mesonephric duct into cloaca; 9 -  Mesonephros: First excretory organ 2. Glomerular capillary network  Tuft of capillaries arise from lateral branches of dorsal aorta Each funnel surrounds a tuft of capillaries ~ 1st renal corpuscle  drains into cardinal vein  cloaca Mesonephric vesicle + Tuft of capillaries = 1st excretory mesonephric organ Week 6: Urine production begins Week 10: Inactive atrophic nephrons Some cells migrate  form adrenal gland & gonads Key: 1 - Nephrogenic cord; 2 - Mesonephric duct; 1&2 – Mesonephros; 3 – Intestine; 4 – Cloaca; 5 – Atrophied pronephros; 6 - Yolk sac; 7 – Allantois; 8 - Outflow of mesonephric duct into cloaca; 9 - Ureteric bud  Metanephros: Definitive kidney 5th week: Final stage of kidney development 2 sources: ureteric bud (collecting system) + metanephric blastema (nephron) Ureteric bud (UB) arises from mesonephric duct Metanephric blastema (MB) becomes distinct, adjacent to UB Loose mesenchymal cells from MB invade UB = Reciprocal inductive signals between MB & UB 1. Signals from MB  UB branches into T-Tubule 2. Signals from UB  MB condenses along surface of UB (BMP4, FGF) = Continuation between UB & MB  Development of Nephron After condensation: Portion of MB aggregates below each side of T-shaped UB  forms peritubular aggregates = Renal vesicle RV establishes contact with epithelium of UB Comma-shape Development at each end of RV: Distal end  Characteristic changes = Bowman’s capsule  Migration & differentiation S-shape Cup-shape Head-shape of endothelial cells = Mature glomerulus Proximal end  Tubule lengthening & elongation (PAX-2 & WNT-4) = Proximal convoluted tubule Loop of Henle Capillary-loop stage Distal convoluted tubule  Canalize with collecting duct  Development of Collecting System Simultaneous to development of nephron UB initially penetrates MB Undergoes repeated patterned branching Forms ureters, renal pelvis, major calyces, minor calyces & tubules  Cortical & Medullary Divisions During branching of UB derivatives & development of nephrons: Kidney divides into: outer cortical region (where nephrons are being induced) AND inner medullary region (where collecting system forms)  Renal Ascent Location of fetal metanephros: Vertebral level S1-S2 = pelvic organ Weeks 6 - 9: Growth of lumbo-sacral region & ureter Kidneys ascend to lumbar site, just below adrenal glands During migration: kidneys are vascularized by aortic sprouts that arise from higher levels Location of definitive adult kidney: Vertebral level T12-L3 Initially, hilum faces anteriorly BUT during ascent: Kidneys rotate 90 degrees  Hilum finally faces medially Development of Urinary Bladder, Urethra & Ureters Weeks 4 – 7: Following division: Urorectal septum divides Ureteric bud elongates & cloaca into urogenital separates from mesonephric sinus & anorectal canal duct Enters upper part of urogenital sinus separately as ureters 3 parts of urogenital sinus: 1st – Urinary bladder Mesonephric ducts gradually absorbed 2nd – Male: prostatic & membranous into wall of urogenital sinus: parts of urethra; Female: whole Trigone of bladder in males & urethra females 3rd – Genital tubercle Genital ducts in male, regresses in (Male: glans penis & penile urethra; female Female: clitoris) Congenital Anomalies Horse-shoe kidney Lower poles pushed close during ascent Fusion of lower poles Position:  Ectopic kidney  Mal-rotation Poor development of UB UB penetrates an abnormal region of MB Duplex kidney/Double ureter/Double pelvis Complete: Formation of 2 UBs/splitting of MB Incomplete: Division of 1 UB Renal agenesis Failed interaction between UB & MB UB failed to branch Congenital Anomalies Ectopic ureteral orifice Abnormal UB migration Exstrophy of bladder Defect in ventral body wall Aberrant renal arteries Lateral body wall folds Persistence of embryonic failed to close in midline vessels Retrocaval ureter Abnormal development of IVC Patent urachus Urachus fails to seal off