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Lecture 5- Embryology of Kidneys and Ureters 1.

Introduction - Urinary system develops alongside genital system - UG organs develop from intermediate mesoderm - development occurs laterally symmetrical (left right) - intermediate mesoderm lying beside the dorsal aorta - initially form mesonephric tubules (epithelial) - these tubules connect to a common duct, mesonephric duct - the mesonephric duct then extends within the mesoderm, rostro-caudally - eventually making contact with the cloaca

Longitudinal elevation of mesoderm is formed to establish a urogenital ridge Nephrogenic cord gives rise to urinary tract whereas medial part of UG ridge forms genital part

2. Nephros 3 stage Development

pronephros development rudimentary [imperfectly developed] and non-functional developed at week 4: represented by paired cervical region cell clusters (nephrotomes) that run caudally and open into cloaca pronephric duct develops pronephroi structures regress soon after formation, but most of ducts persist and are utilised by second kidney system (videos) Mesonephros Caudal to pronephros Forms by induction from pronephros Pronephric duct now becomes mesonephric duct Consists of glomeruli and excretory units : mesonephric tubules, which opens into mesonephric duct (which is originally pronephric duct) that opens into cloaca At week 8: mesonephroi dengenerates with exception of tubules and duct to persist in males as efferent ductules of testes and other adult reproductive derivatives respectively.

Metanephros Occurs at early week 5- definitive kidney is formed from 2 different mesodermal sources I. Ureteric (metanephric) duct Outgrowth from mesonephric duct Is the primordium[earliest indication for development] of the ureter, renal pelvis, calices, and collecting tubules II. Metanephrogenic mass (nephrogenic blastema) Elongating bud penetrates the metanephrogenic blastema ( a mass of cells derived from nephrogenic cord [that forms the nephrons] Gives rise to glomerulus Kidneys begin filtration by week 9, urine by week 10, full function by week 12/13 Up to 15 generations of nephrons formed in kidney, with newest and least mature one in the cortex. Collecting tubules induce metanephric cap[mass of intermediate mesodermal cells that gives rise to formation of nephrons]

3. Kidney Migration [Ascend]

Fetal kidney is lobulated, adult kidney is not Kidney form in future pelvic region and migrate towards abdomen Initially, permanent kidneys lie close to each other in pelvis, ventral[anterior] to sacrum As abdomen and pelvis grow, kidneys gradually ascend in abdomen and move farther apart Attain adult position by week 9

Pronounced shift occurs : combination of migration of kidney and expansion of caudal region of fetus Migration (relative ascend) results mainly from growth of embryos body caudal to kidneys Initially, hilum faces ventrally, with ascent rotates medially 900, hilum directed anteromedially by week 9. Thus, fetal kidney shifts from L4 to L1/T12 vertebral level, displaces laterally and rotates 900 so pelvis of kidney faces midline All movements occur behind peritoneum Mesonephros regresses and descend towards pelvic region Arterial supply forms and reforms

4. Blood supply to Kidneys - As kidneys ascend from pelvis, they receive blood from vessels that are close to them Initially renal arteries are branches of common iliac arteries, then from distal end of aorta When kidneys reach higher level they receive new branches from aorta Normally, caudal branches indergo involution and disappear - Kidneys receive their most cranial branches from abdominal aorta, which become the permanent renal arteries Right renal arteries are longer and often more superior 5. Clinical aspect - Over 1% of newborns involve developmental abnormalities - Some are asymptomatic and inconsequential but many causes infant mortality - Some types of congenital defects in renal development include abnormalities in kidney size, structure, or position. A. Renal agenesis o Complete failure of nephrogenesis due to failure of ureteric bud to develop or early degeneration of ureteric bud.

35-gestational-week-old fetus with suspected renal agenesis, which occurs if metanephric diverticulum fails to develop or to penetrate metanephric blastema. Photograph of stillborn neonate displays appearance of sirenomelia. B. Unilateral o Can be the component of syndrmic disorders like Turners) o Commonly associated with ipsilateral genital anamolies -M: wolffian duct derived structures (vas deferens, seminal vesicles) often absent - F: absence of uterine tube, malformation of uterus & vagina from maldevelopment of mllerian duct o Higher occurrence in males o Left more frequently absent

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Remaining kidneys usually enlarged due to compensatory hyperthrophy, ectopic or malrotated

C. Bilateral; incompatible with life o Associated with oligohydroamnious : reduced fluid in amniotic sac surrounding embryo. o Potter phenotype: pulmonary hypolplasia[incomplete development], deformities of spine and limbs D. Horseshoe kidney (Pelvic kidney) o Kidneys pushed anteriorly and join o Usually the lower poles of kidneys are affected. o The ascent is obstructed by inferior mesenteric artery o Usually symptomless

E. Cystic kidney disease o Can be hereditary, developmental or acquired conditions o Affect one or both kidneys o May or may not occur with other anamolies o Multicystic dysplasia Ducts surrounded by undifferentiated cells Irregular cysts of varying sizes and has no function o Congenital polycystic kidney Non-union bud and blastema Cysts formed from accumulated urine in glomerular part of kidney which then leads to massive enlargement of kidneys Can cause damage to liver and pancreas F. Duplicated ureter o Early division of ureteric bud o Partial or complete duplication

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Occasionally may result from 2 ureteric bud Occasional ectopic ureter More frequently in females, insertion sites can include vagina & vulva, with resulting incontinence Often associated with a ureterocele (cystic dilatation of terminal ureter), with clinical presentation of prompted by UTI & obstruction of bladder neck in children and Infection &/or ureteric stones in adults