Lecture 6 General medicine_3rd semester DEVELOPMENT OF URINARY SYSTEM AND OVERVIEW OF ITS CONGENITAL MALFORMATION DEVELOPMENT OF REPRODUCTIVE SYSTEM: INDIFFERENT STAGE DEVELOPMENT OF INTERNAL AND EXTERNAL SEXUAL ORGANS OVERVIEW OF MOST IMPORTANT CONGENITAL MALFORMATIONS Introduction the urinary system and internal sexual organs develop from the intermediate mesoderm or nephrotomes a part of the third germ layer interposed between the axial mesoderm or somites and lateral mesoderm the intermediate mesoderm extends along the entire length of the dorsal body wall of the embryo it soon loses connection with somites and fuses to form the nephrogenic cords on each side of the primitive aorta the cords rapidly grow, become larger and produce bilateral longitudinal bulges called the urogenital ridges a medial side of each ridge is then separated from the surrounding and is called as the gonadal ridge (see the next chapter) Bez názvu 1upr Bez názvu 1upr AEB_img13-1.jpg Bez názvu 2upr DEVELOPMENT OF KIDNEYS, URETERS, BLADDER, AND URETHRA in the human, three sets of excretory organs develop: the pronephros (-oi) - "forkidney" - is rudimentary and nonfunctional; forkidney is analogous to the kidney of some primitive fishes, the mesonephros (-oi) -" midkidney" - is analogous to kidney of fishes and larval stages of amphibia amphibians; in human embryos, midkidney is in function for a short time and then undergoes involution the metanephros (-oi) - "hindkidney" or permanent kidney, it begins to produce urine in fetuses aged 11 to 13 weeks Obr_13.2.jpg •Pronephros (oi) •occurs early in the fourth week in the cervical region on each side • •it consists of a few solid cell clusters, rarely short pronephric tubules and the pronephric •duct, which runs caudally and opens into the cloaca • •the pronephros soon degenerates, but most of both pronephric ducts are utilized by the •midkidney as mesonephric or Wolffian duct Močový systém - 31 •Mesonephros (oi) •develops later in the 4th week caudal to the pronephros in C6 to L3 region •initially, solid nephrogenic cord (blastema) divides into 40 - 50 mesodermal cell clusters within them lumina •develop - mesonephric vesicles arise •mesonephric vesicles grow into S-shaped mesonephric tubules whose laterally ends become •continuous with the mesonephric duct or Wolffian duct •the medial end of each tubule expands and transforms into •the Bowman´s capsule (capilary loops of the glomerulus are •deriving from the mesonephric artery) •the capsule with glomerulus form a mesonephric corpuscle •together • •cervical and thoracical parts of mesonephroi rapidly degenerate •the lumbar part consisting of a few mesonephric tubules •and mesonephric duct persists and is involved in development •of genital ducts in males (ductuli efferentes, ductus deferens and ductus •ejaculatorius) or vestigial remnants in females (epoophoron and paroophoron) Močový systém - 3 Vývoj mesonefros Močový systém - 33 •Metanephros (oi) •"hindkidney" or permanent kidney begins to develop early in the 5th week • •two different sources: vthe ureteric bud or metanephric diverticulum, which gives rise to the ureter, pelvis, major and minor calyces and system of papillary ducts and collecting tubules vthe metanephrogenic blastema or metanephric mesoderm = a caudal part of the • nephrogenic cord extending between L4 to S1 - it gives rise to the nephrons • Močový systém - 34 Močový systém - 35 Močový systém - 36 the ureteric bud is a dorsal outgrowth of the mesonephric duct near its entry into the cloaca the bud then extends dorsocranially, penetrates the metanephric mesoderm and divides it into cell clusters, located near blind ends of the collecting tubules clusters of mesodermal cells become metanephric vesicles that are later transformed into metanephric tubules the proximal part of each tubule becomes dilated and forms the Bowman´s capsule of a renal corpuscle, while the distal end contacts the respective collecting tubule and both tubules become soon confluent the remaining part of the metanephric tubule undergoes continual lengthening and gradually differentiates into definitive segments of the uriniferous tubule the proximal tubule, the loop of Henle, and the distal tubule Positional changes of the kidneys kidneys develop low in the pelvis from the 2nd trimester, they gradually come to lie in the abdomen the migration of kidneys is mainly resulted from growth of the embryo´s body caudal to the kidneys ascensus renis Development of renal pelvis and ureter both derive from the distal part of the ureteric bud Development of bladder and urethra both organs develop from the ventral part of the cloaca the cloaca is the most caudal part of the gut which is ventrally sealed off by a membrane composed of the ectoderm and endoderm - known as the cloacal membrane cranially, the cloaca continues as the allantois that enters the connecting stalk in higher vertebrates including the human, the cloaca soon divides with the urorectal septum (oriented frontally) into 2 portions : - the anorectal canal situated dorsally - rectum, - the primitive urogenital sinus situated ventrally - bladder + urethra. the caudal part of the urorectal septum then fuses with the cloacal membrane: a part covering anorectal canal is the anal membrane, a part covering the primitive urogenital sinus is the urogenital membrane Močový systém - 37 the urogenital sinus includes three parts: Øvesical segment (presumptive bladder - there is a wide cranial part Øpelvic segment - middle narrow Øphallic segment - it appears wide the vesical segment develops into the definitive bladder - in both sexes the pelvic segment becomes the definitive urethra in females but the prostatic urethra in males the phallic segment of the urogenital sinus becomes the vestibule of the vagina in females but the penile urethra in males Močový systém - 38 CONGENITAL MALFORMATIONS OF KIDNEYS AND URETERS Renal agenesis = absence of a kidney it results from failure of the ureteric bud to growout and is accompanied with an absence of the ureter it may be uni- or bilateral (unilateral agenesis is characterised by compensatory hypertrophy of the kidney that is present; bilateral agenesis is incompatible with survival after birth) incidence is about 2 (3) per 10 000; is more frequent in males than females (3:1) clinically, it is always accompanied by oligohydramnios which results from failure of urine production Pelvic kidney = a kidney (s) is located in pelvis, this malformation results from failure of the kidney to ascend Horshoe kidney - both kidneys are fused at their inferior poles and located in pelvis (failure of kidneys ascend) horshoe kidney is often symptomless and occurs 1 per 600 live birth. Bez názvu 7aupr Polycystic kidney disease = hereditary disease characterised by that one or both kidneys contain numerous small, medium - sized or large urine-filled cysts inhibiting its normal function polycystic kidney disease may be uni- or bi-lateral bilateral p. k. d. has almost bad prognosis because it is incompatible with survival after birth P. k. d. is believed to result from failure of collecting tubules and uriniferous tubules to join up. Polycystic kidney disease occurs in two hereditary forms. One is autosomal recessive or infantile, the other is autosomal dominant, or adult. Duplication of the ureter - ureter duplex and bifid ureter (ureter fissus) Bez názvu 7aupr • •the early genital system is similar in both sexes, and this initial period is referred to as the indifferent •stage •it lasts approximately up to the first half of the 3rd month (10th week) of the fetal development • •the stage is characterized by presence of 3 embryonic organs: vthe indifferent gonad anlage vthe mesonephric duct (Wolffian duct) + remnants of mesonephric tubules vthe paramesonephric duct (Müllerian duct) - • DEVELOPMENT OF INTERNAL SEXUAL ORGANS (gonads and ducts) AEB_img14-1.jpg •The indifferent gonad anlage lies within the gonadal (genital) ridge that is bilateral organ •the gonadal ridge is a mesenchymal structure located on the medial side of the mesonephros (urogenital ridge); initially is of the same length as the mesonephros, but portion from C6 to L2 then rapidly degenerates, the caudal part (S1-S3) is transformed in the gubernaculum • a segment of the ridge extending between L3-L5 forms an anlage of the future gonad and is early invaded with primordial germ cells (PGCs) •PGCs differentiate outside the body (in the yolk sac and the gut) and migrate into indifferent gonad anlage by week 6 •a surface of the future gonad is covered with a coelomic epithelium that thickens and proliferates in the underlying mesenchyma in the form finger-like epithelial cords - called primary sex cord •the indifferent gonad consists of an outer cortex and an inner medulla • •The mesonephric duct and •remnants of mesonephric •tubules - persist from the • "midkidney" stage. Bez názvu 10upr •The paramesonephric duct is primitive genital duct that develops from the longitudinal •invagination of coelomic epithelium covering the lateral aspect of the genital ridge (on each •side) •the proximal end opens into the coelomic, future peritoneal, cavity, the caudal end runs •parallel to the mesonephric duct •in the small pelvis ducts cross ventral to the mesonephric ducts, come together in the •midline, and fuse into Y-shaped uterovaginal primordium or canal •(the primordium projects into the dorsal wall of the urogenital sinus and produces an elevation, called the •sinus tubercle) Bez názvu 11upr devtestis if the indifferent gonad anlage will develop in the testis or ovary, depends on the presence or absence of a Y chromosome • •in presence of a Y chromosome, the gonad anlage differentiates •into the •testis • sexdif the absence of a Y chromosome results in differentiation of the ovary Vývoj urogenitálního systému - 36 Development of testes in embryos with a Y chromosome, the primary sex cords lose their connections with the coelomic epithelium and persist as the testicular cords that soon undergoe transformation into the seminiferous tubules cells of the seminiferous tubules differentiate in the Sertoli cells, PGCs give rise to spermatogonia the interstitial (Leydig) cells arise from the mesenchyma of indifferent gonad anlage the tunica albuginea is developed early as a condensation of the mesenchyma lying between the coelomic epithelium and seminiferous tubules Development of ovaries in embryos lacking a Y chromosome, the primary sex cords degenerate and migrate in the medulla in which form a rudimentary rete ovarii the superficial coelomic epithelium sends off new sex cord, called secondary or cortical sex cords these separate from it and are differentiated into the follicular cells which, in association with PGCs, form the primordial ovarian follicles the mesenchyma extending between the surface epithelium and ovarian follicles gives rise to the thin fibrous capsule - tunica albuginea Vývoj urogenitálního systému - 37 Vývoj urogenitálního systému - 3 devgonads Vývoj urogenitálního systému - 48 Descent of testis Descent of ovary by the 28th week from the peritoneal cavity to the scrotum to the small pelvis Development of genital ducts in the presence of a Y chromosome male sex indifferent stage the absence of a Y chromosome female sex are transformed into efferent ductuli (ductuli efferentes) remnants of mesophric tubules regress (tubules may persist as epoophoron and paroophoron) becomes the ductus epididymidis, ductus deferens and ejaculatory duct the mesonephric (Wolffian) duct regresses cranial end of the duct may persists as appendix vesiculosa, caudal part as the duct of Gartner regresses (rarely it may give rise to a rudimentary appendix testis) regresses (rarely utriculus prostaticus) the paramesonephric duct unfused portion the uterovaginal primordium the oviduct (fallopian tube) the uterus + cranial part of the vagina Bez názvu 20upr Derivatives of the paramesonephric duct: Vývoj urogenitálního systému - 45 external genitalia undergoe the indifferent stage similar as gonads and genital ducts the indifferent stage is characterised by Ø a genital tubercle - is situated at the cranial end of the cloacal membrane it rapidly grows and elongates to form the phallus Ø the cloacal (urogenital) folds - are paired and demarcate the urogenital orifice Ø the labioscrotal swellings - are located laterally to the urogenital folds on each side Ø Development of external genitalia - indifferent stage male sex indifferent stage female sex gives rise to the penis the phallus grows slowly and is transformed in the clitoris fuse in midline and close the urogenital orifice – the cavernous urethra urogenital folds do not fuse and form the labia minora grow toward each other and fuse to form the scrotum labioscrotal swellings remain unfused similar to folds and form the labia majora Vývoj urogenitálního systému - 24 Vývoj urogenitálního systému - 47 the female sex the male sex •because an early embryo has the potential to develop as either a male or a •female, errors in sex development may result in intermediate sex, a condition •known as intersexuality, or hermaphroditism • •a person with ambiguous external genitalia is called intersex, or a •hermaphrodite • •true hermaphrodites - have both ovarian and testicular tissue (ovotestis) occur extremely rare •false hermaphrodites or pseudohermaphrodites - occur about once in •25,000 birth • two forms are distinguished: • - female pseudohermaphrodites - have 46,XX karyotype and ovaries, but external genitalia resemble masculine genitalia (hypertrophied clitoris, the labia majora are partially fused, the persistent urogenital sinus) • malformation mostly occurs in the form of the adrenogenital syndrome, resulting from congenital virilizing adrenal hyperplazia • - male pseudohermaphrodites - 46,XY constitution, they have testes, but external genitalia resemble in various degree of female genitalia • is caused by inadequate production of testosterone, androgen receptor disorders, 5-a • reductase deficiency or MDIF deficiency OVERVIEW OF CONGENITAL MALFORMATIONS OF GENITAL ORGANS •Malformations occuring in males: • •cryptorchidism - (undescended testes) - is found in one in three premature male babies or in one in 30 full-term males • testes are retained in the abdominal cavity or in the inguinal canal • sterility is resulting if the condition persists to the puberty • anomaly may repair spontaneously, if not, the surgical treatment must follows •congenital inguinal hernia - occurs in the case of unclosed processus vaginalis, which connects the tunica vaginalis with the peritoneal cavity • if the abdominal pressure is increased, then intestinal loops herniate through it into the scrotum (rarely labium majus), congenital inguinal hernia is often accompanied with cryptorchidism •hydrocele - if the abdominal end of the processus vaginalis remains open, the peritoneal fluid passes into it and forms a hydrocele of the testis and spermatic cord Bez názvu 19upr •hypospadias - a malformation in which the external urethral orifice is on the ventral surface of the penis instead of at the tip of the glans • it occurs one in about every 300 males • 4 types of hypospadias: glandular, penile, penoscrotal, and perineal • (the glandular and penile constitute about 80 per cent of cases) •epispadias - is a malformation in which the urethra opens on the dorsal aspect of the penis and is often associated with extrophy of the bladder • it occurs once in about 30,000 male infants Bez názvu 19upr agenesis of the penis - extremely rare malformation results from failure of the genital tubercle to develop bifid penis and double penis - very rare - distal part of the penis is divided into two portions, it results from failure of fusion of two parts of the genital tubercle (if two genital tubercles do not fuse - it develops double penis) micropenis - the penis is so small that it is almost hidden by the suprapubic pad of fat ; it is usually associated with hypopituitarism and hormonal deficiency of the fetal testes •Malformations occuring in females: • •ectopic ovary - the ovary shows abnormal location, rare •uterovaginal malformations - result from • (1) improper fusion of both paramesonephric ducts • (2) incomplete development of one paramesonephric duct • (3) failure of parts of one or both ducts to develop • (4) incomplete canalization of the vaginal plate • Ødouble uterus (uterus didelphys) Øbicornuate uterus Øunicornuate uterus with one uterine tube Øabsence of the uterus Øabsence of the vagina - once in about every – 4000 females Øvaginal atresia - results from failure of – canalization of the vaginal plate Ø anorectal agenesis and fistulas - the rectum ends well above the anal canal and is connected to the vagina with a fistula (rectovaginal fistula) is the most common type of anorectal malformations Bez názvu 21upr Močový systém - 2 Vývoj pronefros Bez názvu 19upr Bez názvu 18upr kopie Bez názvu 12upr