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Ovid: Oxford Handbook of Urology

Authors: Reynard, John; Brewster, Simon; Biers, Suzanne Title: Oxford Handbook of Urology, 1st Edition Copyright ©2006 Oxford University Press > Table of Contents > Chapter 16 – Paediatric urology Chapter 16 Paediatric urology P.524
Embryology: urinary tract Following fertilization, a blastocyte (sphere of cells) is created, which implants into the uterine endometrium on day 6. The early embryonic disc of tissue develops a yolk sac and amniotic cavity, from which are derived ectoderm, endoderm, and mesoderm. Organ formation occurs between 3–10 weeks’ gestation. Most of the genitourinary tract is derived from mesoderm. Upper urinary tract The pronephros (precursor kidney; pro = (Gk) before), derived from an intermediate plate of mesoderm, is present between weeks 1–4. It then regresses. The mesonephros (meso = (Gk) middle) functions from weeks 4–8, and is also associated with 2 duct systems—the mesonephric duct and, adjacent to this, the paramesonephric duct (para = (Gk) beside) (Fig. 16.1). The mesonephric (Wolffian) ducts develop laterally, and advance downwards to fuse with the primitive cloaca (hindgut). By week 5, a ureteric bud grows from the distal part of the mesonephric ducts and induces formation of the metanephros in the overlying mesoderm (permanent kidney; meta = (Gk) after). Branching of the ureteric bud forms the renal pelvis, calyces, and collecting ducts. Glomeruli and nephrons are created from metanephric mesenchyme. During weeks 6–10, the caudal end of the fetus grows rapidly and the fetal kidney effectively moves up the posterior abdominal wall to the lumbar region. Urine production starts at week 10. Thus, in both males and females, the mesonephric duct forms the ureters and renal collecting system. The paramesonephric essentially forms the female genital system (fallopian tubes, uterus, upper vagina); in males, it regresses. The mesonephric duct forms the male genital duct system (epididymis, vas deferens, seminal vesicles, central zone of prostate); in the female, it regresses. Lower urinary tract The mesonephric ducts and ureters drain into the cloaca (Latin = sewer), which is later subdivided into the urogenital sinus (anteriorly) and the anorectal canal (posteriorly) during weeks 4–6 (see Fig. 16.1). The bladder is formed by the upper part of the urogenital sinus. The lower part forms the urethra in females. In males, the mesonephric ducts form the posterior urethra and closure of the urogenital groove creates the anterior urethra.

Fig. 16.1 The development of the upper and lower parts of the urinary tract (weeks 4–6)

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Undescended testes The testes descend into the scrotum in the 3rd trimester (passing through the inguinal canal at 24–28 weeks). Failure of testicular descent results in cryptorchidism (or undescended testes). Incidence 3% at birth (unilateral > bilateral). ~80% will spontaneously descend by 3 months. The incidence at 1 year is 1%. Classification

  • Retractile: an intermittent active cremasteric reflex causes the testis to retract up and out of the scrotum.
  • Ectopic (<5%): abnormal testis migration below the external ring of the inguinal canal (to perineum, base of penis, or femoral areas).
  • Incomplete descent (~95%): testis may be intra-abdominal, intra-inguinal, or pre-scrotal.
  • Atrophic/absent

Risk factors Pre-term infants; low birth weight; small for gestational age; twins. Aetiology Abnormal testis or gubernaculum (tissue which guides the testis into the scrotum during development); endocrine abnormalities (low level of androgens, human chorionic gonadotrophin (HCG), luteinizing hormone (LH), calcitonin gene-related peptide); decreased intra-abdominal pressure (prune-belly syndrome, gastroschisis). Pathology Degeneration of Sertoli cells; loss of Leydig cells; atrophy and abnormal spermatogenesis. Long-term complications

  • Relative risk of cancer is 40-fold higher in the undescended testis. Majority are seminomas; carcinoma in situ represents a small percentage (~2%). There is a slightly increased risk of cancer in the contralateral, normally descended testis.
  • Reduced fertility.
  • Increased risk of testicular torsion.
  • Increased risk of direct inguinal hernias (due to a patent processus vaginalis).

Management Full examination to elucidate if testis is palpable and to identify location. Assess for associated congenital defects. If neither testis is palpable, consider chromosome analysis (to exclude an androgenized female), and hormone testing (high LH and FSH with a low testosterone indicates anorchia). Treatment should be performed within the first year. Hormone therapy (HCG, LHRH) stimulates testosterone production. Surgery consists of inguinal exploration, mobilization of spermatic cord, ligation of processus vaginalis, and securing the testis into a dartos pouch in the scrotal P.527
wall (orchidopexy). Laparoscopy can be used in planning surgery and for treatment. Intra-abdominal testes may require division of spermatic vessels to provide extra length (relying on collateral blood flow from vas), 2-stage procedures, or microvascular autotransplantation. P.528
Urinary tract infection (UTI) Definitions UTI is a bacterial infection of the urine (>105 colony-forming units/ml of urine), which may involve the bladder (cystitis) or kidney (pyelonephritis). Classification Children may be asymptomatic or symptomatic. It may be the first (intial) infection, or recurrent UTI due to persistence of the causative organism and re-infection, or an unresolved infection due to inadequate treatment. Incidence Up to age 1, the incidence in boys is higher than girls (males 2.7%:females 0.7%), but thereafter, the incidence in girls becomes greater (school age: males 1%:females 1–3%). Pathology Common bacterial pathogens are Escherichia coli (E. coli), Enterococcus, Pseudomonas, Klebsiella, Proteus, and Staphylococcus epidermis. Bacteria enter via the urethra to cause cystitis, and ascending infection causes pyelonephritis. Alternatively, there can be haematogenous spread from other systemic infections. Risk factors

  • Age. Neonates and infants have increased bacterial colonization of the periurethral area and an immature immune system.
  • Vesicoureteric reflux (VUR)—see p.530.
  • Genitourinary abnormalities (pelviureteric or vesicoureteric obstruction; ureterocele; posterior urethral valves).
  • Voiding dysfunction (abnormal bladder activity, compliance, or emptying).
  • Gender (female > male after 1 year old).
  • Foreskin. Uncircumcised boys have a 10-fold higher risk of UTI in the first year due to bacterial colonization of the glans and foreskin.
  • Faecal colonization (contributes to perineal bacterial colonization).

Presentation Fever, irritability, vomiting, diarrhoea, poor feeding, suprapubic pain, dysuria, voiding difficulties, incontinence, flank pain. Investigation Diagnosis is made on urine analysis and culture. In young children, a catheterized urine specimen or a suprapubic aspirate is most accurate (‘bag’ specimens are less reliable due to skin flora contamination). In toilet trained children, a mid-stream specimen can be collected. Imaging UTI in children <5 years; febrile UTI; infection in non-sexually active boys; and girls (>5 years) with two or more episodes of cystitis require renal tract imaging.

  • Ultrasound scan identifies bladder and kidney abnormalities.
  • Micturating cystourethrogram (MCUG) demonstrates urethral and bladder anomalies, VUR, and ureteroceles.
  • DMSA (dimercaptosuccinic acid) renogram can demonstrate and monitor renal scarring.

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Management Empirical treatment should be started if infection is suspected. Children <3 months old with severe infection or pyelonephritis should receive broad-spectrum intravenous antibiotics (gentamicin and ampicillin) until antibiotic sensitivities are available. Older children, and infants tolerating feeds can be given oral antibiotics (cephalosporins, or nitrofuratoin and trimethoprim-sulphamethoxide after 2 months old). Complications Neonates and young children have an increased risk of associated renal involvement and subsequent renal scarring, which can result in hypertension and renal failure. P.530
Vesicoureteric reflux (VUR) Definition VUR results from abnormal retrograde flow of urine from the bladder into the upper urinary tract. Epidemiology Overall incidence in children is >10%; younger > older; girls > boys (female:male ratio 5:1); Caucasian >Afro-Carribean. Siblings of an affected child have a 40% risk of reflux, and routine screening of siblings is recommended. Pathogenesis The ureter passes obliquely through the bladder wall (1–2cm), where it is supported by muscular attachments which prevent urine reflux during bladder filling and voiding. The normal ratio of intramural ureteric length to ureteric diameter is 5:1. Reflux occurs when the intramural length of ureter is too short (ratio <5:1). The degree of reflux is graded I–V (see Fig. 8.1, p.339). The appearance of the ureteric orifice changes with increasing severity of reflux, classically described as stadium, horseshoe, golf-hole, or patulous. Classification

  • Primary reflux (1%) results from a congenital abnormality of the ureterovesical junction.
  • Secondary reflux results from urinary tract dysfunction associated with elevated intravesical pressures creating damage to the vesicoureteric junction. Causes include: posterior urethral valves (reflux seen in 50%); urethral stenosis; neuropathic bladder; detrusor sphincter dyssynergia.
  • VUR is also seen with duplex ureters. The Weigert–Meyer rule states that the lower pole ureter enters the bladder proximally and laterally, resulting in a shorter intramural tunnel which predisposes to reflux.

Complications VUR associated with UTI can result in reflux nephro pathy with hypertension and progressive renal failure. Presentation Symptoms of UTI, fever, dysuria, suprapubic or abdominal pain, failure to thrive, vomiting, diarrhoea. Investigation

  • Urine analysis and culture to diagnose UTI
  • Urinary tract ultrasound scan and micturating cystourethrogram (MCUG) to diagnose and grade reflux and establish reversible causes
  • Urodynamics if suspicious of voiding dysfunction
  • DMSA to detect and monitor associated renal cortical scarring.

Management Correct problems contributing to secondary reflux. The majority of primary VUR grade I–II will resolve spontaneously (~85%), with 50% resolution in grade III. A period of observation with medical treatment is therefore initially recommended. Medical treatment Low-dose antibiotic prophylaxis should be given to keep the urine sterile and lower the risk of renal damage until reflux resolves. Anticholinergic drugs are given to treat bladder overactivity. P.531
Surgery Indicated for severe reflux, breakthrough UTIs, evidence of progressive renal scarring, and VUR that persists after puberty. Techniques include laparoscopic repair and open ureteric re-implantation (98% success).

  • Intravesical methods involve mobilizing the ureter and advancing it across the trigone (Cohen repair) or reinsertion into a higher, medial position in the bladder (Politano–Leadbetter repair).
  • Extravesical techniques involve attaching the ureter into the bladder base and suturing muscle around it (Lich–Gregoir procedure).
  • Alternatively, endoscopic subtrigonal injection (‘STING’) of collagen into the ureteric orifice has 70% success, rising to 95% with repeated treatments.

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Ectopic ureter Definition The ureteric orifice is situated below the normal anatomical insertion on the trigone of the bladder. Pathogenesis The ureteric bud arises from an abnormal position on the mesonephric duct during embryological development. Females are affected more than males (female:male ratio 3:1). 80% are associated with a duplicated collecting system (which predominantly affects females). A duplex kidney has an upper pole and a lower pole, each with its own renal pelvis and ureter. The two ureters may join to form a single ureter, or they may pass down individually to the bladder (complete duplication). In this case, the upper pole ureter always opens onto the bladder below and medial to the lower pole ureter (Weigert–Meyer rule), predisposing to ectopic placement of the ureteric orifice. Sites of ectopic ureters

  • Females: bladder neck, urethra, vagina.
  • Males: posterior urethra, seminal vesicles, ejaculatory duct, vas deferens, epididymis, bladder neck.

Presentation Acute or recurrent UTI is common in both sexes. Obstruction of the ectopic ureter can lead to hydronephrosis and hydroureter, which may present as an abdominal mass.

  • Females: when the ureteric opening is below the urethral sphincter, girls present with persistent vaginal discharge or incontinence, despite successful toilet training.
  • Males: the ureter is always sited above the external urethral sphincter, so boys do not develop incontinence. UTIs may trigger epididymitis.

Investigation of urinary tract

  • USS demonstrates ureteric duplication, dilatation, and hydronephrosis.
  • IVU identifies duplex systems and gives information on renal segment function.
  • Micturating cystourethrography (MCUG) assesses reflux in lower pole ureters.
  • Cystourethroscopy can directly identify a ureteric opening in the urethra.
  • Isotope renogram (99mTc-DMSA) assesses renal function to help plan surgery.

Treatment An ectopic ureter is often associated with a poorly functioning renal upper pole or single-system kidney. In such cases, surgery consists of open or laparoscopic heminephrectomy or total nephrectomy with excision of the associated ureter. Where some function is retained in a single-system kidney, the distal ureter can be resected and reimplanted into the bladder. P.533
Ureterocele Definition A ureterocele is a cystic dilatation of the distal ureter as it drains into the bladder. Incidence Females are affected more than males (female:male ratio 4:1). They predominantly affect Caucasians. 80% are associated with the upper pole of a duplex system, although they can be found in single systems (more commonly in adults). 10% are bilateral. Classification

  • Intravesical: confined within the bladder
  • Ectopic: if any part extends to the bladder neck or urethra
  • Stenotic: intravesical ureterocele with a narrow opening
  • Sphincteric: ectopic ureterocele with an orifice distal to the bladder neck
  • Sphincterostenotic: orifice is both stenostic and distal to the bladder neck
  • Cecoureterocele: ectopic ureterocele that extends into the urethra, but the orifice is in the bladder

Presentation Infants commonly present with symptoms of UTI. Association with duplicated ureters increases the risk of reflux and reflux nephropathy. Ureteroceles can also cause obstruction and hydronephrosis, which may be identified on antenatal USS, or present in children with an abdominal mass or pain. A prolapsing ureterocele can present as a vaginal mass in girls. Investigation

  • USS shows a thin-walled cyst in the bladder often associated with a duplex system.
  • IVU may demonstrate deviation of upper pole duplex kidney and delayed excretion of contrast signifying altered renal function. In single systems, contrast in the ureterocele gives the appearance of a ‘cobra head’.
  • Micturating cystourethrogram can identify location, size, and associated reflux.
  • Cystoscopy may reveal a defect near the trigone.
  • 99mTc-DMSA assesses renal segment function.

Treatment

  • Single-system ureterocele Initial management is usually endoscopic incision of the ureterocele, which can be followed by surgical ureteric re-implantation to preserve renal function and prevent reflux.
  • Duplex-system ureterocele Treatment options vary with the individual and include: endoscopic incision; upper pole nephrectomy for a poorly functioning unit with ureterectomy or, where there is useful renal function, ureteropyelostomy can be performed.

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Pelviureteric junction (PUJ) obstruction Definition A blockage of the ureter at the junction with the renal pelvis resulting in a restriction of urine flow. Boys are affected more than girls. The left side is more often affected than the right side. They are bilateral in up to 40%. Aetiology In children, most PUJ obstruction is congenital, due to either an intrinsic narrowing (secondary to aberrant development of ureteric/ renal pelvis muscle, abnormal collagen, or ureteral polyps) or extrinsic causes (compression of the PUJ by aberrant vessels). Coexisting vesicoureteric reflux (VUR) is found in 40%. Presentation PUJ obstruction is the most common cause of hydronephrosis found on prenatal and early postnatal USS (differential diagnoses include VUJ obstruction, VUR, renal abnormalities, and posterior urethral valves). Infants may also present with an abdominal mass, UTI, and haematuria. Older children present with flank or abdominal pain (exacerbated by diuresis), UTI, nausea and vomiting, and haematuria following minor trauma. Investigation If prenatal USS has shown a large or bilateral hydronephrosis, a follow-up renal tract ultrasound scan should be performed soon after birth. If there is a prenatal unilateral hydronephrosis (and the bladder is normal), the scan is deferred until day 3–7 (to allow normal physiological diuresis to occur, which may spontaneously improve or resolve the hydronephrosis). If upper tract obstruction persists, a micturating cystourethrogram (MCUG) is indicated (to rule out VUR and examine for posterior urethral valves), and a renogram can assess individual renal function and drainage (DTPA, MAG-3). Treatment Children may be observed with USS and renogram if they remain stable, with good renal function, and no other complications (such as persistent infection or stones). If children are symptomatic or have a significant hydronephrosis with impaired renal function (<40%), pyeloplasty is recommended. P.535
Hypospadias Definition Hypospadias is a congenital deformity where the opening of the urethra (the meatus) occurs on the underside (ventral) part of the penis, anywhere from the glans to the perineum. It is often associated with a ‘hooded’ foreskin and chordee (ventral curvature of the penile shaft). It occurs in 1 in 250 live male births. There is an 8% incidence in off-spring of an affected male, and a 14% risk in male siblings. Classification Hypospadias can be classified according to the anatomical location of the urethral meatus (Fig. 16.2).

  • Anterior (or distal)—glandular, coronal, and subcoronal (~50%)
  • Middle—distal penile, midshaft, and proximal penile (~30%)
  • Posterior (or proximal)—penoscrotal, scrotal, and perineal (~20%)

Aetiology Hypospadias results from incomplete closure of urethral folds on the underside of the penis during embryological development. This is related to a defect in production or metabolism of fetal androgens, or the number and sensitivity of androgen receptors in the tissues. Chordee are caused by abnormal urethral plate development, and the ‘hooded’ foreskin is due to failed formation of the glandular urethra and fusion of the preputial folds (resulting in a lack of ventral foreskin but an excess of dorsal tissue). Diagnosis A full clinical examination will make the diagnosis. However, it is also important to seek out associated abnormalities which will need treatment (undescended testes, inguinal hernias, and hydroceles). Patients with absent testes and severe hypospadias should undergo chromosomal and endocrine investigation to exclude intersex conditions. Treatment Surgery is indicated where deformity is severe, interferes with voiding, or is predicted to interfere with sexual function. Surgery is now performed between 6–12 months of age. Local application of testosterone for 1 month pre-operatively can help increase tissue size. Surgery aims to correct penile curvature (orthoplasty), reconstruct a new urethra, and bring the new meatus to the tip of the glans using urethroplasy, glanuloplasty, and meatoplasty techniques. Severe cases may require staged procedures. Common operations for anterior hypospadias include meatal advancement and glanuloplasty (MAGPI), meatal-based flaps (Mathieu procedure), and tubularization of the urethral plate. Posterior defects require free grafts (buccal mucosa), onlay grafts, and preputial transfer flaps. Complications Bleeding, infection, urethral strictures, meatal stenosis, urethrocutaneous fistula, urethral diverticulum, and failed procedures requiring re-operation.

Fig. 16.2 The anatomical classification of hypospadias according to the location of the urethral meatus. (Adapted from Walsh et al. 2002)1

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Normal sexual differentiation Sexual differentiation and gonadal development is determined by the sex chromosomes (XY male, XX female). The gonads produce hormones which influence the subsequent differentiation of internal and external genitalia. Both sexes Gonads develop from the genital ridges (formed by cells of the mesonephros and coelomic epithelium). At 5–6 weeks, primordial germ cells migrate from the yolk sac to populate the genital ridges. Primitive sex cords are formed, which support germ cell development. From 4 weeks, the mesonephric (Wolffian) ducts are incorporated into the genital system, when renal function is taken over by the definitive kidney. At 6 weeks, coelomic epithelium creates the paramesonephric (Müllerian) ducts, which develop laterally and are fused to the urogenital sinus at their bases. Males The testis-determining gene (SRY) is located on the Y chromosome and stimulates medullary sex cords in the primitive testis to differentiate into Sertoli cells, which produce Müllerian inhibiting substance (MIS) at 7–8 weeks. This triggers regression of the paramesonephric ducts, testosterone secretion from Leydig cells of the testis, and the initial phase of testicular descent. During weeks 8–12, mesonephric ducts differentiate into epididymis, vas deferens, seminal vesicles, and ejaculatory ducts. The prostate is formed from mesenchyme (capsule) and urethral endoderm. After week 23, the testes rapidly descend from the abdomen (via the inguinal canal during weeks 24–28) and into the scrotal sac, guided by the gubernaculum. Testosterone and di-hydrotestosterone (DHT) androgens are responsible for masculinization. DHT is made from testosterone by 5-α-reductase enzyme in the tissues. Development of the external genitalia occurs from week 7. Urogenital folds develop around the opening of the urogenital sinus, and labioscrotal swellings form either side. The penile shaft and glans are formed by elongation of the genital tubercle and fusion of urogenital folds. The scrotum is created by fusion of labioscrotal folds. Females The genital ridge forms secondary sex cords (primitive sex cords degenerate) which surround the germ cells to create ovarian follicles (week 15). These undergo meiotic division to become primary oocytes, which are later activated to complete gametogenesis at puberty. Oestrogen is produced from week 8 under the influence of the aromatase enzyme. In the absence of MIS, the mesonephric ducts regress, and the paramesonephric ducts become the fallopian tubes, uterus, and upper two-thirds of the vagina. The sinovaginal sinus develops at the junction of the paramesonephric ducts and the urogenital sinus. This forms the lower third of the vagina. The genital tubercle forms the clitoris; the urogenital folds become the labia minora; and the labioscrotal swellings form the labia majora.

Fig. 16.3 Differentiation of external genitalia (weeks 7–16)
Fig. 16.4 Differentiation of the genital tract

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Abnormal sexual differentiation Abnormalities of sexual differentiation can be classified into 3 main groups (see Table 16.1).

  • Disorders of gonadal differentiation These are sub-divided into seminiferous tubule dysgenesis (Klinefelter’s syndrome XXY, 46XX males); Turner’s syndrome (45XO); true hermaphrodites (46XX or XY with both ovarian and testicular tissue); mixed gondal dysgenesis (streak gonads and a spectrum of ambiguous genitalia); and pure gonadal dysgenesis (females with streak gonads).
  • Male pseudohermaphrodites 46XY karyotype with differentiated testes. They have defects of testosterone production (3β-hydroxysteroid dehydrogenase, 17α-hydroxylase enzyme deficiencies) or androgen resistance (testicular feminization, 5α-reductase deficiency), resulting in varying degrees of feminization.
  • Female pseudohermaphrodites 46XX karyotype with ovaries, a partially masculinized phenotype, and ambiguous genitalia. The most common type is congential adrenal hyperplasia (CAH), due to 21-hydroxylase deficiency (in 95%). Formation of hydrocortisone is impaired, resulting in a compensatory increase in adrenocorticotrophin hormone (ACTH) and testosterone production. Some forms have a ‘salt wasting’ aldosterone deficiency which can present in the first few weeks of life with adrenal crisis (severe vomiting and dehydration), requiring rehydration and steroid replacement therapy.

Evaluation

  • A detailed history may uncover a positive family history of intersex disorders. Maternal ingestion of drugs such as steroids or contraceptives during pregnancy should be ascertained.
  • General examination may show associated syndrome anomalies (Klinefelter’s and Turner’s syndromes) or failure to thrive and dehydration (salt-wasting CAH). Assess external genitalia for phallus size and location of urethral meatus. Careful palpation may confirm the presence of testes, which excludes a diagnosis of female pseudohermaphroditism. Patients with bilateral undescended testes or unilateral undescended testis with hypospadias should be suspected of having an intersex disorder.
  • Pelvic USS can help locate the gonads or, occasionally, laparotomy with gonadal biopsy is required for diagnosis.
  • Chromosomal analysis confirms karyotype; serum electrolytes, testosterone, and DHT analysis test for salt-wasting CAH; serum 17-hydroxyprogesterone performed after day 3 can also diagnose 21-hydroxylase deficiency; hCG stimulation test can diagnose androgen resistance and 5α-reductase deficiency.
Fig. 16.5 Metabolic pathways for adrenal steroid synthesis

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Management A multidisciplinary approach is required with full parental input. Gender assignment of ambiguous genitalia is guided by the functional potential of gonadal tissue, reproductive tracts, and genitalia, with the aim of optimizing psychosocial well-being and producing a stable gender identity. Patients have a higher risk of gonadal malignancy, which requires surveillance and/or removal of gonadal tissues and hormone replacement.

Table 16.1 The three classifications of abnormal sexual differentiation
Disorder Karyotype Gonad Genitalia Other features Treatment
Gonadal differentiation
Klinefelter’s syndrome 47XXY Seminiferous tubule dysgenesis, small testes Male Tall, gynaecomastia, azoospermia, mild mental retardation, ↑↑ FSH/LH, ↓ testosterone Androgen replacement
46XX male 46XX Seminiferous tubule dysgenesis Male Short stature, gynaecomastia, infertile, hypospadias, ↑ FSH/LH, ↓ testosterone Androgen replacement
Turner’s syndrome 45XO Streak ovaries Female Short stature, sexual infantilism, web neck, widespread nipples, wide carrying angle, coarctation, renal anomalies Growth hormone; oestrogen replacement at puberty
True hermaphrodites 46XX or XY Ovary and testis Ambiguous or male Hypospadias (80%) in ‘males’; clitoromegaly in ‘females’ Gender assignment surgery
Mixed gonadal dysgenesis 45XO/46XY Unilateral undescended testis and streak gonad Ambiguous Wide phenotypic spectrum from Turner’s syndrome-like female to male Gender assignment, gonadectomy (as ↑ cancer risk), screen for Wilms’ tumour
Pure gonadal dysgenesis 46XX Streak ovaries Female Normal stature, sexual infantilism, 1° amenorrhoea Cyclic hormone replacement
Male pseudohermaphroditism
3β-hydroxysteroid dehydrogenase deficiency 46XY Testes Ambiguous Salt wasting, ↓ cortisol, ↓ aldosterone Glucocorticoid and mineralocorticoid replacement
17α-hydroxylase deficiency 46XY Testes Ambiguous ↓ cortisol (causing ↓ ACTH), resulting in ↓?steroids, hypokalaemia, hypertension Glucocorticoid replacement
Complete testicular feminization 46XY Testes Female Androgen resistance, female phenotype, short blind-ending vagina, breasts at puberty. Gonadectomy after puberty, oestrogen replacement therapy
Incomplete testicular feminization 46XY Testes Ambiguous Wide spectrum including hypospadias, infertility, gynaecomastia, pseudovagina Gender assignment surgery ± gonadectomy and hormones replacement
5α-reductase deficiency 46XY Testes Ambiguous Failure to convert testosterone to DHT in androgen-sensitive cells, hypospadias, small phallus, short vagina, virilization at puberty Reconstructive surgery ± hormonal support
Female pseudohermaphroditism
Congenital adrenal hyperplasia 46XX Ovaries Ambiguous Simple virilization or salt-wasting aldosterone deficiency Glucocorticoid, mineralocorticoid replacement, and surgery
Transplacental androgens 46XX Ovaries Ambiguous Virilization by maternal drug use in pregnancy or maternal adrenal tumours External genitalia reconstruction as required

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Cystic kidney disease Congenital cystic kidney disease can be classified into genetic and non-genetic types. Genetic Autosomal recessive polycystic kidney disease (ARPKD) A disease of infancy and childhood, where renal collecting tubules and ducts become cystically dilated and numerous small cysts form in the renal cortex and medulla. Severe forms present early and have a poor prognosis. Prenatal USS demonstrates oligohydramnios (amniotic fluid <200ml) and large, ‘bright’ homogeneously hyperechogenic kidneys, which can cause obstructed labour and respiratory problems. Neonates have large flank masses, limb and facial anomalies. All cases are associated with congenital hepatic fibrosis. Infants develop fatal uraemia and respiratory failure; older children present with renal failure, hypertension, and portal hypertension. Most develop end-stage renal failure by adulthood, requiring haemodialysis and renal transplantation. Autosomal dominant polycystic kidney disease (ADKD) Typically presents in adulthood, although older children can present with complications of haematuria, flank pain, flank mass, UTI, proteinuria, hypertension, and intracerebral bleeds (secondary to berry aneurysm rupture). It is characterized by multiple expanding cysts of both kidneys that ultimately destroy the intervening parenchyma, and accounts for 10% of all chronic renal failure. Familial juvenile nephronophthisis An autosomal recessive disorder which develops in early childhood and accounts for up to 20% of paediatric renal failure. Medullary cystic disease is a similar (autosomal dominant) condition which develops in later childhood. Histology shows interstitial nephritis associated with medullary and corticomedullary cysts. Disease progression causes a reduction in kidney size. Features include polyuria, polydipsia, anaemia, growth retardation, and chronic renal failure. Renal cysts are also a feature of autosomal dominant conditions including Von–Hippel–Lindau syndrome (cerebellar haemangioblastomas, phaeochromocytoma, renal cell carcinoma) and tuberous sclerosis (adenoma sebaceum, epilepsy, learning difficulties). Non-genetic Multicystic dysplastic kidney The most common cystic kidney disorder. The cysts of a ‘multicystic’ kidney are not due to dilatation of renal collecting ducts (as in polycystic disease) but, instead, the entire kidney is dysplastic, with immature dysplastic stroma P.545
and cysts of various sizes. Bilateral disease is incompatible with life. Unilateral disease is often associated with reflux or PUJ obstruction in the contralateral kidney. Affected kidneys may undergo renal aplasia, where they spontaneously shrink to a tiny remnant. USS and renograms (DMSA) help to distinguish this condition from hydronephrosis. Most can be treated conservatively with close surveillance for the associated risks of hypertension and Wilms’ tumour, which would be indications for surgery. Multilocular cystic nephroma Presents in young children with a flank mass. It is included in a spectrum of disease that is closely associated with Wilms’ tumour, and so the recommended treatment is partial or full nephrectomy. P.546
Exstrophy Bladder exstrophy results from defective development of the anterior bladder and lower abdominal walls, leaving the posterior bladder wall lying exposed on the abdomen. Epidemiology 3.3 cases per 100,000 live births. Male to female ratio >2:1. Increased risk in offspring of affected patients and with younger maternal age and increased parity. Embryology An embryological malformation results in the abnormal overdevelopment of the cloacal membrane, which prevents in-growth of lower abdominal tissues. The cloacal membrane normally perforates to form the urogenital and anal openings, but in exstrophy there is premature rupture resulting in a triangular defect below the umbilicus. The timing of this rupture determines the type of defect (bladder exstrophy, cloacal exstrophy, or epispadias). Associated anomalies

  • Bone defects Diastasis (widening) of the symphysis pubis due to outward rotation of the pelvic bones along the sacroiliac joints.
  • Musculofascial defects Umbilical hernias, inguinal hernias, abnormal pelvic floor.
  • Genital defects Males: short, broad penis with lateral splaying of the corporal cavernosa, short urethral plate. Females: bifid clitoris, stenotic vaginal orifice, short vaginal canal, vaginal prolase.
  • Urinary tract defects Majority suffer vescioureteric reflux (VUR) due to lateral displacement of the ureteric orifices.
  • GIT defects Anteriorly displaced anus, rectal prolapse, abnormal anal sphincter contributes to incontinence.

Investigation Typical features seen on prenatal ultrasound scan include a lower abdominal wall mass; absent bladder filling; low-set umbilicus; small genitalia; abnormal iliac crest widening. Diagnosis can help planning of delivery in a centre with facilities to perform early surgical correction. Management At birth, cover the bladder with plastic film and irrigate regularly with sterile saline. Trauma to the bladder mucosa can result in squamous metaplasia, cystitis cystica, or adenocarcinoma and squamous cell carcinoma after chronic exposure. Selected cases are suitable for one-stage repair, but most require a 3-stage procedure:

  • Newborn—pelvic osteotomy (cutting bone to correct deformity) with external fixation with closure of bladder, abdominal wall, and posterior urethra.
  • 6–12 months—epispadias repair.
  • 4–5 years—bladder neck reconstruction (Young–Dees–Leadbetter procedure) and anti-reflux surgery (ureteric reimplantation) is performed when there is adequate bladder capacity and children can participate in voiding protocols. Where bladder capacity is too small, bladder augmentation or urinary diversion is required.

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Epispadias In epispadias, the urethra opens onto the dorsal surface of the penis, anywhere from the glans, penile shaft, or, most commonly, the penopubic region. An incomplete urethral sphincter mechanism results in a high risk of incontinence. Epispadias is also associated with dorsal chordee (causing an upward curvature of the penis), with incomplete foreskin dorsally. Epispadias is part of the exstrophy–epispadias complex (which also includes bladder exstrophy and cloacal exstrophy) (see p.546). Associated anomalies Diastasis of the symphysis pubis results in splaying of the corpora cavernosa and shortening of the penile shaft. Females have a bifid clitoris, poorly developed labia, and demonstrate a spectrum of urethral deformities ranging from a patulous urethral orifice to a urethral cleft affecting the entire length of the urethra and sphincter. There is a 40% risk of vesicoureteric reflux (VUR). Incidence Affects 1 in 117,000 males. Rarely seen in females (male:female ratio is 5:1). Management Urethroplasty with functional and cosmetic reconstruction of the external genitalia (penile lengthening and correction of chordee) at 6–12 months. The modified Cantwell–Ransley technique is commonly used in males. It describes mobilizing the urethra to the ventral aspect of the penis, with advancement of the urethral meatus onto the glans with a reverse MAGPI (meatal advancement-glanduloplasty). The corporal bodies are separated and rotated medially above the urethra and re-approximated. From age 4–5 years, when children can be toilet trained, bladder neck reconstruction can be performed (Youngs–Dees–Leadbetter procedure). This achieves continence, and any bladder residuals may then be emptied by urethral catheterization. If this surgery fails, insertion of artificial urinary sphincters or collagen injections of the sphincter may be tried. P.548
Posterior urethral valves (PUVs) Definition Abnormal congenital mucosal folds in the prostatic (posterior) urethra causing lower urinary tract obstruction. Classification

  • Type I (90–95%) Membranes arise from the distal lateral aspect of the verumontanum,1 which extend distally and anteriorly to fuse in the midline.
  • Type II Longitudinal folds extending from the verumontanum to bladder neck.
  • Type III A ring-like membrane found distal to the verumontanum.

Incidence 1 in >5000 males Aetiology Normal male urethra has small, paired lateral folds (plicae colliculi) which are found between the lateral, distal edge of verumontanum and lateral urethral wall. PUVs probably represent a congenital overgrowth of these folds, due to abnormal insertion of Wolffian ducts into the posterior urethra during fetal development. Presentation Prenatal USS features Bilateral hydroureteronephrosis; dilated bladder and posterior urethra (keyhole sign); thick-walled bladder; oligohydramnios (reduced amniotic fluid); and renal dysplasia. Early features are associated with poor prognosis. Newborn and infants Respiratory distress (secondary to pulmonary hypoplasia); palpable abdominal mass (hydronephrotic kidney or distended bladder); ascites; UTI; electrolyte abnormalities; failure to thrive. Older children Milder cases may present later with recurrent UTI; poor urinary stream; incomplete bladder emptying; poor growth and incontinence. Risk of renal failure, vesicoureteric reflux, and voiding dysfunction (overactive or underactive bladder), also described as ‘valve bladder syndrome’. Associated features ‘POP-off valve syndrome’ is seen in 20%. It describes mechanisms by which high urinary tract pressure is dissipated to allow normal renal development. It includes leaking of urine from small bladder or renal pelvis ruptures (urinary ascites), reflux into a non-functioning kidney (vesicoureteral reflux with renal dysplasia or VURD), and formation of bladder diverticuli. Investigation

  • Ultrasound scan of renal tract.
  • Micturating cystourethrogram: distended posterior urethra (shield-shaped); partially filled anterior urethra; bladder neck hypertrophy; lucencies representing valve leaflets; thick walled bladder (±diverticuli); incomplete bladder emptying; reflux (50%).
  • Isotope renal scan (MAG-3, DMSA): assesses renal function.
  • Videourodynamics: allows diagnosis of associated voiding dysfunction.

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Management Commence prophylactic antibiotics immediately, check serum electrolyes, and drain the bladder with a paediatric feeding tube. If there is improvement, cystoscopy and transurethral ablation of valve (cuts at 5 and 7 o’clock with electrocautery) is recommended (complications include urethral strictures). If upper tracts remain dilated with raised creatinine after bladder drainage, a temporary cutaneous vesicostomy is indicated (communicating stoma between the bladder dome and suprapubic abdominal wall, allowing free drainage of urine). An alternative is ureterostomy drainage. Valve ablation is performed at a later stage. Prognosis 35% poor renal function; 20% develop end-stage renal failure. Footnote 1 Verumontanum is tissue found on the ventral aspect of the prostatic urethra into which drain the ejaculatory ducts and prostatic utricle. P.550
Non-neurogenic voiding dysfunction Definition An abnormal voiding pattern without an underlying organic cause (neurological disease, congenital malformation, or injury) which usually results in urinary incontinence (diurnal, nocturnal, or both). It is often associated with constipation and faecal retention. Normal bladder control

  • Neonates: sacral spinal cord reflex triggers voiding when the bladder is full.
  • Infants: primitive reflexes are suppressed, bladder capacity increases, and voiding frequency is reduced.
  • 2–4 years: development of conscious bladder sensation and voluntary control.

Classification Urinary incontinence can be divided into primary types (never been dry) or secondary (re-emergence of incontinence after being dry for 6 months). Voiding dysfunction can be described as mild, moderate, or major.

  • Mild Daytime urinary frequency syndrome; giggle incontinence; post-void dribbling (urine refluxes into the vagina, then dribbles into underwear on standing); nocturnal enuresis.
  • Moderate ‘Lazy’ bladder syndrome (large capacity, poor contractility, infrequent voids); overactive bladder (detrusor overactivity associated with urgency and frequency). Children may demonstrate holding manoeuvres (leg crossing, squatting, Vincent’s curtsey). There is increased risk of UTI, vesicoureteric reflux, and upper tract dilatation.
  • Major Hinman’s syndrome (non-neurogenic neurogenic bladder) involves dyscoordination between the bladder muscle and external urethral sphincter activity resulting in a small, trabeculated bladder, VUR, UTI, hydronephrosis, and renal damage. Caused by abnormal learned voiding patterns.

Evaluation

  • History Enquire about UTIs; voiding habits (frequency, urgency, primary or secondary incontinence); family history; bowel problems; social history; behavioural problems.
  • Examination Full non-invasive examination (palpable bladder or kidneys). Be vigilant for signs of sexual abuse in children with an atypical history (penile or vaginal discharge). Exclude an organic cause (hairy patch, lipoma, dimple on lower back may indicate lumbosacral spine abnormalities).
  • Investigations Urinalysis (infection, protein, glucose); voiding diary; flow rate. In selected cases: USS renal tract (hydronephrosis, bladder size); micturating cystourethrogram (VUR, post-void residual); videourodynamics (over or underactive detrusor, sphincter dyssynergia); MRI spine (if clinical suspicion of neurological cause).

P.551
Management Behavioural (bladder retraining, timed voiding, change of voiding posture, psychological support); medication (antibiotics for infection, anticholinergics for bladder overactivity and urgency, laxatives or enemas for constipation); intermittent catheterization to drain post-void residuals. Surgery is rarely indicated. Prognosis 15% spontaneously resolve per year. P.552
Nocturnal enuresis Enuresis is normal but involuntary voiding that occurs at an inappropriate time or social setting, during the day, night, or both. Nocturnal enuresis describes any involuntary loss of urine during sleep. Prevalence ~750,000 children over 7 years will regularly wet the bed. The prevalence in adults is ~0.5%.

Age (years) Females Males
5 10–15% 15–20%
7 7–15% 15–20%
9 5–10% 10–15%
16 1–2% 1–2%

Classification

  • Primary Never been dry for more than a 6-month period.
  • Secondary The re-emergence of bed wetting after a period of being dry for at least 6 months.

Aetiology

  • Familial
  • Delay in functional bladder maturation
  • Altered antidiuretic hormone (ADH) secretion; abnormal decrease in ADH levels at night causes increased urine production (nocturnal polyuria)
  • Altered sleep/arousal mechanism
  • Psychological factors
  • UTI (1% of cases)

Evaluation

  • History Frequency of episodes; daytime symptoms; new or recurrent; family history; UTIs; bowel problems; psychosocial history.
  • Examination Exclude organic causes (neurological disease).
  • Investigation Urinalysis (infection, specific gravity is reduced in nocturnal polyuria, glucose, protein); voiding diary.

Management Behavioural Reassurance; bladder training; motivational techniques to improve child’s self-esteem; conditioning therapy (an alarm is connected to the child’s underwear which is triggered with the first few drops of urine). P.553
Pharmacological

  • Imipramine—a tricyclic antidepressant with anticholinergic, antispasmodic properties.
  • DDAVP or desmopressin (synthetic analogue of ADH) given intranasally or orally.

Prognosis 15% spontaneous resolution of symptoms per year. References 1 Walsh PC, Retik AB, Vaughan ED Jr, Wein AJ (eds) (2002) Campbell’s Urology, 8th Edition. Philadelphia: W.B. Saunders/Elsevier, p. 2287.

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