Embryology/Developmental

Question 1

Discuss the body wall abnormality seen in Triad/Prune Belly Syndrome. Explain the histology of the musculature.

Answer 1

Deficiency of abdominal wall musculature = musculature variably affected.

• Medial and inferior abdominal wall most severely affected (peripheral musculature often normal).
• Histology - increased collagen, smaller muscle fibres, myofilamentous disarray and loss.

Also associated with - bilateral hydroureteronephrosis, bilateral undescended testes, megacystis.

Question 2

What are the two parts of the umbilical cord

Answer 2

1. Pars vasculosa (left sided) - umbilical vessels
2. Pars flaccida (right sided) - space into which the intestinal loops will herniate.

Question 3

What are some common associated abnormalities of CDH?

Answer 3

Cardiac (25%) - VSD, tetralogy of Fallot, transposition of great vessels, coarctation of the aorta.

Tracheobronchial (18%) - Tracheal stenosis, trifurcated trachea.

Skeletal (33%)

Neural tube defects - strongly associated with foetal/perinatal demise.

Common syndromes: Trisomy 21, Trisomy 13, Trisomy 18, Beckwith-Wiedemann Syndrome, Goldenhar Syndrome.

Question 4

What are the long term functional implications of OA?

Answer 4

• GORD
  
  • Mobilisation of the distal pouch (affecting the anatomy at the GOJ) plus abnormal motility in patients with OA.
• Stricture
  
  • Anastomotic
    
    • One of the most common implications - Incidence 20-60%
    • Exacerbated by anastomotic leak (20%)/mediastinitis, transanastomotic tube.
  • Peptic
• Recurrent TOF (3-15%)
• Tracheomalacia
• Vocal cord dysfunction (5%)
• Respiratory morbidity
• Scoliosis, rib fusion, chronic pain.

Question 5

What are the associated anomalies that can occur with gastroschisis?

Answer 5

Normally not associated with significant syndromes.

• Jejunoileal atresia (25%)
• Short gut syndrome from insult/necrosis of the herniated bowel - “vanishing gastroschisis
• Always associated with a form of non-rotation of the gut.
• Associated with foetal demise (thought likely due to volvulus)

Question 6

Describe the risk factors associated with developing gastroschisis

Answer 6

Exogenous:

• young maternal age,
• tobacco smoking.
• Oestrogen ‘disruptors’ - i.e.pesticides

Genetic:

• Possible genetic predisposition, unknown at this stage (siblings with gastroschisis).

Question 7

Describe 2nd branchial apparatus anomalies

Answer 7

• Second branchial apparatus anomalies (95%) :
  
  • Tract follows carotid sheath to the level of the hyoid bone.
    
    • Four types:
      
      1. Type 1 = Superficial to the SCM
      2. Type 2 (Most common)= Lies deep to the SCM, abuts the carotid sheath.
      3. Type 3 = Deep to SCM, travels between internal and external carotid arteries, ends lateral to pharynx.
      4. Type 4 = Medial to the carotid sheath, adjacent to tonsillar fossa.

Question 8

What are the features of Triad/Prune Belly Syndrome

Answer 8

Deficiency of abdominal wall musculature

Hydroureteronephrosis

Megacystis

Undescended testis (usually bilateral intra-abdominal)

Question 9

Explain the different types of chest wall deformity, including Poland’s syndrome

Answer 9

Pectus Excavatum (80%)

Present at birth, but worsens with growth (esp puberty)

Physiological implications for cardiac function due to compression (decreased cardiac output, mitral valve prolapse, arrthymias) and respiratory function (decreased chest wall compliance, loss of pump handle movement of sternum).

Pectus carinarum (12%)

Usually affects lower segment or body of sternum (chondrogladiolar)

Often noticed in adolescence following rapid pubertal growth.

Physiological implications - dyspnoea, reduced exercise tolerance, exertional dyspnoea, occasional MV prolapse.

Poland Syndrome - 1 per 30000

Dysplasia of breast, pectoralis muscles, (AND/OR serratus anterior, rectus abdominis, latissimus dorsi) and ribs plus limb deformities.

Question 10

Describe the classification system for jejunoileal atresia

Answer 10

Question 11

By the 10th week gestation, what structures are travelling through the umbilicus

Answer 11

Allantois

Umbilical vein

Umbilical arteries (left and right)

Physiological midgut hernia (returns to abdomen weeks 10-12)

Question 12

Describe the embryological basis and natural history of dermoid cysts

Answer 12

Dermoid cysts are ectodermal inclusions - the elements become trapped beneath the skin along median or paramedic embryonic lines of fusion.

Dermoid cysts typically increase in size due to the ongoing accumulation of sebum. Infection uncommon, rupture possible. Malignant degeneration has been described.

May contain persistent connections to the neural tube/CNS

Question 13

What are the types of CDH and how frequently do they occur?

Answer 13

Bochdalek type (posterolateral - 90%)

Usually left sided (80% due to right side of diaphragm closing before left.

Morgagni (anteromedially - 10%)

Question 14

What are the pathological findings in CDH?

Answer 14

• Lung hypoplasia

Typically occurs during the pseudoglandular stage (and affects all subsequent stages) of lung development when bronchiolar divisions occur. In CDH, there are fewer bronchiolar divisions and increased airways muscle thickness.Affects the development of the acinus - at birth thought to be few ‘normal’ alveoli.

• Thick walled pulmonary vasculature (high resistance)

Pulmonary vasculature develop occurs simultaneously with lung development, with arterial branching corresponding to bronchiolar divisions etc. Therefore there are fewer arterial vessels in the hypoplastic lungs of CDH. Arterioles are also thick walled (adventitia, media) and _non-complian_t. This corresponds to persistently high pulmonary vascular resistance even after birth –> pulmonary hypertension.

Question 15

Describe the development of the respiratory system.

Answer 15

• Respiratory system first appears as a ventral diverticulum off the foregut (oesophagus) at week 4/40.
  
  • Separation of respiratory and GI tract thought to occur due to the tracheo-oesophageal septum that separates the two.
• Tracheal bud/diverticulum then divides into tracheobronchial buds and lung development begins to occur as per the 5 stages:
  
  • Embryonal
  • Pseudoglandular
  • Cannalicular
  • Saccular
  • Alveolar
  • (microvascular)

Question 16

Describe the types of oesophageal atresia

Answer 16

5 types:

• Type A (6%) = Proximal atresia, nil fistula - aka long gap OA .
• Type B (5%) = Proximal fistula, distal atresia
• Type C (85%) = Proximal atresia, distal fistula
• Type D (1%) = Proximal and distal fistula
• Type E (4%) = H type TOF/OA

Question 17

List common associations with duodenal atresia

Answer 17

45-65% of patients with duodenal atresia will have associated anomalies.

• 50% will have Trisomy 21
• 30% will have malrotation.
• 25-65% will have cardiac malformations

Question 18

Describe the embryological basis of thyroglossal duct remnants.

Answer 18

1. Thyroglossal duct begins as a diverticulum from the tuberculum impar (later foramen caecum) at the base of the tongue.
2. Thyroid descends along the thyroglossal duct, anterior to the hyoid bone, settling on the thyroid cartilage. Maintains a connection to the foramen caecum throughout descent.
3. Thyroglossal duct should obliterate once thyroid is settled.
4. If failure to obliterate or abnormal migration of the thyroid, can develop pathology.

Thyroglossal duct should never have an external opening on the skin (as duct never perforates the skin).

Thyroglossal duct cysts occur anywhere along the course of the thyroid descent.

Failure of thyroid migration = lingual thyroid.

Ectopic tissue is found in or near the duct in up to 45%.

Question 19

Describe 3rd and 4th branchial apparatus anomalies

Answer 19

Third and Fourth branchial apparatus anomalies are rare.

• Opening supraclavicular
• 3rd above the superior laryngeal nerve, 4th below superior laryngeal nerve.
• Both enter the pharynx through the pyriform sinus below the hyoid bone.
  
  • 4th are usually left sided, coursing from apex of pyriform sinus to the left lobe of the thyroid.

Question 20

What is exomphalos and what is it associated with?

Answer 20

Exomphalos is a congenital condition characterised by an abdominal wall defect (around the umbilicus) with herniation of abdominal contents, covered in a sac.

Associations:

Congenital heart disease

Trisomy 13, Trisomy 18 (most common 80-90% will have exomphalos), Trisomy 21

Beckwith-Wiedemann (30-80% will have exomphalos)

Question 21

What are the three main physiological abnormalities of CDH?

Answer 21

1. Pulmonary Hypoplasia
2. High pulmonary vascular resistance
3. Right to left shunt (ductus arteriosus remains open, foramen ovale remains open)
4. Persistent high pulmonary vascular resistance → right ventricular hypertrophy

Question 22

What are the 5 stages of lung development and when do they occur?

Answer 22

1. Embryonal (weeks 3-8) - lung bud off the foregut, then trachea and bronchial buds by 4th week.
2. Pseudoglandular (weeks 7-16) - Airway differentiation, bronchial airways develop.
3. Cannalicular (16-24) - development of airspace, crude alveolar sacs take shape, type 1 pneumocytes differentiate (functional gas exchange possible)
4. Saccular (weeks 24-40) - maturation of crude alveolar airspaces, surfactant synthesis.
5. Alveolar (birth until 8yrs) - alveolar maturation and multiplication

Question 23

What are the common pathogens in infected thyroglossal duct cysts?

Answer 23

Infection of thyroglossal duct cysts or sinuses is usually from an oral source.

• Haemophilus influenzae B
• Staphylococcus aureus
• Staphylococcus epidermis

Question 24

Describe 1st branchial apparatus anomalies

Answer 24

• 1st branchial apparatus anomalies (1%): cleft lip and palate, abnormalities of external ear, malformed internal ossicle.
• Type 1 (cystic masses) = only ectoderm, travels lateral to facial nerve, presents as swelling near the ear (adjacent to the external auditory canal - they are in fact duplications of the membranous auditory canal) - contain squamous epithelium but NO cartilage.
• Type 2 (cysts, sinuses or fistulae) = mesoderm and ectoderm, may contain cartilage, travels medial to facial nerve, presents as swelling inferior to the angle of the mandible or anterior to SCM.

Question 25

Describe the 5 types of oesophageal atresia.

Answer 25

Question 26

Describe the embryologic theories for the development of the diaphragm

Answer 26

4 components:

1. Pleuroperitoneal folds (radial ingrowth from lateral mesenchyme - week 4)
2. Septum transversum (from inferior aspect of pericardial cavity - week 4)
3. Oesophageal mesentery (fuses with pleuroperitoneal folds - week 6)
4. Body wall somites 3,4,5 - form the muscular component of the diaphragm (believed to be from the innermost thoracic muscles)

Complete closure of the pleuroperitoneal canals takes place by end of week 8.

Question 27

What are the embryological functions of the umbilicus?

Answer 27

1. Apex of lateral and craniocaudal body folding.
2. Site of vascular connection to placenta/mother (left umbilical vein, two umbilical arteries).
3. Site of physiological midgut herniation between weeks 6 and 10 gestation.

Question 28

What are the causes of umbilical discharge?

Answer 28

• Umbilical granuloma - small mass of granulation tissue from side of the cord.
• Patent urachus remnant - clear fluid/urine,
  
  • Remnant of allantois (failed to obliterate lumen) - connects dome of bladder to umbilical cord.
• Patent vitello-intestinal duct remnant - may be clear liquid or brown liquid.
  
  • Persistent embryological question between midgut and yolk sac.
• Omphalitis, infected urachal cysts → pus.

Question 29

What is omphalitis and what are the risks and why?

Answer 29

Omphalitis - infection of the umbilical stalk.

Associated with necrotising fasciitis.

Umbilicus exposed to bacteria of birth canal, and then becomes colonised after birth.

Necrotising fasciitis occur due to devitalised umbilical tissue with no blood supply and direct access to systemic blood supply via the thrombosed umbilical arteries or vein.

Question 30

What are the theories of CDH development?

Answer 30

1. Primary lung problem - Impaired post-hepatic mesenchymal plate → failed muscularisation of diaphragm
2. Failure to close the pleuroperitoneal canals → CDH → mass effect on lung and impaired lung development → Hypoplasia.

• The lumbocostal triangle remains as a remnant of the pleuroperitoneal membrane, closure requires fusion of the lumbar and costal muscle groups.

Question 31

Describe the histopathological features of the thyroglossal duct.

Answer 31

1. Epithelial lining - stratified squamous epithelium or ciliated pseudo stratified columnar epithelium.
2. May contain mucus secreting glands.
3. May contain ectopic thyroid in 10-45%

Question 32

Name 5 conditions associated with umbilical hernia

Answer 32

Trisomy 13

Trisomy 18

Trisomy 21

Beckwith-Wiedemann

Congenital hypothyroidism

Mucopolysaccharidases

Question 33

Describe the anatomy of an epigastric hernia and explain how they produce symptoms

Answer 33

Epigastric hernia refers to a midline defect in the linea alba (between umbilicus and xiphoid process allowing the protrusion of abdominal contents (pre-peritoneal fat).

• Incarcerated pre-peritoneal fat can cause pain, swelling, erythema (necrosis)

Question 34

What are the types of duodenal atresia and what are the presumed aetiologies?

Answer 34

Type 1 (windsock/obstructing septum or web) - 92% - presumed secondary to failure of recanalisation of duodenum.

Type 2 - 1% - short fibrous cord connects the two blind ends of duodenum. Nil mesenteric defect - failure of recanalisation.

Type 3 - 7% - nil connection between the two ends, V shaped defect in the mesentery (presumed secondary to vascular insult)

Question 35

What are the characteristics of bronchopulmonary sequestration?

Answer 35

• Non functioning lung tissue, supplied by an anomalous systemic artery.
  
  • Nil brachial connection to native tracheobronchial tree.
• Pathogenesis:
  
  • Develops from a supernumerary lobe from abnormal budding early in foregut embryogenesis.
    
    • If this occurs before the development of the pleura → sequestration becomes invested within adjacent lung = intralobar sequestration (pulmonary venous drainage, lower lobes only).
    • If this occurs after the development of the pleura, the bud grows separately and develops its own pleural covering = extralobar sequestration (either systemic or pulmonary venous drainage).
      
      • Extralobar can be within the thorax, within the diaphragm or in a subdiaphragmatic location.

Question 36

What is the underlying aetiology of gastroschisis and when does it occur?

Answer 36

Gastroschisis is thought to occur from a prenatal rupture of the physiological hernia (an acquired condition of intrauterine life rather than a developmental condition).

Believed to occur around the 8th week gestation (midgut returns to abdomen by 10th week)

Question 37

How does the umbilical ring close after birth?

Answer 37

Requires the following:

1. Lateral body wall folding medially.
2. Fusion of the rectus abdominis muscles with the linea alba
3. Umbilical orifice contraction (aided by elastic fibres of the obliterated umbilical arteries, and assisted by fibrous proliferation of lateral connective tissue plates and mechanical stress from the rectus muscle tension).

Failure of any of the above processes results in an umbilical hernia.

Question 38

Describe the natural history of umbilical hernias?

Answer 38

• Umbilical ring continues to close post birth (weeks, months and years after), and the fascia of the umbilical defect strengthens.
  
  • 90% will close spontaneously by 1 year of age.
  • 50% present by 5 years, will close by 11 years.
• Defect diameter > 1.5cm, less likely to close.
• Defect < 1cm, likely to close, and close more quickly.

Question 39

Describe the most widely accepted theory of the development of exomphalos

Answer 39

Combination of the embryonic dysplasia theory along with malfunction of the ectodermal placodes.

• Embryonic dysplasia - early germinal disc defects lead to a number of malformations seen with ‘amniotic band sequence’ (also affects craniofacial region, body wall, limbs).
  
  • Extremely early defect, but manifestations of germ disc defects appear later.
• Embryonal dysgenesis (due to malformation of embryonic placodes in early development).
  
  • Thought to lead to malfunction of the embryonic folding process → body wall defects.
  • Placodes at the umbilical ring serve as a transition zone depositing mesoectodermal cells that will later contribute to the ventral abdominal wall.
    
    • Malformation of the embryonic placodes → abnormal deposition of mesoectodermal cells → underdeveloped ventral body wall and enlarged umbilical ring.

Question 40

What are the sequelae associated with congenital lung lesions?

Answer 40

• Antenatal:
  
  • Large lesions can cause mediastinal shift → hydrops.
• Post-natal
  
  • Infection:
    
    • Recurrent infection and trapping of bacteria (CPAM).
  • Airtrapping, pneumothorax (CPAM).
  • High output cardiac failure (sequestration)
  • Malignancy
    
    • Pleuropulmonary blastoma (Type I CPAM)
    • Bronchioalveolar carcinoma (Type II CPAM)

Question 41

What are the pathological characteristics of CPAM?

Answer 41

• Adenomatoid increase in terminal respiratory bronchioles (extensive overgrowth of immature primary bronchioles localised to a segment of the bronchial tree).
• Cysts are non-functional from gas exchange perspective, but remain connected to tracheobronchial tree.
• Macrocystic (cysts >5mm) vs microcytic lesions appear solid on USS.
• Histology:
  
  • Polypoid projections of mucosa
  • Increase in smooth muscle and elastic tissue in cyst walls.
  • Absence of cartilage
  • Mucus secreting cells.
  • Absence of inflammation

Question 42

What is the pathogenesis of jejunoileal atresias?

Answer 42

Jejunoileal atresias are thought to occur secondary to a prenatal mesenteric vascular insult.

May represent outcome of a volvulus, foetal intussusception

Question 43

Describe a IIIb jejunoileal atresia

Answer 43

• “Apple peel” type of atresia. Aka Christmas Tree or Maypole.
• Blind ending proximal limb with grossly dilated bulb with blood supply from proximal branch of SMA.
• SMA is absent beyond the middle colic branch.
• Distal small bowel coiled around a single vessel (usually ileocolic or right colic arcades - perfusion is in a retrograde fashion)
• 75% associated with short gut syndrome.
• Thought to be secondary to proximal SMA arterial occlusion → extensive infarction of midgut.

Question 44

What conditions are associated with colonic atresia?

Answer 44

Colonic atresia accounts for 15% of all GI atresias.

• ⅓ colonic atresias have associated anomalies.
  
  • Gastroschisis (2.5% of gastroschisis have associated colonic atresia)
  • Hirschsprung disease (though rare)
  • Complex urological malformations
  • Associated small bowel atresias.
  • Skeletal anomalies

Question 45

What are the 3 main pathological components of intestinal duplications?

Answer 45

1. Well developed smooth muscle coat
2. Epithelial lining representative of the GIT (usually the same as adjacent GIT structures) - may contain heterotopic mucosa (25%)
3. Intimate anatomic association with the GIT.

Question 46

What are two common theories for the formation of intestinal duplications?

Answer 46

1. Partial twinning
2. Split notochord theory (allows herniation of endoderm → duplication). Explains neuroenteric cysts.
3. Failure of recanalisation/vacuolisation → diverticuli that remain as duplications.

Question 47

How may a Meckel diverticulum present?

Answer 47

1. Bleeding (50% of all lower GI bleeds in children) - acid secretion from ectopic gastric mucosa causes ulceration and bleeding from mesenteric vessel.
2. Perforation - similar pathology to appendicitis - obstruction, stasis, bacterial overgrowth, oedema, lymphatic obstruction etc.
3. Volvulus - diverticulum with abdominal wall attachment may form axis around which the midgut can volve.
4. Intussusception - can act as pathological lead point in intussusception.
5. Bowel obstruction - mesodiierticular bands can cause band obstruction.

Question 48

Describe the histopathology of a Meckel diverticulum

Answer 48

• True diverticulum - contains all layers of the normal bowel wall.
• Diverticulum almost always occurs on the anti mesenteric border.
• 75% of the time there is no persistent mesodiverticular bands attaching Meckel to abdominal wall.
• Heterotopic mucosa occurs in 15-50% - gastric most common, then pancreatic.
• Neoplastic process present in up to 4% of Meckel diverticulum - malignant tumours predominate (95% occur >20years of age, mean age 56yrs).

Question 49

Discuss the process of normal intestinal rotation.

Answer 49

1. The midgut is attached to the body stalk via the vitelline duct (midpoint of the midgut).
2. During the 4th week gestation, rapid growth of the gut tube results in herniation into the body stalk with the SMA as its axis.
3. The first 90 degree counterclockwise rotation occurs outside the abdomen and results in the duodenojejunal limb on the right, and the caecocolic limb on the left (the caecal bud forms, and the DJ limb becomes elongated and convoluted).
4. At around the 10th week gestation, the midgut begins to return to the abdomen. The DJ limb returns first and rotates further to lie on the left side of the abdomen (the DJ flexure in the LUQ, and the SMA medial to DJ).
5. The caecocolic limb then returns to the abdomen, initially the caecum is in the RUQ before a further 90 degree rotation moves it to the RLQ. The transverse colon comes to lie in front of the duodenum.

Question 50

What is non-rotation of the midgut?

Answer 50

Non-rotation (most common form of malrotation) occurs when the gut fails to rotate at all.

• The DJ limb is on the right of the abdomen, and the caecocolic limb on the left.
• The base of the mesentery is very narrow, predisposing to volvulus.

Question 51

What is incomplete rotation of the midgut?

Answer 51

Incomplete rotation occurs when the midgut doesn’t achieve full 270 anticlockwise rotation (usually 180 degrees only).

• DJ on the right of the midline, caecum remains in RUQ. Associated with Ladd’s bands across the duodenum.
• Narrow base of mesentery predisposes to volvulus.
  
  • Most common form of surgically treated malrotation.

Question 52

What is reverse rotation of the midgut?

Answer 52

Reverse rotation occurs when the midgut loop rotates in the clockwise direction 90 degrees.

• The DJ is anterior to the SMA and transverse colon posterior to SMA.
• SMA can cause obstruction of the transverse colon.

Question 53

Describe the three types of malrotation

Answer 53

Question 54

Describe a classification system of anorectal abnormalities for both males and females

Answer 54

Anorectal malformations were historically classified as high or low malformations. Now classified according to the location of the fistula.

MALES

• Rectoperineal fistula (lowest type - rectum located within the sphincter mechanism).
• Rectourethral fistula (most common type in males) - may be rectobulbar (low) or rectoprostatic (high)
• Rectobladderneck fistula (10%) - high fistula opens into bladder neck.
• Anorectal atresia without fistula - closely associated with Trisomy 21
• Rectal stenosis

FEMALES

• Rectoperineal
• Rectovestibular (most common type) - 5% associated with two hemivaginas and a vaginal septum.
• Anorectal atresia without fistula - closely associated without fistula.
• Cloacal malformation (rectum, vagina and urinary tract fuse to create a single channel).

Question 55

How does ARM affect the surrounding tissues?

Answer 55

• Pelvic floor musculature development is variable - may be severe and almost completely absent, or normal.
• Sensation and proprioception:
  
  • Sensation is affected as most children with ARM don’t have anal canal (usually very sensitive and can discriminate solids, liquids and gases).
  • Proprioception is present to varying degrees - can often sense rectal distension.
    
    • Children with ARM have no control over loose stools or diarrhoea, but can often be toilet trained when they form solid stools and learn how to perceive it.
• Colonic and rectosigmoid motility - impaired in ARM.
  
  • Likely hypomotility of the sigmoid → constipation → chronic rectal distension → further impaired mobility → further distension → loss of proprioception → worsening constipation → megasigmoid → incontinence.
  • Constipation worse in lower ARMs.
• Sacral development affected in ARMs.
  
  • Normal sacral development correlates closely to normal development of pelvic muscles and nerves.
• Tethered spinal cord

Question 56

What are the associations with anorectal malformation

Answer 56

VACTERL

• Genitourinary - 33-50% of ARMs (most commonly with higher lesions)
  
  • Most common pathology is vesicoureteric reflux, next most common renal agenesis.
  • Undescended testis occurs in 20% of males with ARM.
  • Hypospadias occurs in 5% of males with ARM.
• Cardiovascular - 33%
  
  • Most commonly ASD, PDA, TOF, VSD
• Gastrointestinal - 12%
  
  • Oesophageal atresia (10%)
  • Duodenal atresia (2%)
• Spinal - tethered cord.
• Gynecological
  
  • Hydrocolpos
  • Vaginal duplication
  • Uterine malformations

Question 57

What is a ureterocoele? What are the implications of ureterocoele?

Answer 57

Ureterocoele is a cystic dilatation of the intravesical portion of the ureter.

• 80% occur in females.
• Often associated with duplex collecting system, normally upper pole moiety - 80% of complete duplications will have upper pole moiety ureterocoele.
  
  • Utererocoeles are associated with obstructive uropathy.
• When single system ureterocoeles occur, they are more likely to occur in males and are often associated with other abnormalities of the kidney (fusion, ectopic, MCDK).

Question 58

What is megaureter and what are the causes?

Answer 58

Megaureter refers to a ureteric diameter >7mm.

• Primary obstructing megaureter
  
  • Typically caused by a distal dynamic ureteric segment (VUJ obstruction), but can be caused by ureteric valves or ectopic UO.
• Secondary obstructing megaureter
  
  • Obstruction outside of ureter - Urethral obstruction, extrinsic mass/tumour
• Primary refluxing megaureter
  
  • Inadequate valvular mechanism associated with the diameter of the ureter and the length of submucosal ureter within the bladder wall.
    
    • Vesicoureteric reflux.
• Secondary refluxing megaureter.
  
  • Urethral valves, or neurogenic bladder.
• Refluxing AND obstructing megaureter
• Non-refluxing, non-obstructing megaureter

Question 59

List four causes of pelvicoureteric junction obstruction

Answer 59

1. Intrinsic stenosis secondary to failure of recanalisation.
2. Extrinsic compression from crossing lower pole vessels or mass/tumour.
3. Ureteric valve (mucosal fold)
4. Ureteric polyp

Question 60

Describe autosomal dominant polycystic kidney disease and its associations.

Answer 60

Inherited disorder occurring in 1 in 500 births, characterised by cysts throughout the cortex and medulla (neonatal form = glomeruli).

Associations:

• Biliary cysts
• Splenic cysts
• Pancreatic cysts
• Colonic diverticuli
• Berry aneurysms
• Hypertension

Question 61

How do multicystic dysplastic kidneys occur?

Answer 61

MCDK thought to occur secondary to severe, early ureteric obstruction.

• Failure of recanalisation of the proximal ureter.
• Failure in ureteric bud/metanephric cap penetration.

Associated with:

• Contralateral VUR (40%) and PUJ obstruction (10%)
• Increased risk of Wilm’s tumour (4 times the risk of the general public).

Question 62

Describe the radiological findings on MCDK.

Answer 62

Ultrasound: non-reniform shape, multiple cysts without communication “bunch of grapes”, nil central cyst (pelvis), nil cortex. Hyperechoic parenchyma, seen between cysts.

• May also show evidence of hydronephrosis or hydrometer on contralateral kidney (VUR in 40%, PUJ obstruction 10%).

Renogram (DMSA, Mag 3): nil function in affected kidney.

Question 63

What is Potter’s Syndrome? When does it occur - name 3

Answer 63

Potter’s Syndrome occurs from compression of the foetus secondary to oligohydramnios.

• Facies; Low set ears, beaked nose, downward slant to eyes.
• Limb deformities

Associated with:

• Bilateral renal agenesis (incompatible with life)
• Posterior urethral valves
• Autosomal recessive polycystic kidney disease
• Prune Belly/Triad Syndrome

Question 64

Which factors contribute to long term outcome in patients with posterior urethral valves?

Answer 64

3 factors:

• Degree of renal dysplasia/CKD (as per creatinine nadir in first year of life).
• Degree of bladder dysfunction
• Incidence of UTI with or without VUR

Question 65

What are the childhood sequelae of posterior urethral valves?

Answer 65

• Renal dysplasia (secondary to high bladder pressures during development) → CKD → ESRF
  
  • Associated impaired concentrating capacity → polyuria (further exacerbates bladder dysfunction and incontinence)
• Bladder dysfunction
  
  • Thick walled, low capacity, low compliance bladder (abnormal fibrosis and collagen deposition in bladder wall).
• Urinary incontinence (up to 50%)
  
  • Overactive bladder from uninhibited detrusor contractions plus polyuria (impaired ability to concentrate urine)
• Valve bladder
  
  • Persistence of upper tract dilatation, bladder wall hypertrophy, VUR following valve ablation.
  • Bladder often transitions from low capacity, low compliance, over-active to dilated, high pressure, then eventually high volume, low contractility and impaired emptying (myogenic failure).
    
    • Thought to represent irreversible changes to the smooth muscle cells with deposition of type III collagen.

Question 66

What is the embryological theory for formation of Prune Belly Syndrome/Triad Syndrome?

Answer 66

• Theory 1 - Transient Urethral Obstruction
  
  • Prune belly thought to be secondary to transient urethral obstruction during development → megacystis, hydroureteronephrosis → physically obstructs the descent of the testis and causes abdominal wall atrophy.
  • Urethral obstruction may be secondary to delayed canalisation of the urethra (weeks 11-16)
    
    • OR
  • Urethral obstruction secondary to hypoplastic prostate which may cause the urethra to twist and obstruct (prostatic Hypoplasia seen in PBS patients)
• Theory 2 - Abdominal mesodermal maldevelopment
  
  • Unknown event affects the mesoderm between weeks 6 and 10/40.
    
    • Abdominal wall musculature abnormality - Failure of lateral plate mesoderm migration/folding.
    • Genitourinary abnormality - impaired intermediate mesodermal development.
• Theory 3 - Intrinsic defect in the urinary tract.

Question 67

How does the bladder pathology in Prune Belly Syndrome affect function?

Answer 67

Prune Belly Syndrome bladder = reduced muscle fibres, laterally displaced ureteric orifices, bladder neck poorly defined.

Bladder function:

• Normal bladder compliance
• Massive bladder capacity (megacystis)
• Loss of first sensation to void
• Poor detrusor contraction → incomplete emptying.
• Laterally displaced ureteric orifices → increased rate of vesicoureteric reflux.

Question 68

How does Prune Belly Syndrome affect ureteric and renal function?

Answer 68

• Ureteric pathology = laterally displaced UO’s predispose to reflux. Ureters severely dilated and tortuous. Decreased muscle fibres (particularly in the distal ureter).
  
  • Ureteric Function = impaired peristalsis → upper tract stasis and dilatation.
• Renal pathology = low pressure dilated urinary system from renal pelvis to urethra. May be associated with dysplasia (50%) → progressive uropathy occurs and 20-30% end up with ESRF.
  
  • Progression of uropathy caused by recurrent infection and obstruction.
  • Renal Function = dysplasia → CKD, VUR → infection → exacerbates CKD → ESRF

Question 69

What are the non-urologic associations of Prune Belly Syndrome?

Answer 69

• Deficiency of abdominal wall musculature (midline, inferior worst affected)
• Pulmonary (60%)
  
  • Lung Hypoplasia (secondary to oligohydramnios)
    
    • 50% will require neonatal ventilation (combination of lung Hypoplasia and deficiency of abdominal musculature → accessory muscles of respiration)
  • Recurrent infections secondary to inadequate cough (muscle deficiency)
• Cardiac (25%)
  
  • PDA, ASD, VSD, Tetralogy of Fallot
• Gastrointestinal tract
  
  • Incomplete rotation of the midgut.
    
    • Atresias previously documented.
  • Anorectal malformation
• Orthopaedic
  
  • Talipes
  • Scoliosis
  • Pectus

Question 70

How would you differentiated Prune Belly from posterior urethral valves on imaging?

Answer 70

• MCUG:
  
  • Prune Belly Syndrome -
    
    • Bladder: dilated, smooth walled (may have patent urachus).
    • Bladder neck: wide, nil hypertrophy
    • Urethra: Often dilated anterior urethra.
  • Posterior urethral valves -
    
    • Bladder: thick-walled, trabeculated.
    • Bladder neck: hypertrophy
    • Urethra: Normal anterior urethra, obstruction in posterior urethra.

Question 71

Describe the embryology of the urethra.

Answer 71

• Urethra forms in 2 parts: the penile urethra (endoderm) and the glanular urethra (ectoderm)
  
  • Penile urethra begins to form from the genital tubercle at 6/40
    
    • Two genital folds form caudal to the genital tubercle.
      
      • The urethral plate forms between the two genital folds.
      • Paracrine testosterone from the testes cause the inner genital folds to fuse medially and create a tube from the urogenital sinus to the coronal groove.
      • Whole of the penile urethra is complete by the end of the 1st trimester.
  • Glanular urethra
    
    • Forms from ectodermal ingrowth on the glans.
• Following formation of the urethra, the penile structures (dorsal then ventral) and then the prepuce develop.

Question 72

Describe the aetiology of hypospadias

Answer 72

• Following formation of the urethra, the penile structures (dorsal then ventral) and then the prepuce develop.
  
  • When there is an issue with the development of the urethra, the penile and preputial structures developing later are also impaired.
    
    • Hence deficiency of ventral tissue and hooded prepuce.
• Abnormalities in development → hypospadias.
  
  • Caused by:
    
    • Inadequate hormone stimulation, maternal/placental factors and environmental factors
    • Deficient androgen production or failure of conversion to the more potent dihydrotestosterone (5-alpha reductase dependent), insufficient HCG production or faulty androgen receptors.
    • In utero exposure to medications → valproate, loperamide, paroxetine, oestrogen meds.
    • Genetic syndromes:
      
      • WAGR (Wilms’ Tumour, Aniridia, Genitourinary abnormalities, mental retardation) - associated with WT1 gene.
      • Denys-trash syndrome (GU malformations and Wilms’ tumour) - WT1

Question 73

What are the two phases of bladder function?

Answer 73

Storage Phase:

• Detrusor
  
  • Relaxation - sympathetic control (noradrenaline)
• Internal Sphincter
  
  • Contraction - sympathetic control (noradrenaline)

Voiding Phase:

• Detrusor
  
  • Contraction - parasympathetic control (Acetylcholine)
• Internal Sphincter
  
  • Relaxation - parasympathetic control (Acetylcholine)

Question 74

Describe various classifications of neurogenic bladder

Answer 74

• Failure to store:
  
  • Detrusor hyperactivity → poor bladder compliance → elevated bladder pressures and incontinence.
  • Incompetent bladder neck or urethral sphincter mechanism → failure to store urine (even with low pressures) → incontinence.
• Failure to empty:
  
  • Hypotonic bladder, overstretched, myogenic failure → unable to generate pressure to empty.
  • Increased output resistance
    
    • Detrusor/Sphincter Dyssynergy - loss of coordinated detrusor contraction with sphincter relaxation.
• Combination of both

Question 75

How do you calculate the bladder capacity of (a) a 6 month old, (b) a 4 year old?

Answer 75

Infants = 38 + (2.5 x age in months) = 38 + (2.5 x 6) = 53ml

Older children = (Age in years +2) x 30 = 180mL

Question 76

At what bladder storage pressure does renal injury occur?

Answer 76

40cm H20

(Normal filling pressure is 5-10 cm H20)

Question 77

Discuss the factors that determine the potential resolution of vesicoureteric reflux

Answer 77

• Grade of reflux (1-5) - lower grades more likely to resolve.
• Age of child (younger children more likely to resolve)
• Appearance of the UO
• Length of submucosal tunnel
• Intravesical detrusor filling pressures

Question 78

Discuss the reasons for resolution of vesicoureteric reflux

Answer 78

• VUR can resolve, particularly in younger children.
  
  • Increased trigonal growth → improved submucosal tunnel length + trigonal function.
  • Fewer uninhibited detrusor contractions with increasing age → stabilisation of bladder dynamics.

Question 79

What are the bladder/ureter factors that contribute to vesicoureteric reflux?

Answer 79

• Bladder:
  
  • High bladder pressure (PUV, neurogenic bladder)
  • Weak floor of submucosal tunnel (neurogenic bladder, diverticulum)
• Ureter
  
  • Short submucosal tunnel

Question 80

When are the important testosterone surges in development of the male genitalia? Which cells produce testosterone?

Answer 80

Testosterone is produced by the Leydig cells in the testis.

Week 7 to 14 - Testosterone and conversion to dihydrotestosterone in genital skin → male external genitalia

Neonatal - 2nd and 3rd month - brain related male type behaviours.

Question 81

Give an example of 46XX DSD and the mechanism

Answer 81

46XX DSD - overandrogenisation (excess androgen) - most common form of DSD.

• Congenital adrenal hyperplasia -
  
  • Enzyme deficiency results in inability to form cortisol, instead precursors are shunted towards mineralocorticoid or sex-steroid pathways.
    
    • Most commonly 21-hydroxylase deficiency (90% of CAH) - essential for conversion of progesterone into doxycorticosterone → corticosteroid or aldosterone.
  • No negative feedback from cortisol to pituitary → ongoing excess ACTH production → excess androgens → overvirulisation.
  • As adrenal differentiation occurs at 11 weeks gestation (after formation of gonads and reproductive tract) ONLY external genitalia are affected.

Question 82

Describe the types of 46XX DSD

Answer 82

• Type 1 and 2 (21-hydroxylase deficiency - 90%)
  
  • Type 1 - NON SALT WASTING = only affects 21-hydroxylase in zona fasciculata (production of aldosterone preserved).
  • Type 2 - SALT WASTING = affects zona glomerularis (aldosterone production) and zona fasciculata (cortisol production)
    
    • Results in dehydration and or vascular collapse, hyperkalaemia (due to no aldosterone)
• Type 3 (11-beta hydroxylase deficiency)
  
  • Produces virulisation and HTN (excess deoxycorticosterone → Na reabsorption, fluid overload, HTN, hypokalaemic acidosis.
• Type 4 (3-beta-hydroxylase deficiency)
  
  • SEVERE salt wasting, survival uncommon.
  • Occurs in BOTH 46XX and 46XY

Question 83

Describe the mechanism of salt wasting in congenital adrenal hyperplasia

Answer 83

Salt wasting occurs most commonly in Type 2 congenital adrenal hyperplasia.

• 21 hydroxylase deficiency affecting both the zona glomerularis (aldosterone) and zona fasciculata (cortisol).
  
  • Lack of aldosterone → excretion of Na and H20 by the kidney as well as hyperkalaemia.
    
    • Aldosterone normally acts on the distal convoluted tubule to increase ENAC and Na/K ATPase → Na/K exchange (reabsorption of salt, water follows passively).

Also occurs in type 4 CAH - salt wasting severe, survival uncommon.

Question 84

Describe mixed gonadal dysgenesis and potential sequelae

Answer 84

• Mixed gonadal dysgenesis is the second most common form of neonatal ambiguous genitalia.
  
  • Usually have testis on one side and streak gonad on the other (normal ovarian stromal tissue, nil oocytes).
  • Internal ductal structure consistent with ipsilateral gonad (streak gonad will have Fallopian tube and uterus).
• Karyotype = 45 XO/46XY
• Phenotype is ambiguous but usually masculinised.
• Associated with:
  
  • High rates of gonadal tumours (20% in either testis or streak gonad).
  • Associated with increased risk of Wilms tumour.
  • Denys-Drash syndrome in 5% (ambiguous genitalia, Wilms tumour, glomerulopathy, HTN)

Question 85

Describe 3 causes of primary amenorrhoea

Answer 85

• DSD
  
  • Complete androgen insensitivity syndrome (CAIS) - 46XY undervirilisation - phenotypically female (nil paramesonephric duct structures - uterus, fallopian tubes).
  • Leydig cell abnormalities - impaired testosterone production in 46XY → phenotypically female (nil paramesonephric duct structures)
  • Mayer-Rokitansky-Kuster-Hauser Syndrome
    
    • 46XX with normal female phenotype AND normal ovaries and Fallopian tubes, but rudimentary uterus.

Question 86

Discuss the theories of extrophy-epispadias complex

Answer 86

• Overdeveloped cloacal membrane - prevents medial migration of the mesenchymal tissue (lateral plate mesoderm) and impairs the normal development of the lower abdominal wall.
  
  • Presentation depends on timing of rupture of the cloacal membrane.
    
    • Premature rupture of cloacal membrane → more severe forms of extrophy-epispadias complex (prevents mesodermal migration in the midline → defects in bladder, urethra and hindgut.
    • Persistence of cloacal membrane → wedge effect that blocks the medial migration of mesoderm from fusing in the midline.
• Maldevelopment of the bony pelvis → extrophy-epispadias complex.

Question 87

Describe 5 anatomic abnormalities associated with bladder extrophy and epispadias

Answer 87

1. Bony pelvis: increased pubic diastasis, shorter pubic rami, external rotation of AP pelvis.
2. Pelvic floor: irregular pelvic floor musculature (affects ability to achieve continence)
3. Spinal defects: Spina Bifida occulta, scoliosis, spinal dysraphism
4. Abdominal wall defects: triangular abdominal wall defect becomes filled with extrophied bladder and posterior urethra. Umbilicus is at the upper end of the fascial defect.
5. Indirect inguinal hernias - 80% of males, 10% of females.
6. Anorectal defects: anteriorly displaced anus, short and broad perineum.
7. Male genital defect: shortened penis deficiency of anterior corporeal tissue (epispadias), UDT
8. Female genital defect: short vagina, bifid clitoris, cervix on anterior vaginal wall.
9. Urinary tract: small, polyp filled bladder, abnormal UO (100% VUR), upper tract normal (97% of the time)

Question 88

What is OEIS?

Answer 88

OEIS is a severe form of cloacal extrophy:

• O = omphalocoele.
• E = Extrophy
• I = Imperforate anus
• S = Spinal defect

Question 89

What is Mayer-Rokitansky-Kuster-Hauser?

Answer 89

46XX

Normal ovaries and Fallopian tubes.

Rudimentary uterus, short vagina. Associated with primary amenorrhoea

Gastrointestinal association: Anorectal malformation

Genitourinary association: Renal agenesis or ectopia

Other: Polydactyly, cervicothoracic rib defects

Question 90

Classify the types of testicular torsion

Answer 90

Torsion can be classified as perinatal vs adolescent, OR intravaginal vs extravaginal

• Extravaginal torsion (perinatal): torsion of the testis and tunica vaginalis as the tunica vaginalis is not firmly fixed to the dartos layer of the scrotum, allowing both testis and tunica vaginalis to rotate on the vascular pedicle.
• Intravaginal torsion (childhood + adolescence): torsion of the testis within the tunica vaginalis. Associated with bellclapper testis and high investment of the tunica vaginalis on the spermatic cord.
  • Puberty → rapid testicular growth, with horizontal lie, predisposes testis to torsion.

Question 91

What is the embryological origin of testicular appendage versus epididymal appendage?

Answer 91

Epididymal appendage = remnant of the cranial end of the mesonephric duct.

Testicular appendage (Hydatid of Morgagni) = paramesonephric duct remnants (remnants of Fallopian tube)

Question 92

Give 5 differential diagnoses for acute scrotum

Answer 92

Testicular torsion

Torsion of testicular appendage

Torsion of epididymal appendage

Epididymo-orchitis (Bacterial vs viral)

Idiopathic scrotal oedema

Henoch-Schonlein Purpura (vasculitis - ⅓ will develop pain, erythema and scrotal and spermatic cord oedema)

Question 93

What is GLUT1?

Answer 93

GLUT 1 is an erythrocyte glucose transporter of placental origin. It is found in infantile haemangiomas, suggesting a placental origin.

Question 94

Describe the clinical history of infantile haemangiomas

Answer 94

• Infantile haemangiomas are the most common tumour of infancy (occurring in 4% of all infants).
  
  • 3 phases: proliferative, involuting, involuted.
    
    • Median age of onset 2 weeks (though 30-50% have a cutaneous sign at birth)
      
      • Mostly cutaneous (80%)
        
        • Head and neck most commonly (60%), trunk (25%), extremities (15%)
          
          • Superficial dermal tumours - red, raised lesions. Can ulcerate.
          • Deep dermal tumours/subcutaneous fat/muscle - appear bluish, raised overlying skin.
  • Proliferative phase
    
    • Rapid growth for 6-8 months, plateau at 12 months.
  • Involuting phase
    
    • Slow involution between ages 1 and 7 (50% by 5 years, 70% by 7 years). Entirely regressed by 10-12yrs.
  • Involuted phase
    
    • 50% of children have nearly normal skin at the site of previous lesion.
      
      • Larger tumours may leave lax, redundant skin with whitish or yellowish discolouration.
      • Ulcerated lesions will leave scars.

Question 95

Describe the 3 phases of infantile haemangiomas.

Answer 95

• 3 phases = proliferative, involuting and involuted phases.
• Proliferative = from onset of tumour (usually week 2), rapid growth for 6-8 months, then plateau at around 10-12 months.
  
  • Associated with expression of multiple vascular growth factors → rapidly dividing endothelial cells.
• Involuting = slow involution between ages 1-7, with 50% involuted by 5yrs, 70% by 7yrs. All by 10-12 years.
  
  • Associated with tissue factors associated with inhibition of vascular growth (i.e. TIMP1) → flattening of cells → apoptosis and replacement with fibrofatty stroma.
• Involuted = 50% leave no sign of previous vascular tumour. Larger lesions may have lax/reduntant overlying skin or yellowish/white discolouration. Ulcerated lesions may leave scar.

Question 96

What are the complications of infantile haemangiomas?

Answer 96

• Complications depend upon size and location:
  
  • Head and neck -
    
    • Airway compromise for large cervicofacial lesions during proliferative phase
    • Periorbital and eyelid infantile haemangiomas can cause visual axis obstruction.
    • Large, ulcerated lesions will cause significant deformity and scarring.
  • GI lesions -
    
    • Rare, but can present with GI bleeding.
  • Large lesions can cause high output cardiac failure (usually associated with liver haemangiomas).

Question 97

What are the congenital anomalies associated with infantile haemangiomas?

Answer 97

• Infantile haemangiomas are rarely associated with other congenital anomalies.
  
  • Head and neck
    
    • PHACES
      
      • Posterior fossa malformations
      • Haemangioma of the face
      • Cardiac defects and coarctation
      • Eye abnormalities
      • Sternal non-union
      • Supraumbilical raphe
  • Trunk
    
    • Cervicothoracic: sternal nonunion.
    • Perineum: ARM
    • Lumbrosacral: underlying spinal dysraphism
  • Haemangiomatosis - disseminated haemangiomas (cutaneous lesions < 5mm, dome like) - often associated with liver and GI haemangiomas.

Question 98

What are the differences between infantile haemangiomas and congenital haemangiomas?

Answer 98

• Infantile haemangiomas
  
  • Not present at birth, median onset 2 weeks age, grows rapidly (proliferative phase) until 10-12 months. Involution occurs slowly from 1-7yrs.
  • Most commonly on the head and neck.
  • Associated with GLUT1 (erythrocyte glucose transporter)
• Congenital haemangiomas
  
  • Fully developed at birth, nil post natal proliferation, rapid involution within 6-14 months.
  • More common on the limbs
  • NOT associated with GLUT-1

Question 99

What are the types of hepatic haemangiomas of infancy?

Answer 99

• Focal:
  
  • Hepatic equivalent of (RICH - rapidly involuting congenital haemangioma).
    
    • Fully developed at birth, rapid regression/involution.
  • Negative GLUT-1
  • May be associated with transient anaemia and moderate thrombocytopaenia (intralesional thrombosis).
  • May have macrovascular shunts → high output cardiac failure.
• Multi-focal:
  
  • True infantile haemangioma.
    
    • Similar to cutaneous infantile haemangiomas and often associated with them.
  • Positive GLUT-1 staining.
  • Often associated with hypothyroidism, macrovascular shunts may be associated with high output cardiac failure.
• Diffuse:
  
  • True infantile haemangioma, far more dangerous.
  • Similar involution, positive GLUT-1.
  • All patients have severe hypothyroidism secondary to high levels of 3-iodothyronine deiodinase (inactivates circulating thyroid hormones).

Question 100

Describe the pathophysiology and risk factors for NEC

Answer 100

Risk factors: prematurity, very low birth weight, complex comorbidity/sepsis, formula fed.

Pathophysiology - exaggerated immune response to gut pathogens resulting in ischaemia, necrosis and apoptosis → sepsis.

• Gut wall
  
  • Immature gut has impaired motility, abnormal digestion/absorption and abnormal tight junctions between cells. All lead to epithelial cell damage → localised inflammation and bacterial translocation.
  • Immature goblet cells in the epithelium result in production of ineffective mucin (barrier to bacteria and fungi, lubricates gut)
  • Cytotoxic effects of bile acids (increased in formula fed babies)
• Microbiome
  
  • Premature babies and those with NEC have less diverse microbiome, with dominant gram negative bacteria. This is exacerbated by the iatrogenic use of ABx and acid suppression → increased risk of NEC.
    
    • Gram negative bacteria have lipopolysaccharides in their cell wall which induce strong inflammatory response.
• Gut defences
  
  • Toll like receptors (type 4 - TLR4) - larger numbers in NEC. Recognised bacteria within the gut and trigger inflammatory response → impaired cell regeneration and increased apoptosis.
  • IgA (first passive immune response in gut) - low levels present in immature neonates as majority cross placenta after 36/40. Also present in breast milk (along with heparin binding EGF) which is protective.
  • Pro-inflammatory mediators (platelet aggregating factor, lipopolysaccharides, NO) trigger cell damage via cytokine release and oxygen free radicals.
• Gut perfusion
  
  • Neonatal splanchnic circulation dependent upon low vascular resistance. This is mediated by endothelin-1 (vasoconstriction) and nitric oxide (vasodilation)
  • TLR4 inhibit vascular nitric oxide → vasoconstriction → worsening ischaemia and necrosis.

Question 101

Outline the biomarkers of NEC. Discuss their relevance in terms of disease severity.

Answer 101

• Biomarkers for NEC can be categorised as follows -
  
  • Non-specific:
    
    • WCC
      
      • Leucocytosis vs neutropaenia (associated with severe NEC)
    • CRP
      
      • Non-specific marker of inflammation.
      • Useful for assessing response to therapy, progression and complications
    • Platelets
      
      • 50-95% of patients with NEC develop thrombocytopaenia within 24-72 hours of onset of disease.
      • The nadir of platelet count associated with severity of illness
      • Rapid drop in platelets associated with necrosis.
    • IL-6, IL-8, IL-10, platelet aggregating factor
      
      • Non-specific markers of inflammation.
        
        • IL-8 levels are higher in NEC babies who develop surgical vs medical NEC.
        • IL-8 levels are higher in NEC babies with NEC totalis vs multifocal vs unifocal disease
  • Enhanced non-specific:
    
    • Faecal calprotectin
      
      • Higher levels in more severe NEC (systemic illness or perforation)
    • S100A12
  • Gut specific
    
    • IFABP (intestinal fatty acid binding protein) - located on enterocytes in small bowel villi.
      
      • Found in higher levels in NEC babies who develop surgical NEC.
    • Claudin 3
      
      • Cellular tight junction protein detected in blood and urine of patients with bowel inflammation
  • Genomics/proteomics/metabolomics
    
    • Able to assess thousands of chemicals instantaneously and is being used to uncover new biomarkers.

Question 102

Outline routine antenatal screening

Answer 102

• Maternal/Family history
• Blood tests
  
  • Blood group + rhesus status (negative associated increased risk of haemolytic disease of the newborn due to rhesus incompatibility)
  • BHCG
  • PAPP-A
  • Harmony test (chromosome, gender)
• Imaging
  
  • Antenatal USS
    
    • Dating USS 6-8 weeks.
    • Morphology USS- 12 weeks.
    • Growth USS - 20 weeks.
• Other
  
  • Blood pressure
  • Urinalysis
    
    • Infection
    • Proteinuria
  • CTG
  • Amniocentesis/Chorionic villous sampling
  • High vaginal swab

Question 103

Outline diagnostic antenatal testing in paediatric surgery

Answer 103

• Blood tests:
  
  • Alpha fetoprotein - elevated in neural tube defects, exomphalos, gastroschisis, SCT.
  • HCG + PAPPA (+nuchal translucency) - risk assessment for Trisomy 21.
  • Harmony test - sex and chromosome.
• Imaging:
  
  • Ultrasound - sensitive and specific investigation for many conditions, dynamic and can stratify severity of disease (i.e renal tract abnormality), hydrops
    
    • Can be used to screen for others - Amniotic fluid index (oligohydramnios vs polyhydramnios)
  • MRI
  • Echocardiogram
• Invasive tests:
  
  • Amniocentesis, chorionic villous sampling.

Question 104

What are three non-malignant histological changes in a cryptorchid testis (7)?

Answer 104

• Peritubular fibrosis
• Seminiferous tubule atrophy
• Decreased/absent spermatogenesis
• Sertoli cells may demonstrate granular cell change with eosinophilic granular cytoplasmic lysosomes.
• Sertoli cell nodules - nodules of immature, elongated Sertoli cells, may have microliths.
• Increased microliths within seminiferous tubules.
• Retained Leydig cells give appearance of hyperplasia.