Embryology/Developmental Flashcards

Question

Describe the 5 types of oesophageal atresia.

Answer 1

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.

Answer 2

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.

Answer 3

* 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.

Answer 4

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.

Answer 5

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.

Answer 6

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%

Answer 7

Trisomy 13 Trisomy 18 Trisomy 21 Beckwith-Wiedemann Congenital hypothyroidism Mucopolysaccharidases

Answer 8

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)

Answer 9

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)

Answer 10

* _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.

Answer 11

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)

Answer 12

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.

Answer 13

* 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.

Answer 14

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.

Answer 15

* _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)

Answer 16

* 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

Answer 17

Jejunoileal atresias are thought to occur secondary to a prenatal mesenteric vascular insult. May represent outcome of a volvulus, foetal intussusception

Answer 18

* “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.

Answer 19

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

Answer 20

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.

Answer 21

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.

Answer 22

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.

Answer 23

* 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).

Answer 24

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.

Answer 25

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.

Answer 26

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.

Answer 27

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.

Answer 28

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).

Answer 29

* _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_

Answer 30

**_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

Answer 31

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).

Answer 32

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

Answer 33

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

Answer 34

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

Answer 35

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).

Answer 36

_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.

Answer 37

_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

Answer 38

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

Answer 39

* _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.

Answer 40

* 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_.

Answer 41

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.

Answer 42

* _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

Answer 43

* _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

Answer 44

* 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.

Answer 45

* 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.

Answer 46

* 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

Answer 47

_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)

Answer 48

* _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_

Answer 49

Infants = 38 + (2.5 x age in months) = 38 + (2.5 x 6) = 53ml Older children = (Age in years +2) x 30 = 180mL

Answer 50

40cm H20 (Normal filling pressure is 5-10 cm H20)

Answer 51

* 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

Answer 52

* 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.

Answer 53

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

Answer 54

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.

Answer 55

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_.

Answer 56

* _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

Answer 57

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.

Answer 58

* 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)

Answer 59

* 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.

Answer 60

* _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.

Answer 61

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)

Answer 62

OEIS is a severe form of cloacal extrophy: * O = omphalocoele. * E = Extrophy * I = Imperforate anus * S = Spinal defect

Answer 63

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

Answer 64

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.

Answer 65

Epididymal appendage = remnant of the cranial end of the mesonephric duct. Testicular appendage (Hydatid of Morgagni) = paramesonephric duct remnants (remnants of Fallopian tube)

Answer 66

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)

Answer 67

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

Answer 68

* _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.

Answer 69

* 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.

Answer 70

* 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).

Answer 71

* 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.

Answer 72

* _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

Answer 73

* _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).

Answer 74

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 d*ominant 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.

Answer 75

* 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.

Answer 76

* _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

Answer 77

* 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.

Answer 78

* 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.

Embryology/Developmental Flashcards

(104 cards)