Congenital abnormalities

Question 1

What are the types of congenital anomalies of the kidneys and urinary tract? (CAKUT)

Answer 1

Broad range of disorders that result from the following abnormal renal developmental processes:
• Malformation of the renal parenchyma
• Abnormalities of embryonic migration of the kidneys
• Abnormalities of the developing urinary collecting system

Question 2

Why is identificatoin of CAKUT important?

Answer 2

Because CAKUT play a causative role in 30 to 50% of cases of ESRD

Therefore early diagnosis results in:

• earlier treatment to prevent ESRD
• avoid complications of ESRD

Question 3

What % of fetal anomalies detected antenatally are due to abnormalities in kidney and urinary tract?

Answer 3

20-30%

Question 4

Define low risk RPD? Management?

Answer 4

A1
Central calyceal dilation with nil peripherally

Management:

• USS at 32/40
• If remains low risk for PN USS with GP at 1-3/12

Question 5

Define medium risk RPD. Management?

Answer 5

A2
Central calyceal dilation with nil peripherally
>7mm dilated at 20/40 and >10mm at 28/40

Management: - Refer MFM if >10mm

• Repeat USS at 32/40
• D7 PN USS and again at 1-3/12

Question 6

Define high risk RPD. Management?

Answer 6

A3

Dilated RPD AND:

• Peripheral calyceal dilation
• Abnormal parenchymal thickness
• Abnormal parenchymal appearance
• Dilated ureters
• Abnormal bladder wall or ureterocele
• Unexplained oligohydramnios

Plan:

• Refer MFM
• US at day 7 and again at 1-3 months

Additional US within 24-48 hours after birth if suspected bladder outlet obstruction, oligohydramnios , abnormal parenchyma or worrying clinical presentation such as poor urine output.

Clinical assessment drives urgency. Consider catheter placement if US delayed or concern about bladder outflow obstruction

Question 7

What is spina bifida? How does it occur?

Answer 7

It is a congenital neural tube defect, with a spectrum of disease varying from incomplete closure of the vertebral arches at levels L5 or S1, to protrusion of the spinal cord, spinal nerves and meninges through an opening in the back, which can be associated with partial anencephaly.

It is caused by incomplete fusion of the neural arches (precursor to vertebral arches) in the midline. Neural arches are part of the sclerotome, differentiated from the para-axial mesoderm.

The arnold chiari II malformation is a result of the meninges being tethered at the level of the defect, so as the spinal cord tries to shorten (as normal in development) the cerebellum and medulla oblongata are pulled caudally through the base of the skull.

Question 8

What are the types of spina bifida?

What are their prognoses?

Answer 8

Spina bifida occulta (10% births).
- vertebral arches not fused, but no neurological involvement and no serious sequelae. Only sign may be a dimple or tuft of hair at level of defect - usually L5/S1.

Spina bifida cystica (1/1000 births).
- defect in the back allowing exposure of a cystic protrusion that can contain only meninges (SB with meningocele), or meninges with spinal nerves and spinal cord (SB with meningomyelocele). 90% of meningomyelocele cases will also have arnold chiari II malformation where the cerebellum herniates through the base of the skull, and is associated with hydrocephalus.
If meningomyelocele present affecting multiple levels of spinal cord, it is common to have meroencephaly (partial absence of brain).

Prognosis:

• meroencephaly - not consistent with life
• Loss of function lower limbs
• May affect bladder/bowel control
• cognitive impairment
• developmental delay

Degree of disability depends on severity of malformation.

Question 9

What is the embryological development of the heart? When does it start beating?

Answer 9

Starts as angioblastic cord (thickenings of the cardiogenic mesoderm). These become the 2 heart tubes. The heart tubes fuse in the third week to become a single tubular structure. It develops different swelling and strictures, forming (from top to bottom): trunkus arteriosus, bulbus cordis, ventricle, atrium, sinus venosus.

3 paired veins drain into the sinus venous of the heart at this stage: vitelline veins (deoxygenated blood from yolk sac), umbilical veins (oxygenated blood from placenta), common cardinal veins (deoxygenated blood from the body of the embryo).

The bulbs cordis and ventricle grow at a faster rate than the other structures and fold over anterior and to the right of the other chambers, pushing the atria and sinus venous posteriorly.

Partitioning of the atria and ventricles occurs from the 4th-8th week. It starts with he endocardial cushion fusing to separate atria and ventricles.

The atria are separated by the formation and fusion of the septum primum and septum secundum. The foramen primum forms and closes; the foramen secundum forms in the septum primum and is largely covered by the more rigid septum secundum (the the right). The remaining opening is the foramen ovale. After birth the increased pressure in the left atria pushes the soft septum primum onto the septum secundum closing this foramen.

The ventricle is separated by the muscular septum ( crescent of muscular tissue) and is then closed the membranous septum in the 7th week.

The heart starts beating at day 22-23. The atria is the primitive pacemaker. Later the sinus venosus takes over this function, and incorporation of the sinus venous into the atrium forms the SA and AV nodes in the 5th week.

Question 10

What is dextrocardia? How does it occur?

Answer 10

When the heart is on the right, rather than the left in the thorax. Can be accompanied by situs invertus, or not.
Normally the heart folds to the right, so the ventricle lies to the left and bulbs cordis to its right. Dextrocardia happens when the heart folds to the left, pushing the ventricles to the right.

Question 11

What is ectopic cordis? How does it occur?

Answer 11

Where the heart is outside the thorax. Caused by incomplete fusion of the lateral folds to close the thorax. Extremely rare and most babies die within a few days of birth.

Question 12

How do most ASDs occur?
Prevalence?
What is the clinical significance?

Answer 12

Ostium secundum defects (including patent foramen ovale) are the most common.
Formed by failure to close the oval foramen because either: 1) abnormal resorption of the septum primum, 2) an abnormally large oval formamen forms due to defective formation of the septum secundum, so that the septum primum is unable to fully close off the foramen on fusing.

Probe patent foramen ovale affects up to 25% people.

If it is small and an isolated defect is has no clinical significance. However if other defects are present (e.g. pulmonary stenosis) blood will be shunted right to left through the PFA, causing cyanosis.

Question 13

Prevalence and cause of VSD. Management.

Answer 13

Isolated VSDs are commonest type of CHD. Prevalence 2-5 per 1000 births.

Usually caused by defect in membranous part of the septum. If small these will usually close within the first year of life. Large defects allow left to right shunting of blood. Muscular defects are rarer but often more severe and can be associated with transposition of the great arteries.

Question 14

What is transposition of the great arteries? How does it occur? Prevalence? Management?

Answer 14

Most common cause of cyanotic heart disease.
The aorta lie anterior to the pulmonary trunk and arises from the right ventricle, whilst the pulmonary vessels arises from the left ventricle. Usually associated with ASD +/- PDA +/- VSD to allow shunting of blood.

Caused by abnormal formation of the conus arteriosus during incorporation of bulbs cordis to the ventricle.

Question 15

What is tetralogy of fallot?
Presentation?
Management?

Answer 15

4 cardiac defects:

• pulmonary stenosis (obstructed right outflow tract)
• VSD
• Over-riding aorta
• Right ventricular hypertrophy

Often presents in young infants with a ‘Tet spell” or hypercyanotic episode triggered by crying/feeding/defaecating:

• Period of uncontrollable crying / panic,
• Rapid and deep breathing (hyperpnoea),
• Deepening of cyanosis,
• Decreased intensity of heart murmur,
• Limpness, convulsions and rarely, death.

Acutely: knees to chest positon/squatting, metaraminol and beta blockers
Definitive: surgery

Question 16

What is coarctation of the aorta?
Presentation?
Management?

Answer 16

A narrowing of the aorta, most commonly at the level of the ductus arterioles, though can be defined as pre- or post-ductal.
Can present in infant or school age children as:
- Grouchiness
- Pale skin
- Sweating
- Heavy or fast breathing
- Chest pain
- Enlarged liver (hepatomegaly)
- Poor feeding or eating / Poor weight gain
- Cold feet or legs
- Weak pulses in the feet, or no pulses in the feet
- Blood pressure in the arms that is much higher than the blood pressure in the legs
- Pain in lower legs with walking (claudication)

Management:

• cardiac catheterisation and stenting
• surgery

Question 17

What are the derivatives of the 6 pairs of pharyngeal arteries?

Answer 17

1st - parts of maxillary arteries and external carotids (face)
2nd - stapedial arteries in the middle ear (ear)
3rd - common carotids and internal carotids (brain)
4th - left pharyngeal artery = arch of the aorta; right pharyngeal artery = the right subclavian artery (aorta)
5th - Degenerate or never form
6th - left artery = left pulmonary artery and ductus arteriosus; right artery = right pulmonary artery (lungs)

Question 18

Describe the embryological development of the lungs.

Answer 18

The laryngotracheal diverticulum develops as an out growth from the ventral portion of the foregut during the fourth week. The tracheosophageal septum forms separating the fore gut into the laryngotracheal tube (ventral) and oesophagus (dorsal). 2 primordial bronchial/lung buds form at the end of the larygotracheal tube, these divide multiple times to form the bronchi and bronchioles. Surrounding splanchnic mesoderm forms the cartilaginous rings surrounding the trachea and bronchi, and the connective tissue of the lungs.

Question 19

What is TOF?

How does it happen?

Answer 19

An abnormal passage between the the trachea and oesophagus. Often occurs with oesophageal atresia. Incomplete fusion of the tracheosophageal septum leaves a communication between the 2 tubes.

Associated with severe polyhydramnios as fetus unable to swallow amniotic fluid to be reabsorbed from gut and transferred back to mother via fetoplacental unit.

Question 20

What are the stages of lung maturation?

Answer 20

Pseudoglandular period (6-16 weeks)
- development of all structures, except those necessary for gas exchange

Canalicular period (16-26 weeks)

• the lumen of the bronchi and bronchioles become wider
• lung tissue becomes vascular
• terminal bronchioles have developed alveolar ducts and few terminal sacs by 24 weeks (hence why viability occurs around this time)

Terminal sac period (26-32 weeks)

• Many more terminal sacs form
• The epthelium of sacs thin, creating the thin blood-air barrier
• type I pneumocytes develop (across which gas exchange occurs)
• type II pneumocytes that secrete surfactant develop
• Surfactant production increased with increasing gestation, with the greatest amount produced within last 2 weeks of intrauterine life

Alveolar period (32 weeks - 8 years)

• The mature alveoli develops
• Mostly occurs postnatally (95%)
• Lrgely complete by age 3, though ongoing development till 8 years old

Question 21

Describe the embryological development of the kidneys.

Answer 21

3 sets of excretory organs or kidneys develop in the developing embryo.

Pronephros - develops from the nephorgenic cord in the urogenital ridges on each side of the embryo. The pronephros drains into the pronephric duct, then into the cloaca. The pronephros soon degenerates, but the majority of the pronephric duct remains.

Mesonephros - develops caudally to pronephros, and also drains in the pronephric duct, now called the mesoneprhic duct. The mesonephros degenerates by end of first trimester, but the mesonephric ducts does on to form several structures in male reproductive system.

Metanephros - the metanephric diverticulum (or ureteric bud dorsal) is an outgrowth from the mesopnephvic duct close to the cloaca; which will become the ureter, pelvic, calyces, and collecting ducts of urinary system. The metanephric diverticulum elongates and penetrates the metanephrogenic blastema, which forms the parenchyma of the kidney. It ascends from the pelvis to its position in the abdomen, changing its blood supply as it migrates, and rotate 90 degrees to sit laterally. They are formed and functioning by the end of the 9th week when urine production starts to contribute to amniotic fluid.

Question 22

What is the embryological origin of the bladder?

Answer 22

The cloaca is divided by the urorectal septum into the urogenital sinus (ventral) and rectum (dorsal). The urogenital sinus is continuous with the allantois, which later regresses to form the urachus (a fibrous band running from the apex of the bladder to the umbilicus in the median ligament). The trigone is formed by the invagination of the caudal aspect of the mesonephric duct into the urogenital sinus.

Question 23

What is the embryological origin of the female reproductive system?

Answer 23

In the absence of testosterone the mesnonephric duct regresses. In the absence of Mullerian Inhibiting Substance (MIS) the mullerian duct persists.
The mullerian (paramesonephric) ducts originate from the urogenital ridges. The paramesonephric ducts fuse in the midline to form the upper third of vagina, cervix, uterus and come off laterally as the fallopian tubes. 
The lower 2/3 vagina is formed from the urogenital sinus.

Remnants of the mesonephric duct forms the epoophoron of the ovary. It it does not regress completely it can form gartner cysts, usually seen in the anterior wall of the vagina.

Question 24

What is the embryological origin of the male reproductive system?

Answer 24

In the presence of testosterone the mesonephric duct persists. The presence of MIS causes the mullerian/paramesonephric duct to regress.

The mesonephric ducts form the: (from testis to penis) efferent ductules, epididymis, ductus deferens, seminal gland and ejaculatory duct.

Question 25

Cardiac causes of central cyanosis?

Answer 25

A frequently used mnemonic is the “five Ts” of cyanotic CHD:
• Transposition of the great arteries
• Tetralogy of Fallot
• Truncus arteriosus
• Total anomalous pulmonary venous connection
• Tricuspid valve abnormalities