MRCPH PDF
MRCPH PDF
Arrhythmias
Diagnosed at any time during pregnancy: an echocardiogram is required to confirm
normal anatomy and to confirm type of arrhythmia. Fetal electrocardiogram (ECG) is not
yet a routine investigation
Multiple atrial ectopics are usually not treated
Supraventricular tachycardia is usually treated with maternal digoxin or flecainide
Essential Revision Notes in \'aedi,~trics b r the IL4RCPCH 2nd Edition
m Aorta
PV
SVC
TV
IVC
= Pulmonary valve
= Superior vena cava
= Tricuspid valve
= Inferior vena cava
ventricle u Ventricle
Normal heart
litl
i' Ventricular topology
$
Right-hand (normal) or left-hand topology
Ventriculoarterial connection
Type of ventriculoarterial connection
Concordant
Discordant
Double outlet
Single outlet:
Common arterial trunk
Solitary arterial trunk
With pulmonary atresia
With aortic atresia
lnfundibular morphology
Arterial relationships
Associated malformations
Position of heart in the chest - left, right or middle
Systemic and pulmonary veins
Atrial septum
Atrioventricular valves
Ventricular septum
Semilunar valves
Anomalies of great arteries (e.g. double aortic arch)
History
The history-taking is short and to the point. The candidate needs to know:
Was the child born preterm?
Are there any cardiac symptoms of:
Heart failure (breathlessness, poor feeding, faltering growth, cold hands
and feet)
Cyanosis
Neonatal collapse
Is it an asymptomatic heart murmur found on routine examination?
Is there a syndrome such as Down syndrome?
Is there any family history of congenital heart disease?
Did the mother have any illnesses or take any medication during pregnancy?
Examination
Introduce yourself to mother and patient. Ask if you can examine the child.
Position child according to age:
For a 6-year-old - at an angle of 45 degrees
For a toddler - upright on mother's knee
For a baby - flat on the bed
Remove clothes from chest
Stand back and look for:
Dysmorphism
Intravenous infusion cannula
Obvious cyanosis or scars
The following examinations sbould be performed.
Essential Revision Notes in Paediatrics for the AlRCPCH 2nd Edition
Heart failure
The delivery of oxygen to the peripheral vascular bed is insufficient to meet the metabolic
demands of the child. Usually because of left to right shunt with good heart pump function.
A thin, malnourished child (Falteringgrowth)
Excessive sweating around the forehead
Tachycardia
Breathlessness +/- subcostal or intercostal recession
Poor peripheral perfusion with cold hands and feet
A large liver
Never found with ventricular septa1 defect (VSD) or other left to right shunt in first week
of life
An emergency if found up to 7 days of age. Implies a duct-dependent lesion, e.g.
hypoplastic left heart syndrome or coarctation
Cyanosis
Mild cyanosis is not visible - use the pulse oximeter
Clubbing
Visible after 6 months old
First apparent in the thumbs or toes
Best demonstrated by holding thumbs together, back to back to demonstrate loss of
normal nail-bed curvature
Disappears a few years after corrective surgery
Pulse
.
Rate (count for 6 seconds x 10)
Rhythm (only 'regular' or 'irregular', need ECG for 'sinus rhythm')
Character at the antecubital fossa with the elbows straight, using the thumbs - on both
arms together
Palpation
Apex beat 'the most inferior and lateral position where the index finger is lifted by the
impulse of the heartf. Place fingers along the fifth intercostal space of both sides of chest
(for dextrocardia) and count down apex position only if patient is lying at 45 degrees
Left ventricular heave
Right ventricular heave at the left parasternal border
Thrills at upper or lower left sternal edge
Auscultation
Heart sounds and their character
Additional sounds
Murmurs, their character, intensity and where they are best heard
Heart sounds
First heart sound is created by closure of the mitral and then tricusiid valves. It is not
important for the candidate to comment on the nature of the first heart sound.
Second heart sound, however, is more important, created by clbsure of first the aortic and
then the pulmonary valves.
Loud pulmonary sound - pulmonary hypertension
Fixed splitting of second sound (usually with inspiration the sounds separate and then
come together during expiration). Listen when patient is sitting up, at the mid-left sternal
edge in expiration
Atrial septa1 defect
Right bundle-branch block
Single second sound in transposition of great arteries (TGA), pulmonary atresia, or
hypoplastic left heart syndrome
Quiet second sound may occur in pulmonary valve stenosis or pulmonary artery band
Additional sounds
Added sounds present may be a normal third or fourth heart sound heard in the neonate or
these sounds can be pathological, for example in a 4-year-old with a dilated cardiomyo-
pathy and heart failure. An ejection click is heard at aortic valve opening, after the first
heart sound, and is caused by a bicuspid aortic valve in most cases.
Essential Revision Notes in C);7edic7tricsk ~ rthe
= kt RCPCH 22d Eclition
Murmurs
Before listening for any murmurs, the candidate should have a good idea of the type of
congenital heart disease, which is being dealt with. The candidate should know whether
the child is blue (and therefore likely to have tetralogy of Fallot) or is breathless (likely to
have a left to right shunt) or has no positive physical findings before auscultation of the
murmurs (and therefore more likely to either be normal, have a small left to right shunt or
mild obstruction). By the time the murmurs are auscultated, there should only be two or
three diseases to choose between, with the stethoscope being used to perform the fine
tuning. It is best to start at the apex with the bell, and move to the lower left sternal edge
with the diaphragm. Then on to the upper left sternal edge and upper right sternal edge
both with the diaphragm. Additional areas can be auscultated, but provide little additional
information. Murmurs are graded out of 6 for systolic, 1 = very soft, 2 = soft, 3 = moderate,
4 = loud with a thrill, 5 = heard with a stethoscope off the chest, 6 = heard as you enter
the room. Murmurs are out of 4 for diastolic, again 2, 3 and 4.
Pansystolic murmur
Left lower sternal edge (+ I-)
thrill =VSD -
Apex (much less common) = Mitral regurgitation
Rare at left lower sternal edge (+ I-
cyanosis) = Tricuspid regurgitation
(Ebstein anomaly)
Continuous murmur
Left infraclavicular (+I- collapsing pulse) = Persistent arterial duct
+
Infraclavicular (+ cyanosis lateral thoracotomy) = BT shunt
Any site (lungs, shoulder, head, hind-quarter) = Arteriovenous fistula
Diastolic murmurs
Unusual in childhood
Left sternal edgdapex (+ I- thrill or VSD)
carotid = Aortic regurgitation
Median sternotomy (+I- PS (pulmonary stenosis) murmur)
= Tetralogy of Fallot, repaired
Apical (+I- VSD) = Mitral flow/(rarely stenosis)
NB Listening to the back gives little diagnostic information, but is useful thinking time.
Presentation of findings
Few candidates pay enough attention to the case presentation. This should be done after the
examination is complete. The candidate should stand, look the examiner in the eye, put
hands behind hislher back and present. The important positives and negatives should be
stated quickly and succinctly with no 'umms' or 'errrs'. It is important to judge the mood of
the examiner, if helshe is looking bored, then go faster. Practise with a tape recorder or
video-recording.
To complete the examination you would:
Measure the blood pressure
Measure the oxygen saturation
Feel the femoral pulses
Feel the liver edge
The presentation should be rounded off with the phrase 'the findings are consistent with the
diagnosis of . . .'.
3
Patient KEY
I L
AS
Left
aortic stenosls
Femoral Pulses VSD ventricular septa1 defect
No
AYes PS
TGA
pulmonary stenosis
transposition of great arteries
Coarctation ASD atrial septal defect
PSM Pan Systolic murmur
No other pulses
ESM ejection systolic murmur
Critical Aortic Stenosis AVSD atrioventricular septa1 defect
HLHS AV atrioventricular
Absent Left Carotid
Interrupted Aortic Arch
-
7
Yes
Carotid thrill AS
l
?Kartagener with
normal heart
- Apex in left chest
lyes
Precordial thrill -
Yes
VSD or PS
?Abnormal heart
v lNO
Yes PY No Yes PY - No Normal Heart
Fallot TGA PSM Lower S.E. Left VSD
Apex Mitral regurgiktion
ESM Upper S.E. (AVSD is not visibly
cyanosed and may have
apical murmur of left AV
valve regurgitation)
Left Split S2 ASD
Not split PS
Right +
AS Carotid thrill
Ejection click Valvar AS or PS
No ejection click Sub- or supra valvar
Pulmonary sound Loud Pulmonary hypertension
L
The arterial duct is kept patent with prostaglandins El or E2 infusion in children with duct- ---
-.
-.
-
- -
--
-.
dependent circulation such as transposition of the great arteries, or pulmonary atresia. -
=I
-.
-.
-
- =
3s
?If
There will only be cyanosis if the desaturated blood shunts from the right to left side
Common mixing leads to cyanosis and breathlessness
Duct-dependent conditions usually present at 2 days of life
Prostaglandin E2 or El can be used to reopen the duct up to about 2 weeks of life
16
I
CJ rdiology
General principles
No signs or symptoms on first day of life because of the high pulmonary vascular resistance.
Later, at 1 week, infant can develop symptoms and signs of heart failure.
Symptoms of heart failure
Tachypnoea
Poor feeding, Faltering growth
Cold hands and feet
Sweating
Vomiting
I
Signs of heart failure
Thin
Tachypnoea
I Displaced apex
Dynamic precordium
Apical diastolic murmur
Hepatomegaly
i
3.1 Atrial septal defect (ASD)
Types of defect
Secundum ASD
Primum ASD (partial atrioventricular septal defect)
Sinusvenosus ASD
Other
Secundum ASD
A defect in the centre of the atrial septum involving the fossa ovalis.
Clinical features
Asymptomatic
80% of ASDs
Soft systolic murmur at upper left sternal edge
Fixed split S2 (difficult to hear)
ECG
Partial right bundle-branch block (90%)
Right ventricle hypertrophy
Essential Revisiot?Notes in Paediatrics for the MRCPCH 2nd Edition
Chest X-ray
lncreased pulmonary vascular markings
Management
Closure at 3-5 years (ideally)
90% undergo device closure in catheter laboratory
10% undergo surgical closure (too large or personal preference)
Clinical features
Asymptomatic
10% of ASDs
Soft systolic murmur at upper left sternal edge
Apical pansystolic murmur (atrioventricular valve regurgitation)
Fixed split S2 (difficult to hear)
ECG
Partial right bundle-branch block (90%)
Right ventricle hypertrophy
Superior axis
Chest X-ray
lncreased pulmonary vascular markings
Management
Closure at 3-5 years
All require surgical closure (because of the need to repair valve)
Clinical features
Asymptomatic or heart failure
5% of ASDs
Soft systolic murmur at upper left sternal edge
Fixed split S2 (easily heard)
Cardiology
ECG
Partial right bundle-branch block
Right ventricle hypertrophy
Chest X-ray
Increased pulmonary vascular markings
Cardiomegaly
Management
Closure at 1-5 years ,
All require surgical closure and repair to the anomalous pulmonary veins
There are other rare types of ASD, which are similarly treated.
Clinical features
Asymptomatic (80-9O0/0)
May have a thrill at left lower sternal edge
Loud pansystolic murmur at lower left sternal edge (the louder the murmur, the smaller
the hole)
Quiet P2
ECG
Normal
Chest X-ray
Normal
Management
Review with echocardiography
Spontaneous closure, but may persist to adult life
Large defect
Defects anywhere in the septum. Large defects tend to be the same size or larger than the
aortic vabe. There is always pulmonary hypertension.
for the ILIRCPCH 2nd Edition
Essential Revision Notes in Pcieo'iL~trics
Clinical features
Symptomatic with heart failure after age 1 week
10-20% of VSDs
Right ventricular heave
Soft or no systolic murmur
Apical mid-diastolic heart murmur
Loud P2
ECG
Biventricular hypertrophy by 2 months (see Section 15 - ECG)
Chest X-ray
Increased pulmonary vascular markings
Cardiomegaly
Management
Initial medical therapy, diuretics +/- captopril + added calories
Surgical closure at 3-5 months
Clinical features
Asymptomatic usually, rarely have heart failure
Continuous or systolic murmur at left infraclavicular area
ECG
Usually normal
If large, have left ventricle volume loading (see Section 15 - ECG)
Chest X-ray
Usually normal
If large, have increased pulmonary vascular markings
Management
Closure in cardiac catheter laboratory with coil or plug at 1 year
If large, surgical ligation age 1-3 months
NB The presence of an arterial duct in a preterm baby is not congenital heart disease. If
there is a clinical problem, with difficulty getting off the ventilator, or signs of heart failure
with bounding pulses, the problem is usually treated with indomethacin or ibuprofen
(< 34 weeks). If medical management fails, surgical ligation is undertaken.
Clinical features
Rare
Usually develop heart failure
Continuous murmur as for PDA
ECG
If large, have left ventricle volume loading (see Section 15 - ECG)
Chest X-ray
If large, have increased pulmonary vascular markings
Management
If large, surgical ligation age 1-3 months
3.5 Others
There are other rare causes of significant left to right shunt,. such as arteriovenous
malformation. These are all individually rare. Medical and surgical treatment is similar to
that for large ducts or VSDs.
Summary
General principles
Cyanosis in a newborn can be caused by:
Cardiac problems (cyanotic heart disease)
Respiratory problems (diaphragmatic hernia, etc.)
Metabolic problems (lactic acidosis, etc.)
Infections (pneumonia, etc.)
Cardiac cases which present on day 1-3 are usually duct-dependent:
Transposition of great arteries (common)
Tetralogy of Fallot with pulmonary atresia (less common)
Pulmonary atresia with intact ventricular septum (PA/IVS) (rare)
Tricuspid atresia or other complex hearts (rare)
Ebstein anomaly (rare)
Investigations
Chest X-ray (to exclude lung pathology and large 'wall to wall' heart in Ebstein anomaly)
Blood culture (to exclude infection)
ECG (superior axis in tricuspid atresia)
Hyperoxia test, 10 min in 100% O2 + blood gas from right radial arterial line. If
p02 > 20 kPa then it is not cyanotic heart disease - you must not use a saturation
monitor, because this is notoriously inaccurate in the presence of acidosis
Echocardiogram is not first line but should be considered early on
Management
Resuscitate first
Ventilate early
Prostaglandin El or E2 infusion (5-20 ng/kg per min) (may cause apnoeas)
Transfer to cardiac centre
Treat as for specific condition
Clinical features
Asymptomatic usually, rarely have severe cyanosis at birth, worsens as they get older
Loud, karsh murmur at upper sternal edge day 1
Do not usually develop heart failure
ECG
Normal at birth
a RVH when older
Chest X-ray
Usually normal
a If older have upturned apex (boot shaped) t reduced vascular markings
Management
require BT shunt in newborn if severely cyanosed
Most have elective repair at 6-9 months
Clinical features
Cyanosed when duct closes
No murmur usually
Can be very sick, unless diagnosed antenatally
May be associated with VSD, coarctation or pulmonary stenosis-(PS)
ECG
Normal
Chest X-ray
Normal (unusual to detect 'egg-on-side' appearance)
May have increased pulmonary vascular markings
Management
Resuscitate as above
20% require balloon atrial septostomy at a cardiac centre (usually via umbilical vein -
see Section 17 - Cardiac catheterization)
Arterial switch operation usually before 2 weeks
Essential Revision Notes i r ~Pc7edic?fricjfor the M R C 3 V - i I'l?d Edition
ECG
Normal
Chest X-ray
Normal at birth (unusual to diagnose 'boot-shaped' heart, until much older)
Decreased pulmonary vascular markings
Management
Resuscitate as above
BT shunt inserted surgically
Radiofrequency perforation of atretic valve - if appropriate
Clinical features
Not usually duct-dependent
No murmur usually
Usually present with heart failure at 1 month but may present with cyanosis at any age if
collaterals are small
ECG
Bi-ventricular hypertrophy
Chest X-ray
1
Boot-shaped heart
I
Cardiomegaly
Increased pulmonary vascular markings if in heart failure, or reduced vascular marking if
severely cyanosed
Management
Diuretics, if in failure
Further imaging with cardiac catheter or magnetic resonance imaging (MRI)
Staged surgical repair
Clinical features
Cyanosed at birth
Loud murmur of tricuspid regurgitation
Can be very sick
May be associated with maternal lithium ingestion
ECG
May have a superior axis
Chest X-ray
Massive cardiomegaly (wall to wall heart)
Reduced pulmonary vascular markings
Management
Resuscitate as above
Pulmonary vasodilator therapy (ventilation, oxygen, etc., see Section 12)
Try to avoid surgical shunt insertion, in which case prognosis is poor
4.5 Eisenmenger
This is secondary to a large left to right shunt (usually VSD or AVSD (atrioventricular septa1
defect)) where the pulmonary hypertension leads to pulmonary vascular disease (increased
resistance) over many years. Eventually the flow through the defect is reversed (right to left)
so the child becomes blue, typically at 15-20 years of age.
Clinical features
Cyanosed in teenage life
Uncommon
Usually secondary to untreated VSD or AVSD
No murmur usually
evel lo^
right heart failure eventually
Essential Revision Notes in Paediatrics for the MRCPCH 2nd Edition
ECG
Severe RVH + strain
Chest X-ray
Decreased pulmonary vascular markings
Management
Supportive
May need diuretic and anticoagulant therapy
Oxygen at night, consider other therapy (see Pulmonary hypertension, Section 10)
Consider heartllung transplantation
5. MIXED SHUNT
(Blue and breathless)
General principles
Tend to present either antenatally (most often) or at 2-3 weeks. Symptoms are that of
mild cyanosis and heart failure
Includes most of the complex congenital heart diseases
5.1 Complete atrioventricular septa1 defects
There is an atrial and ventricular component to the defect, so there is pulmonary hyper-
tension as with a large VSD. There is a common atrioventricular valve with five leaflets, not
a separate mitral and tricuspid valve.
Clinical features
May be cyanosed at birth
No murmur usually at birth, may develop in first few weeks
Often present on routine echo screening (neonatal Down syndrome)
May present with heart failure at 1-2 months
ECG
Superior axis
Bi-ventricular hypertrophy at 2 months old
Right atrial hypertrophy (tall P-wave)
Chest X-ray
Normal at birth
Increased pulmonary vascular markings and cardiomegaly after 1 month
Management
Treat increased pulmonary vascular resistance at birth if blue
Treat as for large VSD if in failure (diuretics, captopril, added calories)'
Surgical repair at 3-5 months
Clinical features
Cyanosed when duct closes if duct-dependent
No murmur usually
Can be very well at birth
ECG
Superior axis
Absent right ventricular voltages
Large P-wave
Chest X-ray
May have decreased or increased pulmonary vascular markings
Management
BT shunt inserted surgically if very blue
PA band if in heart failure
Hemi-Fontan after 6 months old (see Section 9.2 - Fontan)
Fontan at 3-5 years old
5.3 Others
There are many other types of complex congenital heart disease.
Common arterial trunk
Double inlet left ventricle
Total or partial anomalous pulmonary venous connection (unobstructed)
Right or left atrial isomerism +I- dextrocardia
Individually, these are quite rare and their management is variable, depending on the
pulmonary blood flow, the sizes of the two ventricles, etc. For further information a larger
textbook of congenital heart disease shouId be consulted.
General principles
Often present to general practitioner with murmur
Asymptomatic
Clinical features
Asymptomatic
Always have a carotid thrill
Ejection systolic murmur at upper sternal edge
May be supravalvar, valvar (and ejection click) or subvalvar
Quiet A2 (second heart sound aortic component)
ECG
Left ventricular hypertrophy
J
Chest X-ray
Normal
Management
Review with echocardiography
Balloon-dilate when gradient reaches 64 mmHg across the valve
Clinical features
Asymptomatic (not cyanosed)
May have a thrill at upper left sternal edge
Ejection systolic murmur at upper sternal edge from day 1
May be supravalvar, valvar (ejection click) or subvalvar
Quiet P2
ECG
Right ventricular hypertrophy
Chest X-ray
Normal
Management
Review with echocardiography
Balloon-dilate when gradient reaches 64 mmHg across the valve
Clinical features
Rare
Asymptomatic
Always have systemic hypertension in the right arm
Ejection systolic murmur at upper sternal edge
Collaterals at the back
Radiofemoral delay
Essential Revision Notes i17 Paedi'jtrics h r the MRCPCH 2nd Edition
ECG
Left ventricular hypertrophy
Chest X-ray
Rib-notching
'3' sign, with a visible notch on the chest X-ray in the descending aorta, where the
coarctation is
Management
Review with echocardiography
Stent insertion at cardiac catheter when gradient reaches 64 mmHg, or surgery via a
lateral thoracotomy
Clinical features
Often present with stridor
May have no cardiac signs or symptoms
ECG
Normal
Chest X-ray
May have lobar emphysema as a result of bronchial compression
Management
Diagnose with bariurnlgastrografin swallow
Review with echocardiography
Additional imaging often required (computerized tomography, magnetic resonance
imaging, angiogram)
Surgical treatment
Clinical features
Very common diagnosis
Often diagnosed antenatally
Absent femoral pulses
Should be born in a cardiac centre
If not detected antenatally, presents as sick infant with absent femoral pulses
No murmur, usually
Signs of right heart failure (large liver, low cardiac output)
May be breathless and severely acidotic
Associated with VSD and bicuspid aortic valve
ECG
Normal
Chest X-ray
Normal, or cardiomegaly with heart failure
Management
Resuscitate
Commence prostaglandin El or E2 (5-20 ng/kg per min)
Ventilate early (before transfer to cardiac centre)
Surgery 24 hours later, usually through a left lateral thoracotdmy, to resect the narrow
segment, unless the whole aortic arch is small, in which case the'surgery is performed
via a median sternotomy on bypass.
Clinical features
Common diagnosis (200-400 born annually in UK)
Usually diagnosed antenatally
Should be born in a cardiac centre
If sick, presents with absent femoral + brachial pulses
No murmur
Signs of right heart failure (large liver, low cardiac output)
May be breathless and severely acidotic
Anatomy varies from mitral stenosis to mitral and aortic atresia
Essentiai Revision Notes in Paec~ic~trics
for the MRCPCCH2nd Eclition
ECG
Absent left ventricular forces
Chest X-ray
Normal, or cardiomegaly with heart failure
Management
Resuscitate
Commence prostaglandin El or E2 (5-20 ng/kg per min)
Ventilate early (before transfer to cardiac centre)
Surgery (see Section 9.3 - Norwood) 3-5 days later
Clinical features
Rare diagnosis
Usually diagnosed antenatally
Should be born in a cardiac centre
If sick, presents with absent femoral + brachial pulses
No murmur
Signs of right heart failure (large liver, low cardiac output)
May be breathless and severely acidotic
Poor prognosis
ECG
Left ventricular hypertrophy
Chest X-ray
I/
Normal, or cardiomegaly with heart failure
I/
,
Management
Resuscitate
Commence prostaglandin El or E2 (5-20 nglkg per min)
Ventilate early (before transfer to cardiac centre)
Balloon dilation 24 hours later, may require cardiac surgery
7.4 Interruption of the aortic arch
A gap in the aortic arch, which may occur at any site from the innominate artery around to
the left subclavian artery. It is always duct-dependent.
Clinical features
Rare diagnosis
Presents with absent left brachial + femoral pulses
No murmur
Heart failure (large liver, low cardiac output)
Breathless and severely acidotic
Associated with VSD and bicuspid aortic valve
Associated with 22q11.2 deletion and Di George syndrome (see Section 10.5)
ECG
Normal
Chest X-ray
Normal, or cardiomegaly with heart failure
Management
Resuscitate
Commence prostaglandin El or E2 (5-20 ng/kg per min)
Ventilate early (before transfer to cardiac centre)
Surgery 24 hours later
Clinical features
Uncommon diagnosis
Not a duct-dependent lesion
If obstructed, presents day 1-7 with cyanosis and collapse
No murmur
Signs of right heart failure (large liver, low cardiac output)
May be breathless and severely acidotic
May, however, present later up to 6 months of age if unobstructed, with murmur or heart
failure
Essential Revision Notes in Paediatrics for the ILIRCPCH 2nd Edition
ECG
Normal in neonate
RVH in older child
Chest X-ray
Normal, or small heart
'Snowman in a snowstorm' or 'cottage loaf' because of visible ascending vein and
pulmonary venous congestion. Appearance usually develops over a few months
Management
Resuscitate (ABC)
Ventilate early (before transfer to cardiac centre)
Prostaglandin not effective if obstructed pulmonary veins
Emergency surgery if obstructed
Overview
There are other causes in each column, but these are less common and are unlikely to appear in examinations.
Any child with a complex heart arrangement which is not suitable for a repair with two
separate ventricles will end up with a Fontan operation. If the pulmonary blood flow is
too low at birth (cyanosis), they will have a BT shunt. If the pulmonary blood is too high
(heart failure) they will have a PA band. If physiology is balanced, then conservative
treatment will be undertaken until the Hemi-Fontan is performed
At about 6-8 months, the venous return from the head and neck is routed directly to the
lungs. A connection is therefore made between the superior vena cava and the right
pulmonary artery. The Hemi-Fontan (or a Glenn or Cavopulmonary shunt) is performed
on bypass, via a median sternotomy. Following the operation, the oxygen saturations
will typically be 80-85O/0
At 3-5 years, there will be insufficient blood returning from the head to keep the child
well. Hence a Fontan operation will be performed, where a channel is inserted to drain
blood from the inferior vena cava up to the right pulmonary artery. This means that the
child will be almost pink, saturations around 90-950h
When completely palliated, the ventricle pumps pink oxygenated blood to the body,
whereas the blue deoxygenated blood flows direct to the lungs
Used to palliate hypoplastic left heart syndrome
Stage I at 3-5 days of age
Pulmonary artery sewn to aorta so that right ventricle pumps blood to body, branch
pulmonary arteries are isolated.
Atrial septectomy so that pulmonary venous blood returns to right ventricle
BT shunt from innominate artery or a conduit from right ventricle to pulmonary
arteries
Stage II (Hemi-Fontan) at 5-6 months old
Stage I l l (Fontan) at 3-5 years old
Results of survival to 5 years are approximately 70-80%
Unknown long-term results
9.4 Rastelli
Used for TGANSDIPS
Left ventricle is channelled through VSD to aorta
VSD is closed with a patch of Cortex material
Right ventricle is connected to pulmonary artery with a homograft (donor artery)
Homograft is replaced every 20 years
1 Isomerism
Genetic defect - multifactorial, several candidates isolated
Associated defects
Asplenia (penicillin prophylaxis)
Midline liver
Malrotation of small bowel
Two functional right lungs
Associated defects
Polysplenia (usually functional)
Malrotation (less often than in right isomerism)
Two functional left lungs
10.2 Trisomy
Down syndrome
Genetic defect - trisomy 21
Cardiology
Heart defects
30°h have CHD
Usually VSD and AVSD
All offered surgery with low risk
Associated defects
Diagnosed antenatally - increased nuchal translucency
Edward syndrome
Genetic defect - trisomy 18
Heart defects
VSD
Double outlet right ventricle
Associated defects
Rocker bottom feet
Crossed index finger
Developmental delay
Patau syndrome
Genetic defect - trisomy 15 or 13
Heart defects
VSD
Double outlet right ventricle
Associated defects
Holoprosencephaly
Midline facial cleft
Renal anomalies
Heart defects
Supravalve aortic stenosis
Peripheral pulmonary artery stenosis
Essential Revisicra Notes in R'nec!ic~,tric.sfor the MRCPCH 2ncI Edition
Associated defects
Gene abnormality on long arm of chromosome 7
Hypercalcaemia
Serrated teeth
Carp-shaped mouth
Hypertelorism
Cocktail party chatter
Heart defects
Hypertrophic cardiomyopathy
Pulmonary valve stenosis
ASD
Associated defects
Almond-shaped eyes and shallow orbits
Shield-shaped chest, widely spaced nipples
Short
Not 'male Turner', can be girls
Heart defects
Conotruncal anomalies
Common arterial trunk
Interrupted aortic arch
Tetralogy of Fallot
Familial VSD
Associated defects
22q11.2 deletion
Only have full D i George if there is deletion + heart + two out of three of:
Cleft palate
Absent thymus (T cells low)
Absent parathyroids, hypocalcaemia
Small jaw, small head, pinched nose, hypertelorism
Small baby, slow development
Renal anomalies (20%)
Physical examination
Features to describe or exclude in this syndrome are as follows:
Dysmorphic features of face, skull or pelvis
Exclude cleft palate
Check spine for scoliosis
Check males for hypospadias
Investigations
Full blood count and film (ask for haematologist's report)
Calcium and magnesium levels
Thyroid function tests
Check total CD4 count
Measure total immunoglobulin E levels
Chest X-ray
Thymic ultrasound
If abnormal: T-cell precursors and response to tetanus, H a e ~ p h i l u sinfluenzae type I3
(HIB) and pneumococcus vaccination
Heart defects
Peripheral pulmonary artery stenosis
Essential Revision Notes in fiediatrics for the MRCPC7-I 2nd Edition
Associated defects
Prominent forehead; wide-apart, deep-set eyes
Small, pointed chin
Butterfly vertebra
lntrahepatic biliary hypoplasia - jaundice
Embryotoxon (slit lamp for cornea)
Kidney, growth, abnormalities of development, high-pitched voice
Heart defects
Coarctation of the aorta
Associated defects
Webbed neck
Short stature
Shield-shaped chest, wide-spaced nipples
Infertility
10.8 VACTERL
Heart defects
VSD
Tetralogy of Fallot
Coarctation
PDA
Associated defects
Vertebral
Anorectal
Cardiac
Tracheo-~Esophagealfistula
RenaVRetardation
Limb
Heart defects
ASD
Associated defects
Radial aplasia
Limb abnormalities
10.10 CHARGE
Heart defects
VSD
Tetralogy of Fallot
Associated defects
Coloboma
Heart
Atresiae choanae
Renaketardation
GenitaVgrowth
Ear
Associated defects
Absent sternum
Absent pericardium
Absent diaphragm
Absent heart (ectopic, on the front of the chest)
Absence of normal heart (tetralogy of Fallot)
10.12 Dextrocardia
A clinical diagnosis with the apex beat in the right chest. It is dangerous to use in cardiology
because it gives no information about the connections or orientation of the heart. For
example, if the right lung was collapsed and there was a tension pneumothorax on the left,
it would be possible to find the apex beat in the right chest. However, the child would not
suddenly have developed a cardiac anomaly. We use the term 'apex to right' to imply the
orientation of the heart and then talk about the connections such as situs inversus (right
atrium is on the left and left atrium is on the right) or some other situs.
In practice, most children with dextrocardia have a normal heart. This is most often the case
when the liver is on the left. It may be part of Kartagener syndrome (primary ciliary
dyskinesia) where the organs failed to rotate properly during embryological development. It
is easily diagnosed by performing nasal brushings to look at the dynein arms of the cilia on
electron microscopy. Associated with bronchiectasis, sinus occlusion and infertility.
If the child is blue with dextrocardia, there is almost always complex heart disease with
right atrial isomerism (see above).
Tuberous sclerosis
Genetic defect - TSCl and TSC2 genes
Heart defects - cardiac rhabdomyoma which reduce in size with age
2. P u l m o n a q w e n o t l s r ~ d
2.1 Left-sided atrial or yentricylar heart dis
2.2 Left-sided valvar heart aisease
2.3 Extrinsic compression of central pulmonary v
Fibrosing mediastinitis
Adenopathy/tumours
2.4 Pulmonary veno-occlusive disease
2.5 Other
Essential Revision Notes in Ynedi,?trics for the MKCPCH 2nd Edition
5. Puhanary hyp
Diagnosis
Persistent hypoxia
Low cardiac output
Loud P2 on examination
Oligaemic lung fields
Hepatomegaly
Episodic desaturation, preceding a fall in blood pressure
Echocardiographic appearance of pulmonary hypertension
High-velocity tricuspid regurgitation jet
Dilated right ventricle
Right to left shunt via atrial septum
Long right ventricle ejection time
High-velocity pulmonary regurgitation jet
Right to left shunt via arterial duct
Treatment
Good ventilation (High 02,low C 0 2 )
Use oscillation ventilation if necessary
Sedation with morphine or fentanyl
Paralysis
Good chest physiotherapy
Restricted fluids
Pharmacology
Nitric oxide (5-20 ppm, inhaled)
Prostacyclin (50 ng/kg, nebulized each 15 minutes)
Magnesium sulphate (200 mgkg intravenous)
Extracorporeal membrane oxygenation (ECMO) as last resort
Treatment
Repair defect by 3 months of age to avoid irreversible pulmonary vascular disease
Investigation
Sleep studies
ECC (right ventricular hypertrophy)
Ear/nose/throat opinion (upper airway obstruction)
Chest X-ray
Echocardiogram
Cardiac catheterization with pulmonary vascular resistance study
Treatment
Ensure good airway mechanics
Treat underlying cardiac condition if appropriate
Added 0 2 to keep O2 saturations > 94%
Maintain low C02 (consider night-time ventilation)
If responsive to vasodilators:
Nifedipine (0.1 mg/kg three times per day)
Dipyridamole (2.5 mg/kg/l2 hourly)
Nebulized or intravenous prostacyclin
Consider heartllung transplantation if appropriate
13.2 Anticoagulation
Aspirin - for arterial platelet aggregation prevention orally (5 mgkg per day)
Heparin - for arterial anticoagulation, intravenous
Warfarin - for venous or arterial thrombus prevention
Streptokinase - for thrombolysis
Tissue plasminogen activator - for thrombolysis
13.4 Antiarrhythmia
Supraventricular tachycardia (SVT)
Vagal manoeuvres first
Adenosine intravenous 50-250 pgkg
DC synchronized cardioversion 0.5-2 Jlkg
Conjunctivitis
Extremity involvement (red fingershoes)
+/- coronary artery aneurysms (25% of untreated cases, 4.6% of treated cases)
+/- abdominal pain, diarrhoea, vomiting, irritable, mood change, hydrops of
gallbladder, peeling extremities, thrombocytosis
Pathology
Marked similarity to toxic shock syndrome
Perhaps immune response to disease or toxin
Investigation
Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), white blood count (WBC),
blood culture, antistreptolysin-0 test (ASOT), viral, throat swab, ECG
Heart
Pericardial effusion
Myocardial disease (poor contractility)
Endocardial disease (valve regurgitation)
Coronary disease
Ectasia, dilatation
Small, 3-5 mm, aneurysms - resolve
Medium, 5-8 mm, aneurysms - usually resolve
Giant, > 8 mm, aneurysms - ischaemia later
Greatest risk if male, < 1 year, fever > 16 days, ESR > 100, WBC 1 30,000'
Echocardiogram at 10-1 4 days, 6 weeks, 6 months or longer if abnormal.
Treatment
immunoglobulin 2 g/kg over 12 hours
Aspirin 30 mg/kg per day (four times per day dosage) reduce to 5 mg/kg per day when
fever resolves
Continue aspirin until 6 weeks or longer if abnormal echocardiogram
Examination
Full cardiovascular examination
Exclude myopathy
ECG
Evidence of ischaemia
Arrhythmias - unrecognized tachycardia
Echocardiogram
Exclude anomalous coronary artery
X-ray
Look for arterial calcification
Blood
Metabolic
Carnitine (and acylcarnitine) profile
Amino acids, organic acids, lactate
Creatinine and electrolytes (including phosphate)
Liver function tests and lactate dehydrogenase, creatine kinase-membrane-bound
Selenium and thiamine
Autoimmune
Antinuclear, anti-DNA antibodies; immune complexes
Virology
Full blood count, ESR, CRP,
Polymerase chain reaction for Epstein-Barr virus, coxsackievirus, adenoviruses,
. ec hoviruses
Stools for viral culture
Other investigations include abdominal ultrasound for arterial caltification, electromyogra-
phy and muscle biopsy if there is myopathy. Rare causes include endomyocardial fibrosis,
tropical diseases, amyloid.
Examination
Exclude syndromes, Noonan, Leopard, Friedreich ataxia, neurofibromatosis,
lipodystrophy
Exclude endocrine disease, thyroid (hyper- and hypo-), acromegaly
Exclude hypertension; check for gross hepatomegaly
Check for cataracts, ophthalmoplegia, ataxia, deafness, myopathy
, ~ fix dttl h1RCFCH 2nd E~Biai~il;
Essential Revision Notes in R ~ t l d itrie-s
Echocardiogram
Exclude tumours, amyloid, endocardial infiltration
ECG
Look for short PR + giant complexes (Pompe syndrome)
Look for QRS-T axis dissociation (Friedreich ataxia)
Blood tests
Carnitine (decreased) + acylcarnitine profile
Creatine phosphokinase (increased = glycogen storage disease type III)
Blood film for vacuolated lymphocytes, if positive check white cell enzymes (suggesting
storage disorders)
Calcium (hyperparathyroidism)
Thyroid function tests, fasting blood sugar
Lactate, amino acids
Urine
Glycosaminoglycans (for mucopolysaccharidosis)
Organic acids
Vanillylmandelic acid
If no cause is found, screen family for hypertrophic obstructive cardiomyopathy (HOCM)
and consider a gene probe for HOCM
History
If a child is admitted with an unexplained fever, has or might have congenital heart
disease, has murmurs (1 changing), suspect bacterial endocarditis
Ask for history of recent boils, sepsis, dental extraction, etc.
Suspected bacterial endocarditis may be found postoperatively following insertion of
prosthetic material such as homograft or prosthetic valve
Examination
Full cardiovascular examination
Hepatosplenomegaly, fever, heart sounds and signs of infected emboli: Osler's nodes,
Roth's spots, septic arthritis, splinter haemorrhages, haematuria, nephrosis
Investigations
Six blood cultures from different sites at different times over 2 days, using the most
sterile technique possible, but do not clean blood culture bottles with alcohol (or else
the organisms will be killed off)
Full blood count, ESR, CRP, ASOT throat swab
Echocardiogram and ECG
Consider V1Q scan, white cell differential
Urine test for blood
Dental opinion
Treatment
If proven, treatment is for 6 weeks, predominantly intravenous
Blood antibiotic levels may be taken for back titration after stabilization on antibiotic
regimen - this will be used to assess that there is sufficient antibiotic present to have a
bactericidal effect
Antibiotics chosen should be those with a good record of deep-tissue penetration, e.g.
fusidic acid, gentamicin
Investigations
ASOT
Throat swab for streptococcus A
ECG
Echocardiogram (mitral regurgitation, myocarditis, pericarditis)
Treatment
Penicillin or cefuroxime (if sensitive)
Prophylactic penicillin V orally for 25 years
14.6 Pericarditis
Aetiology
Coxsackieviruses
Enteroviruses
Staphylococcus
Tuberculosis
Ontological
Rheumatic fever
Presentation
Chest pain (inspiratory)
Acute collapse (effusion)
Soft, muff led heart sounds
Examination
Pericardial friction rub
Fever
ECG
ST elevation, convex upwards
T-wave inversion
Treatment
Anti-inflammatory drugs (ibuprofen)
Drain large pericardial effusion
115.1 The ECG and how to read it
Before interpreting a paediatric ECG it is essential to know the following:
How old is the child?
Is the ECG recorded at a normal rate (25 mmls) and voltage (10 mmImV)?
Rate
When measuring the heart rate on the ECG, the number of large squares is counted
between the R-waves. The rate is calculated as 300lnumber of squares.
Rhythm
Sinus rhythm can only be inferred if there is one P-wave before each QRS and if the P-wave
axis is between 0 and 90 degrees.
Axis
QRS axis
This is calculated by adding the total positive deflection (R-wave) and subtracting the
negative deflection (Q+S-wave). The resulting vector is plotted for lead I and AVF:
v
Lead AVF = +90°
The P-wave and T-wave axes should be plotted similarly. This is important. For example, if
there is left atrial isomerism, there is no sinoatrial node (a right atrial structure). This means
that the P-wave axis is abnormal (superior) and can lead to the diagnosis. Similarly, in
cardiomyopathies, such as Friedreich ataxia, there is a difference in the axis between QRS
and Tof more than 75 degrees. This can help to make the diagnosis (see below).
Normal QRS axis for
newborn - 90- 180 degrees
2-5 years - 45-1 35 degrees
> 5 years - 10- 100 degrees
Causes of a superior axis (> 180 degrees)
Atrioventricular septa1 defect
Tricuspid atresia
Ebstein anomaly
Noonan syndrome
Essential Revision Notes in Paediatrics for the M RCPCH 2nd Edition
~olff-Parkinson-White syndrome
< 1% of normals
NB AVSD will have right ventricular hypertrophy, whereas tricuspid atresia usually has no
right ventricular forces. Either can have large P-waves.
The axis should be from 0 to 90 degrees. The normal size is 2 x 2 little squares (0.08
seconds, 0.2 mV). If there are not regular P-waves before each QRS consider the following:
Complete heart block - there is complete dissociation between the QRS and P-waves,
i.e. with no fixed relationship; see below for list of causes
Atrial flutter - usually with 2 : 1 block, there is a typical saw-tooth baseline
Inverted P-waves - these are typically seen with:
Left atrial isomerism (no RA + no sinus node)
Postoperatively
Occasionally in normals (coronary sinus rhythm).
Peaked P-waves - seen in right atrial hypertrophy:
Tricuspid regurgitation (e.g. Ebstein anomaly)
Atrioventricular septal defect
Pulmonary hypertension
Cardiomyopathy
P-R interval
Normal in children is 2-4 little squares (0.08-0.1 6 seconds).
Not often seen in paediatrics. Rare to see signs of infarct. Normal Q-waves are seen in
Vl,V2 in young children and are allowed in other leads if small <0.2 mV.
--
f-
f
-
-
-
-
-
gz
eL2
Causes of Q waves
=
z
-
F
=
F
=
-
-
-
-
=
-
-
a ~extrocardia
==
=-
--
eft ventricular volume overload V5,V6 (e-g. large PDA or VSD)
--
-
QRS-wave
Normal duration is 0.08 seconds. Prolonged in right bundle-branch block, e.g. after repair
of tetralogy of Fallot.
Delta (6)wave - seen in Wolff-Parkinson-White syndrome, the slurred upstroke to
R-wave, represents depolarization via the accessory pathway, with a short P-R interval.
-
-
There will be a wide QRS and the QRS axis will be unusual, even superior. Likely to
-
-
--
=
-
-
f
=
-
- have supraventricular tachycardias (re-entry).
a R-S progression - the best way to assess ventricular hypertrophy. The following pattern
should be seen:
Lead V1 Lead V6
Therefore, if there is persistence of the newborn pattern in an infant then right ventricular
hypertrophy is suggested. Other features of hypertrophy are:
Right ventricular hypertrophy
Upright T-waves V1 (from 1 week to 16 years is abnormal)
; Q-wave in V1
R-waves > 2 0 m m in V1
1 Left ventricular hypertrophy
i Inverted T-waves in V6
Q-waves in V6
5- Left axis deviation for age
2 R-waves > 20 mm in V6
$. Biventricular hypertrophy
! Total voltage (R+S) in V3 or V4 of > 60 mm only sign of large VSD
5-
~ Q Q interval
-T
deasured from the start of the Q-wave to the end of the T-wave (U-wave if present). This
epresents the total time taken for depolarization and repolarization. Normal is < 0.44
eonds for a heart rate of 60lmin. To correct for the heart rate use the Bazett formula:
I
QTc = Q T / ~
S-T segment
Unusual to get marked changes in S-T segments. May represent isctiaemia in Kawasaki
disease, anomalous left coronary artery from pulmonary artery and postoperative cardiac
surgery.
T waves
Normally T-waves are downward in V1 from 1 week to 16 years of age.
T-wave axis should be within 75 degrees of QRS. If not think of:
Friedreich ataxia
Dilated cardiomyopathy
Noonan syndrome
Long Q-T syndrome
Peaked T waves seen in hypokalaemia and digoxin toxicity.
15.2 Tachycardias
Supraventricular tachycardia (SVT)
Likely if the heart rate is > 240/min
Tend to be faster rates 300lmin
N
15.3 Bradycardias
Complete heart block
-
Often present at birth but may be diagnosed antenally. Baby is born (sometimes following
emergency Caesarean section) with heart rate 70lmin but is perfectly well. Usually needs
no treatment for several years. Intervene if Faltering growth, collapses, heart failure, Stokes-
Adams attacks or resting heart rate < 40/min. These would be indications for pacemaker
insertion.
Causes
Maternal systemic lupus erythematosus
Congenitally corrected transposition of the great arteries
Post-operative
Myocarditis
Rheumatic fever
Infantile
Cottage loaf
Total anomalous pulmonary venous connection
Visible ascending vein on upper left border
Globular heart
Usually associated with pericardial effusions, perhaps secondary to pericarditis or dilated
cardiomyopathy.
Situs
Check the heart is on the left along with the stomach bubble, and that the liver is on the
right. This may be helpful in diagnosing right atrial isomerism, etc., as above.
1Z CAFDIAC CATHETERIZATION
17.1 Diagnostic cardiac catheterization
To analyse cardiac catheter data, it is important to start with the aortic.saturations. Follow
the algorithm below.
PA Sao,
/
F I
Cyanotic CHD
\
pGl
I Not TGA
.1 LA S~O,
TGA No L-R shunt L-R shunt
at RA = ASD
-- Tricuspid Atresia
Pulmonary Atresia
at RV = VSD
at PA = PDA
1
Fallot @RV = pLV) AVSD ASD
TGAllVS @RV > pLV) TGAlVSD Small VSD Large VSD
Critical PS Eisenmenger Small PDA Large PDA
7
Ao pressure pPA < RV = Pulmonary stenosis
pAo < LV = Aortic stenosis
pDesc Aorta < pAsc aorta = Coarctation
If pink (aortic Sa02 3 94%) check pulmonary artery Sa02. If this is greater than
systemic venous Sa02, then there is a left to right shunt. If it is the same as venous Sa02
then look for a pressure drop (AS/CoA).
If blue (aortic Sa02 < 94%) check pulmonary artery Sa02. If this is greater than aortic
Sa02, then the diagnosis is transposition of the great arteries. If it is less than aortic SaOz
then the problem is not TGA. Check pulmonary artery pressure. If less than right
ventricular pressure then there is right ventricular outflow obstruction, probably tetralogy
of Fallot.
True diagnostic catheterization is rarely performed, use echocardiography instead
Usually for assessment between staged surgical operations
Pulmonary vascular resistance assessments for left to right shunts to determine
operability
Measure pulmonary artery pressure and resistance (PVR) at baseline
Measure oxygen consumption for accurate determination
Repeat measurement in nitric oxide at two different doses
Repeat measurement in oxygen or prostacyclin
If PVR > 7 Wood units X m2, then inoperable
If PVR falls by more than 20% then i s partly reversible
18. IMAGING
18.1 Echocardiography
Mainstay of diagnostic tools
Doppler to assess velocity (and hence pressure gradient) across valves or VSD
Colour-flow to highlight small defects or turbulent blood flow
Transoesophageal echo for posterior heart structures or during interventional cardiac
catheterization, especially in adults with congenital heart disease
Future uses for intravascular ultrasound, three-dimensional ultrasound and contrast
echocardiography
Brogan PA, Bose A, Burgner D, Shingadia D, Tulloh R, Michie C, Klein N, Booy R, Levin M,
Dillon MJ.2002. Kawasaki disease: an evidence-based approach to diagnosis, treatment,
and proposals for future research. Archives of Diseases in Childhood 86:4, 286-90.
Park MK, Guntheroth WG. 1987. How to Read Pediatric ECGs. Chicago: Year Book
Medical Publishers (still the best ECG book).
Tulloh RMR. 2005. Congenital heart disease in relation to pulmonary hypertension in
paediatric practice. Paediatric Respiratory Reviews 63:3, 1 74-80.
Chapter 2
Child Development, Child
Psychiatry and Community
Paediatrics
Joanne Philpot and Ruth Charlton
CONTENTS
Child Development
1. Developmental assessment
1.1 Milestones
1.2 Developmental examination for the Short Case examination
1.3 Management of the child with global developmental delay
2. Vision 76
2.1 Assessment af visual acuity
2.2 Squints
2.3 Examination of the eyes for the Short Case
3. Hearing
3.1 Assessment of auditory function
6. Dyspraxia
Child Psychiatry
15. Enuresis
22. The Children Act 1989 and Human Rights Act 1998
22.1 Aims of the Children Act
22.2 Human Rights Act 1998
1.1 Milestones
It is important to consider the four areas:
Gross motor
Fine motor and vision
Speech and hearing (language)
Social
3 months Able to raise head and Will fix and follow an object Vowel sounds and Social smile
chest on forearms through 180" in the noises uttered on (infant has
in the prone position horizontal plane social contact awareness that
Head steady when pulled Hands beginning to be Turns head to smile attracts
to sit brought to the mid-line sound, level to attention)
Attempts to make contact the ear May show
with offered object displeasure on
interruption of
social contact
12 months Crawling Pincer grip Two words with Waves bye bye
Pulls to stand Banging bricks together meaning
Cruising Responds to Claps hands
'give it to me' Empties cupboards
Shows recognition
of objects by using
them, e.g. brush
15 months Walking well Pincer grip refined, Expression several Drinks from a cup
tiny objects can be words Indicates wants
picked up delicately Understands words without crying, i.e.
Casting such as cup, pointing, pulling,
names of brothers asking
and sisters
Jargon and jabbering
Echolalia (repetition
of words spoken to
the child)
18 months Stoops and retrieves Delicate pincer grasp Points to parts of body Holds spoon and
objects Scribbles Understands up to gets food to mouth
Carries toys while 50 words .Into everything
walking Knows common Takes shoes and
objects by name, socks off
e.g. cat lndicates toilet
Follows one-step needs
command,
e.g. 'give me a doll'
Expression 25 to
50 words
2 years to Climbs and descends Copies vertical line Uses plurals Plays alone
2.5 years stain one step at a time Tower of eight bricks Follows two-step Eats with spoon
Kicks a ball request, eg 'get the and fork
Climbs furniture ball and put it in the
box'
Identifies objects from
hearing their use
Selects toy from others,
i.e. 'Give me the sheep,
brush'
continues
Age Gross motor Fine motor and vision Language Social
3 years Pedals tricycle Copies a circle Knows some colours Out of nappies
Jumpswell Matches two colours Three- to four-word during the day
Momentarily balancing sentences Separates from
on one foot Name, age and sex mother easily
on request (less apprehensive
Pronouns and plurals about you the
Knows more about candidate)
time, today and Eats with knife
not today and fork
Starts to tell stories Dresses with
supervision
4 years Stands on one foot well Copies a cross and square Count to 10 Shares toys
Hops Draws man with three parts Identifies several Out of nappies by
colours night
100s of questions Brushes teeth
Understands numbers Toilet alone
Past tense
Increasing concentration
5 years Walks down stairs one Copies triangle Comprehension: Chooses friends
foot per step Draws man with six parts 'what do you do if Comforts in distress
Bounces and catches Writes name you are hungry, cold, Acts out role play
ball Do up buttons tired?'
Comprehension of
prepositions: 'put brick
on, under, in front of1;
opposites: hot, cold;
if elephant is big,
a mouse is 'small
definition of words,
e.g. ball, banana
Frimitive reflexes
Sucking and rooting present from 0-6 months
Palmar grasp present from 0-3 months
Stepping present from 0-6 weeks
Asymmetrical tonic neck reflex (ATNR) present from 1-6 months - with the child
supine, the head is rotated to one side leading to extension of the arm and leg on the
side towards which the head is turned and flexion of the arm and leg on the opposite
side. A good way to remember this is the 'Archer's reflex, like firing a bow and arrow. A
strong ATNR is usually abnormal and a sign of cerebral palsy
Moro present from 0-4 months
Head-righting present from 6 months and persists
Parachute reflex present from 9 months and persists
Essential Revision Notes in Yaediatrics fix the MRCPCH 2nd Edition
Inspect
Look for clues. Remember the families will have come equipped for the day. Look for
feeding equipment, nappy bag, the toys they have brought
Is thechildwell?
Does the child look dysmorphic?
Are there any obvious neurological abnormalities?
Assessment
Pitch in at around the age you think the child is, i.e. if they look around 18 months do
not start asking them to copy circles, etc
Assess each of the four developmental categories. Once you have demonstrated they
can do one level push up to the next level until they are not able to perform the task.
For example: if you have demonstrated the child can copy a square do not ask them to
copy a circle as you have already demonstrated the child is past this level, instead see if
they can copy a triangle
Keep control of the situation. If the child is playing already, WATCH. You may be able to
complete the whole assessment by observation alone
If the child is already sitting use the opportunity to assess language, social and fine-
motor development. Do not disrupt the child to do gross-motor tests - you may well
have difficulty settling him again and in the older child gross motor you the least
additional information. Leave it to the end
Use the parents if the child is shy or apprehensive, e.g. ask the parents to draw a circle
for the child to copy or test the child about colours, numbers; stories, etc.
* If the child does not co-operate do not panic. You can still get clues from observing.
Remember stranger awareness and non-compliance are developmental milestones in
themselves
Presentation
Summarize any relevant clinical findings, e.g. this girl looks ill, has a drip in, a Hickman
line, etc, which may be affecting your assessment. If the child looks dysmorphic then
say so
This child has a developmental age of X because:
Gross motor - I have demonstrated that they can do this but not that
Fine motor - I have demonstrated, etc
'Demonstrated' is better than 'can' or 'cannot'. It means that the parents cannot correct you
by saying 'yes he canf! Remember you are only assessing the child over a few minutes.
If you have a developmental discrepancy between the four areas then present this, e.g. this
child has a developmental age of 4 in gross- and fine-motor skills but a developmental level
C'hild Development, Child Psl/chidtr\/ ,?17dCornrnu~ityPaediatrics
of 2 years in speech and language and social skills. Follow this by saying what you would
like to do next, e.g. I would like to formally test his hearing to exclude a hearing problem.
^= Meningitis=- -
Postnatal
Trauma
lntracraniat infections
~ ~ e c a u s e s
Endocrine
Essenti,? 1 Revision Notes in E ~ d i ~ ~ t rt ci c~ the
rs MRCPCH 2nd Edition
History
A good history is essential to help determine the cause and appropriate investigations.
Information is required on prenatal history, perinatal history and postnatal development. Are
there any associated symptoms such as seizures? General health is important when consid-
ering metabolic disorders. Family history may give the strongest clue to a chromosomal
disorder. Enquire about previous pregnancy losses.
Examination
A thorough examination is essential.
Neurodegenerative conditions affecting the grey matter tend to present with dementia and
seizures. Conditions affecting the white matter tend to present with spasticity, cortical
deafness and blindness.
Inspect for:
Sex of child - X-linked conditions such as fragile X, Menkes, Hunter, Lesch-Nyhan
syndromes
Age of the child:
First 6 months - Tay-Sachs disease, Leigh disease, infantile spasms, tuberose
sclerosis
Toddlers - infantile metachromatic leukodystrophy, mucopolysaccharidoses,
infantile Gaucher, Krabbe disease
Older children - juvenile Batten disease, SSPE, Wilson disease, Huntington
chorea
Child Development, Child Psychiatry and Community Paediatrics
Systematic examination
Eyes - corneal clouding, cataract, cherry-red spot, optic atrophy
Neurological examination including gait, scoliosis, tremor, extrapyramidal movements,
tone, power and reflexes of limbs
Associated system involvement (e.g. cardiac abnormalities, organomegaly in metabolic
disease)
Genitalia
Hearing and vision should be checked
Further assessment often involves input from other professionals of the child development
team, e.g. speech and language therapists and physiotherapist.
Investigations
A thorough history and examination may lead to targeted investigations, e.g. a specific
genetic test or metabolic test. For approximately 40% of cases no Cause is found. The two
most useful investigations are genetic studies and brain imaging.
If no specific diagnosis is suggested then consider:
Blood tests
Chromosomal analysis
Thyroid function tests
TORCH serology in infants (TORCH, toxoplasmosis, other (congenital syphilis and
viruses), rubella, cytomegalovirus and herpes simplex virus)
Plasma amino acids
Ammonia
Lactate
White cell enzymes
Urine tests
Urinary organic acids
Urinary amino acids
Urinary mucopolysaccharidoses
Esrenti~lRevision Notes in rcledintrrics 69.
the MKI-YCM 2nd Edition
Brain imaging
This will identify congenital brain abnormalities and diagnose degenerative conditions such
as the leukodystrophies and grey matter abnormalities.
EEG
This will identify SSPE, Batten disease
Management
This is multidisciplinary. The precise make-up of the team depends on local resources. It
can include:
Community paediatrician
Speech and language therapist
Physiotherapist
Occupational therapist
Child psychologist/psychiatrist
Play therapist
Pre-school therapist, e.g. portage
Nursery teachers
Health visitors
Social workers
2. VISION
Each year around 500 children are registered blind or partially sighted. Early diagnosis is
important because:
Appropriate treatment may reduce the severity of the disability.-orstop progression
Other medical conditions associated with visual problems can be diagnosed
Genetic counselling can be offered
Pre-school learning support can be started
Current recommendations
Newborn screening inspecting the eyes for anomalies
Repeat eye examination at the 6-week check
Orthoptist's assessment of all children in the 4- to 5-year age group. This is to assess
acuity and to detect squints. The advantage of screening at this age is easier testing of
visual acuity compared to younger children. Parents will usually recognize a squint but
amblyopia as a result of refractive error will only be detected when the child's vision is
assessed monocularly
Screening very low birth-weight babies to detect retinopathy of prematurity
Visual screening in children with other major disabilities
I
Between the ages of 6 weeks and 4 years identification of visual defects will rely on
concern being raised by the parents or other professionals.
I
i
i Methods of testing visual acuity
d y w ~ tb
~referklitial'looking test.-'ttiis can b; ~l(sedin a ~ h i ltoo 1
g identify ,
objects. iarge cards wiiti pictures on in different positions, i.e. top right-hand
corner, bottom lek-hand corne(are sh_own,to the child and the eye movements
are observed as the child'fbcuses on the picture i s it moves i ~ o u n the d card
Picture cards - children asked to identify . picture
. cards at a set distance. Picture
2.2 Squints
Squints are common, occurring in approximately 4% of children. There is a strong familial
incidence. A squint is usually noticed by the parents first and parental report of squint
should be taken seriously.
A squint is a misalignment of the visual axis of one eye.
It is either:
Latent - i.e. only there at certain times (such as fatigue, illness, stress)
Manifest - i.e. present all the time
It is either:
Alternating - the patient uses either eye for fixation while the other eye deviates. As
each eye is being used in turn, vision develops more or less equally in both
Monocular - only one eye is used for fixation and the other eye consistently deviates.
The child is more prone to develop amblyopia as the deviated eye is consistently not
being used
It is either:
Convergent - i.e. turns in
Divergent - i.e. turns out
It is either:
Non-paralytic
Paralytic
Non-paralytic squint
'This is the more common type of squint and includes the following: -
Comprises the majority of the congenital and infantile convergent squints
The accommodative convergent squint. In some infants accommodation results in over-
convergence or crossing of the eyes. This type of deviation most commonly occurs
around 18 months to 2 years of age. The child is also usually long-sighted. In most cases
the eye crossing can be controlled with glasses that correct for the long-sightedness
In a few cases a non-paralytic squint is the result of an underlying ocular or visual
defect, e.g. cataract, high refractive errors, retinopathy of prematurity, retinoblastoma
Paralytic squints
These are the result of weakness or paralysis of one or more of the extraocular muscles.
They are less common.
The deviation worsens on gaze into the direction of action of the affected muscle.
Congenital paralytic squints are more commonly the result of developmental defects of
the cranial nerves, muscle disease, or congenital infection
Acquired paralytic squints usually signify a serious pathological process, e.g. brain
tumour, central nervous system infection, neurodegenerative disease
Cliild Development, Ctlilcl Psvc.hiCjtrv ancl Cornmunit); Pc~ediatrics
Assessment of squint
Ocular movements assessed to exclude paralytic squint
Corneal reflex examined, looking for symmetry of the light reflex
Cover/uncover test. The child sits comfortably on a parent's lap. Their attention is
attracted and while they are looking at an object one of the eyes is covered. If the
uncovered eye moves to fix on the object there is a squint present, a manifest
squint. This may be a:
Unilateral squint - the squinting eye takes up fixation of the object when the
other eye is covered. When the cover is removed the squinting eye returns to its
original squinting position
Alternating squint - the squinting eye takes up fixation of the object when the
other eye is covered. When the cover is removed the squinting eye maintains
fixation and the previously fixing eye remains in a deviated position, i-e..the
squint alternates from one eye to the other
Order of examination may be influenced by your findings along the way, e.g. if you find an
abnormality such as a squint you may focus on the assessment of that.
Between 1 and 2 children per 1,000 population have permanent childhood deafness, 84%
congenital and 16% acquired. Early detection of hearing problems and treatment have
permanent beneficial effects.
Possible interventions
Hearing aids
Cochlear implant - will allow more deaf children to develop spoken language
Involvement of Speech and Language therapy services
Pre-school/in-school learning support, e.g. signing
At 8 months
Testing of all children by the health visitor. Screening test used is the hearing distraction test.
At pre-school entry
At 4-5 years, testing for all children by school nurse. Screening test used is the sweep
audiogram.
If the screening test is positive the child is referred to an audiologist for further assessment.
Referrals to audiology can also be made at any time if concerns are raised about hearing or
speech and language development, e.g. by the parents.
a 8 months
Hearing distraction test
a 2 years
Visual reinforcement audiometry
Performance games
Speech discrimination test
Free-field audiometry
3 years and over
Pure-tone audiometry
It is important to consider both the developmental and the chronological age when deciding
which test to use.
Distraction test
This test is performed routinely by health visitors on all infants at 8 months. The child sits on
the mother's lap with a distracter sitting in front of them and the noise stimulus presenter
remaining behind the child (out of sight). The test relies on the normal child's response to
turn to locate the source of the sound and on the fact that they have not yet developed
permanence of objects, so that once they have been distracted again by the person in the
front they forget about the tester behind them. A series of sounds at different frequencies are
presented at a level of about 40 dB at a set distance of 1 m behind the child at ear level.
There are standardized sounds and test materials - Manchester rattle, warbler, Nuffield
rattle, voice.
Free-field testing
Suitable for children aged 2 years and over. It does not require understanding or co-
operation so is useful for children with developmental delay or behavioural problems.
Sounds are produced within a free field at different frequencies. The child's reaction to
sound is observed and assessed if satisfactory.
Pure-tone audiometry
By 4 years of age a child should be able to co-operate with this test. Both ears can be tested
separately. The audiometer delivers sounds at different frequencies and intensities. It is
possible to determine the child's threshold at each sound frequency. It takes at least
10 minutes to perform.
The audiogram
Key to symbols used:
x-axis = frequency (Hz)
y-axis = hearing level (dBHL)
0 = air conduction right ear
X = air conduction left ear
A = bone conduction unmasked - vibrator vibrates whole skull no matter which
mastoid it is placed on. Assesses both cochleas unless one ear is masked.
[ = masked bone conduction right
I = masked bone conduction left
1 = off scale (no response)
Air conduction assesses the whole auditory system, bone conduction assesses the auditory
pathway from the cochlea and beyond. A difference between the two suggests a conductive
loss (middle or outer ear). Equal impairment suggests a sensorineural loss. Impairment
greater in air than bone suggests a mixed loss.
Normal range -10 to +20 dBHL
Moderate hearing loss 20-40 dBHL
Profound hearing loss 90-1 20 dBHL
-
Li
88 Child Development, Child Fsychia try and Community Paedia tries
I1
Left ear
120 250 500 1000 2000 4000 8000 250 500 1000 2000 4000 8000
Frequency (Hz) Frequency (Hz)
Sweep audiometry
Same principle as above but quicker to perform because various sound frequencies are
tested at only one intensity (around 25 dB). It is used as a screening test at the pre-school
entry. If the child fails at any frequency then full audiometry is performed.
Tyrnpanometry
The compliance of the tympanic membrane and ear ossicles is assessed by a probe that fits
snugly in the external auditory canal and which is able to generate positive and negative
pressures while recording the sound reflected back from a small microphone within the
probe. Suitable for any age child. Primarily used to check for 'glue.earf. In the normal ear,
the peak is at 0 pressure, reflecting the equal pressures either side of the drum. The trace is
flattened if a middle-ear effusion is present.
8c
I
,,
I 1
m - t
I
.--
a
8E 1.0-
0
-400 -200 0 200 400
Pressure (da Pa)
Essential Revision Not- in Paediatrics tbr the t\,1RCPCh/ 2ntl Eclitiola
0
-400 -200 0 200 400
Pressure (da Pa)
E
5 1.0-
-
0
-400 -200 0 200 400
Pressure (da Pa)
Speech
Expressive - production of speech
Comprehension - understanding what is being said
Comprehension development is ahead of expressive development
Non-verbal communication
Eye contact, pointing, body gestures
Social communication
Reciprocity and sharing of communication, insight into what i s socially acceptable,
sharing communication, listening skills
Problems in speech and language development are very common in pre-school children
(5-1 0%) and more common in boys.
Investigations
It is important to confirm that the hearing is normal (see earlier)
EEG if there is a clear history of loss of language skills to exclude epilepsy syndromes
Chromosomal studies if there are other associated difficulties
Social skills
Non-verbal behaviours, e.g. eye contact, body posture
Failure to develop peer relationships
Lack of social and emotional sharing
Other features
The abnormal functioning is observed in one of these areas of development before the
age of 3 years
The behaviour is not accounted for by another diagnosis. A large number of children
with syndromes and chromosomal abnormalities have autistic features
Over 5O0/0 also have associated intellectual impairment that can affect the behaviours
observed
By middle age 30% havedeveloped epilepsy
Hearing and visual problems are common
Dyspraxia is common
Asperger's syndrome
This is a condition at the mild end of the autistic spectrum. There is normal early language
development and intellectual functioning. In early childhood it becomes apparent that the
child has behavioural and social difficulties and some speech and language problems. The
diagnosis can often be missed.
Management
Each child needs to be assessed as an individual to determine the degree of difficulty in
social and communication skills, and an individual management plan must be decided
upon.
Health
Communication with parents about their concerns and difficulties with management of the
child is essential. Access to more information should be provided, e.g. the National Autistic
Society. Access to psychiatric/psychology services for the individual and the family are
essential.
Education
Liaison with education is essential. Pre-school intervention within the home and nursery is
possible with early diagnosis. Local outreach services may be available to go into the home
to give management advice. Formal pre-school notification by health to education allows
the child's needs to be assessed before school placement. School placement can vary from
mainstream with support through to a special unit depending on the individual child.
Children on the autistic spectrum often require a high teacher to pupil ratio in a highly
structured environment to minimize disruptions. Speech and language input to help
communication skills is also important.
Social services
Living with a child on the autistic spectrum affects all members of the family. Families often
need respite care and support in the home.
6. DYSPRAXIA
Dyspraxia is a common type of sensory-processing problem that causes difficulty in
performing co-ordinated actions. The child is often described as clumsy. There may be
associated problems of language, perception and thought processing. Concern about
dyspraxia is one of the commonest reasons for a referral to a paediatrician from education.
Differential diagnosis
Learning disability
Neuromuscular problem
Attention-deficit hyperactivity disorder
Specific speech and language delay
Visual problem
Remember that a child can have more than one difficulty, e.g. dyspraxia and attention-
deficit hyperactivity disorder.
Assessment
In the pre-school child initial assessment is usually by a paediatrician to exclude other
pathologies, including general developmental delay. The school-age child is also often
assessed by a paediatrician, but information should also be obtained from the school about
the child's difficulties and overall progress. Often a speech and language assessment and
occupational therapy assessment are also required.
The occupational therapist examines:
Fine- and gross-motor developmental levels
Visual motor integration (e.g. doing puzzles or copying shapes)
Visual perception
Balance and posture
Responses to sensory stimulation
Bilateral co-ordination
Motor planning
Management
Dyspraxia is not curable but the child often improves in some areas with maturity. Liaison
between education, health professionals and the child and parents is crucial to help the
child within the classroom and the home environment. The school's special educational
needs co-ordinator (SENCO) and school nurse can play an important role in the commu-
nication between health and education. Speech and language therapists and occupational
therapists give advice to the school to help with difficulties in the classroom. Sometimes
group and individual therapy can help, e.g. a phonology course for articulation difficulties.
Advice for parents to help with home activities is also important.
Essential Revision Notes in Paediatrics tor the M RCPCH 2nd Editi(ln
Pre-school children
Health are required by law to notify the local education authority (LEA) of children over
the age of 2 years who may have special educational needs
The parents, nursery and social services are also able to notify education
The LEA then collects information about the child, which is passed onto the educational
psychologist who decides if a formal assessment for statementing is appropriate
If formal assessment is requested health are asked to write a report on the child's needs,
the 'E medical'. This report will give information about health, e.g. hearing, vision,
epilepsy, physical problems, and a summary of the developmental problems. It also
informs education of other therapists involved such as physiotherapy, speech and
language. It also describes the practical needs of the child, eg. toileting, feeding,
dressing, what to do if the child has a fit. Other professional's also submit reports
including the parents
Once the formal assessment is completed the LEA decides whether to statement the child or
not. (The majority of children are issued a statement after formal assessment)
Schoolchildren
The process is the same, but the initial notification usually comes from the school or the
parents rather than health, as the children are in school.
Child Development, Child Psychiatry and Community Paecliatrics
Child Psychiatry
8. ATTENTION-DEFICIT HYPERACTIVITY DISORDER (ADHD)
It is estimated that 1% of school-age children meet the diagnostic criteria for attention-
deficit hyperactivity disorder (ADHD). Commoner in boys.
Diagnosis
Problems occur in three areas:
Inattention
Hyperactivity
impulsiveness
It is possible to have one of these features without the others, e.g. marked inattention
without the hyperactivity or hyperactivity without inattention.
In addition:
The behaviour should have persisted for at least 6 months
The behaviour should be inconsistent with the child's developmental age
There must be clinically significant impairment in social or academic development
The symptoms should occur in more than one setting
There should be no other explanation for the symptoms, e.g. psychiatric illness
Diagnosis requires detailed history and information gathering from parents, school and other
professionals involved.
Children with ADHD develop emotional and social problems, poor school performance
and problems within the home because of the difficult behaviour. Associated with unem-
ployment, substance abuse and crime in adulthood.
Differential diagnosis
Inappropriate expectations
Language/communication disorder
Social problem
Specific learning difficulty
Chronic illness, e.g. asthma
Epilepsy
Dyspraxia
Management
Management involves a comprehensive treatment programme. There needs to be multi-
professional collaboration including the parents.
Essential Revision Notes in Paediatrjcs for the AilKCtPCM 2nd Edition
i
i
NICE is part of the National Health System (NHS). It provides guidance on medicines, 1
medical equipment, diagnostic tests and clinical procedures and where they should be
used.
Presentation
May be acute or insidious (gradual withdrawal and failing schoolwork).
Child Dcveloptnent, Ci7 ild Psvcl~ia
try c ~ ni101~1rnunit
d y Paedia tries
Differential diagnosis
It may be difficult to distinguish from major mood disturbance, e.g. manic depressive
psychosis or organic causes of psychosis e.g. neurodegenerative or drug-induced episode,
systemic lupus erythematosus, epilepsy, Wilson disease, thyrotoxicosis and vasculitis. (Any
child presenting with psychotic symptoms should have an EEG and brain MRI scan).
Treatment
Drugs - antipsychotics, e.g. clozapine (few extrapyramidal side-effects but risk of
agranulocytosis), chlorpromazine, haloperidol
Individual and family therapy
Adequate educational provision essential
Prognosis
Chronic or relapsing course is common
Good prognostic factors include high intelligence, acute onset, precipitating factors,
older age at onset and normal premorbid personality
Symptoms
These include:
Moodinesslirritability
Withdrawal from friends, family, regular activities
Self-criticallself-blaming
Poor concentration
Essential Revision Notes in Paediatrics for the MKC'YCH 2nd Edition
Treatment
General advice should be given to all children and young people with mild, moderate or
severe depression on:
Self-help materials
The benefits of regular exercise
Sleep, hygiene and anxiety management
Benefits of a balanced diet
Mild depression - if this persists for 4 weeks or more with no significant co-morbid
problems or suicidal ideation offer one of the following psychological therapies for a limited
period of 2-3 months:
Individual non-directive supportive therapy
Group cognitive behavioural therapy
Guided self-help
Antidepressant medication should not be used for the initial treatment of mild
depression
Moderatelsevere depression:
First-line treatment is psychological therapy such as individual cognitive behavioural
therapy or interpersonal therapy or family therapy
If depression is unresponsive consider additional psychological-therapiesor medication
(after multidisciplinary review)
Fluoxetine is the most commonly prescribed but it is not licensed for under 18s and
should be used extremely cautiously, especially in under 11s
Second-line drug treatments unclude sertaline or citalopram
High-risk of suicide, serious harm and self-neglect:
Consider inpatient treatment
Use electroconvulsive therapy very rarely in 12-1 8 year olds
Do not use:
Paroxetine, venlafaxine, tricyclic antidepressants, St John's wort
Consideration should be paid to the parent's mental health particularly the possibility of
depression and substance abuse.
<?ndCommunity Paediatrics
Child Development, Child Psr/chiC~trv
r suicide in adolescents
Male sex
Self-mutilation
Includes scratching, cutting, cigarette burns, tattooing, bruising, biting and inserting
needles
Typically seen in teenage girls with personality problems, e.g. aggressive/impulsive
behaviour, eating disorders, poor self-esteem
Also occurs in those with schizophreniallearningdisability
Essential Revision Notes in Pner/iatrics for the Mh'CPCFl21iclEdition
Aetiology
Familial factors - concordance rate for anorexia nervosa in monozygotic twins is 50%
as compared to 10% for dizygotic twins. Other risk factors include family history of
depression, alcoholism, obesity or eating disorder. Children with anorexia nervosa often
come from overprotective and rigid families where there is a lack of conflict resolution
Individual factors - e.g. previous obesity, fear of losing control, self-esteem dependent
on the opinion of others and previous or ongoing abuse
Sociocultural factors - there is a higher prevalence in high social classes and certain
occupations, e.g. ballet dancers
Neurohumoral factors - controversy remains over the exact role of substances such as
serotonin in the pathogenesis of eating disorders
Child Development, Child PsychiLqtry and Community Paedintrics I
Clinical features
Anorexia nervosa
Usually this begins as a 'typical' adolescent diet to reduce stigmatization from obesity. Once
weight begins to reduce, weight goals are constantly reset and compulsive weighing
becomes a feature. Often physical activity is increased and social contacts diminish.
Disordered thinking and poor concentration develop as the disease process progresses.
Bulimia nervosa
Bulimia is even more common than anorexia in those with a past history of obesity. Self-
loathing and disgust with the body are also greater than in anorexia. Patients are more likely
to seek medical help for their symptoms. Coexisting substance abuse is not uncommon.
Both bulimia and anorexia are frequently associated with major depressive and anxiety
disorders.
Parotitis
Essential Revision Notes in Pacdiatrics fc~rthe MRCYCH 2ncl Edition
Treatment
Most patients with anorexia can be treated as outpatients, with hospital admission only if
adequate weight gain at home is not possible or there are complications such as
depression.
A combined multidisciplinary approach with monitoring of eating and weight, biochemical
monitoring and ongoing psychotherapy is required. At present the psychotherapy usually
involves behavioural, cognitive and psychodynamic components. Rarely medication such
as antipsychotics or antidepressants may be required. Appetite stimulants are used even less
often. Prokinetics such as cisapride and domperidone may be useful in patients with
delayed gastric emptying. Adequate provision for education is essential. Feeding against the
will of the patient can only be done in the context of the Mental Health Act 1983 or the
Children Act 1989.
Young people with bulimia may be treated with cognitive behavioural therapy, adapted to
suit their age and development. A trial of selective serotonin reuptake inhibitors (SSRls) may
be considered but no other drugs are recommended for the treatment of bulimia nervosa.
Treatment
Avoid unnecessary investigation of minor somatic symptoms
Early, if necessary graded, return to school
Support for parents and child
Close liaison with school
In chronic cases a gradual reintegration back into school is required, possibly with a
concurrent specific behavioural programme and targeted family therapy.
Overall two-thirds of children will return to school regularly. Those who do badly are often
adolescents from disturbed family backgrounds.
Truancy
In contrast to the above, truancy always reflects a lack of desire to go to school rather than
anxiety re school attendance and as such may be part of a conduct disorder.
Bullying
Bullying may be defined as 'the intentional unprovoked abuse of power by one or more
children to inflict pain or cause distress to another child on repeated occasions'. Estimates
on the prevalence of bullying vary widely, but many studies report that between 20% and
50% of school-aged children have either participated in or been victims of bullying. Verbal
harassment is the commonest form of bullying and is often not recognized as such.
Although it is important not to stereotype, certain characteristics are commonly exhibited by
bullies:
Poor psychosocial functioning
Unhappiness in school
Concurrent conduct disorders
Emotional problems
Social problems
Alcohol and nicotine abuse
Children who suffer at the hands of bullies may consequently suffer from:
Anxiety
Insecurity
Low self-esteem and self-worth
Mental health problems
Essential Revision Notes in Paediafrics tor the M RCPCH 2nd Edition
Sleep difficulties
Bed wetting
Headaches
Abdominal pain
Carefully planned programmes may reduce the incidence of bullying by 50% or more. Such
strategies rely on teaching appropriate social skills to children who bully, developing clear
rules which they are expected to adhere to, providing an increased level of supervision,
particularly within the school environment, and facilitating access to other services they
may require, e.g. child psychiatry, social services, etc.
Sleep stages
Sleep consists of several stages that cycle throughout the night. One complete cycle lasts
90-1 00 minutes.
i
i
C-llild Develoy~nlent,Child Psvc.hicltry (117d Community Paediatrics
Night terrors
These are most commonly seen in children between the ages of 4 and 7 years. Typically the
child wakes from deep or stage 4 sleep apparently terrified, hallucinating and unresponsive
to those around them. Usually such episodes last less than 15 minutes and the child goes
back to sleep, with no recollection of the events in the morning. It is unusual to find any
underlying reason or stresses contributing to the problem.
Nightmares
These occur during REM sleep and the child remembers the dream either immediately or in
the morning. Underlying anxieties should be sought.
Sleepwalking
This occurs during stages 3 or 4 of sleep and is most often seen in those between 8 and
14 years.
14.4 Tics
These occur transiently in 1O0/0 of children and are much more commonly seen in boys.
Onset is usually around the age of 7 years and, while simple tics are seen most commonly.
Cilles de la Tourette syndrome may occur in childhood. This phenomenon is characterized
by complex tics occurring in association with coprolalia (obscene words and swearing) and
echolalia (repetition of sounds or words).
Treatment
Most resolve spontaneously
Reassure accordingly
a Behavioural or family therapy if appropriate
Medication: haloperidol, pimozide, clonidine (in very severe cases only)
Outcome
Simple tics - complete remission
Tourette's syndrome - 50% have symptoms into adult life
15. ENURESIS
This is defined as the involuntary passage of urine in the absence of physical abnormality
after the age of 5 years. Nocturnal enuresis is much more common than diurnal enuresis,
affecting at least 10% of 5-year-olds. Although most children with nocturnal enuresis are
not psychiatrically ill, up to 25% will have signs of psychiatric disturbance. Diurnal enuresis
is much more common among girls and those who are psychiatrically disturbed.
Aetiology
Positive family history in 70%
Developmental delay
Psychiatric disturbance
Small bladder capacity
Recent stressful life events
Large family size
Social disadvantage
Treatment
Exclude physical basis (history, examination, urine culture, +I- imaging)
Look for underlying stresses
Reassure child and parents of benign course
Star chart
Enuresis alarm (7 years and older)
Drugs (short-term control only) desmopressin, tricyclic antidepressants
It must be remembered that child sexual abuse may present with enuresis and/or enco-
presis.
Treatment
Exclude physical problems, e.g. Hirschsprung's disease/hypothyroidism/hypercalcaemia
Laxatives to clear bowel
Education for parents and child
Star chart
Individual psychotherapy
Family therapy
It is unusual for this problem to persist into adolescence
Prevalence
Approximately 40h
Strong male predominance
Clinical features
Temper tantrums
Oppositional behaviour (defiance of authority, fighting)
Overactivity
Irritability
Aggression
Stealing
Lying
Truancy
Essential Revision Notes in Paediatrics tbr the MRCPCH 2nd Edition
Bullying
Delinquency, e.g. stealing, vandalism, arson in older children/teenagers
'Oppositional defiant disorder' is a type of conduct disorder characteristically seen in
children under 10 years. It is characterized by markedly defiant, disobedient, provocative
behaviour and by the absence of more severe dissocial or aggressive acts that violate the
law or the rights of others.
Aetiology
Family factors: lack of affection, marital disharmony, poor discipline, parental violence1
aggression
Constitutional factors: low IQ, learning difficulties, adverse temperamental features
Oppositional peer group values
Urban deprivation/poor schooling
Differential diagnosis
Young people with conduct disorders have an increased incidence of neurological signs
and symptoms, psychomotor seizures, psychotic symptoms, mood disorders, ADHD and '
learning difficulties.
Treatment
Family/behavioural therapy
Practical social support, e.g. rehousing
Prognosis
Half have problems into adult life
Child Development, Child Psychiatry .?nd Community Paediatrics
Community Paediatrics
18. CHILD HEALTH SURVEILLANCE
The health authority is responsible for ensuring that an adequate surveillance programme is
offered to all children and that it is monitored effectively. The programme should comprise:
Oversight of health and physical growth of all children
Monitoring developmental progress of all children
Provision of adequate advice and support to parents
Programme of infectious disease prophylaxis
Participation in health education and training in parenthood
ldentification of 'children in need' in accordance with the Children Act
ldentification and notification of children with special educational needs in accordance
with the 1981 Education Act
Age Vaccine
Rubella vaccine
Any girl who missed the MMR should be immunized between the ages of 10 and 14 years.
Hepatitis B vaccine
At present the vaccine is recommended only for:
Babies born to mothers who are chronic carriers of hepatitis B virus or to mothers who
have had acute hepatitis B during pregnancy
Families adopting children from countries such as Southeast Asia, in whom hepatitis
status is unknown
MMR Live, attenuated As above + allergy to Malaise, fever, rash within 7 Medical Research
neomycin or kanamycin -1 0 days, Parotid swelling 1% Council and CSM
Febrile convulsion 1/1,000 concluded no link
Arthropathy/thrombocytopenia rare between MMR
Theoretical risk of encephalitis but and autism or
causal evidence lacking bowel disease.
Encephalitis much more likely Separate
secondary to measles in vaccines may be
unimmunized child harmful. Adverse
All side-effects less common after publicity led to a
2nd dose fall in uptake rates
and consequent
increased
risk of measles
outbreak
BCG Live, attenuated As above + Vertigo and dizziness occasional If child has eczema
A and C vaccines positive sensitivity skin Immediate allergy/anaphylaxis rare give at eczema-free
test to tuberculin protein Severe injection site problems site
Generalized septic usually due to poor injectipn Tuberculin skin test
skin conditions technique must be done
Adenitis First in all children
Lupoid-type local reaction (rare) over 3 months
Widespread dissemination of Reaction to
organi;m (v. rare) tuberculin protein
may be suppressed by:
infectious
mononucleosis,
other viral
infection,
live viral vaccines,
Hodgkin's disease,
sarcoid,
corticosteroids,
immunosuppressant
treatment or
diseases
20.2 Fostering
Foster care offers a child care in a family setting but does not provide legal permanency as
parental rights remain with the natural parents, local authority or courts, depending on the
legal circumstances. Different types of foster care include:
Care of babies awaiting adoption
Young children in whom return to parents is anticipated
For some children with strong natural family ties long-term fostering is appropriate.
Foster parents are selected by a foster panel and, as with adoption, their health and that of
the children awaiting fostering is considered.
22. THE CHILDREN ACT 1989 AND HUMAN RIGHTS ACT 1998
22.1 Aims of the Children Act
This Act introduced extensive changes to legislation affecting the welfare of children. Its
main aims included:
Restructuring custody and access in divorce
Moving towards a 'family court' handling all public and private proceedings about
children
Creating a single statutory code for the protection of children through the courts
Promoting interagency co-operation in the prevention, detection and treatment of child
abuse and neglect
Making legal remedies more accessible while also encouraging negotiation, partnership
and agreed solutions which avoid the need to resort to court
In all of the above, the Act stresses that the child's welfare is the paramount consideration. It
provides a checklist of welfare parameters aimed at ensuring that in planning for the child's
protection and upbringing, full account is taken of his or her needs, wishes and character-
istics.
A Care Order
This order confers parental responsibility on the social services (in addition to that of the
i parents) and usually involves removal from home, at least temporarily. It may be applied for
in cases of non-accidental injury, where inquiries will take some time and where the child
is not regarded as being 'safe' at home.
A Supervision Order
This gives social services the power and duty to visit the family and also to impose
&g conditions, such as attendance at clinic, nursery, school or outpatient visits.
$[
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f
E
ta
E 115
Essentia 1 Revision Notes in Bedia trics tbr the /tlKCPCM 2nd Edition
Both care and supervision orders may be taken out by a court if that court is convinced that
thresholds for appreciable harm to the child have been met. The court, however, is under
duties to consider the full range of its power and not to make any order unless doing so
would be better for the child than making no order. Whilst proceedings for either of these
orders are pending, the court may make 8- and then 4-weekly cycles to allow time for the
child's needs to be comprehensively assessed, and for parties to prepare their proposals for
court.
Wardship
If insufficient powers are available via the Children Act then wardship via the High Court
may be applied for. This gives the court almost limitless powers and is used in exceptional
circumstances, such as when a family objects to surgery or medical treatment for religious
reasons.
Despite all the above, the implementation of the Children Act has been associated with a
significant reduction in the number of compulsory child p r o t e ~ i o ninterventions through
the courts, in part because of greater social services' reliance on voluntary help and
increased partnership with parents.
. carer
Ensure nursing care plan takes full account of concerns
Record any differences of medical opinion
Ensure all notes are comprehensive/contemporaneous (include content of all
telephone calls, handovers etc.)
Ask about previous admissions to other hospitals and obtain such information
Ensure full physical examination within 24 hours
Permission for any relevant investigations should be obtained by a doctor above the
grade of senior house officer
The name of the consultant responsible for the child protection aspects of the child's
care should be clear
Within a given location, work from one set of medical records
Discharge arrangements
Permission must be obtained from consultant or middle-grade doctor
Follow-up arrangements must be documented
Must have a GP identified before discharge
Training
National ongoing training programme for doctors should be set up and integrated
within revalidation of doctors
Training should be available for all staff who have regular contact with children
lnteragenG working
Liaison between hospitals and community health services is crucial.
Tqrpes of abuse
Physical injury may be inflicted deliberately or by failure to provide a safe environment
Neglect, e.g. inadequate provision of food
Emotional neglect
Sexual abuse
Potential abuse, e.g. if another child was previously harmed
Examination
If non-accidental injury without sexual abuse is suspected the child should be fully
undressed and examined in a warm, secure environment by an appropriately experienced
doctor. Careful charting of injuries is imperative. The recommendations of Lord Laming's
report should be adhered to.
Certain injuries are 'typical' in abuse:
Bruises - bruises are uncommon in children under 1 year, especially if not mobile;
bruises of different ages or finger-shaped bruises raise concerns, as do bruises on head,
face and lumbar region (often finger marks), bruising around wrists and ankles
(swinging), bruising inside and behind pinna (blow with hand), ring of bruises (bite
mark)
Two black eyes
Strap or lash marks
Torn frenulum - blow or force feeding
Perforated eardrum - slap or blow to side of head
Small circular burns - cigarette burn
Burns or scalds to both feet or buttocks
Fractured ribs - shaking
Epiphyses torn off - swinging
Subdural haematoma - shaking
Retinal haemorrhages - shaking
Multiple injuries and injuries at different ages
Potential pitfalls
Underdiagnosis is much more common than overdiagnosis but beware of:
Mongolian spots - most common in those of Asian origin; look like bruises, seen most
commonly over buttocks
Bleeding disorders - need full blood count and clotting test to exclude these if there
are multiple bruises
Underlying bony disorder - e.g. osteogenesis imperfects or copper deficiency; if
fractures are present, a paediatric radiologist must be able to exclude the former
Case conference
This is a formal gathering of individuals with a legitimate interest in the child and family. It
allows:
Exchange of relevant information
Decision as to whether abuse has taken place
Decision on whether to place name on Child Protection Register
Action plan for protecting child and helping family
Identification of individuals to implement plan
Neglect
This may manifest as faltering growth, failure of normal development or growth, or lack of
normal emotional responses. Other causes need to be excluded, but typically the child
progresses better in a hospital environment than at home.
Poisoning
Rare but consider if symptoms and signs are difficult to explain. Blood and urine will need
to be screened.
Sexual abuse
Presentation
Sexual abuse presents in many ways:
Allegations by child or adult (children rarely lie about this)
Injuries to genitalia or anus (including bleeding or sexually transmitted disease)
Suspicious features including unexplained recurrent urinary tract infection, sexual
explicitness in play, drawing, language or behaviour, sudden or unexplained changes in
behaviour, e.g. sleep disturbance and loss of trust in individuals close to them, taking an
overdose, running away from home
Psychosomatic indicators including recurrent headache, abdominal pain, enuresis,
encopresis, eating disorders
Physical signs
The examination should take place in a quiet, child-centred room with appropriate facilities.
Older children may prefer a doctor of the same gender. Consent is required before the
examination and a forensic pack will be needed if the last assault was within 72 hours. The
signs elicited must be taken in the context of the complete investigation. Careful documen-
tation should be made in the form of sketches and sometimes photographs. As there is
significant chance of coexisting physical abuse a full general examination should also be
performed.
NB It must be remembered that up to 50% of children subject to sexual abuse will have
no abnormal physical signs.
for the M KCPCH 2nd Edition
Essential Revision Notes in R;7ediC~trics
Anal examination
Examine young children on the carer's knee and older children in the left lateral position.
Rectal examinations are rarely necessary and instead inspection should determine the
presence or absence of acute signs such as:
Swelling, reddening, bruising, haematoma, laceration or tears of anal margin
Spasm, laxity and dilatation of anal sphincter
Dilatation of perianal veins
Chronic signs should also be looked for including:
Smooth thickened anal margin with shiny skin
Chronic and acute fissures (single fissure unlikely to be significant)
Spasm laxity and dilatation of anal sphincter
Dilatation of perianal veins
Investigations
In certain cases it may be appropriate to send swabs for:
Gonorrhoea
Trichomonas
Chlamydia
Herpes
And forensic samples to look for:
Spermatozoa
Semen
Grouping of semen
Saliva, etc.
Long-term legacy
The long-term problems associated with child sexual abuse include:
Post-traumatic stress
Suicidal behaviour
Psychiatric illness
Problems with relationships and sexual adjustment
Incidence
UK figures for 2004 - 0.4 per 1,000 live births
Many hypotheses have developed about the causes of SIDS. The search for an individual
cause has shifted towards a more complex model. It seems likely that SIDS is the result of
an interaction of risk factors - developmental stage, congenital and acquired risks and a
final triggering event.
**Smoking increases the risk of SlDS by up to threefold. There is an increase in risk with
increased likelihood of spontaneous apnoea and decreased ability to compensate after such
an episode. Such effects are likely to be enhanced by intercurrent illness.
***Relative risk of SlDS with preterm delivery
Gestational age Relative risk of SlDS
< 28/40 3.6
28-31 weeks 4
32 -33 weeks 2.4
34-36 weeks 1.7
The period for which infants born preterm are at risk of SlDS is also longer than for term
infants.
****Inborn errors of metabolism - around 1% of cases of SIDS are likely to be the result
of the enzyme deficiency: medium-chain acyl coenzyme A dehydrogenase deficiency
(MCAD). It is likely that other enzyme deficiencies contribute to SlDS in a subset of patients,
especially those cases of SlDS which occur at > 6 months. Appropriate investigations
should be initiated.
Parents should have option of being present during resuscitation with nurse supporting
them throughout
Take brief history of events preceding admission, including baby's past illnesses, recent
health and any resuscitation already attempted; identify any predisposing factors for
SlDS
Consultant should decide, in consultation with parents, how long resuscitation should
be continued for (it is usual to discontinue if there is no detectable cardiac output after
30 minutes)
Once baby has been certified dead, consultant paediatrician should break news to
parents, with support nurse present
Explain to parents the need to inform the coroner and arrange a post-mortem
Physical examination
Carried out by most senior paediatrician present as soon as resuscitation has been
completed/abandoned. Need to record:
Baby's general appearance, state of nutrition and cleanliness
Weight, and position on centile chart
Rectal temperature
Marks from invasive or vigorous procedures such as venepuncture, cardiac massage
Any other marks on skin
Appearance of retinae
Lesions inside mouth
Any signs of injury to genitalialanus
Taking of samples
In some centres all samples are taken at post-mortem, however in others some or all of the
following should be taken within the A&E department:
Blood for urea and electrolytes, full blood count, blood culture, toxicology (clotted
sample)
Metabolic screen including amino and organic acids, oligosaccharides, blood spot on
Guthrie card (for MCAD)
Chromosomes (if dysmorphic)
Essential Revision Notes in Paediatrics tbr the MRCPCH 2nd Eciition
-
Nasopharyngeal aspirate, swabs (as appropriate) for bacteriology, suprapubic aspirate for
urine microscopy, culture and sensitivity
Consider skin and muscle biopsy
Communication checklist
The following should be informed as soon as possible about the baby's death:
Coroner
Coroner's officer
Police
Family doctor
Health visitor
Social worker
Medical records
Other paediatric colleagues previously involved in care
Immunization office
Follow-up arrangements
Ideally the paediatric consultant involved should organize to visit the family at home, as
soon as is convenient for them. This allows more information on the family and baby to be
obtained and also presents an opportunity for the parents to ask questions. Follow up
information from such a visit should be included in a report done to assist the pathologist. A
multidisciplinary discussion should be set up and should include all those who have been
professionally involved with the family. Further follow-up visits should be organized, as
necessary, and the post-mortem result should be discussed as soon as available.
Urban safety measures (e.g. crossing patrols, traffic redistribution schemes, improving
safety on individual roads)
Use of home safety devices (e.g. smoke detectors, stairgates, thermostat control of hot
water)
Studies have established that educational programmes alone are not successful in prevent-
ing accidents and that to reduce accidents the educational material must be accompanied
by:
Targeting the families most at risk of accidents
Home visits
Free distribution of devices such as smoke alarms
Aetiology
Whilst viruses such as Epstein-Barr virus and the enteroviruses are ofte-n implicated in the
disease process, direct evidence of this is often hard to find. Case clustering does occur and
while anecdotal cases have suggested that immunization may be a trigger there is no direct
evidence to support this theory. The aetiology is likely to be .a combination of physical,
psychological and behavioural factors. Often a trigger for the child's symptoms can be
found.
Depression may be an associated feature, and the chronic course the disease takes makes
psychological support and evaluation essential.
Epidemiology
The UK prevalence of chronic fatigue syndromelmyalgic encephalomyelitis (CFSIME) in
children and young people is 50-100 per 100,000 with the highest prevalence in
adolescents. Where studies have reported a difference in gender, girls outnumber boys 3 : 1.
Clinical features
The onset may be gradual or sudden. In addition to fatigue other frequently reported
symptoms are:
Headaches
Sleep disturbance
Concentration difficulties
Memory impairment
Essential Revision Notes in R~ediatricsfor the h1RCPCH i'ncl Edition
Depressed mood
Myalgidmusle pain
Nausea
Sore throat
Tender lymph nodes
Abdominal pain
Arthralgidjoint pain
Less commonly there may be:
Feeling too hot or too cold
Dizziness
Cough
Eye pain
Vision or hearing disturbance
Weight gain or loss
Muscle weakness
Diarrhoea
Initial assessment
All patients referred for consideration of the diagnosis require a full and thorough
assessment with an appreciation of the reality of the child's symptoms and acknowledge-
ment of their validity. A thorough history and examination should be taken, exploring
precise symptomatology. Organic and psychological disease shoutd be looked for. Of
particular importance is determining the effect of the child's symptoms on their normal daily
routine including activities at home and attendance at school.
Investigation
Routine tests on all patients should include a blood test and a urine test for the following
investigatons:
Full blood count and film
Erythrocyte sedimentation rate and C-reactive protein
Blood glucose
Blood biochemistry (to exclude renal insufficiency and Addison's)
Creatine kinase
Thyroid function
Liver function
Urine for proteinIglucose and infection screen
Viral titres Epstein-Barr virus IgM, IgG and EBNA
Other investigations may be required if there are specific disease pointers.
<.-/TIMDevclopti~etit,Chili1 Psychb t r y c~ncl
C~~rnrnunity
R7ediatrics
Management
Management is complex and requires the input of many professionals. It needs to be tailor-
made to the individual child. Key points are:
Facilitate the child and family to acknowledge the diagnosis, understand its implications
and embark on a period of rehabilitation
Assess current level of functioning by completing a daily programme to establish periods
of eating, rest and activity
Liaise closely with school/education authority
Set goals:
Attendance at school is a key aim but gradual reintegration is usually required, with
rest periods within school. Part days in school are preferable to exclusive home
tuition
Aim to increase activity levels by around 5% each week
Encourage child to keep a diary
Advice re healthy balanced diet
Help/support with sleeping difficulties
Recognize early any predominant psychological symptoms including school phobia or
depression and seek appropriate psychological or psychiatric help
Appropriate pain management (may include psychological intervention andlor low-dose
amitriptyline or nortriptyline)
Pharmacological interventions such as corticosteroids, antidepressants (particularly
SSRls) and immunoglobulin have been used, but in a recent meta-analysis of treatments
only physiotherapy (with a graded exercise programme) was shown to have a clearly
beneficial effect
There is no evidence to support the use of magnesium injections, essential fatty acids,
high-dose vitamin 812 supplements, anticholinergic drugs, staphylococcus toxoid or
antiviral therapies
Cognitive techniques are used to assist patients to re-evaluate their understanding of the
illness, combat depression and anxiety and look for underlying thoughts and
assumptions that may contribute to disability
Inpatient admission is rarely needed in the context of children with severelvery severe
CFSIME
Prognosis
The prognosis of chronic fatigue syndrome in children, in the absence of complications, is
good. The onset of disease is more rapid and the response to therapy better than in adults,
with a return to normal by 6-12 months after diagnosis in 80-90%.
Good prognostic factors in chronic fatigue syndrome are:
Clearly defined trigger to illness
Short duration of symptoms
Essential Revision Notes in Paediatrics for the MRCPCH 2nd Edition
Clinical Governance
Robert Wheeler
CONTENTS
1. History
2. Definitions
3. External agencies
5. Implementation
5.1 Risk management
5.2 Educationlappraisal
5.3 Clinical effectiveness
5.4 Patient and public involvement
5.5 Interaction
6. Conclusion
7. Electronic sources
8. Further reading
Clinical Governance
1. HISTORY
After the inception of the NHS in 1946 the practice of medicine was governed by
professional judgement. Clinical decisions were made on the basis of knowledge accumu-
lated during an apprenticeship, and this knowledge was validated by certification from the
Royal Colleges. Compulsory registration with the General Medical Council was assumed to
provide an assurance of fitness to practise and propriety, together with sanctions for
transgressions.
Clinical practice itself, based on written and oral precedent, was seen as an evolving body
of knowledge, against which new information cou Id be evaluated.
These arrangements lasted, with varying degrees of satisfaction depending on the commen-
tator, for more than 40 years. However, because of the inexorable rise of the cost of
litigation,' the drug budget, and institutional catastrophes (such as those at the Bristol Royal
lnfirmary2 and the Royal Liverpool Children's ~ o s p i t a l ~there
), has been a profound shift
from the internal standard of medical self-regulation to an externally imposed regulatory
apparatus, conforming to standards derived from state control.
It was with the advent of the hospital Trusts that politicians took renewed interest in quality
issues. The Conservative administration had already coined the- phrase 'Clinical Govern-
ance' .by 1996; the advent of the new Labour government in 1997 confirmed Clinical
Governance as the byword for quality assurance and enforcement.
A White Paper followed in 1 997,4 translating the concept into several national develop-
ments, with a mission to set or enforce standards. These included the National Institute for
Clinical Excellence (NICE), the Commission for Health Improvement (CHI) and National
Service frameworks, the latter to 'drive up' the quality of services for specific groups of
patients, (e.g. cardiac, cancer) by setting national standards and describing service modules.
Into this initiative were drawn several other apparently disparate concepts: Appraisal/Assess-
ment of Doctors, Integrated Care or Managed Pathways, and Evidence-Based Practice.
2. DEFINITIONS
It is fair to report that by late 1998, when interested parties had recovered from the
onslaught of novel watchdogs, words and concepts, a steady stream of contradictory
literature had begun to flow at national and local level, all trying to make sense of what
'Clinical Governance' actually meant.
E.sserrtic~l tor the M RC'PC:H Z nd Editir~~
Revision Notes in E~edi,~trics I
The concept of governance was adapted from industryf5 meaning 'to control and direct,
with a~thority'.~ It was conceived as being based upon seven central 'pillars' (Risk Manage-
ment, Clinical Effectiveness, Education and Training, Patient and Public Involvement, Using
Information, Research and Development, Management and Manpower). Organized within
these broad categories, any aspect of clinical practice that could be regarded as pertaining
to 'quality of care' could be subjected to intense scrutiny.
This arrangement has been rapidly incorporated into hospital practice, measured within the
'star ratingf system. Although the pursuit of 'quality' seems uncontroversial, the reaction by
doctors was not universally fa~ourable;~ many feeling that governance added no further
value to their standard of care, which already exemplified many of the principles contained
within the pillars. This conflict of understanding may have arisen from the necessity for
clinical governance to be delivered by a team, rather than by an individual doctor.
Consultants considered that they still retained 'ownershipf, the basis of continuity of care,
which remained the their touchstone of 'quality'.
The widespread medical disaffection with clinical governance has continued, although
there are high-profile exceptions. Adequate funding for clinical governance has not been
forthcoming, resulting in a cutting-back in both central and local aspirations (i.e. the post of
Commissioner for Patient and Public lnvolvement was abolished in the most recent review).
Shrinkage of the original seven-pillar plan has occurred, resulting in a largely risk-based
agenda. This is reflected in the Standards for Better Health, where only Risk and Patient and
Public Involvement survive as independent specified activities. The rest of the original
agenda is subsumed into the 'core activities', although there is concern that the audit
(clinical effectiveness) and educational elements are insufficiently established properly to
service the Standards agenda.
3. EXTERNAL AGENCIES
Scrutiny of the management of illness nationally is institutionalized through the external
agencies. As a starting point, NlCE was responsible for setting uniform national standards on
which to base clinical practice. (NICE was established in 1999 by the NlCE (Establishment
and Constitution) Order 1999 SI 1999 No. 220, www.nice,org.uk.) The agency provides
guidance in three areas. Technology appraisals review the use of new and existing
medicines and treatments. This gives an opportunity to control expenditure on high-cost
drugs whose claims of efficacy failed to satisfy critical review, although as a government
agency, there remains the concern that the need for financial saving may militate against
the ratification of potentially effective (but expensive) treatment^.^
Clinical guidelines are commissioned to designate the appropriate treatment and care of
specific conditions and diseases. This should lead to clinical uniformity, and make a
'postcode lotteryf less likely. At the same time, guidelines may lead to cost savings, at the
price of reducing patient c h ~ i c e .However,
~ implicit in this is a reduction of clinical
freedom, which has been demonstrated to disadvantage the sickest patients.1°
Finally, reviews are commissioned by NlCE into the safety and efficacy of new interven-
tional procedures, in an effort to restrict the unregulated introduction of new technology.
Clinica 1 Governance
This has led to a host of interventional guidelines, although little or no funding has yet been
provided to establish the central registries that are required.
The resulting 'evidence base' is produced as a compilation." Adherence to the advice may
be seen as regulation by compliance, as opposed to deterrence.12 Although clinicians are
ready to adopt the advice providing the normal criteria apply,13 there is considerable
evidence that NlCE guidance is not being followed.14 There is also a growing recognition
that the plethora of guidance has overloaded the system, and NlCE is now calling for
clinical advice on where to focus attention for future work.15
Scrutiny of the care that health organizations deliver to their patients was initially under-
taken by the CHI (established by s19 of the Health Act 1999, and Commission for Health
lmprovement (Functions) Regulations 2000, S.I. 2000 No. 662, reg 3, transiently reconsti-
tuted as the Commission for Healthcare Audit and lmprovement (CHAI) before being re-
launched on 1 April 2004 as the Healthcare commission (HC) - www.chai.org.uk). The
Commission is an example of regulation by deterrence. Its remit was radical in comparison
with the previous arrangements, which were described in the words of the Bristol inquiry as
'There was, in truth, no system'.16 This abrupt shift to external regulation was recognized as
a momentous event." With a motto of 'Inspecting, Informing, Improving', the HC has an
ever-increasing remit across public and private healthcare provision, including the value for
money derived from healthcare expenditure, and aspects of the complaints procedure.18
Amongst many other functions, the HC is responsible for issuing National Service Frame-
works to promote uniformity and quality in areas of healthcare that are seen to be in need
of support; the most recent was for the care of children.
This element of clinical governance can be run in parallel with other activities. Continuing
education for doctors is now mandatory, and in the future is likely to be reflected in
demands for dedicated fixed consultant education sessions. Colleges have already recog-
nized that education comes in various forms; formal teaching, courses, private reading,
preparing lectures and research, among others.
Assessment and Appraisal are prominent on the political agenda, hence the anxiety of the
General Medical Council to produce a workable formula in 2001, to facilitate revalidation
of a doctor's original medical registration. It is a tribute to the difficulty of the task that by
2005, an adequate solution has yet to be found. To an extent, this has been delayed by the
political reaction to the crimes of Dr Harold Shipman. Although apparently a convenient
moment to incorporate a mechanism to identify potential mass murderers through the
revalidation process, it is becoming clear that this is unworkable, and that cyclical
revalidation of doctors will be largely based on local appraisal. The local appraisal process
remains a matter for individual medical directors. It seems that reforms to the laws
concerning the registration of death are more likely to reduce the risk of another similar
tragedy.
Assessment (which is a mere observation; a measuring of attendance, workload, waiting
times, educational target fulfilment) is a great deal easier to perform than Appraisal (a
process of valuation, estimating the worth and quality of clinical activity).
This is because the individual can perform Assessment themselves; it may involve tedious
and time-consuming data collection and form filling but it is an objective exercise.
Appraisal, however, can only be performed by an outsider, who shares enough of the
appraisee's training to allow pertinent questions to be asked, and relevant feedback to be
given. This is equally time-consuming but is also potentially threatening and more sub-
jective than Assessment.
Audit programmes can be integrated with other aspects of clinical governance. If a clinical
intervention is identified as a risk either by a Risk Assessment, by Critical Incident reporting
or as the result of a cluster of similar complaints, then this gives an ideal opportunity for
audit.
At present, audit remains the single most effective method of performance measurement.
Isolated specialities such as cardiac surgery have developed national databases of results,
allowing comparison between units, but this obviously demands close integration and co-
operation within a professional speciality. The advantage of audit is that it can be performed
equally well in isolation, as long as a gold standard for comparison can be identified.
To maintain enthusiasm for audit within a department is quite a different matter, partly
because some doctors see this as a merely self-fulfilling process. A pragmatic approach is a
rolling audit, where a topic is chosen which continually poses a clinical challenge; the
adherence to the Unit protocol for the management of bronchiolitis would be a recurring
theme.
An audit can be set up along the usual lines, but then the re-audit phases, together with
retrospective comparisons and prospective protocol adjustment, can be undertaken by
successive generations of junior staff. In this way, audit becomes an integrated part of the
working routine, not dependent on additional enthusiasm or drive by the medical team.
Ideally, a combination of rolling 'routine' audit with additional audits reacting to risks
should run simultaneously.
5.5 Interaction
The various elements of clinical governance interact, giving endless opportunities for flow
diagrams and presentations.
If you start with a Risk topic, an audit will measure the Unit's performance. The audit will
demand a gold standard for comparison, which can (possibly) be supplied from the
available Evidence base. Obtaining this evidence or the consensus view may well be the
appropriate use of a consultant's private study time, i.e. Continued Medical Education.
Once the gold standard has been determined, it can be incorporated as a module within
the appropriate Integrated Care Pathway. This may then be subject to rolling audit, etc. The
Patient and Public Involvement element can be involved, to either assess the patients'
perception of the risk, or their reaction to the chosen remedy, or the priority that they feel
should be given to implementing the remedy, given the obvious restrictions on resources.
6. CONCLUSION
There is little doubt that hospital patients and clinicians should equally welcome additional
supervision of clinical activities. Clinical 'freedom' may seem insufficiently controllable to
guarantee adequate quality of care, and it is understandable that any government would
wish to demonstrate an augmented quality of care, rather than merely reiterate a financial
commitment to health. External regulation has become a cornerstone of the government's
'third way' in healthcare.*' This has been achieved by asking doctors to comply with
standards set by NICE, and deterring variance by the employment of agencies such as the
Healthcare Commission. The product of this alliance is implemented by the clinical
governance structure. There remains concern that the evidence base is unreliable, and that
the individual patient's best clinical interest may not be best.achieved by following a
guideline produced from an averaged population. Effectively enforced 'bullet-pointf medi-
cine is likely to interfere significantly with the therapeutic relationship between patients and
their doctors,24 although from a utilitarian point of view, it may confer the least risk on the
greatest number.
7. ELECTRONIC SOURCES
www.chai.org.uk~assetRoot~O4/01/00/32/04010032.pdf
Most recent HC review: of Malden
& South Chelmsford PCT
www.dh.gov.u klpubl ications
www.dh.gov.uk/publicationsandstatistics/bulletins/ChiefExecutiveBulletin
[email protected] k (Standards for Health)
www.healthcarecommission.org.uk~ContactUs/ComplainAboutNHS/fs/en
Essential Revision Notes in Paediatr-ics for the MRCPC'H Z I ~ CEdifion
J
8. FURTHER READING
I. Harpwood V. 2001. Negligence in Healthcare, chapters 10, 11. London: lnforma
Publishing Group.
2. Department of Health. 2001. Repot? of the Public Inquiry into Children's Heart Surgery
at Bristol Royal Infirmary 1984- 1995: Learning from Bristol. London: DOH (Cm5207).
3. Department of Health. 2001. The Royal Liverpool Children's Inquiry Report London:
Stationery Office.
4. Department of Health. 1997. The New NHS - Modern, Dependable. London:
Stationery Office.
5. Originally Sir Adrian Cadbury, referred to by Donaldson L. 2000. Clinical Governance.
Medico-Legal)ournal68:3, 89-1 00.
6. A First Class Service; Quality in the New NHS. 1998. Government White Paper.
7. Klein R. 2000. The New Politics of the NHS, 4th edn. London: Prentice Hall.
8. Newdick C. 2002. NHS Governance after Bristol: holding on or letting go? Medical
Law Review 10,111 -3 1.
9. NICE. 2004. NICE guidance issued on caesarean sections. Medical Law Monitor May
3-4.
10. Dranove D et al. 2002. Is more information better? The effects of 'Report Cards' on
health care providers. National Bureau of Economic Research Wper 8697.
11. NICE. 2003. Summary of Guidance issued to the NHS in England and Wales, Issue 7
October 2003. London: NICE.
12. Reiss AJ. 1984. Selecting strategies of social control over organisational life. In Hawkins
K, Thomas JM(Eds) Enforcing Regulation, Boston, MA, USA: Kluwert Nijhoff.
13. Editorial. 2004. If guidance is clear, based on an understanding of clinical practice, if
the evidence is strong and relatively stable, if adequate fundihg is available and if
guidance is supported and disseminated by professional bodies. 5MJ 329, 999-1003.
14. Freemantle N. 2004. Is NlCE delivering the goods? BM) 329, 1003-1 004.
15. NlCE asks what not to assess. Hospital Doctor, 2004, 9 December, 4.
16. Department of Health. 2001. Report of the Public Inquiry into Children's Heart Surgery
at Bristol Royal Infirmary 1984- 1995: Learning from Bristol. London, DOH (Cm5207),
chapter 6, para. 30; p. 192 para. 2 1.
17. Smith R. 1998. All changed, changed utterly: British medicine will be transformed by
the Bristol case. BMj 316, 1917.
18. Health and Social Care (Community Health and Standards) Act 2003, explained at
www.healthcarecommission.org.uk~ContactUs/CompJainAboutNHS/fden
19. Most recent reviews (e.g. of Maldon and South Chelmsford PCT) www.chai.0rg.uk/
assetRoot/04/01/00/32/04010032. pdf
20. Department of Health. 2004. National Standards, Local Action. Health and Social Care
Standards and Planning Framework 2005/06-2007/08 Annex I Leeds, DOH
www.dh.gov.uk~publications.
21. Editorial. 2004. Commission proposes end to star rating system for hospitals. BMJ 329,
1303.
22. Editorial. 2004. Commission plans to adopt 'a lighter touch' BM] 329, 997.
23. Walshe K. 2002. The rise of regulation in the NHS. BM] 324, 967.
24. Teff H. 2000. Clinical guidelines, negligence and medical practice. In Freeman M,
Lewis A (Eds) Law Medicine: Current Legal Problems, vol. 3. Oxford: Oxford University
Press.
Chapter 4
Clinical Pharmacology and
Toxicology
Steve Tomlin and Michael Capra
i
g
I
t CONTENTS
1. Pharmacokinetics and dynamics
1.1 Absorption
1.2 Distribution
1.3 Half-life
1.4 Hepatic metabolism
1.5 Renal excretion
1.6 Other clinical considerations
2. Formulation
3. Paediatric dosing
5. Drug monitoring
6. Interactions
6.1 Drugs and the liver
6.2 Drugs in breast milk
7. Toxicology
7.1 Paracetamol
7.2 Iron
7.3 Tricyclic antidepressants
7.4 Aspirin overdose
7.5 Lead poisoning
7.6 Carbon monoxide
7.7 Button batteries
: 8. Further reading
Clinical Pharmacology and
loxlcology
1.1 Absorption
Liquid and intravenous forms of drugs (i.e. those already in solution) are readily
absorbed into the body's systemic circulation
Solid dosage forms (tablets and capsules) and suspensions must first be dissolved in the
gastrointestinal tract (dissolution phase) before they can be absorbed, and so absorption
is slower
The term 'bioavailability' is applied to the rate and extent of drug absorption into the
systemic circulation
First-order kinetics
Oral absorption of drugs is often considered as demonstrating first-order kinetics. This is
especially true with oral solutions. 'First-order kinetics' implies that the fractional rate of
absorption is constant, so absorption decreases the less there is left in the stomach. If a drug
is absorbed at a constant rate independent of the amount left to absorb, then it is referred to
as having 'zero-order kinetics'.
Ionization
Absorption of the majority of medicines is dependent on how ionized they are (their pK,)
and the acidity at the site of absorption. Drugs with acidic pK,s (for example: aspirin,
phenoxymethylpenicillin (penicillin V)) will be mainly non-ionized in the acid stomach and
so readily absorbed. Phenobarbital being a weaker acid is better absorbed in the more
alkaline intestine.
Neonates
Neonates (especially those who are premature) have reduced gastric acid secretion, there-
fore the extent of drug absorption is altered and less predictable.
Essential Revision Notes ill P;)cdic7tricstor tlic klRCPCH 2nd Eclition
At birth, drugs with an acidic pK, will have decreased absorption. Twenty-four hours after
birth, acid is released into the stomach therefore increasing the absorption of acidic drugs.
Normal adult gastric acid secretions are achieved by about 3 years of age.
Gastric motility is decreased during infancy, thus increasing the absorption of drugs that are
absorbed in the stomach. However, drugs absorbed from the intestine will have a decreased
or possibly delayed absorption.
1.2 Distribution
The concentration of a drug at various sites of action depends on the drug's characteristics
and those of the tissue. Most drugs are water-soluble and will naturally go to organs such as
the kidneys, liver, heart and gastrointestinal tract.
At birth, the total body water and extracellular fluid volume are much increased, and thus
larger doses of water-soluble drugs are required on a mg/kg basis to achieve equivalent
concentrations to those seen in older children and adults. This has tb be balanced against
the diminished hepatic and renal function when considering dosing:
Extracellular fluid
volume (%) 50 45 40 30 25 25
Total body water (%) 85 75 60 60 60 60
Fat content (%) 3 12 25 30 variable 18
0 For example, phenytoin is highly protein-bound but because there is less protein
binding in neonates (lower plasma protein levels and lower binding capacity) there is
more free phenytoin than in older children and adults. Thus the therapeutic range for
phenytoin in neonates is lower than in the rest of the general population as it is the free
phenytoin that has the therapeutic action and can cause toxicity.
Therapeutic range for neonates = 6-1 5 mg/l
Therapeutic range for children and adults = 10-20 mg/l
The reduced protein binding is the result of:
Low levels of plasma protein, particularly albumin
Qualitative differences in binding capacity
Competition with endogenous substances, particularly increased bilirubin after birth
Volume of distribution
Distribution is measured by a theoretical volume in the body called the 'volume of
distribution'. It is the volume that would be necessary to dilute the administered dose to
obtain the actual plasma level within the body. The volume will be affected by the following
characteristics (body size, body water composition, body fat composition, protein binding,
haemodynamics and the drug characteristics). As a rule of thumb: drugs that are plasma
protein-bound will mainly stay in the plasma and thus have a small volume of distribution;
highly lipid-soluble drugs (especially in people with a high fat content) will have high
volumes of distribution. Water-soluble drugs have increased volumes of distribution in
neonates because of the increased total body water content of neonates.
The parameter can change significantly throughout childhood. Plasma albumin levels reach
adult levels at approximately 1 year of age.
Blood-brain barrier
The blood-brain barrier in the newborn is functionally incornplete'and hence there is an
increased penetration of some drugs into the brain.
Transfer across the barrier is determined by:
Lipid solubility
Degree of ionization
Drugs that are predominantly un-ionized are more lipid-soluble and achieve higher
concentrations in the cerebrospinal fluid. It is as a result of this increased uptake that
neonates are generally more sensitive to the respiratory depressant effects of opiates than
infants and older children.
Some drugs will displace bilirubin from albumin (for example: sulphonamides), so increas-
ing the risk of kernicterus (encephalopathy due to increased bilirubin in the central nervous
system - in at-risk neonates).
Essentin1 Revisiot? Notes in Paediatrics for-the h.1KCPCH 2nd Editic~n -
1.3 Half-life
Half-life is the time taken for the plasma concentration of a drug to decrease to half of its
original value. Thus it follows that less drug will be eliminated in each successive half-life.
.
For example, theophylline:
if there is initially 250 mg in the body, after one half-life (4 h) 125 mg will remain;
after two half-lives (8 h) there will be 62.5 mg left; and so on
When a medicine is first given in a single dose, all the drug is at the absorption site and
none is in the plasma. At this point, absorption is maximal and the rate of elimination is
zero. As time goes on the rate of absorption decreases (first-order kinetics) and the rate of
elimination increases. All the time that the absorption rate is higher than the elimination
rate the plasma level will increase. When the two rates are equal, the concentration in the
plasma will be at a maximum. After this point, the elimination rate will be higher and the
levels will drop. A drug is said to be at 'steady state' after about four to five half-lives. So if
multiple dosing is occurring the plasma levels at any particular point after a dose will
always be the same.
First-pass metabolism
Medication that is absorbed from the gastrointestinal tract goes straight to the liver before
entering the systemic circulation. This is useful for some types of medication, which have
to go to the liver to be activated (pro-drugs), e.g. enalapril. It is, however, limiting for
medications that have to achieve good levels when given orally. Propranolol has a high
first-pass metabolism, so quite large doses need to be given to achieve adequate systemic
levels. Inhaled budesonide is often said to be relatively free of systemic side-effects because
the steroid that is deposited in the throat and swallowed is almost entirely eliminated by
first-pass metabolism.
G6PD deficiency
This is a commonly inherited enzyme abnormality. It is an X-linked recessive disorder. Male
homozygotes show significant drug-related haemolysis, but females only have minor
symptoms. Anaemia is the most common presentation.
Main drugs to avoid:
dapsone, nitrofurantoin, quinolones (ciprofloxacin, nalidixic acid, ofloxacin,
norfloxacin), sulphonamides (co-trimoxazole), quinine, quinidine, chloroquine
Essential Revision Notes in Paediatrics fbr the M RCPCH 2ricl Edition
Succinylcholinesensitivity
Some people are extremely sensitive to the muscle relaxant succinylcholine. Serum
pseudocholinesterase activity is reduced and the duration of action of the muscle relaxant
(usually a few minutes) may be greatly increased, thus leading to apnoea (deaths have been
reported). The incidence is about 1 in 2,500 of the population.
Acetylation status
Differences in the metabolism of isoniazid are seen in certain people and inherited as an
autosomal recessive trait. People who are 'slow inactivators' have reduced activity of
acetyltransferase, which is the hepatic enzyme responsible for the metabolism of isoniazid
and sulphadimidine (and thus affects phenelzine and hydralazine metabolism). Toxic effects
of such drugs may be seen in people who are 'slow acetylators'.
Slow acetylators are also predisposed to spontaneous and drug-induced systemic lupus
erythematosus (SLE).
Liver disease
Toxic substances normally cleared by the liver may accumulate in patients with liver
impairment.
Opioids and benzodiazepines may accumulate and cause central'nervous system
depression, thereby causing respiratory depression
Diuretics (loop and thiazide) may cause hypokalaemia
Rifampicin, which is excreted via the bile, will accumulate in patients with obstructive
jaundice
Cirrhosis may cause hypoproteinaemia and thus reduce the number of binding sites for
highly protein-bound drugs (e.g. phenytoin)
Clotting factors are reduced in liver impairment thus increasing the chances of bleeding
in patients on warfarin
Renal disease
Nephrotoxic drugs will make any renal impairment worse by exacerbating the damage.
Drugs that are renally excreted (most water-soluble drugs) will accumulate in renal
impairment and the dosing intervals will need to be increased to avoid toxicity
Drugs that cause toxicity in severe renal impairment include:
Digoxin - cardiac arrhythmias, heart block
Penicillins/cephalosporins (high-dose) - encephalopathy
Erythromycin - encephalopathy
Nephrotoxic drugs include:
Aminoglycosides (gentamicin, amikacin)
Amphotericin B
Non-steroidal anti-inflammatory drugs (e.g. diclofenac, indomethacin)
2. FORMULATION
Medicinal preparations often contain ingredients (i.e. excipients) other than the medicine
that is being prescribed. These adjuvants can have a pharmacological effect that needs to
be taken into account when looking at medication consumption and assessing possible
toxicity.
Benzyl alcohol and methylparaben can displace bilirubin from albumin-binding sites,
leading to exacerbation of jaundice. Benzyl alcohol may also cause a potentially fatal
'gasping syndrome'
Propylene glycol is a common solubilizing agent. In excess, it may cause severe toxicity
including hyperosmolarity, lactic acidosis, dysrhythmias and hypotension
Polysorbate 20 and Polysorbate 80, which are used as emulsifying agents, have been
associated with renal and hepatic dysfunction as well as hypotension (secondary to
hypovolaemia), thrombocytopenia and metabolic acidosis
Lactose is a common additive, but rarely associated with severe toxicity. It may,
however, be important if a child has lactose intolerance -
.
Sugar and sorbitol are frequently added to liquid preparations for sweetness and
occasionally cause problems. Sugar can cause dental caries and sorbitol may cause
diarrhoea
Alcohol is another common ingredient of many liquid pharmaceutical products and the
quantity is often fairly significant. Products such as phenobarbital BP contains as much
as 3B0/0 alcohol per 15 mu5 ml. Equating this to a mglkg quota, it would not be that
unusual to subject a neonate to the equivalent of an adult swallowing one or two
glasses of wine
Formulation issues are a fundamental problem in paediatric medicine management.
Palatability causes many problems with compliance and it is well demonstrated that taste
preferences change with age. Few medicines are made specifically for children and thus
products needed in clinical use may not be available in a formulation that is appropriate for
young children. This often leads to tablets being crushed and aliquots being given. If this is
necessary the properties of the preparation may change significantly or the dose may be
inaccurate depending on whether the tablet dissolves or disperses and on the release
mechanisms built into the tablet originally (e.g. coating or matrix). A pharmacist should be
consulted if there is any doubt.
Essential Revision Notes in R7edt'atrics tbr the &I RCPCH 2nd Edition
3. PAEDPATRIC DOSING
Pharmacokinetic and pharmacodynamic data are seldom available for the paediatric popu-
lation, this is because most medications are only licensed for adult use and have not
undergone specific pre-marketing clinical studies in children. Data on therapeutic dosing
for children are often anecdotal and based on case reports or very small population studies.
New drugs are usually only studied in adult populations.
Some of the reasons for this are the stringent regulations put in place in 1962 following the
thalidomide tragedy; these had the effect of discouraging research. The legislation surround-
ing drugs trials currently discourages trials in children, although in recent years there has
been a call for more studies and European Legislation should be changing in 2006 to
encourage more drug companies to seek paediatric licences.
The surface area and the weight are the only common methods currently available to
predict paediatric therapeutic doses from those used for adults.
Surface area
The surface-area or percentage method for estimating doses is calculated as follows:
Weight
Adult dose (mg
70kg
0.5 kg to 120 kg) let alone their changes in kinetics. Children should be regularly weighed
so that up-to-date weights can be used for prescribing. However, remember the practical-
ities of what is to be given to the child. If a child is 6.5 kg and requires 2 mg/kg of ranitidine,
it would seem wiser to prescribe 15 mg, which is 1 ml of the oral liquid, rather than 13 mg,
which equates to 0.867 ml. Some knowledge of the therapeutic range of the drug is required
to know when and by how much it is suitable to round doses, however, and sometimes
awkward quantities are required.
5. DRUG MONITORING
Most drugs have wide therapeutic windows and thus toxicity is unlikely at 'normal doses'. It
is usually easy to see a medication effect, e.g. analgesics take away pain. There are,
a
Essential Revision Notes in Paediatrics h r the M RCPCH 2r9d Eclitior~
however, certain circumstances when it is important to measure drug levels to ensure that
there are adequate levels for effect and/or that the levels are unlikely to cause toxicity.
A drug with a narrow therapeutic window has a narrow range between the drug concentra-
tion exhibiting maximum efficacy and that producing minimum toxicity.
Medications that have narrow therapeutic windows are often monitored, as it is hard to
predict whether a dose for an individual patient will be clinically effective or will cause
toxicity.
6. INTERACTIONS
Many situations arise where interactions between different medications are important. Drugs
may either inhibit or induce the liver enzyme systems as follows.
Liver inhibition
Will lead to potentiation of:
Warfarin, phenytoin, carbamazepine, theophylline, cyclosporin
Caused by:
Omeprazole, erythromycin, valproate, isoniazid, cimetidi ne, su lphonamides, acute
alcohol consumption
Absorption interactions
Medication that changes the pH of the stomach or the motility of the stomach may vastly
change the absorption of another medication (see Section 1.I).
Compatibility
When medications are administered, always be aware of their interactions before they enter
the body. This is particularly important with parenteral medication. Many medications
interact to produce non-effective products, toxic products or precipitates.
The frequency and volume of the feeding must also be considered as there will be less
exposure to the drug if the infant is receiving supplementary feeds and/or other liquids.
Further reassurance can be given to a parent if the medication that is being given has a long
term history of safety in children at therapeutic levels.
Taking all this into consideration there are very few drugs that are contraindicated in breast-
feeding women. The table lists the medicines which are usually seen as a contraindication
to breast-feeding. The benefits of breast-feeding usually outweigh the small theoretical risk
of harm to the neonate. This said we should never become complacent and should look for
the evidence and approach newer drugs with more caution.
7. TOXICOLOGY
Each year 40,000 children attend A&E Departments with suspected poisonings/accidentaI
ingestion. These incidents fall into three categories:
Accidental - typically boys in the 1-4 years age group
Intentional - usually teenage girls
Deliberate - suspected if the signs cannot be explained in any other way
Principles of management include the following:
Resuscitation if necessary
Contact a national poisons unit for advice
Induction of emesis (with ipecacuanha for example) is no longer indicated
Consider limiting absorption of poison by:
Activated charcoal - if ingestion is within 1 hour
Gastric lavage - if a life-threateningquantity of poison is ingested
Acid, alkali or corrosive substances should be treated with caution - do not intervene
with the above before seeking advice from the poisons unit
156
Levels of > 250 mg/kg are likely to lead to severe liver damage.
Clinical features
Nausea and vomiting are the only early symptoms although the majority of patients are
asymptomatic
Right subcostal pain may indicate hepatic necrosis
Management
Activated charcoal if ingestion < 4 hours earlier
Measure plasma paracetamol level at 4 hours or as soon as possible thereafter
Acetylcysteine, a glutathione donor, is nearly 100% effective if administered up to
24 hours p ~ singestion
t in preventing hepatotoxicity and nephrotoxicity
Be aware of 'high-risk' factors that may require a lower threshold (total paracetamol
ingestion as low as 75 mg/kg) for active management. These include conditions that
decrease hepatic glutathione stores (e.g. anorexia nervosa, cystic fibrosis,
matnourishment) and drugs that induce cytochrome p450 microenzymes (e.g.
phenytoin, carbamazepine, rifampicin, phenobarbitone)
7.2 Iron
Severity of poisoning is related to the amount of elemental iron ingested.
A 200 mg tablet of ferrous sulphate contains 65 mg elemental iron
A 300 mg tablet of ferrous gluconate contains 35 mg elemental iron
< 20 mg/kg toxicity unlikely
> 20 mg/kg toxicity may occur
> 60 mg/kg significant iron poisoning
Clinical features
1St stage
Within a few hours
Nausea and vomiting
Abdominal pain
Haematemesis
stage
8 to 16 hours
Apparent recovery
Essential Revision Notes in Pnediatrics tor the MKCPC3i 2nd Eclition
3rdstage
a 16 to 24 hours
Hypoglycaemia
Metabolic acidosis (due to lactic acid)
Late stage
Hepatic failure - 2 to 4 days
Management
Initial treatment depends on the likelihood of toxicity, i.e. was > 20 mg/kg ingested?
Plasma iron level
Abdominal X-ray
No iron visible but > 20 mg/kg ingested: give desferrioxamine orally
lron in stomach: gastric lavage with desferrioxamine in the lavage fluid
lron in intestine: desferrioxamine orally, picolax orally - a bowel stimulant
If > 60 mg/kg ingested: administer parenteral desferrioxamine
Clinical features
Depressed level of consciousness
Respiratory depression
Convulsion
Arrhythmia
Hypotension
Anticholinergic effects:
Pupillary dilatation
Urinary retention
Dry mouth
Management
Resuscitation
0 Activated charcoal
ECG monitoring
Sodium bicarbonate and systemic alkalinization
Monitor potassium as sodium bicarbonate can cause hypokalaemia
All antiarrythmics should be avoided especially class la agents. Treat convulsions
aggressively with benzodiazepines and sodium bicarbonate and if refractory, with
general anaesthesia and supportive care
Clinica 1 Pharn~ncologyand Toxicology
Clinical features
In young children dehydration and tachypnoea. In older children and adults tachypnoea
and vomiting with progressive lethargy. Tinnitus and deafness. Hypoglycaemia or hypergly-
caemia can occur.
Three phases
Phase One
May last up to 12 hours
Salicylates directly stimulate the respiratory centre resulting in a respiratory alkalosis
with a compensatory alkaline urine with bicarbonate sodium and potassium loss
Phase Two
May begin straight away, particularly in a young child, and last 12-24 hours
Hypokalaemia with, as a consequence, a paradoxical aciduria despite the alkalosis
Phase Three
After 6-24 hours
Dehydration, hypokalaemia and progressive lactic acidosis. The acidosis now
predominating
Can progress to pulmonary oedema with respiratory failure,. disorientation and coma
Management
Gastric lavage up to 4 hours. Activated charcoal for sustained release preparations.
Salicylate level at 6 hours plotted on a normogram and repeat every 3-4 hours until
level has peaked. Levels between 200 and 450 mg/l can be treated by activated
charcoal and oral or intravenous rehydration while levels greater than 450 mg/l require
alkalinization
Alkalinization of the urine to aid drug excretion, adequate fluids including bicarbonate
sodium and potassium with close monitoring of acid-base and electrolytes
Discuss care with National Poisons Centre
7.5 Lead poisoning
Lead poisoning is uncommon but potentially very serious. It often results from pica
(persistent eating of non-nutritive substances, e.g. soil) and is therefore more common in
pre-school-age children. Other causes include suckinglingesting lead paint, lead pipes,
discharge from lead batteries and substance abuse of leaded petrol.
Lead intoxication can be divided into acute and chronic effects, and results from its
combination with and disruption of vital physiological enzymes.
Acute intoxication
Reversible renal Fanconi-like syndrome
Chronic intoxication
Failure to thrive
Abdominal upset: pain/anorexia/vomiting/constipation
Lead encephalopathy: behavioural and cognitive disturbance, drowsiness, seizures,
neuropathies, coma
Glomerulonephritis and renal failure
Anaemia - microcytidhypochromic, basophilic stippling of red cells
A co-existing iron deficiency is common which first, further exacerbates the anaemia and
second, actually contributes to increased lead absorption. Basophilic stippling is the result
of inhibition of pyrimidine 5' nucleotidase and results in accumulation of denatured RNA.
Treatment involves
Removing source
Chelation:
Mild - oral D-penicillamine
Severe - intravenous sodium calcium edetate (EDTA)
Very severe - intramuscular injections of dimercaprol to increase effect of EDTA
Some US states implement universal screening for elevated lead levels in children.
is normal but the oxygen content of the blood is reduced. Toxicity relates loosely to the
maximum carboxyhaemoglobin concentration. Other factors include duration of
exposure and age of the patient
8. FURTHER READING
Creene SL, Dargan PI, Jones AL. 2005. Acute poisoning: understanding 90°/0 of cases in a
nutshell. Postgraduate Medical]ourna/81, 954, 204-1 6.
Young Y L, Koda Kimble MA. 2001 . Applied Therapeutics: The Clinical Use of Drugs, sixth
edition. Chapters 95 and 96. Lippincott Williams & Wilkins.
Royal College of Child HealthlNeonatal & Paediatric Pharmacists Group. 1999. Medicines
for Children.
Maxwell GW. 1989. Paediatric drug dosing. Drugs 37, 113-1 5.
Rylance GM. 1988. Prescribing for infants and children. British Medica/]ournal296, 984-6.
Watson D et a/. 1993. Principles of drug prescribing in infants and children: a practical
guide. Drugs 46:2, 281 -8.
Chapter 5
Dermatology
Helen M Goodyear
CONTENTS
1. Structure and function of the skin 165
1.I Structure of the skin
1.2 Function of the skin
1.3 Skin biopsy
3. Birthmarks
3.1 Strawberry naevi (capillary haemangioma)
3.2 Salmon patch (stork bite)
3.3 Port wine stain (naevus flammeus)
3.4 Sebaceous naevi
3.5 Melanocytic naevi
5. Blistering disorders
5.1 Epidermolysis bullosa
5.2 Drug eruptions
5.3 Autoimmune blistering disorders
6. Erythemas
6.1 Erythema multiforme
6.2 Erythema nodosum
Essential Revision Notes ir-, Paediatrics t;)r the MRCYCH 2nd Editior?
7. Photosensitive disorders
7.1 Genetic causes of photosensitivity
$. Ichthyoses
8.1 Inherited ichthyoses
8.2 Collodion baby
8.3 Harlequin ichthyosis
E&isrmis
Four layers Cells
Stratum corneum - keratinization Keratinocytes (95%)
Stratum granulosum Merkel cells
Melanocytes
* . Langerhans' cells
al variation in thickness of epidermis
Dermoepidermaljunction
A barrier and a filter
Dermis
15-20% of body weight Celb
Subcutaneoasfat
Epidermal brtnsit time: 52-75 days. Greatiy dec
conditions, e.g. psoriasis
Palmoplantar skin: extra layer, stratum lucidum,
granufosum and stratum corneum
Two types of skin: glabrous skin on palms and soles and hair-bearing sLin
3- BIRTHMARKS
3.1 Strawberry naevi (capillary haemangioma)
Usually appear in first few weeks of life
More common in preterm infants
Precursor is an erythematous/telangiectatic patch +I- pale halo
Three phases:
Proliferative (6-1 0 months)
Stabilization
Spontaneous resolution - pale centre initially
Complications - ulceration, infection, bleeding, cardiac failure
Treat if obstructs vital structures
Often deep component: cavernous haemangioma
Multiple small diffuse haemangiomas in infants < 3 months of age may be associated with
visceral involvement, particularly liver; high mortality if untreated
Kasabach-Merritt syndrome: thrombocytopenia, rapidly enlarging haemangioma, microan-
giopathic haemolytic anaemia, localized consumption coagulopathy
R
CHILD
clothing, chemicals, carpets,
ATOPIC
ECZEMA 1 *
Emotional stress
Exacerbating factors of atopic eczema (URTls, upper respiratory tract infections; AD,
autosomal dominant)
Associated conditioms
lchthyosis vulgaris
* Keratosis piiaris
Food intolerance and allergy
Pityriasis alba
juvenile plantar dermatosis
Asthma
Cataract
Differential diagnoses
lichen simplex chronicus: asymmetrical lesion, chronic rubbing and scratching
infantile seborrhoeic dermatitis: usually in first 3 months, yellow greasy scales on scalp,
forehead, napkin area and skin folds, lack of pruritus. Treat with emollients and 1 %
hydrocortisone if needed (see eczema treatments)
Contact dermatitis
Hyper IgE syndrome (Job's syndrome): IgE > 2,000 IUIml, recurrent cutaneous and
sinopulmonary infections
a Wiskott-Aldrich syndrome: X-linked recessive, thrombocytopenia and recurrent
pyogenic infections. Risk of malignancies, non-Hodgkin's lymphoma most common
Topical treatments
Emollients - bath oil once or twice daily, soap substitute, moisturizer qds (e.g. aqueous
cream, emulsifying ointment). Any of the moisturizers can be used as soap substitutes.
Use antiseptic bath oils, e.g. Dermol 600, Oilatum Plus, and emollients, e.g. Derrnol
500 lotion, if recurrent infection
Steroid creams/ointments - weakest strength possible applied twice'daily using
fingertip unit (FTU) to control the eczema. In general; mild potency 1% hydrocortisone
if < 2 years; moderate potency if needed, e.g. Eumovate, Betnovate 1 in 4, if > 2 years.
Never use potent, e.g. Betnovate, or very potent, e.g. ~ermovate;in children except in
specialized centres. Some evidence that moderate potency three times weekly is as
good as mild potency twice daily. Risk of side-effects increases with potency and
includes skin thinning, irreversible striae and telangiectasia, acne, depigmentation and
Gushing's syndrome
Bandages - zinc impregnated, e.g. ichthopaste, worn with elasticated bandage such as
Coban over the top. Change every 24-48 hours. useful for chronic limb eczema
Wet wraps - cotton tubular bandages of different sizes cut to make double body suit or
ready-made vest and leggings (TubifastIComfifast).Make first layer wet with either water
or cream. Wear at night. Either emollients used under wraps, e.g. aqueous cream, or
dilute steroid cream, e.g. Betnovate, 1 in 10 in aqueous cream
Tacrolimus (Protopic) 0.03O/0 ointment and Pimecrolimus (Elidel) works on skin immune
system, affecting cytokine release, new treatment for moderate or severe eczema not
responding to conventional treatment. Use twice daily for 3 weeks then once daily. Not
for continuous use of > 3-4 months because of concern of cancer risk
Antihistamines - use with caution in children < 1 year
Antibiotics - consider a 10-day course if eczema flares up. Flucloxacillin +I -
penicillin
v or erythromycin. Beware of MRSA (methicillin-resistantS. aureus) and resistance to
erythromycin in some hospital-acquired S. aureus infections
Aciclovir - 1.5 g/m2 per day intravenously for 5 days if eczema herpeticum
(generalized HSV infection of atopic eczema). Oral aciclovir for HSV recurrences.
Suspect eczema herpeticum if eczema deteriorates and vesicopustules or punched out
lesions are present
Diet - avoid obvious trigger foods. Give 3-month trial of cows' milk protein-free diet if
severe eczema < 1 year. Involve paediatric dietitian
Systemic therapy - severe eczema unresponsive to above therapies. Use prednisolone,
starting around 2 mg/kg to control eczema, then weaning down to lowest alternate day
dose which controls eczema. Short-course cyclosporin (up to 5 mg/kg per day) for 3-
6 months also used, but monitor renal and liver function carefully
Alternative remedies - many patients will use these, e.g. homeopathy, Chinese herbal
medicine. Beware of potent steroid creams in Chinese herbal creams and monitor liver
and renal function %monthly if taking herbs. Avoid in children < 2 years
4.2 Urticaria
Transient erythematous/oedematous itchy swellings of the dermis. Lasts from a few minut
to 24 hours. Clears leaving normal skin. 5O0/0 have angio-oedema (swelling of subcutaneo
tissues). Histamine is the principal mediator released from mast cells.
Infection
Wral
Streptococcus
Toxocara canis ,
Food-
172
4,s Infections and infestations
Scabies
As a result of the mite Sarcoptes scabiei humanis. The mite can survive for 24-36 hours off
the human host.
variable intensely itchy skin eruption, about 1 month after infestation, is an immune
response to the mite and includes:
Burrows
Excoriations
Eczematization
Papules
Vesiculopustular lesions
Bullae
Secondary bacterial infection
Nodules
Burrows common on palms, soles and sides of digits. Examine all family members if scabies
is suspected. Treat all family at same time.
Management of scabies
Use aqueous-based preparation (alcohol-based preparation will sting), e.g Malathion
(Derbac M) and Permethrin 5%
Treat all family members at the same time
Two applications from the neck downwards at 7-day interval. Get under nails and in
skin creases. Reapply after hand washing. Caution if < 1-year-o!d, applying for less time
depending on age of child
Apply to lesions on face if present (more common if < 1 yearj
Treat any secondary infection with systemic antibiotics
Treat residual dry skin with emollients
Wash all clothing, bedlinen and towels at the end of treatment
Pediculosis
Usually Pediculus humanus capitis (head louse). May get lice on eyelashes and pubic
hair
Occurs in from < 10% to 40% of children
Spread by head to head contact
Pruritus, scratching and excoriation may lead to secondary bacterial infection and
cervical lymph nodes
Look for nits on hairs. Lice visible if recently had a blood meal
Treat with two applications 7 days apart of malathion-based aqueous lotion or
permethrin 5% cream (off licence use)
Bug busting with wet combing - evidence varies of effectiveness
1
rdj i
Essential Revision Notes in Paediatrics for the MRCPCH 2nd Edition
Viral infections
Tend to be maculopapular erythematous rashes which may be pruritic. Last from < 24 hours
to a few weeks. Associated features include cough, runny nose, diarrhoea, vomiting and
pyrexia.
Tinea
Erythematous, circular scaly lesions with clearly defined margin. Microsporum canis
fluoresces with UV light, Trichophyton tonsurans (of human origin, common in inner cities)
does not. Take skin scrapings.
Impetigo
Superficially spreading skin infection characterized by yellowish-brown crust. May be
bullous. Peaks in late summer and is commonest in children < 5 years. Causative agent
aureus or Group A beta haemolytic streptococcus. Treat with oral antibiotics.
Warts
Caused by human papillomavirus. Commonest on hands and feet (plantar warts/verrucas
but occur at any site. Most resolve spontaneously but can last for several years.
Treat with salicylic acid-based wart paint, e.g. Salactol, applying-each night and rubbing
wart down with an emery board until wart is flat. May need to treat for 3 months or longer.
Freezing with liquid nitrogen is effective but often requires multiple. treatments at monthly
intervals. Poorly tolerated in children < 5 years.
Perianal warts
Usually innocently acquired but consider sexual abuse. Only treat if multiple and spread-
ing. Use podophyllin 15%. May need surgery.
Mollusca contagiosa
'Water warts'. Caused by poxvirus. Dome-shaped papules with an umbilicated centre.
Spread by autoinoculation. Resolve spontaneously but can last for several years. Treatments
tend to be associated with scarring.
NB Both warts and mollusca contagiosa are more common in children who are immuno-
suppressed and in those with underlying skin disorders such as atopic eczema.
Dermatology
4.4 Psoriasis
a Onset: < 2 years in 2% and at < 10 years in 10% of cases of psoriasis. In childhood
onset tends to be between 5-9 years in girls and 15-1 9 years in boys
a Increased epidermal turnover time
a Relapsing and remitting: scaly rash, typically affects extensor surfaces and scalp
(Pityriasis amiantacea)
a Genetic predisposition: risk of psoriasis is 10% if a first-degree relative is affected, risk is
50% if both parents are psoriatic; 73% monozygotic and 20% dizygotic twins have
concordant disease; HLA Cw6 (613 and I317) linked to 9-1 5 times risk, HLA I327
associated with psoriatic arthropathy
Nail involvement: pits, onycholysis, subungual hyperkeratosis; may precede onset of
skin lesions
Arthropathy: may be severe; higher incidence in patients with nail changes
Rovoking factors
Trauma (Koebner phenomenon)
Infection: streptococcal disease especially in throat in guttate psoriasis; may also play a
role in chronic plaque psoriasis
Endocrine: peaks at puberty (and menopause); gets worse in posipartum period
Sunlight: usually beneficial but makes a small number worse . *
Metabolic: hypocalcaemia, dialysis
Drugs: withdrawal of systemic steroids, f3-blockers, antimalarials and lithium
C
Psychogenic factors: stress
Human immunodeficiency virus: psoriasis may appear for the first time or get
dramatically worse
Differential diagnosis
Hyperkeratotic eczema
Lichen planus: flat-topped, purple polygonal papules with white reticulate surface
(Wickham's striae); oral and nail changes may be present; rare in children; 90% resolve
in 12 months
Pityriasis rosea: larger herald patch, smaller lesions in Christmas tree distribution; clears
in 6 weeks; linked to human herpes virus-7
Pityriasis lichenoides chronica: excoriated papules on trunk and limbs in crops; lasts up
to a few years
frii-s k2t- the A 1RCPCH 2r7d Editior I
Essential Revision Notes i17 Pil~cli~l
Management of psoriasis
Avoid triggering factors
Treat streptococcal infection
Topical treatment
Emollients
Tar-based bath emollients, e.g. Polytar
Tar and salicylic acid ointments
Vitamin D-derivative creams - calcipotriol (Dovonex) for mild to moderate psoriasis
(up to 40% of skin area affected)
Mild-potency topical steroid creams with tar, e.g. Alphosyl HC for delicate areas, e.g.
face, flexures, ears, genitals
Carefully supervised dithranol preparations, e.g. dithrocream
Topical retinoids used but unlicensed
Phototherapy: UVB phototherapy if child is old enough to comply. PUVA is
contraindicated in young children
Systemic therapy: severe psoriasis, acute pustular psoriasis, e.g. methotrexate,
cyclosporin, acitretin
5. BLISTERING DISORDERS
inherited
Epidermolysis bullosa
Incontinentia pigmenti
~unousichthyosiform etythroderma
Drugs
Fixed drug erup
Photosensitivity
Sulphonamid7e
Barbiturates +
' I
Autoimmune
Chronic bullous disease of childhood
Pemphigoid
Epidermolysis bullosa acquisita
Dermatitis herpetiforrnis
Pemphigus
Mechanobullous
Trauma/ft.iction
Burns
Insect biteslpapular urticaria
* Contact dermatitis
5.1 Epidermolysis bullosa (EB)
Heterogeneous condition. Need skin biopsy for definitive diagnosis. First-trimester prenatal
diagnosis is possible. Severe types at risk of nutritional deficiencies and anaemia.
There are three broad categories:
EB simplex: mainly autosomal dominant (AD) - defect in basal layer of epidermis
affecting keratins 5 and 14. Usually appears when child begins to crawl or walk, with
blisters at friction sites, e.g. knees, hands and feet. Hair, teeth and nails not affected
Junctional EB: autosomal recessive (AR) - lethal and non-lethal variants. Mucous
membranes can be severely affected and teeth are often abnormal. Laminin-5 defect.
Raw denuded areas show little tendency to heal. Hoarseness as a result of laryngeal
involvement
Dystrophic EB: AD and AR - subepidermal blister. Defect in collagen-VII production.
Lesions heal with scarring. Hair and teeth are normal in dominant form, whilst
involvement of mucous membranes, nails, hair and teeth may all be abnormal in
recessive form. Web formation between digits leads to a useless fist. May develop
squamous carcinoma
Bullous pemphigoid
Can be < 12 months. Palm and sole involvement common. 75% have mucous membrane
changes. Lasts 2-4 years. Linear basement membrane IgG.
Dermatitis herpetiformis
Mean age 7 years. Affects buttocks, elbows, back of neck and scalp. Itchy. 15% resolve
spontaneously. Skin changes can persist up to 18 months after gluten-free diet. IgA in
papillary dermis.
Pemphigus
Very rare. Flaccid blisters. Nikolsky's sign positive (i.e. a blister is induced by rubbing
normal-appearing skin). Mucous membrane involvement in vulgaris type, with stomatitis the
presenting sign in 50% of cases. lntercellular IgG.
6. ERYTHEMAS
6.1 Erythema multiforme
Acute self-limiting onset of symmetrical fixed red papules, some of which form target
lesions. May blister. Can show Koebner phenomenon. May involve lips, buccal mucosa and
tongue.
*
i
Drugs
Sulphonamides
Penicillin
Collagen diseases
. Orf
Deep fungal infections (histoplasmosis)
Systemic lupus erythematosus
Polyarteritis nodosa
Underlying malignancy
Xeroderma pigmentosum
AR group of disorders caused by a DNA repair defect.
Extreme photosensitivity
Severe ophthalmological abnormalities
Skin malignancies in childhood
Neurological complications in 20%
Freckling
Cockayne's syndrome
AD. Cells have increased sensitivity to UV light. Onset of symptoms is in the second year 01
life.
Progressive neurological degeneration and growth failure
Sensorineural hearing loss
Skeletal abnormalities
Dental caries
Pigmentary retinopathy
Cataracts
I
I Derrnatology
I
I
Trichothiodystrophy
!!
i AR. Hair has low sulphur content. Includes following defects - 'PIBIDS':
a Photosensitivity
a lchthyosis
a Brittle hair
a Intellectual impairment
a Decreased fertil ity
a Short stature
Rothmund-Thomson syndrome
AR. Characterized by poikiloderma (atrophic pigmented telangiectasia) by end of first year.
Sparse hair
Skeletal dysplasia
Short stature
Cataracts
Hypogonadism
Hypotrophic nails
Increased risk of osteosarcoma and skin malignancy
Bloom's syndrome
AR.
Growth retardation
Immunodeficiency (IgA and IgM)
Telangiectasia
Pigmentary abnormalities
Malignancies in third decade - leukaemia, lymphomas '
Hartnup's disease
AR. Impaired amino acid transport in kidneys and small intestine. Most children asympto-
matic.
Photosensitivity with pellagra-like appearance is first sign
Can form blisters
Intermittent cerebellar ataxia
Psychotic behaviour
Mild mental retardation
Porphyrias
Croup of diseases leading to accumulation of haem precursors. 5-aminolaevulinic acid
(ALA) and porphobilinogen (PBC) have no cutaneous manifestations. Elevated porphyrins
are associated with either acute photosensitivity or skin fragility with vesiculobullous and
erosive lesions.
Essential Revision Notes in Paec/ic7tricsfor the M RC'PC7-l Zncl Edition 2
8. ICHTHYOSES
Disorders of keratinization, characterized by excessively dry and visibly scaly skin. Heredi-
tary or associated with systemic disease.
Corneal opacities
prolonged labour (placental sulphatase deficiency)
Lamellar ichthyoses
AD and AR. Large, dark, plate-like scales, reptilian appearance.
~ u l l o uicht
s hyosiform erythroderma
AD. Erythroderma and severe blistering at birth. Mutations in keratin 1 or 10.
Refsum's disease
AR. Phytanic acid oxylase defect.
Retinitis pigmentosa
Peripheral neuropathy
Anosmia
Sensory deafness
Variable ichthyosis - ichthyosis vulgaris-type appearance
-
Trichothiodystrophy syndromes Tay's syndrome and 'PIBIDS'
AR. Those with Tay's do not have photosensitivity. Hair has decreased sulphur content.
Essenti'd Revision N o t e in Paedjatrjcs b r the MRCYCH 2nd Edition -
Netherton's syndrome
AR.
Neonatal erythroderma
lchthyosis linearis circumflexa
Atopy
Faltering growth
Recurrent infections
Trichorrhosis invaginata - hair shaft abnormality
Happle's syndrome
X-linked dominant. Conradi-Hunermann syndrome is AD and is now thought not to have
cutaneous manifestations.
Chondroplasia punctata
Cicatricial alopecia
Cataracts
Short stature
Follicular atrophoderma
KID syndrome
Mode of inheritance uncertain - ? AD or AR.
Keratitis
lchthyosis
Deafness
CHILD syndrome
Congenital hemidysplasia, ichthyosiform erythroderma and limb defects.
j a ~chthyosisvulgaris
a Netherton's syndrome
May need up to 250 ml/kg per day fluids. Nurse in high-humidity incubator with up to
1 -hourly application of white soft paraffin and liquid paraffin 50 : 50.
Usually preterm
These phases occur randomly so that no one area is depleted of hair. Anagen lasts for
variable lengths of time depending on site. Usually > 3 years on the scalp.
186
Causes of scalp scaling
Seborrhoeic dermatitis
Atopic eczema
Fungal infection
Psoriasis
Pityriasis amiantacea
Histiocytosis
Causes of hypertrichosis
Hypertrichosis lanug~nosa
Cornelia de Lange syndrome
Rubinstein-Taybi syndrome
Hurler's syndrome
Turner's syndrome
9.2 Nails
Development begins at the 9th week of gestation and is complete after the 22nd week.
Toenail development lags behind that of fingernails.
Essential Revision Notes in Pc7edic7tric-sfor the MRCPCH 2nd Edition
9.3 Teeth
Always look at the teeth as part of a dermatological examination.
Chediak-Higashi syndrome
AR. Incomplete oculocutaneous a1binism, photophobia and severe recurrent infections.
r MKCPCI-i 2nd Edition
Essential Revision Notes in R ~ e d i ~ ~ t rtiic~sthe
Causes of hyperpigmentation
Genetic Endocrine
lncontinentia pigmenti Addison's dise
'"
Metals
Silver, bismuth and arsenic
Slate-grey pigmentation
Dermatology
~ongolianblue spot
Blue skin
Typical site is lower back
Common in Afro-Caribbean and Asian babies
~ncreasednumbers of melanocytes deep in dermis
Tends to disappear by 4 years of age
1 MISCELLANEOUS DISORDERS
111 Granuloma annulare
Ring of firm skin-coloured papules. Usually asymptomatic. May follow non-specific trauma
in 25%. 50% clear in 2 years. 40% have recurrent eruptions. Link to diabetes mellitus
controversial. Always test urine for glucose.
Emergency Paediatrics
Serena Cottrell
CONTENTS
1. Inttoduction
2. Out-of-hospital cardiac arrest
2.1 Airway opening procedures
2.2 Look, listen and feel
2.3 Rescue breaths
2.4 Checking the circulation
2.5 Chest compressions
4. Post-resuscitation management
7. Airway
7.1 Airway obstruction
7.2 Choking
7.3 Inadequate airway protection
8. Respiratory failure
8.1 Apnoea
8.2 Trauma and breathing difficulties
8.3 Management of acute severe asthma
8.4 Ventilating children with bronchiolitis
8.5 Children with pertussis needing admission to PlCU
EssentiCllRevision Notes in Weclic~trics
tor the M KCPCH 2 n d Edition
9. Cardiovascular system
9.1 The child with tachycardia
9.2 Supraventricular tachycardia
9.3 Causes of tachyarrhythmia
9.4 Ventricular tachycardia
9.5 Causes of bradyarrhythmia
9.6 Emergency management of severe heart failure
9.7 Recognizing low cardiac output state
9.8 lnotropes
9.9 The child in shock
15. Trauma
15.1 Life-threatening extremity injuries
15.2 Gunshot wounds and stabbing
16. Drowning
16.1 Pathophysiology
16.2 Treatment
16.3 Re-warming
16.4 Prognostic signs
1. INTRODUCTION
~t is vital to have a structured approach when managing a critically ill child. A structured
approach enables you to prioritize and stabilize most sick children even when the diagnosis
is unknown. Preparation is useful, although not always possible, and good communication
is essential both between members of the multidisciplinary team and with families. The
structured approach concentrates on identifying and managing the immediate threats to life
first: ABC, A for airway, B for breathing and C for circulation.
I UNRESPONSIVE?
4
I
I Shout for help
4
Open airway
4
NOT BREATHING NORMALLY?
4
5 rescue breaths
4
STILL UNRESPONSIVE?
(no signs of a circulation)
4
15 chest compressions
2 rescue breaths
L -
Algorithm for basic life support (Healthcare professionals with a duty to respond)
Call emergency services after 1 minute of CPR (cardiopulmonary resuscitation)
198
Emergency Paediatrics
If there are no signs of circulation, no pulse or a slow pulse, less than 60 beats per minute
with poor perfusion, or you are unsure, start compressions.
Two fingers over the lower third of the sternum for the single rescuer
Hands encircling the chest; two thumb technique for two rescuers
The heel of one or two hands may be used, depending on the size of the rescuer and
the child
3.2 Oxygen
This should be:
Administered immediately in all arrest scenarios
Given by face mask or bag and mask with a flow of 15 litres per minute
With a reservoir or non-rebreath bag attached
Make sure the arrest team and appropriate senior help are called.
Unresponsive?
4
1
Commence BLS
Oxygenatelventilate
ResuscitationTeam
CPR 15:2
Until defibrillatorlmonitor attached
Assess
rhythm
Shockable Non-Shockable
(VFlpulseless VT) (PEA/Asystole)
1
This is the most common arrest rhythm in neonates and children and is usually secondary
to hypoxia and acidosis from respiratory failure. It is often preceded by a bradycardia.
Check the leads are attached correctly
Increase the gain on the monitor
Check the pulses if trained and experienced (no longer than 10 seconds)
4
I
Commence BLS
Oxygenatelventilate
ResuscitationTeam
CPR 15:2
Until defibrillatorlmonitor attached
Shockable Non-shockable
(VFlpulseless VT) 7(PEA/Asystole)
During CPR:
Correct reversible causes'
Check electrode position
v and contact
1 Shock Attemptlverify:
4 Jlkg or AED ivlio access
(attenuated as appropriate) airway and oxygen
Give uninterrupted
compressions when
trachea intubated v
Give adrenaline
lmmediafely resume
every 3-5 min
CPR 15:2
CPR 1 5 2 Consider: amiodarone,
for 2 min
for 2 min atropine, magnesium
*Reversible Causes
Hypoxia Tension pneumothorax
Hypovolaemia Tamponade, cardiac
Hypolhyperkalaemialmetabolic Toxins
Hypothermia Thromboembolism
A pre-cordial thump may be given in the monitored child, if arrest was witnessed.
Time between compressions should be minimized
If the rhythm has altered, do a pulse check
The shock is asynchronous
Adrenaline is given before the third shock and before every other shock (i.e. every 3 to
5 minutes)
Amiodarone (5 mg/kg) is given iv before the fourth shock
4. POSTRESUSCITATION MANAGEMENT
This involves transfer to a paediatric intensive care unit
Regular reassessment should be performed
ECG, pulse oximetry, blood pressure monitoring invasive or non-invasive, temperature,
capnography, urine output and blood gases
Central venous pressure monitoring may also be needed
6. ELECTROCUTION INJURY
May present as a ventricular fibrillation arrest
Severe electrocution injury in children is uncommon
It can occur with faulty electrical appliances such as living room fires
If the injury has been obtained out of the domestic environment it is often associated
with other injuries such as falls or with the child being thrown into the air
Being struck by lightning is another cause
The risk of cardiac arrest is associated with the size of the current, duration of exposure
and whether the current is AC (alternating current) or DC (direct current)
Tetany can occur in the muscles which may make the child cling on to the electrical
source e.g. the bar of an electric fire
If tetanus occurs in the diaphragm and other respiratory muscles, it can lead to a
respiratory arrest which continues until the child is disconnected
Tetany occurs at currents < 100 mA. Defibrillators in resuscitation deliver about 10 A
The child should be examined for entry and exit burns
bnergrncy Paediatrics
The path of the current can be estimated from the site of the entry and exit burns and by
assuming the current will take the path of least resistance from the point of contact to
the earth
~luid and blood have the least resistance whereas skin and bone have a high resistance
The damage is caused by heat. Nerves, blood vessels, skin and muscle are damaged the
most
Swelling of tissues, especially muscles, can lead to compartment syndrome and
myoglobinuria
a Myoglobinuria can lead to renal failure if unrecognized and untreated
6.3 Myoglobinuria
Occurs after muscle injury such as a crush injury or electrocution
Can be detected in the urine
Treatment is maintaining a urine output of greater than 2 mVkg per hour by fluid loading
and diuretics, using mannitol if required
Alkalinize the urine by using iv sodium bicarbonate to improve the excretion of
myoglobin
Alkalinization of the urine is used to keep a toxin in its ionized form, to reduce the
amount of absorption in the renal tubule
This is called forced alkaline diuresis and is also used for aspirin and phenobarbitone
overdose
Essential Revision Notes in Eiedi,? trics tbr the M RCPCH 2nd E d i f i ~ n
7. AIRWAY
The main aspects of airway that need to be addressed are:
Obstruction
Choking
Failure to protect the airway from aspiration of gastric contents
7.2 Choking
A blind finger sweep should not be performed
Assess severity .
v v
- Ineffective cough - Effective cough
v '
I
Unconscious Conscious Encourage cough
Open airway 5 back blows Continue to check
5 breaths 5 thrusts for deterioration
Start CPR (chest for infant) to ineffective
(abdominal cough
for child > 1) or relief of
obstruction
--
u
Infant choking protocol
The baby is placed along one of the rescuer's arms in the head-down position with the
rescuer's hand supporting the baby's jaw, keeping it open in the neutral position
Essential Revision Notes jn Paedjatrjcs tbr the MRCPCH 2nd Editi011 -
a The rescuer then rests his or her arm along the thigh and delivers five back blows with
the heel of the hand
a if the obstruction is not relieved, the baby is turned over and with head down is given
five chest thrusts using the same landmarks as for cardiac compression
The back blows and chest thrusts are at a rate of 1 per second
If the infant is too large, place across the rescuer's lap and perform the same technique
For the choking child, use abdominal thrusts instead of chest thrusts the rest of the
protocol remains the same including the back blows
The Heimlich manoeuvre can be performed in a child but never in an infant because of
the risk of trauma to internal structures. The patient can be standing, sitting, kneeling or
lying for the Heimlich manoeuvre
8. RESPIRATORY FAILURE
Respiratory failure is defined as an inability of physiological compensatory mechanisms to
ensure adequate oxygenation and carbon dioxide clearance resulting in either arterial
hypoxia or hypercapnia, or both.
The most common causes of respiratory failure are an upper or lower respiratory tract
illness; however, disorders of other systems can present with breathing difficulties and
should be considered in the differential diagnosis.
8.1 Apnoea
This is a common sign in neonates and small infants and has a wide differential diagnosis.
Prematurity
Bronchiolitis
Essentia / Revision Notes in t?aedic?tricstor the M KCPCH ?lid Edition
Pertussis
Pneumonia
Sepsis
Severe gastro-oesophageal reflux
Fits
NAI (non-accidental injury)
Vascular ring
If child is intubated
Ketamine is the induction agent of choice as it is a bronchodilator
Ketamine infusion can be added in
Manual decompression of the chest on expiration gives an indicator of the severity
Permissive hypercapnia is a ventilation strategy where the carbon dioxide levels are
allowed to rise as long as the pH remains above 7.2
Finding the ideal level of positive end-expiratory pressure (PEEP) is difficult in a
ventilated asthmatic and is often done by trial and error. Measuring the auto-PEEP can
help
A slow respiratory rate is usually necessary, i.e. < 20
It is important to remember that there is still mortality from asthma and so a respiratory
paediatrician should be consulted in any child with asthma severe enough to need
admission to the paediatric intensive care unit (PICU)
Airways
The oropharyngeal or Guedel airway is poorly tolerated in the conscious patient and
may cause vomiting
The nasopharyngeal airway is better tolerated but may cause haemorrhage from the
vascular nasal mucosa
Non-invasive ventilation
Oscillation
Oscillation is used as a lung protective strategy to prevent damage ta the lungs caused
by high pressures and excessive shearing forces
Oscillation uses a high mean airway pressure to recruit the lung and prevent alveolar
collapse
ECMO
ECMO or extracorporeal membrane oxygenation is a treatment used for reversible
conditions where ventilation has become extremely difficult and the pressures required
to adequately oxygenate are damaging to the lungs
For respiratory disorders vein-vein ECMO is used, where both cannulas are inserted
into veins
It can also be used to support the heart either as a bridge to transplantation or if there is
a reversible cardiac failure; this requires vein-artery ECMO where both a vein and an
artery are cannulated
ECMO is a very specialist therapy and is only performed in ECMO centres
A cardiac surgeon inserts the cannulas for ECMO
9. CARDIBVASCULAR SYSTEM
9.3 The child with tachycardia
~achycardiais one of the most useful clinical signs. There are multiple causes, so having a
structured system is helpful. The following system is one of exclusion and is a useful
bedside exercise.
There are seven main groups of causes for tachycardia
Arrhythmia
Inadequate cardiac output
Preload
lnotropic
Afterload
Tamponade
Ventilation
Hypoxia
Hypercapnia
Anaemia
Blocked tube
Pneumothorax (usually tension)
Central
Pain
Fits
Fever
Anxiety
Pulmonary hypertension
Drugs
Poor ventricular function
The majority of these causes can be excluded on clinical signs or by simple measures such
as giving some pain relief. It is then possible to decide whether it is necessary to get a
cardiac opinion.
Treatment of SVT
ABC
Vagal stimulation
Diving reflex; iced water on the face or immerse the face in iced water for 5 seconds
Carotid body massage on one side only
Valsalva manoeuvre in the older child
Drug management
Intravenous adenosine must be given quickly and into a large vein followed by a saline
flush -the child must be ECG monitored.
Start with a bolus of 100 p@kg
If unsuccessful after 2 minutes increase the dose to 200 kglkg
If unsuccessful after a further 2 minutes increase to 300 pgkg
The maximum total dose is
300 pglkg if child is < 1 month of age
500 W k g if child is > 1 month - to a maximum of 12 mg single dose
Side-effects are short lived though unpleasant (flushing, nausea, chest tightness,
shortness of breath.) Some older children describe a feeling of impending doom
It is important to involve a paediatric cardiologist
They will consider cardioversion, especially if the child is shocked, or further drug
treatment with flecanide, amiodarone, digoxin or 6-blockers
Cardioversion
This should be performed under anaesthesia using a synchronized. DC shock
Initially use 1 ]/kg
Follow with 2 J/kg if unsuccessful
Followed with 2 J/kg if still unsuccessful
Hands-free defibrillation is a safe alternative to using the paddles
A 12-lead ECG is essential to adequately diagnose any change in rhythm.
9.8 Inotropes
An inotrope is used to improve the cardiac output
Cardiac Ouput = Heart Rate x Stroke Volume
In the healthy adult the heart has the ability to change its stroke volume dramatically,
this occurs during exercise and improves with training
Neonates, however, have a more fixed stroke volume so need to increase their heart rate
to improve the cardiac output
Once a neonate or child becomes too tachycardic the heart no longer has time to fill
and the cardiac output will reduce
When a child is in sinus rhythm the atrial kick can provide between 10 and 25% of the
cardiac output, if a child goes into atrioventricular block the blood pressure drops
There is no perfect inotrope as all inotropes have unwanted effects such as increasing
the metabolic demands of the heart
The best way to understand which inotrope to use when, is to understand which
adrenoreceptor of the sympathetic nervous system each inotrope works on
Stimulating pl -receptors increases both the heart rate and contractility. of the heart
Stimulating PI-receptors causes muscle relaxation in the smooth musculature of the
airways, causing bronchodilatation, and also relaxes the peripheral vessels, causing a
peripheral vasodilatation
Stimulating a-receptors causes a peripheral vasoconstriction,' increasing the peripheral
vascular resistance
Most inotropes stimulate increased production of the enzyme adenyl cyclase to promote an
increase in intracellular calcium, which results in increased contractility of the cardiac
muscle.
Adrenaline
Works on all the above receptors but its pl -receptor and a-receptor effects predominate
lncreases heart rate
lncreases cardiac contractility
lncreases blood pressure by increasing the peripheral vascular resistance
However,
It makes the heart stiff, i.e. the ventricle is unable to fully relax in diastole
It greatly increases the metabolic demands of the heart
These effects are also seen with other inotropes.
Etnergency Paediatrics
Stimulates mainly p l -receptors at lower doses but at higher doses it has increasing a-
receptor effects
lncreases heart rate
0 lncreases contractility
There is probably a low-dose renal effect
However, dopamine is more arrhythmogenic than other inotropes.
Dobutamine
Stimulates mainly p1- and P2-receptors at lower doses but at higher doses it has
increasing a-receptor effects
lncreases heart rate
lncreases contractility of the heart
Vasodilates at low doses and vasoconstricts at high doses
Can bronchodilate
Can be given peripherally
However, like dopamine, it is very arrhythmogenic.
Noradrenaline
Stimulates mainly a-receptors, although in large doses it has some preceptor effects
lncreases blood pressure by increasing the peripheral vascular resistance
Milrinone
Septic shock
Spinal shock
Bradycardia
Hypotension
Anaphylaxis
Allergy is an increasingly common problem and is immunologically mediated. It can
present as respiratory distress with either stridor or wheeze, or as cardiovascular collapse.
Treatment
Remove allergen
Assess ABC
Give high-flow oxygen
Adrenaline im 10 @kg = 0.01 mllkg of 1 in 1,000
If complete obstruction,
Obtain a definitive airway
--
,P
If partial obstruction
Give nebulized adrenaline 5 ml of 1 in 1,000
Give hydrocortisone 4 mglkg initial dose then 2-4 mg/kg 6-hourly
If wheeze present, give nebulized salbutamol,
Consider iv salbutamol 1-5 @kg per min
If shock present, give 20ml/kg fluid bolus, consider adrenaline infusion
Chlorpheniramine iv tds 250 @kg if < 1 year; > 1 year dose by age
10.1 Epidemiology
Burn injuries are very common but the majority are minor
7O0/0 occur in children < 5 years
Infants and children with learning difficulties are at increased risk
House fires account for most fatal burn injuries and the cause of death is usually smoke
inhalation
In England and Wales 23 children died in 2001 from burns
There is a strong link between burns and poverty
Late infection is a significant cause of morbidity in children with burns injuries
10.2 Pathophysiology
The severity of the burn depends on both the temperature and the time of contact with
the burn
Six hours contact at 44°C would be needed to cause cellular destruction, whereas at
54°C only 30 seconds contact is needed to cause injury. 30s at 54°C will cause cellular
Essential Revision Notes in Paediatries tbr the MRCPCH 2nd Ec-iition
10.3 Assessment
Signs of inadequate breathing include abnormal respiratory rate, abnormal chest
movement and cyanosis, which is a late sign
Reduced consciousness level may be the result of other injuries causing hypovolaemia,
or of a head injury or it may be secondary to hypoxia
Child protection issues should be considered
10.6 Treatment
High-flow oxygen
Early airway assessment
Ideally two intravenous cannulas should be placed in unburnt areas
Early and adequate analgesia is important
Burns of > 10% will need extra fluid in addition to their maintenance requirements. The
estimated fluid = OO/ burn x weight (kg) x 4 given over 24 hours. Half of this is given in
the first 8 hours from the burn injury. Urinary catheters are essential in severe burns to
assess adequate fluid resuscitation and urine output should be kept at 2 milkg per hour
There is a high risk of rapid heat loss following a burn injury so after initial exposure the
child should be re-covered and kept warm
1
E
a Circumferential burns may need surgical intervention (escharotomies)
Escharotomies are needed when the burn injury affects the whole of the dermis and
the skin loses its ability to expand as oedema progresses. The burned wound is
excised surgically down to the subcutaneous fat
a Carbon monoxide poisoning is discussed in Chapter 3 - Clinical Pharmacology and
Toxicology.
a lnhalation of carbon monoxide may occur when a child has been in a house fire
a Inhalation of carbon monoxide induces the production of carboxyhaemaglobin which
has a much higher affinity for oxygen than normal haemoglobin. Oxygen is therefore
not given up to the cells and cellular hypoxia occurs
The pulse oximeter may show a normal saturation
a The treatment is 100% oxygen or hyperbaric oxygen if very high levels are found
where M A P = mean arterial blood pressure in mmHg and ICP = intracranial pressure in
mmHg.
Emergency Paediatrics
Pressure sores
Risk of infection in ventricular drains
12.4 Imaging
Cervical spine injuries cannot be excluded by a normal X-ray or computerized
tomograph (CT), but must be cleared clinically as well
Regular CT scans of the head are used to monitor progress
Thoracolumbar spinal X-rays exclude a fracture (if the spine is fractured in one place
there is an increased risk of a second spinal fracture)
Secondary survey must be documented in the notes. This is a top-to-toe examination for
other injuries and is important as smaller non-threatening injuries can cause significant
morbidity
13.1 Pathophysiology
Convulsions increase the cerebral metabolic rate
Blood pressure and heart rate increase as a result of a surge in sympathetic activity
Cerebral arterial regulation is impaired and as the blood pressure increases, there is
increased cerebral blood flow, this is followed by a drop in blood pressure if fits are
prolonged and therefore a reduction in cerebral blood flow
There is an increase in lactate and subsequent cell death and oedema
The intracranial pressure rises
Calcium and sodium cellular metabolism is impaired
13.2 Treatment
ABC and treat hypoglycaemia
High-flow oxygen
Follow flow chart in Chapter 18 - Neurology (p 731)
i
i Emergency R3edic-trics
Thiopentone coma
This usually involves a thiopentone infusion sufficient to achieve burst suppression on the
EEG. The coma is continued for 1-3 days. Continuous cerebral function analysis monitoring
is needed
lntracranial pressure monitoring may be useful
Standard neuroprotective measures may be needed if raised intracranial pressure is
suspected
Complications include:
Status epilepticus may persist or fits may restart
Chest infection
Hypotension secondary to thiopentone
Renal impairment secondary to thiopentone infusion
Alternatives include high-dose midazolam or high-dose phenobarbitone
A paediatric neurologist must be consulted
Consider the differential diagnoses:
Meningoencephalitis
Pneumococcal meningitis
Poisoning
Metabolic disorder
Electrolyte imbalance
Trauma
Pyrexia and infection
Hypertension
Essential Revision Notes in Paeciiatrics tor the MRC'YCH 2nd Echtion
Non-accidental injury
Pertussis in a neonate
Apnoea in a neonate leading to hypoxia
Although a cause is often not found.
15. TRAUMA
15.1 Life-threatening extremity imjuries
Crush injuries of the abdomen and pelvis
Traumatic amputation of an extremity; partial amputation is often more life-threatening
than complete amputation
Massive open long-bone fractures
Crush injuries
Splinting of the pelvis required
Embolization of bleeding vessels may be useful
Trauma to the internal organs is more likely in children than adults following crush
injuries
Compression over femoral or brachial artery may help but use of a tourniquet is now
contraindicated
Elevation of the limb
Advice from a specialist centre
Long-bone fracture
Splinting
Consider vascular injury and compartment syndrome
Consider tetanus immunization status
Essential Revision Notes in PaediC7tricstor the hl RCPCH 2nd Edifion -
15.2 Gunshot wounds and stabbing
These are both rare in children but the following tips are useful aid memoires.
a Bullets usually follow the path of least resistance so do not assume the trajectory of the
bullet is in a direct line from the entrance to the exit wound
The entrance wound is often round or oval with a blackened area of burn
The exit wound is often ragged because of tearing of tissues
In both stabbing and gunshot wounds it is important to define which structures are likely
to have been penetrated
16, DROWNING
450,000 people die per year world-wide as a result of drowning
Drowning can occur in even small amounts of water, e.g. a few inches of rainwater in a
bucket
World-wide, for children < 15 years of age, drowning is the commonest cause of
accidental death
The majority of drowning are preventable
Bradycardia and dsyrhythmias are common at this stage as a result of the severe hypoxia
Hypoxia is usually the cause of death
161 Pathophysiology
1
Laryngospasm subsides and fluid is aspirated into the lungs
1
Alveolitis and pulmonary oedema
Pathophysiology of drowning
226
P
f
4=-!
B
g Emergency Paediatrics
16.2 Treatment
ABC
Consider:
Hypothermia
Hypovolaemia
Spinal injury
Electrolyte imbalance
Other injuries
Child protection issues
Contaminated water can lead to infection with unusual organisms
Hypothermia can lead to disorders of coagulation and dysrhythmias and increased risk of
infection.
Remove from the water in a horizontal position to prevent venous pooling and
distributive hypovolaemia
Immobilize the spine
Early and effective basic life support has been shown to improve outcome
Secure an airway early and decompress the stomach with a nasogastric tube
If core temperature is < 30°C prevent further cooling and re-warm
Continue resuscitation until core temperature is > 35°C
Below 30°C ventricular fibrillation may be refractory. Repeated shocks and inotropes
should be delayed until the temperature is above this level, even in circulatory failure
Core re-warming
Only use warm fluids (warm to 39°C)
Warm ventilator gases (42°C)
Warm peritoneal dialysis fluids at 42°C
Gastric or bladder lavage with normal saline
Pleural or pericardial lavage
Extracorporeal blood warming
Respiratory compromise may occur several hours after the drowning episode
Endocrinology
1
I
Heather Mitchell and Vasanta Nanduri
CONTENTS
1. Hormone physiology
1.1 Introduction
1.2 Hormone-receptor interactions
1.3 Regulation
1.4 lnvestigation of hormonal problems
3. Growth
3.1 Physiology of normal growth
3.2 Assessment and investigation
3.3 Growth disorders
3.4 Genetics of growth
7. Glucose homeostasis
7.1 Physiology
7.2 Diabetes mellitus
7.3 Hypoglycaemia
8. Bone metabolism
8.1 Physiology of calcium and phosphate homeostasis
8.2 Disorders of calcium and phosphate metabolism
8.3 Investigation of bone abnormalities
I Plasma transport
I
Most hormones are secreted into the systemic circulation, but those secreted from the
hypothalamus are released into the pituitary portal system.
Many hormones are bound to proteins when in the circulation. These binding proteins
buffer against very rapid changes and act as a reservoir for the hormones - only free
hormones can exert their biological action on tissues.
!
1.2 Hormone-receptor interactions
Types of hormone
There are three main types of hormones:
Amine - catecholamines, serotonin (5-hydroxytryptamine)
Steroid - cortisol, aldosterone, androgens, oestrogen, progesterone
Peptide - growth hormone (GH), insulin, thyroxine
Revision Notes in &ediatrics for the AjRCPCIH 2nd Edition
EssentiC~l
Amine and peptide hormones have short half-lives (measured in minutes) and act on cell-
surface receptors. Their secretion may be pulsatile and they often act via a second
messenger (e.g. cyclic adenosine monophosphate (CAMP), calcium, etc.). Steroid hormones
have longer half-lives (measured in hours) and act on intracellular receptors. They act on
DNA to alter gene transcription and protein synthesis. Thyroxine is the exception to this rule
as it acts as a steroid hormone and binds to intracellular receptors.
Intracellular messengers
CAMP,e.g. glucagon, adrenocorticotrophic hormone (ACTH), luteinizing hormone (LH),
follicle-stimulating hormone (FSH)
Intracellular calcium, e.g. thyrotropin-releasing hormone (TRH), vasopressin,
angiotensin II
Tyrosine kinase, e.g. GH
G-protein receptors
Hormone receptors linked to cAMP do not generate cAMP directly, but act via a G-protein
receptor on the cell surface. The G-proteins may be inhibitory - Gi (e.g. somatostatin) or
stimulatory - G , (e.g. all other hormones) to the formation of adenylate cyclase. Hormones
that use intracellular calcium as an internal messenger activate the cytoplasmic enzyme
phospholipase C (PLC), which then releases inositol triphosphate from membrane phospho-
lipids, which in turn releases calcium from stores in the endoplasmic reticulum.
Second messengers
Insulin-like growth factor-1 (IGF-1) and IGF-2 are GH-dependent peptide factors. They are
believed to modulate many of the anabolic and mitogenic actions of GH. IGF-1 is important
as a post-natal growth factor, whereas IGF-2 is thought to be essential-for fetal growth.
Disorders of hormone-~eceptqr:
+
=- in^^ -
* Syndromes of G-protein abn
Laron syndro
Nephrogenic
~ n d r o ~insensitivity
in syndro
Vitamin D-dependent rickets
1.3 Regulation
The effect and measured amount of a particular hormone in the circulation at any one time
is the result of a complex series of interactions.
Endocrinology
Patterns of secretion
Continuous - e.g. thyroxine
Intermittent:
Pulsatile - FSH, LH, CH, prolactin
Circadian - e.g. cortisol
Stress-related - e.g. ACTH
Sleep-related - e.g. GH, prolactin
2.1 Anatomy
Hypothalamus
The hypothalamus extends from the pre-optic area (anteriorly) to the mamillary bodies
(posteriorly) and includes the third ventricle. The hypothalamus has reciprocal connections
with the frontal cortex and thalamus, and interacts with the limbic system and the brainstem
nuclei involved in autonomic regulation, where it differentiates into discrete nuclei. The
axonal processes extend down into the median eminence where regulatory hormones are
secreted into the portal circulation.
Pituitary gland
Situated inferior to the hypothalamus within the pituitary fossa, above the sphenoid sinus,
medial to the cavernous sinuses which contain the internal carotid arteries and cranial
nerves Ill, IV and V. It is the combined product of an outgrowth of ectoderm from the buccal
mucosa and the down-growth of neural tissue referred to as the 'infundibulum'.
The anatomical relationships of the anterior and posterior pituitary glands are important as
tumours may arise from and/or compress surrounding structures.
Above - optic chiasm, pituitary stalk, hypothalamus
Below - sphenoid sinus, nasopharynx
Lateral - cavernous sinus, internal carotid arteries, cranial nerves'lll, IV, V, VI
Anterior lobe - derived from an invagination of oral mucosa (R'athke pouch)
Posterior lobe - derived from neuronal tissue and contains neurones from the
hypothalamus
Homeobox genes govern the embryonic development and gene expression. PITI is a
homeobox gene that is necessary for the embryonic development of GH, prolactin and
thyrotropin-producing cells.
Regulation
GnRH is released in a pulsatile fashion, which stimulates the synthesis and secretion of LH
and FSH. Expression and excretion of FSH are also inhibited by inhibin, a gonadal
glycoprotein. This has no effect on LH. In the neonate there are high levels of gonado-
trophins and gonadal steroids. These decline progressively until a nocturnal increase occurs
leading up to the onset of puberty (amplification of low-amplitude pulses).
Function
CH has direct effects on carbohydrate and lipid metabolism. The growth-promoting effects
of GH are mediated by somatomedin C (otherwise known as IGF-I), which is produced in
the liver cells following GH binding to cell-surface receptors which results in gene
transcription. IGF-1 and IGF-2 are 70-amino acid peptides, structurally related to insulin.
IGF-I increases the synthesis of protein, RNA and DNA, increases.the incorporation of
protein into muscle, and promotes lipogenesis. The lGFs are bound to a family of binding
proteins (ICFBP-1 to -6) of which IGFBP-3 predominates. These binding proteins not only
act as transporters for the IGFs, but also increase their half-life and modulate their actions
on peripheral tissues.
Regulation
CH secretion is pulsatile, consisting of peaks and troughs. Nocturnal release occurs during
non-dreaming or slow-wave sleep, shortly after the onset of deep sleep. There is a gradual
increase in CH production during childhood, a further increase (with increased amplitude
of peaks) during puberty secondary to the effect of sex steroid, followed by a post-pubertal
fall.
Three peptides are critical to the control of GH secretion:
Growth hormone releasing hormone (CHRH)
Growth hormone releasing peptide (GHRP) - ghrelin
Somatostatin
These peptides mediate stimulation, inhibition and feedback suppression of GH secretion
and form the final common pathway for a network of factors that influence the secretion of
GH, which include sex steroids, environmental inputs and genetic determinants.
Essential Revision Notes in Paedic?tric-sh r thP MKCPCCH2nd Edition -
GHRH and somatostatin act via the activation of G-protein receptors on the somatotrophs,
increasing or reducing CAMPand intracellular Ca2+. GHRH stimulates GH release, whereas
somatostatin inhibits both GH synthesis and its release. GH and IGF-1 exert a tight feedback
control on somatostatin, and probably also on GHRH. GHRP - ghrelin - is an oligopep-
tide derivative of enkephalin and is a 28-peptide residue predominantly produced by the
stomach. It requires fatty acylation of the N-terminal serine for biological activity and is
released in response to acute and chronic changes in nutritional state. The concentrations
of ghrelin fall post-prandially and in obesity and rise during fasting, after weight loss or
gastrectomy and in anorexia nervosa. Both GHRP and GHRH act synergistically in the
presence of a functioning hypothalamo-pituitary axis.
Prolactin
Structure
Prolactin has a similar amino acid sequence to GH, and acts via the lactogenic receptor,
which is from the same superfamily of transmembrane receptors as the GH receptor.
Function
Prolactin is responsible for the induction of lactation and the cessation of menses during the
puerperium. During the neonatal period, prolactin levels are high secondary to fetoplacental
oestrogen; they then fall and remain consistent during childhood but there is a slight rise at
puberty.
Regulation
Dopamine inhibition from the hypothalamus.
Thyroid-stimulatinghormone (TSH)
Structure
TSH is a giycoprotein containing the same a-subunit as LH and FSH but a specific
f3-subunit.
Function
TSH is a trophic hormone and hence its removal reduces thyroid function to basal levels. It
binds to surface receptors on the thyroid follicular cell and works via activation of adenylate
cyclase to cause the production and release of thyroid hormone.
Regulation
TSH synthesis and release is modulated by TRH, which is produced in the hypothalamus
and secreted into the hypophyseal portal veins, from where it is transported to the anterior
pituitary gland. TRH secretion is influenced by environmental temperature, somatostatin
and dopamine. Glucocorticoids inhibit TSH release at a hypothalamic level.
Endocrinology
unction
ACTH is responsible for stimulation of the adrenal cortex and in particular the production of
cortisol. Hypothalamic control of its function is evident in the late-gestation fetus. ACTH
plays a role in fetal adrenal growth.
~egulation
Corticotropin-releasing hormone stimulates ACTH release via increasing CAMP levels.
Arginine vasopressin (AVP) also stimulates ACTH release and potentiates the response to
corticotropin-releasing hormone.
Output
This is controlled by:
Hypothalamic osmoreceptors and neighbouring neurones that secrete AVP
Concentrating effect of the kidney
Input
This is controlled by:
Hypothalamic thirst centre
Regulation
This is largely by the osmolality of extracellular fluid and haemodynamic factors. The
release of AVP is modulated by stirnulatory and inhibitory neural input. Noradrenaline
(norepinephrine) inhibits AVP release and cholinergic neurones facilitate it.
Essential Revision Notes in P a ~ r J i ~ ~ t rhi crsthe MRCPCM 217d Edition
Physiology
The normal mature kidney is able to produce urine in a concentration range of 60
1100 mosmollkg. The ability to vary urine concentration depends on the spatial arrang
ments and permeability characteristics of the segments of the renal tubules.
AVP regulates the permeability of the luminal membrane of the collecting ducts. Lo
permeability in the presence of a low AVP concentration leads to dilute urine.
Acquired
Excess, e.g. intracranial tumours:
lntracranial tumours
Gushing's disease - pituitary adenoma
Deficiency, e.g. secondary to treatment with radiation or surgery:
Pituitary damage
Tumours
Surgery
Radiotherapy
Trauma
Craniopharyngioma
This i s one of the most common supratentorial tumours in children. It commonly presents
with headaches and visual field defects. On imaging, the tumour is frequently large and
238
cystic. Treatment is by resection plus radiotherapy if initial resection is incomplete or
recurrence occurs.
post-operative hormonal deficiencies are common, involving both anterior and posterior
pituitary hormones. Treatment is by hormonal supplementation. There is also the risk of
hypothalamic damage. Remember: the hypothalamus is responsible for other effects that are
not so easily treated by replacement therapy, e.g. temperature, appetite and thirst control.
The obesity associated with hypothalamic damage (secondary to hyperphagia) is very
difficult to manage and has a poor prognosis. The maintenance of fluid homeostasis in
children with the combination of diabetes insipidus and adipsia (loss of thirst sensation) can
be a challenge.
Posterior pituitary
Diabetes insipidus
Defined as insufficient AVP causing a syndrome of polyuria and polydipsia. With an intact
thirst mechanism copious water drinking maintains normal osmolalities. -However, problems
with the thirst mechanism or insufficient water intake lead to hypernatraemic dehydration.
It is important to remember that cortisol is required for water excretion. Therefore, in
children with combined anterior and posterior pituitary dysfunction, there is a risk of
dilutional hyponatraemia if they are cortisol-deficient and receiving DDAVP (1 -deamino-8-
~ a r g i n i n evasopressin) treatment. Hence the emergency management of the unwell child is
to increase their hydrocortisone treatment and to stop their DDAVP.
Essentia 1 Re v i s i ~ nNotes in Paedia trjcs f i r the M RCPCH 1 7 d Edit ion
a
ausesof SIADH
* Central nervous system disorders - meningitis, abscess; trauma; hypoxic-ischaemi
insult
-
Respiratory tract disease pneumonia; cavitation
-
Reduced left atrial filling drugs
Malignancies - lymphoma; bronchogenic carcinoma; idiopathic
zi
Management of SlAOH
Management focuses on treatment of the underlying cause and management of the fluid
and electrolyte imbalance. Accurate input and output charts are required as are twice-daily
weights in the initial period of assessment. Fluid restriction is the mainstay of management.
CH tests
Provocation tests of CH are potentially hazardous. Insulin tolerance tests should only be
performed in specialist centres because of the risk of severe hypoglycaemia. Other CH
provocation tests include the use of glucagon, arginine and clonidine. Physiological tests of
GH secretion include a 24-h GH profile and measurement of GH after exercise or during
sleep.
GH treatment
The following are the licensed indications for treatment with GH.
These recommendations have been endorsed by the National Institute for Clinical Excel-
lence (NICE).
Documented GH deficiency - congenital or acquired
Turner syndrome
Chronic renal failure
Prader-Willi syndrome
Small for gestational age
GH deficiency should be treated by a specialist who has experierlce of managing children
with growth disorders. Most regimens involve daily injections with different doses of GH
depending upon the indications. Close local/community liaison is required for this.
Panhypopituitarism
Panhypopituitarism is much less common than isolated hormone deficiency and may
develop as an evolving endocrinopathy. Management includes replacement with GH,
thyroxine, cortisol during childhood with induction and maintenance of puberty with the
appropriate sex hormone (testosterone or estradiol). Parents of children who are cortisol- or
ACTH-deficient should be given written instructions and training in the management of an
acute illness and must have emergency supplies of intramuscular hydrocortisone available
at all times.
Postnatal growth
There are three principal phases of growth - infancy, childhood and puberty
GHRH Somatostatin
'Pituitary
GH
Auxology
When measuring height, the optimal method is for the child to be measured by the same
trained measurer, on the same equipment and at the same time of day on each occasion to
minimize measurement error. A stadiometer should be used; supine height should be
measured at < 2 years of age and standing height at > 2 years.
A child's height may be compared to the population using centile charts, and also consid-
ered in terms of hislher genetic potential by comparison with the mid-parental height.
244
a
-
s Endocrinology
Mid-parental height
Add 12.6 cm to mother's height to plot on a boy's chart
a Subtract 12.6 cm if plotting a father's height on a girl's chart
a Mid-parental height is half-way between the plotted corrected parental heights
The measurement of skin-fold thicknesses (e-g. triceps, subscapular) gives important infor-
mation about body fat distribution, which changes at different ages. For example, in puberty
there is an increase in truncal fat but a reduction in limb fat. Mid arm circumference can be
used to assess muscle bulk.
To estimate the rate at which a child is growing it is necessary to measure the height on two
separate occasions (at least 4-6 months apart) and divide the change in height by the
period of time elapsed. This is the height velocity and is expressed in cmlyear. The height
velocity can be plotted on standard reference charts.
Chronic illness:
-
Congenital heart disease
isease
mes:
Turner syndrome
Down syndrome
Low birth weight, e.g. Russell-Silver syndrome
Prader-Willi syndrome
for the MKC-PCCH2nd Eclition
Esscnti,?/Revision Notes it7 P~ecli,~trics
Skeletal dysplasia:
Achondroplasia
Hypochondroplasia
Mucopolysaccharidoses
Spondyloepiphyseal dysplasia
Psychosocial/emotional deprivation
As a general rule, if a child has a normal growth rate then the cause of the short stature is in
the past history, whereas a child with a low growth rate requires thought as to what current
process(es) are causing the growth failure.
CH insufficiency
GH insufficiency (CHI) can be congenital or acquired.
Congenital GHI can be inherited as an 'autosomal recessive trait which is very rare.
More commonly it is the result of a structural abnormality of the hypothalamo-pituitary
axis and may be isolated or associated with other midline developmental defects such
as absent corpus callosum and septo-optic dysplasia. It may be an isolated phenomenon
or associated with other anterior or posterior pituitary hormone deficiencies.
Acquired GHI is associated with tumours or trauma in the hypothalamo-pituitary
region. Surgery or radiotherapy to lesions in this region may also result in CHI.
Deficiency can also occur as a genetic condition.
Very rarely there may be high levels of GH associated with a clinical picture of severe
GHI. This is the result of end-organ resistance (receptor abnormalities) resulting in low
levels of IGF-1. This is know as Laron syndrome and is inherited as an autosomal
recessive condition.
. Short limbs
Prominent forehead
Thoracolumbar kyphosis
Midfacial hypoplasia
Disproportionate short stature
Radiology:
Diminishing interpeduncular distances between L1 and L5
Complications:
Short stature
Dental malocclusion
Hydrocephalus
Repeated otitis media
Hypochondroplasia
Definition:
Rhizomelic short stature distinct from achondroplasia
Inheritance:
Probable allelic autosomal dominant disorder
Clinical features:
Affected persons appear stocky or muscular
Usually recognized from 2 to 3 years of age
Wide variability in severity
Radiology:
No change in interpeduncular distances between L1 and L5
Complications:
Short stature
Mucopolysaccharidoses (MPS)
Inheritance:
Autosomal recessive, X-linked recessive
Clinical features - depend on type of MPS:
Short spine and limbs
Coarse facial features
Reduced intelligence and abnormal behaviour in some forms
Hurler syndrome - shortened lifespan
Marked skeletal abnormalities and severe short stature in Morquio syndrome
Russell-Silver syndrome
Inheritance:
Sporadic
Definition:
Syndrome of short stature of prenatal onset
Occurrence i s sporadic and aetiology is unknown
Clinical features:
Short stature of prenatal onset
Limb asymmetry
Shortincurvedfifthfinger
Small triangular face
Caf6-au-lait spots
Normal intelligence
Bluish sclerae in early infancy
Turner's syndrome
Definition:
A syndrome with a 4 5 x 0 (or XO/XX or rarely XO/XY) karyotype associated with
short stature, ovarian dysgenesis and dysmorphic features
Inheritance:
Sporadic
Clinical features:
Neonatal - lymphoedema of hands and feet
Skeletal - short stature (mean adult height is 142 cm); widely spaced nipples,
shield-shaped chest; wide carrying angle; short fourth metacarpal; hyperconvex nails
Facial - prominent, backward-rotated ears; squint, ptosis; high arched palate; low
posterior hairline, webbed neck
Neurological - specific space-form perception defect
Endocrine - autoimmune diseases (hypothyroidism); type 2 diabetes; infertility and
pubertal failure
Associations - horse-shoe kidneys; coarctation of the aorta; excessive pigmented
naevi
Turner syndrome needs to be excluded in all girls whose height is below that expected for
the mid-parental centile as not all girls with Turner syndrome show the classical phenotype.
Tall stature
Constitutional obesity
Remember: if a child is tall and fat it is most probably the result of constitutional obesity.
These children often have a slightly advanced bone age and go into puberty relatively early
(not precocious) and thus end up appropriate (or slightly tall) for parents' heights.
Klinefelter syndrome
Definition:
Karyotype 47XXY
Inheritance:
Sporadic
Clinical features:
Tall and slim
Cryptorchidism
Gynaecomastia
Mental retardation
Azoospermia and infertility
Immature behaviour
Hypothalamus
GnRH
I
Pituitary
/ \
Testosterone Oestrogen
*
Sex steroids
Testosterone is produced by the Leydig cells of the testes. It is present in the circulation
bound to sex-hormone-binding globulin (SHBG). Free testosterone is the active moiety at
the level of target cells. Testosterone is then either converted to dihydrotestosterone by 5a-
reductase or to oestrogen by aromatase. Both dihydrotestosterone and testosterone attach to
nuclear receptors, which then bind to steroid-responsive regions of genomic DNA to
influence transcription and translation.
Oestrogen is produced by the follicle cells of the ovary. The main active form of oestrogen
is oestradiol. This circulates bound to SHBG and causes growth of the breasts and uterus,
the female distribution of adipose tissue and increases bone mineralization.
lnhibin
lnhibin is a glycoprotein produced by Sertoli cells in males and granulosa cells in females.
SHBG
Androgens reduce SHBG formation, and oestrogens stimulate its formation. Therefore
increased free testosterone levels magnify androgen effects.
Hormonal regulation
In the presence of CnRH the gonadotrophins are controlled by the sex steroids and inhibin.
LH and FSH levels are under the influence of negative feedback mechanisms in both the
hypothalamus and pituitary. lnhibin inhibits only FSH and acts at the level of the pituitary.
Positive feedback also occurs during mid-puberty in females. Increased oestrogen primes
gonadotrophins to produce LH until, at a critical stage at the middle of the menstrual cycle,
a large surge occurs causing ovulation.
Tanner stages
Male genitalia development
Stage 1 Pre-adolescent
Stage 2 Enlargement of scrotum and testes and changes in scrota1 skin
Stage 3 Further growth of testes and scrotum; enlargement of penis
Stage 4 Increase in breadth of penis and development of glans; further growth of scrotum and
testes
Stage 5 Adult genitalia in shape and size
Stage 3 Further enlargement and elevation of breast and papilla with no separation of their
contours
Stage 4 Projection of areola and papilla to form a secondary mound above the level of the
breast
Stage 5 Mature stage with projection of papilla only
Pubic hair
Stage 1 Pre-adolescent
Stage 2 Sparse growth of long, slightly pigmented, downy hair
Stage 3 Hair spread over junction of the pubes, darker and coarser
Stage 4 Adult-type hair, but area covered is smaller
Stage 5 Adult in quantity and type
Axillary hair
Stage 1 No axillary hair
Stage 2 Scanty growth
Stage 3 Adult in quantity and type
Puberty starts on average at age 12 yean in boys and 10 years in girls. As nutrition and
health improve, the age of onset of puberty is becoming earlier with each generation.
In the male, acceleration in growth of the testes (from a prepubertal 2-ml volume) and
scrotum are the first sign of puberty. This is followed by reddening and rugosity of scrota1
skin, later by development of pubic hair, penile growth and axillary hair growth.
A 4-ml testicular volume signifies the start of pubertal change. Peak height velocity occurs
with testicular volumes of 10-1 2 ml.
In the female, the appearance of the breast bud and breast development are the first signs of
puberty and occur as the result of production of oestrogen from the ovaries. These are
followed by the development of pubic and axillary hair, which is controlled by the adrenal
gland. Peak height velocity coincides with breast stage 2-3. Menarche occurs late at breast
stage 4, by which stage growth is slowing down. Most girls have attained menarche by age
13 years.
Body composition
Prepubertal boys and girls have equal lean body mass, skeletal mass and body fat. The
earliest change in puberty is an increase in lean body mass.
Growth spurt
The pubertal growth spurt is the most rapid phase of growth after the neonatal period. This
is an early event in girls and occurs approximately 2 years earlier than in boys, i.e. at a
mean age of 12 years. The mean height difference between males and females of 12.5 cm is
the result of the taller male stature at the time of the pubertal growth spurt and increased
height gained during the pubertal growth spurt.
Esseliti,71 Revision Notes in Paecliatric-s tor the MRC-PCH 211~1
Eclitio~i
Adrenarche
Adrenal androgens, dehydroepiandrosterone sulphate (DHEAS) and androstenedione rise
approximately 2 years before gonadotrophins and sex steroids rise. Adrenarche begins at 6-
8 years of age and continues until late puberty. Control of this is unknown. Adrenarche does
not influence onset of puberty.
Gynaecomastia
Gynaecomastia is physiological and occurs in 75% of boys to some degree (usually during
the first stages of puberty), but most regress within 2 years. Management is by reassurance,
support and weight loss if obesity is a factor.
Causes of gynaecomastia
Normal puberty (common)
Obesity (common)
KIinefelter syndrome
Partial androgen insensitivity
Precocious puberty
Definition
Central precocious puberty is consonant with puberty (i.e. occurs in the usual physiological
pattern of development but at an earlier age). It is the result of premature activation of the
GnRH pulse generator. In girls, often no underlying cause is found; however, it is almost
always pathological in males.
Premature thelarche
Usually in girls aged between 1 and 3 years
Isolated breast development (never more than stage 3)
No other signs of puberty
Normal growth velocity for age
Normal bone age
Prepubertal gonadotrophin levels
Progress to puberty at normal age
Delayed puberty
Definition
No signs of puberty at an age when pubertal change would have been expected.
CI-ics
Essential Rcvis-inn hlc~tcsin RIC~C/~,I fix fl7c h 1RC'PC'l-I 1 1 c / Ecljfion
Treatment
ConstitutionsI delay
Reassurance
Androgens - oxandrolone orally daily or depot testosterone injection monthly
Reassess at 4-6 months
Other causes of delayed puberty
Treat underlying cause
Induce and maintain puberty with testosterone in boys, ethinyloestradiol in girls
4.4 intersex disorders (ambiguous genitalia)
Classification
a Virilizedfemale
a Inadequately virilized male
a True hermaphrodite
Useful investigations
Karyotype
Urine steroid profile
Pelvic ultrasound
17-OH progesterone (day 3)
LHIFSH testosteroneldihydrotestosterone
Human chorionic gonadotrophin test
Management
This requires multidisciplinary assessment and management involving endocrinology, pae-
diatric urology, gynaecology and psychology input.
4.5 Amenorrhoea
Amenorrhoea may be either primary or secondary. Patients with primary amenorrhoea have
never menstruated, whereas those with secondary amenorrhoea have lost previously
existing menstrual function.
Essential Revision Notes in Paediatrics for the MRCPCH 2nd Edition
Causes of amennorhoea
Ovarian
Gonadal dysfunction
Secondary to irradiation/chemotherapy/surgery
Polycystic ovarian syndrome
Genital tract
Mullerian dysgenesis
Hypothalamopituitary
Hypogonadotophic hypogonadism
Secondary to tumours/irradiatiorl/chemotherapy/surgery
Functional
Weight loss
Exercise-induced
Chronicillness
Psychogenic
Management of amenorrhoea
Management of amenorrhoea depends on the underlying cause. Structural abnormalities
may need surgical correction. Primary amenorrhoea may require pubertal induction with
exogenous oestrogen. In secondary amenorrhoea the underlying cause needs to be
identified and addressed.
5.2 Physiology
Cortex
The adrenal cortex has three principal functions:
Glucocorticoid production (cortisol)
Mineralocorticoid production (aldosterone)
Androgen production (testosterone, androstenedione)
Mineralocorticoid Glucocorticoid Androgen
pathway pathway pathway
(renin angiotensin) (CRH ACTH) (ACTH)
Cholesterol -
(11
Pregnenolone - (2)
17-OH Pregnenolone - (3)
DHEA-S
Glucocorticoids
Cortisol is the principal glucocorticoid.
It plays a vital role in the body's stress response
It is an insulin counter-regulatory hormone increasing gluconeogenesis, hepatic
glycogenolysis, ketogenesis
It is necessary for the action of other hormones, e.g. noradrenaline (norepinephrine),
adrenaline (epinephrine), gl ucagon
It influences other organ physiology:
Normal blood vessel function
Cardiac and skeletal muscle
Nervous system
Inhibition of the inflammatory response of tissues to injury
Secretion of a water load
Cortisol secretion is under pituitary control from ACTH. ACTH has a circadian rhythm,
being at its lowest at midnight and rising in the early morning. There is also a negative
far the ILIRCPCH 2nd Eclition
Essential Revision Notes in P~~edi~~tsics
-
feedback loop from cortisol. ACTH acts via CAMPand causes a flux of cholesterol through
the steroidogenic pathway.
Mineralocorticoids
Aldosterone has the main mineralocorticoid action:
It increases sodium reabsorption from urine, sweat, saliva and gastric juices in exchange
for potassium and hydrogen
The secretion of aldosterone is primarily regulated by the renin-angiotensin system, which
is responsive to electrolyte balance and plasma volumes. Hyponatraemia and hyperkalae-
mia can also have a direct aldosterone stimulatory effect. ACTH can produce a temporary
rise in aldosterone but this is not sustained.
Renin
Renin is a glycoprotein synthesized in the juxtaglomerular apparatus, and stored as an
inactive pro-enzyme in cells of the macula densa of the distal convoluted tubule. Its release
is stimulated by reduced renal perfusion, hyperkalaemia and hyponatraemia.
Renin hydrolyses angiotensin to form angiotensin I (an a2-globulin synthesized in the liver).
This is converted to angiotensin II by angiotensin-converting enzyme, which is present in
high concentrations in the lung, but is also widely distributed in the vasculature for local
angiotensin II release.
Adrenal androgens
These include testosterone, androstenedione and DHEAS. Secretion varies with age and,
although responsive to ACTH, do not always parallel the cortisol response.'
Addison3 disease
Definition:
Adrenal hypofunction
Aetiology:
Autoimmune
Secondary to tuberculosis
Associated with adrenal leukodystrophy
Presentation:
Often with non-specific symptoms of tiredness and abdominal pain
May present with collapse related to a salt-losing crisis
Deficiency of one of the enzymes in the biosynthetic pathway of the adrenal cortex. The
classical type is deficiency of the enzyme 21-hydroxylase
Other enzyme deficiencies result in non-classical CAH. These enzymes are listed in the
figure on page 259 (Pathways of adrenal hormone synthesis)
Genetics
Two genes encoding 21-hydroxylase expression have been localized to the short arm of
chromosome 6, namely CYP21B and CYP2 7A. Deletion of CYP2 7B is associated with
severe salt wasting and HLA B47, DR7 haplotype
Pathophysiology
In classical CAH, there is a block in the production of cortisol and aldosterone with a
build up of the 17-hydroxyprogesterone, the precursor before the block. The continuing
Endocrinology
ACTH drive leads to the precursors being directed along the androgen biosynthetic
pathway causing virilization
Presentation
a Ambiguous genitalia (in girls with 21-hydroxylase deficiency, and occasionally in boys
with 3 p-hydroxysteroid dehydrogenase deficiency)
a Salt-losing crisis and hypotension
a Hypertension may occur in 1 1P-hydroxylase deficiency
a Precocious puberty (in boys)
a Virilization
Investigation
Karyotype
1 7-hydroxyprogesterone
Urine steroid profile (metabolite pattern will help in diagnosing specific enzyme block)
Adrenal androgen levels
a Bone age in older children
Treatment
Hydrocortisone and fludrocortisone replace the deficient steroids and also suppress the
ACTH drive to the adrenal androgens. Growth is a good method of monitoring replacement
therapy. Children who grow excessively fast with increased height velocity are either getting
inadequate doses or may be non-compliant. Levels of 17-hydroxyprogesterone are also
useful for monitoring treatment.
It is important to teach parents to recognize signs of illness and to be able to administer
emergency hydrocortisone
Additional sodium chloride replacement is also required duringthe first year of life and
electrolytes may need to be monitored over this period .
Surgery may be required in females with virilization
Side-effects of glucocorticoid treatment .
When glucocorticoids are used in non-physiological doses, such as in asthma, chronic renal
failure or rheumatological and immunological conditions, the following side-effects may be
seen.
Gastritis
Osteoporosis
Raised blood glucose/altered glucose tolerance
lncreased appetite and weight gain
lncreased susceptibility to infection
Poor healing
Menstrual irregularities
Unpredictable mood changes
Sleep disturbances
lncreased risk of glaucoma and cataracts
Essential Revision Notes in hedi,?tricstbr the MRCPCH 2nd Edition -
6. THE THYROID GLAND
6.11 Anatomy
The thyroid gland is formed from a midline outpouching of ectoderm of the primitive buccal
cavity which then migrates caudally. It consists of follicles made of colloid surrounded by
follicular cells and basement membrane. Thyroid hormone is synthesized at a cellular level
and stored in thyroglobulin, a glycoprotein that is the main constituent of the colloid.
Between the follicular cells are the parafollicular cells (C cells) which are of neurogenic
origin and secrete calcitonin.
6.2 Physiology
The function of the thyroid gland is to concentrate iodine from the blood and return it to
peripheral tissues in the form of thyroid hormones (thyroxine; tetra-iodothyronine, (T4)and
tri-iodothyronine (T3)). In blood, the hormones are linked with carrier proteins, e.g.
thyroxine-binding globulin and pre-albumin. T4 is metabolized in the periphery into T3
(more potent) and reverse T3 (less potent).
Hormonogenesis
Steps include
Iodide trapping by the thyroid gland
Synthesis of thyroglobulin
Organification of trapped iodine as iodotyrosines (mono-iodotyrosine (MIT) and di-
iodotyrosine (DIT))
Coupling of iodotyrosines to form iodothyronines and storage in the follicular colloid
Endocytosis of colloid droplets and hydrolysis of thyroglobuliri to release T3, T4, MIT and
DIT
Deiodination of MIT and DIT with intrathyroid recycling of the iodine
Thyroid hormone acts by penetrating the cell membrane and then binding to a specific
nuclear receptor. It modulates gene transcription and mRNA synthesis. This leads to
increased mitochondria1activity.
Regulation
Thyroid hormone release is regulated by TSH and by iodine levels. TSH has both immediate
and delayed actions on thyroid hormone secretion.
Immediate actions:
x- .. Stimulates binding of iodide to protein
Stimulates thyroid hormone release
Stimulates pathways of intermediate metabolism
..
Delayed action (several hours):
Stimulates trapping of iodide
Stimulates synthesis of thyroglobulin
physiological variations in iodide modulate trapping by the thyroid membrane.
~odideinhibits the stimulation of CAMP by TSH and pharmacological doses block organifi-
cation.
of hypothyroidism
Congenital piQitary-abnormalities
Receptor resistance
Hyperthyroidism
Causes of hyperthyroidism
Autoimmune thyroiditis, e.g. Graves' disease
Diffuse toxic goitre
Nodular toxic goitre
TSH-induced
FaGtitious
Graves' disease
This is a multisystem, autoimmune disorder involving the eyes, hyperthyroidism and a
dermopathy. There is an increased incidence in adolescence and it is six to eight times more
common in girls than in boys. Thyroid-stimulating immunoglobulin may be demonstrated.
Neonatal thyrotoxicosis
This is a rare condition caused by the transplacental passage of thyroid-stimulating anti-
bodies from mothers with either Graves' disease (active or- inactive) or Hashimoto's
thyroiditis. The neonate usually presents with a rapidly developing tachycardia, dysrhyth-
mia, hypertension and weight loss. A goitre may be present. There may also be associated
jaundice and thrombocytopenia. The condiiion is usually self-limiting in 4-12 weeks but
severely affected neonates will require treatment with propranolol, carbamazepine and
Lugol's iodine. A response is usually seen within 24-36 h.
Thyroid neoplasia
This usually presents as solitary nodules, of which 50% are benign adenomas or cystic
lesions. The prevalence of malignancy in childhood is 30-40% and the risk increases
following radiation to the neck during infancy or early childhood. Hyperfunctioning
adenomas are rare and most (90%) are well-differentiated follicular carcinomas.
Medullary carcinoma may occur as part of multiple endocrine neoplasia type I I (hyper-
parathyroidism and phaeochromocytoma) syndrome.
266
- Endocrinology
In primary hypothyroidism, T4 will be low and associated with a raised TSH. In hyper-
thyroidism, T4 will be raised and TSH will be suppressed.
In secondary hypothyroidism, T4 will be low in association with a low TSH. Further
investigation is with a TRH test. This involves the injection of TRH followed by measure-
ment of TSH at 30 and 60 min post-dose. In an individual with normal thyroid function,
TSH would rise at 30 min but fall by 60 min. However, in patients with hypothalamic
dysfunction, TSH would continue to rise at 60 min post-injection.
'Sick thyroid syndrome' refers to the scenario of a variety of abnormalities on thyroid
function testing in an unwell patient but which spontaneously resolve as the illness
improves. Usually there is a normal free T4 level with raised TSH.
Hyperthyroidism
lnitial medical treatment:
Suppression of thyroid hormone secretion using specific antithyroid treatments, e.g.
carbimazole, propylthiouracil
Blunting the peripheral effects of the thyroid hormones using a-blockade, e.g.
propranolol
Definitive treatment:
' This is contemplated if there has been no remission in symptoms on medical
Essentia1 Revision Notes in E~edi,ltrics tor the M RCPCti 2nd Edition -
treatment, and may involve subtotal thyroidectomy or radioactive iodine, which is
becoming an increasingly popular choice for teenagers
7. GLUCOSE HOMEOSTASIS
7.1 Physiology
The concentration of glucose in the blood is maintained by a balance between food intake
or glucose mobilization from the liver and glucose utilization. Homeostatic mechanisms
keep this within a narrow range.
In the fed state, insulin release is stimulated by a raised glucose and amino acid concentra-
tion. It is also stimulated by gut hormone release. In the fasting state, blood glucose
concentrations fall and insulin production is turned off under the influence of somatostatin.
A low glucose concentration is sensed by the hypothalamus, which regulates pancreatic
secretion and stimulates the release of the counter-regulatory hormones glucagon, ACTH,
GH, prolactin and catecholamines.
Actions of insulin
Liver:
Conversion of glucose to glycogen
Inhibits gluconeogenesis
Inhibits glycogenolysis
Peripheral:
Stimulates glucose and amino acid uptake by muscle
Stimulates glucose uptake by fat cells to form triglycerides .
Causesof diabetesm&itus
The most common cause of diabetes in childhood is type 1 autoimmune diabetes, although
type 2 diabetes is increasingly being reported in association with obesity in teenagers. Type
2 diabetes is a combination of a-cell failure and insulin resistance.
Epidemiology
UK - annual incidence is 20 per 100,000 children
In many countries the incidence is rising, in some the incidence in children < 5 years of
age is increasing
Diabetes before 1 year of age is extremely rare. Incidence increases with age. Minor
peak at age 4-6 years, major peak at 10-1 4 years
No clear pattern of inheritance
Increased risk if one family member is affected
Clinical effects
As the blood glucose level increases, the glucose in the glomerular filtrate exceeds the
ability of the proximal tubules to reabsorb it. This leads to glycosuria. Polyuria then occurs,
because the loop of Hen14 is unable to concentrate the urine because the renal tubules are
insufficiently hyperosrnolar. Extracellular volume depletion leads to thiist and polydipsia.
-'1
Cystic-fibrosis-related diabetes
E
Maturity onset diabetes of the young 1
Genetic syndromes (Down syndrome, Wolfram or DIDMOAD syndrome (diabetes z
insipidus, diabetes mellitus, optic atrophy and deafness)) 3
Risk factors for Type 2 diabetes
Family history of type 2 diabetes
1
High-risk ethnic groups (African, Caribbean, Asian, Hispanic)
Obesity
Female sex
Pubertal
Clinical signs of insulin reistance (acanthosis nigricans, polycystic ovarian syndrome)
Biochemical signs of insulin resistance (high insulin or c-peptide levels)
No islet cell antibodies
Diagnosis
Hyperglycaemia - random glucose > 11.1 mmol/L, fasting glucose > 7.6 mmol/L
Glucose tolerance test is not routinely necessary for diagnosis.
A well child
A subcutaneous insulin regimen may be commenced as outlined below.
Definition
pH < 7.2
Bicarbonate < 15 mmol/L
Raised bloodlurinary ketones
2 70
odema. An initial fluid bolus can be used to resuscitate the child. Normal fluid
requirements are calculated as maintenance + 10% deficit given evenly over 48 h
Rule of thumb:
6mllkgper hourforchildren weighing3-9kg
5 mllkg per h for children weighing 10-1 9 kg
4ml/kgperhourforchildren weighing>20kg
This usually covers ongoing losses, but if excessive they need replacement
Initial fluid is 0.9% saline
When blood glucose is down to 15 mmol1L change to fluid containing glucose,
e.g. 4% glucose + 0.45% saline
Intravenous insulin 0.05-0.1 IUIkg per hour with the rate of infusion adjusted according
to the blood glucose concentration
Monitoring of glucose
Replacement of potassium and monitoring of electrolytes
Diet
The aim is for a healthy diet containing adequate protein, small amounts of fat and complex
carbohydrates that are digested slowly. The body cannot cope with sugary foods, the
carbohydrate of which is rapidly absorbed, and these should be limited (including sugary
drinks). The intensive insulin regimens allow for a more flexible eating pattern as the rapidly
acting insulin can be adjusted according to the carbohydrate content of individual meals.
However, the twice-daily insulin regimen requires a consistency of meal times with regular
snacks and consistent carbohydate content of meals.
Exercise
Exercise is important not only to maintain cardiovascular fitness but also to reduce blood
glucose levels.
7.3 Hypoglycaemia
Persistent:
Persistent hyperinsulinaemic hypoglycaemia of infancy
lnsulinoma
Exogenous insulin
Investigation of hypoglycaemia
Blood taken for a diagnostic screen is only useful if taken when the patient is hypoglycae-
mic (glucose < 2.6 mmol/L) and should include the following:
Blood
Glucose
Insulin (C peptide)
Cortisol
GH
Lactate
Free fatty acids
Amino acids
Ketone bodies ($-hydroxybutyrate and acetoacetate)
Urine
Organic acids
In hypoglycaemic states in the absence of ketones it is impohant to look at the free fatty
acids (FFA). Normal FFA suggests hyperinsulinism and raised FFA suggests a fatty-acid
oxidation defect. Hypoglycaemia in the presence of urinary ketones suggests either a
counter-regulatory hormone deficiency or an enzyme defect in the glycogenolysis or
gluconeogenesis pathways.
8. BONE METABOLISM
8.1 Physiology of calcium and phosphate homeostasis
Principal regulators of calcium concentrations
Vitamin D (and its active metabolites)
Parathyroid hormone (PTH)
Calcitonin
Essential Revision Notes in Paediatr-icsfor the hfKCPCH 2nd ~dition
Vitamin D
Vitamin D3 (cholecalciferol) is produced in the skin from a pro-vitamin as a result of
exposure to ultraviolet light. Excess sunlight converts pro-vitamin D to an inactive com-
pound thus preventing vitamin D intoxication. Vitamin D is also ingested and is a fat-
soluble vitamin. Vitamin D is converted to its active form by hydroxylation - intially to its
25-hydroxyl form in the liver and the subsequent 1,25-hydroxylation occurs in the kidney.
25-hydroxylation 1-hydroxylation
(liver) (proximal renal tubule)
Cholecalciferol
1
- 2dcholecalciferol
1
- 1.25-dihydrocholecalciferol
Parathyroid hormone
The PTH gene is located on chromosome 11. Active PTH is cleaved from a pro-hormone
and then secreted by the parathyroid glands. Low calcium, cortisol, prolactin, phosphate
and vitamin D all affect PTH secretion, but maximal PTH secretion occurs at a calcium
concentration of < 2 mmol/L.
Calcitonin
Produced by the C cells of the thyroid gland and synthesized as a large precursor molecule;
its primary functions are:
2 74
I
Endocrinology
8.2.2 Hypoparathyroidism
Causes
Parathyroid absence or aplasia
Di George syndrome (thymic abnormalities/cardiac defectslfacial appearances)
Autoimmune
Associated with multiple endocrinopathy
Iatrogenic - post-thyroid surgery
Treatment
In primary hypoparathyroidism, the management of neonatal tetany consists of intravenous
calcium gluconate and oral 1,25-dihydroxycholecalciferol
Subsequent management is with vitamin D and an adequate intake of calcium
8.2.3 Pseudohypoparathyroidism
Clinical features
Mental retardation
Short stature
Characteristic facies
Shortening of fourth and fifth metacarpal and metatarsal
Ectopic calcification
Aetiology
Due to end-organ resistance
Associations
TSH resistance and raised TSH levels
8.2.4 Pseudopseudohypoparathyroidism
Phenotypic features of pseudohypoparathyroidism are present but are not associated with
the biochemical abnormalities.
Essenti,?1 Revision Notes in Paec!intrics tor the IC?RQIPCH 2nd Edition
8.2.5 Hypercalcaemia
Clinical features are non-specific, often with anorexia, constipation, polyuria, nausea and
vomiting in a child with faltering growth.
Causes of hypercalcaemia
Low PTH:
Vitamin D intoxication
Infantile hypercalcaemia
Transient
William syndrome
Associated with tumours
High PTH:
Primary hyperparathyroidism
Familial hypocalciuric hypercalcaemia
Management of hypercalcaemia
This includes treatment of the underlying cause, hydration with intravenous saline, increas-
ing urinary excretion of calcium using loop diurectics such as furosemide and the use of
biophosphonates to inhibit osteoclast activity.
8.2.6 Rickets
Causes of rickets include:
Hypocalcaemic
Calcium deficiency:
dietary
malabsorption
Vitamin D deficiency:
dietary
malabsorption
lack of sunlight
liverdisease
anticonvulsants
biosynthetic defect of vitamin D
1a-hydroxylase deficiency
liver disease
renal disease
Defective vitamin D action
Phosphopenic:
Renal tubular loss
isolated, e.g. X-linked hyphosphataemia
mixed tubular, e.g. Fanconits syndrome
Abnormal bones
Renal osteodystrophy
Endocrinology
Causes of obesity
Nutritional:
Simple obesity/constitutional obesity
Syndromes:
Down
Laurence-Moon- Biedl
Prader-Willi
Endocrine:
Hypothalamic damage
Hypopituitarism, GH deficiency
Hypogonadism
Hypothyroidism
Cushing syndrome
Pseudohypoparathyroidism
Hyperinsulinism
Iatrogenic -glucocorticoids; oestrogens
Inactivity
Psychological disturbances
Essential Revision Notes in Pacdiatrics for the MKCPCH 2nd Edition
In general, simple constitutional obesity is associated with tall stature in childhood, whereas
endocrine causes of obesity tend to be associated with short stature or a reduction in height
velocity.
Consequences of obesity
Childhood
Insulin resistance and abnormal glucose tolerance
Type 2 diabetes
Non-alcoholic steatohepatitis
Psychological problems
Orthopaedic problems
Obstructive sleep apnoea (pickwickian syndrome)
lncreased cardiac diameter
Adulthood - all the above plus:
Hyperlipidaemia
Hypertension
Diabetes
lncreased risk of death from cardiovascular disease
Laurence-Moon-Biedl syndrome
Clinical features:
Mental retardation
Obesity - marked by 4 years of age
Retinitis pigmentosa~strabismus
Polydactylylclinodactyly
Moderate short stature
Endocrinology
Hypogonadism
Associations:
Renal abnormalities
Diabetes insipidus
Management of obesity
ldentification and treatment of underlying cause
Dietary measures
Reduction in sedentary behaviour
Increased exercise
1'
1 1 FURTHER READING
Brook, CGD, Hindmarsh PC (eds). 2001. Clinical Paediatric Endocrinology, 4th edition.
Oxford: Blackwell Science.
Creighton, S, Minto C. 2001. Managing intersex. British Medical Journal 323, 1264-6.
'Beneficial effects of intensive therapy of diabetes during adolescence: Outcomes after the
conclusion of the Diabetes Control and Complications Trial (DCCT)' 2001. journal of
Pediatrics, 13 9(6), 804-8 12.
Hindmarsh, PC. 2002. Optimization of thyroxine dose in congenital hypothyroidism.
Archives of Disease in Childhood 86, 73-5.
Hughes IA. 1989. Handbook of Endocrine Investigations in Children. Wright.
NICE Guideline. July 2004. Type I Diabetes: Diagnosis and managment of Type 1 Diabetes
in Children and Young People. London: NICE.
Wright, CM, Booth, IW, Buckler, JMH. 2002. Growth reference charts for use in the United
Kingdom. Archives of Disease in Childhood 86, 1 1-1 4.
Chapter 8
Ethics and Law
Vic Larcher and Robert Wheeler
CONTENTS
Ethics
9. Confidentiality
9.1 Confidentiality and children
9.2 Confidentiality and child protection
13. An introduction
18. Consent
19. Children's capacity
19.1 16-17years
19.2 Preschool
19.3 The intervening years
19.4 Fraser Guidelines
Strengths of utilitarianism
Consequences of actions do matter
Gives a clear answer to the question of what individuals should do
Essentia / Revision Notes i n Paechtrics for the MRCPCH 2nd Edition
Weaknesses of utilitarianism
Difficult to predict consequences with precision
No easily definable, universally agreed single measure of the components of the
utilitarian calculus
Some actions are wrong even if they lead to best consequences, e.g. use of torture to
gain information to prevent harm
Maximizing happiness of the majority may be unjust to the minority, especially the
weak and vulnerable and those who lack capacity
Which counts more - intensity or length of happiness?
Although the application of the principle of utility requires a potentially difficult calculation
of the effects of uncertain consequences, this does not differ from any other exercise that
involves balancing value judgements. Some form of calculation of harmdbenefits is required
in the distribution of health care to populations and in the allocation of scarce resources.
2.2 Deontology
Deontological theory is based on a doctrine of moral obligation or duty. To be moral is to
do one's duty, or intend to do it, regardless of the consequences. To do one's duty involves
obeying moral rules, which can be derived by rational consideration or discovery in the
same way as natural laws, e.g. the laws of gravity or motion, can be deduced from physical
events. Moral rules must be universal (apply to everyone), unconditional (no exceptions)
and imperative (obligatory or absolutely necessary). Some obligations are deemed right
regardless of consequences, e.g. truth telling, avoidance of harm to others.
Moral individuals should be capable of discerning rules (rational), able to formulate and
carry out plans and govern their conduct by rules and values. A free choice must be
available ('ought implies can'). Rational, autonomous beings have their own intrinsic value
and are worthy of respect. They may not be used as means to further the ends of others,
however laudable these may be. Thus if we wish to eliminate a disease in society by mass
immunization programmes but do not obtain informed consent from subjects then we use
them as means to achieving our ends without respecting their intrinsic worth.
Strengths of deontology
General belief that some actions are wrong irrespective of consequences
Upholds dignity and intrinsic value of individual
Rational and supports equality
'Do as you would be done by'
Ethics d17d Law
Weaknesses of deontology
Impossibility of truly free decisions - 'Autonomy is a philosopher's myth'
Absolutist, austere, no place for duty of beneficence (obligation to benefit patients by
acting in their best interests)
Consequences do matter at times
What if duties conflict? For example, the duties to avoid harms and to tell the truth
Societies may also regard other rights and obligations as important. Deciding between
competing moral duties is difficult without taking some account of the consequences or
likely consequences of actions.
2.4 Principles
An alternative approach to the day-to-day application of moral theories is the use of four
prima facie moral principles that are compatible with a wide range of moral theories. There
i s widespread acceptance of the relevance and validity of using principles that transcend
religious, cultural and philosophical differences.
~ ~ s e n t iRevision
al Notes in paedicltrics for the M RCyPCH -117dEdition
When faced with an ethical dilemma it may be helpful to apply the following four moral
principles that set out prima facie moral obligations. A prima facie moral obligation is one
which in circumstances where duties conflict is the one which it is morally most important
to follow.
The principles are: I
Respect for autonomy - this involves respecting the rights of patients to exercise as
much self-determination as they are capable of exercising. It involves giving sufficient
information to permit informed choice and a duty to respect decisions of autonomous
patients even when they conflict with those of professionals
Beneficence - an obligation to benefit patients by acting in their best interests, e.g. by
providing treatments that are intended to produce net clinical benefits. In every day life
we do not usually have an obligation to benefit others, apart from those with whom we
have a special relationship e.g. family and close friends. In contrast doctors do have
duties, which are often referred to as superrogatory to benefit their patients.
Non-maleficence - an obligation not to cause net harm to patients even though some
treatments may produce initial harms, e.g. chemotherapy. Applies to all, not just patients
Justice- the obligation to act fairly and without discrimination, e.g. the distribution of
healthcare resources
286
Ethics and Law
Ethical examination of cases can follow this approach by starting from the features of the
particular case and seeking to recall similar cases, which might help in resolving it. For
example, in dealing with a 15-year-old who is refusing further chemotherapy that his/her
doctors recommend we might examine how similar cases were resolved and what ethical
principles were relevant to them.
Whatever technique is used it is important that arguments used to justify positions adopted
are fair-minded and are based on valid and sound reasoning. It is also important that there
is a reflective equilibrium between intuitive or emotional responses to moral dilemmas and
moral theory. Emotional responses to dilemmas - 'the yuk factor' - cannot be discounted
altogether because emotional responses may be morally important, moral intuitions have a
role in moral reasoning and emotional responses to others are an essential component of
the doctor-patient relationship. Nevertheless, such emotional responses require rational
analysis and justification
6. CHILDREN'S RIGHTS
Rights are justifiable moral claims made on behalf of individuals that confer obligations on
others. They provide status and protection for individuals, especially those who lack
capacity or rationality. Rights are often regarded as being doiived from fundamental moral
principles or they may be part of a social contract. Possession o f rights enables individuals
to seek redress if their rights are infringed. Rights may be positive or negative and may be
defined by special relationships, e.g. parent-child.
Examples Exarnples
Rights to information and Freedom of movement
best available health care speech, religious beliefs
The UN Convention of Rights of the Child sets out in a series of articles rights that apply to
all aspects of a child's life. The World Medical Association (WMA) has codified those rights
~ssentialRevision Notes in Paediatrics for the htRCPCH 2nd Edition
rights to be exercised in full. It is not clear whose rights take precedence and mere appeal
to rights may be insufficient to protect children's interests
Clinicians cannot be forced to administer LST that they believe is not in the best
interests of the child, even when the parents insist on it, e.g. severe brain damage as a
consequence of microcephaly and cerebral palsy
Permanent vegetative state, dependent on tube feeding for survival. The Court ruled that
tube feeding was medical treatment and could be withdrawn because it was not in the
best interests of the patient
There is no legal distinction between withdrawing and withholding LST
Non-provision of cardiopulmonary resuscitation was acceptable in circumstances of
very severe brain damage
Adults who are competent to do so may request that LST be withdrawn, especially if
they face continuation of life that they regard as being worse than death
Requests for assisted suicide or active euthanasia have been rejected by English Courts
The legality of withdrawal of fluids from children who are not close to death or in a
permanent vegetative state remains unclear and many professionals have ethical concerns
about it. Even considering UK Human Rights legislation, C O Uappear ~ to accept that there
are circumstances in which the continued provision of LST no longer serves the broader
concept of best interests, perhaps because of its intolerable burden.
There should be openness and transparency in discussions within teams and with
parentslchildren
Consider second opinions to clarify position
294
1
B
Ethics and Law
Children may have the legal capacity to give consent but even if they do not they still have
the right to information given in a form and at a pace that they can comprehend. If their
views are to be overridden they should receive an explanation as to why this will happen. it
is good practice to seek their assent, i.e. agreement, and where a treatment or intervention
is not immediately necessary to delay it until they have had further opportunity to discuss it.
9. CONFIDENTIALITY
There is a general duty of confidentiality over the disclosure of personal information about
patients (including children) to third parties.
in general such information should not be disclosed without the consent of the patient or
those with parental responsibility in the case of children.
The ethical justifications for non-consensual disclosure are:
Respect for children's autonomy and right for control over their own data
Confidentiality is a professional duty - implied promise not to disclose
The duty of the virtuous doctor is to keep patient details confidential
Better consequences follow if patient's know they can trust their doctors not to reveal
information
General principles of confidentiality:
Wherever possible consent for disclosure should be sought
Data should be made anonymous if unidentifiable data will serve the purpose
Only information necessary for the purpose in question should be disclosed
Information can be shared within healthcare teams unless patients specifically object
because sharing of clinical and other information is implicit in and necessary for the
effective delivery of health care.
Although there is no specific law of confidentiality the Law's approach to breaches of
confidentiality is to consider whether there is a public interest in favour of breaching
confidentiality or not breaching it.
DiscIosure of information is a legal duty in certain circumstances:
Notification of certain specified infectious diseases
Notification of births and deaths
If the Court makes a specific request for it
Disclosure of information is discretionary in circumstances where:
There is risk of significant harm to a third party
It is necessary to do so for detection or prevention of serious crime including child
abuse
Essential Revision Notes in Paediatrics for the MRCPCH 2nd Edition
Although there may be ethical justification for the prescription of contraception in such
circumstances, there has been dispute over its legality. It was held that 'Parental right.. .[to
determine whether their child should undergo medical treatment]. . .terminates if. . .and
I
when the child achieves sufficient understanding and intelligence to enable him or her to
understand fully what is proposed'.
It is clear that children under the age of 16 may have the capacity to consent to medical
treatment provided that they understand the nature and purpose of what is involved and its
implications for themselves and their family.
The legal (Fraser's) criteria for the prescription of contraception (including emergency
contraception) to adolescents are:
Ability to understand implications for self and family
There is a sustained and consistent refusal to discuss with parents
The young person has made a decision to start or continue to have sexual intercourse,
despite attempts at persuasion
The adolescent's health will suffer or is likely to suffer if contraception is not given
Prescribing contraception is in the young person's best interests
11. ABORTION
Children and young people may request abortion under the terms of the Abortion Act 1967
as amended in 1990. This provides that abortion may be carried out in pregnancies that do
not exceed 24 weeks if:
The continuation of the pregnancy would result in injury to the physical or mental
health of the woman or any existing children in her family
The termination is necessary to prevent that risk
The continuation of the pregnancy would involve risk to the life of the mother, greater
than if it were terminated
There is a substantial risk that if the child were born it would suffer from such physical
or mental abnormalities as to be seriously handicapped
Under the Act the young person needs to be assessed by two doctors who must be satisfied
that the abortion is justified.
The ethical justifications for abortion in young women are essentially similar to those in
adults but a more paternalistic approach with appeal to best interests is reasonable in those
who cannot consent because they lack the capacity to do so.
Child law
13. AN INTRODUCTION
It is not feasible, here, to state comprehensively the law pertaining to paediatric medicine,
let alone the body of law applicable to children. This section simply touches on some of the
legal topics that frequently vex doctors, and reviews child law in England and Wales. he
stage is set by consideration of the very wide remit of the Children Act 1989. Subsequentl$
the status of the child and those with parental responsibility are considered, before
discussing the most frequently exercised issue of medical law in childhood, namely the
provision of valid consent.
their own decisions concerning health care. The significance of the 21st birthday as a
landmark occasion in our society derives in part from this being the age of majority, until
legislation in 1969 (the Family Law Reform Act 1969). Under the same Act, 16- and 17-
year-olds were given the legal right to agree to treatment independently of their parents,
although the courts have not interpreted this statute as giving a right to refuse.
Essential Revision Notes in Paedi,itrics fi)r the M K(-PC 'H 2nd Fdition
There is a legal presumption that the man who is married to the mother is the biologica
and thus legal father, whatever the truth of the situation. If married to the mother at the time
of the birth, the father will have parental responsibility. An unmarried father whose name
appears on the birth certificate on or after 1 December 2003 automatically has parenta
responsibility, and it can be acquired by other unmarried fathers by formal agreements wit
the mother, or the court.
Guardians, local authorities, adoption agencies and prospective adopters can share parent
responsibility with the parents but the parents only surrender their parental responsibili
when the child reaches majority, or is adopted away from them.
In terms of the residual 'rights' of parenthood, the naming of the child, the determination
education and religion, and the right to appoint a guardian remain. The other 'incidents'
parenthood (i.e. to provide a home, to protect and maintain, to provide for education, t
discipline, etc.) would largely be viewed as duties or responsibilities, placed by the state o
the parent.
17.3 Wardship
In ancient times, wardship described a right to have custody over an infant who was th
heir to land. Combined with the sovereign's powers to act as the parent of any abandoned
(or orphaned) child, it can be seen that this was a potent mechanism for a land-hung
monarch (Parens patriae: Latin: 'parent of the fatherland' or 'parent of the homeland';
law, it refers to the power of the state to act as the parent of any child or the power to act
on behalf of any individual who is in need of protection, such as an incapacitated
individual or a child whose parents are unable or unwilling to take care of the child).
In the modern era, the High Court can use wardship as one means of exercising its parens
patriae powers, to ensure that no important or major steps in the life of a ward of court can
be taken without prior consent from the court. This certainly extends-to medical treatments
because for a ward of court, the court has parental responsibility. In general terms, one of
the aims of the Children Act 1989 was to reduce the necessity for wardship proceedings, by
incorporating its more worthwhile powers into the statute.
17.4 Guardians
Guardianship is confusing (see Bainham 2005), because there are several separate roles that
adults play in relation to children which have acquired this label.
mother's unilateral wish for a change of a child's surname following divorce, even if they
had lost custody of the child. This natural or parental guardianship has been abolished by
the Children Act 1989, removing the final vestiges of parental legal inequality.
Children's guardian
Children%guardians represent children in court during proceedings involving state interven-
tion in the family; they are one of a number of individuals, collectively described as 'officers
of the service', falling within the remit of the Children and Family Court Advisory and
Support Service (CAFCASS). They are appointed on the basis of their expertise in social
work and childcare law. Their role is to inform the court of the child's wishes and feelings,
while providing all the information that may be relevant to the ihild's welfare. They are
loosely equivalent to guardians ad litem, who represent children i n civil litigation.
Special guardian
This is a new legal concept (introduced by the Adoption and Children Act 2002), providing
legal security for permanent carers of children but falling short of adoption, for situations
where adoption has been thought inappropriate for the child.
18. CONSENT
Those with parental responsibility have a duty to provide consent for the child's medical
treatment.
Consent is required before any intervention, because society opposes the uninvited touch.
At its simplest, the outstretched hand, by implication, invites touching. However, the patient
who consults their doctor does not assume that their very presence in the consulting room
gives the doctor licence to touch them. The uninvited touch is, historically, an act of
common assault. However, it is not the avoidance of this rather dramatic accusation that
Essential Revision Notes it-, Paedi'7tric-s tor t/?cMKhI3CH2nd Edition
drives most contemporary doctors to obtain consent, although very occasionally the charge
is still made.
What is far more relevant is the concept of negligence, where the doctor causes some harm
by failing to deliver a reasonable standard of care to the patient, to whom there is
undoubtedly a duty to provide such care.
One aspect of this standard of care is obtaining valid consent. This entails the provision of
all necessary information for the patient to make an informed decision. Often, the only
record of this provision is the annotated and signed consent form. This document thus acb
both as a shield against a claim of assault, and objective evidence that some formal
provision of information has occurred.
There are two excellent documents concerning consent which provide comprehensive
guidelines (the DOH Reference Guide and the BMA report of the Consent working party).
The main questions to be considered when obtaining consent may be summarized as
follows.
When is consent required?
Consent is required for any intervention
Who should obtain consent?
The person who will perform the proposed treatment
In what form should consent be taken?
There is no legal requirement for written consent, which can equally be verbal, or b#
acquiescence, provided the patient is correctly informed. However, a written
document, which is signed by the patient, forms a piece of objective evidence that
consent has been taken. Furthermore, if the document also records the details of the
information given, it increases the certainty that relevant issues have been discussed.
If the consent were verbal, it would be prudent to record the. circumstances, topics
discussed and outcome in the clinical notes
From whom should consent be obtained?
Anyone with parental responsibility for a child may provide consent for his or her
medical treatment. To consent to treatment, an individual must have the capacity
(i.e. intelligence and understanding) fully to understand what treatment is being -
proposed (see below)
It is assumed that a young person of 16 years has such capacity, and because the law
provides that they can give valid consent, no additional consent from parents is
required. In the period between 16 and 18 years, if the young person is
incapacitated, their parents may consent on their behalf
A child of less than 16 years may give consent if capacity can be established, but the
test is relatively rigorous
In the absence of a parent, where a child is unable to consent because of lack of capacity,
can the doctor treat in the emergency situation?
If emergency treatment is necessary to save life or avoid a significant deterioration in
health, the doctor may treat on the basis of this necessity. However, the views of the
parents and the child (if known), the likelihood of improvement with treatment and
the need to avoid restricting future treatment options where possible must all be
considered in this situation
~ t h i c sand Law
19.2 Preschool
It is self-evident that children in this age group are unable to provide valid consent but they
still have autonomy and their interests should be considered. It is gdod practice to involve
them where possible in the process of obtaining consent, particularly offering to answer
their questions, and to remind them of the obvious consequences of a procedure (e.g. the
scar).
consenting to a particular procedure, their age is probably the least consideration. The
House of Lords have provided the means for the determination, in their ruling on the Cillick
case (Gillick v West Norfolk & Wisbech AHA (1985) 3 All ER 402, HL). The child would
need to:
Understand that a choice exists
Understand the purpose and nature of the proposed treatment
Understand the risks, benefits and alternatives
Understand the consequences of not undergoing the treatment
Furthermore, the child must:
Be able to remember the information for long enough to make a considered decision
Be free from undue pressure
It is clear that the ability of the child to pass this 'test' is entirely dependent on the propo
procedure, and the child's experience. It is not difficult to picture 14-year-olds with ne
diagnosed leukaemia, bewildered and terrified, who would be entirely incapable
providing valid consent to a diagnostic lumbar puncture. On the other hand, a youn
child who has spent months on the oncology ward, already had numerous si
procedures, and witnessed the consequences in many of his fellow patients, may well
competent.
It should be reiterated that the Gillick test, understandably, sets a high threshold for capaci
that would probably be unattainable by many adults.
As with the 16- to 17-year-olds, the ability of Gillick-competent children to provide val
consent does not extend to a right to refuse.
Hope T, Savulescu J, Hendrick 1. 2003. Medical Ethics and Law: the Core Curriculum.
on don: Churchill Livingstone.
Kennedy I, Grubb. A. 2000. Medical Law Text and Materials, 3rd edn. London:
Butterworths.
Montgomery J.2002. Health Care Law, 2nd edn. Oxford: Oxford University Press.
Raphael DD. 1994. Moral Philosophy, 2nd edn. Oxford: Oxford University Press.
RCPCH. 2004. Withholding or Withdrawing Life Sustaining Treatment in Children; a
framework for practice, 2nd edn. Available on RCPCH web-site: www.rcpch. ac.uk
Sokol DK, Bergson G. 2000. Medical Ethics and Law; Surviving the Wards and Passing
Exams. London: Trauma Publishing.
UK Clinical Ethics Network www.ethics-network.0rg.uk
Chapter 9
CONTENTS
1. Basic anatomy and physiology
1 .I Anatomy
1.2 Digestion
Nutrition
2.1 Nutritional requirements
2.2 Nutritional assessment
2.3 Breast-feeding
2.4 Iron
2.5 Folate
2.6 Vitamin B12
2.7 Zinc
2.8 Fat-soluble vitamins
2.9 Nutritional impairment
2.1 0 Protein-energy malnutrition
2.1 1 Faltering growth
2.1 2 Organic causes of faltering growth
3. Nutritional management
3.1 Nutritional supplementation
3.2 Enteral nutrition
3.3 Total parenteral nutrition (TPN)
3.4 Short-bowel syndrome
4. Food intolerance
4.1 Cows' milk protein intolerance
4.2 Peanut allergy
4.3 Food-induced anaphylaxis
4.4 Carbohydrate intolerance
5. Gastro-oesophageal reflux
5.1 Differential diagnosis of reflux oesophagitis
5.2 Feeding problems in cerebral palsy
5.3 Barrett's oesophagus
6. Peptic ulcer disease
6.1 Helicobacter pylori infection
6.2 Other causes of antral gastritis and peptic ulceration
6.3 Zollinger-Ellison syndrome
7. Chronic diarrhoea
7.1 Coeliac disease
7.2 Cows' milk protein sensitive enteropathy
7.3 Giardiasis
7.4 Cystic fibrosis
7.5 Schwachman- Diamond syndrome
7.6 Bacterial overgrowth (small bowel)
7.7 Intestinal lymphangiectasia
11. Gastroenteritis
11.I Post-gastroenteritis syndromes
12. Constipation
12.1 Perianal streptococcal infection
12.2 Hirschsprung disease
Stomach
Lined by columnar epithelium. Chief cells produce pepsin. Parietal cells produce gastric
acid and intrinsic factor. Secretions in adults are 3 I/day. Gastric acid secretion is stimulated
by vagal stimulation, gastrin and histamine h a HZ receptors on parietal cells. Secretion is
inhibited by sympathetic stimulation, nausea, gastric acidity and small intestinal peptides.
Blood supply from coeliac axis.
Small intestine
Main function is absorption, mostly in the duodenum and jejunum apart from bile salts and
vitamin BIZ which are absorbed in the terminal ileum. Blood supply from mid-duodenum
onwards is the superior mesenteric artery. Adult length 2-3 metres.
Colon
Functions primarily for salt and water reabsorption. Blood supply from superior mesenteric
artery until the distal transverse colon and then the inferior mesenteric artery after that.
Approximately 1 m long in adults.
Pancreas
Retroperitoneal. Endocrine function (2% of tissue mass) and exocrine function (98%). Blood
supply from coeliac axis.
s h r the hiR('PCH 2 n d Fdition
Esst'nti,~/Revision Notes in \<ledii~trj~
1.2 Digestion
Carbohydrate digestion
Carbohydrates are consumed as monosaccharides (glucose, fructose, galactose),
disaccharides (lactose, sucrose, maltose, isomaltose) and the polysaccharides (starch,
dextrins, glycogen)
Salivary and pancreatic amylase break down starch into oligosaccharides and
disaccharides. Pancreatic amylase aids carbohydrate digestion but carbohydrate
digestion is not dependent upon it
Disaccharidases (maltase, sucrase, lactase) in the microvilli hydrolyse oligo- and
disaccharides into monosaccharides:
Maltose into glucose
lsomaltose into glucose
Sucrose into glucose and fructose
Lactose into glucose and galactose
Monosaccharides are then absorbed, glucose and galactose by an active transport
mechanism and fructose by facilitated diffusion
Protein digestion
In the stomach, gastric acid denatures protein and facilitates the conversion of
pepsinogen into pepsin
Trypsin, chymotrypsin and elastase, secreted as the inactive precursors, are produced by
the exocrine pancreas. Enterokinase (secreted in the proximal duodenum) activates mt
Fat digestion
Entry of fats into the duodenum causes release of pancreozymin-cholecystokinin which'
stimulates the gallbladder to contract
Hydrolysis of triglycerides by pancreatic lipase takes place
Free fatty acids, glycerol and monoglycerides are emulsified by bile salts to form
micelles which are then absorbed along the brush border of mucosal cells
Short-chain fatty acids enter the portal circulation bound to albumin. Long-chain fats are
re-esterified within the mucosal cells into triglycerides which combine with lesser
amounts of protein, phospholipid and cholesterol to create chylomicrons
Chylomicrons enter the lymphatic system and are transported via the thoracic duct into
the bloodstream
Pancreatic function
The pancreas secretes more than a litre of pancreatic juice per day, which is bicarbonate-
rich and contains enzymes for the absorption of carbohydrate, fat and protein. Faecal
elastase is a commonly used screen for pancreatic function.
Gut hormones
The main gut hormones are:
Gastrin - stimulated by vagal stimulation, distension of the stomach. Stimulates gastric
acid, pepsin and intrinsic factor. Stimulates gastric emptying and pancreatic secretion
Secretin - stimulated by intraluminal acid. Stimulates pancreatic bicarbonate secretion,
inhibits gastric acid and pepsin secretion and delays gastric emptying
Cholecystokinin-pancreozymin - stimulated by intraluminal food. Stimulates
pancreatic bicarbonate and enzyme secretion. Stimulates gallbladder contraction,
inhibits gastric emptying and gut motility
Enterohepatic circulation
Bile is produced by the liver and stored in the gallbladder. It is secreted into the duodenum
following gallbladder contraction (stimulated by cholecystokinin-pancreozymin release).
Bile acids aid fat digestion. They are formed from cholesterol. Primary bile acids are
produced in the liver. Secondary bile acids are formed from primary bile acids through
conjugation with amino acids by the action of intestinal bacteria. Primary and secondary
bile acids are deconjugated in the intestine, reabsorbed in the terminal ileum and
transported back to the liver bound to albumin for recirculation. -
2. NUTRITION
2.1 Nutritional requirements
This is age dependent and there are standard tables available (Reference Nutrient Intake,
RNI). The energy needs per kilogram of the infant are higher than the older child.
I Daily requirements
1 2 -year-old boy
Fluid 55 mllkg
Calories 50 kcallkg
Protein 1 g/kg
Sodium 2 mmollkg
Potassium 2 mmollkg
Energy requirements list calories but nutrient and micronutrient requirements are also
important to ensure that intake is balanced. It is essential for example to have an
appropriate balance of fat, carbohydrate and protein. Calcium is essential for bone growth.
Iron is required to prevent anaemia.
Energy requirements include Resting Energy Expenditure (Basal Metabolic Rate), which
represents 60-70% of requirements and the component which arises as a consequence of
physical activity (Physical Activity level).
Physical status (metabolic condition, bedridden, physical activity level) will impact on
requirements
Requirements in disease are generally greater than requirements in health
Ensure that you understand relevant social and family factors that may impact on the child's
nutrition.
2.3 Breast-feeding
Breast-feedingand infection
Ten per cent of the protein in mature breast milk is secretory immunoglobulin A (IgA).
Lymphocytes, macrophages, proteins with non-specific antibacterial activity and comple-
ment are also present. There have been many studies in developing countries to show that
infants fed formula milk have a higher mortality and morbidity particularly from gastro-
intestinal infection. In the UK, studies have shown:
Breast-feeding for more than 13 weeks reduces the incidence of gastrointestinal and
respiratory infections
The response to immunization with the Hib vaccine is higher in breast-fed than formula-
fed infants
The risk of necrotizing enterocolitis in low-birth-weight babies is lower in those who are
breast-fed
Breast-feedingand allergy
The incidence of atopic eczema in infants born to atopic mothers is reduced by breast-
feeding. Overall, however, there is no definitive proven reduction in atopy apart from this
specific circumstance.
Breast-feedingand diabetes
Infants who are breast-fed have a reduced risk of developing diabetes.
Contraindications to breast-feeding
Maternal drugs and breast-feeding are discussed in Chapter 4 - Clinical Pharmacology and
Toxicology, section 6.2 and in Chapter 16 - Neonatology.
With regard to tuberculosis; infants can be immunized at birth with isoniazid-resistant
BCG and treated with a course of isoniazid
With regard to human immunodeficiency virus (HIV); the virus has been cultured from
breast milk and is transmitted in it. In the Western world this makes breast-feeding
contraindicated in HIV-positive mothers, as it will increase the perinatal transmission
Essential Revision Notes in E3ediatrics for the M RCPCH 2nd Ecjifiorl
rate. The problem is not so straightforward in the developing world where the risks of
bottle feeding are high because of contaminated water supplies.
2.4 Iron
Dietary sources include cereals, red meat (particularly liver), fresh fruit, green vegetables
Absorbed from the proximal small bowel. Vitamin C, gastric acid and protein improve
absorption. 5-1 0% of dietary iron is absorbed
Deficiency causes hypochromic microcytic anaemia. Associated with poor appetite and
reduced intellectual function
Common causes of deficiency include poor diet (particularly prolonged or excess milk
feeding), chronic blood loss, malabsorption
Low serum ironlhigh transferrin suggests deficiency; low ironllow transferrin suggests
chronic disease. Ferritin is an indicator of total body stores but is also an acute-phase
reactant
Treatment is directed against the underlying cause. Dietary advice and iron
supplements, of which numerous commercial preparations are available, are indicated
in most patients. Side-effects of iron supplements include abdominal discomfort and
constipation. Iron supplements can be fatal in overdose
2.5 Folate
Dietary sources include liver, green vegetables, cereals, orange, milk, yeast and
mushrooms. Excessive cooking destroys folate
Absorbed from the proximal small bowel
Deficiency causes megalobiastic anaemia, irritability, poor weight gain and chronic
diarrhoea. Thrombocytopenia can occur
The serum folate reflects recent changes in folate status and the red-cell folate is an
indicator of the total body stores
Treatment of deficiency is with oral folic acid
Folate levels are not affected by the acute-phase response
Ga.stroenterology and Nutrition
2.7 Zinc
Dietary sources include beef, liver, eggs and nuts
Deficiency occurs secondary to poor absorption rather than poor intake
Clinical features include anaemia, growth retardation, periorofacial dermatitis, immune
deficiency, diarrhoea
Responds well to oral zinc
Acrodermatitis enteropathica
Autosomal recessive inheritance
Basic defect is impaired absorption of zinc in the gut
Presents with skin rash around the mouth and perianal area, chronic diarrhoea at the
time of weaning and recurrent infections. The hair has a reddish tint, alopecia is
characteristic. Superinfection with Candida sp. is common as are paronychia, dystrophic
nails, poor wound healing and ocular changes (photophobia, blepharitis, corneal
dystrophy)
Essentia1 Revision Notes in Baediatrics tbr the A4RCPCH 2 1 7 ~ 1Edition
-
Diagnosis is by serum zinc levels and the constellation of clinical signs. This is difficult
as the serum zinc is low as part of the acute-phase response. Measurement of white-cell
zinc levels is more accurate. The plasma metallothionein level can also be measured.
Metallothionein is a zinc-binding protein that is decreased in zinc deficiency but not in
the acute-phase response
Zinc deficiency in the newborn can produce a similar clinical picture
The condition responds very well to treatment with oral zinc
i
!
Vitamin E
Is an antioxidant
Found in green vegetables and vegetable oils
Deficiency causes ataxia, peripheral neuropathy and retinitis pigmentosa
Abetalipoproteinaemia
11
I -
Autosomal recessive inheritance
Pathogenesis is failure of chylomicron formation with impaired absorption of long-chain
I
i
fats with fat retention in the enterocyte
1I , 'i
1 9
I i
Malabsorption occurs from birth
Presents in early infancy with faltering growth, abdominal distension and foul smelling,
bulky stools
Symptoms of vitamin E deficiency (ataxia, peripheral neuropathy and retinitis
i
1; pigmentosa) develop later
Diagnosis is by low serum cholesterol, very low plasma triglyceride level, acanthocytes
I
I
on examination of the peripheral blood film, absence of betalipoprotein in the plasma
I Treatment is by substituting medium-chain triglycerides for long-chain triglycerides in
I
the diet. Medium-chain triglycerides are absorbed via the portal vein rather than the
I thoracic duct. In addition, high doses of the fat-soluble vitamins (A, D, E and K) are
required. Most of the neurological abnormalities are reversible if high doses of vitamin E
, are given early
I '
I
and Nrttrition
Gc~strocnterology
t
B
t
F
Vitamin K
Is contained in cows' milk, green leafy vegetables and pork. There is very little in breast
milk
Deficiency in the newborn presents as haemorrhagic disease of the newborn. This
usually presents on day 2 or 3 with bleeding from the umbilical stump, haematemesis
and melaena, epistaxis or excessive bleeding from puncture sites. lntracranial bleeding
can occur. Diagnosis is by prolongation of the prothrombin and partial thromboplastin
times with the thrombin time and fibrinogen levels being normal. Treatment is with
fresh-frozen plasma and vitamin K
There is no proven association between intramuscular vitamin K and childhood cancer
Pathogenesis of malnutrition
It is essential to think about the pathogenesis of malnutrition when assessing nutrition and
looking at nutritional supplementation. Malnutrition can only result from:
Inadequate intake or excessive losses
lncreased metabolic demand without increased intake
Malabsorption
One or all of these may contribute to malnutrition in an individual.
A good example i s cystic fibrosis in which:
Pancreatic malabsorption causes increased losses
lncreased energy needs are caused by:
Chronic cough
Dyspnoea
Recurrent infection
Inflammation
Reduced intake is caused by:
Anorexia
Vomiting
Psychological problems
Together, all of these factors result in an energy deficit. They all need to be taken into
account when nutritional supplementation is considered.
Essential Revision Notes in Paediatrics for- the MKCPCH 2nd Edition
2
a 2.11 Faltering growth
Faltering growth (previously called 'failure to thrive') refers to the failure to gain weight at
an adequate rate. It is common in infancy. It occurs because of one or a combination of the
following:
Failure of carer to offer adequate calories
Failure of the child to take sufficient calories
Failure of the child to retain adequate calories
Clearly this can be organic or non-organic. lnsufficient calories may be offered as a
consequence of parental neglect or because of a failure of the carer to appreciate the
calorie requirements of the child. lnsufficient calories may be taken as a consequence of
feeding difficulties (for example, cerebral palsy) or increased needs (for example, cystic
fibrosis) and calories may not be retained because of absorptive defects or loss through
vomiting or diarrhoea.
The investigation of faltering growth is generally only fruitful when specific pointers to
organic problems are elucidated in the history or on physical examination..
The management of non-organic faltering growth requires health 'visitor input and often
dietary assessment. In difficult cases hospital admission is indicated for evaluation and to
ensure an adequate weight gain can be obtained if sufficient calaies are given.
This 13-year-old boy has cerebral palsy. Comment on his nutritional status. What strategies
could be used to improve his nutrition? Why do you think his nutritional status is so poor?
This child's principal problem is likely to be with intake, either because of reflux or
secondary to bulbar problems or both. In addition to nutritional supplements, this child may
benefit from help with feeding practices including the involvement of a dietitian, speech
and language therapist, occupational therapist and neurodevelopmental paediatrician.
Other medical problems may be relevant such as recurrent chest infections secondary to
aspiration, intractable fits. Consideration needs to be given to feeding via nasogastric tube
or gastrostomy tube if appropriate. In some instances a fundoplication will also be required.
This boy has cystic fibrosis. Comment on his nutritional status. What can be done to help?
The additional factor in this child is malabsorption for which pancreatic supplementation is
required. Children with cystic fibrosis often dislike food and need either a nasogastric tube
or gastrostomy to help with administration. The energy requirements are high and calorie
supplementation with energy-dense supplements is required.
Nutritonal supplement
Normal infant feeds or milk contain 0.7 kCal/ml
Feeds can be concentrated
Carbohydrate supplements can be used, usually as glucose polymer in powder form to
add to feeds
Combined carbohydrate and fat supplements can be used
Feeds with a higher calorie density can be used, e.g. 1 kCal/ml, 1.5 kCal/ml
Special feeds can be used, e.g. hydrolysed protein formula feeds, soya-based feeds,
lactose-free feeds, medium-chain-triglyceride-basedfeeds
Milk-based or juice-based supplements can be given
There are many commercially available products available
Neuromuscular disease
Coma and severe facial and head injury
Severe mental retardation and cerebral palsy
Dysphagia secondary to cranial nerve dysfunction, muscular dystrophy or myasthenia
gravis
Malignant disease
Obstructing disease
Head and neck
Oesophagus
Stomach
Abnormality of deglutition following surgical intervention
Gastrointestinal side-effects from chemotherapy and/or radiotherapy .
Terminal supportive care
Pulmonary disease
Bronchopulmonary dysplasia
Cystic fibrosis
Chronic lung disease
Congenital abnormalities
Tracheo-oesophageal fistula
Oesophageal atresia
Cleft palate
Pierre Robin syndrome
Other
Anorexia nervosa
Cardiac cachexia
Chronic renal disease
Severe burns
Severe sepsis
Severe trauma
h ~ the
Essential Revision Notes in Pc~ci.dic~trics r M KCPCM 2nd Editif )n
I Dysmotility
/ The motility of the gut is a key factor in feed tolerance. Preterm infants, and children with
cerebral palsy have delayed gastric emptying which impacts significantly on the ability to
1I/I feed, particularly if nutrition is dependent upon nasogastric or gastrostomy feeding. Abdorn-
inal pain, bloating and constipation are common features of gut dysmotility.
Therapeutic strategies include the recognition of the problem, administration of a prokinetic
agent such as Domperidone, laxatives and occasionally, if there is a need for distal gut
deflation, suppositories. It may be necessary to give feeds by continuous infusion. Milk-free
diets can be used and in difficult cases full gastrointestinal investigation including upper
and lower gastrointestinal endoscopy, barium radiology, pH studies and scintigraphy may
be indicated. A number of children, particularly those with cerebral palsy, respond to milk
exclusion using a hydrolysed protein formula feed as an alternative.
Gastrc>enterologyand Nutrition
Nasojejunal feeding
This is indicated when nasogastric feeding is not tolerated because of delayed gastric
emptying or gross gastro-oesophageal reflux. Feed usually needs to be given continuously
to avoid dumping. If nasojejunal feeding is required long term a jejunostomy can be
fashioned.
11
Exclusion of luminal nutrients:
Crohn's disease
Organ failure:
Acute renal failure or acute liver failure
1 Hypercatabolism:
Extensive burns
Severe trauma
! Practical issues
I TPN prescribing
1 There are standard regimens for TPN prescribing. This will include the starter regimen which
i then increases in nutrient density over the first few days. Protein is supplied as amino acid,
I
1 carbohydrate as glucose and fat as a lipid emulsion. Electrolyte, calcium and phosphate
content needs to be carefully controlled. Fat- and water-soluble vitamins and trace elements
are added to the mix. Calorie density is increased through increase in carbohydrate and
lipid as tolerated. It is important to use standard regimens adjusted according to fluid
1 balance, electrolyte status and tolerance, e.g. of increases in glucose. It is important not to
and Nutrition
Gastroentero/~gy
push calorie density up too much without expert advice as this may result in poor tolerance
and toxicity with a net reduction in metabolized energy intake. The use of a TPN
pharmacist in conjunction with a nutrition team is essential in difficult cases.
Complications
Essentic~l
K e v i s i o ~Notes
~ tr-ic.s h r t l ~ thlh'l
in Pc~,letJi,r i 't'('t-l.?/)(lEdif1t 111
Line infection
Infections are one of the potentially life-threatening hazards of TPN. Coagulase-negative
staphylococcal infection is the most common. Children on TPN long term are at significant
risk of life-threatening bacterial sepsis. A child on TPN should have cultures taken and
antibiotics started promptly if there is a high fever. Children with short gutlenteropathy are
at highest risk because of bacterial translocation; they should have regular g i t decontamina-
tion particularly if infections are frequent. It is important that appropriate procedures are in
place to ensure that lines are dealt with aseptically and only by trained personnel. Long-
term feeding lines should not, for example, be used for blood letting. -
TPN-induced liver disease
TPN-induced liver disease develops in 40-60°/0 of infants who require long-term TPN for
intestinal failure. The clinical spectrum includes cholestasis, cholelithiasis, hepatic fibrosis
with progression to biliary cirrhosis, and the development of portal hypertension and liver
failure. The pathogenesis is multifactorial and is related to prematurity, low birth weight,
and duration of TPN. The degree and severity of the liver disease is related to recurrent
sepsis, including catheter sepsis, bacterial translocation and cholangitis. Lack of enteral
feeding leading to reduced gut hormone secretion, reduction of bile flow, and biliary stasis
are important mechanisms in the development of cholestasis, biliary sludge and cholelithia-
sis. The management strategies for the prevention of TPN-induced liver disease include
early enteral feeding, a multidisciplinary approach to the management of parenteral
nutrition, and aseptic catheter techniques to reduce sepsis. The administration of ursodeoxy-
cholic acid may improve bile flow and reduce gallbladder and intestinal stasis. Fat-soluble
vitamin replacement is essential by the intravenous route when child is parenterally fed but
may be given orally with regular monitoring during the transition to orallenteral feeding.
and Nutrition
C;,str-~)enterolc)~v
I
II Consequences of trace element abnormalities described during parenteral nutrition
1-
Growth failure
-
g Copper Refractory hypochromic anaemia
Neutropenia
Osteoporosis
s#
is
-
-
Subperiosteal haematoma
Soft tissue calcification
Selenium Cardiomyopathy
Skeletal myopathy, pain and tenderness
-I Pseudoalbinism
I Chromium Glucose intolerance Renal and hepatic impairment
Peripheral neuropathy
--
% Weight loss
*
Manganese Lipid abnormalities Liver toxicity
Anaemia Damage to basal ganglia
Molybdenum Tachycardia
Central scotomata
Irritability
Coma
Ii Aluminium Anaemia
Osteodystrophy
I . Encephalopathy
1
3.4 Short-bowel syndrome
a1 This is defined as intestinal failure secondary to massive resection.
I Aetiologies:
Neonatal - necrotizing enterocolitis, intestinal atresia, volvulus
I Older child - trauma, inflammatory bowl disease, vascular abnormalities
Ii than jejunum
Essential Revision Notes in Paecliatrics tor the MRCPCH 2nd Edition
Presence of ileocaecal valve - loss of ileocaecal valve results in faster transit. Backflow
(loss of the one-way valve) makes bacterial overgrowth more likely. There is a need for
vitamin BIZ replacement longer term
Improved outcome if colon still present which facilitates salt and water resorption
Coexistent disease, e.g. enteropathy is an adverse risk factor
Presence of liver disease is an adverse risk factor
Management
There are three phases of intestinal adaptation - acute (TPN-dependent, postoperative
ileus), adaptive (increasing enteral nutrition, can take months to years) and chronic. The
priority is to maintain normal growth and development through adequate calorie, nutrient
and micronutrient intake during these phases. The early introduction of enteral feeds
promotes intestinal adaptation and will improve subsequent feed tolerance. Feeds are
usually best given as a continuous infusion in the first instance and should only be
increased if tolerated, i.e. no diarrhoea (or excess stoma output if present). Explosive stools
imply feed intolerance which will increase the risk of metabolic upset and bacterial
translocation leading to sepsis. TPN should not be weaned until feed is tolerated and
absorbed. Weight needs careful monitoring during weaning of TPN. Artificial feeds (e.g.
hydrolysed feeds) are often better tolerated although osmolality is higher. Liver disease is a
serious complication of TPN and may lead to death from liver failure. It may be reduced by
maximizing feeds, avoidance of sepsis, artificial bile salts (e.g. ursodeoxycholic acid) and
vitamin supplementation. Bacterial overgrowth with the risks of malabsorption and bacterial
translocation is common and requires treatment with oral antibiotics given in cycles, either
metronidazole alone or in combination with gentamicin. Loperamide may help reduce gut
transit and thus increase absorption. Monitoring of micronutrients and fat-soluble vitamins is
essential during long-term TPN. Bowel lengthening surgery may reduce stasis and thus
translocation. In severe cases, isolated liver transplant or intestinal transplantation may be
considered. Multidisciplinary management is required, including attkntion to the child's oral
skills, social and psychological development and the needs of the family.
4. FOOD INTOLERANCE
1 It is important to distinguish between allergy and intolerance. An allergy implies an
1 immune-mediated reaction to food antigen (protein). Classically this is by IgE-mediated,
type I hypersensitivity. The signs of this include anaphylaxis, urticaria and atopic dermatitis.
I; Intolerance implies a reaction to food taken either in small quantity or in excess. It is a non-
1 specific term. Examples range from symptoms as a result of a non-lgE-mediated immune
1, reaction to food, such as coeliac disease, through to symptoms induced by simple over-
indulgence. An intolerance does not necessarily need to be to a protein and includes, for
I example, lactose intolerance.
I
~astroenterolog,~
and Nutrition
Management
Milk exclusion with a milk substitute. Soya preparations are commonly used and are
palatable. There is, however, a cross-reactivity between cdws' milk and soya protein of
up to one-third and so hydrolysed protein formula feeds'are preferred. Soya products
should not be used in infants < 6 months
The natural history of cows' milk intolerance is one of resolution with 80-90% back on
a normal diet by their third birthday. It is sensible to challenge regularly. This will
depend on the child's presentation. It is usual to organize challenges in hospital,
particularly if the initial reaction was severe, because of the risk of anaphylaxis
Children with a past history of anaphylaxis or severe respiratory symptoms following
allergen ingestion require an adrenaline pen for use either in the home or school setting
in the event of accidental exposure to the offending food antigen
It is common in children with milk allergy to see reactions to other foods, the most common
of which are soya, egg, wheat and peanut.
Skin-prick testing and IgE RAST testing are most useful in children with peanut, nut and egg
allergy.
Essential Revision Notes in Paediatrics for the MRCPCH 2nd Edition
Secondary (acquired)
Post-enteritis (rotavirus), neonatal surgery, malnutrition
Late-onset lactose intolerance
Gasiroenterology and Nutrition
Secondary (acquired)
Post-enteritis, neonatal surgery, malnutrition
Lactose intolerance
Carbohydrate intolerance is usually lactose intolerance and is usually acquired. The
deficient enzyme is the brush-border enzyme lactase which hydrolyses lactose into glucose
and galactose. The intolerance will present with characteristic loose explosive stools. The
diagnosis is made by looking for reducing substances in the stool following carbohydrate
ingestion. Clinitest tablets (which detect reducing substance in the stool) are used as the
standard test, the detection of more than 0.5% is significant. Formal confirmation of the
specific offending carbohydrate is through stool chromatography. Treatment is with a
lactose-free formula in infancy and a reduced lactose intake in later childhood.
Following gastroenteritis, carbohydrate intolerance can be either to disaccharides or mono-
saccharides. It is usually in children who have been infected with rotavirus. Both types of
intolerance are usually transient and both respond to removal of the offending carbohydrate.
Both mono- and disaccharide intolerance will result in tests for reducing substances in the
stool being positive.
Glucose-galactose malabsorption
This is a rare autosomal recessively inherited condition, characterized by rapid-onset watery
diarrhoea from birth. It responds to withholding glucose (stopping feeds) and relapses on
reintroduction. f i e diagnosis is essentially a clinical one. Reducing substances in the stool
will be positive and small-bowel biopsy and disaccharide 'estimation will be normal.
Treatment is by using fructose as the main carbohydrate source. Fructose is absorbed by a
different mechanism to glucose and galactose.
Sucrase-isomaltase deficiency
This is a defect in carbohydrate digestion, with the enzyme required for hydrolysis of
sucrose and alpha-limit dextrins not present in the small intestine. Symptoms of watery
diarrhoea andlor faltering growth develop after the introduction of sucrose or complex
carbohydrate into the diet.
Symptoms can be very mild
Reducing substances in the stool are negative (non-reducing sugar)
Diagnosis is by stool chromatography. Management is by removal of sucrose and complex
carbohydrate from the diet.
Essential Revision Notes in Paediatrics h r the MRCPCH 2nd Edition
Faecal calprotedin
Neutrophil protein
Stable in faeces
Found in both adults and children to be a simple and non-invaiive measure of bowel
inflammation
Faecal elastase
Pancreas-specific enzyme which is stable during intestinal transport
Stable in faeces
Reliable indirect marker of pancreatic function
False-positives in short gut and bacterial overgrowth
5. GASTRO-OESOPHAGEALREFLUX
Gastro-oesophageal reflux i s common and implies passage of gastric contents into the lower
oesophagus. It i s a normal physiological phenomenon. It is common in infancy and is also
seen in older children and adults, particularly after meals. It is secondary to transient
relaxation of the lower oesophageal sphincter not associated with swallowing.
Differential diagnosis of gastro-oesophagealreflux
Infection, e.g. urinary tract infection, gastroenteritis
Intestinal obstruction, e.g. pyloric stenosis, intestinal atresia, malrotation
Food allergy and intolerance, e.g. cowsf milk allergy, soy allergy, coeliac disease
Metabolic disorders, e.g. diabetes, inborn errors of metabolism
Psychological problems, e.g. anxiety
Drug-induced vomiting, e.g. cytotoxic agents
Primary respiratory disease, e.g. asthma, cystic fibrosis
. Sleep disturbance
Neurobeha
events
toms - breath hol
% of time pH < 4
I Mild reflux 5-10
Moderate reflux 10-20
Severe 20-30
Simple measures
Explanation and reassurance
Review of feeding posture
Review of feeding practice, e.g. too frequent feeds, large volume feeds
Use of feed thickeners or an anti-reflux milk
Older children
Life-style and diet
Avoid excess fat, chocolate, tea, coffee, gaseous drinks
Avoid tight-fitting clothes
Specific treatment
Antacids
Acid suppression
HZblockers, e.g. ranitidine
Proton-pump inhibitors, e.g. omeprazole, lansoprazole
Prokinetic drugs
Metoclopramide
Domperidone
Gastroenterology and Nutrition
Erythromycin
Cisapride
Cisapride is no longer licensed for use in children because of anxieties about potential
cardiotoxicity. It can still be used on a named patient basis but seldom is.
Surgery is required for reflux resistant to medical treatment. High-risk groups include those
with neurodisability or intractable respiratory symptoms exacerbated by reflux.
Requires aggressive medical treatment, regular endoscopic assessment and because the
risk of malignancy is felt to relate to the extent of persistent exposure of the distal
oesophagus to acid, surgery is often considered
Notes
7. CHRONIC DIARRHOEA
Chronic diarrhoea refers to diarrhoea that has persisted for more than 2-3 weeks. Children
with chronic diarrhoea and faltering growth need further assessment as the underlying
cause may be a malabsorption.
Small-bowel biopsy
Usually performed through a gastroscope - previously via a Crosby capsule
Coeliac disease results in total villous atrophy with characteristic features (see Section
7.1); partial villous atrophy, which is less commonly seen, has a wide differential
diagnosis
free diet itself has no long-term complications, although in the young child its use should
be supervised by a paediatric trained dietitian.
The standards for the diagnosis of coeliac disease are set out by the European Society of
Paediatric Gastroenterology. Diagnosis is confirmed by characteristic histology and a clinical
remission on a gluten-free diet. There are indications for a subsequent gluten challenge and
these include initial diagnostic uncertainty and when the diagnosis is made under the age '
of 2 years. The latter being because at that age there are other causes of a flat jejunal biopsy
(see above). A gluten challenge involves an initial control biopsy on a gluten-free diet
followed by a period on gluten with a repeat biopsy after 3-6 months and then again after
2 years, sooner if symptoms develop. The response to a challenge can be monitored by
antibody screening. There are reports of late relapse following gluten challenge.
Antibody testing in the screening of children with faltering growth or other gastrointestinal
symptoms in whom coeliac disease is a possibility and in the ongoing management of
children with coeliac disease is helpful. The biopsy, however, currently remains the 'gold
standard' for diagnosis.
7.3 Giardiasis
Ciardia is a protozoal parasite which is infective in the cyst form. lt also exists in the
trophozoite form and is found in contaminated food and water.
Clinical manifestations vary; can be asymptomatic, acute diarrtioeat disease, chronic
diarrhoea. Partial villous atrophy is occasionally seen
Diagnosis is by stool examination for cysts or examination of the duodenal aspirate at
small-bowel biopsy
Treatment is with metronidazole and is often given blind in suspicious cases
with symptom-free periods, periumbilical, lasts 1-3 hours, type of pain (e.g. burning,
stabbing) unclear, rarely causes a child to wake from sleep, not usually related to meals,
activity or bowel movement. Loose diagnostic criterion is three or more episodes in
3 months. Pain interferes with normal activity, e.g. results in time off school. Extraintestinal
symptoms common (e.g. headache). Family history common. Child often offered positive
reinforcement for symptoms.
Normal examination. Normal investigations.
Associations
Timid, nervous anxious characters
Perfectionists - over achievers
Increased number of stresses and more likely to internalize problems than other
children, but no increase in the risk of depression or other psychiatric problems when
compared with children with organic pain
School absence common - may be a degree of school refusal - may be issues at
school
Remember children with organic pathology can suffer from non-organic pain and children
with non-organic pain can also have organic pathology.
Colitis can be indeterminate, i.e. the histological features are consistent with inflammatory
bowel disease but not diagnostic of either Crohn's disease or ulcerative colitis.
Essential Revision Notes in Paedi'ltr-ic-s tilr the IL1KC:PC 'H 2nd Edition
Cytarnegalovirus
Entamoeba histoq.tca
Causes of noh-infective coliti
utcerative c'olitis
~rohn'sdisease
Necrotizing enterocolitis
Microscopic colitis
.Beh~etdiskse
Food allergic colitis
Enterobius ve~icularis
- 1
10.2 Intussusception
Peak incidence aged 6-9 months. Male to female ratio 4 : 1 -
Usually presents with spasmodic pain, pallor and irritability. Vomiting is an early feature
and rapidly progresses to being bile stained. Passage of blood-stained stools often occurs
and a mass is frequently palpable. The presentation, however, is often atypical
The intussusception is usually ileocaecal, the origin being either the ileocaecal valve or
the terminal ileum
An identifiable cause is commoner in those who present later - Meckel's diverticulum,
polyp, reduplication, lymphosarcoma and Henoch-Schonlein purpura being examples.
Diagnosis is usually on clinical grounds. Confirmation is by plain abdominal X-ray,
ultrasound or air-enema examination.
Treatment is either with air-enema reduction if the history is short or surgically at
laparotomy. Resuscitation with saline is often required. Contraindications to air enema
include peritonitis and signs of perforation.
Essential Revision Notes in R?edj,?tric*stor the h1RCIPCIH 2nd Editinn
10.4 Polyposis
Juvenile polyps
These make up 85% of the polyps seen in childhood. Present at age 2-6 years with pain-
less blood per rectum. Most polyps are solitary and located within 30 cm of the anus.
Not premalignant. Juvenile polyposis refers to multiple juvenile polyps and can be
premalignant.
!
1
I Peutz- Jeghers syndrome
i Autosomal dominant inheritance. Diffuse gastrointestinal hamartomatous polyps associated
f
I
F
i
i1 11. GASTROENTERITIS
/I
i
Gastroenteritis is a common problem. The majority of cases can be managed at home. Oral
rehydration therapy is the mainstay of treatment, with rapid rehydration over 4-6 hours with
ij reassessment and the early reintroduction of normal feeds after that. Breast-feeding should
not be stopped. Antimicrobials are only of use in very specific circumstances. Antidiarrhoeal
1 agents are of no use. Complications such as carbohydrate intolerance and chronic diarrhoea
1 and faltering growth are relatively rare.
treatment. European ORS contain between 35 and 60 mmol/l sodium with varying concen-
trations of glucose and potassium. There remains controversy over the best combination but
it would appear that all of the available formulations are effective and safe. Home-made
solutions, usually with an excess of salt, put children at risk of hypernatraemic dehydration.
Causes of gastroenteritis
Unknown - in both the developed and developing world, no pathogens are identified
in up to 50' of cases, even when the condition is fully investigated
Viral - rotaviruses (commonest), adenovirus, small-round viruses and astroviruses
Bacterial - Campylobacter spp. (commonest), Shigella spp., Salmonella spp.,
enteropathogenic E. coli, enterotoxigenic E. coli 0157:H7 (rare but associated with
haemolytic-uraem ic syndrome), Vibrio cholerae, Yersinia enterocolitica
Protozoa - Cryptosporidium sp. (particularly in the immunocompromised host),
Giardia sp., which has a varied presentation ranging from the asymptomatic carrier state
to chronic diarrhoea with growth failure, Entamoeba histolytica (amoebic dysentery)
Differential diagnosis
This is potentially wide and includes many other potential conditions including:
Other infections, e.g. otitis media, tonsillitis, pneumonia, septicaemia, urinary tract
infection, meningitis
Gastro-oesophageal reflux
Food intolerance
Haemolytic-uraemic syndrome
lntussusception
Pyloric stenosis
Acute appendicitis
Drugs, e.g. laxatives, antibiotics
Essentia 1 Revision Notes in Paecli,?trics for the MKCPCIH 2nd Edition
Remember
Less than 3% of dehydration is clinically not apparent
A normal capillary refill time (<2 seconds) makes severe dehydration very unlikely
(measured by pressing the skin and measuring the time taken for the skin to re-perfuse)
Useful signs include reduced skin turgor, dry oral mucosa, sunken eyes and altered
consciousness level
12. CONSTIPATION
Childhood constipation is common. Most children do not have an underlying cause and
their constipation is functional.
Many factors can trigger constipation including:
lntercurrent illness with poor fluid and food intake
Perianal pathology such as anal fissure or streptococcal infection resulting in stool
withholding
Difficult early toilet training resulting in stool withholding
If associated with a mega rectum then soiling is common. A plain abdominal X-ray may be
helpful in the assessment of such patients with the potential to assess severity and extent.
This can be helpful particularly in the obese patient when clinical assessment is often
difficult. The soiling occurs because the normal sensory process of stool being in the
rectum, resulting in distension and the urge to defecate, is lost when the rectum is
permanently distended. This should be distinguished from encopresis in which stool is
passed in to the pants at inappropriate times and in inappropriate places with no underlying
constipation - the latter being a primarily psychological problem.
Gc2sfroentc3rol o 7' ncl Nulrition
Underlying physical causes need to be considered for the purpose of the examination,
including Hirschsprung disease, endocrine causes such as thyroid disease and meconium
ileus equivalent or distal intestinal obstruction syndrome seen in children with cystic
fibrosis.
Hirschsprung disease is very rare in children who have at some stage of their life had a
normal bowel habit and usually presents in the neonatal period.
Most constipation is short term and is readily treated with bulk and/or stimulant laxatives.
The management of chronic functional constipation is more difficult and often requires a
multidisciplinary approach. Many factors are often involved in the perpetuation of the
problem including local pathology such as anal fissure, lower abdominal pain, poor diet,
poor fluid intake, lack of exercise, previous difficult toileting experiences, and psychosocial
problems. High doses of stimulant and bulk laxatives are required, usually for a prolonged
period. Enema therapy, which can reinforce difficult toi leting experiences, should be
reserved for the more difficult cases. An essential part of management is explanation and
reassurance and practical advice and support in the institution of a toileting regimen.
Children need to sit on the toilet regularly, this is best 15-30 minutes after meals.
Commonly used laxatives include lactulose, sodium docussate, Senokot, sodium picosul-
phate. Enemas are occasionally required but can exacerbate the stool withholding cycle.
Constipation is common in children with nocturnal and diurnal enuresis and treatment of
the constipation frequently results in a significant improvement in the wetting.
Usually presents in infancy, failure to pass meconium with presentation in the older
child being rare - the diagnosis in this group usually being chronic functional
constipation; most children with Hirschsprung will have never had a normal bowel
habit
Enterocolitis commonly can occur before or after surgery
Definitive test is by rectal biopsy to confirm the absence of ganglion cells in the
submucosal plexus; histochemistry will demonstrate excessive acetylcholinesterase
activity and the absence of ganglion cells
Surgery is excision, usually with temporary colostomy followed by pull-through at a
I
later stage
I
1 Ultrashort-segment Hirschsprung disease is very rare and can present significant
diagnostic difficulty
,
I
13. FURTHER READING
I
Ball PA, Booth IW, Holden CE, Puntis JW (Eds). 1998. Paediatric Parenteral Nutrition, 3rd
I
edn. Pharmacia and Upjohn Nutrition.
Bremner AR, Beattie RM. 2002. Therapy of Crohn's disease in childhood. Expert Opinion in
I
I Pharmacotherapy 37, 809-25.
1 Goulet 0, Ruemmele F, Lacaille F, Colomb V. 2004. Irreversible intestinal failure. Journal of
j' Paediatric Gastroenterology and Nutrition 38, 2 50-69.
i I
Preedy V, Grimble C, Watson R (Eds). 2001 . Nutrition in the infant: Problems and Practical
Procedures. Greenwich Medical Media Ltd.
Plunkett A, Beattie RM. 2005. Recurrent abdominal pain in childhood. Journal of the Royal
Society of Medicine 98; 101 -6.
Shulman R, Phillips S. 2003. Parenteral nutrition in infants and children. Journal of
Paediatric Gastroenterology and Nutrition 36, 587-607.
Walker WA, Goulet 01, Kleinman RE, Sherman PM, Schneider BL, Sanderson IR (Eds).
2004. Paediatric Gastrointestinal Disease. Pathophysiology, Diagnosis and Management, 4th
edn. BC Decker Inc.
Wal ker-Smith JA, Murch SH. 1999. Diseases of the Small Intestine in Childhood, 4th edn.
lsis Medical Media.
Wyllie R, Hyams JS (Eds). 2006. Paediatric Gastrointestinal and Liver Disease, 3rd edn.
Elsevier.
Chapter 10
Genetics
Louise Wilson
CONTENTS
1. Chromosomes
1.1 Common sex chromosome aneuploidies
1.2 Common autosomal chromosome aneuploidies
1.3 FISH testing
1.4 Microdeletion syndromes
1.5 Genetic counselling in chromosomal disorders
2. Mendelian inheritance
2.1 Autosomal dominant (AD) conditions
2.2 Autosomal recessive (AR) conditions
2.3 X-linked recessive (XLR) conditions
2.4 X-linked dominant (XLD) conditions
2.5 Constructing a pedigree diagram (family tree)
3. Molecular genetics
3.1 DNA (Deoxyribonucleic acid)
3.2 RNA (Ribonucleic acid)
3.3 Polymerase chain reaction (PCR)
3.4 Reverse Transcription PCT (rt PCR)
5. Mitochondria1 disorders
6. Genomic imprinting
7. Genetic testing
9. Fetal teratogens
9.1 Maternal illness
9.2 Infectious agents
9.3 Other teratogens
1. CHROMOSOMES
Background
Within the nucleus of somatic cells there are 22 pairs of autosomes and one pair of sex
chromosomes. Normal male and female karyotypes are 46,XY and 46,XX respectively. The
normal chromosome complement of 46 chromosomes is known as diploid. Genomes with
a single copy of each chromosome or three copies of each are known respectively as
haploid and triploid. A karyotype with too many or too few chromosomes, where the total
is not a multiple of 23, is called aneuploid.
Chromosomes are divided by the centromere into a short 'p' arm ('petit') and a long 'q'
arm. Acrocentric chromosomes (13, 14, 15, 21, 22) have the centromere at one end.
Lyonization is the process whereby in a cell containing more than one X chromosome, only
one is active. Selection of the active X chromosome is usually random and each inactivated
X chromosome can be seen as a Barr body on microscopy.
Mitosis occurs in somatic cells and results in two diploid daughter cells with nuclear
chromosomes which are genetically identical both to each other and the original parent cell.
*
I
@j)
Homologous chromosomes
align independently on the spindle
Mitosis
355
Essentic21Revision Notes in Paediatrics tor the MRCIPCH 2nd Edition
Meiosis occurs in the germ cells of the gonads and is also known as 'reduction divisionr
because it results in four haploid daughter cells, each containing just one member (homo-
logue) of each chromosome pair and all genetically different. Meiosis involves two divisions
(meiosis I and 11). The reduction in chromosome number occurs during meiosis I and is
preceded by exchange of chromosome segments between homologous chromosomes called
crossing over. In males the onset of meiosis and spermatogenesis is at puberty. In females,
replication of the chromosomes and crossing over begins during fetal life but the oocytes
remain suspended prior to the first cell division until just before ovulation.
Meiosis II
Chromatids move to opposite poles
and the cells divide
010 chromosomes align on
spindle
4 haploid daughter
cells, all genetically
different
-
Meiosis
Translocations
Reciprocal - exchange of genetic material between non-homologous chromosomes
Robertsonian - fusion of two acrocentric chromosomes at their centromeres, e.g.
(1 4;2 1 )
Unbalanced - if chromosomal material has been lost or gained overall
Balanced - if no chromosomal material has been lost or gained overall
Carriers of balanced translocations are usually phenotypically normal but are at increased
risk for having offspring with chromosomal imbalance.
Carriers of a Robertsonian translocation involving chromosome 21 are at increased risk of
having offspring with translocation Down syndrome. For female and male (14;21) transloca-
tion carriers the observed offspring risks for Down syndrome are -15O/0 and 5%, respec-
tively. Remember, they can also have offspring with normal chromosomes or offspring who
are balanced translocation carriers like themselves.
Genetics
47,XYY males
These males are phenotypically normal but tend to be tall. Intelligence is usually within
normal limits but there is an increased incidence of behavioural abnormalities.
Essential Revision Nntcls in Pnedi,?trir-sk ~ the
r MRC-PC'H 2r1d Edition
2. MENDELIAN INHERITANCE
1 2.1 Autosomal dominant (AD) conditions
These result from mutation of one copy of a gene carried on an autosome. All offspring of
an affected person have a 50% chance of inheriting the mutation. Within a family the
severity may vary (variable expression) and known mutation carriers may appear clinically
normal (reduced penetrance). Some conditions, such as achondroplasia and neurofibroma-
tosis type 1, frequently begin de novo through new mutations arising in the egg or (more
commonly) sperm.
Y I
, 2.2 Autosomal recessive [AR] conditions
I 1
1
These result from mutations in both copies of an autosomal gene. Where both parents are
carriers, each of their offspring has a 1 in 4 (25%) risk of being affected, and a 2 in 4 (5O0/0)
, chance of being a carrier.
Examples of autosomal recessive conditions:
Al kaptonuria Glycogen storage diseases
Ataxia telangiectasia Homocystinuria
$-Thalassaemia Haemochromatosis
Congenital adrenal hyperplasias Mucopolysaccharidoses (a1l except Hunter)
Crigler-Najar (severe form) Oculocutaneous albinism
Cystic fibrosis
Dubin-Johnson
Fanconi anaemia
Galactosaemia
GIucose-6-phssphatase
deficiency (von Gierkes)*
*Donot confuse with glucose-&phosphate dehydrogenase deficiency (favism) which is X-linked recessive.
0 Sex unspecified
w - o o r q l / q Separated or divorced
Affected male
?
Proband (propositus)
db Dizygotic twins (one female, one male)
3. MOLECULAR GENETICS
3.1 DNA (Deoxyribonucleic acid)
DNA is a double-stranded molecule composed of purine (adenine + guanine) and
pyrimidine (cytosine and thymine) bases linked by a backbone of covalently bonded
deoxyribose sugar phosphate residues. The two anti-parallel strands are held together by
hydrogen bonds which can be disrupted by heating and reform on cooling:
Adenine (A) pain with thymine by two hydrogen bonds
Guanine (G) pain with cytosine (C) by three hydrogen bonds
Mutation detection
Single cell PCR of in vitro fertilised embryo to diagnose genetic disease before
implantation
Detection of viral and bacterial sequences in tissue (Herpes Simplex Virus in CSF,
Hepatitis C, HIV in peripheral blood, meningococcal strains).
Genetics
4
Cool to - 55°C to allow annealing of primers
primer -
- primer
r
after 1 PCR cycle
t
........................ :.-..-.Target sequence ................................
5. MITOCHONDRIAL DISORDERS
Mitochondria are exclusively maternally inherited, deriving from those present in the
cytoplasm of the ovum. They contain copies of their own circular 16.5-kilobase chromo-
some carrying genes for several respiratory chain enzyme subunits and transfer RNAs.
Mitochondria1genes differ from nuclear genes in having no introns and using some different
amino acid codons. Within a tissue or even a cell there may be a mixed population of
normal and abnormal mitochondria known as heteroplasmy. Different proportions of
abnormal mitochondria may be required to cause disease in different tissues, known as a
threshold effect. Disorders caused by mitochondrial gene mutations include:
MELAS (mitochondrial encephalopathy, lactic acidosis, stroke-like episodes)
MERRF (myoclonic epilepsy, ragged red fibres)
Mitochondrially inherited diabetes mellitus and deafness
Genetics
6- GENOMIC IMPRINTING
For most genes both copies are expressed but for some genes, either the maternally or
paternally derived copy is preferentially used, a phenomenon known as genomic imprint-
ing. The best examples are the Prader-Willi and Angelman syndromes both caused by
either cytogenetic deletions of the same region of chromosome 15q or by uniparental
disomy of chromosome 15 (where both copies of chromosome 15 are derived from one
parent with no copy of chromosome 15 from the other parent).
2
3 < I
Beckwith-Wiedemann syndrome
Prenatal onset macrosomia, facial naevus flammeus, macroglossia, ear lobe creases, pits on
the ear helix, hemihypertrophy, nephromegaly, exomphalos (omphalocele) and neonatal
hypoglycaemia. There is an increased risk of Wilms tumour, adrenocortical and hepatic
tumours in childhood. The condition appears to result from abnormalities of chromosome
11p15 which contains several imprinted genes including the KF-2 (insulin-like growth
factor 2) gene. r'
A
'7, GENETIC TESTING
Genetic tests can be thought of as diagnostic, predictive or for carrier status. Informed
verbal, and increasingly written, consent (or assent) should be obtained prior to genetic
testing.
Diagnostic tests
Those where the diagnosis is already suspected on clinical grounds but genetic testing is
useful for confirmation, or for counselling or predictive testing in the wider family.
hedictive tests
When an individual is clinically normal but is at risk for developing a familial disorder.
Predictive testing is not usually offered without a formal process of genetic counselling over
more than one consultation with time built in for reflection. Where there are intervening
relatives whose genetic status may be indirectly revealed there are additional issues which
must be taken into consideration. Written consent for predictive testing is required by most
laboratories. Nationally agreed guidance is that predictive testing in children for disorders
which have no implications in childhood should not be undertaken until the child is old
enough to make an informed choice.
Carrier tests
These are usually undertaken in autosomal recessive or X-linked recessive disorders where
the result has no direct implications for the health of the individual, but is helpful in
determining the risks to their offspring. Carrier status may be generated as a by-product of
diagnostic or prenatal testing. National guidance is that specific testing for carrier status
should be avoided in children until they are old enough to make an-informedchoice.
I
I
I
8.1 Ambiguous genitalia
Normal development of the reproductive tract and external genitalia
i
A simplified outline is shown below.
i
3
I
1
I
N 1
-2 , Genetics
0'
TESTES , undifferentiated
gonads
v
0 @ \
.c
I
regress Mullerian ducts FALLOPIAN TUBES
I
UPPER VAGINA
i p
dihydro- I
testosterone
I EPlDlDYMlS
I
I SEMINAL
wolffian ducts
b- . regress
I VESICLES
1-,,-,,,--
I
undifferentiated * FEMALE
external genitalia GENITALIA
* by default
Outline of the normal development of the reproductive tract and external genitalia
The 6-week embryo has undifferentiated gonads, Mullerian ducts (capable of developing
into the uterus, Fallopian tubes and upper vagina), Wolffian ducts (capable of forming the
epididymis, vas deferens and seminal vesicles) and undifferentiated external genitalia.
In the presence of a Y chromosome the gonads become testes which produce testosterone
and Mullerian inhibiting factor (MIF). Testosterone causes the Wolffian ducts to persist and
differentiate and, after conversion to dihydrotestosterone (by 5a-reductase), masculinization
of the external genitalia. MIF causes the Mullerian ducts to regress.
In the absence of a Y chromosome the gonads become ovaiies which secrete neither
testosterone nor MIF and in the absence of testosterone the Wolffian ducts regress and the
external genitalia feminize. In the absence of MIF, the Mullerian ducts persist and
differentiate.
The causes of ambiguous genitalia divide broadly into those resulting in undermasculiniza-
tion of a male fetus, those causing masculinization of a female fetus, and those resulting
from mosaicism for a cell line containing a Y chromosome and another which does not.
They are summarized in the diagram below.
abnormal 46, XY 46,XX
UNDERMASCULINIZED MASCULINIZED
MALE FEMALE
NB. Complete testicular failure and complete androgen insensitivity (=testicular feminization
syndrome) cause apparently normal female genitalia.
In around one-third of boys with Duchenne muscular dystrophy, the condition has arisen as
a new mutation.
NFS NF2
Major features a 6 Cafe-au-lait patches Bikteral acoustic neurorn
Axillary/inguinal freckling (vestibular schvvannom
Lisch nodules on the iris Other-cmnidia d spinal tu
Peripheral neurofibromas
Minor features Macrocephaly Caf6-au-lait patches (usually
Short stature Peripheral schwannomas
P l e x i f m neuromas
Striae
8.7 Homocystinuria
(see also Chapter 15 - Metabolic Medicine)
This is most commonly the result of cystathione-P-synthase deficiency and causes a Marfan-
like body habitus, lens dislocation (usually down), mental handicap, thrombotic tendency
and osteoporosis. Treatment includes a low methionine diet +I- pyridoxine.
8.9 Achondroplasia
A short-limb skeletal dysplasia resulting from specific autosomal dominant mutations in the
FGFR3 (fibroblast growth factor receptor 3) gene on chromosome 4: There is a high new
mutation rate. Important complications are hydrocephalus, brain-stem or cervical cord
compression resulting from a small foramen magnum, spinal canal stenosis, kyphosis and
sleep apnoea.
3 74
.K
Genetics
9. FFTAL TERATOGENS
9.1 Maternal illness
Maternal diabetes
Maternal diabetes is associated with fetal macrosomia, neonatal hypoglycaemia and in-
creased risk of a wide variety of malformations, particularly cardiac (transposition of the
great arteries, aortic coarctation, septa1 defects, cardiomyopathy), vertebral (sacral abnorm-
alities, hemivertebrae), renal (agenesis, duplex collecting systems), intestinal (imperforate
anus, other atresias), limb abnormality (short femurs, radial ray abnormalities).
Fetal toxoplasmosis
lnfection with Toxoplasma, a protozoan, may be associated with microcephaly, hydroce-
phalus, intracranial calcification, chorioretinopathy, and mental handicap.
Fetal rubella
lnfection with rubella virus is most often associated with deafness particularly in the first
and early second trimesters, but cardiac abnormalities (persistent ductus arteriosus, periph-
eral pulmonary stenosis, septal defects), microcephaly, chorioretinopathy, cataract, and
learning disability are also associated.
CONTENTS
1. Haemoglobin
1.1 Haemoglobin synthesis
1.2 Red cell physiology
1.3 Oxygen-dissociation curve
2. Haemoglobin abnormalities
2.1 Thalassaemia
2.2 Sickle-cell disease (SCD)
2.3 Other haemoglobinopathies
5. Anaemia
5.1 Iron deficiency anaemia
5.2 Aplastic anaemia
5.3 Hereditary haemolytic anaemias
5.4 Haemoglobin defects
8. Platelets
8.1 Thrombocytopenia
8.2 Immune thrombocytopenic purpura
Essential Revision Notes in E2edintrics for the .kIRCP<.Yf2r7d Edifior-,
9. Blood film
9.1 Approach to a blood film at MRCPCH level
10. Coagulation
10.1 Natural anticoagulants
10.2 Coagulation disorders
Glycine
Haem synthesis
Glucose
I n fiNAoPH
+ uj
G 6-P *
I Hexose
i
F 6-P *
monophosphate
shunt
The Embdim-Meyerhof and
associated pathways
M ~ C NAD
Met Hb NADH
d 2,3-DPG, 2,3-diphosphoglycerate;
ATP 1 F 6-P, fructose 6-phosphate;
F 1,6-DP, fructose 1,6-diphosphate;
m G 6-P, glucose 6-phosphate;
Pyruvate
G 6-PD,glucose 6-phosphate
1
Lactate
dehydrogenase;
Met Hb, methaemoglobin;
PK, protein kinase
When oxygen is unloaded from a molecule of oxygenated haemoglobin, the F-chains open
up, allowing 2,3-DPG to enter. This results in the deoxygenated haemoglobin having a low
affinity for oxygen, preventing haemoglobin from stealing the oxygen back from the tissues.
This 2,3-DPG-related affinity for oxygen gives the oxygen-dissociation curve its nearly
sinusoidal appearance rather than that of a straight line.
Factors that cause this dissociation curve to shift are summarized in the figure below.
Factors shifting the oxygen-dissociation curve: HbF, fetal haemoglobin; HbS, sickle-cell
haemoglobin
Shift of the curve by changes in the blood C 0 2 is important to enhance oxygenation of the
blood in the lungs and also to enhance the release of oxygen from the blood to the tissues.
This is the Bohr effect.
As COz diffuses from the capillaries into the alveoli within the lungs, p(C02) is reduced and
the pH increases. Both of these effects cause the curve to shift left and upwards. Therefore
the quantity of oxygen that binds with the haemoglobin becomes considerably increased,
so allowing greater oxygen transport to the tissues. When the blood reaches the capillaries
the exact opposite occurs. The C 0 2 from the tissues diffuses into the blood, decreasing the
pH and causing the curve to shift to the right and downwards; that is, the curve shifts to the
right in the tissues and to the left in the lungs.
and thalassaemia genes are allelomorphic (different genes can occupy the same locus on a
chromosome) - which is the reason why mixed haemoglobinopathies can occur in one
patient. For example, HbS and thalassaemia may occur in one patient.
2.1 Thalassaemia
Thalassaemia results from a genetically determined imbalanced production of one of the
globin chains. a-, (3-, a- and y-globin chains make up normal fetal and adult haemoglobin
in the following combinations:
Fetal Hb:
HbF -a* + yz
HbBarts-y4
Adult Hb:
HbA-a2 + P2 (97%)
HbA2 -a2 + 02 (2.5%)
Chelation treatment
The challenge here is to balance the complications of iron overload (cardiac failure is the
leading cause of death) with the inherent challenges of desferrioxamine, currently the
chelating agent of choice although not an ideal drug. It is not absorbed orally, it has an
extremely short half-life, it is expensive and it has significant complications. It is estimated
that approximately two-thirds of the world's 72,000 patients with thalassaemia do not have
access to desferrioxamine. As a result, the search for a less toxic, more affordable and more
effective chelator continues. Although promising, the benefit of the new oral chelator
Deferiprone ( L l ) remains controversial despite it being licensed for use in the European
Union but not in North America.
When to initiate chelation therapy remains unclear but it is recommended that a liver
biopsy is performed after 1 year of a transfusion programme to establish the iron burden.
Serum ferritin, although helpful, is not entirely accurate especially at the high levels seen in
such patients.
Curative treatment
Bone marrow transplant remains the only curative option but this treatment option must be
carefully balanced against the morbidity (and significant mortality) associated with allo-
geneic transplantation. Lawson (see further reading) report on 55 children with P-thalassae-
mia who received allogeneic bone marrow transplants in two major UK centres over the
10-year period between 1991 and 2001 who had 8-year overall survival and thalassaemia-
free survival rates of 95% and 82% respectively. The thalassaemias are likely to benefit from
specific gene therapies in the future although to date no such treatment option is available.
Aplastic crisis
Occurs when red cell production is temporarily reduced while the ongoing haemolytic
process continues - resulting in severe anaemia. Parvovirus is usually the aetiological
agent. The haemoglobin can fall to 3 gldl and is the cause of presentation - malaise,
lethargy, syncope and congestive heart failure. Urgent transfusion is necessary but must be
performed slowly because the patient may develop cardiac failure acutely.
Stroke
Stroke occurs in 5-10% of people with SCD, with the highest risk being between the ages
of 1 and 9 years. Treatment should follow the general principles for SCD - infection
control, oxygen, hydration and blood parameters. In addition, an exchange transfusion is
indicated as soon as possible.
Hb C disease
Is the result of a substitution of lysine for glutamic acid in the P-globin chain at the same
point as the substitution in HbS
Milder clinical course than HbS
Prevalent in West Africa
Hb O and Hb E disease
Hb D is prevalent on the north-west coast of India, while Hb E is in south-east Asia -
both demonstrate mild anaemia only
Sickle-cell-Hb C disease
Typically has a similar clinical picture to that of HbS, although-fewer infections and
fewer crises are described
Associated with avascular necrosis of the femoral head and-iascular retinal changes
Asplenia
Definition - loss of splenic function can be partial (splenic hypofunction) or complete
(asplenia)
Causes - surgical resection of the spleen, autosplenectomy (due to infarction secondary
to haemoglobinopathy), congenital (e.g. lvemark syndrome (asplenia syndrome))
Management - there are four important management areas:
Penicillin is the antibiotic of choice - given twice a day. When to discontinue
prophylactic antibiotics remains controversial. Some centres discontinue at 5 years of
age while others continue for life
Appropriate immunization - routine immunization should be followed. In addition,
pneumococcal and meningococcal vaccination is recommended. For pneumococcal
vaccination in children < 2 years use conjugated heptavalent; in children 3 2 years
use 23 valent conjugated vaccination. For meningococcal vaccination use
polysaccharide quadrivalent vaccination (NB this does not offer protection against
Neisseria meningitidis serogroup B)
Aggressive management of suspected infection - patients with suspected infection
Essential Revision Notes in &edi,i trics tor thc hl RCf CH 2nd Edition
Group 0 A B AB
Genotype 00 AA or A 0 BB or BO AB
Antigens 0 A B AB
Naturally occurring anti-A and anti-B anti-A none
antibodies anti-B
Frequency in the U K 46% 42OO/ 9% 3OO/
Haematology and Oncology
Group 0 Group A
H 0 H 0
A m+ A W)
O v
0 antigen present but both A and B A carbohydrate called A antigen has
have no carbohydrate to cover the been produced to sit on the distal
immunogenic distal portions of their portion of A. B remains exposed
chains. Anti-A and anti-6 will therefore immunogenic - anti-6
therefore be produced. will be produced.
Group A 6
H 0 H 0
A m+ A m+)
P
bd
1
w
A carbohydrate called B antigen has Carbohydrates A and B have been
been produced to sit on the distal produced to sit on the distal portions
portion of B. A remains exposed of A and 6. No immunogenic distal
-
therefore immunogenic anti-A will portions are exposed therefore no
be produced. antibodies will be produced..
-
A, B, AB and 0 blood groups
Causes severe acute reaction with rapid onset of hypotension, rigors and circulatory
collapse
Clinical characteristics are in keeping with acute respiiatory distreis syndrome, therefore
treat as such
Caused by donor antibodies reacting with recipient's leukocyte
Patients are usually parous women
Anaphylactic reaction
A rare but life-threatening complication
Increased risk with transfusion containing large volumes of plasma, e.g. fresh-frozen
plasma or platelets
Clinical presentation - hypotension, bronchospasm, periorbital and laryngeal oedema,
vomiting, erythema, urticaria, conjunctivitis, dyspnoea, chest,abdominal pain
Occurs in patients pre-sensitized to allergen-producing immunoglobulin E (lgE)
antibodies, less commonly with IgG or IgA antibodies
5. ANAEMIA
Anaemia can be classified by decreased substrate, abnormal production and destruction of
red cells, as below.
Factory Product
The most common reason in infancy is the early weaning to cows' milk. Giving an infant
iron-supplemented formula milk instead of cows' milk not only prevents anaemia but
reduces the decline in developmental performance observed in those given only cows'
milk.
Classification o
Constitutional
Essential Revision Notes in Paediatrics for the MRCPCH 2nd Editiori
Steroids and/or anti-thy,mocyte globulin have some beneficial effects in a few cases. The
prognosis is invariably poor in severe cases, with bone marrow transplantation the only
viable treatment option available.
Membrane defects
Hereditary spherocytosis
Commonest hereditary haemolytic anaemia in north Europeans
Autosomal dominant
Complex defect but involves the spectrin structural protein
Diagnosis made on appearances of blood film - the presence of spherocytes identified
by demonstrating that the cells are osmotically active using the osmotic fragility test
The serum bilirubin and lactate dehydrogenase (LDH) may be elevated
Treatment, by splenectomy, is reserved for severe cases
Hereditary elliptocytosis
Usually autosomal dominant
Most cases are asymptomatic
-
-
-
-
-
-
E
-
-
=
Infections, especially parvovirus, can produce dramatic haemolysis
9.
-
=
3
Splenectomy may be beneficial
=a
I
f 5.4 Haemoglobin defects
es See also Section 2 - Haemoglobin abnormalities.
i
f Autoimmune haemolytic anaemia (AIHA)
t
E
Coombs test (anti-human globulin) positive (see page 396)
g--
-
- Uncommon in childhood, but if present is usually the result of an intercurrent infection
1
s
- predominantly viral but occasionally mycoplasmal in origin
In the older child, AIHA may be a manifestation of a multisystem disease, e.g. systemic
lupus erythematusus (SLE)
Causes include drugs (high-dose penicillin), infections (non-specific viral, measles,
varicella, EBV), multisystem disease (SLE, rheumatoid arthritis) and lymphoproliferative
disease (Hodgkin lymphoma)
Can be divided into warm and cold types depending on the temperature at which the
causative cell-bound antibody i s best detected
Warm (usually IgG) - multisystem disease
Cold (usually IgM) - infective causes
Hypersplenism
The red cell lifespan is decreased by sequestration in an enlarged spleen for whatever
cause
Infections
Malaria
Septicaemia
Essential Revision Nc1tt.s in Piiedidtrics k ~ttatl
r kiKCPCH2nd Edition
Miscellaneous
Burns
Poisoning
Hyperphosphataemia
A-beta1ipoproteinaemia
T lymphocytes
lrnrnunocytes
-€ B lymphocytes
Leukocytes
Monocytes
Phagocytes
-€ Neutrophils
-€
Granulocytes
Eosinophils
Basophils
In addition, growth factors affect the function of the mature myeloid cells:
Optimizing phagocytosis, superoxide generation and cytotoxicity in the neutrophil
Optimizing phagocytosis, cytotoxicity and production of other cytokines in the
monocyte
Increasing membrane integrity and surface-adhesion properties of target cells
GM-CSF can immobilize phagocytes at local sites of inflammation thereby causing
accumulation at these sites
6.1 Neutrophils
Neutropenia
Neutropenia is defined as a reduction of the absolute neutrophil count below the normal
for age.
The normal range of white blood cell (WBC) and neutrophil counts for children at
different ages
Neutropenia can be divided according to the severity, indicating the likely clinical
consequences:
Mild - 1.O- 1.5 (1o9/I)- Usually no problem
Moderate - 0.5-1.0 (1o9/I) - Clinical problems more common
Severe - < 0.5 (109/1) - Potentially severe and life-threatening, especially if prolonged
beyond a few days
Bacterial infections such as cellulitis, superficial and deep abscess formation, pneumonia
and septicaemia are the commonest problems associated with isolated neutropenia, while
fungal, viral and parasitic infections are relatively uncommon.
The typical inflammatory response may be greatly modified with poor localization of
infection, resulting in a greater tendency for infection to disseminate.
Although challenging in some cases, it is important to identify the cause of the neutropenia,
see following box, especially for the two following reasons:
1, Haernatology and Oncology
I
The clinical significance of the neutropenia will depend upon whether or not there is
underlying mirrow reserve
Identifying the cause can help in predicting the duration of the neutropenia and
therefore effect subsequent management
Marrow suppression (decreased production) will usually cause a severe neutropenia. The
majority of children treated with chemotherapy will be in this group. Increased consumption
or sequestration will cause mild to moderate neutropenia.
Shwachman syndrome
Chediak-Higashi syndrome
Cartilage hair hypoplasia
Dyskeratosis congenita
Essential Revision Notes in P;ledi~tricsh r the MKCPCH 2r1d Fdition
The risk of infection is directly proportional to the duration of neutropenia. If the duration of
neutropenia is predicted to be prolonged, preventive measures against possible future
infective episodes may be considered, for example:
Good mouth care and dental hygiene
Prophylaxis against Pneumocystis spp. (co-trimoxazole)
Prophylaxis against fungal infections (fluconazole)
Prophylaxis against recurrent herpes simplex virus infection (aciclovir)
Regular throat and rectal swabs looking for Gram-negative colonization
Dietary avoidance of unpasteurized milk and salads
Avoidance of inhaling building/construction dust because of the risk of acquiring
Aspergillus infection
Neutrophilia
The neutrophil count can be increased in one of the following three ways:
lncreased production of neutrophils as a result of increased progenitor cell proliferation
or an increased frequency of cell division of committed neutrophil precursors
Prolonged neutrophil survival within the plasma as a result of impaired transit into
tissues
lncreased mobilization of neutrophils from the marginating pools or bone marrow
Acute neutrophilia
Neutrophils can be mobilized very quickly, within 20 minutes of being triggered, from the
marginating pool. A stress response (acute bacterial infection, stress, exercise, seizures and
some toxic agents) releases adrenaline (epinephrine) from endothelial cells which decreases
neutrophil adhesion. This results in the neutrophils adhering to the endothelial lining of the
vasculature (the marginating pool) being dragged into the circulation.
The bone marrow storage pool responds somewhat slower (a few hours) in delivering
neutrophils in response to endotoxins, released from micro-organisms, or complement.
Corticosteroids may inhibit the passage of neutrophils into tissues, thereby increasing the
circulating number.
Chronic neutrophilia
The mechanism in chronic neutrophilia is usually an increased marrow myeloid progenitor-
cell proliferation. The majority of reactions last a few days or weeks. Infections and chronic
inflammatory conditions (e.g. juvenile chronic arthritis, Kawasaki disease) are the predomi-
nant stimulators of this reaction. Less common causes include malignancy, haemolysis or
chronic blood loss, burns, uraemia and post-operative states.
Splenectomy or hyposplenism may result in a reduced removal of increased neutrophils
from the circulation.
I Hdematology dnd Oncohgy
I
6.2 Eosinophils
Eosinophils enter inflammatory exudates and have a special role in allergic responses, in
defence against parasites and in removal of fibrin formed during inflammation. Eosinophils
are proportionately reduced in number during the neonatal period. The causes of eosino-
philia are extensive but some of the major causes are:
I
Allergic diseases, e.g. asthma, hay fever, urticaria
Parasitic diseases, e.g. worm infestation
Recovery from infection
Certain skin diseases, e.g. psoriasis, dermatitis herpetiformis
Ii Pulmonary eosinophilia
Drug sensitivity
,
Polyarteritis nodosa
Hodgkin disease
1
6.3 Basophils
Basophils, the least common of the granulocytes, are seldom seen in normal peripheral
blood. In tissues they become mast cells. They have attachment sites on their cell
membrane for IgE - which, when attaching, will cause degranulation to occur resulting in
the release of histamine.
6.4 Monocytes
Monocytes, the largest of the leukocytes, spend a short time in the bone marrow and an
even shorter time in the circulation (20-40 hours) before entering tissues where the final
maturation to a phagocyte takes place. A mature phagocyte bas a lifespan of months to
years.
Formation
The bone marrow and thymus are the two primary sites in which lymphocytes are
produced, not by specific antigens but by non-specific cytokines. Thereafter they undergo
specific transformation in secondary or reactive lymphoid tissue - the lymph nodes,
spleen, the circulating lymphocytes and the specialized lymphoid tissue found in the
respiratory and gastrointestinal tracts.
Diagrammatic illustration of immunocyte production
T cells are produced in the bone marrow and undergo transformation in the thymus,
whereas the exact location where the B lymphocytes are transformed remains unknown.
In peripheral blood 80% of the lymphocytes are T cells, while only 20% are B cells. T cells
are responsible for cell-mediated immunity (against intraceilular organisms and transplanted
organs). B cells and plasma cells (differentiated B cells) are responsible for humoral
immunity by producing immunoglobulins.
8 PLATELETS
Megakaryocytes, produced in the bone marrow, develop into platelets by a unique process
of cytoplasm shedding. As the megakaryocyte matures the cytoplasm becomes more
granular, these granules develop into platelets and are released into the circulation as the
cytoplasm is shed.
Platelet production is under the control of growth factors, particularly thrombopoietin and
1L-6, while GM-CSF and IL-3 have megakarocyte colony-stimulating factor (MG-CSF!
properties.
I
H,~emato/ogyand Oncology
The main function of platelets is the formation of mechanical plugs during the normal
haemostatic response to vascular injury.
8.1 Thrombocytopenia
A useful classification of thrombocytopenia is listed below.
ITP does not have a predictable course, although it usually follows a benign self-limiting
course. Approximately 20% of cases, in older girls predominantly, fail to remit over
6 months (chronic ITP).
Investigations
A bone marrow biopsy is not indicated in a typical case, but when the diagnosis is
uncertain it is a necessity
Autoantibodies against platelet surface glycoprotein can be commonly detected,
although they are neither a useful diagnostic test nor a useful prognostic indicator
Management
No clear benefit of inpatient management
Written information about ITP, sensible advice (avoidance of contact sports, what to do
in the event of an accident, etc.) and a contact person to call are usually sufficient
Treatment to raise the platelet count is not always required as the few remaining
platelets, even if profoundly low in number (< 10 x 1o9/I), function more efficiently.
The risk of serious bleeding from ITP, as compared to that from thrombocytopenia
related to marrow failure syndromes, is low
Less than 1% of cases suffer an intracranial haemorrhage. In a recent national audit in
the UK (performed over a 14-month period in 1995) no intracranial bleeds were
reported in 427 patients
Treatment includes the following modalities:
Steroids
Given at a dose of 1-2 mg/kg daily for up to 2 weeks. There is evidence that a higher dose
of 4 mg/kg for 4 days may raise the platelet count as quickly as IVIG.
Anti-D
This has been shown to be effective in children who are Rh-positive. It is a rapid single
injection, although it may cause significant haemolysis.
Splenectomy
Rarely required and is only indicated in a patient with chronic ITP who has significant
bleeding unresponsive to medical treatment. The failure rate after splenectomy is at
least 25%.
~aematologyand Oncology
Transfusions
Platelet transfusions are generally not indicated in ITP as it is a consumptive disorder.
Other agents
Vincristine, cyclophosphamide and cyclosporin have all been used with varying degrees of
success. The combination of cyclophosphamide and rituximab (an anti-CD20 antibody) is
currently demonstrating promising results.
Adhesion
Adhesion of platelets to the subendothelial lining requires interactions between platelet
membrane glycoproteins, elements of the vessel wall (e.g. collagen) and adhesive proteins
such as von Willebrand factor (vWF)and fibronectin.
Release reaction
Collagen exposure results in the release or secretion of the contents of platelet granules:
fibrinogen, serotonin, ADP, lysosomal enzymes, heparin-neutralizing factor. The cell mem-
brane releases an arachidonate derivative which transforms into thromboxane A2 - a
stimulus for aggregation as well as being a powerful vasoconstrictor.
PEndothellal cell 1
Platelet
Vasodilator Vasoconstrictor
platelet anti-aggregating agent platelet aggregating agent
1 - I
I- __-
Procoagulant activity
Functional platelet abnormalities -classification
Congenital
Defects of platelet membrane
@ Clanzmann thrombasthenia
rare, autosomal recessive, failure to aggregate, normal platelet count and
morphology
@ Bernard-Soulier syndrome
rare, autosomal recessive, failure of adhesion, no receptor to bind to vWF, giant
platelets, moderate platelet count reduction
Deficiency of storage granules
@ Wiskott-Aldrich syndrome
@ Chediak-Higashi syndrome
Defects of thromboxane deficiency
@ e.g. thromboxane synthetase deficiency
- cyclo-oxygenase deficiency
Acquired
@ Renal failure
@ Liver failure
Myeloproliferative disorders
Acute leukaemia, especially myeloid
@ Chronic hypoglycaemia
@ Drugs
@ Aspirin, non-steroidal anti-inflammatory drugs (NSAIDs), penicillin, cephalosporin,
sodium valproate
Investigations
A prolonged bleeding time and normal or moderately reduced platelet count are the
characteristic hallmarks of a congenitallhereditary platelet disorder (or von Willebrand
disease)
@ Platelet size followed by tests of aggregation and secretion in response to ADP, collagen,
arachidonate and ristocetin will be necessary
Esser-rtialRevision Notes in R7ediatrics tbr the MRCPCH 2nd Edition
9. BLOOD FILM
9.1 Approach to a blood film at MRCPCH level
I s the pathology in the red or white blood cell?
This is the first and most vital question you need to ask yourself when presented with a
blood film to interpret. Apart from the accompanying history being important in helping
you to answer this question, the other clue will be the number of white cells seen. If there is
an abundance of white cells the likelihood that the pathology will be in the white cells is
very high, and I will go as far as to say that acute lymphoblastic leukaemia will be top of
your differential diagnosis. If only an occasional white cell is seen then red cell pathology is
likely. Platelet pathology will be unlikely at MRCPCH level - the only real possibility is
one of giant platelets (same size as a red cell, or bigger) in Bernard-Soulier syndrome.
Shape
Sickle-shaped cells, as in sickle-cell disease
Fragments of red cells (e.g. helmet cells, etc.) indicative of microangiopathic haemolysis
such as in the haemolytic-uraemic syndrome
All different shapes, i.e. poikilocytosis as in thalassaemia, sickle-cell, iron deficiency
anaemia
Size
Small cells or microcytosis in iron deficiency anaemia
Large cells or macrocytosis in vitamin BIZ. andlor folatedeficient'anaemia
Different sizes: anisocytosis (haemoglobinopathies, anaemias)
COAGULATION
A representation of the coagulation cascades is shown below. It consists of an extrinsic
pathway (tissue thromboplastin is the initiator) and the intrinsic pathway (what happens in
the blood when it clots away from the body). These two pathways share a common final
pathway resulting in the production of a fibrin clot.
1
Factor XI1
Factor XI
Tissue
Factor IX
thromboplastin
Factor Vlll
Platelet phospholipid
Calcium
Factor VI I
1
Factor X
Factor V
Calcium
1
Factor I1 (Prothrombin)
rThr-in-l
Fibrinogen - Fibrin
(APTT)
(PT)
41 1
Revision Notes in P'ediatrics for the MRCPCH 2nd Edition
Essentic~l
The system can be divided into boxes, each box representing one of the following three
basic screening tests of coagulation:
Prothrombin time (PT) measures the extrinsic system and common pathway
Activated partial thromboplastin time (APTT) measures the intrinsic system and
common pathway
Thrombin time (TT) measures the final part of the common pathway, it is prolonged by
the lack of fibrinogen and by inhibitors of this conversion, e,g. heparin and fibrin
degradation products
vWD will therefore result when the synthesis of vWF is reduced or when abnormal vWF is
produced.
The clinical presentation of vWD will include the following:
Mucous membrane bleeding
Excess bleeding following surgicalldental procedures
Easy bruising
Three types (at least) have been described
Type 1 vWD
Most common, accounts for at least 7O0/0 of vWD
Due to a partial deficiency of vWF
Autosomal dominant
Type 2 vWD
Due to abnormal function of vWF
Type 3 vWD
Due to the complete absence of vWF
Can often be mistaken for haemophilia A because factor Vlll levels will be low as there is
no vWF to protect factor Vlll from proteolysis. Laboratory results are important in distin-
guishing the types of vWD and in the differentiation from haemophilia. Ifl vWD type 1 the
following results will be expected:
Platelet count N
Bleeding time N/f
Factor Vlll 1
vWF 1
Ristocetin cofactor activity 1
Ristocetin, an antibiotic, is now confined to laboratory-only use after it was documented to
cause significant thrombocytopenia. Ristocetin, when added to a patient's plasma, will bind
vWF and platelets together causing platelet aggregation (hence, the clinical thrombocyto-
penia). In the absence of vWF, no platelet aggregation will be seen (vWF type 3). In the
presence of decreased vWF, diminished aggregation will ensue (vWD type 1). Hence, when
faced with the clinical picture of haemophilia A (bruising, normal platelet count, slightly
increased bleeding time and a decreased factor VIII), the ristocetin cofactor test will be able
to differentiate between vWD (decreased) and haemophilia A (normal).
1 MALIGNANT PATHOLOGY
There are 1,200 new cases of malignancy diagnosed each year in the UK in children
under 15 years of age (an incidence of 1 in 600 children < 15 years)
The relative incidence rates for the different tumour types is illustrated below
Leukaemia, together with lymphoma, accounts for nearly 5O0/0 of all cases
Brain and spinal cord tumours are the most commonly occurring solid tumours
Overall, childhood cancer is about one-third more common in boys than girls
35%
25% Key
Leuk la+emia
20% Lymph lymphoma.
BmidS braidspinalcord
S0ftti.s softtissue
15%
Wtlms Wtlms' tumwr
Nwmb neuroblnstoma
10% Rstlno raUnoMastoma
G m C gemcell tumour
5% Epith epithdbmas
0%
Leuk Lymph BralnlS SoR Us Wtlms Nwrob h e Retino Germ C Epith Other
1 1 . Leukaemia
The leukaemias can be divided into acute and chronic leukaemia. Chronic leukaemia
accounts for less than 5% of all leukaemias in childhood - all of these cases would be
chronic myeloid leukaemia (CML) as chronic lymphoblastic leukaemia does not exist in
childhood.
txics tbr the MRCPCH 2nd Edition
Esserltial Rcvisiol? Notes in Pc~edic~
LEUKAEMIA
41 6
Hnematology and Oncology
11.2 Lymphoma
Two types of lymphoma are recognized: non-Hodgkin lymphoma (NHL) and Hodgkin
lymphoma (HL). In NHL the originating cell is either a B or T lymphocyte or an immature
form thereof, while in HL the originating cell is a B-lineage lymphoid cell. Histologically,
the presence of the Reed-Sternberg cell remains pathognomonic of HL.
Non-Hodgkin lymphoma
NHL is the term adopted to describe a heterogeneous group of malignant proliferations
of lymphoid tissue
The classification of NHL is complicated, and controversial. A practical way of
classifying NHL is to divide the entities into immature forms (T- or B-cell acute
lymphoblastic lymphoma), mature form (e.g. Burkitt lymphoma - a mature B-cell NHL)
and large cell lymphomas (e.g. anaplastic large cell lymphoma, diffuse 6-cell large cell
lymphoma, peripheral T-cell lymphoma)
The acute lymphoblastic lymphoma form of NHL is derived from the same T- and 8-
lineage lymphoid cells as ALL, but an important difference exists between these two
Essential Revision Notes it? Paedi,~tric-stor the k1KCPCH 2nd Edition
entities. In ALL, 80% of cases are pre-B-cell-derived; while 20% are T-cell-derived. In
NHL this is reversed, with T-cell tumours predominating
The following sites are commonly affected, in descending order of frequency:
Abdomen - usually with 6-cell disease
Mediastinum - typically T cell in origin
Head and neck - no specific cell
Chemotherapy is the mainstay of treatment because NHL i s a systemic disease, despite the
apparent local sites of disease
Vomiting 65
Headache 64
Changes in personality and mood 47
Squint 24
Out-of-character behaviour 22
Deterioration of school performance 21
Growth failure 20
Weight loss 16
Seizures 16
Developmental delay 16
Disturbance of speech 11
Astrocytoma
Most commonly occurring brain tumour
Range from low-grade (benign) tumours, usually in the cerebellum, to high-grade
(malignant) tumours, usually supratentorial and brainstem
The glioblastoma multiforme tumour has a near-fatal prognosis
11.11 Hepatoblastoma
Hepatoblastoma, an embryonal tumour of the liver, occurs in an otherwise normal liver
(compared to hepatocellular carcinoma) and generally presents in children under the
age of 2 years
Patients with Beckwith-Wiedemann syndrome or familial adenomatous polyposis have
an increased incidence of hepatoblastoma
There is evidence to suggest that low-birth-weight babies are predisposed to
hepatoblastoma
Treatment involves chemotherapy and surgery (partial liver resection or in some cases
liver transplantation)
Overall survival figures of 70-80% have been reported
The first step in achieving this goal in patients with haematological malignancies, such as
leukaemia, is to get the patient into remission. This is achieved with induction chemo-
therapy, usually over a 4-week period. To ensure that this remission is durable, further
treatment in the form of consolidation, intensification and maintenance chemotherapy is
required.
Patients with solid-tumour malignancies, on the other hand, generally require sequential
multimodal treatment. The tumour, depending on multiple factors including histological
type, stage, size, anatomical location, age of patient and degree of resectability, is either
surgically resected at the start of treatment, with adjuvant treatment in the form of chemo-
therapy andlor radiotherapy required thereafter to ensure complete eradication of remaining
tumour cells. If the localized primary tumour is too large to be safely resected or in cases of
metastatic disease, chemotherapy and/or radiotherapy are commenced to shrink the tumour,
thereby enabling resection at a later stage of treatment.
Cardiac
Cardiomyopathy is the most likely complication, particularly with anthracyeline-containing
chemotherapy, which is commonly used in treating solid tumours and, to a lesser extent,
leukaemia. This toxicity is exacerbated by thoracic radiotherapy.
Pulmonary
Pulmonary fibrosis may result from bleomycin chemotherapy used, for example, in Hodgkin
disease and germ-cell tumours.
Neurocognitive
There are insufficient data at present to claim a definite association between chemotherapy
and neurocognitive difficulties, although this may very well exist. Methotrexate is the one
exception where an association has been made.
Auditory
Ototoxicity may result from platinum-containing agents, for example, cisplatinum and
carboplatinum, used commonly in the treatment of CNS and other solid tumours.
Renal
Decreased renal function as measured by the glomerular filtration rate (GFR) may be caused
by the same platinum-containing agents as above. In addition, a Fanconi syndrome with
electrolyte abnormalities may result from numerous chemotherapeutic agents.
Radiotherapy
The developing child is extremely susceptible to the damaging effects of radiotherapy,
particularly in the following areas:
Neurocognitive - especially in the younger child
Endocrine abnormalities - particularly growth and hypothyroidism
Second malignancies - particularly sarcomas and lymphoma
Musculoskeletal atrophy
Organ damage - for example, cardiac, lung, gastrointestinal
Hepatology
Nancy Tan and Anil Dhawan
CONTENTS
1. Jaundice in infancy
1.I Bilirubin metabolism
1.2 Approach to a jaundiced infant
1.3 Unconjugated hyperbilirubinaemia
1.4 Conjugated hyperbilirubinaemia
I
2. Acute hepatitis
2.1 Acute infective hepatitis
2.2 Drug-induced liver disease
5, Portal hypertension
8. Further reading
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Essential Revision Notes in Paediatrics for the MRCPCH 2nd mition
Physiologicaljaundice
5O0/0 of term and 80% of preterm babies are jaundiced in the first week of life
Jaundicewithin the first 24 h of life is always pathological and cannot be attributed to
physiological jaundice
The aetiology of physiological jaundice is not precisely known but may be related to
immaturity of bilirubin uridine diphosphate glucuronosyl transfe~ase(UGT) activity
Jaundice peaks on day 3 of life
Treatment is by phototherapy or by exchange transfusion for severe hyperbilirubinaemia
Breast-milkjaundice
Occurs in 0.5-2OIi of neonates
Develops after day 4 (early pattern) or day 7 (late pattern)
Jaundice peaks around the end of the second week
May overlap with physiological jaundice or be protracted for 1-2 months
Diagnosis is supported by a drop in serum bilirubin (350% in 1-3 days) if breast-
feeding is interrupted for 48 hours
Haemolysis
Commonly the result of isoimmune haemolysis (Rh, ABO incompatibility), red cell
membrane defects (congenital spherocytosis, hereditary elliptocytosis), enzyme defects
(glucose-6-phosphate dehydrogenase or pyruvate kinase deficiency) or of
haemoglobinopathies (sickle cell anaemia, thalassaemia)
Findings of jaundice in the presence of anaemia and a raised reticulocyte count would
necessitate further investigation for the cause of haemolysis
Gilbert syndrome
Mild deficiency (350% decrease of UCT activity) occurring in 7% of population
Polymorphism with TA repeats in the promoter region (TATA box) in Whites compared
to exon mutations in Asians on chromosome 2q37
Correlation between hepatic enzyme activity and serum bilirubin levels is unpredictable
because up to 40% of patients with Gilbert syndrome have a reduced red blood cell
life-span
Higher incidence of neonatal jaundice and breast-milk jaundice
Usually presents after puberty with an incidental finding of elevated bilirubin on blood
tests or jaundice after a period of fasting or intercurrent illness
More common in males
No treatment required, compatible with normal life span
Crigler-Najjar type I1
Moderate deficiency
May require phototherapy and phenobarbitone
Crigler-Najjar type I
Severe deficiency of UGT
High risk of kernicterus
Requires life-long phototherapy or even liver transplantation
Autosomal recessive inheritance. Both Gilbert syndrome and Crigler-Najjar type II can' also
have autosomal dominant transmission.
Congenital spherocytosis
Hereditary elliptocytosis
Infantile pyknocytosis
Erythrocyte enzyme defects
Glucose-6-phosphate dehydrogenase deficiency
Pyruvate kinase deficiency
Haemoglobinopathy
Sickle cell anaemia
Thalassaemia
Others
Sepsis
Microangiopathy
Haemolytic-uraemic syndrome
Ineffective erythropoiesis
Drugs
Infection
, En~losed~haematom
Polycythaemia
s
Diabetic mother
Fetal transfusion (recipient)
Delayed cord clamping
Decreased deHvewy of unconjugated bilirubin (in plasma)
Right-sided congestive heart failure
Portocaval shunt
Decreased bilirubin uptake across hepatocyte membrane
Presumed enzyme transporter deficiency
competitive inhibition .
Breast-milk jaundice
Lucy-Driscoll syridro
'0 Drug inhibition7(radio~~ntrast
mate
Decreased biotransformation (conjugation)
Physiological jaundice
Inhibition (drugs)
Hereditary (Crigler-Najjar)
Type I (complete enzyme deficiency)
Type II (partial deficiency)
Gilbert disease
Hepatocellular dysfunction
Enterohepatic recirculation
Intestinal obstruction
Ileal a
Hirschsprung disease
Cystic fibrosis
Pyloric stenosis
Antibiotic administration
Brea
Investigations Pathology
General investigations
Liver function tests Type and level of jaundice
Degree of liver failure
Normal GGT levels (PFIC1, PFIC2 and
defects of bile acid synthesis)
Essenti,~/Revisio~~
Notes in Pc?ecliatricsfor the MKCPCH 2nd Edition
Investigations Pathology
Infections
Urine cultures Urinary tract infection
Endocrine
Thyroid function test High TSH, low T4, free T4 and T3
(hypothyroidism, hypopituitarism)
Investigations Pathology
Metabolic
Serum a, -antitrypsin levels Low level and PI ZZ (al
-antitrypsin
and PI type deficiency)
Very long chain fatty acids (VLCFA) Elevated (peroxisomal enzyme deficiency)
Plasma transferrin isoforms Characteristic patterns in congenital
disorders of glycosylation
Genetic testing
Karyotyping Trisomy (trisomies 2 1 and 18)
Duplication of chromosome 22
(cat eye syndrome)
Specific mutations
Immune
Autoantibodies Anti-Ro and anti-La antibodies (neonatal
lupus erythematosus)
Essential Revision Notes in Rjediatrics for the MRCPCH 2nd Edition
-
-
Investigations Pathology
Biopsy
Liver Biliary atresia
Giant cell hepatitis
lmmunostaining for PFlC
Bile duct paucity (syndromic and non-
syndromic causes)
Gaucher cells (Gaucher syndrome)
Foamy histiocytes (Niemann-Pick, Wolman)
Imaging
Hepatobiliary ultrasound Adrenal calcification (Wolman)
Triangular cord sign and absent or small
- irregular gall bladder (biliary atresia)
Structural abnormalities (e.g. choledochal
cyst)
Investigations Pathology
Type 1A ., Type 16
\
S"
Type II
-
,.-- -
- '/
Diagnosis is suggested by
Hepatobiliary ultrasound (fasting)- will show absent gallbladder or irregular outline
and triangular cord sign
Radionuclide imaging (phenobarbitonepriming) - no excretion indicates possible
biliary atresia; excretion indicates that it is not biliary atresia
Liver biopsy - expanded portal tracts with bile duct proliferation, bile plugs and
fibrosis
Gold standard for diagnosis is exploratory and operative cholangiography
Portoenterostomy (Kasai operation) should be offered to all children unless there is
decompensated liver disease
Between 70 and 80% achieve partial bile flow with 50% becoming jaundice free after
surgery
Ascending bacterial cholangitis follows the first year of surgery in 45-50%
It is a progressive disease even with a successful Kasai although prognosis may be better
if procedure is performed within 8 weeks of birth
Majority (8O0/0) require liver transplantation by 20 years of age
Fat-soluble vitamin supplementation is essential
Role of choleretic agents like phenobarbitone and ursodeoxycholic acid and steroids is
unproven
I
and progressive liver disease, requiring liver transplantation in the first few years of life.
Byler disease
Mutation of the FlCl gene on chromosome 18q21-22
Pancreatitis, persistent diarrhoea, short stature and sensorineural hearing loss
Normal GGT, serum cholesterol
Elevated serum bile salts, sweat chloride
Low chenodeoxycholic acid in bile
a1-Antitrypsindeficiency
Commonest inherited cause of conjugated jaundice
Autosomal recessive
Essen ti^ l Revision Notes in E7ccJiatric.c for the ib1KC-PCH I rx-l Edition
Causes of conjugatedja
Infections
Bacterial
Urinary tract infection
0 Septicaemia*
Syphilis
Listeriosis
Tuberculosis
Parasitic
Toxop~asmosis
* Malaria
Viral
Cytomegalovirus
Herpes simplex virus*
Human herpes virus type 6*
Herpes zoster virus
Adenovirus
Parvovirus*
Enterovirus
Reovirus type 3
Human immunodeficiency virus
Hepatitis B virus*
? Hepatitis A
? Rotavirus
Metabolic disorders
Carbohydrate metabolism
Galactosaemia*
Fructosaemia*
Glycogen storage type 4
Congenital disorders of glycosylation*
Protein metabolism (amino acid)
Tyrosinaemia*
Hypermethioninaemia
Urea cycle defects (arginase deficiency)
Lipid metabolism
Niemann-Pick disease (type C) ,
Wolman disease*
Cholesterol ester storage disease
Bile acid disorders*
Disorders of oxid
Endocrine diso
Chromosomaldisorders
Down syndrome
Trisomy E
Patau syndrome
Alagille syndrome
Byler syndrome (PFIC 1)
Bile salt export protein defect (BSEP defect, PFlC 2 )
Multidrug resistant 3 deficiency (MDR 3, PFlC 3)
Hereditary cholestasis with lymphoedema (Aagenaes syndrome)
Notes in Paedic3tricstbr the MRCPCH 2nd Edition
Essential Revisio~?
2. ACUTE HEPATITIS
Acute hepatitis is characterised by liver inflammation and necrosis. The underlying trigger
varies, including infective, autoimmune, toxic (e.g. drugs) and metabolic causes.
Hepatology
Hepatitis A infection
Commonest form of acute viral hepatitis, accounting for 20-25OlO of all clinically
apparent hepatitis world-wide
Picornavirus family, RNA virus
Orofaecal route of spread
Incubation period 2-6 weeks
Infectivity from faecal shedding begins during the prodromal phase, peaks at the onset
of symptoms and then rapidly declines. Shedding may persist for up to 3 months
Usually asymptomatic, less than 5% of infected people have an identifiable illness
Symptomatic infection increases with age of acquisition
Mortality is 0.2-0.4% of symptomatic cases and is increased in individuals > 50 or
< 5 years
Morbidity and mortality are associated with:
Fulminant hepatic failure
Prolonged cholestasis
Recurrent hepatitis
Extrahepatic complications
Neurological involvement - Guillain-Bar& syndrome, transverse myelitis, postviral
encephalitis, mononeuritis multiplex
Renal disease - Acute interstitial nephritis, mesangioproliferative
glomerulonephritis, nephrotic syndrome, acute renal failure
Acute pancreatitis
Haematological disorders - autoimmune haemolytic anaemia, red cell aplasia,
thrombocytopaenic purpura
Non-specific elevation of conjugated bilirubin and aminotransferase enzymes. Degree of
elevation does not correlate with severity of illness or likelihood of c~mplications
Confirmation of diagnosis relies on detection of:
Anti-HAV IgM - indicator of recent infection; peak levels occir during acute illness
or early convalescent phase; persists for 4-6 months after infection
Anti-HAV IgG - appears early; peaks during convalescent phase; persists lifelong,
conferring protection
Supportive symptomatic treatment and adequate hydration. Complete recovery is usual
within 3-6 months
Active immunization with a formaldehyde-inactivated vaccine is available
Passive immunization with human normal immunoglobulin offers up to 6 months of
protection and is effective if given within 2-3 weeks of exposure
Viral
Viral hepatitis - A, B, B + D, E e
3
-
teptospirosis
Drugs
Acetaminophen
Halc "
Antiretroviral drugs
Synergistic drug interactions
Isorriazid + rifam~icin
Trimethoprim + iulfarnethoxazole
Barbiturates + acetaminophen
-
-
-
3
-
-
-f
-
Toxins
Amanita phalloides (mushroom poisoning)
Herbal medicines
Carbon tetrachloride
Yellow phosphorus
Industrial solvents
Chlorobenzenes
Metabolic
Galactosaemia
Tyrosinaemia
Hereditary fructose intolerance
Neonatal haemochromatosis
Niemann-Pick dise
Wilson disease
Mitochondria1c)rtop
Congenital disorders of glycosylation
Acute fatty liver of pregnancy
Budd-Chiari syndrome
Causes of neonatal acute liver failure
Perinatal herpes simplex virus infection
Neonatal haemochromatosis
Galactosaemia
Tyrosinaemia
Haemophagocytic lymphohistiocytosis
Septicaemia
Mitochondria1 cytopathies
Congenital disorders of glycosy lation
Severe birth asphyxia
-
=
-A
x
---
--.
.
-
- -
-
.
.-.
---
---
Nutrition
Enteral feeding (1-2 g protein/kg per day)
Parenteral nutrition is rarely indicated
Specific therapy
~cetaminophentoxicity - N-acetylcysteine (100 rng/kg per day)
Hereditary tyrosinaemia - NTBC
Neonatal haemochromatosis - iron chelation and antioxidant cocktaillN-
acetylcysteine (100 mg/kg per day intravenous infusion)/selenium (3 pglkg per day
intravenous)/desferrioxamine (30 mg/kg per day intravenous)/prostaglandinE l (0.4-
0.6 pg/kg per hour intravenous)/vitamin E (25 U/kg per day intravenousloral)
Mushroom poisoning - benzylpenicillin (1,000,000 U/kg per day) or thiotic acid
(300 mg/kg per day)
Hepatic support with liver assist devices such as molecular adsorbent recirculating
system (MARS) are still under investigation
Emergency liver transplantation
Mainly one large dose in a suicidal attempt, occasionally accidental over-ingestion over a
=
---
=
--
-
i
several days. -=
A
=-a
--
-
-
Direct dose dependent hepatotoxic effect -5z
I
--
-
-
.
--
--
--
Metabolism -
I
-
.
!-
--
--.
95%
Paracetamol Conjugated to sulphate 1
lucuronide '
s%& Cytochrome P450
I N-acetyl-p
benzoquinonemine I I Excretion in urine
I
Rapidly bound to
intracellular glutathione
-
Hepa tology
Diagnostic considerations
Confirming the presence and type of liver disease
Compensated - may be asymptomatic
Decompensated - presence of liver synthetic failure and occurrence of
complications
End-stage - a persistent rise in bilirubin, prolongation of the INR > 1.3, persistent
fall in serum albumin to < 35 g/l, faltering growth despite intensive nutritional
support, severe hepatic complications such as chronic hepatic encephalopathy,
refractory ascites, intractable pruritus, or recurrent variceal bleeding despite
appropriate medical management
Determining aetiology
Assessing complications
Hepatorenal syndrome
Diagnostic criteria
oliguria: urine output < 1 mllkg per day
fractorial excretion sodium < 1OO/
urine-to-plasma creatinine ratio < 10
1 glomerular filtration rate, t creatinine
absence of hypovolemia
other kidney pathology excluded
Type 1 rapidly progressive with poor prognosis
Type 2 less precipitous loss of renal function
Mortality of > 90% with severe liver disease
Reversed with liver transplantation
Causes of chronic liver disease in children
Onset in infancy
Structural
Extrahepatic biliary atresia
Alagille syndrome, biliary hypoplasia
Choledochal cyst, tumours, stones
Storage/metabolic diseases
Carbohydrate defects
galactosaemia, fructosaemia, glycogen storage Ill and IV
Amino acid defects
tyrosinaemia, urea cycle disorders
Metal storage defects
Lipid storage diseases
Gaucher disease, Niemann-Pick type C
Fatty acid oxidation defects
Peroxisomal disorders
Zel lweger syndrome
Mitochondria1disorders
Progressive familiar intrahepatic cholestasis syndrome
Total parenteral nutrition-associated cholestasis
Cystic fibrosis liver disease
Haematological
Langerhans cell histiocytosis
Infection/inflammation
Neonatal hepatitis
Hepatitis B and hepatitis C
Onset in childhood
All of the above and
Autoimmune liver disease
Autoimmune hepatitis
Autoimmune sclerosing cholangitis
Sclerosing cholangitis
Drugsltoxins (e.g. chemotherapy-induced veno-occlusive disease)
Fibropolycystic disorders
Chronic hepatic venous outflow obstruction
Hepatic vein thrombosis
Budd-Chiari syndrome
Veno-occlusive disease
Cardiac cirrhosis
4.1 Autoimmune hepatitis
Autoimmune hepatitis has a 75% female preponderance. Other autoimmune disorders are
I
present in 20°h and 40% of first-degree relatives may also have autoimmune disease.
Clinical presentation is variable: !
E
Acute hepatitis
Insidious onset
Portal hypertension
Diagnostic criteria are based on: 1
Serum non-organ-specific autoantibodies
Type 1
Anti-nuclear antibody (ANA)
Anti-smooth muscle antibody (SMA)
Type 2
Anti-liver-kidney microsomal (LKM-1)
Up to 20% may not have antibodies detectable at presentation
Serum biochemistry
7 Aminotransferases
Serum IgG
> 1.5 X normal
Liver histology
Absence of
Markers of viral infection and metabolic disease
Excessive alcohol consumption
Use of hepatotoxic drugs
Treatment involves:
Corticosteroids
Azathioprine for poor response or as steroid sparing
Liver transplant for fulminant hepatic failure or failure of medical therapy
7
Host HBV status ALT HBV DNA cAb sAg sAb 'eAg eAb
Treatment
Immunomodulation - interferon-a, pegylated interferon
Antivirals - lamivudine, famciclovir, adefovir
Not much paediatric experience
50% of patients seroconvert with therapy (adult data)
Liver transplantation for fulminant HBV disease, chronic liver disease, hepatocellular
carcinoma
5, PORTAL HYPERTENSlON
The portal vein contributes to two-thirds of the liver's blood supply. Portal venous pressure
is a product of blood flow from the splanchnic circulation and vascular resistance within
the liver.
Portal hypertension is defined as a portal vein pressure > 5 mmHg or portal vein to
hepatic vein gradient > 10 mmHg
A rise in portal pressure leads to splenomegaly and development of portosystemic
collaterals and varices
A gradient of > 12 mmHg is associated with the development of oesophageal varices.
The junction between the mucosal and submucosal varices in the lower 2-5 cm of the
oesophagus is the usual site of variceal bleeding
Not all portal hypertension is a result of intrinsic liver disease although chronic liver
disease is the commonest overall cause. Portal vein occlusion is the most frequent
extrahepatic cause of portal hypertension
General factors
Developmental malformation
Septicaemia
Thrombophilia
Myeloproliferative disorders
Paroxysmal nocturnal haemoglobinuria
Protein C deficiency
Protein S deficiency
Antithrombin Ill deficiency
Factor V Lieden mutation
Anti-phospholipid antibodies
ctor II gene mutation ((320210A)
rnocysteinaemia
Local factors
Umbilical sepsis, catheterization, infusion of irritant solutions
Intra-abdominal sepsis and portal pyaemia
Abdominal trauma
Structural lesions
Cholangitis/choledochal cyst
Pancreatitis
Malignant disease/lymphadenopathy
Splenectomy
Intrahepatic
Pre-sinusoidal
Hepatoportal sclerosis
Neoplasia
Hepatic cyst
Sinusoidal
Chronic liver disease and congenital hepatic fibrosis
Post-sinusoidal
Veno-occlusive disease
Post-hepatic
Budd-Chiari syndrome
Chronic constrictive pericarditis
Right ventricular failure
Bilirubin
Conjugated (direct) hyperbilirubinaemia
Specific to liver disease
Conjugated fraction > 20% of total bilirubin is indicative of hepatic dysfunction
Unconjugated (indirect) hyperbi l irubinaemia
Normal bilirubin levels does not exclude liver cirrhosis
Arninotransferases
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT)
Most common tests of liver cell dysfunction
lntracellular enzymes
Indicate hepatic necrosis
AST is produced in the cytosol and mitochondria of the liver, heart, skeletal muscle,
kidney, pancreas and red cells
ALT is found in the cytosol of liver and muscle cells and so is more liver specific
In isolated AST or ALTelevations, a normal creatine kinase level is helpful in ruling out
muscle pathologies
ALT: AST ratio > 1 is suggestive of fibrosis in some liver pathologies like steatohepatitis
and chronic hepatitis C
There is no correlation between the enzyme levels and the severity of disease
Levels may be normal in compensated cirrhosis or end-stage liver disease
Gamma-glutamyltransferase (GGT) B
I
Present in biliary epithelia, hepatocytes, renal tubules, pancreas, brain, breast and small !
intestine 51
Reference range is age related. Normal levels in newborns are five to eight times higher i
than those of adults but reach adult values by 9 months I
Most sensitive test for hepatobiliary disease but cannot differentiate between extra- or
intrahepatic biliary disease
May be normal in familial intrahepatic cholestasis, bile acid synthesis disorders, ARC i
t
syndrome (arthrogryposis, renal and cholestasis) and very advanced liver disease
Albumin concentration I
5
Reflects the synthetic capacity of the liver
Produced in the liver
Long half-life, so is not decreased in acute liver injury
Levels < 35 g/dl in chronic liver disease suggest decompensation i
1
462
Prothrombin time (PT)
Prolongation of PT > 3 s above normal or INR 1 1.3 may indicate vitamin K deficiency
Failure of INR to normalize after a parenteral dose of vitamin K (1 mg/year of age up to a
maximum of 5 mg) suggests liver failure
Reflects the decreased synthesis of factor VII and IX which have short half-lives
Useful in monitoring progress of acute liver failure
Causes of hepatosplenomegaly
Cirrhosis (early) biliary atresia, sclerosing cholangitis, congenital hepatic fibrosis
Haematological thalassaemia, spherocytosis, sickle cell anaemia
Infection infectious mononucleosis, TORCH, malaria, septicaemia
Immune juvenile rheumatoid arthritis, systemic lupus erythematosus,
immunodeficiency states
Metabolic a1 -antitrypsin deficiency, tyrosinaemia, cystic fibrosis
Proliferative leukaemia, lymphoma, Langerhans cell histiocytosis
Storage diseases Gaucher (long-term), Niemann- Pick, mucopolysaccharidoses
7. THE PANCREAS
7.1 Acute pancreatitis
Defined clinically as the sudden onset of abdominal pain associated with a rise in
amylase or lipase of at least three times the upper limit in the blood or urine
Rare in children
Involves premature activation of trypsinogen
Presents with epigastric or back pain. May have prominent nausea and vomiting. Less
commonly there may be fever, tachycardia, hypotension, jaundice, and abdominal signs
such as guarding, rebound tenderness and a decrease in bowel sounds
Causes of acute pancreatitis
Idiopathic
Pancreatitis associated with systemic illness
Trauma
Structural abnormalities of pancreas, pancreatic or common bile duct
Medications (valproate, L-asparaginase, prednisolone, azathioprine, 6-mercaptopurine,
frusemide, phenytoin)
Infections (mainly viral, e.g. mumps, enterovirus, Epstein-Barr virus, hepatitis A, CMV,
rubella, cosackievirus, rubeola, measles, influenza)
Gallstones
Familial (PRSSI, SPlNKI or CFTR mutation)
Post-endoscopic retrograde cholangiopancreatography
Metabolic
Diabetic ketoacidosis
Hypercalcaemia
Hypertriglyceridaemia
Cystic fibrosis
Recurrent acute pancreatitis is seen in 10% of children after a first episode of acute
pancreatitis and is commonly associated with structural abnormalities, idiopathic or
familial pancreatitis
Commonest cause of familial pancreatitis
Mutations in cationic trypsinogen gene (e.g. PRSSI) enhance trypsin activation
Mutations in the SPlNKl (serine protease inhibitor Kazal type 1.) gene result in an
abnormal pancreatic secretory trypsin inhibitor
Mutations of the CFTR (cystic fibrosis transmembrane conductance regulator) gene,
which reduces the pancreatic fluid secretion capacity,-increase the risk of keeping
activated trypsin in the pancreas for a longer period of time
The mainstay of current treatment is analgesia, intravenous fluids, pancreatic rest, and
monitoring for complications
Acute pancreatitis scoring system for children that predicts severity of disease and
mortality include the following parameters
Age (< 7 years)
Weight (<23 kg)
Admission white blood cell count (> 18.5 X 1og/litre)
Admission lactate dehydrogenase (>2000 lullitre)
48-hour fluid sequestration (>75 m/kg per 48 h)
48-hour rise in urea (> 5 mgldl)
Each criterion is assigned a value of 1 point, cumulative score predicts the outcome
of patients
0 to 2 points - 8.6% severe, 1.4% death
2 to 4 points - 38.5% severe, 5.8% death
5 to 7 points - 80% severe, 10% death
Surgical management is limited to debridment of infected necrotic pancreas or
cholecystectomy or endoscopic sphincterotomy in the presence of gallstones
Essential' Revision Notes ill Paecji,~trbcs hl-the lLlfiC-/'(-/ i 211~1
Edilion
Complications of pancreatitis
Local Systemic
-
Oedema Shock
Inflammation Pulmonary oedema
Fat necrosis Pleural effusions
Phlegmon Acute renal failure, coagulopathy
Pancreatic necrosis Haemoconcentration
Sterile Bacteraemia, sepsis
lnfected Distant fat necrosis
Abscess Vascular leak syndrome
Haemorrhage Multiorgan system failure
Fluid collections Hypermetabolic state
Pseudocysts Hypocalcaemia
Duct rupture and strictures Hyperglycaemia
Extension to nearby organs
8. FURTHER READING
American Academy of Pediatrics. 2004. Management of hyperbilirubinemia in the newborn
infant 35 or more weeks of gestation. American Academy of Pediatrics clinical practice
guidelines. Pediatrics; 114:1, 297-31 6.
Decker BC. 2004. Pediatric Gastrointestinal Disease, 4th edn. Ontario, Canada: BC Decker
Inc.
Dhawan A, Cheeseman P, Mieli-Vergani G. 2004. Approaches to acute liver failure in
children. Pediatric Transplantation 8, 584-588.
Kelly, D (Ed). 2004. Diseases of the Liver and Biliary System in Children, 2nd edition.
Oxford: Blackwell Publishing.
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition 2004.
Guideline for the evaluation of cholestatic jaundice in infants: recommendations of the
North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. Journal
of Paediatric Gastroenterology and Nutrition 3 9, 115- 12 8. .
Chapter 13
Jmmunology
Waseern Qasirn and Bobby Gaspar
CONTENTS
1. Introduction 471
5. Combined immunodeficiencies
5.1 Severe combined immunodeficiency (SCID)
5.2 Combined immunodeficiency
7. Defects of neutrophils
7.1 Congenital neutropenia
7.2 Schwachman-Diamond syndrome
7.3 Cyclical neutropenia
7.4 Leukocyte-adhesion deficiency
7.5 Chronic granulomatous disease
7.6 ChGdiak-Higashi syndrome
7.7 Rac deficiency
1. INTRODUCTION
Immunity against specific infectious agents is brought about by a complicated set of
interactions between host and pathogen which, under normal circumstances, maintains an
adequate balance between the two. From early in life humans come into contact with a
wide variety of infectious agents including bacteria, fungi and viruses. Some of these
become commensals, some cause troublesome infections in the neonatal period, some are
pathogenic throughout childhood, while others remain significant pathogens throughout
life. Increased susceptibility to infectious diseases occurs in individuals with a wide variety
of abnormalities including anatomical, metabolic, haematological, ontological and immu-
nological abnormalities.
The immune system can be divided into specific and non-specific components. Non-
specific immunity refers to the first-line of defence against pathogens which, if breached,
leads to the specific or adaptive immune response being activated. This first-line of defence
consists of a variety of components including mechanical barriers (e-g. skin), secretions (e.g.
tears), mucus in the respiratory tract and gut, bile and enzymes in the gastrointestinal tract,
acidity of urine and gastric acid fluid and the normal commensals of the skin and gut which
prevent colonization with pathogenic organisms. Second-line, non-specific mechanisms
include complement components which bind to phagocytic receptors found on cells, and
particularly neutrophiIs and macrophages, which may interact with antigens in a non-
specific way.
Specific immunity is divided into humoral and cellular responses. Humoral immunity refers
to the production of antibody specific for an invading pathogen or antigen, while cellular
immunity is mediated via cells of the immune system. Lymphocytes are central to both arms
of the specific immune system. B lymphocytes produce antibodies and present antigens to T
lymphocytes. T lymphocytes themselves may act as cytotoxic cells killing virally infected
cells, or as helper cells providing help or suppression to other cells involved or recruited
into the specific immune response.
The crucial difference between the specific and non-specific arms of the immune system is
the ability of the specific arm to develop memory. This immunological memory allows the
rapid mobilization of specific immune mechanisms on the second and subsequent challenges
with a particular antigen such as a virus. This response may be mediated via the humoral
(antibody) or cellular (T-cell) system. Either way, the consequence of memory is the protection
from recurrent infection with the same antigen. Memory is learnt during the development of
the immune system and explains the difference in frequency between infections in adults and
children.
Essential Revision Notes in R~ediatricsh r the MRCPCH 2nd Edition
The immune system is a complicated structure/organ made up of many parts that have, with
time, evolved and become increasingly sophisticated. Different aspects of the immune
system are discussed below.
B-cell development
Thymic cortex
- Proliferate
rearrange TCR
- Small cells
rearrange TCR
i
Thymic medulla !
i
T-cell development
-
~ 5 s e a 2 1 ~ , r/ Rct,i3 & .:I : \i;t jssi~)f--~:j~,lfi.~e
:it";
. ., L." LJ8 &i:;t-.*
l, "j ~ c
j'" ,8 < -
cr,211j3i-EJ'>i..id ;C.i; '
i i e i ,&-;t / $ t > [ i
BINDING
chain
Antibody structure
2-4 Complement
10% of serum proteins
Links innate and adaptive immunity
Classical pathway: Cl q, Cl r, C l s, C4, 6 2 , C3
Alternative: Factor B, D
Membrane attack complex: C5, 6, 7, 8, 9
U p-regulating factors: properdin
Down-regulating: C1 inhibitor, C4 binding protein, factor H, factor !, S protein
Membrane control proteins: decay accelerating factor (DAF)
Nomenclature rules
@ Numbered in order of discovery
@ Cleavage fragments called a, b, c
Usually 'a' is smaller and 'b' bigger
C1 has three parts q, r, s
A line above the number indicates activation
@ Alternative components use upper-case letters
Alternative
antibody or MBL bacteria/LPS
/ C3 Activation
I
Membrane
Attack
Complex
Complement pathway
Antigen rn
TCR P
I CD4lCD8 I
i
I I
i I
I
Antigen presentation
A number of polysaccharide and polymerized flagellin antigens carry numerous repeating
epitopes that can stimulate B cells without assistance from T cells (T-independent). They
usually give rise to low-affinity immunoglobulin M (IgM) antibodies because of limited
class-switching potential, and do not generate memory B cells. Most antigens are T-
dependent because B cells process and present the antigen to CD4 T cells in association
with MHC class II molecules. Once activated, T cells express the CD40 ligand on their
surface, which in turn binds CD40 on the 6 cell, and induces processes of somatic
hypermutation and immunoglobulin class switching. Defects of CD40 ligand result in
immunodeficiency associated with increased serum levels of IgM.
Cytokines are soluble factors that mediate signalling between immune cells. They may act
in an autocrine, paracrine or endocrine manner.
Cytokine Origin Action
-
3.1 History
Recurrent infections at different sites
Regular courses of antibiotics
Infections at multiple sites or infections that persist and do not clear easily with
antibiotics
Infection with atypical or unusual organisms
Prolonged separation of the umbilical cord may be linked to leukocyte adhesion
deficiency (LAD)
Family history of early infant deaths; take careful X-linked history because a number of
conditions are X-linked
Consanguineous family history
Essential Revision Notes in &ecJi,~tricstor-the MRCPCM 2nd Eclitiori
3.2 Examination
Faltering growth and falling off centile charts after 4-6 months (i.e. after protection from
maternal immunoglobulin has waned)
Absence of lymphoid tissue, especially tonsils and lymph nodes
Dysmorphism (e.g. Di George syndrome)
Eczema +I- petechiae in Wiskott- Aldrich syndrome
Evidence of chronic organ disease (e.g. in lungs or liver)
Evidence of scar tissue or granuloma formation may be indicative of LAD or chronic
granulomatous disease (CGD)
Gingivitis is associated with LAD
Ataxic gait and evidence of telangiectasia
3.3 Investigations
These need to be directed by accurate history and examination. Initial investigations would
include the following:
Full blood count and differential
Serum IgG, IgA and IgM (must be compared with age-related normals)
IgC subclasses
Antigen-specific antibodies (e.g. diphtheria, tetanus, Haemophilus influenzae type b
(Hib)) (reference values for a normal response are available in specialist laboratories)
Lymphocyte subsets
T-cell stimulation (response to phytohaemagglutinin, Candida antigen, tetanus or
tuberculin)
Nitroblue tetrazolium test (NBT) if history is suggestive of CCD
Total haemolytic complement (THC), C3, C4 (if history is suggestive of complement
defect, i.e. recurrent meningitis)
Human immunodeficiency virus (HIV) testing (if clinically appropriate)
(Always check that patient has not received blood products or intravenous immunoglobulin
(IVIG) before interpreting immunoglobulin levels - if the patient has received such
products, it is necessary to wait approximately 3 months before reassessment.)
Lymphocyte markers
CD3 - T cell
CD4 - helper T cell
CD8 - memorylcytotoxic T cell
CD19120 - B cell
CD14 - monocyte
CD16lCD56 - natural killer (NK) cell
CD34 - haematopoietic stem cells
Normal numbers and percentages of lymphocyte subsets vary with age and with clinical
state, i.e. viral infection may lead to a relative CD8 lymphocytosis.
Immunology
More specialized tests include testing for specific defects, e.g. adenosine deaminase (ADA)
metabolites in ADA deficiency or expression of Bruton tyrosine kinase for diagnosis of X-
linked agammaglobulinaemia. These can be carried out in specialist laboratories.
a Severe cases present before the age of two, milder cases may not diagnosed until school
age
poor or no responses to vaccines and low levels of isohaemagglutinins are found
In some atypical forms there is a small number of circulating B cells and some make
immunoglobulin
Patients respond well to lVlG therapy
The patients with persistently low immunoglobulin levels benefit from supplemental IVIG
infusions. Prophylactic antibiotics are given to those with recurrent infection despite IVIG.
Severe cases may require bone marrow transplantation.
5. COMBINED IMMUNODEFICIENCIES
5.1 Severe combined immunodeficiency (SCID)
SClD arises from severe defects in both cellular and humoral immunity
Same phenotype arises from different molecular defects
Both X-linked and autosomal recessive forms of SCID exist
Characterized by recurrent infections, often severe, involving opportunistic pathogens
Overall prognosis for SClD without effective management is very poor
Only curative option is bone marrow transplantation; but for certain types of SClD other
treatments such as gene therapy (presently for X-linked SCID) and enzyme replacement
therapy (for ADA SCID) are available (see below)
Incidence
Rare
Estimated at 1 : 50,000 to 1 : 500,000 for all forms of SClD
Males affected more than females because of X-linked inheritance in one specific type
of SClD
Clinical manifestations
Mean age of presentation is approximately 6-7 months
Respiratory complications - interstitial pneumonitis caused by Pneumocystis carinii,
respiratory syncytial virus, cytomegalovirus, adenovirus, influenza and parainfluenza
infections. Bacterial and fungal pneumonias are also described
Diarrhoea and faltering growth - there may be a viral aetiology (rotavirus, adenovirus)
but in many cases no cause is defined. Faltering growth as a result of diarrhoea or
recurrent infection is seen in nearly all patients.
Skin rash - may be the result of a viral infection but an erythrodermic macular rash is
often indicative of maternal T-cell engraftment or Omenn syndrome
HIV infection can also present as faltering growth with a similar spectrum of infectious
pathogens, and may need to be formally excluded (see Section 7.1, Chapter 14).
Immunological phenotype
SClD is characterized by both humoral and cellular defects
Abnormality in T-cell development with variable defects in 8-cell and NK-cell
development
IgC present early on because of maternal transfer, but igM and igA production impaired
SClD is categorized by the pattern of TIBINK-cell development and this can be
indicative of the underlying molecular defect
Essential Revision Notes in Paedi'7trics for the M RCPCH 2/70' Eclitiora
Genetic diagnosis
The molecular basis of the known SClD types is shown in the table on p. 484.
Diagnosis is made on the basis of pedigree, immunological phenotype and genetic
analysis
Management
Prophylactic - septrin for prevention of F! carinii pneumonitis, immunoglobulin
replacement, aciclovir for antiviral prophylaxis and itraconazole/fluconazole for
antifungal prophylaxis
Supportive - nutrition, skin care, genetic counselling for family
Specific treatment of infectious complications
Gene therapy
Gene therapy has been used to treat X-linked SClD and ADA deficiency
The patient's own bone marrow is harvested and stem cells are collected
In the laboratory, a modified retrovirus, incapable of replication, is used to deliver a
corrected copy of the defective gene
The retrovirus stably integrates into the genome of the stem cells
The gene-modified stem cells are then infused back to the patient
Immune reconstitution follows over a period of several months
Although this approach has been shown to be potentially curative, there have been
some serious complications, with the development of leukaemic changes in some
patients
It is thought that the retrovirus may activate oncogenes in some situations
This approach is currently offered if no matched donors are available for transplant
- --
1.br the M RCPCH ? / i d Editioti
Essential Revision Notes in Pc?edi~trics
=
T
--
-
E
--
--
-
zegz
-- -
--. +
-- =
- -
-
-
-
-
-
-
-
-
-
-
=
-
=
-
Diagnosis
Diagnosis is made on clinical phenotype, platelet count morphology, x-lin ked pedigree and
mutation analysis of the WASP gene.
Management
Management is orientated to the different clinical problems.
Topical care of eczema
Thrombocytopenia sometimes responds to high-dose immunoglobulin (2 glkg) and
steroids
In most cases splenectomy is successful in improving the platelet count
Immune defect is treated by prophylactic antibiotics, lVlG and aggressive management
of active infection
Only curative option is BMT which can be difficult if a fully matched donor is
unavailable
BMT after 5 years of age is associated with worse prognosis
Parathyroid hypoplasia may lead to hypocalcaemic tetany, and thymic hypoplasia may
lead to profound cellular immunodeficiency (less than 500/mm3 CD3 T cells)
Dysmorphic features include lateral displacement of the inner canthi, short philtrum,
micrognathia and ear abnormalities. Learning difficulties are common
Increased likelihood of autoimmune phenomena in older children
Usually confirmed by the detection of the 22q11.2 deletion by fluorescent in situ
hybridization
Attempts to correct T-cell deficiency by thymic transplantation have been unsuccessful
Management
Includes the use of irradiated blood products before surgery and then management of
specific syndromic problems. Management of immunodeficiency is dependent on the
severity of immune compromise and varies from prophylactic antibiotics to BMT.
Treatment
Is difficult
In affected boys identified by family history, prophylactic lVlG and antibiotics do not
provide protection from severe EBV infection
Retuximab (anti-CD20) is used to treat EBV by eliminating B cells
BMT offers only curative option but i s difficult to perform if child is in acute phase
7. DEFECTS OF NEUTROPHILS
Neutrophil immunodeficiency may arise because of reduced numbers of circulating neutro-
phils, a failure of neutrophil precursor maturation or defective neutrophil function.
7 3 Cyclical neutropenia
Patients recurrently become neutropenic for between 3 and 6 days, and may develop
stomatitis, mouth ulcers or bacterial infections
There is usually a 21 -day cyclical pattern, but this can range between 14 and 36 days
The condition is autosomal dominant and has been linked to mutations in the elastase
gene, €LA2
Immunology
X-linked chronic granulomatous Xp21 gp9 lphox Component of phagocyte NADPH oxidase- Nitroblue tetrazolium test gp9lphox by
disease phagocytic respiratory burst immunoblotting mutation analysis
X-linked Xq22 Bruton tyrosine lntracellular signalling pathways essential for Btk by immunoblotting or FACS analysis and
agammaglobulinaemia kinase (Bth pre-B-cell maturation mutation analysis
X-linked hyper-lgM syndrome Xq26 CD40 ligand lsotype switching, T-cell function CD154 expression on activated T cells by
(CD40 ligand deficiency) (CD154) FACS analysis mutation analysis
Wiskott-Aldrich syndrome Xpl 1 WASP Cytoskeletal architecture formation, WASPexpression by immunoblotting
immune-cell motility and trafficking mutation analysis
X-linked lymphoproliferative Xq25 SAP Regulation of T-cell responses to EBV and Mutation analysis SAPexpression - under
syndrome other viral infections development
Properdin deficiency Xp2 1 properdin Terminal complement component. Properdin levels CDlllCD18 expression by
Leukocyte-adhesion 21q22 CD11/CD18 Defective leukocyte adhesion and migration FACS analysis; mutation analysis
deficiency type 1
Chronic granulomatous 7q11 p47phox Defective respiratory burst and phagocytic p47phox, p67phox, p22phox, expression by
disease 1q25 p67phox intracellular killing immunoblotting; mutation analysis
16~24 p22phox
Chkdiak-Higashi syndrome 1q42 LYST - Abnormalities in microtubule-mediated
lysosomal protein trafficking
Giant inclusions in granulocytes; mutation
analysis
MHC class II deficiency 16~13 CllTA (MHXZTA) Defective transcriptional regulation of MHC HLA-DR expression; mutation analysis
19~12 RFXANK II molecule expression
lq21 RFCS
13q13 RFXAP
Autoimmune lymphoproliferative 10q24 APT1 (Fas) Defective apoptosis of lymphocytes Fas expression; apoptosis assays; mutation
syndrome (ALPS) analysis
Ataxia telangiectasia 11q22 ATM Cell-cycle control and DNA damage DNA radiation sensitivity; mutation analysis
responses
Inherited mycobacterial 6q23 Interferon-y Defective I F N y production and signalling Interferon-y receptor expression; IL-12
susceptibility 5q3 1 receptor function expression; IL-12 receptor expression;
a
-L
19~13 11-12 p40
11-12 receptor?/I
mutation analysis
Essentic~I
Revision Notes 1 for the MRCPCH 2r7d Editicsn
i7 Pc7edir7tri~-s
Late complications
These include: incomplete immune reconstitution; chronic GvHD; growth retardation and
endocrine problems; and cognitive impairment in some patients.
10. ROUTINE VACCINATION IN THE IMMUNOSUPPRESSED
All live vaccines are contraindicated in SClD and only poor responses are obtained to
killed vaccines
In the UK the new five in one immunization contains inactivated vaccines and is safe to
give, though responses may be poor
Bacillus Calmette-Cuerin (BCG) is contraindicated in all primary immunodeficiencies;
chemotherapy patients; and patients on significant steroids or immunosuppressants
HIV patients in UK should not be given BCG; other live vaccines can be given if
asymptomatic
No specific contraindications for complement deficiencies
Interferons
Steihm ER (Ed.). 1995. immunologic Disorders in Children and Infants, 4th edn. WB
Saunders.
Vergani D, Peakman M. 2000. Basic and Clinical Immunology. Churchill Livingstone.
Gaspar, HB, Gilmour, KC. 2001. Severe combined immunodeficiency - molecular
pathogenesis and diagnosis. Archives of Diseases in Childhood 84, 169-73.
Chapter 14
Infectious Diseases
Katy Fidler, Nigel Klein and Karyn Moshal
CONTENTS
1. Notification of infectious diseases
2. Pathogenesis of infection
5. Mycobacterial infections
5.1 Tuberculosis (TB)
5.2 Atypical mycobacteria
6. Fungal infections
6.1 Cutaneous fungal infections
6.2 Candidiasis (thrush, moniliasis)
6.3 Aspergillosis
7. Viral infections
7.1 Human immunodeficiency virus (HIV)
7.2 Hepatitis
Essentia 1 Revisiol~Notes in Pc3edi,~tricsfor the M RCPCH 2nd Edition
i
Epstein-Barr virus (EBV)
Cytomegalovirus (CMV)
Herpes simplex virus (HSV)
Varicella zoster virus (VZV)
Parvovirus B19 (erythema infectiosum, 'slapped cheek' or fifth disease)
Roseola infantum (exanthem subitum or HHV-6)
Measles
Mumps
Rubella (German measles)
Adenovirus
Enteroviruses
Molluscum
8. Parasitic infections
8.1 Toxoplasmosis
8.2 Head lice (pediculosis capitis)
1
12.6 Oxazolidinones: a new class of antibiotics
12.7 Echinocandins: a new class of antifungals -
12.8 Erythema multiforme (EM)
12.9 Erythema nodosum
12.10 Anthrax
12.11 Botulism 3
12.12 Bovine spongiforrn encephalopathy (BSE) and new variant Creutzfeldt-~akob
disease (nv-CJD)
Notifiable diseases
2. PATHOGENESIS OF INFECTION
The course and outcome of any infectious disease is a function of the interaction between
the pathogen and host.
The pathogens
Human infections are caused by bacteria, viruses, fungi and parasites. However, despite
the vast array of potential pathogens, only a minority have the capacity to cause infection in
a human host. Many factors determine an individual organism's ability to initiate disease,
but successful organisms have three essential characteristics: the ability to invade a host; the
ability to travel to an environment within the host which is conducive to their propagation;
and the ability to survive the host's defence mechanisms. Increasing understanding of the
molecular mechanisms underlying these pathogenic events should enable the development
of new treatment strategies.
The host
The essential elements of all components of the immune system are present at birth. Initially,
however, the baby's circulating immunoglobulin is derived predominantly -from the mother.
It is only after encountering a wide range of potential pathogens that defences fully mature
to provide adequate protection in later life. Meanwhile, these children are particularly
susceptible to infections. \
The importance of acquiring a fully competent host defence system is illustrated clinically
by the problems encountered in immunodefective individuals, e.g. primary immunodefi-
ciencies, acquired immunodeficiency syndrome (AIDS) and those receiving chemotherapy
and radiotherapy. These patients suffer not only from severe and persistent infections caused
by common organisms, but are also vulnerable to a range of unusual or opportunistic
pathogens. The role played by each component of the host defence system can be deduced
from the nature of infections associated with specific immunological defects, many of which
present in childhood.
Infectious Diseases
Bacterial meningitis
Neisseria meningitidis is the commonest cause of community-acquired bacterial
meningitis in the UK, with most cases being N. meningitidis B since the introduction of
the conjugate meningococcal C vaccine.
Streptococcus pneumoniae is the second most common cause
The incidence of Haemophilus influenzae type B (Hib) meningitis has dropped from
around 2,500 cases per year to less than 40 per year since the introduction of the Hib
vaccine
A rare, but serious, form of bacterial meningitis is caused by Mycobacterium
tuberculosis. This organism can affect patients of all ages and should be considered in
any atypical presentation of meningitis, particularly in patients presenting with an
insidious illness
Neonatal meningitis
In the neonatal period, group B streptococcus is the predominant meningeal pathogen,
followed by Gram-negative bacilli, Strep. pneumoniae and Listeria monocytogenes.
Complications
Convulsions occur in 20-30°h of children, usually within 72 h of presentation
Subdural collections of fluid are common, particularly during infancy. They are usually
sterile and rarely require aspiration
The commonest long-term complication of meningitis is sensorineural deafness. The
overall rate of deafness following meningitis is less than 5%. Hearing impairment is
higher in cases of pneumococcal meningitis than in meningococcal infections
Prevention
Conjugate vaccines against Hib and group C N. meningitidis are now routinely given in the
U K as part of the primary course of immunization at 2, 3 and 4 months of age. Conjugated
pneumococcal vaccines are available, but are not yet part of the routine vaccination
schedule. They are recommended for children with conditions which predispose them to
pneumococcal infections.
Osteomyelitis
This is either haematogenous (most common), resulting from bacterial seeding to the bone
secondary to a bacteraemia, or non-haematogenous, which is secondary to trauma resulting
in compromised bone tissue which then becomes infected. Long bones, followed by
vertebrae, are the most common sites of infection.
Most common in those under 1-year-old or 3-1 0 years of age
More frequent in boys than girls
Mild (often unnoticed) trauma causes bone compromise, allowing bacterial seeding
during transient bacteraemic events and subsequent osteomyelitis
Destruction of the growth plates can occur in neonates, but not in older children
Acute haematogenous osteomyelitis presents as an acute bacteraemic illness with fever and
localized bone symptoms within a week.
Subacute haematogenous osteomyelitis has an insidious onset, over 1-4 weeks, with fewer
systemic features and more pronounced localized bone signs.
Chronic osteomyelitis lasts for months, often as the result of an infection that has spread
from a contiguous site, e.g. a fracture, or an infection with an unusual organism e.g
mycobacteria.
Organisms
Staphylococcus aureus is the most common organism causing osteomyelitis in the normal
host, followed by streptococci. Consider Mycobacterium tuberculosis in patients who
present with chronic or atypical osteomyelitis, as well as Kingella kingae, a more recently
recognized pathogen.
Diagnosis
Increased white cell count (inconsistent) with neutrophil ia, increased erythrocyte
sedimentation rate (ESR) and C-reactive protein (CRP) - present in 92-98% of cases,
but is non-specific
Blood cultures positive in only 40-60% of cases
Needle aspiration of periosteal space or bone or arthrocentesis if associated septic
arthritis
Tuberculin skin test if tuberculosis is suspected
Characteristic X-ray changes occur after 10-1 4 days with periosteal elevation and
radiolucent metaphyseal lesions
Technetium bone scan is positive within 24-48 h of infection
Magnetic resonance imaging detects changes early in the disease
Differential diagnosis
Malignant and benign bone tumours, e.g. Ewing sarcoma, osteosarcomas, leukaemia with
bony infiltrates and bone infarcts, e.g. sickle-cell disease.
Treatment
4-6 weeks of intravenous antibiotics depending on the organism. The'commonest cause
is Staph. aureus and should be treated with an anti-staphylococcal penicillin. Some
authorities also add fusidic acid. A definitive diagnosis from bone culture at
debridement is optimal. Positive blood cultures or joint fluid cultures provide useful
information
Surgery is required if dead or necrotic bone is present
Associated septic arthritis (especially the hip) requires incision and drainage
Subacute or chronic infections, or disease caused by atypical organisms e.g
mycobacteria, require longer courses of antibiotics
Complications
Serious damage to the growth plate can cause differential limb length and a limp (if leg is
involved).
Septic arthritis
Serious pyogenic infection of the joint space
Slightly more common than osteomyelitis
Secondary to bacteraemia - caused by haematogenous spread
Most common in children less than 3 years old and in sexually active young women
Usually monoarticular, except in neonates when it is often multifocal
Essential Revision Notes in Paedatric-s fur the MRCPCH 2nd Edtion
Clinical presentation
Characterized by fever and a swollen, painful joint. Similar to haematogenous osteomyelitis.
Neonates often present with crying when changing their nappy because of the movement of
the hip joint.
Organism
Depends on age and immune status of the child
Infectious arthritis may be caused by viral, fungal (very rare in immunologically normal
hosts, but is well documented in the premature neonatal population) or bacterial agents
Septic arthritis implies pyogenic arthritis secondary to bacterial infections, including
Mycobacterium tuberculosis
Organisms are similar to those in osteomyelitis with Staph. aureus being the most
common. Croup A streptococci are also often implicated. Neisseria spp. should be
considered
N. meningitidis infection may present with acute or occasionally chronic arthritis
N. gonorrhoeae infection is not uncommon in sexually active teenagers who have
polyarticular septic arthritis
Brucella spp. may cause chronic septic arthritis
Differential diagnosis
Viral infections such as rubella, mumps, parvovirus B19 and hepatitis B
Post-infectious, reactive and immune-complex arthritides
Intermittent polyarticular arthritis of Borrelia burgdorferi (Lyme disease)
Migrating arthritis of rheumatic fever
Connective tissue diseases
'Irritable hip' - a transient synovitis of the hip in children < 5 years old following an
upper respiratory tract infection; there is mild fever and limp with minimal systemic
features, a normal ESR and white cell count and an almost full range of movement of
the affected limb
Diagnosis - Clinical
Ultrasound scan and aspiration of joint fluid for Gram staining and microbiological
culture
Look for associated osteomyelitis
Technetium bone scan
Computerized tomography and magnetic resonance imaging can provide useful
information early in the disease
Blood cultures will be positive in 50% of cases
Treatment
Antibiotic treatment depending on the organism for at least 2 weeks
Open surgical drainage is indicated for recurrent joint effusions and for any case of
septic arthritis of the hip at the time of presentation
Needle aspiration of fluid in other joints +/- washout of the joint
Infectious Diseases
Septic arthritis of the hip in a child is an emergency. Immediate open drainage reduces the
intra-articular pressure and avoids aseptic necrosis of the femoral head. The femoral
metaphysis can be drilled during this procedure if osteomyelitis is suspected.
Definitions
SlRS (systemic inflammatory response syndrome) is defined by the presence of two or
more abnormalities in temperature, heart rate, respiratory rate and white blood count.
SlRS can follow any severe insult including infection, trauma, major surgery, burns or
pancreatitis
Sepsis is used to describe SlRS in the context of bacterial infection.
Severe sepsis is used to describe a state characterized by hypoperfusion, hypotension
and organ dysfunction
Septic shock is restricted to patients with persistent hypotension despite adequate fluid
resuscitation, and/or hypoperfusion even following adeq;ate inotrope or pressor support
Pathophysiology of sepsis
Lipopolysaccharides from Cram-negative bacteria and a variety of other microbial products
have the capacity to stimulate the production of mediators from many cells within the
human host.
Tumour necrosis factor, interleukin-1 and interleukin-6 are just a few of the many
inflammatory mediators reported to be present at high levels in patients with sepsis.
Recently, a family of receptors has been identified capable of transducing cellular signals in
response to bacteria. These are known as human Toll-like receptors.
It is the cytokines and inflammatory mediators which are produced in response to microbial
stimuli that stimulate neutrophiIs, endothelial cells and monocytes and influence the
function of vital organs, including the heart, liver, brain and kidneys.
The net effect of excessive inflammatory activity is to cause the constellation of pathophy-
siological events seen in patients with sepsis and septic shock.
Treatment
Successful treatment involves the administration of appropriate antibiotics, intensive care
with particular emphasis on volume replacement and inotropic and respiratory support. A
number of adjuvant therapies have been investigated, but, at present, none are used
routinely.
in children aged 9-1 1 months. Seasonal variation in the disease incidence has been
reported, with the peak occurrence during the winter and spring months.
Slight male predominance (1.6 : 1)
Diagnosis of KD
There is no diagnostic test for KD, therefore diagnosis is based on clinical criteria
The differential diagnosis includes toxic-shock syndrome (streptococcal and
staphylococcal), staphylococcal scalded-skin syndrome, scarlet fever and infection with
enterovirus, adenovirus, measles virus, parvovirus, Epstein-Barr virus, CMV,
Mycoplasma pneumoniae, rickettsiae and Leptospira spp.
Diagnostic criteria
Fever of 5 days' duration plus four of the five following criteria:
Conjunctival injection
Lymphadenopathy
Rash
Changes in lips or oral mucosa
Changes in extremities
or: the presence of fever and coronary artery aneurysms with three additional criteria is
required for the diagnosis of 'complete' cases
'Incomplete' cases comprise those with fewer than the prerequisite number of criteria.
Irritability is an important sign - which, although virtually universally present, is not
included as one of the diagnostic criteria
Other relatively common clinical findings in KD include arthritis, aseptic meningitis,
pneumonitis, uveitis, gastroenteritis, meatitis and dysuria as well as otitis. Relatively
uncommon abnormalities include hydrops of the gallbladder,. gastrointestinal ischaemia,
jaundice, petechial rash, febrile convulsions and encephalppathy or ataxia. Cardiac
complications other than coronary arterial abnormalities include cardiac tamponade,
cardiac failure, myocarditis, endocardial disease and pericarditis
Acute-phase proteins, neutrophils and the ESR are usually elevated. Thrombocytosis
occurs towards the end of the second week of the illness and therefore may not be
helpful diagnostically. Liver function may be deranged. Sterile pyuria is occasionally
observed, and also CSF pleocytosis (predominantly lymphocytes) representing aseptic
meningitis
Treatment of KD
Treatment of KD is aimed at reducing inflammation and preventing the occurrence of
coronary artery aneurysms and arterial thrombosis. Patients receive aspirin and intravenous
immunoglobulin, 2 @kgas a single dose infused intravenously.
An echocardiogram is performed at 10-1 4 days, 6 weeks, 6 months and then at further
times if an abnormality is detected.
Essential Revision Notes in Paediatrics for the MRCPCH 2nd Edition
Cardiac complications of KD
20-40% of untreated KD patients develop coronary artery abnormalities
50% of these lesions regress within 5 years, and regression occurs within 2 years in most
cases of mild coronary artery aneurysms (3-4 mm)
The risk of these complications is markedly reduced with the use of intravenous
immunoglobulins
In 1993, a report from the British Paediatric Surveillance Unit (BPSU) indicated a mortality
rate of 3.7% in the UK for KD. Current mortality rates reported from Japan are much lower
at 0.1 4%.
Organisms
Most common organisms
Native valve:
Streptococcus viridans group (Strep. mutans, Strep. sanguis, Strep. mitis)
Staph. aureus
Enterococcus (e.g. Strep. faecalis, Strep. bovis)
Prosthetic valves:
Staph. epidermidis
Staph. aureus
Strep. viridans
Uncommon organisms
Strep. pneumoniae, H. influenzae, Coxiella burnetii (Q fever), Chlamydia psittaci,
Chlamydia trachomatis and Chlamydia pneumoniae, Legionella spp., fungi and the
HACEK organisms (Haemophilus spp. (H. parainfluenzae, H.aphrophilus, H.
paraphrophilus), Actinobacillus actinomycetem comitans, Cardiobacterium horninis!
Eikenella corrodens and K. kingae)
Clinical presentation
Acute: fever and septicaemia
Non-acute: more common - prolonged fever, non-specific symptoms, e.g. fatigue,
myalgia, arthralgia, weight loss, or no symptoms at all
New murmurs or changes in known murmurs, splenomegaly, neurological
Infectious Diseases
Investigations
At least three separate blood cultures taken from different sites and at different times
over 2 days, cultured on enriched media for > 7 days. This increases the likelihood of a
positive yield, as does an increased volume of blood inoculum in each blood culture
bottle.
Look for raised white cell count, high ESR, microscopic haematuria
Echocardiography - the presence of vegetations or valvular abnormalities
Treatment
Broad-spectrum intravenous (iv) antibiotics, e.g. penicillin and gentamicin or
vancomycin and gentamicin (depending on the most likely organism), at high
bactericidal levels should be started as soon as possible after the blood cultures have
been taken, because delay causes progressive endocardial damage
Treatment duration is usually 4-6 weeks, but may be shorter for fully sensitive
organisms
Surgical intervention may be required
Revention
Antibiotic prophylaxis before and after various procedures, &g. dental extraction in
high-risk patients
Proper dental care and oral hygiene. The teeth and gums are an important source of
bacteria and poor dental hygiene significantly increases the risk of bacteraemic and
septicaemic episodes
Diagnostic criteria
Fever > 38.8"C
Diffuse macular erythroderma
Desquamation 1-2 weeks after onset, especially on palms and soles
Hypotension
Involvement of three or more organs - gastrointestinal tract, renal, hepatic, muscle,
CNS; mucositis, disseminated intravascular coagulation
Diagnosis
Clinical
Identification of toxin or antibodies to toxin
Treatment
Supportive
Intravenous antibiotics
Intravenous immunoglobulin
4.5 Brucellosis
Brucella species (e.g. B. abortus, B. melitensis) are non-motile Cram-negative bacilli
Zoonotic disease, transmitted to humans by ingestion of unpasteurized milk'or by direct
inoculation to abraded skin
Incubation period 1-4 weeks
Disease is often mild in children
Acute brucellosis
Fever, night-sweats, headaches, malaise, anorexia, weight loss, myalgia, abdominal
pain, arthritis, lymphadenopathy, hepatosplenomegaly
Complications include meningitis, endocarditis, osteomyelitis
Chronic brucellosis
Fevers, malaise, depression, splenomegaly
Diagnosis
Prolonged culture of blood, bone marrow or other tissue, paired serology
Treatment
Co-trimoxazole at high dose for 4-6 weeks
Infectious Diseases
Clinical manifestations
There are three stages:
Early localized - distinctive rash (bull's eye lesion) - erythema migrans - red macule/
papule at site of tick bite, which expands over days/weeks to large annular erythematous
lesion with partial clearing, approximately 15 cm in diameter. Associated with fever,
malaise, headache, neck stiffness
Early disseminated - 3-5 weeks post bite - multiple erythema migrans, cranial nerve
palsies especially the Vllth cranial nerve, meningitis, conjunctivitis, arthralgia, myalgia,
headache, malaise, rarely carditis
Late disease - recurrent arthritis, pauciarticular, large joints, neuropathy,
encephalopathy
Diagnosis
Clinical
Serology and immunoblotting to detect production of antibodies to 8.burgdorferi can be
problematic because they are negative in early disease and, once present, persist
beyond resolution of disease
Polymerase chain reaction (PCR) amplification - is currently a research tool only
Treatment
Doxycycline for child > 8 years (avoid sun exposure), or amox;acillin if < 8 years for
14-2 1 days if early disease, 2 1-28 days if disseminated or late disease
Intravenous ceftriaxone or iv penicillin if meningitis, encephalitis, carditis or recurrent
arthritis
4.7 Listeriosis
Caused by Listeria monocytogenes, a Gram-positive bacillus
Variable incubation of 3-70 days
Isolated from a range of raw foods, including vegetables and uncooked meats, as well as
processed foods and soft cheeses and meat-based pates
The majority of cases are believed to be food-borne. Some cases are the result of direct
contact with animals. Mother to fetus transmission in utero or during birth or via person-
to-person spread between infants shortly after delivery
Unborn infants, neonates, immunocompromised individuals, pregnant women and the
elderly are at high risk
Essential Revision Notes in Paediatrics tbr the M RCPCH 2nd Edition
Clinical manifestations
Influenza-like iIIness or meningoencephalitis/septicaemia; spontaneous abortion
Maternal infections can be asymptomatic
Treatment
Ampicillin
4.8 Leptospirosis
This is a spirochaetal disease caused by Leptospira spp.
Many wild and domestic animals, e.g. rats, dogs and livestock, harbour and excrete
Leptospira spp. in their urine
Transmission is by direct contact of mucosal surfaces or abraded skin with urine or
carcasses of infected animals; or by indirect contact, e.g. swimming in water
contaminated by infected urine
Incubation period is 1-2 weeks
Clinical manifestations
This is an acute febrile illness which can be biphasic. The initial phase is septicaemic in
nature and varies in severity from a mild self-limited illness to life-threatening disease.
The initial illness lasts 3-7,days. Clinically, there is abrupt onset with fevers, rigors,
headaches, myalgia, malaise and conjunctival injection
Recovery can then be followed, a few days later, by an immune-mediated disease.
Clinical presentation includes fever, aseptic meningitis, uveitis, myalgias,
lymphadenopathy and vasculitis rashes
90' will be anicteric; however, 10% will be severely unwell with jaundice, renal
dysfunction, respiratory, cardiac and CNS disease. There is a case fatality rate of 5-40%
in this group
Diagnosis
Blood and CSF culture in the first 10 days of illness and urine after 1 week. Yield is low,
the incubation period is prolonged and special culture media are required
Serology, although retrospective, is the most reliable diagnostic tool
PCR is available in a few laboratories but for research purposes only
Treatment
Penicillin iv for severe disease
Oral doxycycline (if child is > 8 years old) or oral amoxicillin for < 8 years old for mild
disease
lnfectious Diseases
Clinical manifestations
Fever and mild systemic symptoms occur in 30% of patients
A skin papule is often found at the site of presumed bacterial inoculation
Predominant sign is regional lymphadenopathy, involving the nodes that drain the site of
inoculation
In up to 30% of cases the lymph node will suppurate spontaneously
Complications
Encephalitis, aseptic meningitis, neuroretinitis, hepatosplenic microabscesses and
chronic systemic disease occur occasionally but are more common in the
immunocompromised patient
Diagnosis
lmmunofluorescence antibody assays are the most useful diagnostic tests
PCR is available in some laboratories but is not recommended
Histology of the lymph node and staining with Warthin-Starry silver stain may show
characteristic necrotizing granulomata and/or the causative organism.
Treatment
Most disease is self-limiting so treatment is symptomatic
For those who are severely unwell and for immunocompromised patients, antibiotics
such as ciprofloxacin, rifampicin, azithromycin and iv gentamicin are used
5. MYCOBACTERIAL INFECTIONS
5.1 Tuberculosis (TB)
Disease caused by infection with Mycobacterium tuberculosis, an acid-fast bacillus
Incubation period, i.e. infection to development of positive tuberculin skin test, is 2-
12 weeks (usually 3-4 weeks)
Incidence is increasing again in the UK (especially in immigrant patients and those with
human immunodeficiency virus (HIV))
Host (immune status, age, nutrition) and bacterial (load, virulence) factors determine
whether infection progresses to disease. Defects in interferon-y and interleukin-12
pathways predispose to infection
Essential Revision Notes in Paediatrics tbr the MRCPCH 2nd Edition
Children usually have primary TB, adults may have either new infections or reactivation
disease
Children are rarely infectious
Children are usually infected by an adult with 'open', i.e sputum-positive pulmonary TB,
therefore notification and contact tracing are essential
Approximately 30% of healthy people closely exposed to TB will become infected, of
whom only 5-1 O0Io will go on to develop active disease. Young children exposed to TB
are more likely to develop disease than healthy adults
Risk of disease is highest in the first 6 months after infection
Pathogenesis
Majority of infections are acquired via the respiratory route, occasionally ingested
Organisms multiply in periphery of the lung and spread to regional lymph nodes, which
may cause hilar lymphadenopathy
Pulmonary macrophages ingest bacteria and mount a cellular immbne response
In the majority of children, this primary pulmonary infection is controlled by the
immune system over 6-1 0 weeks. Healing of the pulmonary foci occurs, which later
calcifies (Chon focus). Any surviving bacilli remain dormant but may reactivate later in
life and cause tuberculous disease which can be smear positive and contagious
Clinical syrnptoms/signs
TB infection - usually asymptomatic, may develop fever, malaise, cough or hypersensitivity
reactions - erythema nodosum or phlyctenular conjunctivitis.
Congenital TI3
(See Section 11, this chapter)
Diagnosis
Tuberculin tests
Tuberculin tests involve an intradermal test of delayed hypersensitivity to tuberculin
purified-protein derivative,
Heaf test - used for mass screening, if positive refer to TB clinic. Positive is grade 2-4
if no previous BCG, grade 3 or 4 if BCG received previously. This is not an appropriate
test for contact tracing
Mantoux test - dose in UK is 0.1 mi of 1 : 1,000, i.e. 10 tuberculin units (use
1 : 10,000 if risk of hypersensitivity, e.g. erythema nodosum or phlyctenular
conjunctivitis). Mantoux tests are more accurate than Heaf tests and should be used for
all patients where disease is suspected and for contact tracing. Measure induration, not
erythema, at 48-72 h. Interpretation is difficult but test is positive if:
> 15 mm induration in anyone (equivalent to Heaf 3-4)
> 5-14 mm induration (equivalent to Heaf 2) if not had BCG and at high risk, e.g.
found at contact or new immigrant screening, or in child< 4 years old
NB - A negative Mantoux test does not exclude a positive diagnosis - the test may
be negative if it was incorrectly inserted; if anergy is present (in 10% of the normal
population and also occurs in the very young), if there is overwhelming disseminated
TB and in some viral infections, e.g. HIV, measles, influenza
~ssentialRevision Notes in Paediatrics for the MRCPCH 2nd Edition
Microbiological tests
Ziehl-Neelsen stain for acid-fast bacilli, and culture for 4-8 weeks of sputum, gastric
washings, bronchoalveolar lavage fluid, CSF, biopsy specimens (culture is required
because it will provide details of type and sensitivities)
All have low yield in children because there are lower numbers of bacteria
Other
Histology - caseating granuloma and acid-fast bacilli
PCR - poor sensitivity and specificity at present
Chest X-ray - typical changes of hilar lymphadenopathy +/- parenchymal changes
Treatment
Chemoprophylaxis
Chemoprophylaxis is required:
For those with TB infection (i.e. a positive Mantoux test, well child, normal chest X-ray)
to prevent progression to disease
For close contacts of smear-positive TB patients if they are HIV-positive or
immunosuppressed patients because they may not develop a positive Mantoux response
Options for chemoprophylaxis are:
lsoniazid for 6 months (+ pyridoxine for breast-fed infants and malnourished)
or isoniazid and rifampicin for 3 months
A repeat chest X-ray at the end of treatment is not required if there has. been good
compliance and the child is asymptomatic.
Chemotherapy
For those with signs of disease four drugs are used in the initial 2 months of treatment
because of the increase in isoniazid resistance (now 6% in London, UK). The fourth drug
(usually ethambutol/streptomycin) can be omitted if there is a low risk of isoniazid
resistance, i.e. previously untreated, Caucasian, proven or suspected HIV-negative patients,
or those who have had no contact with a TB patient with drug resistance.
Pulmonary and non-pulmonary disease (except meningitis) - isoniazid and rifampicin
for 6 months with pyrazinamide and a fourth drug for the first 2 months
Meningitis - 12 months' total therapy with isoniazid and rifampicin with pyrazinamide
and a fourth drug for the first 2 months
Multidrug-resistant TB - seek expert advice
NB Directly observed therapy is recommended if there is any chance of non-
compliance
Corticosteroids should be used for 6-8 weeks if there is TB meningitis, pericarditis,
miliary TB and endobronchial disease with obstruction, but only with anti-TB therapy
Infectious Diseases
Prevention
Improvement of social conditions and general health
BCG vaccination (live attenuated strain of M. bovis) gives approximately 5O0/0
protection. It is effective in the prevention of extra-pulmonary disease in the < 4-year
age group. In the UK, BCG given at birth to high-risk groups and at 12-1 4 years of age
to tuberculin test-negative children
Clinical presentations
Lymphadenitis (usually cervical), pulmonary infections, cutaneous infections and
occasionally, osteomyelitis
Diagnosis
Isolation and identification by culture (PCR in some laboratories) '
Treatment
For non-tuberculous mycobacterial lymphadenitis - surgical excision alone
If excision is incomplete, or other site is involved, medical treatment with at least two
drugs for 3-6 months is required
NB For differential diagnosis of persistent cervical lymphadenopathy see Section 12.2.
6. FUNGAL INFECTIONS
Many fungi are ubiquitous, growing in soil, decaying vegetation and animals
Infection is acquired by inhalation, ingestion and inoculation from direct contact
Often produce spores
Superficial infections are common
Essential Revision Notes in Paediatrics for the MRCPCH 2nd Edition
Ringworm (dermatophytoses)
These are caused by filamentous fungi belonging to three main genera - Trichophyton,
Microsporum and Epidermophyton, diagnosed by skin scrapings.
Clinical manifestations
Mild mucocutaneous infection
Oral thrush and/or nappy-area dermatitis are common in infants
Vulvovaginal candidiasis occurs in adolescents
lntertriginous lesions, e.g. in neck, groin, axilla
lnvasive disease
Disseminated disease to almost any organ, especially in very low-birth-weight newborns
and those who are immunocompromised
Diagnosis
Microscopy showing pseudohyphae or germ-tube formation (C. albicans only)
Culture
Treatment
For minor mucocutaneous disease - use oral nystatin or topical nystatin/clotrimazole/
miconazole
For severe or chronic mucocutaneous disease - use an oral azole, e.g. fluconazole
For invasive disease - treat as for Aspergillus infection (see below)
6.3 Aspergillosis
Caused by Aspergillus fumigatus, A. niger, A. flavus and, rarely, others
No person-to-person transmission
Clinical manifestations
Allergic bronchopulmonary aspergillosis - episodic wheezing, low-grade fever, brown
sputum, eosinophilia, transient pulmonary infiltrates. Usually in children with cystic
fibrosis or asthma. Treat with steroids
Sinusitis and otomycosis of external ear canal - usually benign in immunocompetent
patients
Aspergilloma - fungal balls that grow in pre-existing cavities or bronchogenic cysts -
non-invasive
lnvasive aspergillosis - extremely serious
May cause peripheral patchy bronchopneumonia with clinical manifestations of
acute pneumonia
Often disseminates to brain, heart, liver, spleen, eye, bone and other organs in the
immunocompromised patient population
Essential Revision Notes in Paedi,ltrics for t l MRCYCH
~ 2nd Edition
Diagnosis
High clinical index of suspicion
Microscopy shows branched and septate hyphae
Culture
Treatment
For invasive disease treat with liposomal amphotericin in high dose +I- a second
antifungal, e.g. caspofungin, an azole or flucytosine depending on culture results
Surgical excision of localized lesion
7. VIRAL INFECTIONS
7.1 Human immunodeficiency virus (HIV)
HIV is a retrovirus, i.e. it contains the enzyme reverse transcriptase, which allows its
viral RNA to be incorporated into host-cell DNA
Two main types are known: HIV-I (widespread) and HIV-2 (West Africa)
Mainly infects CD4 helper T cells, causing reduction of these cells and acquired
immunodeficiency
Transmission
Vertical (most common mode of transmission in children)
Prenatal
lntrapartum (most common)
Postnatally via breast milk
Blood or blood products, e.g.
Haemophiliacs (of historical interest only in the UK now)
Unsterile needle use
Via mucous membranes, e.g.
Sexual intercourse, NB sexual abuse
Diagnosis
Virus detection by PCR (rapid, sensitive, specific)
Detection of immunoglobulin G (IgG) antibody to viral envelope proteins (gp120 and
subunits)
infectious Diseases
Clinical manifestations
These include AIDS-defin ing and non-defining illnesses.
Clinical categories for children c 13 years with HIV infection. CDC Classification to
be used in conjunction with the CDC immunological classification
--- - -
1997 - 20% of vertically infected children developed AlDS in infancy, most common
AIDS-defining illness was I? carinii pneumonia
2001 - improved antenatal detection and prophylaxis, therefore fewer AIDS-defining
illnesses in infancy
Approximately 5% of children with HIV develop AlDS per year
Faltering growth
This is frequently multifactorial, e.g.:
Reduced nutrient and fluid intake - psychosocial reasons or oral and oesophageal
thrush
lncreased nutrient and fluid requirement with chronic disease (30-50%)
Increased fluid loss with diarrhoea - look for gut pathogens, microsporidiosis,
cryptosporidiosis, Giardia, atypical Mycobacteria and viruses
Treatment: improve immune function with highly active antiretroviral therapy (HAART);
treat specific infections; provide dietary supplements
HIVencephalopathy
May present with regression of milestones, behavioural difficulties, acquired
microcephaly, motor signs, e.g. spastic diplegia, ataxia, pseudobulbar palsy
Exclude CNS infections and lymphoma
Treatment: HAART
Thrombocytopenia
Not associated with other indicators of disease progression
Treatment: only if symptomatic or platelet count persistently < 20,000/mm3. Options
include intravenous immunoglobulin, steroids, HAART, or last-resort splenectomy (not
recommended because it further increases the risk of sepsis)
Opportunistic infections
Protozoa
I? carinii pneumonia +I- CMV pneumonitis:
Most common at 3-6 months of age; presents with persistent non-productive cough,
hypoxaemia, dyspnoea, minimal chest signs on auscultation
Chest X-ray shows bilateral perihilar 'butterfly' shadowing; diagnosis by
bronchoalveolar lavage; ensure no concurrent CMV infection
Treatment: supportive, may need to be treated in paediatric intensive care unit.
High-dose co-trimoxazole (septrin) for 21 days in conjunction with steroids.
Ganciclovir iv if there is concurrent CMV disease. Once stable, commence HAART.
Prophylactic low-dose septrin following treatment
Cerebral toxoplasmosis
Rare in childhood HIV infection; may present with focal signs +I- fits
Computerized tomography shows multiple intraparenchymal ring-enhancing lesions.
Positive toxoplasmosis serology
Treatment: 6 weeks of pyrimethamine and sulfadiazine with folinic acid and
HAART
Cryptosporidosis
Cryptosporidium parvum causes severe secretory diarrhoea, abdominal pain and
sometimes sclerosing cholangitis
Diagnosis by stool microscopy +/- small-bowel biopsy
Treatment: supportive, paromomycin
Fungi
Candida albicans - oropharyngeal, oesophageal, vulvovaginal, disseminated (rare)
Treatment: chronic antifungal therapy, e.g. fluconazole, voriconazole, iv liposomal
amphotericin B if severe
Cryptococcus neoformans - meningitis (insidious onset), pneumonia
Diagnosis by CSF examination (Indian ink stain, antigen, culture), serum culture,
antigen
Treatment: fluconazole. In severe disease, two antifungal agents should be used
Viruses
CMV - retinitis, colitis, pneumonitis, hepatitis, pancreatitis
Diagnosis by serum PCR, immunofluorescence in relevant sample and characteristic
retinal changes if present; differentiate disease from carriage
Treatment: iv ganciclovir; HAART
Herpes simplex virus
Types 1 and 2 - extensive oral ulceration
Treatment: iv aciclovir, oral prophylaxis if recurrent and severe; HAART may help
Measles, varicella zoster virus, respiratory syncytial virus, adenovirus - all may cause
severe disease in HIV-infected children, especially pneumonitis
TB and atypical TB
Increased risk of TB and atypical TB, especially disseminated M. avium complex
See Section 5
Tumours
These are rare in children.
Kaposi sarcoma - tumour of vascular endothelial cells, associated with human
herpesvirus-8 (HHV-8); involves skin, gut, lung and lymphatics
Treatment: HAART, local radiotherapy, chemotherapy if disseminated
Lymphoma - non-Hodgkin B-cell primary CNS lymphoma
Focal neurological signs +/- fits; computerized tomography shows single lesion
Definitive diagnosis by brain biopsy
Treatment: radiolchemotherapy; poor prognosis
Infectious Diseases
HIV treatment
Highly active antiretroviral therapy (HAART).
When to start treatment in children differs in each country
In the UK, start treatment if there are an AIDS-defining illness, many 6-category
symptoms and rapidly decreasing CD4 count (< 20% in children under 2 years of age,
and < 15% in older children)
Three-drug therapy is the gold-standard. This reduces resistance and suppresses viral
load to undetectable levels
Standard HAART regime comprises a backbone of two nucleoside reverse transcriptase
inhibitor (NRTls) and either a non-NRTI or a protease inhibitor. Liaise with tertiary
centre
Monitor for efficacy (viral load and CD4 count) and side-effects
l? carinii prophylaxis
For first 12 months of life if vertically infected
If CD4 count < 15%
Drug Side-effect
Protease inhibitors
Ritonavir Gastrointestinal side-effects common in first 4 weeks,
paraesthesia
Kaletra (Lopinavir Raised transaminases
boosted with ritonavir)
Nelfinavir Diarrhoea
NB Protease inhibitors and D4T are associated with lipodystrophy
7.2 Hepatitis
(See Chapter 12 - Hepatology)
Chickenpox d
Incubation: chickenpox: 11-24 days
Transmission: direct contact, droplet, airborne; infectious from 24 h before rash appears
until all spots have crusted over (approx. 7-8 days)
Clinical presentation: prodrome of fever and malaise for 24 h; rash appears in crops,
papular then vesicular and itchy, usually start on trunk and spread centripetally; crops
continue to appear for 3-4 days and each crusts after 24-48 h. Household contacts,
who receive a higher viral inoculum, tend to have more severe disease
Complications:
Secondary bacterial infection often with group A streptococcus
Thrombocytopenia with haemorrhage into skin
Pneumonia
Purpura fulminans
Post-infectious encephalitis
lmmunocompromised patients - severe disseminated haemorrhagic disease
Diagnosis: clinical, viral culture, serology and immunofluorescence assay, PCR
Treatment: supportive; intravenous aciclovir for immunosuppressed or severely unwell
patient
Prophylaxis: zoster immunoglobulin (ZIG) if high risk (e.g. immunodeficiency,
immunosuppressive treatment). NB If mother develops chickenpox within 5 days' pre-
to 2 days' post-delivery give neonate ZIG. If baby develops chickenpox treat with iv
aciclovir. NB The incubation period in children who have received.ZIG is extended to
28 days
Herpes zoster
Increased incidence if immunosuppressed
Clinical presentation:
Prodrome of pain and tenderness in affected dermatome with fever and malaise;
within a few days the same rash as varicella appears in distribution of one
(sometimes 2 or 3) unilateral dermatomes
If infection of Vth cranial nerve occurs, it may affect the cornea (ophthalmic branch)
If Vllth nerve is involved, may develop paralysis of facial nerve and vesicles in
external ear (Ramsey-Hunt syndrome)
Complications: dissemination in immunocompromised; post-herpetic pain rare in
children
Infectious Diseases
NB VZV vaccine now available routinely in the USA, and for at-risk patients in the U K
7.9 Measles
Incubation: 7- 14 days
Transmission: respiratory droplets; infectious from 7 days after exposure, i.e. from pre-
rash to 5 days after rash starts
Essential Revisiot~Notes ill I:recliatrics for the h4RCPCW 2nd Fclition
Clinical presentation:
Prodrome: 3-5 days, low fever, brassy cough, coryza, conjunctivitis, Koplik spots
(pathognomonic white spots opposite lower molars)
Eruptive stage: abrupt rise in temperature to 40°C associated with macular rash
which starts behind ears and along hairline, becomes maculopapular and spreads
sequentially to face, upper arms, chest, abdomen, back, legs; lasts approximately
4 days
Complications:
Otitis media, laryngitis, bronchitis
Interstitial pneumonitis, secondary bacterial bronchopneumonia, myocarditis
Encephalomyelitis: mainly post-infectious, demyelinating (1 : 1,000 cases)
Subacute sclerosing panencephalitis (see Chapter 18 - Neurology)
Temporary immunosuppression for up to 6 weeks post-infection, causing increased
susceptibility to secondary bacterial infections
Diagnosis: clinical, viral culture, immunofluorescence, serology
Treatment: symptomatic; human pooled immunoglobulin < 5 days of exposure to high-
risk patients only. Vitamin A in children who are malnourished or who have severe
measles. Ribavirin has been used in immunocompromised children, but no controlled
studies demonstrating efficacy have been performed
Prophylaxis: immunization - measles, mumps, rubella (MMR)
7.10 Mumps
Incubation: 14-21 days
Transmission: respiratory droplets, infectious 24 h pre- to 3 days post-parotid swelling
Clinical presentation: mild prodrome of fever, anorexia, headache; painful bilateral (may
be unilateral) salivary +/- submandibular gland swelling
-
Complications: occur as a result of viraemia early in the infection:
Meningoencephalitis clinically 10% (subclinically 65%):
Infectious - symptoms same time as parotitis
Post-infectious - symptoms approx. 10 days post-parotitis
Orchitis/epididymitis:
Rare in childhood, 14-35'10 in adolescentsladults
Occurs within 8 days of parotitis, abrupt onset of fever and tender, swollen
testes
Approx. 30-40% of affected testes atrophy; may cause subfertility
Pancreatitis, nephritis, myocarditis, arthritis, deafness, thyroiditis
Diagnosis: viral culture, serology
Treatment: supportive
Prophylaxis: vaccination (MMR)to ensure 'herd immunity'
Infectious Diseases
7.12 Adenovirus
Transmission: respiratory droplets, contact, fomites, very contagious, strict infection
control policy
Incubation: 2 - 14 days
Clinical presentation:
Upper respiratory tract infection
Conjunctivitis +/- pharyngitis
Gastroenteritis - more common in those < 4 years old
Complications: severe pneumonia (more common in infants); disseminated disease in
immunocompromised patients
Diagnosis: viral culture, PCR
Treatment: supportive, Ribavirin has been used with limited success in
immunocompromised patients
7.13 Enteroviruses
These include polioviruses: types 1-3; coxsackieviruses: A and B and echoviruses.
Transmission: faecal/oral and respiratory droplets, infections peak during summer and
early autumn
Clinical presentation:
Non-specific febrile illness: abrupt onset of fever and malaise +/- headache and
myalgia, lasts 3-4 days
Respiratory manifestations: pharyngitis, tonsillitis, nasopharyngitis, lasts 3-6 days
Gastrointestinal manifestations: diarrhoea, vomiting, abdominal pain
Essential Revision Notes in Paedi~tricsfor rhe MRCPCH 2nd Edition
7.14 Molluscum
Incubation: 2 -8 weeks
Transmission: direct contact with infected person or fomites or autoinoculation
Clinical presentation: discrete, pearly papules 1-5 mm, face, neck, axillae and thighs
Diagnosis: clinical, microscopy
Treatment:
Self-limiting but may last months-years
Need to treat in immunodeficient patients or it will become widespread, e.g. remove
with liquid nitrogen
8. PARASITIC INFECTIONS
8.1 Toxoplasmosis
Caused by Toxoplasma gondii
World-wide distribution and infects most warm-blooded animals
Cat is the definitive host and excretes oocysts in stools
Intermediate hosts include sheep, pigs and cattle who have viable cysts in their tissues
Human infection is by eating undercooked meat containing cysts or by ingestion of
oocysts from soil; may also be acquired from blood transfusion or bone marrow
transplantation
Congenital infection (See Section 11)
Clinical manifestations
Often asymptomatic, or non-specific fever, malaise, myalgia, sore throat
May also have lymphadenopathy or mononucleosis-like illness
Complications rarely include myocarditis, pericarditis and pneumonitis, encephalitis
Intkctious Diseases
Diagnosis
By serology (PCR in special cases)
Isolation of 7: gondii is difficult and is not performed routinely.
Atypical lymphocytosis, eosinophilia and inversion of CD4 : CD8 ratio
Treatment
Supportive if mild
Pyrimethamine (and folinic acid) and sulfadiazine if symptomatic. If sulfadiazine is not
tolerated, clindamycin can be used instead. A prolonged course of treatment, up to
1 year, is usual but the optimal length of treatment is not established
Transmission
Occurs by direct contact with hair of infested individuals
Diagnosis
Clinical, can confirm by microscopy
Treatment
Two applications, 1 week apart, of a parasiticidal lotion, left on overnight, e.g.
permethrin and malathion. Resistance is developing, so if the treatment fails try another
insecticide for the next course. Many people use mechanical means of louse control,
e.g. 'nit comb'. Remember to treat the whole family (+/- school class) at the same time.
Always obtain a travel history because imported infections in returning travellers, those from
abroad holidaying in the UK and recent immigrants are part of the differential diagnosis of
fever.
In the last decade, 100 people of all ages have died in the UK from malaria contracted in
malarious areas. Only one of these people was taking full doses of what would currently be
considered an adequate antimalarial. Of these 100 cases, 94 were contracted in Africa and
six in the countries of South Asia. Four African countries accounted for 67% of all the fatal
cases (Kenya 25%, Nigeria 17%, the Gambia 14O/0 and Ghana 11%).
However, it is not just in the developing world and in the tropics that diseases unknown in
the UK occur. There are a number of diseases, endemic to the Americas, that need to be
considered in travellers returning from those regions. Babesiosis and Lyme disease are found
on the east coast of the United States, Rocky Mountain Spotted Fever (a rickettsia1 infection)
and Ehrlichiosis occur in the south and south-west of the country, as does coccidiomycosis,
a fungal respiratory infection. Outbreaks of Hantavirus infections have occurred in Texas
and Arizona and also in Eastern Europe, where tularaemia can also be found. Leishmaniasis
occurs in the Mediterranean as well as in Africa, and should be considered in patients
returning from European holidays with symptoms. The list continues. However, a good
travel and contact history can point to the possibility of an imported idection in a timely
fashion, even if the precise nature of the infection is initially elusive. . .
9.1 Malaria
Caused by Plasmodium spp. (t! vivax, t! malariae, t! ovale and t! falciparum) invading
erythrocytes
Endemic in the tropical world, especially sub-Saharan Africa and parts of South-East
Asia
Transmitted by bite of the female Anopheles mosquito
Congenital infection and blood transfusion-acquired infection may also occur
t! vivax and t? ovale have hepatic stages and may cause relapses of infection
Recrudescence of FI falciparum and FI malariae occurs from persistent low levels of
parasitaemia
f? falciparum malaria is the most severe and potentially fatal disease. This is the
predominent species in Africa
Infectious Diseases
Clinical manifestations
Symptoms appear 8-15 days after infection, with high fevers, chills, rigors and sweats,
which classically occur in a cyclical pattern depending on the type of Plasmodium spp.
involved. Patients can present with malaria up to 3 months after returning from an endemic
area and a high index of suspicion is the key to making the diagnosis
Headaches, abdominal pain, arthralgia, diarrhoea and vomiting are common
Pallor and jaundice occur secondary to haemolysis
Hepatosplenomegaly is more common in chronic infections
Nephrotic syndrome may occur with I? malariae, because of immune-complex
deposition in the kidney
/? falciparum may present as a febrile or flu-like illness with no localizing signs, or as
one of the following clinical syndromes:
Cerebral malaria - with confusion, fits, decreased level of consciousness, coma
Severe anaemia with signs of haemolysis
Hypoglycaemia from disease (metabolic requirements of parasites) and also quinine
treatment
Pulmonary oedema (rare in children)
Renal failure with acute tubular necrosis, or 'blackwater fever' as a result of
haemaglobinuria resulting from severe, acute intravascular haemolysis (rare in
children)
Diagnosis
Thick blood films allow the detection of parasites, thin films allow species identification
and determination of parasitaemia (O/O of erythrocytes harbouring parasites)
Need at least three negative films at 12- to 24-h intervals to be confident of negative
result if there is a high index of clinical suspicion
New tests being evaluated include PCR and malarial ribosbma! RNA (urine dipstix are in
use in the developing world)
NB In hyperendemic areas, low-level parasitaemia, indicating a semi-immune state in
childeren over the age of 4 years, is common and malaria is not necessarily the cause of
the symptoms. However, people who move from these endemic areas do not retain their
semi-immune status and any parasitaemia does become significant
Treatment
Look for and treat hypoglycaemia
Chemotherapy is based on the infecting species, possible drug resistance and disease
severity
Essential Revisiora Notes in Pdedi,liric-s tor the MRCPCH 2nd Edition
f? falciparum malaria
In the UK, we assume that all cases of F! falciparum malaria are chloroquine-resistant
and treat with quinine, orally if possible, or iv if severely unwell for 3-7 days (monitor
glucose and ECC if iv regimen used). One dose of pyrimethamine-sulfadoxine
(Fansidar) is given on the last day of quinine therapy, or, increasingly, a 3-day course of
Atovaquone/proguanil (Malarone) because fansidar resistance is on the increase in
Africa
Exchange transfusion may be warranted if parasitaemia exceeds 10%
Monitor sequential blood smears
f? malariae malaria
Treat with chloroquine (if no resistance)
Prophylaxis
From dusk to dawn (because the Anopheles are night-biters) use protective clothing,
mosquito repellents, bed nets impregnated with insecticide
Prescribe chemoprophylaxis from 1 week before departure until 4 weeks after return:
Chloroquine-sensitive area - chloroquine once a week or proguanil daily
Chloroquine-resistant areas - mefloquine once a week or doxycycline daily
Complications
Intestinal perforation occurs in 0.5-3%, severe haemorrhage occurs in 1-1 0% of
children
Focal infections, e.g. meningitis, osteomyelitis, endocarditis, pyelonephritis more
common in the immunocompromised host
Osteornyelitis and septic arthritis in children with haemoglobinopathies
I Infectious Diseases
\
Chronic carriage - local multiplication in the wall of the gallbladder produces large
numbers of Salmonellae, which are then discharged into the intestine and may cause
chronic carriage and shedding (in 5% of adults but much less in children)
Diagnosis
Perform bacterial cultures on blood, stool, bone marrow or rose spot aspirate
Microscopy of stool reveals many leukocytes, mainly mononuclear
Blood leukocyte count is at the low end of normal. Frank neutropenia can occur
Treatment
Drug choice and route of administration depend on susceptibility of organism, host
response and site of infection - includes:
Ampicillin, ceftriaxone, cefotaxime, chloramphenicol; in view of resistance, a
fluoroquinolone is now frequently used as first-line therapy for 14 days
For osteomyelitis - as above for 4-6 weeks
For meningitis - ceftriaxone or cefotaxime for 4 weeks
To eradicate carriage - high-dose ampicillin or amoxicillin or cholecystectomy
Prophylaxis
Personal hygiene and proper sanitation for food processing and sewage disposal
Vaccine is available, but only 17-66% effective depending on type
Clinical manifestations
Include fever for 1-7 days, frontal or retro-orbital headaches, back pain, myalgia and
arthralgia ('breakbone' fever), nausea and vomiting
1-2 days after defervescence a generalized morbilliform rash occurs lasting 1-5 days.
As this rash fades the fluctuating temperature reappears, producing the biphasic
temperature curve
Esscr~ti~l
Revision Notes in fi1edi~7tt-i~~ r MRCPCH 2r7d Edition
i c ~ the
-
Complications
Dengue haemorrhagic fever (DHF) - fever, haemorrhage, including epistaxis and
bleeding of the gums and capillary fragility and fluid leakage. Complications include
hepatitis, pneumonia, encephalopathy and cardiomyopathy. DHF occurs with the
second infection with the arbovirus and there is an immunological component which
causes augmentation of the disease and an increased severity of the clinical
presentation. Rare in childhood
Diagnosis
PCR, serology, isolation of virus (NB Prior yellow-fever vaccination will give positive
dengue IgG)
Treatment
None is specific, supportive only. Aggressive fluid resuscitaton in DHF markedly
decreases mortality
Diagnosis
Serology
Treatment
Intravenous ribavirin for Lassa fever, especially in the first week of illness, reduces
mortality
Prevention
Strict isolation of patient and contacts. These infections are highly contagious.
For suspected cases - examine a malarial film only (labelled 'Very high risk' for
laboratory staff awareness). If negative, i.e. diagnosis is NOT malaria, then contact local
microbiologist/public health laboratory service urgently for transfer of the patient to the
designated unit.
Infectious Diseases
8.5 Hantaviruses
These are bunyaviruses and cause two different clinical syndromes. Rodents are the
definitive hosts and are asymptomatic carriers that shed virus in their saliva and excreta.
Disease is contracted through contact with infected rodents and their excreta
Old World hantaviruses cause haemorrhagic fever with renal syndrome. Found
throughout Asia and Eastern and Western Europe. Cause up to 100,000 cases a year
New World hantaviruses, which occur in the southwest states of the USA and in the
Andes region of South America, cause hantavirus pulmonary syndrome
Both have an incubation period of 1-6 weeks and present with a prodrome of a non-
specific flu-like illness
Clinical presentation
Haemorrhagic fever with renal syndrome (Old World)
Prodrome characterized by vascular instability followed by renal failure presenting with
oliguria followed by polyuria, hypotension, bleeding and shock
The European disease is milder and presents most commonly as non-specific flu-like
symptoms and proteinuria. Acute severe renal failure is rare
Diagnosis
Serology
Characteristic full blood count abnormalities in pulmonary syndrome which include:
haemoconcentration, thrombocytopenia and neutrophilia with the presence of
immunoblasts on blood film
Treatment
Supportive and symptomatic as required. lntubation and ventilation in pulmonary
syndrome. Dialysis is rarely required in haemorrhagic fever. Meticulous fluid
management
Ribavirin has been used and thought anecdotally to be useful, but evidence for efficacy
is lacking
3
9.6 Giardia
Caused by Giardia lamblia, a protozoan that produces infectious cysts
Faecal-oral transmission
Infection limited to small intestine and/or biliary tract
Worldwide distribution, some animals and humans infected, may infect water supply
Clinical manifestations
Very varied
Acute watery diarrhoea with abdominal pain, or foul-smelling stools and flatulence with
abdominal distension and anorexia
Diagnosis
Stool microscopy, rarely by duodenal biopsy
Treatment
Metronidazole
9.7 Amoebiasis
Caused by Entamoeba histolytica, a protozoan, excreted as cysts or trophozoites in stool
of infected patients
Faecal-oral transmission of cysr
World-wide distribution, with infection rates as high as 20-50°h in the tropics
Clinical manifestations
Intestinal disease - asymptomatic or mild symptoms, e.g. abdominal distension,
flatulence, constipation, loose stools
Acute amoebic colitis (dysentery) - abdominal cramps, tenesmus, diarrhoea with blood
and mucus - complications include toxic megacolon, fulminant colitis, ulceration and,
rarely, perforation
~xtraintestinaldisease
Liver abscess - acute fever, abdominal pain and liver tenderness, or subacute with
weight loss and vague abdominal symptoms; rupture of the abscess into the abdomen or
chest may occur
Rarely, abscesses in the lung, pericardium, brain and genitourinary tract
Diagnosis
Microscopy of stool, biopsy specimens and aspirates, serology if extraintestinal disease
l n f e c t i o ~ ~Diseases
s
Treatment
To eliminate the tissue-invading trophozoites as well as cysts
Metronidazole followed by a luminal amoebicide, e.g. paromomycin
9.8 Hookworm
Caused by Ancylostoma duodenale and Necator americanus
Prominent in rural, tropical areas where soil may be contaminated with human faeces
Humans are the major reservoir
Infection is by infectious larvae penetrating the skin, usually the soles of feet
Clinical manifestations
May be asymptomatic
May develop pruritis and papulovesicular rash for 1-2 weeks after initial infection
Pneumonitis associated with migrating larvae in this phase is uncommon and usually
mild
Diagnosis
Stool microscopy
Treatment
Antihelminthic drug, e.g. mebendazole. (NB Also treat any associated iron-deficiency
anaemia)
9.9 Leishmaniasis
Leishmania species are obligate intracellular parasites of monocytes/macrophages
Variety of hosts including canines and rodents
Vector is the sandfly
Incubation period is usually days-months, but may even be years
Three major clinical syndromes:
Cutaneous leishmaniasis - shallow ulcer at site of sandfly bite; lesions commonly
on exposed skin, i.e. face and extremities; may have satellite lesions and regional
lymphadenopathy
Mucosal leishmaniasis - initial cutaneous infection disseminates to midline facial
structures, e.g. oral and nasopharyngeal mucosa
Visceral leishmaniasis (kala-azar) - parasites spread throughout the reticular
endothelial system and are concentrated in the liver, spleen and bone marrow.
Presents with fevers, weight loss, splenomegaly (may be massive), hepatomegaly,
lymphadenopathy, anaemia, leukopenia, thrombocytopenia and
hypergammaglobulinaemia
Essential Revision Notes in K7ediatrics for the MKCPCH 2nd Edition
Diagnosis
Microscopic identification of intracellular leishmania1 organisms from skin or splenic
biopsy, or bone marrow
Serology may be helpful
Treatment
Sodium stiboglutonate or amphotericin B. Liposomal amphotericin is particularly
effective and is the treatment of choice in the developed world
9.10 Schistosomiasis
Caused by the trematodes (flukes) Schistosoma mansoni, Schistosoma japonicum,
Schistosoma haematobium and others
Humans are the principal host, snail is intermediate host
Eggs are excreted in urine or stool into fresh water, hatch and infect snails; after further
development, cercariae emerge and penetrate human skin
Clinical manifestations
Usually infection is asymptomatic
May have initial transient pruritic, papular rash
May have acute infection - Katayama fever: 4-8 weeks after infection an acute illness
with fever, malaise, cough, rash, abdominal pain, diarrhoea, arthralgia,
lymphadenopathy and eosinophilia
Chronic infection with Schistosoma mansoni and Schistosoma japonicum riay cause
diarrhoea, tender hepatomegaly, chronic fibrosis, hepatosplenomegaly and portal
hypertension
Chronic infection with Schistosoma haematobium may cause dysuria, terminal
microscopic haematuria, gross haematuria, frequency and obstructive uropathy
Haematogenous spread to the lungs, liver and central nervous system may occur
Diagnosis
Identification of the eggs in stool/urine, respectively
Bladder biopsy
Serology
Treatment
Praziquantel
Clinical manifestations
Diarrhoea, abdominal cramps, nausea, bloating, urgency, and malaise; sometimes
vomiting also occurs
Nature of stool may indicate particular organism
TD usually lasts from 3 to 7 days, but is rarely life-threatening
Treatment
Antimotility agents should NOT be used in children. Occasionally in adolescents, like
adults, they may be used to provide prompt symptomatic but temporary relief of
uncomplicated TD. However, they should not be used by people with high fever or with
blood in their stools
Oral rehydration solutions and plenty of fluids should be drunk to prevent dehydration
Antibiotics should be reserved for: those with severe diarrhoea that does not resolve
within several days; if there is blood or mucus, or both, in the stools; if fever occurs with
shaking chills
fix the MKCPCH 2nd Eclitiisn
Essentidl Revision Notes in hediC~trics
Prevention
Treatment of water:
Boiling for at least 5 minutes is the most reliable method to make water safe to drink
Chemical disinfection can be achieved with either iodine or chlorine, with iodine
providing greater disinfection in a wider set of circumstances
Food:
Any raw food can be contaminated, particularly in areas of poor sanitation
Foods of particular concern include salads, uncooked vegetables and fruit,
unpasteurized milk and milk products, raw meat and shellfish
Some fish are not guaranteed to be safe even when cooked because of the presence
of toxins in their flesh. Tropical reef fish, red snapper, amber jack, grouper and sea
bass can occasionally be toxic at unpredictable times if they are caught on tropical
reefs
1 1 CONGENITAL INFECTIONS
Congenital infections are acquired in utero, usually transplacentally, during maternal
infection.
Manifestations are most severe if acquired in the first trimester.
Suspect if:
Small for gestational age
Microcephaly or hydrocephalus
Ocular defects
Hepatosplenomegaly
Thrombocytopenia
Developmental delaylfits
1 1 Diseases
CMV,congenital rubella syndrome, toxoplasmosis
Approximately two-thirds of pregnancies complicated by rubella during the first 8 weeks
of gestation will result in fetal death or severe abnormality
There is a 40% risk of toxoplasmosis transmission from mother to fetus
a In CMV and toxoplasmosis, approximately 1 0% of infected infants are clinically affected
at birth, although symptoms will often become apparent during childhood
NeurologicaI:
Sensorineural hearing loss ++ +
Microcephaly ++ +
Hydrocephalus - ++
Calcification ++ ++
(peri- (widespread)
ventricular)
Eyes:
Micro-ophthalmia
Cataracts
Chorioretinitis
Growth retardation:
Hepatosplenomegaly
Petechiae ('blueberry
muffin' rash)
Cardiac malformations
Pneumonitis
Bony involvement
Parvovirus B19
Women who become infected with parvovirus 819 during first 20 weeks of pregnancy
have a 9% fetal loss
Hydrops fetalis occurs in approximately 3% if the mother is infected between 9 and 20
weeks' gestation
Congenital varicella
Infection during the first or second trimester may rarely cause congenital varicella
syndrome (0.5-2%)
Skin scarring, limb malformation/shortening, cataracts, chorioretinitis, micro-ophthalmia,
microcephaly, hydrocephalus
Inkctious Diseases
Syphilis
High transmission rate, 40% mortality if left untreated
'Snufflesf, congenital nephrotic syndrome, chorioretinitis, glaucoma
Osteochondritis, periostitis
Hepatosplenomegaly, lymphadenopathy
Rash - maculopapular, desquamative, bullous, condylomas
Mycobacterium tuberculosis
Very rare, high mortality
Presents as disseminated disease with fevers and often respiratory distress
Needs Mantoux testing, chest X-ray, lumbar puncture, quadruple therapy + steroids if
meningitis is confirmed
Diagnosis
'TORCH screenr - Toxoplasmosis, 'Otherf, Rubella, CMV and Herpes-specific igM in
neonates < 4 weeks old implies congenital infection
Screen for specific infection based on clinical findings in neonate and mother, rather
than requesting a TORCH screen
NB Look at specific antibody responses in mother's booking-visit blood samples and
post-delivery blood samples to see rise/fall in titres depending on time of infection
acquisition
PCR can be useful in some infections
Ophthalmological examination - characteristic retinal changes
Treatment
Prevention through vaccination is the only way to reduce the risk of congenital rubella
Spiramycin may be used for toxoplasmosis in pregnancy to reduce transmission to the
fetus. Affected infants are treated with pyrimethamine and sulfadiazine after birth
Canciclovir may be used in cases of congenital CMV, aciclovir for herpes simplex,
penicillin for syphilis
Highly active antiretroviral therapy (HAART) used for HIV infection
Anti-TB treatment
Essential Revision Notes in Paediatric-stor the MKCPCH 2nd Eclition
12. MISCELLANEOUS
12.1 Differential diagnosis of prolonged fever
Systemic bacterial disease: Viral disease:
Salmonellosis CMV
Mycobacterial infection Hepatitis viruses
Brucellosis EBV
Leptospirosis Human herpesvirus-6
Spirochaete infections
Non-infectious diseases:
Tuberculosis
Malaria
Causes
Idiopathic (> 50%)
Herpes simplex
Mycoplasma
Viruses - enterovirus spp.
Drugs - sulphonamides, penicillins, barbiturates
Treatment
Treat underlying cause; supportive; steroids in severe EM (early)
Treatment
Antimicrobials specific to the infection
Steroids: systemic most effective
Ir~fectiousDiseases
12.10 Anthrax
Caused by the Gram-positive organism Bacillus anthracis
Wild and domestic animals in Asia, Africa and parts of Europe carry the bacterium
The bacterium can exist as a spore, which allows the bacterium to survive in the
environment (e.g. in the soil)
Inhalation anthrax
Much less common. Caused by breathing in anthrax spores. Symptoms begin with a flu
like illness, followed by respiratory difficulties and shock after 2-6 days. High fatality
rate
Intestinal anthrax
Very rare form of food poisoning, which results in severe gut disease, fever and
septicaemia. Mortality of up to 50%
Vaccine - available for very high-risk groups only
Post-exposure prophylaxis with antibiotics can be very effective in preventing disease,
providing it is given early enough
Treatment
High-dose penicillin and doxycycline or ciprofloxacin
12.11 Botulism
Botulism is caused by a botulinum toxin, produced by the bacterium Clostridium
botulinum
The bacterium is anaerobic and common in the soil in the form of spores
Food-borne botulism occurs when the spores of C. botulinum have germinated and the
bacteria have reproduced in an environment (usually food) outside the body and
produced toxin. The toxin is consumed when the food is eaten
The toxin is destroyed by normal cooking processes
Clinical manifestations
Botulism is a neuroparalytic disorder that can be classified into three categories:
Foodborne:
Onset of symptoms is usually abrupt, within 12-36 h of exposure
Essential Revision Notes it?E7edi;ltric-ctor fhc MRCPCIW 2r7d Eclition
Diagnosis
Enriched selective media are used to culture C. botulinum from stools and food
A toxin neutralization assay can identify botulinum toxin in serum, stool or food
* Electromyography has characteristic appearances
Treatment
Supportive care, especially respiratory (e.g. ventilation) and nutritional
Antitoxin
Concerns about the effectiveness and side-effects of the vaccine against botulism; it is
not widely used
Immunity to botulism toxin does not develop, even with severe disease
Prevention
Education regarding food preparation.
Therapeutics
Botulinum A toxin, in small doses, is used therapeutically to prevent excessive muscular
activity, e.g. in torticollis, cerebral palsy, and recently in cosmetics to reduce wrinkles.
Kuru
A disease of motor incoordination, it was endemic in Papua New Guinea in the 1950s and
1960s. Kuru was a TSE spread by the ritual cannibalism of deceased relatives. Cannibalism
ceased in the late 1 9 5 0 ~but
~ there are still a few cases in older adults indicating a long
incubation period.
CONTENTS
1. Basic metabolism
1.1 Carbohydrate metabolism
1.2 Protein metabolism
1.3 Fat metabolism
1.4 Vitamins
4. Organic acidaemias
4.1 Propionic, methylmalonic and isovaleric acidaemias
4.2 Glutaric aciduria type 1 (GA-1)
7. Mitochondria1 cytopathies
7.1 Mitochondrial genetics
7.2 Clinical features
8. Disorders of carbohydrate metabolism
8.1 Glycogen storage disease
8.2 Galactosaemia
8.3 Hereditary fructose intolerance
9. Hyperlipidaemias
9.1 Hypertriglyceridaemias
9.2 Hypercholesterolaemias
12. Sphingolipidoses
12.1 Tay-Sachs disease
1 2.2 Gaucher disease
12.3 Niemann-Pick disease
12.4 Fabry disease
13. Miscellaneous
13.1 Porphyria
13.2 Smith-Lemli-Opitz syndrome
13.3 Congenital disorders of glycosylation (CDG)
13.4 Lesch-Nyhan syndrome
13.5 Menkes syndrome
14. Screening
14.1 Principles of screening
14.2 UK neonatal screening programme
1. BASIC METABOLISM
1.1 Carbohydrate metabolism
Glucose has three metabolic fates in the body: oxidation for energy, storage as glycogen,
and conversion to amino acids and triglycerides.
A steady supply of adenosine triphosphate (ATP) is needed to power each cell's essential
processes. This ATP is usually supplied from the oxidation of glucose provided in the diet
and from glycogen stores. In the fasted state, the hormone-mediated response is to draw on
the body's reserves - fat and protein (catabolism) - to make up the fuel shortfall to
generate ATP.
The diet rarely contains glucose as the only carbohydrate source, other carbohydrates, e-g.
fructose, galactose, lactose etc., need to be converted to glucose first before they can be
used for energy.
Glycolysis
Glycolysis takes place in the cytoplasm of all cells and describes the break down of one
molecule of glucose to produce two molecules of pyruvate:It can occur under aerobic
(large energy production via the tricarboxylic acid (TCA) cycle and oxidative phosphoryla-
tion) or under anaerobic conditions (small energy production via lactate). Glycolysis
provides an emergency mechanism for energy production when oxygen is limited, i.e. in
red cells (which have no mitochondria, thus glycolysis is their only means of energy
production) or in skeletal muscle during exercise. Glycolysis also provides intermedidtes for
other metabolic pathways, e.g. pentoses for DNA synthesis. The three enzyme steps are
irreversible.
Pyruvate metabolism
Pyruvate, produced by glycolysis and other metabolic pathways, can be converted to
oxaloacetate (by pyruvate carboxylase) for entry into the TCA cycle, or acetyl-CoA (by
pyruvate dehydrogenase) which has a number of potential fates. These being:
Oxidation in TCA cycle
Fatty acid synthesis
Ketone body synthesis
Steroid synthesis
Esseratic~/ c s the MRC-PCH 217d Edition
Revision Notes in Y ~ e d i ~ t l - ifor
Glycogen metabolism
Glycogen is a branched glucose polymer stored in liver, kidney and muscle for the rapid
release of glucose when needed. Liver glycogen is a store to release glucose to the rest of
the body, whereas muscle glycogen supports muscle glycolysis only.
Glycogen synthesis is promoted by insulin and involves :
UDP glucose synthesis (glucose donor) from glucose-1-phosphate
Elongation of glycogen (glucose linked to existent glycogen strand (a-1,4 glycosidic
bond)
Branch formation (a-1,6 glycosidic bond)
Glycogenolysis is promoted by adrenaline and glucagon and involves:
Shortening of chain to release glucose-1-phosphate
Sequential removal until the branch point is reached
Removal of branch point
1.4 Vitamins
Vitamins are organic compounds needed in very small quantities in the body.
Fat-soluble vitamins A, D, E and K are stored in the liver and can be toxic in excess,
especially vitamins A and D.
Water-soluble vitamins are the B group vitamins and vitamin C. They are required
regularly in the diet because the body does not store them in significant quantities.
2.2 Presentation
Presentation is notoriously non-specific, therefore clues should be sought in the history. The
commonest misdiagnosis is sepsis.
Intoxication
Key feature is a symptom-free period before decompensation whilst the toxic metabolites
build up, i.e. once feeds are established and the neonate no longer relies on the placenta
Essential Revision Notes in Paediatrics tbr the MRCPC-H 2nd Fclition
Energy insufficiency
Absence of symptom-free period with immediate onset of symptoms in congenital lactic
acidosis. There is a spectrum of severity and some may take longer to decompensate. The
group includes conditions that only present if there is a delay in fuel provision, e.g. fat
oxidation defects, and glycogenolysis and gluconeogenesis defects; these may not present
for some months or longer.
Respiratory chain defects
Pyruvate metabolism defects (pyruvate dehydrogenase, pyruvate carboxylase)
Fat oxidation defects - medium-chain acyl-CoA dehydrogenase (MCAD), long-chain
hydroxyacyl-CoA dehydrogenase (LCHAD), very-long-chain acyl-CoA dehydrogenase
(VLCAD)
Glycogen storage disease (GSD) types I and Ill
Defects of gluconeogenesis - fructose bisphosphatase deficiency
2.3 Examination
Clinical examination may reveal few clues in many disorders of intermediary metabolism.
Dysmorphic features may suggest certain diagnoses. Odours are usually unhelpful and
rarely significant (exceptions include MSUD, in which the nappies smell sweet, and
isovaleric acidaemia, i'n which there is a pungent sweaty odour). ~ ~ should
e s be carefully
examined for corneal clouding (mucopolysaccharidoses, cystinosis), cataracts (galactosae-
mia, peroxisomal, mitochondrial), pigmentary retinopathy (fat oxidation, mitochondrial) and
cherry-red spot (Tay-Sachs, Niemann-Pick, Sandhoff, CM1).Organomegaly is a key reveal-
ing sign. Hepatosplenomegaly is a feature of storage disorders. Massive hepatomegaly in
the absence of splenomegaly suggests glycogen storage disease because glycogen is not
stored in the spleen. More prominent splenomegaly is suggestive of Gaucher disease.
2.4 Investigation
Perform investigations at the time of decompensation when diagnostic metabolites are most
likely to be present and avoid the need for stress tests at a later date.
Metabolic Medicine
Acid-base status
Anion gap = Na+ + K+ - (CI- + HC03-)
A normal anion gap (10-1 8 mmolll) in the presence of metabolic acidosis signifies
bicarbonate loss rather than an excess of acid, e.g. renal or gut. Marked ketosis is unusual
in the neonate and is therefore highly suggestive of an underlying metabolic disorder. Urea
cycle defects may initially present with a mild respiratory alkalosis because ammonia acts
directly on the brainstem as a respiratory stimulant.
Hypoglycaemia
Hypoglycaemia is defined as a blood glucose concentration of G 2.6 mmol/l, and should
always be confirmed in the laboratory. The key additional investigation is the presence or
absence of ketosis. Hypoketotic hypoglycaemia has a limited differential diagnosis that can
usually be resolved on history and examination:
Hyperinsulinism (endogenous or exogenous)
Fat oxidation defects (e.g. MCAD)
Liver failure
Hyperinsulinism is suggested by a persistently increased glucose demand > 10 mglkg per
min
Glucose requirement (mglkg per min) = (ml/h x OO
/ dextrose) / (6 x weight (kg))
Lactate
Lactate is a weak acid which can be used directly as a fuel for the brain and is readily
produced during anaerobic respiration. Secondary causes of lactate level anomalies (e.g.
hypoxia, sepsis, shock, liver failure, poor sampling, etc.) are much more common than
primary metabolic causes. Ketosis is usually present in primary metabolic disease, unlike in
secondary causes, with the exception of pyruvate dehydrogenase deficiency, GSD type I
and fat oxidation defects. The level of lactate is unhelpful in distinguishing the cause, and
the lactate : pyruvate ratio usually adds little. A low ratio (< 10) may indicate pyruvate
dehydrogenase deficiency. Exacerbation when a patient is fasted is a feature of gluconeo-
genesis defects, of GSD type I compared to GSD type I l l and of respiratory chain disorders
in which lactate may increase post-prandially. The markedly raised lactate in decompen-
sated fructose bisphosphatase deficiency characteristically rapidly resolves on treating the
hypoglycaemia.
Met2 holic Medicine
Cerebrospinal fluid (CSF) lactate is raised in mitochondrial disorders, central nervous system
(CNS) sepsis and seizures.
Ammonia
Hyperammonaemia may result from poor sampling (squeezed sample) andlor delays in
processing. The level of ammonia may prove discriminatory as to the cause.
Normal
Sick patient, fat oxidation defect, OA, liver failure, UCD
Fat oxidation defect, OA, liver failure, UCD
OA, liver failure, UCD
Liver failure, UCD, (OA rarely)
OA, organic acidaemia; UCD, urea cycle defect.
Transient hyperammonaemia of the newborn (THAN) is characterized by very early onset,
usually in the first 36 hours before feeding is truly established. It is associated with low
glutamine. THAN is managed as other urea cycle defects but has an excellent prognosis if
treated early as the hyperammonaemia is secondary to blood bypassing the liver (e.g. patent
ductus venosus), rather than a block in the urea cycle.
Amino acids
Amino acids are measured in both blood and urine. The latter: ieflects renal threshold, e.g.
generalized aminoaciduria of a proximal renal tubulopathy or the specific transporter defect
of cystinuria (Cystine, Ornithine, Arginine, Lysine). An increase in the serum levels of a
specific amino acid may be missed if only a urine sample is analysed and the renal
threshold has yet to be breached. Plasma amino acids are useful in the work up of a
number of metabolic disorders, and are essential in monitoring some metabolic disorders.
f Leucine, isoleucine and valine - maple syrup urine disease (MSUD)
TGlutamine, 1arginine (+I- f citrulline) - f UCDs
fAlanine - lactic acidosis
* TGlycine - non-ketotic hyperglycinaemia, OAs
f Phenylalanine - phenylketonuria
?Tyrosine - tyrosinaemia
Organic acids
These are measured in urine only and are diagnostic in many organic acidaemias, e.g.
increased propionate in propionic acidaemia, increased isovalerate in isovaleric acidaemia,
etc. but are also essential in the diagnosis of other disorders.
fOrotic acid - UCDs, mitochondrial, benign hereditary
Essential Revision Notes in P;lediatrics tor the MRCIPCCH2nd Edition
Acylcarnitines
Carnitine conjugates with acyl-CoA intermediates proximal to the block in fat oxidation
defects. The chain length of the acylcarnitines formed is diagnostic of where the block lies,
e.g. medium-chain (MCAD), very long-chain (VLCAD), etc. Likewise, conjugation with
organic acids allows diagnosis of organic acidaemias, e.g. propionylcarnitine. Total and free
carnitine levels can be measured at the same time.
Urate
Urate is the end product of the breakdown of purines. Raised levels in plasma may indicate
increased production (eg Lesch-Nyhan syndrome, GSD type I, rhabdomyolysis) or de-
creased excretion (familial juvenile hyperuricaemic nephropathy, FJHN). It is essential to
measure a concurrent urinary urate because urate clearance in children is so efficient that
plasma levels may be in the upper normal range in Lesch-Nyhan syndrome, whereas
urinary levels are grossly elevated. In FJHN the reverse is true with high plasma urate, but
low urinary urate. Low plasma urate is seen in molybdenum cofactor deficiency as a result
of a block in the conversion of purine bases to urate.
-
=
-
Acute patient screening 3-
Specific metabolites are used to screen acute patients for specific disorders or groups of
disorders.
Metabolite Disorder
Very-long-chain fatty acids Peroxisomal disorders, e.g. Zellweger
syndrome, adrenoleukodystrophy
Transferrin isoelectric focusing Congenital disorders of glycosylation
Urate Purine disorders
7-Dehydrocholesterol Smith-Lemli-Opitz syndrome
Biotinidase Biotinidase deficiency
Urinary glycosaminoglycans Mucopolysaccharidoses and
and oligosaccharides mucolipidoses
Urinary reducing substances Galactosaemia
Urinary sulphites Sulphite oxidase deficiency,
molybdenum cofactor deficiency
Urinary purine and pyrimidine Purine and pyrimidine disorders
metabolites
M e t .bolic Medicine
Enzymology
Definitive diagnosis is confirmed on enzymology. The sample requirement depends on
which tissues express the enzyme, e.g. galactosaemia (blood), OTC deficiency (liver),
mitochondrial (muscle). Genotype has superseded invasive biopsy in some conditions, e.g.
GSD type I (glucose 6-phosphatase deficiency).
White cell enzymes are often requested in patients with potential neurodegenerative or
storage disorders. Laboratories usually undertake different lysosomal assays for different
presentations. The neurodegeneration panel includes Tay-Sachs, Sandhoff, Sly mucopoly-
saccharidosis (MPS VII) and mannosidosis in plasma; GM1 gangliosidosis, arylsulphatase A
deficiency, Krabbe and fucosidosis in white cells. The organomegaly panel includes Sly
(MPS VII), and mannosidosis in plasma, GM1gangliosidosis, Gaucher, Niemann-Pick A and
B, mannosidosis, fucosidosis and Wolman disease in white cells.
Phenylalanine hydroxylase
Phenylalanine v *Tyrosine
Biopterin
Diagnosis
Detection of a raised phenylalanine level on neonatal screening;' confirmed on plasma
amino acids and exclusion of biopterin defects.
Management
Phenylalanine is an essential amino acid and therefore cannot be totally excluded from the
diet. The developing brain is most vulnerable to the deleterious effects of high phenylala-
nine; however, evidence is increasing that dietary restrictions should be continued for life.
Patients with milder elevations of phenylalanine have hyperphenylalaninaemia and may or
may not require treatment dependent on how elevated their levels are.
Phenylalanine restriction (given as exchanges of natural protein titrated against
phenylalanine levels monitored on home fingerprick blood tests)
Amino acid supplement (no phenylalanine)
Special PKU products (minimal or no phenylalanine)
Free foods (negligible phenylalanine)
Neurotransmitter replacement in biopterin defects (+ I- acid)
folinic
/L,letaholicMedicine
Diagnosis
Tyrosine is raised in the plasma and the presence of succinylacetone in urine is patho-
gnomonic. Coagulation is almost always deranged even in the minimally symptomatic
patient and should be actively sought in a patient with renal tubulopathy. Confirm by liver
enzymology (furnarylacetoacetase).
Management
acetoacetate
A low phenylalanine and low tyrosine diet supplemented with a tyrosine-free and phenyla-
lanine-free amino acid supplement has been the mainstay of management; improving both
liver and renal function but failing to prevent the development of hepatocarcinoma.
Nitisinone has revolutionized the management by blocking the catabolic pathway proximal
to the production of the damaging metabolites. Nitisinone is a derivative of the bottle-brush
plant originally developed as a weed-killer. Dietary restriction remains but it is hoped that
the risk of tumours is greatly reduced. Liver transplantation is reserved for patients failing to
respond to nitisinone, or who develop tumours or progressive cirrhotic liver disease. Tumour
surveillance includes interval hepatic MRI and monitoring of a-fetoprotein.
Essentic?tRevision Noles 1 h r the MKCPCH 2nd Edition
i7 Pt~edi~?trics
Clinical features
The severe neonatal form presents as a classic intoxication with encephalopathy and
seizures. Biochemical disturbance, i.e. acidosis, ketosis, may be minimal and therefore the
diagnosis is often delayed with the illness often being attributed to sepsis. The neonate has a
sweet odour, hence the name. Intermittent forms may present at a later age, patients
appearing entirely symptom-free between bouts. Cerebral oedema is a well-recognized
complication during acute episodes.
Diagnosis
Elevated branch-chain amino acids plus alloisoleucine
Elevated branch-chain 0x0-acids on urinary organic acids
Enzymology on fibroblasts
Management
Long-term management centres on controlling leucine levels with a low-protein diet
supplemented with an amino acid supplement that is free of branch-chain amino acids.
Valine and isoleucine may require additional supplementation because levels may fall too
low while controlling leucine. The enzyme cofactor thiamine is given in the hope of
improving residual enzyme activity.
3.4 Homocystinuria
Homocystinuria may result from a number of metabolic defects. Classical homocystinuria
(cystathione-$-synthasedeficiency) presents with a typical dysmorphology similar to Marfan
syndrome. Differences include lower lQ, stiff joints, direction of lens dislocation and malar
flush.
Metabolic Medicine
Diagnosis
Measurement of total plasma homocysteine is becoming the method of choice, superseding
free homocysteine plasma levels. In classical homocystinuria, the plasma methionine is
elevated. Definitive diagnosis is based on enzymology in fibroblasts.
Management
Treatment aims to reduce plasma total homocysteine to reduce the risks of thrombosis and
lens dislocation. Protein restriction is used in patients diagnosed on screening, but is
particularly difficult to institute in the cases who present later. Fifty per cent of patients
respond to cofactor supplementation (pyridoxine). Folate should also be supplemented as
depletion affects response. Betaine is effective at lowering homocysteine by remethylation
and is particularly useful in the pyridoxine non-responsive patient.
Diagnosis
The first clue is usually elevated glycine on urinary or plasma amino acids. The diagnosis is
confirmed by measuring simultaneously the CSF : plasma glycine ratio (>0.09). Enzymol-
ogy is traditionally assessed in the liver, but a new assay using lymphocytes is now
available.
Management
Glycine is reduced with sodium benzoate but has little effect on neurological outcome.
Dextromethorphan (a partial N-methyl-D-aspartate(NMDA)) receptor antagonist helps block
the central action of glycine and has helped reduce fits in some patients compared to
conventional anticonvulsants. Prognosis remains poor for development. Newer NMDA
receptor blockers are currently under investigation. Prenatal testing is available.
f ; ~fhc
Fsc~nti,l/Revision ,*t'ott~s in R7+-'c/iclfri~-:; r h J K C 'PC%! 2I ?c/f c / i f i o / ?
Defects in the catabolism of amino acids result in the accumulation of organic acids which
are detected in urine. Propionic acidaemia (PA) and methylmalonic aciduria (MMA) result
from blocks in branched-chain amino acid degradation, isovaleric acidaemia (IVA) is the
result of a block in leucine catabolism and glutaric aciduria type 1 (GA-1) results from a
block in lysine and tryptophan metabolism.
Diagnosis
Marked acidosis with ketosis is a key feature. Lactate and ammonia are invariably raised.
Blood glucose may be low, normal or raised. Propionate is partly produced by gut
organisms, therefore decompensation in PA and MMA may be precipitated by constipation.
Neutropenia is another useful clue to the diagnosis. The key metabolites are detected on
urinary organic acids, and enzyme deficiency is confirmed on enzyniology.
Management
Long-term management is based on dietary protein restriction. Carnitine supplementation
helps eliminate organic acids via conjugation and renal excretion. Glycine is used similarly
in IVA. Some forms of MMA are vitamin BIZ responsive. Metronidazole is used in MMA
and PA to alter the gut flora to reduce propionate production and help avoid constipation.
Liver transplantation is gaining acceptance as a definitive treatment in PA in view of the
high risk of subsequent neurological decompensation; however the procedure does not
eliminate the risk of neurological deterioration in MMA.
Diagnosis
The diagnosis must be actively sought in children with large heads and no other explana-
tion, in an effort to prevent metabolic decompensation and subsequent severe neurology.
GA-1 may mimic non-accidental injury with encephalopathy and bilateral subdurals. Diag-
nosis is made on urinary organic acid metabolites and acylcarnitine analysis (low free
carnitine and raised glutaryl-carnitine). A minority of cases are non-excretors, therefore
fibroblasts are required for definitive enzymology in cases that have a strongly suggestive
clinical picture but negative organic acids.
Management
In the absence of screening, the diagnosis is usually only made post-decompensation. In
prospectively treated siblings, protein restriction in conjunction with aggressive treatment of
infections and hyperalimentation has improved the prognosis; however, there is a broad
spectrum of phenotypes and some children still decompensate in spite of treatment.
Diagnosis
UCDs are suggested by the presence of a respiratory alkalosis in the child with encephalo-
pathy. Indication of the exact level of the enzyme block depends on plasma amino acids
and urinary organic acids for the presence or absence of orotic acid. Orotic aciduria
Essential Revision Notes it7 Pr7ediC? r IL.1KCPCH 2nd Edition
trics h ~ the
indicates a block at the level of OTC or beyond. Final confirmation of the diagnosis requires
enzymology.
Management
Treatment follows the basic principles as detailed at the beginning of this chapter. Elimina-
tion of ammonia is accelerated by dialysis because earlier reduction in ammonia improves
the long-term neurological outcome. Sodium benzoate and sodium phenylbutyrate conju-
gate with glycine and glutamine, respectively, to produce water-soluble products that can
be excreted by the kidney, therefore bypassing the urea cycle and reducing the nitrogen
load on the liver. Arginine becomes an essential amino acid in UCDs (except argininaemia)
and is supplemented. Long-term protein is restricted and medicines are adjusted according
to growth, amino acids and ammonia.
Liver transplantation has been used successfully in patients with brittle control; however,
numbers are small and follow-up is limited.
Diagnosis
Detection requires a strong clinical suspicion to ensure that appropriate investigations are
performed at the time. The presence or absence of ketosis should be sought in all cases of
hypoglycaemia. Plasma-free fatty acids are raised, while ketone formation is impaired.
Urinary organic acids reveal a characteristic dicarboxylic aciduria in the acute state, but
may be normal between episodes. Acylcarnitines detect an elevated octanoyl carnitine, and
genotyping is used for confirmation. The G985 common mutation accounts for > 90% of
allelles in clinically presenting cases in the UK. It is therefore a useful tool with which to
assess at-risk siblings. A newborn screening pilot study began in the UK in 2004 (see
Section 14.2).
Management
Prevention is better than cure. Mortality is 25% on first presentation, and 33% of survivors
have neurological sequelae. Once the diagnosis is known, further decompensations can be
avoided by employing an emergency regimen of glucose polymer drinks during intercurrent
illnesses or admission for a 10% dextrose infusion if the drinks are not tolerated. In the at-
risk neonate born to a family with a previously affected sibling, feeds should be frequent
with intervals no longer than 3 hours, and top-up feeds ekablished if needed while
acylcarnitine results are awaited. Neonatal deaths have been reported.
Diagnosis
Characteristic dicarboxylic aciduria is noted in acute episodes on urinary organic acids.
Creatine kinase may rise acutely and frank rhabdomyolysis can occur. Acylcarnitines form
the mainstay of diagnosis with confirmation on fibroblast flux studies. There is a common
LCHAD mutation. Urine and blood samples from infants born to mothers with AFLP or
HELLP should be screened post-delivery.
Management
Long-chain fat intake is severely restricted and the diet is supplemented with medium-chain
fat and essential fatty acids. Normoglycaemia is maintained with frequent bolus feeds during
the day, and overnight nasogastric or gastrostomy feeds in infancy. Uncooked cornstarch
can be introduced from 2 years of age to smooth and prolong glycaemic control. An
emergency regimen is used during intercurrent infections with admission for intravenous
therapy if not tolerated. Carnitine supplementation is used to correct acute depletion,
secondary to increased excretion of carnitine-fatty acid conjugates in the urihe.
7. MITOCHONDRIAL CYTOPATHIES
Mitochondria are the power stations of the cell, producing ATP to drive cellular functions.
The respiratory chain, the site of oxidative phosphorylation, is embedded in the inner
mitochondrial membrane and consists of five complexes. Electrons are donated from
reduced cofactors and passed along the chain, ultimately reducing oxygen to water, while
the energy so produced pumps hydrogen ions from the mitochondrial matrix into the
intermembrane space. Discharge of this electrochemical gradient through complex V (ATP
synthase) generates ATP.
Outer membrane
0,- H,O +
ADP - ATP
Thirty-three per cent of paediatric patients present in the neonatal period, and 8O0/0 in the
first 2 years. Many syndromes have been described; however, these were initially reported
in adults and are associated with mtDNA mutations which are less common in children
(e.g. mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes
(MELAS), myoclonic epilepsy-ragged red fibres (MERRF) and Kearns-Sayre syndrome).
Syndromes may also be incomplete.
CNS - Leigh syndrome, hypotonia, deafness, epilepsy, stroke-like episodes
Muscle - myopathy, fatigue
Heart - hypertrophic cardiomyopathy, heart block
Kidney - proximal tubulopathy
Liver - failure, cirrhosis
Gut - diarrhoea, malabsorption, pancreatic insufficiency, Faltering growth
Eye - external ophthalmoplegia, pigmentary retinopathy
Bone marrow - refractory anaemia
Endocrine - short stature, diabetes, endocrinopathies
Investigation
Studies of mtDNA are preferred if a classic mitochondrial syndrome is identified. Usually
mitochondrial disease is suspected when there is multiorgan involvement in apparently
unrelated organs: so-called 'illegitimate associations'. Peripheral lactate may be persistently
elevated. Further organ involvement may be sought before muscle biopsy for histochemistry
(staining for complex II and IV), and respi;atory chain enzymology (complexes I-IV).
CNS - magnetic resonance imaging, brainstem auditory evoked potentials, CSF lactate
Heart - echocardiography, electrocardiogram (ECG)
Kidney - proximal tubular proteins, tubular resorption of phosphate
Liver - biopsy, enzymology
Gut - stool elastase
Eye - fundoscopy, electroretinogram, visual evoked responses
Marrow - full blood count, aspirate
Endocrine - electrolytes
Management
Management remains supportive. A variety of antioxidants and respiratory-chain pick-me-
ups have been described with success in only a handful of cases, e.g. ubiquinone,
riboflavin. Dichloroacetate resolves the raised lactate but does not appear to improve
outcome.
Metabolic Medicine
gluconeogenesis is not blocked, and glycogen can be pruned to near the branch points.
Nephromegaly is not a feature. Myopathy is notable and may be progressive in type Illa.
Cardiomyopathy is a rare complication. Adenomas, liver fibrosis and cirrhosis are rare.
Lactate level rises, unlike in type I, on glucose loading. The diagnosis may be confirmed on
white cell enzymology. Dietary management is similar to but not as intensive as for type I.
A high protein diet has been suggested for the type Illa.
Muscle GSDs
GSD V (muscle phosphorylase deficiency) McArdle disease and CSD VII (phosphofructo-
kiniise deficiency)
Weakness and fatigue with post-exercise stiffness are the presenting features. Serum creatine
kinase is usually elevated along with uric acid. On exercise, lactate fails to rise with
excessive increases in uric acid and ammonia. After a brief rest, exercise can be restarted
('second-wind') as fatty acids slowly become available as an alternative fuel. Protein in the
diet may be beneficial. Glucose is of benefit in McArdle disease because glycolysis is still
intact. Extreme exercise should be avoided but regular gentle exercise is probably of
benefit.
8.2 Galactosaemia
Clinical featuresof galactosaemia
Neanatat onset -- jsundice, hepatomegaly, coagulopathy and oil-drop cataracts,
usually at the end of the first week
8 Later presentation wiih Faltering grpvth,
months
Association with ~scherichiacolibsepsis
Diagnosis
Diagnosis is based on the clinical picture, the presence of reducing substances in the urine
and enzymology for galactose 1-phosphate uridyltransferase (Gal 1-Put) in red cells. If the
child has already received a transfusion, the parents should be screened for carrier-level
activity instead. Even in the absence of obvious major liver involvement, the clotting is
nearly always slightly prolonged. Galactosaemia should be considered in all cases of severe
early-onset jaundice.
Management
This consists of a strict lactose/galactose-free diet for life. Milk is replaced with a soya-based
formula. Long-term complications, in spite of good control, include developmental delay,
particularly involving speech, feeding problems and infertility in girls.
Diagnosis
Lactic acidosis and hyperuricaemia are common features. Confirmation is by exposure to
fructose and measurement of aldolase b activity in liver. Genotyping is used when liver
biopsy is contraindicated because of coagulopathy.
Management
Lifelong avoidance of fructose.
High-density lipoprotein (HDL) - carries cholesterol from the peripheries to the liver.
Inverse association with ischaemic heart disease ('good cholesterol')
9.1 Hypertriglyceridaemias
Defective chy lomicron removal - lipoprotein lipase deficiency, apol ipoprotein C-ll
deficiency
Overproduction of VLDL - familial hypertriglyceridaemia
Hypertriglyceridaemias are rare. Clinical features include colic, hepatosplenomegaly, erup-
tive xanthomas and creamy plasma. Complications include abdominal pain and pancreatitis
but rarely develop in patients until the triglyceride level exceeds 20 mmol/l. Secondary
causes of elevated triglycerides include obesity, chronic renal failure, diabetes mellitus and
liver disease. Treatment comprises a very low-fat diet supplemented with essential fatty
acids. Drugs used to lower triglycerides include fibric acid derivatives, niacin or statins.
Fibrate drugs reduce hepatic triglyceride synthesis and enhance peripheral triglyceride
clearance, statins reduce triglycerides, probably by reducing VLDL synthesis.
9.2 Hypercholesterolaemias
Defective LDL removal - familial hypercholesterolaemia
Familial combined hyperlipidaemia
Familial hypercholesterolaemia is a monogenic disorder with a heterozygote incidence of
1 : 500, and homozygote 1 : 1,000,000. It is the commonest hyperlipidaemia, resulting from
LDL-receptor gene mutations. Patients are picked up through premature ischaemic heart
disease, or through screening for hypercholesterolaemia following diagnosis in a relative.
Family history is an important risk factor for ischaemic heart disease, particularly at a young
age and especially in females. In homozygotes, xanthomas may appear in -the first decade,
and angina before the age of 20.
In children, diet and exercise are the mainstay of treatment. These were previously
supplemented with binding resins, e.g. cholestyramine and colestipol, which bind cholester-
ol and bile acids in the gut, increasing their loss in the faeces, and were preferred in
paediatrics because they are not systemically absorbed. However, taking the sachets can be
likened to drinking wet sand and so compliance was low. The new cholesterol-lowering
margarines containing plant sterols are a more palatable alternative, reducing cholesterol
absorption in the gut, but are expensive and have to be paid for by the families. Smoking is
strongly discouraged. Increasingly, statins are being used in the over-10s as more safety data
becomes available. However, theoretical concerns remain over their safety in this age
group, particularly with regard to puberty. Statins are teratogenic. Liver function and
creatine kinase are regularly monitored for adverse-effects. Their mechanism of action is the
competitive inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting step of
cholesterol synthesis. Liver transplantation, or plasma apheresis, is the treatment of choice
for homozygotes.
Metabolic Medicine
Sensorineural deafness
Ocular abnormalities -
retinopathy, cataracts
Diagnosis
Loss of all peroxisomal functions - raised very-long-chain fatty acids, phytanate and bile
acid intermediates and decreased plasmalogens. Confirmatory enzymology on fibroblasts.
Treatment
Management is supportive. Docosahexaenoic acid supplementation has been tried but nc
clear benefit has been demonstrated. Death usually occurs within the first year.
The paediatric cerebral form presents with severe neurological degeneration, usually be-
tween 5 and 10 years, progressing to a vegetative state and death within a few years.
Brothers in the same family may present at different ages.
Adrenal involvement may precede or follow neurological symptoms by years. Some only
develop neurological symptoms, and others just have adrenal insufficiency. All males
developing adrenal failure should have very-long-chain fatty acid measurements taken to
ensure that the diagnosis is not missed. Neurological symptoms may occur for the first time
in adults (adrenomyeloneuropathy) resembling a cord syndrome with spastic gait and
bladder involvement. Female carriers may develop multiple sclerosis-like symptoms in
adulthood.
Diagnosis
Elevated very-long-chain fatty acids, blunted synacthen response or frank hypoglycaemia.
Neuroimaging shows bilateral, predominantly posterior, white-matter involvement. The
differential diagnosis for neurodegeneration in the school-age child includes:
Subacute sclerosing panencephalitis
Batten disease
Wilson disease
Niemann-PickC disease.
Management
Lorenzo's oil (oleic and erucic acid) normalizes the very-long-chain fatty acids but fails to
prevent progression. Bone marrow transplantation is the mainstay of therapy in patients
before neurodegeneration, i.e. prospectively diagnosed siblings, and those diagnosed after
presentation with adrenal insufficiency or other problems. Serial psychometry and neuroi-
maging are used to detect the first signs of neurological deterioration - the stimulus for
transplantation. Adrenal function should be closely monitored, and steroid replacement
therapy should be given once it is indicated.
n. MUCOPOLYSACCHARIDOSES (MPS)
Mucopolysaccharides (glycosaminoglycans) are structural molecules integral to connective
tissues such as cartilage. Degradation occurs within lysosomes, requiring specific enzymes.
Patients with MPS appear normal at birth and usually present with developmental delay in
the first year. The features of storage become more obvious with time.
Hurler syndrome is the classical MPS with storage affecting the body and CNS. Sanfillipo
syndrome predominantly affects the CNS and Morquio and Maroteaux-Lamy syndromes
affect the body. Atlantoaxial instability is common in the latter two, often necessitating
prophylactic cervical spinal fusion in the first 2-3 years. Hunter syndrome is phenotypically
similar to Hurler syndrome, however there is no corneal clouding and scapular nodules are
seen.
Diagnosis
Urinary screen for glycosaminoglycans (raised dermatan and heparan sulphate). Enzymol-
ogy confirmed on white cells.
Management
Treatment depends on early recognition to allow early bone marrow transplantation, which
significantly modifies the phenotype. Enzyme replacement clinical trials are currently
underway. Supportive care is the mainstay of untransplanted patients, with particular regard
to the chest and airway requiring 3-monthly sleep studies.
12. SPHINGOLIPIDOSES
Sphingolipids are complex membrane lipids. They are all derived from ceramide and can
be divided into three groups: cerebrosides, sphingomyelins and gangliosides. Lysosomal
hydrolases break these molecules down; deficiencies result in progressive storage and
disease. Typical features include psychomotor retardation, neurological degeneration in-
cluding epilepsy, ataxia and spasticity, with or without hepatosplenomegaly.
.*
Diagnosis
The presence of vacuolated lymphocytes on the blood film i s a further clue. Hexosamini-
dase A deficiency is confirmed on white cell enzymology.
Management
Currently, management is supportive. However, research into substrate-deprivation therapy,
thereby avoiding accumulation in the first place, is under investigation.
Diagnosis
Elevated angiotensin-converting enzyme (ACE) and acid phosphatase are markers for the
disease. Bone marrow aspiration may reveal Gaucher cells (crumpled tissue-paper cyto-
plasm). White cell enzymes for glucocerebrosidase give the definitive diagnosis. The
enzyme chitotriosidase is markedly elevated and may be used to follow disease activity.
Management
Enzyme replacement therapy is effective in visceral disease in qpes 1 and 3. Bone marrow
transplant has been used in the past, and may have benefit for cerehral involvement in type
3. Splenectomy has been used to correct thrombocytopenia and anaemia and relieve
mechanical problems but may accelerate disease elsewhere. There is no effective treatment
for type 2.
Diagnosis
Bone marrow aspirate for Niemann-Pick cells. White cell enzymes. Genotyping may help
distinguish between the two types before the onset of neurological signs.
Management
Supportive.
Hepatosplenomegaly
Neurological deterioration (variable age of ons
Dystonia
-Cherry-red spo
Vertical ophthalmoplegia
Type D (Nova Scotia variant)
As above, single mutation (founder effect)
~tdet~~bolic
Medicine
Diagnosis
Niemann-Pick cells on bone marrow aspirate; however, white cell enzymes show normal
or mildly decreased sphingomyelinase deficiency. Definitive diagnosis requires cholesterol
studies on fibroblasts.
Management
Supportive. Prognosis is guided by age of onset.
Diagnosis
Maltese crosses (bi-refringent lipid deposits) in urine under microscope. White cell
enzymes.
Management
Analgesia, dialysis and renal transplantation are the established therapies. Enzyme replace-
ment therapy has now been licensed for the treatment of Fabry disease in adults, with
clinical trials in children underway.
13. MISCELLANEOUS
13.1 Porphyria
Porphyrias are a group of disorders of haem biosynthesis that may be classified as acute
(neuropsychiatric), cutaneous or mixed. Symptoms in children are extremely rare. Inheri-
tance is autosomal dominant except in congenital 8-aminolaevulinic acid dehydratase
deficiency, erythropoietic porphyria and hepatoerythropoietic porphyria.
Essential Revision Notes in t.'?edi,?tricshr-the MR(cPC-H 2nd Edition
Diagnosis
Acute attacks
Raised urinary aminolaevulinic acid and porphobilinogen during attacks (fresh urine)
Faecal porphyrin analysis to distinguish type
Cutaneous forms
Total plasma porphyrins (raised if active lesions)
Total faecal porphyrins
Erythrocyte porphyrins
Management
Cutaneous forms are managed by avoidance of precipitants, especially sunlight, and good
skin care. Acute attacks are managed with glucose and haem arginate, reducing synthesis of
aminolaevulinic acid by negative feedback. Many drugs precipitate atta'cks, therefore only
those known to be safe should be used during an attack.
Drugs used:
Pain - opiates
Psychosis - chlorpromazine
Tachycardia, hypertension - (3-blockers
Seizures - gabapentin, vigabatrin
Mental retardation
Renal anomalies
Faltering growth
Diagnosis
SLO is the result of a block in the penultimate step of cholesterol biosynthesis, therefore
cholesterol is low with a raised 7-dehydrocholesterol level, the immediate precursor.
Management
At present, management is supportive. However, trials are underway evaluating the use of
statins to block the build-up of precursors. Cholesterol supplementation has not shown
convincing benefit.
Diagnosis
Transferrin isoelectric focusing is used to screen for CDG syndromes. Enzymology is
performed on white cells and fibroblasts.
Management
CDG lb is effectively managed with mannose supplementation. The other types are treated
symptomatically.
Essential Revision Notes in 6 ' r ? c d i ~ t 5r ih)r
~ f \ ~ t ~ I L l K ~ - b 2~1(7-~f JEc/ition
/
Diagnosis
Elevated urate and hypoxanthine in urine. Plasma urate may be normal because of the
excellent renal clearance in childhood and so a urinary urate must also be measured.
Enzymology red cells or fibroblast studies.
Management
Allopurinol and liberal fluids are used to reduce the risk of renal complications. Seating and
positioning are essential to aid development and avoid self injury in conjunction with
relaxation techniques and communication skills. A full multi-disciplinary team is essential.
A low-purine diet is often undertaken but the evidence base for its use is limited.
Diagnosis
LOW serum copper and caeruloplasmin, although these may be normal in the neonatal
period. Confirmed on copper-flux studies in fibroblasts, and ultimately by genotyping.
Management
Daily copper-histidine injections have proven effective in altering the neurological out-
come if the diagnosis is made early and treatment is not delayed. The connective tissue
complications subsequently dominate the clinical picture in treated patients.
14. SCREENING
14.1 Principles of screening
Screening for defined disorders aims to prevent avoidable morbidity and mortality. The
sensitivity of a screening test is the rate of true-positives, and its specificity i s the rate of
true-negatives. The aim is not to miss any cases with the minimum of false-positives. The
necessary requirements for including a condition in a screening programme are:
important health problem
Accepted treatment
Facilities available for diagnosis and treatment
Latent or asymptomatic disease
Suitable test
Natural history understood
Agreed case definition
Early treatment improves prognosis
Economic
Case-finding may need to be continuous
The UK National Screening Committee added a further requirement; randomized controlled
trial evidence to support introduction of new screens.
Current UK programme
Universal
Congenital hypothyroidism (thyroid-stimulating hormone)
Phenylketonuria (phenylalanine)
Haemoglobinopathies (sickle-cell disease and thalassaemia)
Some regions
MCAD
Cystic fibrosis (to become universal)
Galactosaemia
Homocystinuria
Duchenne muscular dystrophy
Haemoglobinopathies and cystic fibrosis have now been agreed for inclusion in the national
screening programme. MCAD screening commenced in March 2004 in six laboratories
screening half of the UK (300,000 births each year) to compare outcomes between the
screened and unscreened populations with the aim of subsequent roll out nationally at the
end of the study.
Duchenne muscular dystrophy is an example of a condition not fulfilling the criteria (being
ultimately incurable); however, the public and professional support for the programme has
grown with time. An 'important health problem' has been interpreted on an individual
rather than a population basis. Potential benefits include 'avoidance of the diagnostic
odyssey', with all its associated emotional and financial expense before the correct diag-
nosis is made, influences on reproductive choice in the parents (at a time before subsequent
pregnancies) and the hope that earlier identification may lead to positive interventions to
influence outcome and better research.
Newer screening technologies, such as tandem mass spectrometry, further challenge the
established criteria because it is now much easier to diagnose a w h ~ l enumber of not only
inborn errors of metabolism, but also liver disease, haemaglobinopathies, etc. Although
additional screening costs may be minimal because the current system of blood-spot
collection can be utilized, there is a large burden placed on diagnostic and support services
dealing with the new caseload. Rarity may no longer preclude screening a whole popu-
lation when there is an effective treatment available, e.g. biotinidase deficiency cured with
biotin supplementation.
The number of conditions screened for has been massively increase in some countries. The
US is expanding to 30 conditions; however, for many of these disorders the natural history
is poorly understood and the diagnostic test does not always clearly decide who will
develop symptoms. Concerns remain that individuals will be given a diagnostic label on the
basis of a raised marker or mutation, but will never develop symptoms. The so-called 'un-
patient'. Considering MCAD screening, many new mutations have been detected since the
introduction of screening, many of which have never previously been found in clinically
presenting cases.
Metabolic Medicit~e
CONTENTS
1. Embryology, obstetrics and fetal medicine
1.1 Embryology of the cardiovascular system
1.2 Embryology and post-natal development of the respiratory system
1.3 Embryology of the gastrointestinal system
1.4 Embryology of the central nervous system
1.5 Embryology of the genitourinary system
1.6 Maternal conditions affecting the fetus and newborn
1.7 Placental physiology, fetal growth and wellbeing
1.8 Amniotic fluid, oligohydramnios and polyhydramnios
1.9 Body composition at birth
1.10 Hydrops fetalis
1.1 1 Fetal circulation, adaptation at birth and persistent pulmonary
hypertension of the newborn
2. Prematurity -
definitions and statistics
2.1 Mortality - definitions
2.2 Incidence and causes/associations of pre-term birth
2.3 Outcome after pre-term birth
2.4 Small-for-gestational-age babies
I 3. Respiratory problems
i
3.1 Surfactant deficiency
3.2 Chronic lung disease (bronchopulmonary dysplasia)
I 3.3 Meconium aspiration syndrome (MAS)
1
3.4 Pneumonia
3.5 Pulmonary air leak
3.6 Congenital lung problems
I 3.7 Chest wall abnormalities
I 3.8 Upper airway obstruction
3.9 Principles of mechanical ventilation in neonates
3.1 0 Extracorporeal membrane oxygenation (ECMO)
I 4. Cardiovascular problems
1 4.1 Patent ductus arteriosus (PDA)
4.2 Hypotension
for the h1RCPCH 217d Editiot~
Essential Revision Notes in Pc~ediatrics
4.3 Hypertension
4.4 Cyanosis in the newborn
6. Neurological problems
6.1 Peri-intraventricular haemorrhage (PIVH)
6.2 Periventricular leukomalacia (PVL)
6.3 Neonatal encephalopathy
6.4 Neonatal seizures
6.5 Causes of hypotonia in the newborn
6.6 Retinopathy of prematurity (ROP)
7. Genitourinary problems
7.1 Congenital abnormalities of the kidneys and urinary tract
7.2 Haematuria in the newborn
7.3 Causes of acute renal failure in neonates
7.4 Ambiguous genitalia
8. Infection
8.1 Bacterial infection
8.2 Congenital viral infection
8.3 Fungal and protozoal infections
Only severe cases require treatment with P-blockers and antithyroid drugs because it
resolves spontaneously as antibody levels fall over the first few months
Neonatal hypothyroidism may be caused by maternal antithyroid drugs taken during
pregnancy.
Thrombocytopenia
Transplacental passage of maternal antiplatelet antibodies causes neonatal thrombocyto-
penia. If the mother is also thrombocytopenic the cause is likely to be maternal idiopathic
thrombocytopenia (also associated with maternal SLE).
Platelet count proportional to that of mother
Rarely causes very low neonatal platelet counts or symptoms
Risk of intracranial haemorrhage if platelet count < 50 x 1o9/I (may occur antenatally,
therefore Caesarean section not always protective)
Treatment: intravenous immunoglobulin G (IgG) and platelet transfusion
Alloimmune thrombocytopenia occurs following maternal sensitization if mother is P L ~ '
antigen-negative.
Approximately 3% of White people are P L ~ antigen-negative
'
First pregnancies may be affected; severity is usually greater in subsequent pregnancies
Antenatal intracranial haemorrhage is common (20-50%)
Treatment - washed irradiated maternal platelets or intravenous IgG and random donor
platelets
See Chapter 11 - Haematology and Oncology
Myasthenia gravis
Babies of mothers with myasthenia gravis have a 10% risk of a transient neonatal form of
the disease.
Usually the result of transplacental passage of anti-acetylcholinesterase receptor
antibodies but baby may produce own antibodies
Risk is increased if a previous baby was affected
Maternal disease severity does not correlate with that of baby; a range of symptoms from
mild hypotonia to ventilator-dependent respiratory failure may occur
Neonatology
Maternal smoking
Reduces birth weight by 10% on average
Increases risk of sudden infant death syndrome
Maternal drugs
Teratogenic drugs include:
Phenytoin (fetal hydantoin syndrome) - dysmorphic face (broad nasal bridge,
hypertelorism, ptosis, ear abnormalities)-
* Valproate - neural tube defects, fused metopic suture, mid-face hypoplasia, congenital
heart disease, hypospadias, talipes, global developmental delay
Retinoids (isotretinoin) and large doses of vitamin A - dysmorphic face (including cleft
palate), hydrocephalus, congenital heart disease
Cocaine - SGA, prune belly and renal tract abnormalities, gut, cardiac, skeletal and
eye malformations
Other teratogenic drugs include thalidomide (limb defects), lithium, carbamazepine,
chloramphenicol and warfarin
within 1-2 days of birth but may be delayed until 7-1 0 days and continue for several
months; onset is later and symptoms persist for longer with methadone
Symptoms are:
Wa kefuIness
Irritability
Tremors, temperature instability, tachypnoea
High-pitched cry, hyperactivity, hypertonia
Diarrhoea, disorganized suck
Respiratory distress, rhinorrhoea
Apnoea
Weight loss
Autonomic dysfunction
Lacrimation
Also - seizures, myoclonic jerks, hiccups, sneezing, yawning
Surfactant deficiency is less common
Sudden infant death syndrome is more common
Management - monitor using withdrawal score chart. Less than 50% require
pharmacological intervention. Indications for this are severe withdrawal symptoms or
seizures. Oral morphine is the usual treatment of choice. Methadone, phenobarbital,
benzodiazepines and chlorpromazine have also been used
Oestrogen
Initially produced by the corpus luteum and then in increasing amounts by the placenta
as pregnancy progresses
Causes the uterine smooth muscle to proliferate
Enhances development of the uterine blood supply
Changes pelvic musculature and ligaments to facilitate birth
Causes breast development by increasing proliferation of glandular and fatty tissue
Neonatologv
Progesterone
Limited amounts produced by the corpus luteum in the early part of pregnancy - much
larger amounts produced by the placenta after the first trimester
Causes endometrial cells to store nutrients in first trimester
Relaxes uterine smooth muscle; decrease in secretion of progesterone in the final few
weeks of pregnancy coincides with onset of labour
Facilitates glandular development of breasts
1 Oxytocin
Produced by the hypothalamic-posterior pituitary axis
Release is stimulated by irritation of the cervix
@ Oxytocin causes contraction of uterine smooth muscle
4g Causes milk secretion - stimulation via the hypothalamus
B
B
C Prolactin
f;
Produced by the hypothalamic-anterior pituitary axis
h Production is inhibited during pregnancy by high levels of oestrogen and progesterone
4
:I produced by the placenta; the sudden decrease in these after delivery of the placenta
increases prolactin release
€1
Prolactin causes secretion of milk from the breasts
Hypothalamic production of a prolactin inhibitory factor increases if the breasts are
engorged with milk and decreases as the baby breast-feeds
Prolactin inhibits follicle-stimulating hormone immediately post-partum, thereby
I preventing ovulation
Biophysical profile - fetal movement, posture and tone, breathing, amniotic fluid
volume and cardiotachograph assessed
Causes
Immune cause is usually Rhesus disease.
Non-immune causes include:
Anaemia:
Twin-to-twin transfusion
Fetomaternal haemorrhage
Homozygous a-thalassaemia
Heart failure:
Arrhythmias (supraventricular tachycardia, complete heart block)
Structural (cardiomyopathy, hypoplastic left and right heart, etc.)
High-output (arteriovenous malformations, angiomas)
Chromosomal abnormalities (Turner syndrome, trisomy 21 and other trisomies)
Congenital malformations:
Congenital cystic adenomatoid malformation
Diaphragmatic hernia
Cystic hygroma
Chylothorax and pulmonary lymphangiectasia
Osteogenesis imperfects
Asphyxiating thoracic dystrophy
Infection:
Parvovirus B19
Cytomegalovirus (CMV)
Toxoplasmosis
Syphilis
Chagas disease (a South American parasite infection)
Congenital nephrotic syndrome
Idiopathic - 15-20% cases
dissociation curve of HbF, but the lower p50 leads to a decreased rate of unloading to
tissues. Levels of 2,3-DPG rise rapidly in the first few days to meet the increased
metabolic requirements that occur after birth. Pre-term infants have lower 2,3-DPG
levels and therefore have a limited ability for oxygen to be unloaded from red blood
cel Is
Approximately 80% of haemoglobin is HbF at term. This falls to < 10% by 1 year
The following also shift the oxyhaemoglobin dissociation curve to the left:
Alkalosis
Hypocarbia
Hypothermia
Nitric oxide
Free radical
Synthesized in endothelial cells from L-arginine by the enzyme nitric oxide synthase -
also known as endothelium-derived relaxing factor
In vascular smooth muscle - nitric oxide activates guanylate cyclase to increase
Neona tcdo,,ry
3. RESPIRATORY PROBLEMS
3.1 Surfactant deficiency
Endogenous surfactant is produced by type 2 pneumocytek, which line 5-10% of the
alveolar surface. Surfactant-containing osmiophilic granular inclusion bodies cause these to
appear different from the thinner and more numerous type 1 pneumocytes, which are
responsible for gas exchange.
Phosphatidylserine
Sphingomyelin
Surfactant-associated proteins
Surfactant protein A
Mainly immune function but also has a role in spreading and recycling of surfactant
Has been shown to increase microbial killing by alveolar macrophages
Increases resistance to inhibitors of surface activity which occurs in sepsis
Surfactant protein B
Major role in adsorption, spreading and recycling of surfactant
Case reports suggest that congenital deficiency of surfactant protein B is a lethal,
autosomal recessive condition
Surfactant protein C
0 Similar function to surfactant protein B
Surfactant protein D
Immune function
Synthetic DPPC
Hexadecanol Hours 5 1 1
Ty loxapol Lipids (inc. DPPC) Minutes 11 11 11
Animal
Surf. proteins B+C
CLDIBPD, chronic lung disease/bronchopulmonary dysplasia
Neonatology
Radiological stages
Stage 1 1 st few days indistinguishable from surfactant deficiency
Stage 2 2nd week generalized opacity of lung fields
Stage 3 2-4 weeks streaky infiltrates
Stage 4 >4 weeks hyperinflation, cysts, areas of collapse/consolidation,
cardiomegaly
Inhaled steroids - only proven benefit is to reduce the need for systemic steroids
Bronchodilators
Diuretics - only likely to be of benefit in the presence of PDA, cor pulmonale or
excessive weight gain
Respiratory syncytial virus (RSV) prophylaxis with monoclonal antibodies (Palivizumab)
has been shown to reduce hospitalization in high risk cases, but use is controversial
because of the high cost of the drug and the need for monthly intramuscular injections
throughout the RSV season
fields may develop over the next 48 hours as chemical pneumonitis becomes more of a
problem. In severe cases, changes similar to chronic lung disease may develop over the
following weeks.
Uncontrolled trials of vigorous airway suction immediately after delivery suggest that it is
possible to reduce the incidence of MAS. Intubation for lower airway suction is only needed
if meconium can be seen below the vocal cords. Thoracic compression and routine
bronchial lavage have no proven benefit. Intermittent positive-pressure ventilation with a
relatively long expiratory time to prevent further gas trapping may be required in moderate
to severe MAS. Surfactant replacement therapy in infants with MAS has proven benefit, but
large doses may be required. Extracorporeal membrane oxygenation (ECMO) may be used
in the most severe cases.
3.4 Pneumonia
Pneumonia can be congenital, intrapartum or nosocomial.
Congenital
Onset is usually within 6 hours of birth.
Bacterial
Streptococci (group B streptococcus)
Coliforms (E. coli, Klebsiella, Serratia, Shigella, Pseudomonas etc.)
Pneumococci
Listeria
Viral
CMV
Rubella virus
Herpes simplex virus
Coxsackievirus
Other
Toxoplasmosis
Chlamydia
Ureaplasma urealyticum
Candida
Intraparturn
Onset is usually within 48 hours.
Bacterial
Group B streptococci
Coliforms (as above)
Haemophilus
Staphylococci
1
eI Neonatology
Pneumococci
Listeria
.
Viral
Herpes simplex virus
Varicella zoster virus
Nosocomial
Onset is after 48 hours.
Bacterial
Staphylococci
Streptococci
Pseudornonas
Klebsiella
Pertussis
Viral
RSV
Adenovirus
Influenza viruses
Parainfluenza viruses
Common cold viruses
Other
Pneurnocystis carinii
Pneumomediastinum
May complicate surfactant deficiency or other forms of neonatal lung disease, when it
may coexist with pneumothorax or may be iatrogenic following tracheal rupture
secondary to intubation
No symptoms may occur in isolated pneumomediastinum, but respiratory and
cardiovascular compromise are more likely to occur if pneumothorax is also present
outcome because the hernia usually occurs later, allowing for reasonable lung growth.
In utero repair and tracheal plugging have been attempted but with variable outcomes
Respiratory distress (usually severe), heart sounds on the right side of the chest, bowel
sounds on the left side, a scaphoid abdomen and vomiting may be found at birth. Less
severe cases may not present initially but develop increasing respiratory distress over the
first 24 hours as the gut becomes more air-filled. Differential diagnosis is congenital
cystic adenomatoid malformation (or even pneumothorax)
During resuscitation
Bag and mask positive-pressure ventilation should be avoided
Wide-bore nasogastric tube should be placed as soon as possible to deflate gut and to
confirm diagnosis, and therefore distinguish between differential diagnoses of congenital
cystic adenomatoid malformation or pneumothorax on subsequent chest X-ray
Consider paralysing baby to avoid air swallowing and to reduce the risk of
pneumothorax
Surgical management
There is some evidence to suggest that stabilizing the baby before surgery improves
outcome
Malrotation is corrected if present; the diaphragmatic defect is usually closed with a
synthetic patch
Post-operative care
High-frequency oscillation, nitric oxide or ECMO may be of benefit, but evidence for
routine use of these is lacking
Mortality overall is approximately 50-6O0/0
Survivors may have problems associated with underlying puimonary hypoplasia
Type 1 CCAM
Single or small number of large cysts
Commonest type (50% cases)
May cause symptoms by compression or may be asymptomatic initially
Good prognosis after surgery
Type 2 CCAM
Multiple small cysts
Usually cause symptoms by compression of surrounding normal lung
Prognosis variable
Type 3 CCAM
Airless mass of very small cysts giving the appearance of a solid mass
Worst prognosis
Chylothorax
Effusion of lymph into the pleural space as a result of either:
Underlying congenital abnormality of the pulmonary lymphatics
Iatrogenic following cardiothoracic surgery
Diagnosis by antenatal ultrasound scan allows antenatal drainage by insertion of
intercostal drains, which may reduce the risk of pulmonary hypoplasia and facilitate
resuscitation after birth
Ventilatory support may be required post-natally, along with intermittent intercostal
drainage
Volume of chyle can be reduced by using a medium-chain triglyceride milk formula or
avoiding enteral feeds for up to several weeks as the underlying abnormality resolves
with time; protein and lymphocyte depletion may complicate this
Surgical treatment is needed for the small number of cases that do not resolve
spontaneously
Neonatology
Thanatophoric dysplasia
Usually sporadic
Very short limbs - femur X-ray described as 'telephone handle' shape
Very small, pear-shaped chest
Death from lung/chest hypoplasia occurs in the neonatal period
Camptomelic dysplasia
Autosomal recessive
Very bowed, shortened long bones
Death from respiratory insufficiency usually occurs in childhood
Choanal atresia
Incidence is 1 : 8,000
More common in females
Occurs as a result of a failure of breakdown of bucconasal membrane
May be unilateral or bilateral, bony or membranous
60% associated with other congenital abnormalities including the CHARGE association:
C = colobomata, H = heart defects, A = atresia of choanae, R = retarded growth and
development, G = genital hypoplasia in males, E = ear deformities
Essential Revision Notes ill Paediatrics tbr the MRCPCH 2nd Edition
Presents at birth with respiratory distress and difficulty passing a nasal catheter. Oral
airway insertion relieves respiratory difficulties. Diagnosis confirmed by contrast study or
CT scan
Surgical correction by perforating or drilling the atresia requires post-operative nasal
stents
Laryngomalacia
Commonest cause of stridor in the first year of life
lnspiratory stridor increases with supine position, activity, crying and upper respiratory
tract infections
Usually resolves during the second year of life
Upper airway endoscopy is merited if persistent accessory muscle use occurs, with
recurrent apnoea or faltering growth
Subglottic stenosis
May be congenital but usually acquired.
Systemic steroids may facilitate extubation in mild to moderately severe subglottic stenosis.
Laser or cryotherapy to granulomatous tissue seen on upper airway endoscopy may also be
Neonatology
of benefit in these cases. Severely affected babies require surgery - anterior cricoid split or
tracheostomy.
Tracheomalacia
Causes expiratory stridor
Usually caused from extrinsic compression - most commonly as a result of vascular
rings
Also associated with tracheo-oesophageal fistula
Surgical treatment of underlying pathology usually leads to resolution, but tracheostomy
and positive-pressure ventilation may be required
4. CARDIOVASCULAR PROBLEMS
4.1 Patent ductus arteriosus (PDA)
Uncommon in term infants after 1-2 days
Often presents around third day of life in VLBW infants because left to right shunt
increases as pulmonary vascular resistance falls; approximately 40% of VLBW infants
with surfactant deficiency have clinically significant PDA on day 3 of life
Clinical signs - systolic or continuous murmur, bounding pulses, wide pulse pressure,
active precordium and possibly signs of cardiac failure and reduced lower body
perfusion
A clinically significant PDA in VLBW infants is associated with an increased risk of:
Pulmonary haemorrhage
Chronic lung disease
lntraventricular haemorrhage
Necrotizing enterocolitis
Mortality
Neonatology
a Early treatment of PDA with indomethacin has been shown to reduce necrotizing
.
enterocolitis and chronic lung disease
Ibuprofen is likely to be equally effective in closing PDA but has fewer side-effects
than indomethacin
4.2 Hypotension
Arrhythmias
Supraventricular tachycardia
Complete heart block
Reduced venous return
Pulmonary air leak
Pericardial effusionltamponade
Lung hyperinflation (more common in high-frequency oscillation' or with high
positive end-expiratory pressure (PEEP))
4.3 Hypertension
Causes of hypertension in n
Vascular
Renal artery thrombosis (associated with umbilical artery catheterization)
Aortic thrombosis (associated with umbilical artery catheterization)
Renal vein thrombosis (more common in infan%of diabetic mothers)
Renal artery thrombosis % .
a Coarctation of aorta
Middle aortic syndrome
Renal
Obstructive uropathy
Dysplastic kidneys
Polycystic disease
*
Renal tumours r
Intracranial hypertension
a Endocrine
Congenital adrenal hyperplasia 5+
Hyperthyroidism -
Q Neuroblastoma i '
Phaeochromocytoma
Drug-induced
Systemic steroids
lnotropes
Maternal cocaine
Neonatology
Risk factors
Prematurity
Antepartum haemorrhage
Perinatal asphyxia
Polycythaemia
PDA
PROM
Early enteral feeding has also been suggested as NEC rarely occurs in infants who have not
been fed. However, randomized controlled trials suggest that early feeding with small
amounts of breast milk is beneficial. The incidence of NEC in pre-term infants is 6-10 times
Essential Revision Notes in Paedic7tricstbr the M RCPCH 2nd Edition
higher in those fed formula milk compared to those given breast milk. There is some
evidence that enteral vancomycin before initiating milk feeds reduces the incidence of
NEC.
The severity of NEC can be classified using Bell's staging:
Complications
Perforation occurs in 20-30°h of confirmed NEC cases
Overwhelming sepsis
Disseminated intravascular coagulation (DIC)
Strictures - occur in approximately 20% cases of confirmed NEC,
Recurrent NEC - occurs in < 5% cases (consider Hirschsprung disease)
Short-bowel syndrome following extensive resection
Lactose intolerance
Medical management
Cardiorespiratory support as required
Stop enteral feeds for 7-14 days (depending on the severity of illness)
Nasogastric tube on free drainage
Give intravenous fluids/total parenteral nutrition (TPN)
Give intravenous antibiotics
Treatment of thrombocytopenia, anaemia, DIC
Serial abdominal X-rays (to exclude perforation)
5.3 Breast-feeding
Physiology
A surge in maternal prolactin (from the anterior pituitary) occurs immediately post-
partum, which stimulates milk production
Suckling stimulates prolactin receptors in the breast and oxytocin release (from the
posterior pituitary). Oxytocin facilitates the 'let-down' reflex by contraction of breast
myoepithelial cells
Colostrum is produced over the first 2-4 days. Subsequent milk production is controlled
mainly by the amount of suckling or expression
Benefits of breast-feeding
See Chapter 9 - Gastroenterology and Nutrition (Section 2.3 - Breast-feeding)
Contraindications to breast-feeding
See list of contraindicated maternal drugs below and Chapter 9 - Gastroenterology and
Nutrition (Section 2.3 - Breast-feeding)
Complications
Mother - breast engorgement, breast abscess, poor milk production
Baby - poor weight gaidinitial excessive weight loss, breast milk jaundice
Dapsone
Doxepin
Ergotamine
Gold
lndomethacin
Iodides
Lithium
Oestrogens (decrease lactation)
Opiates (high dose should be avoided but weaning to a low dose may facilitate
withdrawal in infant)
Phenindione
Vitamin D (risk of hypercalcaemia with high dose)
Daily nutritional requirements per kg for stable, growing preterm babies are approximately
as follows:
Protein - 3.0-3.8 g
Energy - 110-1 20 kcal
Carbohydrates - 3.8-1 1.8 g
Fat - 5-20% of calories
Sodium - 2-3 mmol
Potassium - 2-3 mmol
Calcium - 2-3 mmol
Phosphate - 1.94-4.52 mmol
+ other minerals (iron, zinc, copper etc.), trace elements (selenium, manganese etc.) and
vitamins
Clinical presentation
Polyhydramnios
Excessive salivation
Early respiratory distress
Abdominal distension
Vomitingkhoking on feeds
Inability to pass nasogastric tube
Absence of gas in gut on X-ray if no tracheo-oesophageal fistula
Other anomalies in 30-5O0Io - VACTERL (Vertebral, Anal, Cardiac, Tracheo-
oesophageal fistula, Ears, Renal, Limb), rib anomalies, duodenal atresia
Prematurity common
Management
Respiratory support as needed
Riplogle tube (large-bore, double-lumen suction catheter) on continuous suction is
placed in the proximal oesophageal pouch
Surgical management includes early division of the fistula and early or delayed
oesophageal anastomosis. This depends on the distance between the'two ends of atretic
oesophagus - for wide gaps, delayed anastomosis to allow growth may improve
outcome. Cervical oesophagostomy or colonic transposition may also be used in this
situation.
H-type tracheo-oesophageal fistula (tracheo-oesophageal fistula without oesophageal
atresia) is much less common and is usually not associated with pre-term birth or other
severe anomalies. It may present in the neonatal period or later with respiratory distress
associated with feeding, or recurrent lower respiratory infections.
Duodenal atresia
Approximately 70% are associated with other congenital anomalies (trisomy 21,
congenital heart disease, malrotation, etc.)
Often diagnosed antenatally with ultrasound 'double-bubble' or polyhydramnios
Usually presents post-natally with bilious vomiting
Neonatology
Malrotation
a Occurs as a result of incomplete rotation of the midgut in fetal life resulting in
intermittent and incomplete duodenal obstruction by Ladd's bands
a Associated with diaphragmatic hernia, duodenal and other bowel atresias and situs
inversus
a Presents with bilious vomiting and some abdominal distension with sudden deterioration
in the event of midgut volvulus
a Upper gastrointestinal contrast studies show the duodenal-jejunal flexure on the right of
the abdomen with a high caecum
Meconium ileus
Commonest presentation of cystic fibrosis in neonates (10-1 5% cases)
> 90% of babies with meconium ileus have cystic fibrosis, therefore genetic testing for
all common mutations and serum immune reactive trypsin must be used for
confirmation
May present with antenatal perforation, peritonitis and intra-abdominal calcification or
post-natally with intestinal obstruction
Water-soluble contrast enemas may lead to resolution of meconium ileus
Important to distinguish between meconium ileus and meconium plug - with
meconium plug, symptoms usually resolve after passage of plug and the problem is not
associated with cystic fibrosis
Anorectal atresia
May have other features of VACTERL association
May be high or low with the puborectalis sling differentiating.- more likely to be a low
lesion in females
Colostomy is needed for all high atresias
Renal tract ultrasound scan, micturating cystogram +/- cystoscopy are needed to
exclude rectovaginal, rectourethral or rectovesical fistula or other urinary tract anomaly
High atresias often have problems with faecal incontinence, whereas those with
intermediatellow lesions usually have good outcomes
Hirschsprung's disease
Occurs as a result of an absence of ganglion cells in either the short or long segment of
the bowel; the rectum and sigmoid colon are most often affected but cases extending to
the upper gastrointestinal tract have been described
May present with delayed passage of meconium (> 24 hours), bowel obstruction
relieved by rectal examination (may be explosive!), enterocolitis or later constipation
Diagnosis is made by rectal biopsy
Regular rectal washouts are required before temporary colostomy formation (usually
reversed at 6 months)
br-t l ~ M
Essentia1 Revision Notes in Y;7cdic~tric.s c RCPCH 2nd Edition
Results from failure of the gut to return into the abdominal cavity in the first trimester
The defect is covered by peritoneum which may be ruptured at birth
Approximately 75% cases have other congenital anomalies - trisomies, congenital
heart disease, Beckwith- Wiedemann syndrome
Primary or staged surgical closure is required
Gastroschisis
Rarer than exomphalos and much less likely to be associated with other congenital
anomalies
Aetiology unknown but may be associated with teenage pregnancy
Bowel is not covered by peritoneum and therefore becomes stuck together with
adhesions; this leads to functional atresias and severe intestinal motility problems post-
surgical repair of the abdominal wall defect
Prognosis is mostly good
6. NEUROLOGICAL PROBLEMS
6.1 Peri-intraventricular haemorrhage (PIVH)
The germinal matrix or layer occurs in the caudothalamic notch of the floor of the lateral
ventricles. It is the site of origin of migrating neuroblasts from the end of the first trimester
onwards. By 24-26 weeks' gestation this area has become highly cellular and richly
vascularized. This remains so until 34 weeksf gestation by which. time it has rapidly
involuted. The delicate network of capillaries in the germinal matrix is susceptible to
haemorrhage, which is likely to occur with changes in cerebral blood flow. Preterm infants
have decreased autoregulation of the cerebral blood flow, which 'contributes to the
pathogenesis. In term infants PIVH may originate from the choroid plexus.
Hypotension
PDA
Timing of PIVH
0 350% in first 24 hours
Approx. 10-20% day 2-3
Approx. 20-30% day 4-7
Approx. 10% after the first week
Classification of PIVH
Grade 1 - germinal matrix haemorrhage
Grade 2 - intraventricular haemorrhage without ventricular dilatation
Grade 3 - intraventricular haemorrhage with blood distending the lateral ventricle
Grade 4 - echogenic intraparenchymal lesion associated with PIVH; previously this
was thought to be an extension of bleeding from the lateral ventricles into the
surrounding periventricular white matter but it is likely to be venous infarction
Several classification systems have been described. The most widely accepted is that of
Papile (above). It may, however, be better to use a more descriptive classification.
Prevention of PIVH
The following have been shown to reduce the incidence of PIVH:
Antenatal steroids
Maternal vitamin K
lndomethacin (but long-term neurodisability is not reduced)
The following have been evaluated but have no proven benefij -
Vitamin E
Ethamsylate
Phenobarbital
Fresh-frozen plasma (FFP)
Nimodipine
Sequelae of PIVH
Death
Mortality was 59% in one series of large grade 4 PIVH
Adverse neurodevelopment
Cerebral palsy is the commonest adverse neurodevelopmental sequel but other and
global problems may also arise
Approximate risk of adverse outcome is as follows:
4% in grades 1 and 2 PIVH if ventricles remain normal size
50% in grade 2 with PHVD or grade 3 PIVH
75% in PIVH requiring shunt
89% with large, grade 4 lesions (difficult to quantify because pathology is varied)
Clinical presentation
This can be staged according to the scheme suggested by Sarnat and Sarnat.
Stage 1 - hyperalert, irritable; normal tone and reflexes; signs of sympathetic
overactivity; poor suck; no seizures; symptoms usually resolve < 24 hours; good
outcome in approximately 99%
Stage 2 - Lethargic, obtunded, decreased tone and weak suck and Moro reflexes;
seizures are common; approximately 75430% have good outcomes; this is less likely if
symptoms persist for > 5 days
Stage 3 - Comatose with respiratory failure; severe hypotonia and absent suck and
Moro reflexes; seizures less common but EEG abnormalities common - flat background
or bunt suppression; over 50% die and majority of survivors have major handicap
Essentia 1 Revision Notes in PaediCjtricsfor the IL1RCPCH 2nd Ectitio~l
Management
Management is largely supportive but brain cooling may offer improved outcomes in the
future.
Neuromuscular disease
Spinal muscular atrophy
Congenital myotonic dystrophy
Congenital myopathies
Myasthenia gravis
ROP stages
Stage 1 - demarcation line
Stage 2 - ridge
Stage 3 - ridge with extraretinal fibrovascular proliferation
Stage 4 - subtotal retinal detachment
Stage 5 - total retinal detachment
Stage 1 and 2 disease resolves without risk of visual impairment if there is no
progression
Stage 3 disease increases the risk of visual impairment
Stages 4 and 5 always leads to visual impairment
ROP location
Zone 1, 2 or 3 (where zone 1 is the most central (i.e. posterior) around the optic disc)
The risk is greatest if zone 1 is affected
ROP extent is described in terms of the number of clock hours
Plus disease includes tortuosity of the retinal vessels, pupil rigidity and vitreous haze
Usually stage 3 plus disease should be treated with either cryotherapy or laser therapy, but
location and extent of ROP also determines the need for treatment.
See also Chapter 19 - Ophthalmology.
7. GENITOURINARY PROBLEMS
7.1 Congenital abnormalities of the kidneys and urinary tract
Nephrogenesis (branching and new nephron induction) continues up to 36 weeks' gesta-
tion, but glomerular filtration rate is still < ~ O / O of adult values at this stage. This increases
rapidly in the 1 st week and then more gradually over the next 2 years to adult values.
The renal function of a neonate is limited by:
Renal blood flow
Glomerular filtration rate
Tubular concentrating and diluting ability
Tubular excretion
Urine output
More than 90% of neonates pass urine within 24 hours of birth. The collecting ducts have
increased sensitivity to antidiuretic hormone (ADH) after birth and urine concentrating
ability increases rapidly.
Preterm infants have immature tubular function leading to a high fractional excretion of
sodium and high sodium intake requirements.
Antenatally, congenital renal abnormalities may present with:
a Oligohydramnios (Potter syndrome if severe)
a Urinary ascites - as a result of obstructive uropathy
a Other abnormalities seen on antenatal ultrasound scan include:
Obstructive uropathy - dilated renal tracts
Cystic dysplasia/polycystic disease
Obstructive uropathy
Posterior urethral valves
Mucosal folds in posterior urethra of male infants leading to dilatation of renal tract
proximal to obstruction
Bladder is often hypertrophied
Diagnosed by micturating cystourogram
Suprapubic catheter is inserted initially, followed by surgical resection by cystoscopy or
vesicostomy, followed by later resection
Ureterocele
Dilatation of distal ureter leading to obstruction
Urethral stricture
Hypotension
Dehydration
lndomethacin
Renal
Cystic dysplasia and infant polycystic kidney disease
Renal arterylvein thrombosis
Congenital nephrotic syndrome
DIC
Nephrotoxins - gentamicin
Obstructive nephropathy
Differential diagnosis
a True hermaphroditism:
Testes and ovaries both present (rare)
a Male pseudohermaphroditism - underdevelopment (1 virilization) of male features
Androgen insensitivity (= testicular feminization) - most common
Defects in testosterone synthesis
Some forms of congenital adrenal hyperplasia
Panhypopituitarism (should be suspected if hypoglycaemia is also present)
Defects in testosterone metabolism (5a-reductase most common)
Defects in testicular differentiation (rare)
a Female pseudohermaphroditism - virilization of female
Congenital adrenal hyperplasia - commonest enzyme deficiency is 21-hydroxylase
deficiency (117a-hydroxyprogesterone)
Chromosomal abnormalities
45X/46XY mosaicism (rare)
Investigations
Ka'Yotype
Daily electrolytes until diagnosis is established
Blood pressure monitoring
Blood sugar monitoring
Abdominal ultrasound scan
Serum hormone assay - 17a-hydroxyprogesterone, 11-deoxycortisol, testosterone,
oestradiol, progesterone, luteinizing hormone, follicle-stimulating hormone
Urine steroid profile
Genitogram/micturating cystourogram
8. INFECTION
8.1 Bacterial infection
Group B streptococcus (GBS)
Up to 20% of pregnant women have genital tract colonization with GBS
Three serotypes have been identified
Neonatal GBS infection may be early (within first few days, usually presenting by
24 hours) or late (after first week, usually at 3-4 weeks)
Early disease often presents with septicaemia and respiratory distress (pneumonia or
persistent pulmonary hypertension of the newborn)
Late disease is usually septicaemia or meningitis - may be vertical or nosocomial
Essential Revision Notes i r ~P~edi,?tricstbr the M RCPCH 2nd Edition
transmission; antibiotics given intrapartum or in first few days do not always prevent late
GBS disease
Serotype 3 is more common in late-onset GBS disease or meningitis if this is part of
early-onset disease
Escherichia coli
Usually causes vertical infections in neonates and is often associated with preterm birth;
can also cause nosocomial infection
K1 capsular antigen is commonest serotype
Septicaemia and meningitis are commonest presentations if vertically transmitted;
urinary tract infections and NEC have been noted in nosocomial E. coli sepsis in
neonates
Coagulase-negativestaphylococci
Commonest nosocomial pathogen in neonatal intensive care units
VLBW infants with indwelling catheters are most at risk
Often resistant to flucloxacillin
Listeria monocytogenes
Gram-positive rod
Outbreaks have been caused by dairy products, coleslaw, pat6 and undercooked meat
May present with a flu-like illness in pregnant women and then lead to stillbirth or
severe neonatal septicaemia and meningitis
Early- and late-onset disease have been noted, similar to GBS
Early-onset disease is associated with preterm birth and 'meconiumf-stained amniotic
fluid (which is in fact often pus rather than meconium)
A maculopapular or pustular rash is typical
Amoxicillin and gentamicin is the antibiotic combination of choice *
Diagnosis
Rising specific IgG antibodies in mother or baby
Specific IgM may be raised for up to 16 weeks after primary infection
Virus can be isolated from urine or throat swab
Detection of early-antigen fluorescent foci (DEAFF) is a newer technique used to detect
viral antigen from urine and other body fluids
Essentia Revision Notes in Paediatrics ti>r the h1RCPCH 2 ' 1 7 ~ 1Edition
Aciclovir has been used with some success in immunosuppressed adults but may be
toxic in neonates and is not of proven efficacy
Rubella
First-trimester infection of the fetus results in congenital rubella syndrome. The most
common features of this are:
Congenital heart disease
Cataracts
Deafness
IUGR, microcephaly, hepatosplenomegaly, thrombocytopenia, choroidoretinitis and osteitis
may also occur similar to congenital CMV infection. Vaccination of children has virtually
eradicated congenital rubella in the UK.
Parvovirus
Parvovirus is a DNA virus. Serotype B19 causes epidemics of erythema infectiosum
('Slapped cheeks' syndrome or Fifth disease) in winter months. Fetal infection, particularly
in the first trimester, leads to severely decreased red cell production and subsequent severe
fetal anaemia, resulting in heart failure and non-immune hydrops. Fetal blood can be used
to confirm the diagnosis by viral antigen detection with polymerase chain reactions. Fetal
blood transfusions may reverse hydrops and improve outcome.
Vaccinations should be given routinely to infants of HIV-positive mothers with the following
cautions:
Give killed (Salk) rather than live (Sabin) polio vaccine
Give BCG early
Hepatitis B virus
Babies of women who are hepatitis B surface antigen (HbsAg)-positiveor who have
active hepatitis B during pregnancy should all receive hepatitis B vaccine in the
neonatal period, and at 1 and 6 months
Hepatitis B immunoglobulin should be given within 48 hours of birth to all babies of
mothers who are HbsAg-positive apart from those with the hepatitis B e antibody
Breast-feeding is not contraindicated
Toxoplasmosis
Toxoplasmagondii is a unicellular, protozoan parasite.
Cats are the definitive hosts. Infection of humans occurs following ingestion of
sporocysts after handling cat faeces, contaminated vegetables or undercooked meat.
0 Toxoplasmosis is a mild illness in healthy adults
Congenital infection is more likely with increasing gestation as the placenta provides
less of a barrier with age. However, severe infection becomes less likely, falling from
75% in the first trimester to < ~ O / O in the third.
Severe congenital toxoplasmosis causes:
IUGR
Pre-term birth
Hydrocephalus and sequelae
Choroidoretinitis
lntracranial calcification
Hepatitis
Pneumonia
Myocarditis
Babies born with no symptoms may go on to develop choroidoretinitis after months or even
years. Serological diagnosis is made by specific lgG and IgM titres. Treatment of affected
pregnant women with spiramycin reduces the rate of transmission to the fetus but does not
reduce the severity of disease. Affected infants are treated with pyrimethamine and
sulfadiazine for up to 1 year.
1 Revision hlotcs ir;e /<~rdi,~tri(-s
Essenti,~ tbr the hlKCPCH2r7d Editio17
i 9-2 Panhypopituitarisrn
I
r
I
f Presents with:
Persistent hypoglycaemia
Poor feeding
Micropenis
Hyperbilirubinaemia (conjugated)
Midline facial defects (cleft palate etc.)
Optic atrophy
Low growth hormone, cortisol (may cause hyponatraemia) and thyroid-stimulating
hormone
Enterohepatic circulation
Breast-fed babies have higher maximum serum bilirubin levels and remain jaundiced for
longer.
Phototherapy
This is used to treat moderately severe unconjugated hyperbilirubinaernia. Phototherapy
photo-oxidizes and isomerizes bilirubin, facilitating increased excretion via urine and bile.
Complications of phototherapy are mainly minor and include:
Diarrhoea
Transcutaneous fluid loss
Rashes
Exchange transfusion
This is used to treat severe unconjugated hyperbilirubinaemia, often with concomitant
anaemia, most commonly as a result of haemolysis. The procedure dilutes bilirubin,
removes sensitized red blood cells and corrects anaemia.
Usually a double-volume exchange transfusion is performed via arterial and central venous
lines over 1-2 hours, replacing the baby's blood volume twice with donor blood.
Complications of exchange transfusion include:
Infection and other line-related complications
Fluid and electrolyte disturbance
Essential Revision Notes in Paediatrics for the M KCPCH 2nd Edition
Causes
IUGR
Maternal diabetes
Delayed cord clamping
Twin-to-twin transfusion
Maternofetal transfusion
Trisomies (13, 18, 21)
Endocrine disorders (congenital adrenal hyperplasia, thyrotoxicosis, Beckwith syndrome)
Complications
Hypoglycaemia
Jaundice
NEC
Persistent pulmonary hypertension of the newborn
Venous thromboses -
Stroke
Treatment
Treatment is recommended if the haematocrit is > 65% and the patient is symptomatic. A
I
partial dilutional exchange transfusion should be carried out using normal saline.
prothrombin time and activated partial thromboplastin are prolonged with normal
thrombin time and fibrinogen
Treat with fresh-frozen plasma and intravenous vitamin K +/- blood transfusion
Late haemorrhagic disease may occur between 8 days and 6 months; intracranial
haemorrhage is more common in these cases
11.4 Haemophilia A
Almost 40% of cases present in the neonatal period with inpaventricular haemorrhage,
cephalhaematoma or excessive bleeding elsewhere
Antenatal diagnosis is possible by chorionic villous biopsy, if there is a family history
Vaginal birth is safe if uncomplicated but ventouse delivery should be avoided
Oral vitamin K (rather than intramuscular) should be given
Bleeding should be treated with recombi'nant factor VIII, but prophylactic treatment is
controversial
Clinical features of haemophilia B are similar to those of haemophilia B.
CONTENTS
1 Embryology
4. Physiology
4.1 Glomerular filtration rate (GFR)
4.2 Renal tubular physiology
4.3 Renin-angiotensin-aldosterone system
4.4 Erythropoietin system
4.5 Vitamin D metabolism
5. Investigations
5.1 Urinalysis
5.2 Urine microscopy
5.3 Haematuria
5.4 Proteinuria
5.5 Renal imaging
5.6 Renal biopsy
7. Renal tubulopathies
7.1 Proximal tubulopathies
7.2 Loop of Henle
7.3 Distal tubule
7.4 Collecting duct
8. Nephrotic syndrome
8.1 Definitions
8.2 Clinical features
8.3 Complications
8.4 Treatment
8.5 Congenital nephrotic syndrome
9. Glomerulonephritis
9. General clinical features
9.2 Acute post-streptococcal glomerulonephritis
9.3 Henoch-Schonlein nephritis
9.4 IgA nephropathy
9.5 Systemic lupus erythematosus nephritis
9.6 'Shunt' nephritis
14. Hypertension
14.1 Ambulatory blood pressure monitoring
14.2 Causes of secondary hypertension
14.3 Evaluation of hypertension by increasing level of invasiveness
14.4 Treatment of hypertension
15. Inherited diseases
15.1 Polycystic kidney disease
15.2 Alport syndrome
15.3 Nephronophthisis
1. EMBRYOLOGY
At the start of week 5 of embryogenesis, the ureteric bud appears
A small branch of the mesonephric duct evolves into a tubular structure which elongates
into the primitive mesenchyme of the nephrogenic ridge
Ureteric bud forms the ureter, and from week 6 onwards repeated branching gives rise
to the calyces, papillary ducts and collecting tubules by week 12
The branching elements also induce the mesenchyme to develop into nephrons -
proximal and distal tubules, and glomeruli
Branching and new nephron induction continues until week 36
Abnormalities in the signalling between branching ureteric bud elements and the
primitive mesenchyme probably underlie important renal malformations including renal
dysplasia
There are on average 600,000 nephrons per kidney. Premature birth and low weight for
gestational age may both be associated with reduced nephron numbers
This in turn may underlie the later development of glomerular hyperfiltration, glomerular
sclerosis and hypertension, and may explain the firmly established inveke association
between birth weight and later adult-onset cardiovasular morbidity
I Creatinine 3
clearance
1
-C Newborn
20 25 30 35 40
Gestational age (weeks)
Normal FENa in older children and adults is around I%, and < 1% in sodium- and
water-de~rivedstates
It is vefhigh in the premature fetus, falling with increasinggestation; and it is
significantly lower in the newborn (see figure below), as the kidney adapts to the
demands of extrauterine life where renal tubular conservation of sodium and water is
important
Premature neonates still have a relatively high FENa because of immmature renal tubular
function, and require extra sodium supplementation to avoid hyponatraemia.
Essential Revision Notes in Paediatrics for the MRCPCH 217d Ecfitiun
Fractional
sodium 10 - +-Newborn
excretion
20 25 30 35 40
Gestational age (weeks)
Fractional sodium excretion (O/O) in the human fetus and newborn infant
3.6 Hypospadias
Opening of urethral meatus is on ventral surface of penis, at any point from glans to
base of penis or even perineum
Meatus may be stenotic and require meatotomy as initial intervention
Foreskin is absent ventrally; it is used in surgical reconstruction of a deficient urethra so
circumcision should not be performed
Chordee is the associated ventral curvature of the penis, seen especially during erection,
and this requires surgical correction also; caused by fibrous tissue distal to the meatus
along the ventral surface of penis
x 4~rnt/m1n/1.73 m'
plasma creat (pmol/L) -
,
This method will tend to overestimate CFR in malnourished children with poor muscle mass
It is measured on a single injection plasma disappearance cbrve, using inulin, or a radio-
isotope such as chromium-labelled EDTA. Following an intravenous injection of a known
amount of one of these substances, a series of timed blood samples are taken over 3-5 h,
and the slope of the curve generated by the falling plasma levels of the substance gives the
GFR. This technique does not require any urine collection, thus making it suitable for
routine clinical use.
NB: Creatinine clearance, based on a timed urine collection and paired plasma sample
using the formula:
proximal tubule
Phosphate
Amino acids
Uric acids
Loop of Henle
Diagram of tubular function, showing sites of active (solid arrows) and passive (broken
arrows) transport. The boxed numbers indicate the percentage of glomerular filtrate
remaining in the tubule, and the non-boxed numbers the osmolality of the tubular fluid
under conditions of antidiuresis (reproduced from Godfrey and Baum, Clinical Paediatric
Physiology, p. 368, Cambridge: Blackwell Scientific Publications, with permission)
Proximal tubule
The primary active transport system is the Naf -K+-ATPase enzyme, reabsorbing 5O0/0 of
filtered NaC. Secondary transport involves coupling to the Na+-H+ antiporter, which
accounts for 90% of bicarbonate reabsorption with some CI-. In addition:
Glucose is completely reabsorbed unless the plasma level is high, in which case
glycosuria will occur
668
Nephrology
Amino acids are completely reabsorbed, though premature and term neonates
commonly show a transient aminoaciduria
a Phosphate is 80-90% reabsorbed under the influence of parathyroid hormone (PTH),
which reduces reabsorption and enhances excretion of phosphate
a Calcium is 95% reabsorbed - 60% in proximal tubule; 20% in Loop of Henle; 10% in
distal tubule; 5% in collecting duct
a A variety of organic solutes including creatinine and urate, and some drugs, including
trimethoprim and most diuretics, are secreted in the proximal tubule
Loop of Henle
a A further 40% of filtered Na+ is reabsorbed via the Naf -K+-2CI- cotransporter in the
thick ascending limb of the LoH
a The medullary concentration gradient is generated here because this segment is
impermeable to water
a Loop diuretics block CI- binding sites on the cotransporter
a There is an inborn defect in CI- reabsorption at this same site in Bartter syndrome - see
Section 7.2
Distal tubule
A further 5% of filtered Naf is reabsorbed here, via a Na+-CI- co-transporter
Thiazide diuretics compete for these CI-binding sites; and may have a powetful effect if
combined with loop diuretics which increase NaCl and water to the distal tubule
Aldosterone-sensitive channels (also present in the collecting duct) are involved in
regulating K+ secretion. Kf secretion is proportional to:
Distal tubular urine flow rate
Distal tubular Na+ delivery: so natriuresis is associated with increased K+ secretion
and hypokalaemia (e.g. Bartter syndrome; loop diuretics) -
Aldosterone level - so conditions of elevated aldosterone are associated with
hypokalaemia
[pH]-'
Collecting duct
A final 2% of filtered Na+ is reabsorbed via aldosterone-sensitive Na+ channels, in
exchange for K+
Spironolactone binds to and blocks the aldosterone receptor, explaining its diuretic and
K+-sparing actions
H+ secreted into urine by H+-ATPase
Anti-diuretic hormone (ADH) opens water channels (aquaporins)to increase water
reabsorption
Essential Revision Notcs in Y,?edi,l trics h ~ the
r ht RCPCH 2nd Edition
<
vasoconstriction
angiotensinogen -
4
angiotensin l -+angiotensin ll
If
f
aldosterone
from adrenals
5. INVESTIGATIONS
5.1 Urinalysis
Dipstick testing of urine is routinely used to detect blood, protein, glucose and pH.
~ u l t i s t i xcan,
~ in addition, detect leukocyte esterase (a marker of the presence of
polymorphs) and nitrite (produced by the bacterial reduction of nitrate). If the urine appears
clear to the naked eye and all panels on a ~ultistix"are negative, urine infection is almost
certainly excluded.
NB: Urinary haemoglobin and myoglobin (from rhabdomyolysis) produce a false positive
dipstick test for blood; microscopy of urine will not however reveal red blood cells.
5.3 Haematuria
The main causes are:
UTI - other infections including tuberculosis and schistosomiasis
Glomerulonephritis:
Often with proteinuria and urinary casts
Isolated haematuria with no other evidence of clinical renal disease may be the
presenting feature of several important glomerulonephritides, including Alport
syndrome and immunoglobulin A (IgA) nephropathy
Trauma - usually a history
Essential Revision Notes in Paediatrics for the MRCPCH 2nd Edition
5.4 Proteinuria
This is usually detected on dipstick testing. The minimum detectable concentration is 10-
15 mg/dl, so in a patient producing a large volume of dilute urine the sticks may be negative
even though the total amount of protein excreted per day may be significant.
In normal afebrile children, urine protein excretion should not exceed 60 mg/m2/24 h.
Collection of an accurate 24-h urine collection is difficult in small children. Assessment of
proteinuria may be made on a spot early morning urine sample by measuring urinary
albumin (mg/L) and creatinine (mmol1L):
Normal - < 3.5 mg/mmol
Microalbuminuria - 3-30 mg/mmol
Proteinuria - > 30 mg/mmol
Orthostatic proteinuria is detectable when the patient has been in an upright position for
several hours but not when the patient is recumbant. It is important to assess protein excretion
both when recumbant and when upright, because orthostatic proteinuria is a benign
condition with a good prognosis, and does not warrant investigations such as renal biopsy.
ultrasound may not detect minor degrees of scarring. It is not sensitive or specific at
detecting VUR. Doppler ultrasound may reveal renal artery stenosis, but there is a signifi-
cant false-negative rate.
Micturating cystourethrogram
Used to look for VUR and the appearance of the bladder outline; also the urethra,
specifically posterior urethral valves in males.
Intravenous urography
Little used now because the combination of ultrasound and isotope scans provides the
required information in most cases, and avoids the risks of anaphylaxis and radiation dose
that are involved with intravenous urography. Has a role in:
Emergency evaluation of painful haematuria, if ultrasound is uninformative, when
intravenous urography may reveal a ureteric stone
@ Determining ureteric anatomy, course, and insertion if ectopic ureter is suspected
Renal arteriography
Used to diagnose renal artery stenosis. Approach is via femoral artery; usually requires
general anaesthesia in children. Therapeutic approaches include balloon angioplasty of
stenoses; and embolization of intrarenal arteriovenous aneurysms.
Essential Revision Notes in I?aedic?tricsk ~ the
r MRCPCH 317dEdition
Interstitial lntravascular
Osmoregulation
A small (3-4%) increase in ECF osmolality stimulates hypothalamic osmoreceptors to cause
posterior pituitary ADH release, leading to water retention and return of osmolality to
normal. Increases in ECF osmolality also stimulate thirst and water drinking. Significant
(> 10%) ECF depletion, even if iso-osmolar, will cause carotid and atrial baroreceptors to
stimulate ADH release.
usually defined as plasma Na+ > 150 mmol/L. There is a shift of H 2 0from the ICF to the
ECF compartments, so that in hypernatraemic dehydration, ECF volume is not markedly
reduced and thus typical signs of dehydration are less obvious. The causes again are
twofold.
Gain of Na in excess of H 2 0
Increased volume of urine with high Na+ content
Iatrogenic - excess hypertonic intravenous fluid, e.g. NaHCO,, hypertonic saline
Incorrect reconstitution of infant formula
Accidental or deliberate (e.g. Munchausen syndrome by proxy) salt poisoning
Treatment - recognition and removal of underlying cause; access to water while
kidneys excrete excess salt load
Hypokalaemia
Normal plasma K+ is 3.4-4.8 mmol/L. The main causes of hypokalaemia are:
lnadequate provision of K+ with prolonged intravenous fluid administration
Extrarenal losses
Gastrointestinal losses
Renal losses
High plasma renin levels
- diuretic use - loop and thiazide diuretics
- osmotic diuresis - DKA (hypokalaemia becomes evident when metabolic
acidosis and insulin deficiency are corrected)
- Fanconi syndrome - see Section 7.1
- Bartter syndrome - see Section 7.2
- Gitelman syndrome - see Section 7.3
- Distal (type 1) RTA
fix tlw MKQIPCIH2nd Eclitiotl
Essential Revision N o t ~ sin R~edi~jtrics
Hyperkalaemia
The main causes are:
Excess administration in intravenous fluid
Renal failure - acute and chronic
Shift from ICF to ECF
Metabolicacidosis
Rhabdomyolysis - acute tumour lysis (both often associated with acute impairment
in renal function which compounds the hyperkalaemia)
Hypoadrenal states
Salt-wasting congenital adrenal hyperplasia
Adrenal insufficiency
Pseudohypoaldosteronism - see Section 4.3
Potassium-sparing diuretics - spironolactone
Treatment includes:
Exclusion of K+ from diet and intravenous fluids
Cardiac monitor - peaked T waves -+ prolonged PR interval -+widened QRS +
*
ventricular tachycardia -+terminal ventricular fibrillation
Calcium gluconate to stabilize myocardium
Shift K+ from ECF to ICF:
- correct metabolic acidosis if present - in acute renal failure
- salbutamol: nebulized or short intravenous infusion
- insulin and dextrose - but extreme caution in young children as there is a risk of
hypoglycaem ia
Remove K+ from body
- calcium resonium
- dialysis
Beware in correcting acidosis in renal failure, where total and ionized Ca2+ often already
low:
.
Acute rise in pH with NaHCOl treatment leads to t protein-bound Ca2+ which lead to j
ionized Ca2+, which may cause tetany
Monitoring of ionized Ca2+ is useful in intensive-care patients, where changes in acid-
base and albumin levels make interpretation of total plasma Ca2+ difficult
~~pocalcaemia
The main symptoms are tetany, paraesthesiae, muscle cramps, stridor, seizures. The main
causes are:
Calcitriol (1,25(Oti)2-D3)deficiency
Dietary deficiency of vitamin D
Malabsoprtion of vitamin D - fat malabsorption syndromes
Renal failure (acute and chronic) - 1a-hydroxylase deficiency
Liver disease - 25-hydroxylase deficiency
Hypoparathyroidism
Transient neonatal
Di George syndrome - 22q11.2 deletion
Post-parathyroidectomy
a Pseudohypoparathyroidism
Autosomal dominant; end-organ resistance to raised levels of PTH
Abnormal phenotype with short stature, obesity, intellectual delay, round face, short
neck, shortened 4th and 5th metacarpals
Acute alkalosis (respiratory or metabolic); or acute correction of acidosis in setting of
already reduced Ca2+
Hyperphosphataemia
Renal failure (acute or chronic)
Rhabdomyolysis; tumour lysis syndrome
Deposition of ca2+
Acute pancreatitis
Treatment includes:
Intravenous 10% calcium gluconate, 0.2 ml (0.045 mmol)/kg, diluted 1 : 5 with
dextrose 5%, over 10-1 5 min with ECG monitoring; followed by intravenous
infusion of 10% calcium gluconate at 0.3 ml (0.07 mmol)/kg/day
Oral Ca2+ supplements
Vitamin D, or the analogue alfacalcidol (1a-OH-cholecalciferol) for nutritional
deficiency, hypoparathyroidism, and renal failure
Hypercalcaemia
The main symptoms are constipation, nausea, lethargy and confusion, headache, muscle
weakness and polyuria and dehydration. The main causes are:
Vitamin D therapy
Renal failure
Dietary vitamin D deficiency
Essential Revision Notes in Ejedi~tricstbr the MRCPCH 2nd Editioi?
Primary hyperparathyroidism
Neonatal
Part of multiple endocrine neoplasia syndromes I and II
William syndrome
Heterozygous deletions of chromosomal sub-band 7q11.23 leading to an elastin
gene defect in > 90% (detected by fluorescent in situ hybridization)
Hypercalcaemia rarely persists beyond 1 year of age
Familial hypocalciuric hypercalcaemia
Inactivation of ca2+-sensingreceptor gene in parathyroid cells and renal tubules
leads to an inappropriately high plasma PTH level and inappropriately low urine
Ca2+
Macrophage production of 1,25(OH)2-D3
Sarcoidosis
Subcutaneous fat necrosis -prolonged or obstructed labour
Malignant disease
Treatment includes:
Intravenous hydration plus a loop diuretic
Correction/removal or specific treatment of underlying cause, e.g. steroids for
sarcoidosis
Rarely, bisphosphonates
Normally, TRP > 85%. If the TRP is < 85%, in the presence of low plasma PO4 and a
normal PTH level, this implies abnormal tubular leakage of PO4.
Hypophosphataemia
With appropriately high TRP ie low urinary PO4
Dietary PO4 restriction
Increased uptake into bone - the 'hungry bone syndrome' seen after
parathyroidectomy for prolonged hyperparathyroidism, or after renal transplantation
with preceding hyperparathyroidism of CRF; see also Hypocalcaemia
With inappropriately low TRP, i.e. high urinary PO4
Hypophosphataemic rickets - see Section 7.1
Fanconi syndrome - see Section 7.1
Nephrology
7. RENAL TUBULOPATHIES
7.1 Proximal tubulopathies
Cystinuria
Defect in reabsorption of, and hence excessive excretion of, the dibasic amino acids
cystine, ornithine, arginine and lysine
Not to be confused with cystinosis - see below
Autosomal recessive; two separate cystinuria genes on 2p and 19q
Cystine is poorly soluble in normal urine pH; has increased solubility in alkaline urine
Clinical manifestation is recurrent urinary stone formation
Stones are extremely hard and densely radio-opaque
Diagnosis based on stone analysis, or high cystine level in timed urine collection
Treatment based on high fluid intake (a1.5 um2/day)and alkalinization of urine with
oral potassium citrate
If stones still form, oral D-penicillamine leads to formation of highly soluble mixed
disulphides with cystine moieties
Essential Revisiori Notes in Paediatrics for the MRCPCH 2rid Edition
Fanconi syndrome
Diffuse proximal tubular dysfunction, leading to excess urinary loss of:
Glucose - glycosuria with normal blood glucose
Phosphate - hypophosphataemia, low TRP, rickets
Amino acids - no obvious clinical consequence
HC03-- leading to proximal RTA
K+ - causing hypokalaemia
Na+, CI- and water - leading to polyuria and polydipsia, chronic ECF volume
depletion, faltering growth
Tubular proteinuria - loss of low molecular weight proteins including retinol
binding protein, and N-acetyl glucosaminidase
a Usual clinical features include polyuria and polydipsia, chronic ECF volume depletion,
faltering growth, constipation and rickets; with features of any underlying condition in
addition
Cystinosis
Autosomai recessive defect in the transport of cystine out of lysosomes. Gene is localized to
chromosome 17p and encodes an integral membrane protein, cystinosin.
Predominant early clinical features are of:
Fanconi's syndrome - see above
Photophobia as the result of eye involvement with corneal cystine crystals
Hypothyroidism
Late features include:
Renal failure around 8-1 0 years of age, if untreated
Pancreatic involvement with diabetes mellitus
Liver involvement with hepatomegaly
Gonadal involvement with reduced fertility
Neurological deterioration and cerebral atrophy
Diagnosis is based on:
Cystine crystals in cornea seen by slit lamp
Peripheral blood white cell cystine level
Antenatal diagnosis available for families with positive history
Treatment is:
Supportive - PO4, NaCI, K+, and NaHC03 supplements, and high fluid intake;
alfacalcidol; thyroxine
Specific - cystearnine, which increases cystine transport out of the lysosome;
commencing treatment in early infancy appears to delay onset of renal failure
Other - indomethacin reduces the CFR, and hence the severe polyuria and secondary
polydipsia, and electrolyte wasting
tor-the MKCfTH 2nd Edition
~ssentialRevision Notes il: P~cdi~ltrics
8.0
7.0
5
2
lu
.-C
5
6.0
5.0
10 12 14 16 18 20 22 24 26 28
Arterial plasma [HCO,-1, (mmol/l)
Pseudo-Bartter syndrome
The same plasma biochemistry - hypochloraemic hypokalaemic alkalosis - but
appropriately low levels of urine CI- and Na+ - < 10 mmolll
Main causes are:
Cystic fibrosis - sweat loss of NaCl and water
Congenital chloride diarrhoea - gastrointestinal loss
Laxative abuse - gastrointestinal loss
Cyclical vomiting
NB: All the changes of Bartter syndrome, including the high urine electrolyte levels, may be
produced by loop diuretics, which block the same site in the thick ascending limb of the
loop of Henle.
Patients have hypokalaemic metabolic alkalosis, raised renin and aldosterone, and
hypomagnesaemia with increased urinary magnesium wasting, and hypocalciuria, a
feature which helps distinguish it from classical Bartter syndrome (in which urinary Ca2+
is normal or high - see above)
Biochemical changes resemble those produced by thiazide diuretics, which inhibit this
distal tubule co-transporter
8. NEPHROTIC SYNDROME
A triad of oedema, proteinuria and hypoalbuminaemia. It is almost always idiopathic in
childhood. It is best classified by response to steroid treatment -,steroid-sensitive nephrotic
syndrome (SSNS; 85-90% cases) or steroid-resistant nephrotic syndrome (SRNS; 10-1 5%
cases), because this is the best predictor of outcome.
8.1 Definitions
Remission - negative urinalysis on first morning urine for three consecutive mornings
Relapse - 3+ proteinuria on three or more consecutive first morning urines
Frequently relapsing - two or more relapses within 6 months of diagnosis; or four or
more relapses per year
Steroid resistant - no remission after 4 weeks of prednisolone 60 mg/m2/day
i 8.2 Clinical features
i
SSNS SRNS
Long term prognosis excellent, even if frequently poor - significant risk of long-
relapsing term hypertension and renal
failure
8.3 Complications
Infection
Typically with Streptococcus pneumoniae
Pneumonia
Primary pneumococcal peritonitis
* lncreased risk as a result of:
Tissue oedema and pleural and peritoneal fluid
Loss of immunoglobulin in urine
immunosuppression with steroid treatment
Thrombosis
lncreased risk as a result of:
Loss of antithrombin I l l and proteins S and C in urine
lncreased production of procoagulant factors by liver
lncreased haematocrit secondary to reduced oncotic pressure
Swelling of legs, ascites and relative immobility
Steroid therapy
Hypovolaemia
Reduced plasma oncotic pressure leads to shift of plasma water from intravascular space
to interstitial space
Symptoms include oliguria, abdominal pain, anorexia and postural hypotension
f i r the MRCPCH 2nd Edition
Essential Revision Notes in E1edi~7tric-s
Drug toxicity
Most morbidity arises from side-effects of steroid treatment
Nephrotoxicity from cyclosporin A or tacrolimus (see below)
8.4 Treatment
Initial presentation
The most commonly used prednisoione regimen in the UK is:
Prednisolone 60 mg/m2/day for 4 weeks; then reduce to 40 mg/m2 on alternate days for
4 weeks; then stop
However, there is good evidence from controlled trials that longer duration of initial
prednisolone treatment is associated with fewer relapses and lower total prednisolone dose
over the first 2 years. An example of a 6-month initial course is:
60 mg/m2/day for 4 weeks; then 40 mg/m2 on alternate days for 4 weeks; 30 mg/m2 on
alternate days for 4 weeks; 20 mg/m2 on alternate days for 4 weeks; 10 m g l d on
alternate days for 4 weeks; 5 mg/m2 on alternate days for 4 weeks; then stop
Relapse
In cases of relapse the most commonly used prednisolone regimen js:
Prednisolone 60 mg/m2/day until in remission; then 40 mg/m2 on alternate days for three
doses; and reduce alternate day dose by 10 mg/m2 every three doses until 10 mg/m2 on
alternate days is reached; then 5 mg/m2 on alternate days for three doses; then stop
Steroid-resistantnephrotic syndrome
Patient should be referred to specialist renal unit for assessment including renal biopsy
Usually resistant to other drug treatments also, so full remission not achieved
Aim is to reduce proteinuria so that patient is no longer nephrotic
Commonest treatment is alternate day prednisolone combined with cyclosporin long-
term; ACE inhibitor (e.g. enalapril) andlor angiotensin II receptor blocker (e.g. losartan)
often used to treat hypertension, with the added benefit of antiproteinuric effect
Significant chance of hypertension and progression to renal failure
If histology is focal segmental glomerulosclerosis (FSGS), associated with 20-40%
chance of recurrence after transplant
9. GLOMERULONEPHRITIS
1 General clinical features
Inflammation of the glomeruli leading to various clinical features, or renal syndromes,
which may include
Haematuria and/or proteinuria
Nephrotic syndrome
Acute nephritic syndrome with reduced renal function, oliguria and hypertension
Rapidly progressive crescentic glomerulonephritis - rapid onset severe renal failure
and hypertension, usually associated with the histological lesion called a crescent
These renal syndromes are not specific to particular conditions and the same condition
may present with different renal syndromes in different patients
Chronic glomerulonephritis may lead to scarring of the tubulo-interstitial areas of the
kidney, with progressive renal impairment
The main causes of glomerulonephritis, and the associated changes in serum
complement, include the following.
Reduced complement
GN, glomerulonephritis
Nephrology
.
Onset of reddish-brown ('Coca-Cola-coloured') urine 10-1 4 days after streptococcal
throat or skin infection
May have any of the renal syndromes described above
Deposition of immune complexes and complement in glomeruli
.
investigations include:
Throat swab
Antistreptolysin 0 (ASO) titre; anti-DNAase B
Typically, 1 Cj, normal C4
Biopsy if there is significant renal involvement - diffuse proliferative
glomerulonephritis is seen, with crescents, in severe cases
Treatment is mainly supportive, with an excellent prognosis for recovery; in very severe
cases involving renal failure, steroids have been used
NB: Always check C3 and C4 3 months after acute illness - should normalize; if still
lowered there may be another diagnosis, e.g. systemic lupus erythematosis or MCGN,
which have much worse prognoses.
Treatment as for Henoch-Schonlein purpura nephritis; ACE inhibitors used for long-term
control of hypertension and to minimize proteinuria
..
Acute tubular necrosis as a result of:
Uncorrected pre-renal failure as above
Toxins - gentamicin; X-ray contrast; myoglobinuria; and gentamicin toxicity most
.
Tubulo-interstitial nephritis
Drugs - non-steroidal anti-inflammatories; frusemide; penicillin; cephalosporins
1 . 1 Main causes
The main causes are:
Congenital dysplasia +I- obstruction
Reflux nephropathy
Chronic glomerulonephritis - FSGS; MCGN
Genetically inherited disease
hereditary nephritis - Alport syndrome, nephronophthisis
polycystic kidney disease
Systemic disease - Henoch-Schonlein purpura; systemic lupus erythematosus
Dietary considerations
Inadequate calorie intake and catabolism worsens acidosis, uraemia and hyperkalaemia
in chronic renal failure; aggressive nutritional management is crucial to control these,
and to achieve growth
Children with chronic renal failure often have poor appetite, and infants in particular
benefit from nasogastric or gastrostomy tube feeding
Congenital dysplasia +I- obstruction typically causes polyuria, with NaCl and HCQ-
wasting, and these need supplementing along with generous water intake; note that salt
and water restriction is inappropriate in many children with chronic renal failure, until
they reach end-stage renal failure
Protein intake should usually be the recommended daily intake for age; note that
protein restriction is inappropriate for children with chronic renal failure
Dietary restriction of PO4 (dairy produce) combined with use of PO4 binders (e.g.
calcium carbonate) is essential in controlling secondary hyperparathyroidism
Dietary restriction of K+ (fresh fruits, potatoes) is also commonly needed
Anaemia
Dietary iron deficiency
Reduced red blood cell survival in uraemia
Erythropoietin deficiency; recombinant human erythropoietin is available for treatment
Renal osteodystrophy
There are two main contributing processes:
Phosphate retention leads to hypocalcaemia, and both increased PO4 and decreased
Ca2+ stimulate secondary hyperparathyroidism
Subperiosteal bone resorption
Deficient renal 1a-hydroxylase activity and deficient 1,25(OH)2-D3 also contributes to
hypocalcaemia, and leads to rickets
Treatment includes control of hyperphosphataemia (see above); and alfacalcidol (1a-
OH-cholecalciferol) or calcitriol
Metabolic acidosis
Contributes to bone disease, because chronic acidosis is significantly buffered by the
uptake of H+ into bone in exchange for Ca2+ loss from bone
Hypertension
Depends on the underlying cause of the chronic renal failure
Congenital dysplasia +/- obstruction - patients tend to be polyuric, salt wasting
and normotensive
Chronic glomerulonephritis, polycystic kidney disease, systemic disease -
hypertension is common; usually secondary to increased renin, so ACE inhibitors are
often effective
11.4 Dialysis
Once the GFR falls to 10 ml/min/1.73 m2, the child will usually need dialysis, or trans-
plantation, to be maintained safely. The two main types of dialysis, peritoneal dialysis and
for fhe MRCPCH 2nd Edition
Essentia1 Revisic~nNotes in PaediC-ttric-s
haemodialysis, both use a semi-permeable membrane to achieve solute removal (K+, urea,
PO4,creatinine, etc), and fluid removal.
Infants and small children are better suited to peritoneal dialysis, which i s more 'physio-
logical' and avoids abrupt haemodynamic changes
Frequency and duration daily (usually overnight) via thrice weekly, 4-h/session
automated PD machine
11.5 Transplantation
The proportion of living related donor transplants in paediatric units (-50% of
-
transplants) is higher than the national figure overall a parent is usually the donor
Transplantation before the need for dialysis is usually the aim
There are advantages to living related donor transplantation
Better long-term survival of the graft kidney: approximate figures are 90% at 1 year;
75-80% at 5 years; 60% at 10 years
Surgery is planned, so family life can be organized to deal with it
Increases the chance of achieving transplantation without dialysis
Human leukocyte antigen (HLA) matching is based around HLA-A, -B and -DR; on
average a parent and child will be matched for one allele, and mismatched for one
allele, at each site
The main immunosuppressive drugs are prednisolone, tacrolimus and azathioprine
Nephrology
..
transplantation - immunization is available for all these infections
children must weigh 3 10 kg for transplantation to be performed
The main complications of transplantation include
Early surgical complications - bleeding; transplant artery thrombosis; wound
.. infection
Rejection - diagnosed on biopsy; usually treatable with extra immune suppression
Opportunistic infection - fungal infections; cytomegalovirus; Pneumocystis
. pneumoniae
Drug toxicity - hypertension; Cushingoid changes; hirsutism and nephrotoxicity
. from cyclosporin
Post-transplantation lymphoproliferative disorder - lymphoma-like condition,
especially associated with primary Epstein-Barr virus infection when
immunosuppressed
Controlled studies show no benefit for surgery over conservative management for
grades 1-111
Surgery may be indicated where prophylaxis fails to control infection and where
there is progressive reflux nephropathy; options are reimplantation of ureters or
endoscopic injection of synthetic material at ureteric orifice
Screening of newborn siblings or offspring of index children or parents should be
considered
In children who have normal bladder control and no symptoms of detrusor
dysfunction, and who have been free of infection on prophylaxis, evidence suggests
that there is little benefit from continuing prophylaxis beyond 5 years old
Incomplete bladder emptying
Posterior urethral valves
Neuropathic bladder
Catheterization or instrumentation of urinary tract
Stones
I II 111 IV v
Investigation of UTI
Aims
To identify scarring
To identify underlying abnormalities likely to cause recurrent infection - VUR;
incomplete emptying
Suggested protocol
under 1 year - ultrasound + DMSA -I-MCUG
over 1 year - ultrasound + DMSA; MCUG only if
ultrasound or DMSA is abnormal
pyelonephritis clinically
recurrent UTI
family history
Nephrology
There is much debate about the investigation of UTI but the above scheme is cautious
and commonly used
Indirect radioisotope reflux study (e.g. DTPA) - see Section 5.5
May be adequate for initial investigation for VUR in girls, but initial contrast MCUC
should always be performed in boys to exclude posterior urethral valves
Prevention of UTI
on-pharmacological methods
Avoidance of constipation; correct bottom wiping
Frequent voiding and high fluid intake; double voiding
Lactobacilli in liveyoghurt;cranberryjuice
Clean intermittent catheterization
prophylactic antibiotics
Treatment of UTI
Empirical antibiotic treatment until culture and sensitivity results are known; > 90%
childhood UTls are E. coli
intravenous antibiotics for unwell infants and children with clinical pyelonephritis -
high fever and rigors, loin pain, vomiting, neutrophilia, raised C-reactive protein
Obstructed kidneys may need drainage
Stones may need removing
Augmented bladders may improve with mucolytic and bacteriostatic washouts
Parvolex washouts; chlorhexidene washouts
Causes
Spina bifida; sacral agenesis (maternal diabetes)
Tumour; trauma
Transverse myelitis
Principles of management
Videourodynamic assessment of type of bladder dysfunction
Careful assessment of kidney structure, scarring, function, blood pressure
Improve emptying with clean intermittent catheterization
* Anticholinergics (oxybutinin) may help reduce unstable contractions
Augmentation cystoplasty - larger capacity, lower pressure
13.1 Definitions
Primary nocturnal enuresis (-80%) - never achieved night-time dryness
Secondary nocturnal enuresis - recurrence of bedwetting having been dry for 3 1 year
Initial successful response - 14 consecutive dry nights within 16 weeks of starting
treatment
Relapse - more than two wet nights in 2 weeks
Complete success - no relapse within 2 years of initial success
13.2 Aetiology
Rarely an organic cause; should be distinguished from true incbntinence, e.g. as a result
of neuropathic bladder or ectopic ureter, when child is never dry
Genetic component
More common where there is a first-degree relative with history of enuresis
Concordance in monozygotic twins twice that in dizygotic twins
No significant excess of major psychological or behavioural disturbance, though family
stress, bullying at school etc. may trigger secondary enuresis and such factors should be
sought in the history
Evidence from studies that
In younger children, bladder capacity is reduced compared with non-enuretic
children
In older children and adolescents, there is reduction in the normally observed rise in
nocturnal ADH levels and in the decrease in nocturnal urine volume (hence
rationale for DDAVP treatment - see Section 13.4)
Nephrology
13.3 Assessment
Careful history is crucial
Examination should exclude abnormalities of abdomen, spine, lower limb neurology,
hypertension
Investigations should be limited to urinalysis
13.4 Treatment
Sustained and frequent support and encouragement for child and parents from an enthusias-
tic carer (doctor, nurse) is the most essential factor in seeing improvement. Any treatment
must involve the child, and depends for success on their motivation.
Star charts; colouring-in charts - simple behavioural therapy that is successful in many
children; and should be part of the monitoring of all interventions
Enuresis alarms
Mat on bed attached to bed-side buzzer, or
Small moisture sensor worn between two layers of underwear with vibrator alarm
attached to pyjamas (has the advantage of detecting wet underwear rather than
waiting to detect a wet bed)
May see 85% dry within 4 months, with a low 1Ooh relapse rate
More effective than drug therapies in direct comparative trials
Should be mainstay of treatment, but enthusiastic and supportive care, and
involvement of child (e.g. they should get up and change bedding) is crucial to
success
Drug therapy
lmipramine - low long-term success rate; high relapse ratq potentially serious side-
effects; rarely used
Desmopressin (oral or intranasal) - meta-analysis of all published trials showed
relatively poor short-term complete response rate, high relapse rate, and poor long-
term cure rate; more effective in older children; useful for short-term control for
special situations, e.g. school trip
-
Oxybutinin should be restricted to those children with a clear history of detrusor
instability - daytime urgency, frequency, urge incontinence -many of whom also
wet the bed
What is normal?
Blood pressure rises throughout childhood, related to age and height
Depends on method and frequency of measurement
US Task Force on Blood Pressure Control produce centile charts based on 60,000
normal children and teenagers
What is abnormal?
Consistently above the 95th centile for age
Loss of normal diurnal pattern
Infants and toddlers may require admission to hospital for blood pressure monitoring to
make diagnosis
o ! . 8 . . . . s . , , , .;--+++,; . " . . . . , ,
11121314151617181920212223 0 1 2 3 4 5 6 7 8 9 1011
Time (hours)
! 7rne (hours) j
i
! j
1
Renal
Reflux nephropathy if unilateral only
Polycystic kidney disease Y
Glomerulonephritis, e.g. FSGS X
Renal artery stenosis d
Middle aortic syndrome e.g. NF1; William syndrome d
Coarctation d
Endocrine
Phaeochromocytoma d
Cushing syndrome d
Other depends on cause
15.3 Nephronophthisis
Autosomal recessive condition; gene (called NPHP7) on chromosome 2
Produces polyuria (concentratingdefect), growth delay, and often severe anaemia
Urinalysis typically 'bland' - sometimes a trace of glucose
Progresses to end-stage renal failure towards the end of the first decade
Sometimes associated with tapeto-retinal degeneration: Senior-Loken syndrome
Essential Revision Notes in Paeciiatrics tbr the MRCPCH 2nd Edition
Cause
Neurology
Neil H Thomas
CONTENTS
1. Developmental abnormalities of the nervous system
1.1 Normal development of the nervous system
1.2 Neural tube defects
1.3 Hydrocephalus
1.4 Disorders of cortical development
1.5 Other nervous system maldevelopments
2. Neonatal neurology
2.1 Neonatal seizures
2.2 Hypoxic-ischaemic encephalopathy
2.3 Periventricular-intraventricular haemorrhage
2.4 Periventricular leukomalacia
2.5 Brachial plexus injuries
3. Disorders of movement
3.1 Cerebral palsy
3.2 Ataxia
3.3 Dystonia
3.4 Tics, Tourette syndrome
4. Developmental disabilities
4.1 Learning disability
4.2 Autism
4.3 Attention-deficit hyperactivity disorder
4.4 Deficits in attention, motor control and perception (DAMP)
5. Epilepsy
5.1 Diagnosis
5.2 Definition and classification
5.3 Generalized epilepsies
5.4 Partial epilepsies
5.5 Assessment and treatment of epilepsy
5.6 Anticonvulsant drugs
5.7 Management of status epilepticus
E~sentiaIRevision Notes in Paediatrics for the MRCPCH 2nd Edition
6. Non-epileptic seizures
6.1 Anoxic seizures
6.2 Psychogenic seizures
7. Headaches
7.1 Tension headaches
7.2 Migraine
7.3 Other headaches
9. Neuromuscular disorders
9.1 The floppy infant
9.2 Duchenne muscular dystrophy
9.3 Becker muscular dystrophy
9.4 Other muscular dystrophies and congenital myopathies
9.5 Anterior horn cell disease
9.6 Neuropathies
9.7 Acute neuromuscular disorders
9.8 Disorders of neuromuscular junction
12. Neuro-oncology
12.1 Posterior fossa tumours
12.2 Brainstem tumours
12.3 Supratentorial tumours
--
* 1. DEVELOPMENTAL ABNORMALITIES OF THE NERVOUS
SYSTEM
1.1 Normal development of the nervous system
The exact details of the normal development of the nervous system are complex, but the
important stages can be summarized in the table below:
Organ induction:
3-7 weeks Neural tube closure Anencephaly, spina
bifida
(b) Ventral 5-6 weeks Forebrain, facial Holoprosencephaly
development
Neuronal and glial 8- 16 weeks Neural proliferation Microcephaly
proliferation and early cellular
E
B
SE
=
-
.- Neuronal migration 12-1 9 weeks
differentiation .
Neuronal migration Lissencephaly,
and formation of - pachygyria,
corpus callosum agenesis of corpus
callosum
Neuronal organization 22 weeks to Orientation of Cortical dysplasia
postnatal cortical structures
Myelination 24 weeks through C. Dysmyelination
=
sEz early childhood
s
-
a
years
-
-
F
<
.=
Anencephaly
Failure of closure of the rostra1 aspect of the neural tube; 75% of affected infants are
stillborn.
Encephalocele
Protrusion of cerebral tissue through midline cranial defect located in frontal or occipital
regions.
Meningocele
Cyst formed by herniation of meninges, usually over dorsum of spine. Neurological
disability minimal, risk of bacterial meningitis.
Meningomyelocele
Herniation of meninges, nerve roots and spinal cord through dorsal vertebral defect. Leads
to motor and sensory deficits below lesion, including sphincter disturbance. May be
*associated with other malformations of spinal cord including Arnold-Chiari malformation
(downward displacement of cerebellar tonsils through foramen magnum). Hydrocephalus
may coexist, secondary to Arnold-Chiari malformation or aqueduct stenosis.
1.3 Hydrocephalus
Defined as excess fluid within the cranium. Usually refers to increased volume of
cerebrospinal fluid (CSF).
Production of CSF
Secreted by choroid plexus (as plasma ultrafiltrate which is then modified)
Flows through lateral ventricles, through third and fourth ventricles into posterior fossa
and basal cisterns
Reabsorbed through arachnoid granulations
Neurology
Diagnosis (clinical)
May be asymptomatic
Irritability
Headache
Vomiting
Drowsiness
Increased head circumference
Tense anterior fontanelle
Splayed sutures
Scalp vein distension
Loss of upward gaze (sunsetting)
Neck rigidity
Decreased conscious level
Cranial nerve palsies
Investigations
Ultrasonography (when fontanelle open)
Computerized tomography (CT)
Magnetic resonance imaging (MRI)
Measurement of CSF pressure by neurosurgical intervention may be indicated
C
Management
Decide need for operation by considering symptoms and rate of head growth
Surgical:
Ventriculostomy
Shunting (ventriculoperitoneaI, ventriculoatrial)
717
Essentia 1 Revision Notes in Pa e d i trics
~ for the A4 RCPCH 2 nd Eclition
Polymicrogyria
Increased numbers of small gyri, especially in temporoparietal regions.
Periventricular heterotopia
Aggregation of neurones arrested in their primitive positions. May be part of complex brain
malformation syndromes. X-linked periventricular nodular heterotopia is seen in females,
characterized often by focal epilepsy and is associated in a proportion of cases with
mutations in the FLNl gene.
Pachygyria
Thickened abnormal cortex. Depending on extent, it may lead to cerebral palsy or to
epilepsy.
Aqueduct stenosis
Cause of hydrocephalus in 11% of cases. Aqueduct may be reduced in size or may be
represented by numerous channels within aqueduct location. Can occur in X-linked
syndrome.
g Neurology
B
[ 2. NEONATAL NEUROLOGY
[ 2.1 Neonatal seizures
Seizures are a major neurological problem in the first 28 days of life.
Classification
Tonic seizures - stiffening of trunk and extremities
Mulitfocal clonic seizures - rhythmic clonic movements of different parts of the body
and various seizures
Focal cionic se - repetitive clonic movements of the same part of the body
Subtle seizures - episodes of stereotyped bicycling, sucking and
swallowing movements
Myoclonic seizures - isolated repetitive brief jerks o
Causes
Hypoxic-ischaemic encephalopathy
lntracranial haemorrhage
lntracranial infection
Cerebral malformations
Metabolic disturbances
Withdrawal seizures
Familial neonatal convulsions
Clinical features
Five-minute Apgar score of less than 6, a metabolic acidosis and hypotension are all
suggestive of asphyxia in term infants.
c encephalopathyinterm in
Stage 1 - Hyper-alert, tremulousness, poor feeding;
Stage 2 - Lethargic, obtunded, hypotonic; seizures may occur
Stage 3 - Comatose; seizures within 1 2-24 h
Essential Revision Notes in Pcq~cli,rtrics tor tht3 A1KcPC-H 2nd Ec/itic~n
Potential consequences
Asymptomatic
Catastrophic collapse
Cerebral infarction
Post-haemorrhagic hydrocephalus
Erb's palsy
C5-C6 lesion
Affects deltoid, serratus anterior, supraspinatus, infraspinatus, biceps, brachioradialis
muscles
Arm is flaccid, adducted and internally rotated
Elbow is extended, wrist is flexed ('waiter's tip')
Klumpke's paralysis
C8-TI lesion
Affects intrinsic hand muscles so that flexion of wrist and fingers is affected
Cervical sympathetic involvement may lead to an ipsilateral Horner syndrome
i5
=T Neurology
$
Management
Physiotherapy
Consideration of nerve root surgery
3. DISORDERS OF MOVEMENT
3.1 Cerebral palsy
Cerebral palsy may be defined as a disorder of tone, posture or movement, which is the
result of a static lesion affecting the developing nervous system. Despite the unchanging
nature of the causative lesion, its existence in a developing nervous system means that its
manifestations may change over time.
Epidemiological studies suggest that at least 80% of cases of cerebral palsy are the result of
prenatally acquired causes. A minority are the result of intrapartum asphyxia.
Classification
Based on the distribution of motor impairment and tone variations.
Spastic (characterized by fixed increase in muscular tone)
Hemiplegia
Diplegia
Quadriplegia
Essential Revision Notes in R~ecliatricst i ~the
r R.1RCPCH 2nd Edition
3.2 Ataxia
Acute cerebellar ataxia may occur following viral infection. It appears to be the result of
both infectious and post-infectious processes; most commonly 'following varicella virus
infection. Also measles, mumps, herpes simplex and Epstein-Barr viruses, coxsackievirus
and echovirus.
Occult neuroblastoma may also lead to acute ataxia.
A common cause is overdosage of drugs such as carbamazepine, phenytoin, benzo-
diazepines. Also piperazine, antihistamines.
Other causes
Posterior fossa tumour
Migraine
Friedreich's ataxia
Classified as a spinocerebellar degeneration
~utosomalrecessive condition (9q13)
Gene product frataxin
~nvolvedin modulation of mitochondria1function
Clinical characteristics:
Onset of symptoms in first or second decade
Loss of proprioception
Increasing impairment of cerebellar function
Development of pes cavus
Cardiomyopathy develops
Deterioration so that patients are usually not ambulant in their 20s or 30s
Treatment:
Currently symptomatic
Physiotherapy
Suitable aids and appliances
;
3.3 Dystonia
Dystonia is a condition in which muscle tone is abnormal without pyramidal involvement.
In many dystonias, muscular tone varies with the position of the limbs. There may be a
dystonic component to cerebral palsy of hypoxic-ischaemic origin, but there are a number
of clearly defined syndromes in which dystonia is the main feature.
Dopa-responsive dystonia
Described by Segawa
Idiopathic dystonia
Symptoms vary throughout the day
Essential Revision Notes in Paediatrics tbr the MRCPCH 2nd Edition
Simple tics
Commonly affect children for a few months in mid-childhood
Up to 25% of children
Spontaneous resolution
Multiple tics
Some children are prone to tics of different types
Different motor tics, vocal tics
May not remit entirely
Tourette syndrome
This is defined by:
Multiple motor tics
One or more vocal tics
Onset before 21 years of age
Duration of > 1 year
There is probably a continuum between multiple tics and Tourette syndrome.
Treatment
Tics may respond to haloperidol.
F Neurology
4. DEVELOPMENTAL DISABILITIES
4.1 Learning disability
The term 'learning disability' is now generally used in preference to the term mental
retardation. It covers a wide variety of conditions in which cognitive functioning is
depressed below average levels. In the United States, the term mental retardation is
retained, with learning disability being used to refer to failure to achieve cognitive potential.
Learning disability tends to be grouped according to severity: moderate learning disability
usually refers to IQ 50-70, with severe learning disability being defined as IQ <50. The
term profound learning disability is sometimes used to refer to IQ <20.
r
; The prevalence of learning disability is difficult to estimate. The prevalence of severe
learning disability has been estimated at 3 to 4 per 1000 but although moderate learning
disability is clearly more common, its exact prevalence remains obscure.
Aetiology
This is easier to determine in severe learning disability.
t
In severe learning disability, the following potential causes are recognized:
Chromosomal
Genetic
Congenital anomalies
@ Intrauterine insults
' @ Central nervous system infection
Familial
Unknown (20°/0)
In moderate learning disability,
fl the following potential causes are tiecognized:
Same range of problems as severe learning disability
Unknown (55%)
4.2 Autism
Autism is a disorder characterized by:
Disturbance of reciprocal social interaction
Disturbance of communication (including language, comprehension and expression)
Disturbance of behaviour, leading to restriction of behavioural range
All the above findings may be seen in learning disabled individuals.
See also Chapter 2 - Child Development, Child Psychiatry and Community Paediatrics,
section 5.
Asperger syndrome
Often considered to be on the autistic spectrum. It is characterized by autistic features in
individuals of otherwise normal intelligence. Specifically characterized by:
Impairment in social interaction
Stereotypic behaviour
No specific impairment of 6nguage
Treatment needs to include not only assessment but also educational help and a
physical programme (occupational therapy)
5. EPILEPSY
5.1 Diagnosis
Diagnosis of 'fits, faints and funny turns' is based primarily on clinical assessment of such
events with recognition of characteristic patterns, supported by the results of special
investigations.
or generalized I s~pileisy
;. A with.'?continuous
*. , spike-waves
~nsIow-wave sfeep
~andau-~leffner syndrome
Myoclonic seizures
Brief sudden generalized muscular jerks. Drugs of choice are sodium valproate, benzodia-
zepines, lamotrigine. May be exacerbated by carbamazepine.
Infantile spasms
Onset in first 12 months. Brief sudden muscular contractions resulting in extension or
flexion of the body. Attacks occur in runs. Associated with disorganized EEG described as
hypsarrhythmia, as well as developmental arrest or regression. May be idiopathic or
symptomatic (causes include tuberous sclerosis, perinatal hypoxic-ischaemic injury, inborn
errors of metabolism). Treatment of choice is corticosteroids (or adrenocorticotropic
hormone) or vigabatrin.
Management
Explanation of potential risks and benefits of different therapies
Medication - start, depending on frequency and number of seizures
Maintenance of seizure freedom with medication for perhaps 2 years
Subsequent withdrawal of medication
Essentic]/ Revision Notes in R;tecliatrics for the M RC-PCH 2174Edition
Some forms of partial epilepsy may be amenable to epilepsy surgery - when seizure
disorder is intractable - site of seizure onset can be localized - site is non-eloquent
brain
Other forms of treatment - steroids, ketogenic diet, vagal nerve stimulation
1
measure temperature
measure blood sugar
easy intravenous access + difficult
i
i.v.1i.o. lorazepam 0.1 mglkg
J.
rectal diazepam
1
or
i.v. diazepam 0.25 mglkg
still fitting
+
stopped
investigate
continues fitting
f
i.v.1i.o lorazepam 0.1 mglkg
1
intravenous access
f
phenytoin 15 mglkg
i.v. over 20 minutes
J.
general anaesthetic
paralyse, ventilate
Ragnosis
7OoA of children with epilepsy are seizure-free by their 16th birthday. Remission is less likely
in: partial epilepsy, symptomatic epilepsy, some epilepsy syndromes such as juvenile
myoclonic epilepsy or epileptic encephalopathies such as Lennox-Gastaut syndrome.
6. NON-EPILEPTIC SEIZURES
6.1 Anoxic seizures
Anoxic (or anoxic-ischaemic) seizures form a group of paroxysmal disorders which are
often the main differential diagnosis to epilepsy. Diagnosis is predominantly by clinical
assessment. There are two important types seen in childhood: breath-holding attacks and
reflex anoxic seizures.
Breath-holding attacks are seen in young children, often in the setting of a tantrum. The
thwarted child screams and screams and holds his or her breath, becoming cyanosed and
sometimes exhibiting subsequent cdnvulsive movements. It may be possible to encourage
the child to take a breath by gently blowing on his face. The tendency to have such
episodes abates as children become older.
Reflex anoxic seizures are the clinical manifestation of vagocardiac attacks. The precipitant
may be a sudden, unexpected, painful stimulus or, occasionally, vomiting. Increased
sensitivity of the vagus nerve leads to bradycardia, or even brief asystole, leading to pallor
and cerebral anoxia-ischaemia. Following collapse, the child may then exhibit convulsive
movements. Recovery is spontaneous. Apart from the risk of injury during a collapse, the
prognosis is good with few, if any, individuals suffering adverse cerebral effects. The
tendency to have such attacks improves with age but is often not completely abolished.
Diagnosis can be confirmed by eliciting bradycardia under controlled monitoring conditions
by exerting eyeball pressure.
7. HEADACHES
Headache is a common complaint in childhood. Population studies estimate that up to 35%
of children have complained of headache at some time. The commonest cause of headache
in Western populations is tension or psychogenic headache.
Classificationof headache J
or psychogenic headache
* Arteriovenous malform
Refractive errors.'
Carbon monoxide p
Management
Reassurance
Supportive psychotherapy
fbr the MRCPCH 2nd Editior~
Essential Rcvision Notes in R~edi~trics
7.2 Migraine
Defined as 'familial disorder characterized by recurrent attacks of headache widely variable
in intensity, frequency and duration. Attacks are commonly unilateral and are usually
associated with neurological and mood disturbance. All of the above characteristics are not
necessarily present in each attack or in each patient'.
Classification of migraine
Common migraine (no aura)
Classical migraine (aura preceding onset of headache)
Complicated migraine (persisting neurological deficit after migraine attack)
Basilar migraine
Migraine variance
Cluster headaches
Treatment
Acute - analgesics, relaxation, occasionally antiemetics
Prophylaxis - avoidance of triggers such as cheese, pizotifen, propranolol
8.1 Macrocephaly
Consider
Familial macrocephaly
Hydrocephalus
Chronic subdural haematomata
Associated disorders such as tuberous sclerosis or neurofibromatosis
Metabolic conditions
1) ,; -
734
1
investigations depend on rate of growth, deviation from normal and presence or absence a
&normal neurological signs.
Treatment
~fnecessary, this is based on the underlying pathology.
82 Microcephaly
~efinedas occipitofrontal head circumference, below two standard deviations for age, se,
and gestational age.
Consider
a Insults during pregnancy
Perinatal insults
a Encephalopathies in infancy
a Autosomal recessive microcephaly
Investigations
Chromosomes
Antibodies to congenital infections
Metabolic screen
MRI scan
Consider measurement of maternal plasma amino acids to exclude maternal
phenylketonuria
Craniosynostosis
Premature closure of one or more cranial sutures. Ultimate skull deformity will depend
upon which sutures are involved and the timing of their fusion.
I
Apert syndrome
Acrocephaly, facial underdevelopment, syndactyly, learning disability.
Crouzon syndrome
Acrocephaly, scaphocephaly or brachycepha1y, hypertelorism, exophthalmos, increased
intracranial pressure, learning disability.
9. NEUROMUSCULAR DISORDERS
9.1 The floppy infant
It is important to realize that much of the process leading to a diagnosis in the floppy infant
is the clinical assessment of the infant by history and examination. It is this assessment
which should direct diagnostic investigations. In an era when specific genetic tests for
conditions are increasingly available, a clearer idea of possible diagnoses is even more
important.
Causes of hypotonia in infants
C
cular dystrophy * 0-A
Molecular genetics
Caused by mutations in the dystrophin gene
Gene comprises approximately 2 million base pairs
Duchenne muscular dystrophy patients produce no dystrophin
Becker muscular dystrophy (allelic, milder form) patients produce abnormal but
functional protein
Dystrophin is localized to muscle cell membranes
/ i ~ f01-
Essent i n / Revision Notes in R ~ e ~trjcs l the ,A4 RCPCH 21id E c l i t i o ~ ~
Clinical features
Onset in early years
Some cases are identified presymptomatically by abnormal transaminases measured
during intercurrent illness
Sometimes leads to faltering growth
Early delay in motor milestones
Difficulties in climbing stairs
Lordosis with waddling gait
Pseudohypertrophy of calves
Progressive muscular weakness
Tendency to joint contractures
Typically, boys lose ability to walk between 8 and 12 years
When dependent on wheelchair, boys are prone to develop scoliosis
Respiratory failure supervenes
Also
Increased incidence of learning disability
Cardiomyopathy occurs
Survival to late teens, early twenties
Diagnosis
High plasma creatine kinase (greater than 5000 lull)
Mutations in dystrophin gene
Muscle biopsy - dystrophic picture with absent dystrophin
Treatment
There is no curative treatment
Physiotherapy
Appropriate seating
Management of scoliosis
Non-invasive respiratory support
Corticosteroids improve muscular power, but it is unclear as to when, how and for how
long they should be administered
Diagnosis
~ ~ c h e n nand
e Becker muscular dystrophies are distinguished clinically and on muscle
biopsy findings. Nature of genetic mutation can provide a pointer as to the severity of the
condition but current routine genetic testing does not distinguish reliably between Duch-
enne muscular dystrophy and Becker muscular dystrophy; it just identifies a dystrophino-
pathy.
Congenital myopathies
A group of disorders characterized by hypotonia and weakness from birth. Differentiated on
clinical and histological features.
Central cord disease
Nemaline myopathy
Myotubular myopathy
Myotonic dystrophy
Common (incidence 13.5 per 100,000 live births) neuromuscular condiion
Autosomal dominant inheritance (19q13)
Severity appears to be related to size of triplet repeat (CTG) in gene mutation
Diagnosis
Gene mutation analysis
a Electromyogram in older children upwards (>3 to 4 years of age) shows characteristic
'dive bomber' discharges
Clinical
Symmetrical muscle weakness of trunk and limbs, more marked proximally than distally
and in legs more than arms
Tongue fasciculation
Investigations confirming neurogenic abnormalities
Genetics
Autosomal recessive
Gene at chromosome 5q11-13
Disease caused by mutations of the SMN gene
Severity-determining mechanism remains unclear
t b r the MRCPCH 2nd Eclition
Essential Revision Notes i r ~Pacdic~trics
Diagnosis
Electromyography
Muscle biopsy
Genetic analysis
9.6 Neuropathies
Hereditary motor and sensory neuropathies are the most common degenerative disorders of
the peripheral nervous system. Often known by their eponymous title Charcot-Marie-Tooth
disease or peroneal muscular atrophy.
Previously X-linked, autosomal recessive and autosomal dominant forms were recognized,
but the advent of molecular genetics has identified numerous genetically distinct forms (see
table below).
Clinically, affected individuals develop slowly progressive distal weakness with areflexia. In
the early phases, foot drop is often the main clinical problem. In later stages, which in the
common forms may be several decades after onset, hand weakness, joint deformity and
distal sensory loss may be problematic.
Neurology
Type I (Demyelinating)
CMT 1A AD Duplication
17~11.2
PMp22
1
CMT 1 B
CMT l C
AD
AD
1 q2 1-q23 PO
I Low motor nerve
conduction velocity
First decade
CMT 4 AR
C
Type I1 (Axonal)
X-linked forms
Hereditary motor and sensory neuropathies and Friedreich's ataxia are sometimes confused.
In the hereditary motor and sensory neuropathies, there is areflexia and evidence of distal
weakness. In Friedreich's ataxia is there much clearer ataxia with evidence of loss of joint
position sense. On neurophysiological testing, the patients with hereditary motor and
sensory neuropathy have abnormal motor conduction, whereas Friedreaich's ataxia patients
have evidence of a sensory neuropathy.
Clinical features
Sudden onset of weakness, usually affecting lower limbs
Ascending paralysis
Usually symmetrical weakness
Pain often a prominent feature
Sensory involvement in about 50%
Respiratory muscle weakness may occur
Diagnosis
High CSF protein
A marked slowing of motor neurone conduction velocity
Conduction block
Course
Deterioration over the first 10-20 days
Plateau
Recovery
Mortality is 2-3% in children
Treatment
Symptomatic
Respiratory support
Plasma exchange
High-dose immunoglobulin
Juvenile dermatomyositis
A systemic illness affecting primarily the skin, muscles and gastrointestinal tract.
Unlike adult dermatomyositis, juvenile dermatomyositis is not associated with malignancy.
Clinical
Age of onset between 5 and 10 years
May present with fever, muscle pain
Onset can be insidious
Increasing muscular weakness, mainly proximal
Rash involving upper eyelids (heliotrope rash) and periorbital region develops
Rash on extensor surfaces. Calcinosis is a feature
May have difficulty swallowing
Children are often miserable in advance of other symptoms
Diagnosis
Creatine kinase may or may not be raised
Muscle biopsy may show perifascicular atrophy, but changes can be patchy
Neurology
Treatment
Corticosteroids
Other immunosuppressive treatment such as methotrexate or cyclosporin
Clinical features
Onset after 1 year
Adolescent girls most commonly affected
Generalized form affects extraocular muscles first
Then goes on to affect proximal limbs and bulbar muscles
Variable natural course
Diagnosis
Edrophonium test
Electromyography confirming neuromuscular block
Demonstration of anti-acetylcholine receptor antibodies
Treatment
Anticholinesterase drugs
lrnmunosuppressants
Thymectomy
Plasma exchange or immunoglobulin infusion acutely
Age Organism
Neonatal Group B streptococcus
Escherichia coli
Listeria monocytogenes
Staphylococcus aureus
First 2 months Group B streptococcus
Escherichia coli -
Haemophilus influenzae =-
-
Streptococcuspneumoniae
Older infants and Haemophilus influenzae
young children Neisseria meningitidis
Streptococcu
Clinical features
In neonates meningitis is usually part of a septicaemic illness. Symptoms and signs may
be non-specific, e.g. lethargy, poor feeding, respiratory distress. Neck stiffness is rarely
seen
In young infants also, signs may be non-specific and meningeal irritation may be absent
In older children, signs are more typical - lethargy, headache, photophobia, neck
stiffness. Meningococcaemia is associated with a haemorrhagic rash
Outcome
Neurological sequelae may occur in up to 30% of children - focal neurological
deficits, learning disability, hydrocephalus and deafness may alr occur
Mortality is improving with earlier diagnosis and treatment
Diagnosis
Lumbar puncture and CSF analysis are definitive
White cell count is raised with a predominance of neutrophils, CSF glucose is reduced
and protein is raised
Cram staining of CSF and immunoassays may allow identification of the organism
Lumbar puncture is contraindicated if there are signs of raised intracranial pressure or if
consciousness is impaired. Treatment then needs to be aimed at the most likely
organisms. Blood cultures can be taken before starting treatment
Management
Antibiotic treatment - agent will depend on age of patient and probable infecting
organism
Watch for subdural effusions and hydrocephalus - measure head circumference
Evidence concerning steroid use to prevent neurological sequelae is unclear - some
evidence to support the prevention of deafness in Haemophilus influenzae meningitis
Neurology
Viral meningitis may resuIt from a wide variety of viruses: coxsackievirus, echoviruses, and
mumps, measles, herpes simplex, poliomyelitis and varicella zoster viruses.
Symptoms similar to bacterial meningitis, but less pronounced
Specific diagnosis may be suggested by other disease stigmata
CSF clear with lymphocytosis
Prognosis of uncomplicated viral meningitis is good
Tuberculous meningitis
Generally occurs within 6-8 weeks of primary pulmonary infection or during miliary
tuberculosis (TB). Commonest in age range 6 months to 3 years.
Leads to basal arteritis, which may cause hydrocephalus and cranial neuropathies. Symp-
toms otherwise are often non-specific, lethargy, fever, headache.
CSF - high white cell count, predominantly lymphocytes, raised protein often > 2 dl, low
glucose, tuberculous cultures may be positive.
Treatment
Antituberculous chemotherapy
Optimal treatment not determined
Usually triple therapy (rifampicin, isoniazid, pyrazinamide) for at least 6 months but
many authorities suggest a fourth drug for the first 2 months
The place of corticosteriods in treatment is unclear but these are often used in the first
few months to reduce inflammation
Mortality and morbidity remain high despite treatment.
10.2 Encephalitis
Numerous viruses may lead to inflammation of the brain: herpes viruses, adenoviruses,
arboviruses and enteroviruses for example. The underlying causative agent in undiagnosed
encephalitis may remain obscure. It is therefore usual practice to treat with cefotaxime/
ceftriaxone, aciclovir and erythromycin/azithromycin until results are available.
Clinical features - confusion, coma, seizures, motor abnormalities
Infection usually starts to resolve 7-1 4 days after the onset. However, recovery may be
delayed for several months
Treatment
Supportive (fluid management/ventilation if necessary)
Aciclovir
Mycoplasma encephalitis
Mycoplasma pneumoniae is the commonest cause of community-acquired pneumonia in
adults and commonly leads to infection in the paediatric age range. It may cause
encephalitis, predominantly through immune-mediated mechanisms which may respond to
steroid administration. The evidence base is small.
1 CEREBROVASCULAR DISEASE
1 1 . Arterial occlusion
May result from embolism or thrombosis.
plasma homocysteine
Clotting studies, especially factor V Leiden, prothrombin 2021 OA, iipoprot
The place of measurement of antithrombin Ill protein C and protein S in the genesis of
childhood stroke remains controversial.
Causes
Sepsis
Otitis media
Sinusitis
Cutaneous infection
Dehydration
Coagulopathy
for the M RCPCH 2nd Edition
Essential Revision Notes in P~edi~tt-ics
Treatment
Disputed
Heparin may be given in the acute phase
12, NEURO-ONCOLOGY
Brain tumours are the second commonest malignancy in children after leukaemia. In
infants, supratentorial tumours predominate, whereas in older children, infratentorial
tumours are much more common. The trend reverses in children over 8 years of age with a
slight preponderance of supratentorial tumours.
Central nervous system tumours are of varying degrees of malignancy. Those which do
metastasize tend to do so within the central nervous system. It is also important to note that
a 'benignt tumour situated so that it cannot be removed may have a more serious effect than
a 'malignantf tumour that is differently situated.
General symptoms and signs associated with brain tumours in children may include
headache, vomiting, papitloedema, cranial nerve palsies, and other focal symptoms such as
ataxia.
Medulloblastoma
A common tumour. Highly malignant, rapidly growing. Arises from the cerebellar vermis.
Often leads to hydrocephalus. May metastasize along CSF pathways. Often solid tumours.
Treatment - surgery and radiotherapy. Trials have sought to clarify the position of
chemotherapy
Outlook has improved - 75% 5-year survival, 50°/0 10-year survival. Prognosis is
poorer in young children. Evidence is emerging that the specific genetic constitution of
tumour is most important in determining outcome
Ependyrnoma
6-10% of childhood tumours. Arises from fourth ventricle. May lead to hydrocephalus and
may metastasize.
Treatment - surgical resection and radiotherapy
Poor five-year survival often related to localization of tumour
Neurology
Ependymoma
30-4O0/0 of ependymomas are supratentorial
These are more malignant than their infratentorial counterparts
They have a tendency to metastasize and so prognosis is poor
Optic gliomas
One-third are prechiasmatic, two-thirds are chiasmatic or postchiasmatic
Generally, these tumours are pilocytic astrocytomas. One-quarter occur in the setting of
neurofibromatosis type 1
Essential Revision Notcs in R~ecii,~
tric-s tor the h/lKCPCH 2nd Ecliticsn
Clinical presentation - prechiasmatic lesions may present late with proptosis with
associated visual loss. Postchiasmatic lesions lead to visual loss
Treatment - controversial. Often conservative, but surgery and radiotherapy may be
indicated
Craniopharyngioma
Tumour arises from small aggregates of cells which are remnants of Rathke's pouch. Tumour
is either suprasellar or suprasellar and intrasellar. Often cystic.
.
Local features:
Visual disturbance (bitemporal hemianopia)
Depressed consciousness
Vomiting
Nystagmus
Investigations
Skull X-ray may show erosion of dorsum sellae, also calcification.
MRI scan will delineate lesion better
Also, endocrine investigations and visual field mapping
Treatment
Controversial
Surgery
Radiotherapy
13.1 Neurofibromatosis
Neurofibromatoses are predominantly inherited disorders.
Neurology
Neurofibromatosis type 1
Gene is localized to chromosome 17q11.2.
Neurological manifestations
Macrocephaly
Learning disability
Epilepsy
Optic gliomas
Neurofibromatosis type 2
Gene is localized to chromosome 22q11.2.
Diagnostic criteria
Bilateral Vlllth nerve neurofibromas
Unilateral Vlllth nerve mass in association with any two of -the following:
meningioma, neurofibroma, schwannoma, juvenile posterior capsular cataracts
Unilateral Vlllth nerve tumour or other spinal or brain tumour as above in first-degree
relative
Retinal hamartomas
Renal angiolipomatas
Cardiac rhabdomyomata
Brain imaging may reveal cortical tubers, subependymal nodules with calcification.
Clinical features
Progressive ataxia
Scleral telangiectasia
Abnormalities of cell-mediated and humoral immunity leading to increased
sinopulmonary infections and high incidence of reticuloendothelial malignancies in
later life
Diagnosis
Elevated a-fetoprotein level
Reduced IgA
Reduced IgD
Inversions and translocations involving chromosomes 7 and 14 .
Gene mutation analysis
Incontinentia pigmenti
Rare
Probably inherited as X-linked dominant
Characterized by skin lesions - initially erythematous, papular, vesicular or bullous
lesions on trunk and limbs, then pustular lesions, then pigmented lesions
30-50% of neurological features:
seizures
encephalopathy
Eye lesions in 30%
Neurology
~ ~ ~ o m e l a n oofs Ito
is
Also rare
a Sporadic inheritance
a Hypopigmented areas
a Central nervous system involement common including seizures, hemimegalencephaly
Canavan disease
n-Acetylaspartic aciduria
Autosomal recessive (17p13-ter)
Leads to spongy degeneration of the subcortical white matter
Progressive neurological impairment occurs
Death in first decade
Autosomal recessive
Glycine accumulates in body fluids
Neuropathology - identifies poor myelination
Revision Notes in P;ledi'~tric-sfor the hf RCPCH 2nd Edition
E~senti~ll
Clinical
Poor respiratory effort at birth
Hypotonia
Gradual improvement over first week
Evolution of myoclonic encephalopathy
Severe seizure disorder and major developmental delay ensues
Specific syndromes
Keams-Sayre
syndrome
MERRF
MELAS
Alpers disease
Progressive external o
cerebellar dysfunctio
Myoclonic epilepsy w
Mitochondria1 myop
stroke-tike episodes
Subacute necrotizing encephalopathy - hypotonia,
progressive deterioration in neurolagical abilities *
~
s
Neurology
Clinical
Onset in the neonatal period or early infancy
Hypothermia, poor weight gain
Hair is sparse, brittle
Progressive cerebral infarction occurs leading to seizures and neurological impairment
Diagnosis is confirmed by biochemical or genetic means or by hair examination
Death in first 2 years
Sphingolipidoses
These are lysosomal diseases involving disorders of the sphingolipid metabolism. Sphingoli-
pids are important components of central nervous system membranes. See Chapter 15 -
Metabolic Medicine, Section 12.
GM2 gangliosidosis (Tay-Sachs disease) - neurodegenerative, onset 3-9 months,
startles, seizures, blindness 3c -
&- qI,*- $?--%
-r
j-
f
. Niemann-Pick disease - types A and C have neurological involvement leading to
progressive deterioration
Fabry disease - presents with painful hands and feet. May run a slow progressive
course with renal involvement
E
Mucopolysaccharidoses
These are disorders characterized by accumulation of mucopolysaccharides or glycosarni-
noglycans in lysosomes. There are numerous different types. See Chapter 15 - Metabolic
Medicine, Section 11.
Hurler disease (MPS 1H) - characteristic facies, marked dwarfism, corneal clouding,
neurological involvement progressive. Hydrocephalus may ensue
Sanfilippo disease (MPS Ill) - typical mucopolysaccharidosis features may be mild.
However, severe neurological involvement with intellectual deterioration and seizures
-. ---
Peroxisomal disorders
See Chapter 15 - Metabolic Medicine, Section 10.
Zellweger syndrome
Presents in the neonatal period , :,
High forehead, patent fontanelles. Severe hypotonia and poor sucking or swallowing
Very poor subsequent neurological development
Often associated with cerebral gyral abnormalities
X-linked adrenoleukodystrophy
Relatively common disease which involves the central nervous system and adrenal
glands
Over half present with central nervous system features. This group present at 4-8 years
with cognitive decline and progressive gait disturbance
Brain imaging shows leukodystrophy
Levels of very-long-chain fatty acids (VLCFAs) are elevated
i
14.6 ~ e u k o d ~ s t r o ~ hand
i e s other neurodegenerative disorders
Leukodystrophies are degenerative disorders which affect the white matter of the brain
through abnormalities of myelin. In some, the metabolic features are known, in others the
diagnosis is based on clinical features.
Leukodystrophies
a With known metabolic defect
Metachromatic leukodystrophy
Krabbe leukodystrophy
Adrenal leukodystrophy
Canavan disease (see Section 14.1 above)
a Without recognized metabolic defect
Pelizaeus-Merzbacher disease
Cockayne disease
.Alexander disease
Leukodystrophy with subcortical cysts
Leukodystrophy with vanishing white matter
Late infantile NCL 18 months to Epilepsy, marked ataxia, . Death 5-1 5 years
4 years late visual deficit
I
B5
IL
Juvenile NCL
Adult NCL
4-7 years
Adulthood
Visual failure, later dementia
Slow
C
i
Mutation analysis has shown that mutations in this gene lead to severe neonatal encephalo-
pathy in boys.
Angelman's syndrome
Previously known as 'happy puppet' syndrome, this syndrome is caused by the deletion of
chromosome 15q11.2-12, which is maternally inherited. Deletion includes the gene for P3
subunit of GABA receptor.
Clinical features include:
Severe learning disability
Ataxia
Jerky movements
Seizures
Often cheerful demeanour
Clinical assessment
Level of consciousness
Respiratory pattern
s5
Pupil size and reaction
Brainstem signs
Leakage of &rebmspinal fluid
Focal signs
consider potential of cervical spine fracture
Management
Airway, breathing, circulation
/ X-ray cervical spine
: Assess intracranial pressure
CT scan
Fluid restriction
After first 4-5 days - supportive care
Late complications
Learning disability (global and specific)
Behavioural disturbance
Motor deficits
Post-traumatic epilepsy
Headaches
Essen fia 1 Revision Notes in Pclediatrics tior the h.1K CPCH 217d Edition
Mechanism
Unclear
Cerebral parenchyma may be damaged by blunt trauma
Recent evidence suggests brainstem injury leading to apnoea and ischaemic injury
Prognosis
Non-accidental head injury may lead to death
Prognosis for neurological recovery is guarded
Moebius syndrome
Bilateral facial paralysis with bilateral abducens paralysis
Other lower cranial nerves may be affected
Up to one-quarter have learning disability
Congenital ophthalmoplegia
Can affect all the above nerves
Nystagmus
Involuntary, rhythmical, conjugate, oscillatory movements of the eyes which may occur
in any plane
Results from dysfunction of complex mechanisms that maintain ocular fixation
Essential Revision Notes in Paedir?tric-sfor the MKCPCH 2nd Eclition
TYP~ Cause
Pendular Congenital
Acquired - disease of brainstem/cerebellum
Horizontal jerk:
Vestibular End organ
Gaze evoked Posterior fossa
Rotary Vestibular or medullary lesions
Differential diagnosis
Roving eye movements of blind children
Opsoclonus
Uses
lnvestigation of patients with seizures
Detection of cerebral dysfunction
Evaluation of depressed consciousness
lnvestigation of neurodegenerative disorders
Neurology
Three cycles per seond (c/s) spike and wave in typical absences ('petit mal')
Four d s spike and wave and poly-spike and wave bursts in juvenile myoclonic epilepsy
Clusters of high-amplitude spike and wave complexes in one or both Rolandic areas in
benign focal epilepsy with Rolandic spikes
Epileptic encephalopathies
High-voltage chaotic slow waves and spike and sharp waves in hypsarrythmia
Spike and waves in absence of seizures and loss of language skills in Landau-Kleffner
syndrome
Slow spike wave discharges at 1.5-2.5 d s in Lennox-Gastaut syndrome
Electroretinogram (ERG)
Measures response of retina to repeated light flashes
Used in investigation of low vision and in neurological regression
Electromyography
Denervation - shorter and lower voltage action potentials; later giant potentials
Myopathic change - reduced action potentials
~ ~ g n e tresonance
ic imaging (MRI)scanning
Useful in:
Detection of parenchymal lesions, especially white matter lesions
Posterior fossa lesions
Ophthalmology
William H Moore and Ken K Nischal
CONTENTS
1. Basic anatomy of the eye
1.1 Orbits
1.2 Extraocular muscles
1.3 The globe
2. Amblyopia
3. Ophthalmic examination
3.1 Refractive errors
3.2 Slit-lamp biomicroscopy
3.3 Fundoscopy
3.4 Visual fields
3.5 Colour vision
3.6 Electrophysiology
4. Eyelid abnormalities
4.1 Congenital eyelid abnormalities
4.2 Infections and inflammations of the lids
4.3 Haemangiomas
4.4 Ptosis
4.5 Lid retraction
4.6 Lid lag
6. The orbit
6.1 Abnormalities of the position of the globe
h r the ItlKCCPCH?rid Edition
Essential Revision Notes in t';x~clic~h.icri -
7. The conjunctiva
7.1 Conjunctivitis
7.2 Conjunctival pigmentation
8. The sclera
8.1 Pigmentation of the sclera
8.2 Scleral inflammation
9. The cornea
9.1 Developmental anomalies
9.2 Corneal clouding
9.3 Keratitis
9.4 Keratoconus
19. Nystagmus
19.1 Character of nystagmus
19.2 Physiological nystagmus
19.3 Early-onset nystagmus
19.4 Later-onset nystagmus
19.5 Ocular causes of nystagmus
The action of the external ocular muscles with the patient confronting the examiner.
Anterior chamber
Bulbar
Vitreous
The eyeball.
Cornea
A transparent avascular tissue joined to the sclera at the limbus that refracts light en route to
the retina. Sensory innervation is supplied by the first division of the trigeminal nerve. The
transparency of the cornea is the result of its uniform structure, avascularity and the active
transport functions of the corneal endothelium, which keep it relatively dehydrated.
Conjunctiva
Thin, transparent membrane that covers the posterior surface of the eyelids and the anterior
surface of the sclera (bulbar conjunctiva).
Sclera
The fibrous outer protective coating of the eye.
Uveal tract
Consists of iris, ciliary body and choroid, each of which has a rich vascular supply and
pigment. The choroidls vasculature provides nutrition for the outer sensory retina (photo-
receptors and outer nuclear layer).
Anterior chamber
Fluid-filled space between the cornea and iris diaphragm. The aqueous fluid is secreted by
the ciliary body and provides nutrition for the corneal endothelium. It reaches the anterior
chamber through the pupillary space and drains via the trabecular meshwork and canal of
Schlemm (in the periphery of the anterior chamber) into the venous'circulation.
Lens
Lies posterior to the iris and anterior to the vitreous humour, suspended by zonules from the
ciliary body. Anterior to the lens is the aqueous humour. The lens of the newborn infant is
more spherical than that of the adult and as such has a greater refractive power which can
compensate for the relative shortness of the young eye.
Vitreous
A transparent gelatinous structure which fills the posterior four-fifths of the globe. It is firmly
attached to the pars plana anteriorly and has a loose attachment to the retina and optic
nerve posteriorly. The vitreous is ~ 9 9 O water.
/ ~
Retina
The retina contains the sensory receptors (rods and cones) and their complex network of
connections leading to the optic nerve. The fovea centralis is the centre of the macula; it
has the greatest concentration of cones and subsequently the best potential for visual acuity.
Light falling onto the retina is converted into nerve impulses by the rods and cones. Nerve
fibres from the ganglion cell layer of the retina coalesce to form the optic nerve and synapse
in the lateral geniculate body. Fibres from the temporal retina travel without crossing at the
~ssentialRevision Nr~tesin &edic3trics for the M RCPCH 2 ncl Edition
chiasm to the ipsilateral visual cortex. Nerve fibres from the nasal retina will decussate at
the chiasm and are directed toward the contralateral visual cortex. The decussation of nerve
fibres causes portions of each retina to be represented in each visual cortex (see visual fields
box on page 776)
2. AMBLYOPIA
This is the commonest cause of decreased vision in childhood between birth and 8 years of
age. It is the reversible decrease in vision as a result of abnormal visual experience during
the first few years of life. It is reversed in unilateral cases by occluding the good or better
seeing eye. Causes include strabismic, ammetropic (bilateral large refractive errors), ani-
sometropic (difference in refraction of the two eyes) and meridional (due to astigmatism)
amblyopia. In bilateral cases alternate eye occlusion may be attempted.
3. OPHTHALMIC EXAMINATION
Examination begins with observation of the child in the waiting area or in bed, in their
parents' arms and as they enter the examination room. Note eye movements, eye contact,
sensitivity to lighting changes and gross and subtle dysmorphic features. Observation of the
family may give clues to inherited conditions.
History, as in all medicine, is paramount to a correct diagnosis. This time is also useful for
examining the behaviour of the child and building the rapport and trust needed to produce
a fruitful examination.
Visual acuity measurement is the most important test of visual function. The age of the,child
and their level of development dictate which type of test is used. Th.e table of observable
visual behaviour indicates expected levels of vision up to the age of 1 year.
Ophthalmology
- - -
Blink to flash
Turn to diffuse light
Fix & Follow near face
Watches adult 0.75 m
Fix & Follow 6.5 cm ball
Watches adult 1.5 m
Converges to 6.5 cm
Fixates 2.5 cm brick 0.3 m
Blinks to Threat
Watches adult 3 m
Fixates 1.25 cm (Smarties)
Fixates 1.25 mm
(100s & 1000s)
Bold text indicates upper limit of normal; Neo. neonate; wk, weeks; m, months.
Anisometropia - this is where the two eyes have differing refractive errors. A small
degree may be acceptable for visual development but amblyopia will almost certainly
develop if hypermetropic and > 1 dioptre
3.3 Fundoscopy
By diredindirect ophthalmoscope, facilitated by dilatation of the pupil.
homonymous hemianopia.
Bit~mporalhentianopia
Chiasmal lesion (pituitary
abnodities).
0 Tilted optic discs
Nasal-retinal disease (retinitis pigmentosa)
B i n k t hebnihopia
Glaucoma, hmporal retinal disease (retinitis pigm
Bilateral occipital disease,
Cen&aBscotanra
Macular disease, optic neur
k e oc*toma
Glaucoma, ischaemic optic neuropathy (craniosy
myopia
field
~ltitks l dsfect
Glaucoma, optic nenrdchias
lschaemic optic neuropathy,
Acquired visual loss
Acquired visual loss is rare in children. A thorough ovular examination including visual
field analysis is very important.
History is vital to ascertaining whether this is acquired rather than present from birth.
r congenital amaurosis
Essentic?lRevision Notes in E~edi~ltrics
tor the MKCPCH 2nd Edition
-
3.6 Electrophysiology
Visual evoked potentials - can be used to define visual development'in infants. This
measures the time taken for light stimuli to induce excitation of the visual pathways
from the retina to the occipital cortex and gives an indication of the latency and
amplitude of the response. A measure of visual acuity can be extrapolated from this with
varying size of stimuli
Electroretinogram - this is an electrical recording of the response of the retina to a
visible stimulus, e.g. flash of light. Useful in retinal disease.
4. EYELID ABNORMALITIES
4.1 Congenital eyelid abnormalities
Cryptophthalmos
A rare condition. The eyebrow is usually absent and the globe is microphthalmic (complete
cryptophthalmos), may be part of Fraser syndrome; evaluation by electrodiagnostics and
ultrasound is required before surgery can be considered.
Coloboma
Incomplete formation of upper or lower lids. May be associated with Goldenhar syndrome
(upper lid), First Arch syndrome, amniotic band syndrome and other clefting syndromes
Ophthalmology
lower lid). In the first instance management is with lubricants to prevent exposure
keratopathy, followed by reconstruction of the lids.
Ablepharon
congenital absence of the lids. Copious lubricants are required until reconstruction is
performed.
~~kyloblepharon
partial or complete fusion of the eyelid margins. Surgical division may be required.
Sagging of lateral part of lower eyelid reducing apposition to globe, e.g. in Kabuki
syndrome.
Ectropion
Congenital ectropion is an outward rotation of the upper or lower eyelid margin. It may be
idiopathic or associated with conditions such as ichthyosis (collodion baby) or Down
syndrome. Management may consist of lubrication alone or surgery +/- skin graft to prevent
exposure keratopathy.
Entropion
Inward rotation of the lid margin with eyelashes rubbing against the cornea and conjuncti-
va. Usually seen in conjunction with epiblepharon or microphthalmos. Simple lubrication
alone may be required or surgery may be indicated to prevent keratopathy.
Epiblepharon
The presence of a fold in the skin and orbicularis muscle of the lower eyelids which may
cause lashes to rub against the cornea. Most commonly seen in oriental patients and usually
self-resolving. It is more common than congenital entropion, which more frequently affects
the upper lid.
Symblepharon
An abnormal connection between the lid and the conjunctiva usually acquired (e.g.
Stevens-Johnson syndrome) but may be congenital. Management is best with lubrication to
prevent occurrence.
Epicanthus
Epicanthal folds are folds of skin that extend from the upper lid towards the medial canthus.
This may give rise to the false appearance of strabismus (pseudosquint). pic an thus inversus
extends from the lower lid to the medial canthus.
s for the MKC 'PC'H 2nd Edition
Ejser-rtialRevisior~Ni~tesill R~ed~,~tric
Telecanthus
There is an increased width between the medial canthi with normal interpupillary distance.
Hypertelorism
Increased interorbital distance. May be idiopathic (e.g. Greig syndrome), congenital (eag.
craniosynostoses, clefting syndromes), or acquired (e.g. trauma, fibrous dysplasia).
Hypotelorism
Reduced interorbital distance. May be idiopathic or congenital, e.g. craniosynostos
(metopic suture).
Blepharophimosis
Small eyelids. Horizontal and vertical narrowing of the palpebral fissure, usually seen
blepharophimosis syndrome (ptosis, telecanthus and epicanthus inversus).
Chalazion
A chronic, painless, granulomatous inflammation of the Meibomjan gland which results
from obstruction of the gland duct. Treatment includes warm compresses, hygiene and
massage to try to encourage drainage of the lipid material. ~ o s small
t chalazia resolve
spontaneously but incision and drainage may be required for ones.
Molluscum contagiosurn
Common eyelid lesion caused by a poxvirus. Often situated on the lid margin and
associated with chronic conjunctivitis. Usually self-limiting but curettage of the lid lesion
may hasten resolution.
Reseptal cellulitis
Occurs when the infection is anterior to the orbital septum. More common than orbital
cellulitis. Causes include eyelid trauma, extraocular infection and upper respiratory tract
infection. Usually unilateral with no proptosis. Causative organisms vary with age: strepto-
coccal pneumonia and staphylococcal abscess in the neonatal period and Haemophilus
influenzae in later infancy. Treatment is with antibiotics.
782
Ophthalmology
4.3 Haemangiomas
Capillary haemangioma
The commonest tumour of the eyelids or orbits in childhood. May be associated with
dermal Kasabach-Merritt syndrome.
capillary haemangiomas appear 2 or 3 weeks after birth, grow rapidly until 4 months of age
and then stop growing by 6 months, regressing thereafter. They may cause ptosis, amblyopia
from astigmatism or rarely compress the optic nerve. Treatment may involve intralesional
and/or systemic steroids, and/or surgical excision; it almost always involves amblyopia
therapy.
4.4 Ptosis
Drooping of the upper lid, which may be uni- or bilateral, congenital or acquired.
Ptosis may be measured in terms of palpebral aperture or margin reflex distance. The latter
is the distance between the upper lid margin and the central corneal light reflection when
using a torch as a target for the patient to look at. This should be 3.5-4.5 mm.
Drugs (vincristine)
Homer syndrome
This is caused by sympathetic denervation. It may be congenital (caused by obstetric
trauma, with cervical vertebral abnormalities; rarely it may also be seen as a result of
neuroblastoma) or acquired (caused by trauma, surgery or tumours). Features include, ptosis
(partial), miosis (pupil constriction), enophthalmos, anhidrosis (ipsilateral), heterochromia
iridis (congenital type) and normal direct and consensual reflex to light.
Treatment of ptosis
Ptosis of sufficient degree to interfere with vision requires early correction to preven
permanent loss of vision (amblyopia). Surgical treatment includes levator resection or brow
suspension.
The mainstay of treatment is artificial tears but punctual occlusion should be considered.
6. THE ORBIT
6.1 Abnormalities of the position of the globe
Enophthalmos
This is when the globe sits furthe; back in the orbit than normal caking a narrowing of the
palpebral fissure. It is most commonly seen after a traumatic blow-out fracture of the orbit
or in cases of microphthalmos.
-
Infection this is more frequent in children over 5 years of age and is usually
secondary to ethmoiditis. It may be the result of Haemophilus influenrae,
taphyloc~cusaureus or Streptococcus pneumoniae. In severe cases there may
e visual compromise and/or cavernous sinus thrombosis. The child usually
presents with pyrexia, chemosis, lid oedema and axial proptosis with limitation
Bacterial
(topical).
Viral
Common contagious usually bilateral condition. Commonest cause is' adenoviral an
presents with watery discharge, hyperaemia, follicular conjunctivitig, preauricular lympha-
denopathy. Rarely may be caused by herpes simplex virus.
Allergic
Presents with hyperaemia, itching, chemosis (conjunctival oedema). May be seasonal or
perennial. Topical antihistamines andlor mast cell stabilizers are helpful. Sometimes
systemic antihistamines are also helpful.
Vernal
Usually occurs later in the prepubertal period. Atopy may be a factor. It results in a
cobblestone appearance of the palpebral conjunctiva. Treatment consists of systemic
antihistamines, topical mast cell stabilizers andlor antihistamines. Topical steroids may be
needed and occasionally, topical ciclosporine.
Miscellaneous
Kawasaki disease causes marked hyperaemia and Stevens-Johnson syndrome and toxic-
epidermal necrosis cause marked conjunctival erosions and discharge. These last two need
topical steroids and lubrication.
I
Red eye
..
Infectious conjunctivitis
Bacterial
. Viral
Chlamydia1
Blepharoconjunctivitis
Allergic conjunctivitis
Trauma
* Foreign body
iritis
iscleritis/scleritis
rug, toxin, chemical
econdary infection with nasolacrimal duct obstruction
b-conjunctival haemorrhage
rbital disease - cellulitis, tumour (rhabdomyosarcoma)
Non-pigmented lesions
Phlycten - uncommon, straw yellow, limbal lesion. It is most commonly caused by S.
aureus hypersensitivity seen in blepharitis. May also be caused by tuberculosis or herpes
simplex infection. Treatment is with topical steroid and antibiotics
Limbal dermoid - white or cream coloured limbal lesion. May have hairs growing on
the surface. It may be associated with Goldenhar or Treacher-Collins syndromes.
Surgical removal may be needed but usually topical lubrication is adequate
Bitot spot - foamy plaques temporal to the limbus as a result of vitamin A deficiency
Plexiform neurofibroma - diffuse, elevated lesion extending from lid to the superior
conjunctiva. Associated with neurofibromatosis type 1
r A1KC'P(
Essential Revisior-r Notes in I%etli,~trics f i ~ tho 't-I~ - rEdition
d
8. THE SCLERA
8.1 Pigmentation of the sclera
Blue sclera - may be seen in high myopes, osteogenesis imperfects I, Marshall-Smith,
Russell-Silver and Ehlers-Danlos syndromes
Yellow sclera - seen in jaundice
Black pigmentation - metabolic causes include alkaptonuria and haemochromatosis.
Thinning of the sclera will result in the choroid showing through
Scleritis
This is tender and painful. It may be diffuse, nodular or necrotizing. A systemic associati
must be excluded, e.g. connective tissue disorders, vasculitides, enteropathies, or gra
matous disorders. Treatment of the underlying condition together with systemic
inflammatory drugs are needed.
9. THE CORNEA
9.1 Developmental anomalies
Microcornea
Corneas < 10 mm in diameter, may be associated with various syndromes, e.g. Warburg
syndrome and glaucoma.
Cornea plana
A flat cornea most commonly seen with sclerocornea.
Sclerocomea
Congenital, non-inflammatory extension of opaque scleral tissue and fine vascular tissue
into the cornea. Usually bilateral and may be associated with cornea plana, glaucom
microphthalmos.
Ophthalmology
~~galocornea
A cornea > 13 mm in the absence of glaucoma. Usually X-linked condition. Megalocornea
with glaucoma is called buphthalmos and is the result of congenital or infantile glaucoma.
peters' anomaly
usually a bilateral opacity of the cornea as a result of a defect in the posterior cornea, with
or without iridocorneal or keratolenticular adhesions. May be associated with aniridia,
Axenfeld-Rieger anomaly (see Section 12.5) or systemic conditions e.g. Peters' Plus
syndrome. Glaucoma should be excluded and corneal transplant considered.
posterior embryotoxon
This is a prominent, anteriorly displaced white line usually seen on the slit-lamp. It is seen
in 20°h of normals but in the presence of prolonged jaundice in a neonate, Alagille
syndrome should be excluded.
9.3 Keratitis
This is inflammation of the cornea as a result of infections, exposure keratopathy, or
neuropathy (usually seen in patients with facial nerve palsy andlor corneal anaesthesia).
Infectious keratitis needs prompt diagnosis and topicallsystemic treatment. Exposure and
neuropathic keratitis demand frequent ocular lubrication.
Essenti,7/ Revisic~nNotes it, E ~ d i ,trit-s
? tor the h?KC:PCH 2nd Edition
9.4 Keratoconus
This condition results in corneal thinning leading to a conical shape of the cornea with high
levels of astigmatism. It may be associated with systemic disorders, e.g. Ehlers-Dados
syndrome type IV
10.4 Anophthalmia
In this condition there may be an actual absence of the globe or a clinically absent globe.
Patients with clinical anophthalmos have a high incidence of developmental anomalies
involving both eyes (88%), the brain (71%) and the body (58%). Orbital expanders are
needed to provide normal stimulus for normal facial growth.
~~sociations
~tmay be isolated or associated with ocular features such as retinochoroidal/optic nerve
c~loboma,microcornea, microphthalmos, microphthalmos with cyst, nystagmus and catar-
acts. Although iris coloboma can be associated with almost any chromosomal abnormaliv
they are frequently seen in:
Cat-eye (tri-tetrasomy 22), colobomatous microphthalmia, anal atresia and pre-auricular
skin tags
CHARGE association
Rubinstein-Taybi syndrome
Triploidy, trisomy 13 (Patau syndrome )
Treatment
Review for correction of refractive error and cataract progression if lens opacity is present.
Autosomal dominant aniridia is a bilateral panocular disorder (as a result of mutation on the
PAX6 gene on the short arm of chromosome 11). The most obvious finding is absence of
much/most of the iris tissue.
In addition to iris involvement, foveal and optic nerve hypoplasia may be present, resulting
in a congenital sensory nystagmus and leading to a reduced visual acuity of 6/30 or worse.
Anterior polar cataracts (50-85%), glaucoma (-50%) and corneal opacification often
develop later in childhood and may lead to progressive deterioration of vision.
Associations
Wilms' tumour, genitourinary abnormalities and retarded growth sr development (AGR
triad) or both (WAGR) or associated with ataxia and neurodevelopmental delay (Gillespie
syndrome).
Treatment
All children with sporadic aniridia should have repeated abdominal ultrasonographic and
clinical examinations. The child should be seen 3-monthly until 5 years, 6-monthly until
10 years, then yearly to 16 years. However, the examinations are best continued until
chrornosornal and then intragenic mutational analyses have confirmed a PAX6 mutation
only. If chromosomal deletion is found, 3-monthly scans should be performed.
Iris transillumination
The congenital causes include albinism (both ocular and oculocutaneous). Small iris
transillumination defects just visible near the iris root in blue-eyed children may be
idiopathic with no clinical significance.
Secondary tumours
Juvenilexanthogranuloma
Iris involvement occurs almost exclusively in infants. Usually unilateral yellow nodule
diffuse infiltration may be seen. Spontaneous hyphaema (blood in anterior chamber) an
unilateral glaucoma may occur. All children with juvenile xanthogranuloma should have
ocular screening because even asymptomatic ocular lesions may be associated
glaucoma. Most ocular lesions will regress with topical steroids. Some cases may
systemic steroids and others a small dose of radiotherapy treatment.
1ischnodules
Neural crest hamartomas, usually light brown and usually seen in neurofibromatosis 1
focular findings in this condition include optic nerve glioma, glaucoma, plexiform neurofi-
broma of lid or conjunctiva or both, hamartoma of optic disc and retina, meningioma) but
also seen in neurofibromatosis 2 (bilateral acoustic neuromas and other central nervous
system tumours, cataract, 66% before 30 years of age, combined hamartomas of retina and
retinal pigment epithelium).
~angerhanscell histiocytosis
lncludes eosinophilic granuloma, Letterer-Siwe and Hand-Schuller-Christian disease,
although similar to juvenile xanthogranuloma; these are systemic malignancies and need
appropriate managernent/chemotherapy.
Usually limited to orbital involvement but iris nodules or choroidal involvement may rarely
occur in Letterer-Siwe disease.
~eukaemia/lymphoma
Leukaemia iris infiltrates, although rare, have been reported with most types of childhood
leukaemia (most commonly in acute lymphoblastoid leukaemia) and lymphoma and is an
ominous finding since the median survival time after discovery of leukaemic iris involve-
ment is 3 months.
Anterior chamber paracentesis or iris biopsy may be required to exclude an infectious
aetiology. Chemotherapy may not be effective and low dose radiotherapy has been used
successfuIly.
Hypochromic heterochromia
Congenital
Horner syndrome
Waardenburg syndrome (autosomal dominant), telecanthus, prominent root of the
nose, white forelock and sensorineural deafness
Piebaldism trait
Acquired
Fuch's heterochromic iridocyclitis - rare type of unilateral uveitis
Non-pigmented iris tumours
Hyperchromic heterochromia
Congenital
Iris mammilations - unilateral villiform protuberances that cover the iris, usually in
association with oculodermal melanosis or neurofibromatosis
Congenital iris ectropion
Unilateral iris coloboma (affected iris is darker)
Port wine stain (haemangioma)
Acquired
Cataract surgery in children (operated eye is darker if operated early in life)
Topical medications (latanaprost - a prostaglandin analogue used in treatment of
glaucoma - darkens iris)
Pigmented iris tumours (naevus, melanoma)
Rubeosis iridis (iris neovascularization) - causes include; retinopathy of prematurity,
retinoblastoma, Coats disease, iris tumours
Siderosis - as a resulst of intraocular metallic foreign body
12.2 Dyscoria
An abnormality of the shape of the pupil.
Congenital causes- persistent pupillary membrane, iris coloboma, iris hypoplasia and
ectopia lentis et pupillae
Acquired causes - most commonly uveitis, trauma (accidentallsurgical)
Ophthalmology
12.3 Miosis
A small pupil usually < 2 mm, which reacts poorly to dilating drops.
Congenital miosis (microcoria) may be the result of an absence of the dilator pupillae
muscle or fibrous contraction secondary to persistent pupillary membrane. It can be
seen in congenital rubella syndrome, Marfan syndrome, in 20% of Lowe
(oculocerebrorenal) syndrome and in ectopia lentis et pupillae
12.4 Mydriasis
A large pupil usually > 4 mm. May be true mydriasis or pseudo-mydriasis.
True mydriasis
This may be congenital but blunt trauma causing iris sphincter rupture, ciliary ganglionitis
(unilateral most commonly after chickenpox/varicella zoster virus infection - also known
as Adie pupil) or acquired neurological disease must be excluded (especially third-nerve
palsy)
Many cases of congenital mydriasis are actually part of the aniridia spectrum. Congenital
iris ectropion is often mistaken as an enlarged pupil. lris ectropion is eversion of the
posterior pigment epithelium onto the anterior surface of the iris. lris ectropion can occur as
an acquired tractional abnormality, often in association with rubepsis iridis or as a
congenital non-progressive abnormality. Congenital iris ectropion may be associated with
congenital andlor developmental glaucoma. Associated conditions include neurofibromato-
sis type 1, Prader-Willi syndrome and facial hemihypertrophy. Review to exclude glaucoma
or associations.
12.5 Corectopia
Displacement of the pupil. Normally the pupil is displaced inferonasally, about 0.5 mm,
from the centre of the iris.
Sector iris hypoplasia, colobomas, ectopia lentis et pupillae, Axenfeld-Reiger anomaly (an
autusomal dominant form of iris hypoplasia with posterior embryotoxon with or without iris
adhesions, corectopia, dyscoria, pseudopolycoria and glaucoma in 50% of cases), anterior
segment dysgenesis syndromes, and iridocorneal endothelium syndromes.
~ssentidlRevisio~~
Notes i l l E1t~li~7tri(-s r hlKC-P(_-H2nd Edition
f i ~ t/ie
12.6 Anisscoria
A difference in the size of the two pupils > 1 mm. The three main causes that need
differentiation in children are:
Physiological
Horner syndrome
Adie pupil (ciliary ganglionitis)
Examination
The child should be examined in bright light and then in the dark. If the anisocoria is
physiological then the difference between the two pupils will remain constant and is usually
< 2 mm. If the anisocoria is accentuated in bright surroundings then the larger pupil is at
fault because it cannot constrict (parasympathetic). The commonest cause for this is ciliary
ganglionitis (Adie pupil). If the anisocoria is accentuated in the dark then the smaller pupil
is at fault (sympathetic nervous system). The commonest cause for this is Horner syndrome.
Horner syndrome
Miosis, with ipsilateral ptosis (1-2 mm) and sometimes anhidrosis.
Congenital Horner syndrome is associated with hypopigmentation of the iris on the affected
side.
Acquired Horner syndrome may be the result of:
Central (first-order neurone) lesions (posterior hypothalamus down to spinal cord
C8-T2)
Pre-ganglionic (second-order) lesions (C8-T2 to superior cervical ganglion in the neck)
Post-ganglionic (third-order) lesions (from cervical ganglion via internal carotid to
cavernous sinus then via VI to nasociliary and ciliary nerves to-eye)
Even if there is heterochromia irides, metastatic neuroblastoma should be excluded. In an
otherwise healthy child, at least a chest X-ray and spot urine vanillylmandelic acid (VMA)
should be performed.
Adie syndrome
Commonest association is chickenpox infection but other viral infections may also cause
ciliary ganglionitis.
Accommodation is usually affected and the child may need reading spectacles.
Ophthalmology
inflammation of the uveal tract. Cells and flare can be seen in the anterior chamber, with
deposition on the corneal endothelium (keratatic precipitates) seen on slit-lamp examina-
tion. Symptoms range from asymptomatic white eyes (pauciarticular arthritis) to photopho-
bia, injectedlred eyes with pain and reduced visual acuity.
Causes are idiopathic (35-50%), oligoarticular arthritis (juvenile idiopathic arthritis) - 33%
are involved, female : male ratio of 3 : 1. Bilateral and asymptomatic and may precede
arthritis (follow-up 3- to 6-monthly). Accounts for about 40% of paediatric uveitis.
Other causes are measles, mumps, chickenpox, Lyme disease, Kawasaki disease, Reiter
syndrome, Beh~etdisease and sarcoidosis.
Treatment is with topical steroids and mydriatics (to prevent posterior synechiae between
lens and iris) and anti-glaucoma medications as needed. Local steroid injections (triamcino-
lone/betnesol/dexamethasone) may be indicated as may systemic immunosuppression
(steroids and steroid-sparing agents).
Complications of the disease andlor treatment include Band keratopathy, cataract and
secondary glaucoma.
Photophobia
Common causes are:
Essential Revision Notes in R2ediatr-ics for the M RCPCH 2 f7cl Eclifi017
-
14. LENS ANOMALIES
14.1 Aphakia
Absent lens
The commonest cause is after cataract extraction without lens implantation because o f
congenital cataracts.
Treatment
Refractive correction of aphakia and surveillance to exclude glaucoma, which can develop
at any time.
Treatment
Lensectomy with sparing of the capsule for possible secondary lens implantation is one
option, but lens removal with intraocular lens implantation has become more common.
Amblyopia therapy with correction of the refractive state is essential.
Juvenile cataract
Associations include:
Hereditary
Ocular - coloboma, ectopia lentis, aniridia, retinitis pigmentosa and posterior
lenticonus
Systemic
Renal disease - Alport syndrome
Skeletal disease - Marfan syndrome
Skin disease - atopic dermatitis, Marshall syndrome, Lamellar ichthyosis.
Chromosomal disorders - trisomy 21
Metabolic disease - galactokinase deficiency, Fabry disease, Refsum disease,
mannosidosis, diabetes mellitus, hypocalcaemia
Neurological disorders - myotonic dystrophy, Wilson disease
Miscellaneous - chronic uveitis, drug-induced (steroids), neurofibromatosis type 2,
Stickler syndrome.
Treatment comprises lens aspiration with implant. Amblyopia therapy with correction of the
refractive state is essential.
he-retinal haemorrhages
Haemorrhage lies between posterior vitreous face and retina.
May be associated with Sickle cell retinopathy, trauma, subarachnoid haemorrhage (Terson
syndrome), non-accidental injury but never seen in isolation; widespread retinal and sub-
retinal haemorrhages also seen with or without retinal schisis (a splitting within the retina).
Retinal haemorrhages
These may be flame-shaped, dot and blot or Roth spots (white centred superficial retinal
haemorrhage).
May be seen in retinal vein occlusions, acute papilloedema, optic disc drusen, acute
hypertensive retinopathy, retinal perivasculitis (early cytomegalovirus retinitis). Roth
1
B
spots are seen in severe anaemia, leukaemia, bacterial endocarditis and may also be 4
seen in trauma. Dot and blot haemorrhages may be seen in diabetes mellitus-related
retinopathy, these are full thickness in the retina. They may also be seen in shaken baby 1
4
syndrome but should be associated with superficial and sub-retinal haemorrhages. 2
1i?
5
i
802
Ophthalmology
sub-retinal haemorrhages
Red, raised area over which the retinal blood vessels are clearly visible.
May be seen in sickle cell anaemia, Coats disease (retinal telangiectasia), trauma
including shaken baby syndrome and rarely retinal neovascularization.
15.2 H a d exudates
yellow waxy deposits which may be retinal or sub-retinal. Focal or diffuse exudates may be
seen in diabetic retinopathy (unusual to see in children), old branch retinal vein ~ ~ c l u s i o n ,
radiation retinopathy (years later) or retinal telangiectasia.
A macular star (stellate pattern of exudates centred on the macular) may be seen in
malignant hypertension, papilloedema, neuroretinitis and very rarely retinal angioma (von
Hippel-Lindau syndrome or idiopathic).
Sub-retinal exudates may be seen in Coats disease (occurs in males, peaks in 8- to 1O-year-
olds, usually unilateral, peripheral retinal telangiectasia and aneurysmal dilatation lead to
extensive areas of yellow-white retinal exudation).
15.6 Maculopathy
Abnormality of the macula - may be the result of wrinkling, bull's eye appearance or
deposition/degeneration/inflammation.
Wrinkled appearance
Striated appearance radiating out from the centre of the fovea, which causes a drop in
vision. May be idiopathic (commonest), or the result of juvenile retinoschisis (X-linked) or
chronic intraocular inflammation.
Cherry-redspots
A change in the nerve-fibre layer surrounding the fovea, such as ischaemia or deposition of
abnormal metabolic by-products, results in an accentuation of the normal deep-red colour
of the fovea, producing a typical cherry-red spot macula. Seen in central retinal artery
occlusion, metabolic disorders such as Tay-Sachs, Sandhoff, Niemann-Pick disease,
generalized gangliosidosis and sialidosis I and 11.
15.8 Pale retinal lesions
Inflammatory lesions
Single focal lesions - these may be caused by toxoplasmosis, toxocariasis, candidiasis
and cryptococcus
a Multiple focal lesions - these may be cause by candidiasis, sarcoidosis, Lyme disease,
choroidal pneumocystosis, presumed ocular histoplasmosis syndrome, Beh~etdisease,
Vogt-Koyanagi-Harada syndrome (an inflammatory condition affecting the eyes, brain
and skin), sympathetic ophthalmitis and tuberculous choroiditis
a Diffuse lesions - these may be seen in cytomegalovirus retinitis, acute retinal necrosis,
herpes simplex retinitis and measles retinitis. Appropriate serologic and radiological
investigations need to be undertaken
Non-inflammatorylesions
Focal pale lesions
Coloboma of the retina and choroid; may be associated with a serous retinal
detachment
Retinal astrocytoma, a hamartoma seen in 5O0/0 of patients with tuberous sclerosis
Retinoblastoma, most common childhood intra-ocular malignancy, 1 : 14,000-20,000
births. Diagnosis commonest between 1 and 1.5 years of age, 90% before 3 years.
Presenting signs: leukocoria 6O0/0, squint 22%; < 25% of cases have a positive family
history
Treatment - uniocular enucleation (cure if no metastases) .
Bilateral - enucleate most involved eye, local resectionlfocal irradiationlsystemic
chemotherapy/cryotherapyllaser for smaller tumours -
Long-term follow-up and genetic counselling for patients with retinoblastoma
.
Location of ROP uses the optic nerve as a reference point
Zone 1 is an area located around the optic nerve twice the radius of the distance
from the optic nerve to the fovea
Zone 2 is concentric to Zone 1 extending to the nasal periphery
Zone 3 is the remainder of the retina
Extent of ROP is described by how many clock-hours of the retina are involved. These
may be contiguous or separate areas
ROP is a progressive disease. It begins with mild changes at the junction of the
vascularized and non-vascularized retina and may progress to, or regress from, any stage 33
'I
before 'Stage 3 with plus disease' at which point treatment is usually instigated 3
i!
1
-
Stages of ROP
Stage 1 -Demarcation line
This is a white line, lying within the plane of the retina and separating avascular from
vascular retinal regions.
Stage 2 -Ridge
The line of stage 1 has increased in volume to extend outside the plane of the retina.
Isolated vascular tufts may be seen posterior to the ridge at this stage.
Stage 3 - Ridge with extraretinal fibrovascu
This may be:
tion
-
achment total
tina is usually pulled into a funnel shape tissue. Eyes with '
ge 5 ROP usually have no useful vision, even if surgery is performed to repair the
If ROP does develop it usually does so between 34 and 40 weeks gestational age, regardless
of the gestational age at birth. Treatment (diode laser or cryotherapy) is used to destroy the
avascular retina. The fundamental principle of treatment is to remove the stimulus for vessel
growth, i.e. to ablate the peripheral avascular retina. Treatment is given once 'Threshold
ROP' develops.
Threshold ROP is defined as:
Stage 3 ROP:
Involving five or more contiguous, or eight or more cumulative, clock hours
In the presence of congestion of the posterior pole vessels - 'plus' disease.
Essentia1 Revision Notes in /'act-lic?tric-sh r the MRCIT'H 2nd Eciition
Examination protocol
Which babies should be screened?
Birth at < 32 weeks gestational age
Birth weight s 1500 g
When?
All babies must be screened at 6-7 weeks postnatal age. For the more mature baby one
examination before discharge may be all that is necessary even if undertaken before
6 weeks because this gives enough information about retinal vascular development to
indicate the need for further examinations.
Subsequent examinations
At least every 2 weeks until vascularization has progressed into zone 3.
Because of the short time available for treatment, if stage 3 is imminent or present it is
sometimes necessary to examine a baby more frequently
Hearing difficulties
Usher syndrome
USH 1 - retinitis pigmentosa onset by 1O years, cataract, profound congenital
sensory deafness, labyrinthine defect
USH 2 - retinitis pigmentosa onset in late teens, childhood sensory deafness
USH 3 - postlingual, progressive hearing loss, variable vestibular dysfunction,
retinitis pigmentosa symptoms by second decade
Alstrom syndrome - retinal lesions cause nystagmus and early loss of central vision
(unlike other pigmentary retinopathies where peripheral vision is lost first), dilated
cardiomyopathy (infancy)/congestive heart failure, atherosclerosis, hypertension, renal
failure, deafness, obesity, diabetes mellitus
Infantile Refsum disease (peroxisomal biogenesis defect) - mental retardation, minor
facial dysmorphism, retinitis pigmentosa, sensorineural hearing deficit, hepatomegaly,
osteoporosis, faltering growth, hypocholesterolaemia
Classical Refsum disease (later onset) - retinitis pigmentosa, chronic polyneuropathy
and cerebellar signs
Cockayne dwarfism - precociously senile appearance, pigmentary retinal degeneration,
optic atrophy, deafness, marble epiphyses in some digits, photosensitivity, mental
retardation, sub-cl inical myopathy
Mucopolysaccharidoses
Kearns-Sayre - ophthalmoplegia, pigmentary retinal degeneration and heart block are
leading features
Skin disorders
Refsum disease
Cockayne syndrome
Renal disorders
Senior-Loken syndrome - renal dysplasia, retinitis pigmentosa, retinal aplasia,
cerebellar ataxia, sensorineural hearing loss
Rhyns syndrome - retinitis pigmentosa, hypopituitary, nephronophthisis, mild skeletal
dysplasia
Bardet-Biedl syndrome - obesity, rod-cone dystrophy, hypogonadism, renal anomalies,
polydactyly, learning difficulties, onset by end of second decade
Cystinosis
Alstrom syndrome
Skeletal disorders
Bardet-Biedl syndrome
Cockayne syndrome
Jeune syndrome - chondrodysplasia that often leads to death in infancy because of a
severely constricted thoracic cage and respiratory insufficiency, retinal degeneration
Mucopolysaccharidoses IH, IS, I1and Ill
Infantile Refsum disease
Hepatic disorders
r
Zellweger syndrome - hypotonia, seizures, psychomotor retardation, pigmentary
retinopathy and cataracts
Neurological/neuromuscular
Kearns-say re syndrome
j Chronic progressive external ophthalmoplegia - retinitis pigmentosa and restrictive eye
movements
3
Bilateral
Association - papilloedema, malignant hypertension, cavernous sinus thrombosis,
buried optic nerve drusen and bilateral papillitis. In papillitis vision is always affected
whereas in papilloedema vision is only affected if chronic
Secondaryoptic atrophy
This is preceded by swelling of the optic nerve head, as a result of pressure, ischaemia or
inflammation, i.e. chronic papilloedema or papillitis.
810
Ophthalmology
Consecutiveoptic atrophy
This is caused by diseases of the inner retina or its blood supply.
a Associations - include retinitis pigmentosa, cone dystrophy, diffuse retinal necrosis (e.g.
cytomegalovirus retinitis, acute retinal necrosis and Beh~etdisease), 'cherry red spot'
syndromes and mucopolysaccharidoses
-
Recessive type, DIDMOAD - diabetes insipidus, diabetes mellitus, optic atrophy and
deafness (onset 5 -1 4 years)
-
Leber's hereditary optic neuropathy (onset 16-30 years)
Epicanthic folds - symmetric corneal reflexes confirm the absence of true esotropia
Narrow interpupillary distance - seen in hypotelorism
True esodeviation
Cornitant esotropia
Infantile esotropia - develops before 6 months old with a large and stable angle, cross-
fixation (right eye looks left, left eye looks right) normal refractive error for age
Non-accommodative esotropia - develops after 6 months with normal refraction
Refractive accommodative esotropia - onset usually between 2 and 3 years associated
with hypermetropia (long-sighted)
Non-refractive accommodative esotropia - between 6 months and 3 years. No
significant refractive error but excessive convergence for near (high ratio of
accommodative convergence : accommodation (AC/A ratio))
Sensory esotropia - reduction in vision, with one eye worse than the other, which
disrupts fusion, e.g. uniocular cataract
Convergence spasm - intermittent esotropia with pseudomyopia and small pupil as a
result of accommodative spasm which may be seen after trauma or as the result of a
posterior fossa tumour but may be the result of a functional element
lncomitant esotropia
VI nerve palsy - may be congenital or acquired (associated with raised intracranial
pressure). Esotropia is more obvious looking into the distance
Mobius syndrome - bilateral gaze palsies, with esotropia in 50% (as the result of
superimposed VI nerve palsies). There is usually bilateral VII nerve palsies and may be
associated V, IX, X nerve palsies
Duane syndrome - caused by miswiring of the horizontal recti muscles, which leads to
co-contraction of the medial and lateral recti. This leads to limited abduction with
approximately normal adduction (Type I), limited adduction with approximately normal
abduction (Type II),or limited abduction and adduction (Type Ill). The palpebral fissure
narrows on adduction (as a result of globe retraction) and widens on abduction. Types I
and Ill may have an esotropia in the primary position of gaze
Note: if a child has a limitation of abduction but is straight in the primary position this
must be Duane syndrome not a VI nerve palsy
True exodeviation
Cornitant exotropia
Intermittent exotropia - a common condition with exotropia more often present for
distance than for near. In bright sunlight the child will characteristically close the
diverging eye
Sensory exotropia - much less common in children than sensory esodeviation
Convergence insufficiency - usually seen in older children. Convergence exercises
may help but there should be a low threshold to neuroimage if there are.any
neurological signs or worsening despite convergence exercises
Incornitant exotropia
Congenital Ill nerve palsy - exodeviation and hypodeviation of the affected eye, with
ptosis and miosed pupil. There is limitation of up-gaze and adduction
Acquired Ill nerve palsy - Rare; same signs as congenital condition but the pupil is
dilated
Duane syndrome Type I1 (see above)
Essentia/ Revisior-,Notes in Pdedi,ltrics for the MRCPCH 2r1d Edition
Limitation of abduction
VI nerve palsy - there is always an esotropia in primary position of gaze unlike Duane
types I and I1where there may or may not be
Any restrictive myopathy of the medial rectus - myositis, pseudo-tumour, thyroid eye
disease (very rarely in children)
Limitation of adduction
Ill nerve palsy - may be congenital or acquired (see above)
Internuclear ophthalmoplegia - a lesion in the medial longitudinal fasciculus leading to
an ipsilateral adduction deficit and an abducting nystagmus of the contralateral eye
Myasthenia gravis - very rare but may mimic an adduction deficit
Acute myositis - restriction of movement in direction of the field of action of the
affected muscle
Duane types II and Ill - (see above)
Ophthalmology
Brainstem lesions - usually encephalitis but tumours of the brainstem (glioma) may also
present with ophthalmoplegia
Other causes
Chronic progressive ophthalmoplegia - may be associated with a mitochondria1
cytopathy in which case it may be isolated or part of the Kearns-Sayre syndrome
Myotonic dystrophy - may be seen in children either as the congenital variant or the
type I autosomal dominant variant which has demonstrated anticipation
Drug toxicity - most commonly seen with phenytoin
Acquired saccadic initiation failure (ocular motor apraxia) - may be seen in lesions of
the frontoparietal cortex. Both vertical and horizontal saccades are affected. May be
seen in Gaucher type Ill. In congenital saccadic initiation failure, vertical saccades are
unaffected
Metabolic causes - Tay-Sachs disease and occasionally other lipid-storage diseases
Congenital fibrosis syndrome - familial, may affect all extraocular muscles. Eyes often
fixed in down-gaze with bilateral ptosis and chin-up head posture
CONTENTS
1 Introduction
2. Embryology
3. Trauma
3.1 Anatomical and physiological differences in the paediatric skeleton
3.2 Fractures unique to the immature skeleton
3.3 Fractures involving the upper limb
3.4 Fractures involving the lower limb
4. Metabolic disorders
4.1 Rickets and osteomalacia
4.2 Osteogenesis imperfects
4.3 Idiopathic juvenile osteoporosis
5. Neuromuscular disorders
5 .I Arthrogrypotic syndromes
5.2 Spina bifida (myelomeningocele)
5.3 Myopathies
6. Lower limb
6.1 Developmental dysplasia of the hip
6.2 Perthes disease (Legg-Calv6-Perthes disease)
6.3 Slipped capital femoral epiphysis
6.4 Congenital talipes equinovarus
6.5 Irritable hip
7. Upper limb
7.1 Orthopaedic brachial plexus palsy
8. Infection
8.1 Osteomyelitis
8.2 Septic arthritis
i7 t+edic?fi*ir.sf ; ~ the'
Essenti,?lRevision Notes 1 r MRC-K-H .'r1(1 Fdition
9. Paediatric spine
9.1 Scoliosis
9.2 Kyphosis
1. INTRODUCTION
This chapter aims to provide the doctor who is training to be a paediatrician with an insight
into the subspecialty of Paediatric Orthopaedics. The contents of this chapter are by no
means exhaustive but will offer a mode of quick revision to the paediatrician.
2- EMBRYOLOGY
The primitive streak appears at about 12 days after conception
Caudally, cells migrate from ectoderm and endoderm to form mesoderm. The mesoderm
forms the connective tissue
Cranially, the formation of the notochord appears in the second to third week of
gestation
Neural crest cells differentiate to form the peripheral and autonomic nervous systems
Somites form on each other side of the notochord and develop into a specific
dermatome, myotome and sclerotome
Limb buds develop between 4 and 6 weeks
Bone develops either in a cartilage model (endochondral ossification), or in a membrane
model (intramembranous ossification)
Primary ossification centres appear between 7 and 12 weeks. They form in the mid-
portion of the bone anlage. This is responsible for the formation of the diaphysis and the
metaphysis
Secondary ossification centres develop in the chondroepiphysis. The ossification centre
for the distal femur occurs at 40 weeks of gestation. This is of medico-legal importance
because the presence of this centre is indicative of a complete pregnancy. All the other
secondary centres occur post-natally
There are two types of growth plates
Physis - which responds to compressive forces
Apophysis - which responds to tensile forces
fix the AlRCPCH 2i7d Eclitioi-,
Esset7tic?lRevision Notes i f 7 Pc1edir1ti.i~~
3. TRAUMA
Orthopaedic trauma accounts for 15-20% of Accident and Emergency department visits
in the UK
There are a number of anatomical and physiological variations in the paediatric skeleton
which make this practice different from that of the adult practice
Greenstick fractures
Greenstick fractures are the most common (5O0/0)fracture affecting the paediatric
patient. They are also called unicortical fractures because one cortex is in continuity.
There is often rotation and angulation of the fracture
Elbow
The most common fractures in the elbow occur in the distal humerus. About 75% of
such fractures affect the supracondylar region
Supracondylar fractures occur through the distal metaphysis of the humerus
Clinical examination is very important to assess the vascularity and nerve supply distal
to the fracture. Compartment syndrome should be considered. Any of the three major
nerves can be affected by this fracture
A vascular insult can cause Volkman's ischaemic contracture (about 1-2%). lschaemia
causes fibrotic contractures in the forearm muscles. Treatment depends on the type of
fracture, varying from just immobilization of the affected elbow to manipulation under
anaesthesia and stabilization with wires
Femur fractures
Incidence is about 1% in children under the age of 12 years
Peak age i s between 2 and 5 years
70% occur in the middle third, 20% in the proximal third and 10% in the distal third
Waddellfs triad - fractured femur, head injury and thoracic injury
Consider non-accidental injury in a child with a femur fracture
Clinical symptoms include pain and deformity. Examine for distal neurovascular deficit
Treatment - analgesia, splinting, traction, spica, internal fixation (plates osteosynthesis,
intramedullary nails)
Complications include leg-length discrepancies
Knee
The main injuries include meniscal injuries, anterior cruciate ligament injuries and osteo-
chondral defects. Others include Osgood-Schlatter disease and chondromalacia patellae.
Meniscal injuries
Usually a twisting injury
Symptoms include pain, effusion, locking, giving way and snapping
Evaluation consists of clinical examination, diagnostic a~hroscopyand magnetic
resona,nce imaging
Treatment is usually arthroscopic meniscectomy
Anterior cruciate ligmament injury
Incidence = 0.3 per 1000 per year
Usually a sporting injury
Can be associated with injury to other ligaments
Management involves physiotherapy and reduced activity with or without internal
fixation
Osteochondral defects (osteochondritis dissecans)
Defect involving bone and cartilage within the knee
Causes discontinuity of the articular cartilage
Aetiology unknown
Most commonly seen in the lateral surface of the medial femoral condyle
Signs and symptoms - pain, locking, effusion, may present with an acutely locked
knee
Treatment - analgesia, rest, splintage (if subchondral bone is intact)
Arthroscopic assessment is required. If there is a 'loose body' then that should be
removed
Osgood-Schlatter disease.
Inflammation of the tibia1 tubercle as a result of repeated tensile forces
Incidence of about 2% of all growth plate injuries
Generally a self-limiting condition. Bilateral in about one-third of patients. Boys
affected more than girls
Rest and analgesia are all that may be required
Adolescent anterior knee pain (chondromalacia patella)
Pain about the knee is a common complaint. Initially hip pathology should be
excluded
'Chondromalacia patella' has been converted from a term meaning softening of the
articular cartilage to that of an innocent condition of ill-defined anterior knee pain
Symptoms should be considered to be due to an unknown cause until a specific
aetiology is established. If none is determined 'idiopathic anterior knee pain' is
treated with physiotherapy and normally resolves
4. METABOLIC DISORDERS
Bone metabolism is explained in detail in Chapter 7 - Endocrinology.
Clinical manifestations
Apathetic and irritable
Short attention span
82 8
Short stature (height below the third percentile)
Frontal bossing
Enlargement of skull sutures (hot cross bun skull)
Delayed dentition
Enlargement of costal cartilages (Rachitic rosary)
Pectus carinatum
Delayed weight-bearing milestones
Deformities of lower limbs (genu varum)
Enlarged epiphyseal regions of the long bones
Radiological findings
Cupping and widening of epiphysis
Osteopenia of the metaphysis
Looser's zones represent areas of weakening in the bone. Although they can predispose
to fractures, they do not themselves imply that there is a fracture
Further investigation
Bone scan may help in mild cases
Clinical features
Increased fragility of bones but fracture healing process is unaffected
Short stature
Scoliosis
Defective dentinogenesis
Conductive deafness
for the R.1KCPCf-I 2nd Edit1017
Essential Revision Motes in P,~etJi,?trics
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Ligamentous laxity
Blue sclerae and tympanic membranes
Diagnosis
History
Clinical examination
X-rays - thin cortices and osteopenia
Histologically - wide Haversian canals, osteocyte lacunae
Management
Aims include fracture management and rehabilitation
May need special techniques to aid fracture management (i.e. Sofield's osteotomy)
Ideally would have an internal fixation
Calcitonin and calcium supplements reduce the incidence of fractures
Bisphosphonates
Clinical features
Bone and joint pain
Growth arrest
Vertebral collapse
Metaphyseal fractures
Diaphysis is less affected (cf osteogenesis lmperfecta in which bone is uniformally
affected)
Diagnosis
Serum calcium and phosphorus are normal
Alkaline phosphatase is normal or slightly elevated
Hypercalciuria may be present
Diagnosis is usually by exclusion
Differential diagnoses - osteogenesis Imperfecta, haematological malignancies,
thyrotoxicosis, Cushing syndrome
Orthopaedic:
Management
Treatment of fractures is similar to that in the normal child
Bracing for scoliosis
5. NEUROMUSCULAR DISORDERS
5.1 Arthrogrypotic syndromes
Arthrogryposis multiplex congenita
Non-progressive disorder
Congenitally rigid joints
Sensory function is maintained but there is loss of motor function (may mimic polio)
Aetiology
May be neuropathic, myopathic or mixed
Decrease in anterior horn cells in the spinal cord
Possible associations
Oligohydramnios
Intrauterine viral infection
Clinical features
Normal facies
Normal intelligence
Multiple joint contractures
No visceral abnormalities
Associated with teratological hip dislocations, club feet and vertical talus
C-shaped scoliosis
Treatment
Orthopaedically it is aimed at release of soft-tissue contractures, physiotherapy and
functional bracing
Larsen syndrome
Joints less rigid than in arthrogryposis
Multiple joint dislocations
Flattened facies
Scoliosis
Cervical kyphosis
fi)r tl9c ItlR(,.PCtl ~ I ~ Ecfitio/7
Essential Kevisic~riNottls in P;lecliC~trics c J -
Antenatal diagnosis
Raised a-fetoprotein
Ultrasound (anomaly visible on scan)
Clinical features
Neonatal findings such as hip dislocations, hyperextension of the knee, and club feet
are common
Fractures are common but as there are problems with sensory function, diagnosis can be
difficult
Signs and symptoms depend on the level of the spinal defect
Increased incidence of allergic reactions, mainly latex sensitivity
Hips
Flexion contractures with higher level involvement
Dislocation of the hip
Late hip dislocation can be a sign of tethering of the cord -
Knees
Quadriceps weakness causing difficulty in ambulation (key'level is L4)
Flexion contractures
Valgus deformity
Ankle and foot
Rigid club foot
Tight Achilles tendon
Valgus hind foot
Spine
Scoliosis can be bony or muscular (thoracic level paraplegia) in origin
Rapid curve progression can denote hydrocephalus or a tethered cord
Rinciples of treatment
Treatment should be directed to mobilize the patient.
Soft-tissue contracture release
Corrective osteotomy, as required
Functional bracing
Orthopaedics
a Surgical treatment may be required, directed at a specific problem, i.e. hip dislocation
or scoliosis
a Specialized physiotherapy
a Custom-made wheelchair
5.3 Myopathies
Duchenne muscular dystrophy
This is a sex-linked recessive myopathy
'Clumsy walking'
Calf pseudohypertrophy
Cower's sign is positive (gets up using the hands to move up the body to compensate for
loss of antigravity muscles)
Hip extensors are the muscle groups to be affected first
Markedly elevated creatine phosphokinase
Muscle biopsy shows absent dystrophin
Muscle biopsy also shows foci of necrotic tissue infiltration
Treatment is directed to keeping the patient ambulatory
Patients are usually wheelchair-bound by the age of 15 years
Scoliosis is a major concern in treatment
Becker dystrophy
This is a sex-linked recessive myopathy
Similar to Duchenne but less severe clinical picture
Red/green colour blindness
Patients live beyond their teens
Dystrophin is present but abnormal
Facio-scapulo-humera1dystrophy
, This is an autosomal dominant disorder
Facial abnormalities
Winging of scapula
Normal creatine phosphokinase
Myotonic myopathies
Myotonia congenita
Defect is in chromosome 7
Affects chloride channels in the muscles
Hypertrophy seen with no weakness of muscles
Improves with exercise
tor tlie MKCP(1HL'nd Edition
Essential Revisioli Notes in Yae~li~~trics
-
Paramyotonia congenita
Defect is in chromosome 17
Affects the sodium channels in the muscles
Symptoms worsen with exposure to cold
Worse in distal upper extremity
Dystrophic myotonia
. Defect is in chromosome 19
Small gonads
Low IQ
Distal involvement
6. LOWER LIMB
6.1 Developmental dysplasia of the hip
Comprises a spectrum of abnormalities from complete dislocation of the hip to mild
acetabular dysplasia
Types of developmental hip dysplasia include dislocated hip, dislocatable hip,
subluxable hip and dysplastic hip
Incidence is 1 in 1,000 for established dislocation (15 per 1,000 for neonatal instability)
Risk factors include being a first-born, being female, having a breech presentation and
family history
Other associated conditions include congenital torticollis, skull or facial abnormalities,
hyperextension of the knee and club feet
Clinical examination includes Ortolani test (for reducing a dislocated hip) and Barlow
test (for dislocatable or subluxatable hip)
Hip click suggests an audible or palpable noise while examining the hips, when there
are no signs of instability
Thigh skin creases may or may not be asymmetric
Teratological dislocation means that there are other associated conditions such as
arthrogryposis. These are typically stiff, high-riding and irreducible dislocations
Screening for this diagnosis includes a neonatal physical examination and, possibly,
ultrasound of the hips
Screening can be general (all newborn babies undergo an ultrasound examination) or
selective (only babies with specific risk factors undergo the ultrasound). A protocol is
illustrated below.
I
8 I 1
Normal hips Normal hips with Abnormal hrps
risk lactars
I I f
NQ wthopaedic folow-up Ultrasound xwening Double nappies
Clinic 6 weeks Ultrasound dinic 2 weeks
Warmal hips
I
1 Qysplastic kip
Treatments
@ Early diagnosis - Pavlik harness has a success rate of about 85%
Failed Pavlik harness or late presenters ( > 3 months ) will undergo either a closed or an
open reduction augmented with a hip spica
Late presenters, more than 2 years old, will almost certainly have, along with the above
procedure, a femoral shortening osteotomy
Even with a successful closed reduction, about 50% of patients will need a pelvic
osteotomy later because there is usually a residual acetabular dysplasia
Complications
Avascular necrosis of the proxin~alfemoral physis
Growth disturbances
Coxa magna
Residual acetabular dysplasia
Clinical features
Pain (may present with referred pain in the knee)
Decreased range of motion
Limp
Skeletal age at onset is the most significant indicator of prognosis (onset at more than
6 years carries a significantly poorer prognosis)
15% bilateral involvement (always asymmetric involvement, compared to multiple
epiphyseal dysplasia which is symmetric).
Differential diagnosis includes septic arthritis of the hip, epiphyseal dysplasia,
hypothyroidism
Investigation
This is by plain X-ray of the pelvis with both hips anteroposterior and frog lateral
Stages
Initial stage
Fragmentation
Healing
Residual
Severity
This is described in many ways but the most commonly used classification is the Herring
lateral pillar classification:
Croup A - lateral pillar, lateral one-third of the femoral head shows collapse of less
than 3O0/0
Group B - 30-50% collapse
Group C - > 5Ooh collapse of the lateral one-third of the capital femoral epiphysis
Treatment
Aims to maintain the range of movement and to contain the femoral head in the
acetabulum. Soft tissue release and corrective osteotomy may be required to achieve
this
Clinical symptoms
Pain in the hip or knee
a Antalgic gait
a Externally rotated limb
a Decreased internal rotation of the affected limb
Classification
Classification depends on the duration of the symptoms or on ability:
a Acute - less than 3 weeks
a Acute on Chronic
a Chronic - more than 3 weeks
a Stable (can weight bear) or Unstable (unable to weight bear)
Investigations
Plain X-ray pelvis anteroposterior and frog lateral
Grading on the extent of slip
Treatment
Screw fixation of the epiphysis
Corrective osteotomy may be required in delayed presentations
Prophylactic pinning of the contralateral hip may be considered
Complications include avascular necrosis of the femoral head (usually occurs after
treatment which includes manipulation of the head before pinning).
7. UPPER LIMB
7.1 Orthopaedic brachial plexus palsy
Paralysis of the upper limb muscles noted at birth
Incidence is 0.4 per 1,000 live births
Causes include pelvic dystocia, shoulder dystocia (upper cervical roots), and breech
(lower cervical roots)
4 years
In babies for whom this does not resolve, a residual Erb's palsy is noted
This is a C5-6 root problem manifesting with weakness in the shoulder abductors and -
external rotators and elbow flexion and supination
A rarer problem involving the lower roots can sometimes ensue. This affects the C7, C8
and T1 roots and presents as loss of sensation in the hand and loss of finger flexion
A mixed palsy (even rarer) can sometimes occur
Electromyograms can sometimes be helpful but they are not preferred because of the
baby's age and the discomfort they can cause. It is better to follow these children
clinically
Treatment involves physiotherapy to keep the joints mobile and supple
Failure of restoration of elbow flexion by 3 months necessitates referral for consideration
of surgery
838
8. INFECTION
8.1 Osteomyelitis
Common in children but the incidence is decreasing
In children it is usually acute and follows haematogenous spread (in the adult it usually
follows direct inoculation)
Pathophysiology - because the physis forms an avascular barrier there are a lot of end
arteries in the metaphyseal ends of the long bones. Blood flow is very slow there and
this helps bacteria to settle and multiply there, thus causing infection
Acute (diagnosis with symptoms for less than 2 weeks), subacute (symptoms for more
than 2 weeks) and chronic (missed early diagnosis) phases are noted. This depends, to
an extent, on the virulence of the affecting organism and the host immune response
Clinical features - fever, pain in the affected limb, avoidance of using the limb, limping
(90% affect the lower limb), reduction of adjacent joint movement (not as severe as
septic arthritis)
Previous history of flu-like illness should be elicited and questions regarding otitis,
pharyngitis and impetigo must be asked
Investigations include full blood count, erythrocyte sedimentation rate, C-reactive
protein, blood cultures, plain radiographs (may be normal in acute osteomyelitis) and
bone scan (may sometimes be needed to confirm diagnosis)
Magnetic resonance imaging and ultrasound may also be required
Differential diagnoses include septic arthritis, fractures, neoplasms and acute infarction
episodes
Complications include chronic osteomyelitis, pathological fractures, septic arthritis and
growth arrests or physeal bars
Common causative organisms - Staphylococcus aureus (commonest), group B
streptococcus, Escherichia coli, Haemophilus influenzae .
Treatment should include antibiotics to cover the respective' organisms. This should
usually last for 6 weeks. C-reactive protein is a good investigation with which to monitor
the progress of treatment
Investigations
Full blood count, erythrocyte sedimentation rate, C-reactive protein (normal values
do not necessarily rule out infection in this age group)
Blood cultures
Microscopy, culture and sensitivity of the joint aspirate
Plain X-rays
Ultrasound
Magnetic resonance imaging and bone scan (can be normal if there is a tense
effusion in the joint) may sometimes be required because diagnosis is often difficult
Treatment
Consists of early administration of antibiotics and drainage of the purulent effusion in
the joint
Splintage may sometimes be required
Prognosis is good if diagnosis is early and treatment is instigated immediately. Delay in
treatment can lead to early secondary arthritis with significant post-septic sequelae
Most common organisms:
Neonate - Staphylococcus aureus, group B streptococcus
Child < 5 years - S. aureus, group A streptococcus, Streptococcus pneumoniae
Child > 5 years - S. aureus, group A streptococcus
Adolescent - S. aureus, Neisseria gonorrhoeae
NB Atypical presentations - tuberculosis is on the increase in the Western world so
have a high index of suspicion.
9. PAEDIATRIC SPINE
9.1 Scoliosis
Prevalence is 0.5 to 3 per 100 (for curves between 10 and 30 degrees)
Generally girls are affected more commonly than boys (but this may change for different
age groups)
Three-dimensional deformity (lateral curve and rotational deformity)
Studies show both X-linked and autosomal dominant inheritance
Recent studies have shown that certain hormonal factors, like melatonin, play an
important part in the progression of this condition
Classification
It can be idiopathic, neuromuscular, congenital, hysterical, functional and mixed with
other associations (mesenchymal, traumatic, osteochondrodystophies etc.)
It can also be classified into: Infantile (0-3 years), Juvenile (3-1 0 years), Adolescent
(>10 years)
Clinical features
Asymmetry of the shoulder
Asymmetry of the top of the pelvis
Adams forward bend test shows a rib prominence to the side of the curve
Lateral deviation of the head is measured (from the natal cleft) by dropping a plumb line
from the C7 vertebra
Lower limb lengths should be assessed for true and apparent limb length discrepancy
Truncal shift should also be assessed
Associated features, such as caf6-au-lait spots (neurofibromatosis), hairy patch in the
lumbosacral area (spinal dysraphism), joint laxity (connective tissue disorder) should be
noted
Full neurological examination of the lower and upper limbs should be carried out
Plain X-rays of the whole spine posteroanterior and lateral (standing views)
Magnetic resonance imaging and computerized tomography may be indicated
depending on the neurology present and to assess for any congenital bony anomalies
Treatment
Identify the curves that are more likely to progress (to be done by a paediatric spinal
surgeon)
Bracing (controversial in the UK but more commonly used in the USA)
Surgery with or without spinal fusion
Treat any intraspinal abnormalities like syringomyelia or dysraphism before attempting
curve correction
9.2 Kyphosis
Normal in the thoracic and sacral regions of the spine
Between T5 and TI 2, an angle of 20-40 degrees is considered normal; 40-50 degrees
is considered borderline normal; < 20 degrees is termed hypokyphosis and
> 50 degrees is termed hyperkyphosis.
Essential Revision Notes in Paediatrics fbr the MRCPCH 2nd Edition
Causes o f kyphosis
7
Hyperkyphosis Hypokyphosis
-
Congenital Scoliosis
Neuromuscular Iatrogenic
Postural
Scheuermann's disease
Connective tissue disorders
Metabolic
Trauma
Respiratory
Jane C Davies
CONTENTS
1. Anatomy and physiology
1.1 Embryology
1.2 Fetal and postnatal lung growth
1.3 Changes at birth and persistent fetal circulation
1.4 Control of respiration
1.5 Ventilation
1.6 Perfusion
1.7 Interpretation of oximetry and blood gases
1.8 Lung function testing
1.9 Respiratory defente mechanisms
1.1 0 Environmental influences on lung disease
3. Asthma
3.1 Pathophysiology
3.2 Drug treatment
3.3 Acute attack
4. Cystic fibrosis
4.1 Background
4.2 Genetics
4.3 Presentation and management
4.4 Newlemerging therapies
4.5 Transplantation
Essential Revision Notes i n P,lrr/i,jfric:c b r the /MKCPCH _71?c-Erlition
6. Bronchopulmonary dysplasia
Infections
7.1 Epiglottitis
7.2 Tonsillitis
7.3 Croup
7.4 Tracheitis
7.5 Bacterial pneumonias
7.6 Empyema
7.7 Bronchiolitis
7.8 Tuberculosis and atypical mycobacterial infection
7.9 Infections in the immunocompromised host
9. Pneumothorax
846
Respiratory
1.5 Ventilation
Air passes through the trachea, major bronchi and terminal bronchioles (anatomical dead-
space) before reaching the sites of active gas exchange, the alveoli. In normal health,
alveolar walls are thin (one cell thick) facilitating O2 and C02 exchange. In diseases
affecting the alveolus, gas exchange will be impaired, leading to an increase in respiratory
rate in response to both a low 0 2 and a raised C02.
1.6 Perfusion
Perfusion is matched to ventilation via hypoxia-mediated pulmonary vasoconstriction, i.e.
vascular constriction leads to diversion of blood flow away from poorly ventilated to well-
ventilated areas, decreasing ventilation-perfusion (VQ) mismatch. Pulmonary arterial flow
will be increased by vasodilatation in response to both high O2 and low C02, whereas
pulmonary vasoconstriction, and thus hypertension, is exacerbated by hypoxia and hyper-
carbia.
Older children
From the age of between 5 and 7 years, children will usually be able to perform standa
lung function tests. The following values can be obtained.
FVC - Forced vital capacity, is the total amount of air exhaled upon forced expiration.
FEV, - Forced expiratory volume in the first second, gives a measure of large (a
medium-sized) airway obstruction.
The ratio of these two values gives an indication as to the nature of an abnormali
Restrictive lung diseases such as fibrosis lead to reduction in both parameters, wit
preservation of the normal ratio (approximately 80°/0), while obstructive diseases (asth
cystic fibrosis) lead to a greater reduction in FEVl and thus a reduced FEVl : FVC ratio.
FEF2s75 - Forced expiratory flow between defined vital capacity (25% being $ empty) is
measure of flow at lower lung volumes, is non-effort-dependent, and is thought to be
reasonable representation of small airways function. However, the coefficient of variati
even in healthy adults, is high.
PEFR - Peak expiratory flow rate. Although useful as a home monitoring device in p
with asthma, it can be quite effort-dependent and can undefestimate significant small
airways obstruction.
All of the above measurements can be obtained using a simple spirometer. For more
complex measurements of lung volume, patients perform plethysmography, which involves
sitting inside an airtight box.
RV - Residual volume is the amount of air left in the lungs after maximal expiration. It is
increased in diseases such as asthma because narrowed small airways prevent complete
emptying of more distal lung and result in air-trapping.
In addition to the above, transfer factor for CO and corrected total lung CO (corrected for
lung volume) give an estimate of the lung diffusion capacity. These measures are reduced in
diseases where alveolae are abnormal and gas exchange is impaired, and increased in the
presence of red blood cells which can absorb CO (e.g. pulmonary haemorrhage or
haemosiderosis).
848
.c
Respiratory
Lung volumes
A
PEF
FEF75
TLC
FEF25
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lnsp
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Seen in:
Chest wall deformity -
Neuromusculardisease
Fibrosing alveolitis
Interstitial pneumonitis
- Respiratory
Mechanical defences
a Mucociiiary clearance whereby cilia beat in a co-ordinated fashion bathed in a normal
volume and composition of airway surface liquid, to bring inhaled particles to the throat
where they are swallowed. Abnormal in primary ciliary dyskinesia (problem with ciliary
microstructure) and cystic fibrosis (normal cilia but decreased airway surface liquid
volume)
a Cough clearance
Immunological defences
a Innate
Phagocytosis by macrophages and neutrophils
Soluble factors including hydrophilic surfactant proteins A&D, lactoferrin, lysozyme,
defensins
Acquired
Humoral: largely immunoglobulin A (IgA) upper airway, IgG lower airways
Cell-mediated
Allergic rhinitis
This presents as rhinorrhoea, sniffing, altered sense of smell (and taste), +/- itchy eyes an
conjunctivitis. It may be either seasonal (usually triggered by pollens, grasses, etc.) or rela
to environmental allergens (e.g. house dust mite, dogs, cats, horses). Often associated
an atopic family history, and there may be other features in the child, e.g. asthma, ecze
Degree of disturbance to a sufferer of severe rhinitis is probably underestimated (proble
with concentration, poor sleep quality, etc.). Management should include allergen avoi
ance and topical (nose +I - administration of corticosteroids or cromoglycate-bas
eyes)
agents. In severe cases, oral antihistamines may be required. Children with allergic rhinit
may also have nasal polyps.
Nasal polyps
These occur in atopic children and in cystic fibrosis (CF) (must consider CF diagnosis in a
child with polyps). Children present with runny nose, nasal obstruction, decreased sense
smell and distortion of nasal shape. Polyps may respond to topical corticosteroids but a
often difficult to treat, necessitating surgical removal. Recurrence post-surgery is unfort
nately common.
Epistaxis
Nose bleeds are reasonably common in childhood. Usually from Little's area on the septu
and often triggered by nose-picking. They are more common in inflamedhnfected nos
(e.g. allergic rhinitislpolyps). If recurrent/severe must rule out a bleeding disorder, e.
idiopathic thrombocytopenic purpura, haemophilia, leukaemia, etc. or anatomical abno
ality (e.g. haemangioma, telangiectasia). Pressure under the nasal bridge.is usually adequ
to halt bleeding. If severe, nose may need packing. Cauterization may be undertaken fo
recurrent episodes.
Sinusitis
Frontal sinuses are not aerated until the age of 3-5 years, so frontal sinusitis is not see
before this age. Later, it presents with headachelfacial pain (made worse by coughing/
bending down), nasal congestion/discharge, concentration problems.
Sinusitis is associated with CF (almost 100°/~of adult patients have opaque sinuses so X-ray
is not very useful). It may also be associated with humoral immunodeficiency, e.g. IgA or
IgG subclass deficiency.
Treatment involves decongestants and antibiotics; surgical drainage is required in a
minority.
Complications (rare but serious):
Orbital cellulitis
Frontal osteomyelitis
Meningitislcerebral abscess
lntracranial (including cavernous sinus) thrombosis
852
Respiratory
Main problems
a Cosmetic - Lip cleft is repaired early at approximately 2-3 months of age
Feeding
Special teats for bottles are available for some infants
Feeding is facilitated by a palatal plate if cleft is severe
May be associated oropharyngeal inco-ordination and aspiration of feeds
Cleft palate surgery is usually performed by the age of 1 year
Speech and hearing - often associated with frequent ear infections and glue ear
Large cleft can cause speech difficulties
Airway .obstruction - If due to Pierre Robin sequence, some infants require a
nasopharyngeal tube to maintain patency of the upper airway
2.3 Ears
Chronic otitis media
Chronic otitis media (glue ear) is a major cause of hearing problems and speech delay and
is caused by the accumulation of thick secretions in the middle ear and recurrent acute
infections. It may be associated with adenoidal hypertrophy; adenoidectomy may improve
symptoms. Long-term antibiotics are not very useful.
Insertion of gro'mmets to release the fluid and pressure is often performed. Normally they
are extruded spontaneously after about 6-9 months. Studies have suggested that swimming
is not harmful to a child with grommets (but they should not dive).
Deafness
Deafness can be conductive or sensorineural.
Conductive deafness
Most common of the two types, detected in up to 3 4 % of schoolchildren, often
mild
Almost always secondary to chronic otitis media
Preservation of bone conductance with diminished air conductance
Sensorineural:
Less common, 0.2-0.3% of children
More likely to be severe
Caused by either cochlear or neuronal damage (may be iatrogenic, eg.
aminoglycoside toxicity)
Equal impairment of both bone and air conductance
Treatment:
Hearing aids may be useful if there is some preservation of hearing
Cochlear implants in seleckd cases
Multidisciplinary approach
Mastoiditis
This has become rare with the use of antibiotics to treat acute otitis media. It results fro
the breakdown of the bony walls of mastoid air cells, secondary to ongoing bacterial mid
ear infection. Presents with high fever, toxicity, irritability, marked focal tenderness over
mastoid process, discharging ear +I- deafness. If early in the process it may respond
parenteral antibiotics; in more severe cases, surgical intervention may be required.
2.4 Throat
Adenotonsillar hypertrophy and airway obstruction
Adenotonsillar hypertrophy is common in childhood, although most cases require no
specific treatment and will resolve with age. More severe cases are associated with certain
disease groups, for example sickle-cell anaemia and human immunodeficiency virus (HIV)
infection.
Symptoms either relate to recurrent infections, or airway obstruction. Obstruction may be
obvious to parents (snoring +I- apnoeic pauses, mouth-breathing), or may present with right
heart failure and cor pulmonale if not recognized until late. Polysomnography may reveal
854
Hesp ira tory
obstructive episodes (increased chest excursion with diminished airflow +/- hypoxia and
hypercarbia if severe), although in the majority of cases diagnosis can be made on the
history.
Management is by surgical removal in selected cases.
2.5 Larynx
Web
Rare. If complete is obviously incompatible with life. More commonly, results in partial
laryngeal obstruction, respiratory distress and stridor. Diagnosed by direct visualization and
requires surgical repair.
Cleft
Very rare. Failure of closure of tracheo-oesophageal septum at 35 days of embryonic
development. Presents with aspiration, choking, episodes of cyanosis +I- apnoea. May
coexist with other abnormalities. Diagnosed by laryngo/bronchoscopy. Requires surgical
repair.
Haemangioma
Presents with airway obstruction, cough or stridor. It may coexist with cutaneous haeman-
giomata so examine the child completely. Visible as a soft mass on instrumentation of the
airway and may bleed copiously if traumatized or if biopsy is attempted. Topical application
of adrenaline may be life-saving in such a situation. Surgical removal often is hazardous. It
may decrease in size in response to local corticosteroid injection.
Essential Revisior-,Notes in Pacdi,africs for.the h4RCPC'M 2nd Eclitiol-,
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-
Papillomatosis g
1
&
Rare cause of hoarseness if affecting the larynx. It may present with stridor or barking 4
cough. Diagnosed on upper airway examination or bronchoscopy. ,ss!
!
Notoriously difficult to treat. There is some evidence of response to cimetidine. Initial hapes
of a response to interferon appear unfounded. -S$s+
2.6 Malacias
Any tubular component of the respiratory tract may be malacic (floppy).
It results in partial or complete collapse on inspiration although patency is well maintained
on expiration.
--
Presentation
inspiratory stridor, respiratory distress
Apnoea
Feeding problems
Recurrent croupy episodes
Diagnosis can be conf/rmed on laryngo/bronchoscopy (although it is usually possible
clinically)
Mild cases (the majority) become less severe with growth
Severe cases may benefit from aortopexy or airway stenting
Croup
Laryngo/tracheomalacia
Subglottic stenosis/granuloma (post-i
Vascular ring
Inhaled foreign body (if large and proximally lodged)
Rarer
Epiglottitis (much less comm
Externat M e a l compressio
Mediastinai mass, e.g. lymp
Tuberculous lymphadenopathy 5
Enlargement of hearVgreat vessels associated with congenital cardiac m
Laryngeal web
Haemangioma, papillomatosis
Vocal cord palsy
Vocal cord dysfunction
~ypoc~lcaemia
2.7 Sleep disordered breathing
A spectrum of problems, ranging from snoring through to hypoxialhypercarbia leading to
pulmonary hypertension and cor pulmonale. It may be related to local (e.g. adenotonsillar
hypertrophy) or systemic (e.g. neuromuscular) disease. Take a careful history. Ask specifi-
cally about pauses in breathing signalling sleep apnoea. It may lead to disrupted sleep/
nocturnal enuresisldaytime somnolence/morning headaches (high C02)/underachievement
at school. Definitive diagnosis on polysomnography (see Section 10.4 on management of
rnyopathies). Treatment is tailored to cause.
3. ASTHMA
3.1 Pathophysiology
Chronic inflammatory disease of the airways with a well-recognized genetic component
which many cells are involved, including eosinophils, lymphocytes and mast cells. Ai
inflammation leads to airway oedema, and hyper-reactivity resulting in reversible bronc
constriction.
If left untreated, the inflammatory changes may eventually become chronic and irreversib
a process termed 'airway remodelling'.
From both laboratory and epidemiological studies, a protective role for infection against
subsequent development of asthma has been demonstrated, e.g. there is a decrea
incidence in children with older siblings or raised on farms.
T-lymphocyte populations are biased towards a T-helper (TH2)cell phenotype (interleu
(11)-4 and 11-5 secreting, involved in IgE production), as opposed to the THI phenoty
which is more commonly found in response to infection.
Symptoms
Symptoms may be classical wheeze and dyspnoea, or a cough variant. They are often wor
at night or in the early morning.
Triggers
Viruses
Allergens (e.g. house dust mite, cats, dogs)
Cold air
Cigarette smoke
Exercise
Stress/emotional
Inhaler devices
You should know how to demonstrate each device. It is very important to choose an inhaler
that is suitable'for the child.
Inhaler devices
Inhaler devices
MDls have poor lung deposition (most of the drug remains in the mouth and pharynx) and are not to be
recommended for use alone.
Long-acting bronchodilators are useful to gain control instead of increasing steroid dose and
in exercise-induced asthma. Now available in combination delivery devices with corticos-
teroid, which may improve compliance.
istal bronchomalacia
bliterative bronchiolitis
4. CYSTIC FIBROSIS
4.1 Background
Cystic fibrosis (CF) is the commonest lethal recessive disease of Caucasians, with a carrier
frequency of 1 : 25, leading to disease in 1 : 2,500 Caucasian births (> 6,000 patients in the
UK). Previously regarded as a disease of childhood, increases in survival have swelled the
adult CF population. Median survival for a child born today is estimated at 40 years.
The gene responsible encodes CF transmembrane-conductance regulator (CFTR) and is on
chromosome 7. The primary function of CFTR is as a chloride-ion channel, but it also
inhibits the epithelial sodium channel. CF respiratory epithelium therefore fails to secrete
chloride ions (fails to absorb in the sweat gland, hence high sweat electrolytes), and
hyperabsorbs sodium ions and thus HzO, dehydrating the airway surface. Secretions are
viscid, impairing mucociliary clearance and thus host defence.
CFTR is now known to have other functions (related to the transport of other substances,
e.g. bicarbonate, and receptors for bacteria) but they are controversial.
Other organs affected for similar reasons include gut, pancreas, liver and reproductive tract.
Diagnosis
Sweat test
'Gold standard'. Values of sodium ions or chloride ions (better) > 60 mEq/l are
diagnostic (although a value of > 40 in infants is very likely to indicate CF)
Traditionally the test required at least 100 mg sweat, but newer methods (e.g.
macroduct) require less. Conductivity (increased in CF) is also used by some
laboratories.
Essential Revisior~Notes in R3ediafric-cf c ~ the
r MKCPCH 2nd Edititrrl
Cases of CF with normal sweat electrolytes have been reported, so if there is a high
suspicion for disease a normal sweat test does not rule out a diagnosis of CF.
If values are in the grey area (40-60 mEq/l) a fludrocortisone suppression test is useful:
3 mg/m2 b.d. for 2 days before the sweat test: normalizes in non-CF, no effect in CF.
Genetic testing
See Section 4.2
lmmunoreactive trypsin
Useful in the first 6 weeks of life. Raised in CF. Often used as first test in areas with newborn
screening.
4.2 Genetics
Over 1,000 mutations in CFTR have been identified to date. They fall into five classes.
Commonest is AF508, a class I1 mutation which leads to defective protein folding and thus
failure to reach the apical membrane. There is a relationship between pancreatic status and
genotype, but correlations for lung disease have been poor to date. It should not be used to
provide prognosis.
Most clinical laboratories test for up to 31 of the commonest mutations (which detects
> 90% of Caucasian cases). This is useful for antenatal testing of subsequent pregnancies.
Neonatal screening was approved by the government in 2001, although widespread
implementation may take several years. It is universal in Australia and New Zealand.
I
Respiratory
Pulmonary
Lungs are thought to be normal at birth. Early symptoms such as cough, frequent chesty
episodes and wheeze may be missed or labelled 'viral infections'. Early infection with a
narrow range of organisms.
Staphylococcus aureus - most children in U K receive long-term prophylaxis
Haemophilus inflenzae
Pseudomonas aeruginosa - up to 80% of CF patients are chronically infected by the
time they reach adolescence. Bacteria become mucoid, forming biofilms and are more
difficult to eradicate when chronic. Treat with long-term nebulized antibiotics
(colomycin +I- gentamicin or tobramycin). Intermittent courses of intravenous
antibiotics (always at least two). Macrolide antibiotics are in more common use now.
Shown to improve lung function, although mechanism of actian unclear; may be anti-
inflammatory
Allergic bronchopulmonary aspergillosis (ABPA) - presents with dry cough, wheeze,
variable infiltrates on chest X-ray. Diagnosed with high IgE, raised radioallergosorbent
test (RAST) and precipitins. Skin-prick testing may be helpful. Treated with steroids +/-
itraconazole, which may need to be prolonged.
Burkholderia cepacia - Gram-negative, often highly resistant. Meropenem may be
useful. Associated in approximately 20% with l ife-threatening septicaemia ('cepacia
syndrome'), patient-to-patient spread is well-documented (segregation vital)
Stenotrophomonas maltophilia - an emerging pathogen; there is accumulating
evidence that it does not lead to significant deterioration.
Atypical mycobacteria - quite common. May be an incidental finding. Treat if
symptomatic, persistent, or if patient is immune-suppressed, e.g. on steroids.
Airway inflammatory response is excessive. End-result of infection/inflammation is bronch-
iectasis (upper lobes common), chronic sputum production, clubbing (asthma DOES NOT
cause clubbing) and hypoxia. May present with asthma-like symptoms (consider CF in cases
of difficultlatypical asthma). May have haemoptysis (high bronchial arterial flow and if
severe, embolization). 90% of patients die of respiratory failure.
Essentia1 Revision Notes i n &edict trics t o r the MRCPCH 2nd Edition
Extrapulmonary involvement
Pancreas
Exocrine insufficiency
Presents with steatorrhoea and faltering growth
Low stool elastase, high 3-day faecal fat
Treat with pancreatic enzyme supplements (e.g, Creon)
Fat-soluble vitamin supplementation
Nutritional supplements if required
Gastrostomy and supplemental nutrition if severe weight problems
Endocrine problems
Diabetes is more common in older children (8-1 5%)
Insidious, non-specific onset
Ketoacidosis is extremely rare (residual pancreatic function)
Usually require insulin. Some evidence that early use of low-dose insulin in pre-diabetic
phase may protect lung function
Gastrointestinal tract
Distal intestinal obstruction syndrome (previously called meconium ileus equivalent)
Rehydrate and administer Gastrografin, Golitely, etc.
Attention to dietary fibre and enzymes
Hepatic cirrhosis
Ursodeoxycholic acid may be useful
Nose
Polyps (up to 30%): topical steroid or surgery - often recur
Sinusitis
Common - daused by obstruction
Same causative organisms as lungs
Respira tory
infertility
a 99% males (obstruction and abnormal development of vas deferens)
a Females subfertile, but many successful pregnancies. Pulmonary health may be severely
affected during pregnancy - need careful monitoring.
Arthritis
a Probably immune-complex-mediated
a Correlates with pulmonary function tests
Osteoporosis
More common with increasing age and severity of lung disease; also long-term steroid
use. Many clinics monitor using bone densitometry.
4.5 Transplantation
Heart-lung or bilateral lung transplants are performed, limited by the number of organs
available. More recently living-related donors have been used; currently no advantage but
will possibly improve with further experience.
Psychological issues are of major importance.
Possible contraindications (vary slightly with different centres)
Long-term use of high-dose steroids
Multiresistant organisms
Previous thoracic surgery
Essential Revision Notes in &ccfi,~tricstor the MRCPCW 211d Ech~ion
Classically occurs after pertussis, although may also follow measles. May occur after severe
infection with any organism.
Post-airway obstruction
Highlights importance of early detection and removal of foreign bodies (see Section 8).
Tuberculosis - obstructive lymphadenopathy.
Respiratory
Recurrent infection
For example, immune-deficiency (see Section 7.9).
Recurrent aspiration
Idiopathic
This explains up to 60% of cases but other causes must be excluded.
Congenital
Rare.
6. BRONCHOPULMONARY DYSPLASIA
Chronic lung disease resulting from premature delivery, surfactant deficiency and neonatal
artificial ventilation.
Various definitions exist, all including the requirement for O2 at 28 days.
Other aetiological factors include:
Birth asphyxia
High-concentration O2 administration
Fluid overload
Infection
Vitamin A deficiency - antioxidant effects
Of these, barotrauma from ventilation and oxygen toxicity is most important. Centres using
non-invasive ventilation as the first-line therapy (e.g. nasal continuous positive-airways
pressure (CPAP)), have lower incidence of bronchopulmonary dysplasia.
Incidence is reduced greatly by both antenatal steroids (increases lung maturation and
surfactant production) and exogenous surfactant. (For further details see Chapter 16 -
Neonatology).
Treatment
Long-term 0 2
Corticosteroids
Diuretics and fluid restriction may be useful
Immunization including 'flu and Pneumovax
Consider use of palivizumab (see Section 7.7)
Aggressive treatment of infections
Bronchodilators may be useful in wheezy cases
Consider and treat coexisting gastro-oesophageal reflux (immature swallow, reduced
muscle tone, prolonged intubation all increase risk)
for the MMKCTPC,7i ?!id Edition
Essenti~lRevision Notes in p;7edjc7tl.jcs
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Longer-term complications
Reactive airways disease (e.g. risk of severe disease with RSV)
Complications of intubation (e.g. subglottic stenosis, granulation tissue, tracheomalacia)
Gastro-oesophageal reflux
Pulmonary hypertension and cor pulmonale
Growth and nutritional delay
Neurodevelopmental disability
7. INFECTIONS
7.1 Epiglottitis
Usually caused by Haemophilus influenzae type b. Rare since introduction of Hib vaccine.
Presents with acute-onset stridor, fever, anxiety in child.
7.2 Tonsillitis
Acute tonsillitis is common and self-limiting in childhood. presentation may be non-specific
in the small child, e.g. irritability, refusal of feeds, fever, febrile convulsion. Older child
usually complains of sore throat. Bacterial and viral causes (commonly adenovirus,
rhinovirus, fl-haemolytic streptococcus); exudate does not imply bacterial cause.
7.3 Croup
* Viral laryngotracheobronchitis- parainfuenza virus, influenza virus, RSV, rhinoviruses
Common between 6 months and 5 years of age; more common in boys than girls
Barking cough and stridor
Child not usually toxic, may have low-grade fever
No evidence in support of humidification
Respiratory
.
Good evidence for a role for steroids
Oral single dose seems to be as good as intramuscular (dexamethasone used in most
. studies)
Some evidence for high-dose nebulized steroids, e.g. budesonide
Nebulized adrenaline will help in acute situation but effect is short-lived
Severe cases may require intubation and ventilation
May be recurrent
7.4 Tracheitis
Presentation as for croup
Viral (same as croup) and bacterial (Staphylococcus aureus and Haemophilus
influenzae) aetiologies
Bacterial cases often more toxic
Severe cases may require intubation
Aetiology
Pneumococcus sp. is commonest causative organism
With increasing age, Mycoplasma sp. are more prevalent
Staphylococcus aureus is associated with lung abscess (both staphylococci .and
streptococci may follow varicella virus infection)
Rarely H. influenzae, streptococci, Klebsiella sp. (remember most pneumonias are viral
in younger child)
Management
Mild cases can be diagnosed clinically and treated with oral antibiotics out of hospital
More severe cases - cultures (sputum if available, upper airway secretions, blood)
White blood cell count and differential and C-reactive protein are useful for
monitoring response to treatment (but do not differentiate well between bacterial and
viral infections, intravenous antibiotics)
Hydration (see below)
O2therapy if required
Rarely, severe cases will require respiratory support
Complications
Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) is common. Leads to
fluid retention and thus hyponatraemia, which if severe can lead to cerebral oedema and
convulsions. Monitor electrolytes and osmolality (serum and urine). Management is by fluid
restriction and NOT by administration of sodium.
7.6 Empyema
Collection of pus in pleural space resulting from spread of infection from lung tissue:
Presents with signs of pneumonia plus unilateral decreased air entry, dull percussion note.
Patient often has scoliosis toward the affected side +/- mediastinal shift. Fluid demonstrated
on chest X-ray. Ultrasound may confirm presence of loculation or fibrin strands.
Management
@ Requires drainage (not just aspiration)
Some recent evidence that urokinase may assist recovery by breaking down fibrinous
material
Intravenous antibiotics
A minority may need surgery - decortication
Video-assisted thoracic surgery (VATS) is gaining in popularity
Complications
Bronchopleural fistula
Lung abscess
SIADH
Presentation
Respiratory distress and coryza
Fever
Hyperinflation
Apnoea in very young infants
Crackles widespread throughout lung fields +I-
wheeze
Diagnosis
lmmunofluorescence on nasopharyngeal aspirate
Management
Largely supportive
Adequate hydration
Humidified O2 as required
Evidence for use of bronchodilators (e.g. ipratropium bromide or salbutamol) not strong,
but used frequently, often with apparent success
Specific treatments
Ribavirin
No longer being used to any great extent because of poor efficacy, difficulties with
administration (clogs up ventilator circuits) and potential teratogenicity. Used mainly in
severe immunocompromise (e.g. bone marrow recipients) sometimes in conjunction with
an intravenous preparation.
Essential Revision Notes in Paedi'ltt-ic-s for the MRCPCH 2nd Edition
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Vaccination
No active vaccine is currently available, and early studies with attenuated virus have led to
increased severity in the subsequent infective episode. Anti-RSV immunoglobulin was useful
in early studies in high-risk cases, but there were problems obtaining sufficient quantities
and the usual concerns re blood products.
Humanized monoclonal anti-RSV antibody (palivizumab, Synagis) has been available in
Europe since 1999 (1 year earlier in USA).
Given as monthly intramuscular injections during the RSV season
Shown in trials of babies with bronchopulmonary dysplasia to reduce admissions, but
no effect on the severe end of the disease (paediatric intensive care, mortality)
Recommendations for use vary (commonly chronically 02-dependent in first 2 years
of life)
Pulmonary TB
The major route of infection is via the respiratory tract (more rarely via the oral route leading
to gut TB - must rule out immunodeficiency).
Once organisms have been inhaled they establish themselves in the periphery of the lungs,
and elicit a host inflammatory response (largely via macrophages).
Spread to regional lymph nodes may also cause hilar adenopathy.
If inflammatory response is sufficient to keep the infection in check, the lesion may calcify
and form a Chon focus, which may be identified later on chest X-ray, and may be the only
evidence of previous TB in an otherwise well subject. This is much rarer in children than in
adults, and the majority of TB presenting in children results from the primary infection,
resulting in the period from infection to disease often being as short as weeks.
Respiratory
Symptoms
These vary and may be non-specific.
Fever
Irritability
Weight loss and lethargy
Cough
Airway obstruction from lymphadenopathy; may lead to lobar collapse or less frequently
to air trapping
Dyspnoea and respiratory distress in severe cases especially if miliary
Erythema nodosum
Radiology
Can vary greatly from isolated focus to hilar lymphadenopathy, lobar collapse/
consolidation to miliary (seed-like) shadowing throughout lung fields
Large caseating lesions not common in children
Extrapulmonary
TB can infect most organs, in particular the brain, kidneys, gut and bone. Children are more
prone than adults to extrapulmonary infection, the details of which will not be discussed
further here.
Diagnosis of TB
High index of suspicion is important.
Tuberculin testing
lntradermal administration of purified tuberculin protein will lead to a T-cell-mediated
reaction in sensitized individuals. Depending on the clinical situation, and whether bacillus
Calmette-Guerin (BCC)has been administered, the size of reaction considered significant
may differ.
Young age
>5mm Contact with an open known case (if no BCG)
Clinical or radiographic evidence
HIV infection
Essential Revision Notes in Paediatrics tor the MRCPCH 2nd Edition
Microbiology
Sputum (rare in children)
.
I Gastric aspirates (morning)
* Bronchoalveolar lavage fluid
Acid-fast bacilli may be visible on staining, otherwise culture requires up to 6-8 weeks
Some laboratories will test with polymerase chain reaction, although because this is ve
sensitive, false-positives can arise.
Treatment
developing country.
Drug treatment is given in an initial phase of three or four drugs, followed by a maintenance
phase of two drugs.
874
Respiratory
Children are rarely open cases (i.e. smear-positive) and it is therefore unusual that they
would be capable of transmitting the infection. After the first 2 weeks of treatment the child
should be allowed to re-commence normal activities.
Neonatal contact
A neonate born to a mother with active TB is at serious risk of acquiring the disease. If at
the time the maternal diagnosis is realized (and treatment commenced) the infant has no
signs of TB, the child should receive isoniazid prophylaxis, be closely followed up, and
receive a tuberculin test at approximately 3-4 months. Thereafter, the guidelines for older
children should be followed.
Contact tracing is a major public health issue. Cases of paediatric TB still arise in families
where a parent is known to be infected but children are not screened.
Treatment
Longer than for M. tuberculosis (up to 2 years). Choice of agents depends on organism and
sensitivities. Usually a combination of the following is used.
Rifampicin
Clarithromycin/azithromycin
Amikacin
Ciprofloxacin
Clofazimine
Ethambutol
Notification and contact tracing are not required.
Cytomegalovirus
Presentation
Usually insidious - radiological appearance and likely immunodeficiencies similar
to l? carinii pneumonia
May be congenital or acquired
May coexist with extrapulmonary infection - ophthalmic examination required
Diagnosis
Antigen (DEAFF, detection of early-antigen fluorescent foci) or polymerase chain
reaction on NPA, BAL
Detection in other body fluids, e.g. urine, does not confirm cytomegalovirus as the
cause of pneumonitis
Other
Dual infection with F! carinii is not uncommon
Other infections
Organisms causing a similar interstitial picture in immunocompromised patients include:
Measles
Varicella
Herpes simplex
Adenovirus
Fungi
Mycobacteria
Lymphocytic interstitial pneumonitis
Although not related to any particular pathogen, this disorder is often confused with the
opportunistic infections above, and thus is included here. Seen in children with HIV or
occasionally other immunodeficiency states. Less common in adults.
Tends to coexist with marked lymphadenopathy - parotid hyperplasia, and to decrease
with falling CD4 count
Presents either as chronic cough or hypoxia and clubbing if severe.
May be asymptomatic and detected radiologically only.
Treatment - nil if well, usually responds to steroids
Suspect signs
Sudden-onset cough/wheeze/breathlessness
May or may not give history of aspiration
Ask about presence of older siblings in the case of an infant
Unilateral signs: wheeze, absent or diminished air entry, tracheallmediastinal deviation if
severe
Chest X-ray
Either volume loss or hyperexpansion from air trapping on affected side
Hyperexpansion best visualized on expiratory film
Management
Removal under rigid bronchoscopy (flexible bronchoscopy not recommended because
removal is more difficult)
Follow-up ventilation scan should be considered, especially in cases of non-inert foreign
body, e.g. food. Peanuts are a particular problem because nut oil is very irritant and
proinflarnmat~r~. If removal is delayed, anti-inflammatory agents, e.g. steroids, may be
useful to reduce airway narrowing
Consider post-operative antibiotics, depending on findings
Education is important, particularly the avoidance of peanuts in young children
9. PNEUMBTHORAX
In children this is usually associated with underlying disease.
Gas trapping (e.g. severe asthma, CF)
Buliae (e.g. Marfan syndrome)
Other - Langerhans cell histiocytosis (in association with fibrotic, honeycomb changes
on chest X-ray)
Iatrogenic (high-pressure ventilation), traumatic and post-operative
Management
Depends on size on chest X-ray (all patients should have one)
If small with minimal symptoms, can be managed conservatively and observed
If larger with significant symptoms give O2 (aids air absorption from pleural space) and
drain. Aspiration may be sufficient, othetwise intercostal drain
Recurrent
Consider pleurodesis
Visceral pleura adheres to chest wall with either talc or bleomycin
Painful. May exclude possibility of future transplantation, e.g. in CF. Consider with care
Confused with:
Neonatal cysts, diaphragmatic hernia, severe hyperinflation, e.g. inhaled foreign body
1 . NEUROMUSCULAR DISORDERS
Can impair respiratory function at any of following sites: spinal cord, peripheral ,-,ewe,
neuromuscular junction and muscle.
t Myelomeningocele
1 Rarely affects respiration unless very high.
F
..
Specific treatments
Intravenous immunoglobulin
Plasmapheresis in some cases
Botulism
Rare
Toxins produced by Clostridium botulinum (usually food-borne) lead to impaired release
of ACh at neuromuscular junction. Bulbar muscles involved early, with respiratory
failure in most cases. Good prognosis with adequate support. ~btulinumtoxin is
currently being used as treatment for certain diseases with muscular spasm as major
component.
Tick paralysis
Very rare
10.4 Muscle
Myotonic dystrophy
Floppy infant in severe form
Diaphragm involvement (eventration)
Feeding problems +/- aspiration
Maternal (when congenital) myotonia (muscles slow to relax eg. hard shake)
Later problems - learning difficulties, cardiac conduction defects, baldness
Triplet-repeat disease (others are Huntington disease, Fragile X, Friedreich ataxia) with
increasing severity in subsequent generations (genetic anticipation)
Respiratory
Myopathies
Respiratory involvement variable depending on type
Symptoms include:
Respiratory infections
Morning headaches (C02 retention)
Daytime drowsiness
Management
Always consider possibility of respiratory involvement
Lung function testing
Polysomnography (overnight 02,C02, nasal airflow, chest wall movement, heart
rate, respiratory rate +/- EEG, pH probe)
Non-invasive ventilation increasingly used (see below). Use once evidence of
respiratory failure. Some evidence against prophylactic use in Duchenne muscular
dystrophy
Positive pressure
Both continuous (CPAP) or bi-level (Bi-PAP) positive airway pressure can be administered
through either a nose or face mask.
Both systems can be used at home with or without oxygen depending on the pathology,
The devices are in general well-tolerated, the only major problem being one of pressure
sores resulting from the tight-fitting mask.
Negative pressure
Devices, including the cuirass jacket, have also been used in these settings. The jacket is
worn around the chest, with closely fitted seals at either end. Negative pressure applied to
the jacket causes inspiration. Expiration can be passive or assisted.
The benefits of this approach include a more physiological respiratory cycle. However,
movement of the child is limited by the devices, which can also be very noisy.
In the UK, negative pressure is used much less frequently than positive. It is important to
remember that significant weakness of the bulbar muscles, especially with any airway
malacia, can lead to airway collapse and obstruction during applied negative pressure,
which can lead to failure of the device.
Bronchogenic cyst
Remnant of primitive foregut derived from abnormal tracheobronchial budding
Form up to 1O0/0 of mediastinal masses in children
Contain normal tracheal tissue, filled with clear fluid
May exist in various sites including paraoesophageal, with symptoms varying
accordingly
May be either symptomatic or associated with
Airway compression
Stridor
Lobar collapse
Obstructive emphysema
Infection
Haemorrhage
Barium swallow may detect filling defect. Surgical removal rkcorpmended to prevent
infection, airway obstruction, or malignant transformation. Pre-operatively avoid high-
pressure ventilation and air travel - cysts may expand and rupture.
Lobar sequestration
Mass of non-functional lung; abnormal communication with airway and usually
supplied by systemic circulation
Intra- or extralobar (often associated with other congenital abnormalities and
polyhydramnios). May have derived from accessory lung bud, although exact aetiology
is uncertain. Lower lobes most commonly affected, more often the left. Many cases are
asymptomatic. Present most commonly with recurrent pneumonia in same site
Chest X-ray - solid or cystic (if intralobar +/- air-fluid level) mass
Angiography required to demonstrate and delineate systemic blood supply
Surgical removal required even in asymptomatic cases because infection will ensue if
untreated
Scimitar syndrome
Hypoplastic right lung with anomalous venous drainage (usually to inferior vena cava or
right atrium) +/- systemic collateral arterial supply. 'Scimitar' sign is the vertical line
caused by the right uppler lobe pulmonary vein running into the inferior vena cava
May be asymptomatic or lead to recurrent infection
* Right lung usually functions well and surgical correction of the vascular abnormalities is
usually recommended
Diaphragmatic hernia
Incidence estimated at around 1 per 2,500-3,500 births. More common on the left.
Main problems arise from the associated pulmonary hypoplasia, both on the affected
side and the contralateral side when there is significant mediastinal shift. Diagnosis ma
be made antenatally on ultrasound
Postnatal presentation includes respiratory distress, scaphoid abdomen and vomiting.
Chest X-ray shows bowel loops inside thorax which may be confused with either cystic
malformation or pneumothorax (use nasogastric tube both to confirm the diagnosis and
to deflate the stomach reducing the chance of rupture)
Often associated with other malformations, in which case prognosis is worse
Treatment
Surgery required
No clear evidence, but some suggestion, that high-frequency oscillatory ventilation
may help
Pulmonary hypertension is quite common. May respond to nitric oxide or
vasodilators
Prognosis
Even with optimal management' mortality about 50-6O0/0 .
Survivors may have problems associated with underlying pulmonary hypoplasia
Alveolar proteinosis
Aetiology is uncertain, although some cases presenting as neonates are now known to
be the result of deficiency of surfactant-associated protein B and others are linked to
granulocyte-macrophage colony-stimulating factor. Lipid-laden type I1 pneumocytes
desquamate into the alveolar spaces leading to increasing hypoxia and respiratory
distress
884
a Chest X-ray - resembles interstitial lung disease with widespread confluent airspace
shadowing
a Diagnosis - made on lung biopsy
a Prognosis - poor
a In older child, whole lung lavages may help, but in infants, the disease is almost
universally fatal. Genetic counselling required
Haemosiderosis
Repeated episodes of pulmonary haemorrhage lead to accumulation of haemosiderin at
the alveolar level
Haemorrhage may be symptomatic with haemoptysis, or unrecognized, presenting with
anaemia
Aetiology is uncertain, although a subgroup of cases are associated with cows' milk
protein allergy and positive antibodies and respond to dietary manipulation
Another subgroup have Goodpasture syndrome (positive antiglomerular basement
membrane antibodies)
Similar clinical picture may occur with mitral stenosis or connective tissue diseases
Symptoms - usually episodic: fever, dyspnoea, wheeze +I- haemoptysis
Chest X-ray - may be normal but more commonly patchy shadowing
Diagnosis - haemosiderin-laden macrophages in BAL
Management -difficult
Acute - treat hypoxia, anaemia
Longer term - steroids, hydroxychloroquine or alternative immunosuppressive drugs
Sarcoid
Extremely rare in childhood
Multisystem granulomatous disease, may be confused with TB and chronic
granulomatous disease
Symptoms
Dry cough, dyspnoea
Clinical examination often unremarkable in early stages (may lead to clubbing later
CXR
Hilar lymphadenopathy
Patchy lung infiltrates
May be associated with extrapulmonary disease (skin, eye, kidney, gut)
Diagnosis
Usually made on biopsy (Kveim test no longer performed)
Treatment
May be self-limiting
Steroids +I -
hydroxychloroquine if treatment required
Group of conditions not well defined in terms of aetiology which lead to inflammation and
fibrosis at the alveolar level, sometimes also termed 'cryptogenic fibrosing .alveolitisf (CFA).
Gradual onset dry cough, dyspnoea, hypoxia, clubbing. Widespread crackles throughout
both lung fields.
Chest X-raylcomputerized tomography - ground-glass appearance
Differential diagnosis includes pneumonitis from opportunistic pathogens, e.g. l? carinii
may be used)
Prognosis - highly variable ranging from subacute respiratory failure to a plateau phase
with intermittent symptoms, or even recovery in some patients
Respird tory
Pulmonary hypertension
Increased pulmonary vascular pressure may be primary (rare) or more commonly occurs
secondary to another disease.
These include:
Any cause of chronic lung disease, e.g. bronchopulmonary dysplasia, CF. Chronic
hypoxia leads to pulmonary vasoconstriction and arterial wall changes
High pulmonary arterial flow from left to right shunt, e.g. large ventricular septa1 defect
Obstructed pulmonary venous drainage or left heart failure (rare in childhood)
Primary pulmonary hypertension presents with hypoxia, dyspnoea and, if severe, right heart
failure. May present in the neonatal period as persistent fetal circulation (see Section 1.3).
May respond to pulmonary vasodilators:
High O2
Prostacyclin
Nifedipine
Nitric oxide
viagraTM(Sildenafil)
Prognosis is usually poor unless transplantation is an option
CONTENTS
I
4. Childhood vasculitis
4.1 Henoch-Schonlein purpura
4.2 Kawasaki disease (mucocutaneous lymph node syndrome)
4.3 Polyarteritis nodosa
4.4 Takayasu disease (giant-cell arteritis)
4.5 Vasculitis with granuloma
4.6 Differential diagnosis of childhood rheumatic disorders
i
E s s e t j t j ~ lrevisit^^^ Notes i n Paedic?trics i ~ the
r MRCPCH 217dEdition
5, Miscellaneous disorders
5.1 Osteogenesis imperfecta
5.2. Osteopetrosis
5.3 Osteoporosis
5.4 Hemihypertrophy
5.5 Hypermobility
5.6 Toe walking
5.7 Foot drop
5.8 Reflex sympathetic dystrophy
5.9 Non-accidental injury
Systemic disease
High remittent fever and rash with one or more of the following: hepatomegaly,
splenomegaly, generalized lymphadenopathy, serositis (occasionally pericarditis)
Arthritis may be absent at the onset, but myalgia or arthralgia are usually present
Polyarticularonset
Five or more joints develop in the onset period, usually somewhat insidiously and
symmetrically
May be further divided by the presence of immunoglobulin M (IgM) rheumatoid factor
Oligoarticular onset
The commonest mode with four or fewer joints involved, particularly knees and ankles
Three clear subgroups have emerged, notably young children with positive antinuclear
antibodies who are at risk from chronic iridocyclitis, older boys (aged 9 upwards) who
Essenti,?~'Kevision Notes in Pc7edic?tricstor the hl KC'PC7H 2 nd Ertitic
frequently carry the histocompatible leukocyte antigen (HLA) 827 and develop enthesitis
(now classified as enthesitis-related arthritis), and those that extend past four joints
(extended oligoarticular juvenile idiopathic arthritis)
Others presenting in this way include juvenile psoriatic arthritis, the arthritis of
inflammatory bowel disease and Reiter syndrome, while some are as yet unclassified
Clinical features
High once-daily fever spikes for > 2 weeks
Myalgia
Arthralgia
Malaise
Rash - salmon pink or red maculopapular eruption
Lymphadenopathy - cervical, epitrochlear, axillary and inguinal
Hepatosplenomegaly
Serositis - occasionally pericarditis
Hepatitis
Progressive anaemia
Disseminated intravascular coagulation
Arthritis - knees, wrists and carpi, ankles and tarsi, neck, followed by other joints
Investigations
Erythrocyte sedimentation rate (ESR) - high
Haemoglobin - low (normochromic, normocytic)
White blood cell count - raised (neutrophil leukocytosis)
Platelets - raised (>400 x 106/1)
IgM rheumatoid factor - negative
Antinuclear antibodies (ANA) - negative
Management
Physiotherapy to maintain joint mobility and muscle function
Non-steroidal anti-inflammatory drugs (NSAIDs) to control pain, inflammation and fever
Corticosteroids in severe disease, either as pulsed intravenous, single daily dose or given
on alternate days
Methotrexate especially for arthritis
Cyclosporin for systemic features
Etanercept (tumour necrosis factor (TNF) receptor) or Infliximab/adalimumab (anti-
tumour necrosis factor (TNF) receptor antibody) for disease that is resistant to other
medical management or for patients in whom there i s significant drug toxicity - very
little is known of long-term toxicity, use in specialist centres only
Anti-interleukin-1 (anti-IL-1; Anakinra) effective when other treatments failed or side-
effects
Clinical features
Polyarthritis can affect any joint; the most commonly affected are the knees, wrists,
ankles and proximal and distal interphalangeal joints of the hands;
.
metacarpophalangeal joints are often spared
Limitation of neck and temporomandibular movement is common
Flexor tenosynovitis
Low-grade fever, occasionally
Mild lymphadenopathy and hepatosplenomegaly, occasionally
Investigations
ESR - elevated
Haemoglobin - may be reduced
White blood count - mild neutrophil leukocytosis
Platelets - moderate thrombocytosis
IgM rheumatoid factor - negative
ANA - occasionally positive
Clinical features
Polyarthritis affecting any joint, but particularly the small joints of the wrists, hands,
ankles, and feet; knees and hips often early, with elbows and other joints later
Rheumatoid nodules on pressure points, particularly elbows. Vasculitis - uncommon
and often late, nail-fold lesions, ulceration
Investigations
ESR - usually elevated
Haemoglobin - moderate anaemia
IgM rheumatoid factor - persistently positive and in high titre
ANA - may be positive
HLA DR4 - frequently present
Radiographically - early erosive changes of affected joints, particularly of hands and
feet
Management
Physiotherapy to maintain and improve joint and muscle function
Splinting to preserve function
NSAlDs
Slow-acting drugs early
Methotrexate
Anti-TNF treatment if other DMARDs failed
Surgical intervention, such as replacement arthroplasties, often required later
1.4 Oligoarticular (persistent and extended)
General characteristics
Under 6 years of age
Female predominance
Clinical features
Arthritis affecting four or fewer joints: commonly knee, ankle, elbow or a single finger
Early local growth anomalies
a Risk (2 : 3) of chronic iridocyclitis in the first 5 years of disease, ANA associated
If four or fewer joints after 6 months then defined as persistent oligoarticular, if more
than four joints are affected then it is described as extended oligoarticular
Investigations
ESR - may be elevated or normal, initially
Haemoglobin - normal
White blood count - normal
Platelets - normal
IgM rheumatoid factor - negative
ANA - frequently positive
HLAA2, DR5 and DR8
Management
Physiotherapy to maintain muscle and joint function
NSAlDs
Local corticosteroid injection - triamcinolone hexacetonide is most effective
Frequent ophthalmological assessment (3-6-monthly)
Methotrexate for extended oligoarticular juvenile idiopathic arthritis
Anti-TNF treatment in extended if other DMARDs failed
Clinical features
Peripheral arthritis predominantly affecting the joints of the lower limb
Enthesopathies - plantar fascia, Achilles tendon, patella tendon
Acute iritis
Sacroiliac pain in some either of these can be
Axial disease in some the presenting feature
Investigations
ESR - normal to high
Full blood count - usually normal
IgM rheumatoid factor - negative
HLA B27 - present 90°h
Management
Physiotherapy, including hydrotherapy, to maintain mobility: particularly important if
spinal involvement occurs
NSAlDs
Local corticosteroid injections, hip arthroplasty may be needed in a small proportion
Sulfasalazine i s the disease-modifying drug of choice, methotrexatg is also effective
Anti-TNF treatment if other DMARDs failed
Clinical features
Asymmetrical arthritis
Flexor tenosynovitis
Occasionally severe destructive disease
Systemic features rare
Nail pitting
Rheumatology
Onycholysis
Psoriasis
Investigations
ESR - varies with number of joints, may be high
Haemoglobin - may fall
White blood count - may increase (neutrophils)
IgM rheumatoid factor - negative
ANA - can be positive
Management
Physiotherapy
NSAlDs
Severe destructive form may require immunosuppressants such as methotrexate
Anti-TNF treatment if other DMARDs failed
1.7 Unclassified
All those that do not meet the criteria for the above.
Clinical features
Arthritis usually occurs after the onset of bowel symptoms, but occasionally begins
coincident with, or even precedes, them
Arthritis is usually oligoarticular: knees, ankles, wrists and elbows
Essential Revision Notes in Paecli,~trics tior the MRCPCH 217cJ Edition
Two forms:
Benign peripheral arthritis coinciding with active bowel disease
In older patients, who belong to the spondylitic group, the joint activity does not
necessarily link with bowel activity
Associated features
Erythema nodosum
Pyoderma gangrenosum
Mucosal ulcers
Fever
Weight loss
Growth retardation
Acute iritis - in the spondylitic group
Investigations
Platelets - normal/elevated
ESR - usually elevated
Haemoglobin - usually low (normochromic, normocytic)
White blood count - normal
IgM rheumatoid factor - negative
ANA - negative
HLA B27 present in the spondylitic group
Management
Physiotherapy as appropriate
Treatment of the underlying bowel disorder
NSAlDs with care, because of gastrointestinal side-effects (ibuprofen may be the drug
choice and use antacids such as ranitidine
Sulfasalazine may be helpful for both subgroups
lnfliximab (anti-TNF treatment) is effective
Leptospirosis
Histoptaammis
C Rheumatology
8
Clinical features
Arthritis Typical triad
Urethritis/baIanitis/cystitis for Reiter
Conjunctivitis syndrome
Mouth ulceration
Fever
Rashes, including keratoderrna blennorrhagica (macules - pustular on palms, soles,
toes, penis)
If only two salient features occur, it is often referred to as 'incomplete Reiter syndrome'.
Investigations
ESR - raised
Haemoglobin - normal
Mild neutrophil leukocytosis
Essential Revision Notes ill R~edinfricsfor the MRCPCH 2nd Edition
2-
I Management
1
i Antibiotics initially, if an organism is found
:1
//
Physiotherapy to maintain function of joints and muscles
NSAlDs
Sulfasalazine if joint problems persist
Reiter sync$ome -
~rthntisof inflammatory bowel disease and psoriasis
Acute irjdocyclitis 7
Investigations
ESR - raised if not in cardiac failure
Haemoglobin - may fall with chronic disease
White blood count - normal or slight rise
IgM rheumatoid factor - negative
ANA - negative
ECG - may be abnormal, prolonged PR
Echocardiogram - may show valvular or myocardial dysfunction
Management
Bed rest in the acute phase
Penicillin to eradicate residual streptococcal infection
Salicylate therapy
Corticosteroids in patients with significant carditis
i Prophylactic oral or intramuscular penicillin after an attack required into adult life
f
5
2.5 Infectious arthritis
B Viral
Adenovirus, parvovirus, cytomegalovirus, rubella virus, mumps virus, varicella virus
Lyme disease
I'
a Borrelia burgdorferi
Essential Revision Notes in f%edic~trir.s
fill- t/ie M KCPCH r 7 d Fdition
Bacterial
Haemophilus sp. (young), staphylococcus, streptococcus, meningococcus, gonococcus
Mycobacteria - both typical and atypical
Fungal
Blastomycosis, coccidiomycosis, cryptococcus
Histoplasma capsulatum
Other
Mycoplasma
Guinea worm
Orthoses
Orthoses are useful in helping to prevent contractures, in maintaining a good position if
contractures have been repaired and in providing joint stability
They are particularly useful in aiding individual children with mobility
The type of orthoses depends on the child's individual needs
For example they may be ankle-foot orthoses if there is just ankle and foot involvement,
extending to the knee if the knee is involved. Should there be a scoliosis, thoracolumbar
orthoses are available.
Side-effects of commonly used drugs
NSAlDs - gastrointestinal (may need ranitidine, omeprazole), neurological (headaches,
mood)
Steroids - bone (use calcium, vitamin D), growth, cataract, weight gain
Methotrexate - nausea (may need ondansetron) liver and bone marrow toxicity
(requires monitoring of blood count and liver function)
Anti-TNF treatment - hypersensitivity reactions, infections, particularly tuberculosis
Antinuclear antibodies
Not diagnostic or specific for any particular disease
React with various nuclear constituents
Causes of ANA positivity in children
Systemic lupus erythematosus
Juvenile idiopathic arthritis
. ,.
Chronic active hepatitis
S'cleroderma
Mixed connective tissue disease
General characteristics
Non-suppurative myositis with characteristic skin rash and vasculitis
Occurs in girls more often than in boys
Peak incidence 4-1 0 years of age
Clinical features
Muscle pain and occasional tenderness
Muscle weakness - limb, girdle, neck, palate, swallowing
Oedema
Skin rash - periorbital heliotrope eruption and oedema
Deep red patches over extensor surface of finger joints (Gottron's patches), elbows,
knees and ankle joints
Vasculitis and skin ulceration
Nail-fold and eyelid dilated capillaries
Retinitis in some
Myocarditis with arrhythmias can occur
Arthralgialarthritis with contractures
Essential Revision Notes in Bediatrics tbr the MRCPCH 2 r ~ Edition
I
Investigations
ESR - usually normal
Serum muscle enzymes (creatine kinase, lactate dehydrogenase) - elevated
Electromyogram - shows denervationlmyopathy
Muscle biopsy shows inflammation andlor fibre necrosis and small-vessel occlusive
vasculitis
ANA - positive in some
Management
Gentle physiotherapy and splinting, followed by more active physiotherapy as muscle
inflammation subsides
Corticosteroids in sufficient dosage to restore function and normalize enzymes
Cytotoxic drugs ciclosporin, methotrexate, azathioprine, cyclophosphamide, if required
Anti-TNF treatment
Careful monitoring is essential, with particular attention to palate and respiratory
function, as well as to possible gastrointestinal problems
Clinical features
General malaise
Weight loss
Arthralgia or arthritis
Myalgia and/or myositis
Fever
Mucocutaneous lesions:
Malar rash
Papular, vesicular or purpuric lesions
Vasculitic skin lesions
Alopecia
Oral ulcers
Photosensitivity
Renal disease common, even at onset
Pulmonary - pleuritis, interstitial infiltrations
Cardiac - pericarditis, myocarditis, Libman-Sacks endocarditis
CNS involvement - seizures, headache, psychosis
Cerebral dysfunction - blurred vision, chorea, transverse myelitis
Gastrointestinal involvement - hepatosplenomegaly, mesenteric arteritis, inflammatory
bowel disease
Eye - retinitis, episcleritis, rarely, iritis
Raynaud phenomenon, occasionally
Investigations
ESR - raised
Haemoglobin - low: autoimmune haemolytic anaemia in some; anaemia of chronic
disease
Leukopenia - mainly lymphopenia
Thrombocytopenia in some
IgM rheumatoid factor - may be positive
ANA - strongly positive
Antibodies to double-stranded (ds) DNA usually present in two-thirds
Total haemolytic complement and its components low
Anti-cardiolipin antibodies and lupus anticoagulant may be present
Management
Hydroxychloroquine for skin, joints, pulmonary involvement
Corticosteroids for systemically ill patients
Cytotoxic drugs for serious intractable disease
Antiplatelet drugs for thrombotic episodes
Rituximab for refractory renal, CNS and haematological disease
Essential Revision Notes in Paediatrics tor the MRCPCH 2ncl Edition
A person shall be said to have systemic lupus erythematosus i f any four or more of
11 criteria are present:
Clinical features
Rash - lesions of discoid lupus or subacute cutaneous lupus
Congenital heart block - occasional endocardial fibroelastosis
Thrombocytopenia
Hepatic or pulmonary disease, haemolytic anaemia - uncommon
Investigations
ANA - particularly RoILa
Thrombocytopenia, anaemia, leukopenia
Platelet antibodies - positive Coombs test
ECG
Course and prognosis
Cutaneous and haematological manifestations transient
Congenital heart block permanent
Hepatic fibrosis occasional
Some risk of systemic lupus erythematosus in teenage or adult years
Management
Symptomatic for transient manifestations
Heart block may require pacemaker
Clinical features
Oral ulcers
Genital ulcers
Severe uveitis - may lead to glaucoma and blindness
Arthritis
Rash - skin hypersensitivity
Bowel involvement
Meningoencephalitis, brainstem lesions and dementia
Treatment
Steroids, thalidomide, anti-TNF treatment are all effective
Scleroderma
Localized (majority of paediatric cases)
Morphea:
Single patch
Multiple patches
Linear:
Face, forehead and scalp (en coup de Sabre)
Limb (en bande)
Investigations
ESR - high
Haemoglobin - often low
White blood count - usually normal
Platelets - can be low
ANA - positive
i Anti-RNP antibodies in high titres indicate the designation of mixed connective tissue
I
1 disease
I Anti-DNA antibodies - negative or in low titre
I
IgM rheumatoid factor - occasionally positive
i
I
Rhetrrnatology
Management
Mild disease is managed with NSAlDs and/or antimalarials
More severe disease may require corticosteroids, with or without a cytotoxic agent
Careful monitoring is required to detect signs of potentially serious systemic disease (e.g.
nephritis)
4. CHILDHOOD VASCULITIS
Childhood vasculitis encompasses a wide range of clinical syndromes that are characterized
by inflammatory changes in the blood vessels. The clinical expression of the disease and its
severity depend on the type of pathological change, the site of involvement and the vessel
size. The two most common forms seen in children are Henoch-Schonlein purpura and
Kawasaki disease.
Clinical features
Petechiae
Rash - urticaria1 lesions evolving into purpuric macules, usually on the legs, feet and
buttocks
Cutaneous nodules - particularly over the elbows and knees
Localized areas of subcutaneous oedema that affect the forehead, spine, genitalia, hands
and feet
Arthritis - transient, involving large joints
Gastrointestinal involvement - colicky abdominal pain and/or gastrointestinal bleeding
Renal involvement - nephritis, occasionally nephrosis
Investigations
ESR - normal or high
Full blood count - normal
Haematuria and/or proteinuria and/or casts
IgA complexes in glomeruli and involved skin
E.
Management
Supportive care
Corticosteroids in severe disease
I
Investigations
ESR - high
Haemoglobin - lowered
White blood count - raised
Polymorph leukocytosis
Platelets - raised
ANA - negative
IgM rheumatoid factor - negative
Echocardiography - arteriograms
i
t Diagnostic criteria
L
Clinical features
As in diagnostic criteria, plus:
Irritability
Pericarditis
Valvular dysfunction
Coronary artery disease
Arthritis and/or arthralgia
Gastrointestinal symptoms
Urethritis
Central nervous system problems - aseptic meningitis
lritis
Management
Supportive care
Careful observation to detect and manage complications
Salicylate therapy
Intravenous gammaglobulin
Steroids are used
Clinical features
Fever
Abdominal pain
Arthralgia/myalgia
Rash:
Petechial or purpuric in the generalized form
Tender subcutaneous nodules and livedo reticularis in the cutaneous form
Hypertension
Renal involvement
Neurological disease
Essential Revision Notes in Pacdic7fr-irsfor the MRCPC'H 2nd Edition
Investigations
ESR - high
Haemoglobin - below 10 g/l
Leukocytosis
Urinary abnormalities
Anti-streptolysin-0 titre - elevated in some
Histology - focal necrosis in small- and medium-sized arteries
Management
Steroids - high dose (2 mg/kg per day) in the generalized form
Steroids and immunosuppressants for severe cases
Penicillin prophylaxis, if streptococcal aetiology is proved
Clinical features
* Claudication - in the arms and also the legs, and absent pulses
Myalgia
Hypertension
Malaise
Fever
Investigations
ESR - high
0 Haemoglobin - low
White blood count - neutrophil leukocytosis
Using a combination of Doppler ultrasound and angiography it is possible to show
occlusion, stenosis, or aneurysms
Management
Steroids with or without cytotoxic therapy
Reconstructive surgery when the disease is inactive
Clinical features
Lung involvement - asthma, transient pulmonary infiltrates
Rash - palpable purpuras and tender subcutaneous nodules
Peripheral neuropathy
Renal involvement - occasionally
Wegener granulomatosis
General characteristics
This also is a necrotizing granulomatous vasculitis of the upper and lower respiratory
tracts, accompanied by glomerulonephritis
Clinical features
Pulmonary granulomata
Destructive granulomata of the ears, nose and sinuses
Rash
Clomerulonephritis
Eye lesions
Special investigation
Antineutrophil cytosolic antibodies
Management
Combined therapy with steroids and cyclophosphamide
Biochemical abnormalities
Genetic andlor congenital anomalies
* Oddities do occur
5. MISCELLANEOUS DISORDERS
5.1 Osteogenesis imperfecta
Osteogenesis irnperfecta is a disorder of connective tissue characterized by bone fragility.
The disease encompasses a phenotypically and genetically heterogeneous group of inher-
ited disorders that result from mutations in the genes that encode for type 1 collagen. The
disorder is manifest in tissues in which the principal matrix is collagen, namely bone,
sclerae and ligaments. The musculoskeletal manifestations vary from perinatal lethal forms,
to moderate forms with deformity and a propensity to fracture to clinically silent forms with
subtle osteopenia and no deformity, as discussed below.
Osteogenesis imperfecta'type 1
This is characterized by osteoporosis and excessive bone fragility, distinctly blue sclera and
hearing loss. It has autosomal dominant inheritance, and occurs in 1 per 30,000 live births.
Fractures may be obvious from birth. Hearing impairment is the result of otosclerosis and
affects most patients from the 5th decade, but is rare in the 1st decade. Some families have
dentinogenesis imperfecta - with yellow transparent teeth which are fragile. There is
spontaneous improvement with puberty. X-rays show generalized osteopen.ia, evidence of
previous fractures and callus formation at the site of new bone formation. The skull X-ray
shows Wormian bones.
Management
For osteogenesis irnperfecta type I1 no therapeutic intervention is helpful. For other forms,
careful nursing of the newborn may prevent excessive fractures. Beyond the newborn
period, aggressive orthopaedic treatment is the mainstay of treatment aimed at prompt
splinting of fractures and correction of deformities. Genetic counselling is important.
Reliable prenatal diagnosis is not available for all forms of osteogenesis irnperfecta, although
severely affected fetuses may be confidently recognized by X-rays, ultrasound scanning and
biochemistry.
5.2 Osteopetrosis
Osteopetrosis (marble bone disease, Albers-Schonberg disease) is characterized by a
generalized increase in skeletal density. There are multiple types. The most important two
are listed below.
Osteopetrosis congenita
This presents in infancy (autosomal recessive) with faltering' growth, hypocalcaemia,
anaemia, thrornbocytopenia and, rarely, fractures. Bone encroaching on the marrow cavity
leads to extramedullary haemopoiesis. Optic atrophy and blindness 'are common, secondary
to bone pressure. Diagnosis is by skeletal survey. Bone marrow transplant can be curative.
Osteopetrosis tarda
This presents in later childhood, usually with fractures, and manifestations are less severe
and treatment is symptomatic.
5.3 Osteoporosis
This can be idiopathic
Most commonly secondary to corticosteroid use
Seen in conditions causing decreased mobility such as cerebral palsy, neuromuscular
diseases
Dual energy X-ray absorptiometry scan for bone mineral density
Can cause pathological fractures particularly of vertebrae
Treat with calcium/vitamin D and bisphosphonates
Essenti'?1 Revision Notes it? lDtlec/iC~trics
h r the MKCPCH ,IIIC/ EcIition
5.4 Hemihypertrophy
This is often difficult to recognize. It may involve the whole of one side of the body, or be
limited in extent, e.g. to just one leg. It may be congenital, in which case the tissues are
structurally and functionally normal. It has been associated with mental retardation,
ipsilateral paired internal organs and rarely with Wilms' tumours or adrenal carcinomas.
Hemihypertrophy can be confused with regional overgrowth secondary to neurofibromatosis
type I, haemangiomas and lymphangiomas.
6. FURTHER READING
Ansell BM, Rudge S, Schaller JG. 1991 . A Colour Atlas of Paediatric Rheumatology.
Aylesbury: Wolfe.
lsenberg DA, Miller JJ. 1999. Adolescent Rheumatology. London: Martin Dunitz.
Mier RJ, Brower TJ. 1994. Paediatric Orthopaedics. Dordrecht, Netherlands: Kluwer
Academic.
Cassidy JT, Petty RE. 2001 . Textbook of Pediatric Rheumatology, 4th edn. New York, NY,
USA: WB Saunders.
Chapter 23
Statistics
A ngie Wade
CONTENTS
1. Study design
1.1 Research questions
1.2 Confounding
1.3 Experimental studies
1.4 Crossover studies
1.5 Observational studies
2. Distributions
2.1 Types of data
2.2 Skewed distributions
2.3 Normal distribution
2.4 Standard deviation
3. Confidence intervals
3.1 Standard error (SE or SEM)
4. Significance tests
4.1 Null hypotheses and p-values
4.2 Significance, power and sample size
4.3 Parametric and non-parametric tests
6. Screening tests
7. Further reading
Statistics
STUDY DESIGN
1.1 Research questions
A research study should always be designed to answer a particular research question. The
question usually relates to a specific population. For example:
Does taking folic acid early in pregnancy prevent neural tube defects?
Is a new inhaled steroid better than current treatment for improving lung function
among cystic fibrosis patients?
Is low birth weight associated with hypertension in later life?
Random samples of the relevant populations are taken. For example: pregnant women,
cystic fibrosis patients, low-birth-weight and normal-birth-weight individuals.
Based on the differences found between the different groups of samples, inferences are
made about the populations from which they were randomly sampled. For example:
If the women in the sample taking folic acid have fewer neural tube defects'it may be
inferred that taking folic acid during pregnancy will reduce the incidence of neural tube
defects in the population
If, among our sample of cystic fibrosis patients, those taking steroids have better lung
function, on average, than those on current treatment, the inference might be that
steroids improve lung function among cystic fibrosis patients in general. Note that some
of the patients in the sample who were on current treatment may have had better lung
function than some of those using steroids, but it is the average difference that is
considered
If there is a difference in hypertensive rates between samples of individuals who were
and were not of low birth weight, it may be inferred that birth weight is associated with
later hypertension in the population in general
Some quantification of how the groups differ between the samples will be needed.
Dependent on the nature of the data, the averages, percentages or proportions may be
calculated for the samples taken. Prevalence or incidence of a disease or occurrence may
be of interest.
Prevalence is the number of cases within a defined population at a specified time,
incidence is the number of new cases arising in a given period in a specified population.
For example, diabetes has high prevalence but low incidence, whereas the common cold
has low prevalence and high incidence.
Essential Revision Notes in K~cdiatricsfor the MRCPCH 2nd Edjtir~n
For the research questions given above, the suitable summaries of the outcomes may be:
The risk of neural tube defect (number of cases divided by the number of women
studied) among women taking folic acid and those who do not. The relative risk (risk in
group taking folic acid divided by the risk in those that take placebo treatment) would
give a measure of how effective the intervention is in preventing neural tube defects
The difference in average lung function between those given the new steroid and those
given standard therapy will provide a measure of the effectiveness of the new treatment
compared to standard
The difference in percentages of subjects developing hypertension between those who
were low birth weight and normal birth weight (sometimes known as the attributable
risk reduction) would provide a useful summary measure
Statistical analysis enables us to determine what inferences can be made. Studies are either
experimental or observational.
1.2 Confounding
Confounding may be an important source of error. A confounding factor is a background
variable (i.e. something not of direct interest) that:
Is different between the groups being compared, and
Affects the outcome being studied
For example:
In a study to compare the effect of folic acid supplementation in early pregnancy on
neural tube defects, age will be a confounding factor if:
Either the folic acid or placebo group tends to consist of older-women, and
Older women are more, or less, likely to have a child with a neural tube defect
When studying the effects of a new inhaled steroid against standard therapy for cystic
fibrosis patients, disease severity will be a confounder if:
One of the groups (new steroidktandard therapy) consists of more severely affected
patients, and
Disease severity affects the outcome measure (lung function)
In the comparison of hypertension rates between low and not low birth weight, social
class will be a confounder if:
The low-birth-weight babies are more likely to have lower social class, and
Social class is associated with the risk of hypertension
If a difference is found between the groups (folic acidlplacebo, new steroidlstandard therapy
and lowlnormal birth weight) we will not know whether the differences are, respectively,
the results of folic acid or age, of the potency of the new steroid or the severity of disease in
the patient, or of birth weight or social class.
Confounding may be avoided by matching individuals in the groups according to potential
confounders. For example, we could age-match folic acid and placebo pairs or deliberately
recruit individuals of low and normal birth weight from similar social classes. We could find
Statistics
pairs of cystic fibrosis patients of similar disease severity and randomly allocate one of each
pair to receive the new steroid while the other receives standard therapy.
Case-control, cross-sectional and cohort are particular types of observational studies that,
respectively, consider features of the past, the present and the future to try and identify
differences between the groups.
If we take groups of individuals with and without hypertension with the aim of
identifying different features in their past that might explain a causal route for the
hypertension this is a case-control study
If we take groups of low- and normal-birth-weight babies and follow them forward in
time to see whether one group is more prone to hypertension then this is a cohort study
The relative risk (RR) can be used as a measure of effect in a cohort study. A similar
measure based on the odds (number of cases divided by the number of non-cases) rather
than risk (number of cases divided by the number studied, i.e. cases and non-cases) in each
group, known as the 'odds ratio' (OR), is appropriate for case-control studies.
2, DISTRIBUTIONS
2.1 Types of data
Data may be either categoric or numeric. If a variable is categoric then each individual lies
in one of several categories. Numeric data are measured on a number scale.
Ranks give the order of increasing magnitude of numeric variables. For example:
Sample of seven readings:
In order of magnitude:
Ranks:
Note that there are seven values in the sample and the largest value has rank 7. Where
there are ties (for example, the two values 1.3)) the ranks are averaged between the tied
values.
The mode is the value that occurs most often. In the example above:
The median is the middle value when the values are ranked. This is the 50th centile. In the
example above:
Median = 2.3
Statistics
Mode Mode
Median Median
Mean Mean
(a) Negative or downward or left skew; (b) positive or upward or right skew
In a sample of this type the mean is 'pulled towards' the values in the outlying tail of the
distribution and is unrepresentative of the bulk of the data.
Note that the skew is named according to the direction in which the tail points. In the left-
hand diagram (a), the tail points to the left, to negative values and downwards.
If the distribution i s skewed then the median is preferable as a summary of the data. For
example, the distribution of earnings is an upward skew, a relatively few high earners will
tend to raise the mean unrepresentatively. The median (50th centile) gives a more accurate
description of what most people earn - half will earn less than this-figure and half above it.
Normal distribution
Essentia/ Revision Notes in Paec/ic1tric-stor the M KCPCH 2nd Edition
3. CONFIDENCE INTERVALS
3.1 Standard error (SE or SEM)
The standard error is a measure of how precisely the sample mean approximates the
population mean. It is calculated by dividing the standard deviation by the square root of
the sample size.
The standard error is smaller for larger sample sizes (i.e. as the sample size increases, SEM
decreases). The more observations in the sample the more precisely the sample mean
estimates the population mean (i.e. the less the error).
Statistics
The more variable the outcome (as quantified via the standard deviation) the larger the
standard errors, implying less precision for a given sample size.
The SEM can be used to construct confidence intervals (CI).
The interval (mean f 1.96 SEM) is a 95% confidence interval for the population mean
The interval (mean k 2 SEM) is an approximate 95% confidence interval for the
population mean
The interval (mean f 1.64 SEM) is a 90% confidence interval for the population mean
There is a 5% (or 0.05 or 1 in 20) chance that the true mean lies outside the 95%
confidence interval. We are 95% confident that the true mean lies inside the interval.
There is a 1O0/0 (or 0.1, or 1 in 10) chance that the true mean lies outside the 90%
confidence interval. We are 90% confident that the true mean lies inside the interval.
Note the difference between the standard deviation and the standard error:
Standard deviation (SD) gives a measure of the spread of the data values
Standard error (SE) is a measure of how precisely the sample mean approximates the
population mean
For example, consider again the FEVl measurements from 100 students with mean 4.5 litres
and standard deviation 0.5 litres. The standard error is calculated by combining the standard
deviation and the sample size thus:
An approximate 95% confidence interval for the population mean FEVl is given by:
i.e. we are 95% confident that the population mean FEVl of students ties in the range 4.4-
4.6 litres.
Confidence intervals can similarly be constructed around other summary statistics, for
example the difference between two means, a single proportion or percentage, the
difference between two proportions. The standard error always gives a measure of the
precision of the sample estimate and is smaller for larger sample sizes.
4. SIGNIFICANCE TESTS
Statistical significance tests, or hypothesis tests, use the sample data to assess how likely
some specified null hypothesis is to be correct. The measure of 'how likelyt is given by a
probability known as the pvalue. Usually, the null hypothesis is that there is 'no differencet
between the groups.
Essentiaf Revision Notes if-,Paediatrics fbr the MRCPCH 2nd Edition -
On the basis of the study results, we may decide to disbelieve (or reject) the null hypothesis.
In reality, the null hypothesis either is or is not true. This gives the fourfold situation
illustrated below:
Null hypothesis:
An unpaired (or two-sample) t-test is used to compare the average values of two indepen-
dent groups (e.g. patients with and without disease, treated versus placebo, etc.).
Essential Revision Notes in Paed;atrics for the MRCPCH 2nd Edition
A paired (or one-sample) t-test is used if the members of the groups are paired. For example,
each individual with disease is matched with a healthy individual of the same age and sex;
in a crossover trial the measurements made on two treatments are paired within individuals.
Non-parametric tests are usually based on ranks (see Section 2.1). Examples are:
Wilcoxon
* Sign
Spearman's Rank Correlation
Mann-Whitney U
Chi-squared (x2)
The chi-squared test is used to compare proportions (or percentages) between two groups.
6 I
0 ! I I I
3
I
4
0 1 2
Age (years)
I
CD4 count versus age
If the units of measurement change then so will the regression equation. For example, if age
is measured in months rather than years then the value of the slope (the average change in
CD4 for a unit increase in age) will alter accordingly.
6. SCREENING TESTS
Screening tests are often used to identify individuals at risk of disease. Individuals who are
positive on screening may be investigated further to determine whether they actually have
the disease.
Some of those who are screen-positive will not have the disease
Some of those who have the disease may be missed by the screen (i.e. test-negative)
This gives a fourfold situation as shown in the box below (a, b, c and d are the numbers of
individuals who fall into each of the four categories).
Screening test
Positive (indicating possible disease) a
Negative
There are several summary measures that are often used to quantify how good a screening
test is:
Sensitivity is the proportion of true positives correctly identified by the test a I (a + c)
Specificity is the proportion of true negatives correctly identified by the test d 1 (b + d)
Positive predictive value is the proportion of those who test positive who actually have
the disease, i.e. a I (a + b)
Negative predictive value is the proportion of those who test negative who do not have
the disease, i.e. d I (c + d)
For all of these measures, larger values are associated with better screening tests. The values
are usually multiplied by 100 and presented as percentages. For example, if 75 out of 100
individuals with the disease test positive, the sensitivity is 751100 = 0.75, expressed as a
percentage this gives a sensitivity of 75O/0.
NB The positive and negative predictive values depend on the prevalence of the disease
and may vary from population to population. (Recall from Section 1.1 that prevalence is the
proportion of diseased among the total, i.e. (a + c) / (a + b + c + d))
Likelihood ratios
These compare the probability of the test result given that the individual has the disease to
the probability of the result occurring if they are disease free. They are calculated from the
sensitivity and specificity and are not dependent on disease prevalence.
sensitivity
The likelihood ratio (LR) for a positive test result LR + =
(1 - specificity)
1 - sensitivity
The likelihood ratio for a negative test result, LR - =
specificity
Example
A screening test is applied to patients with and without disease X. Of 100 who have the
disease, 60 test positive; of 200 without the disease, only 20 test positive.
The following table can be constructed:
The following can, therefore, be estimated from this sample of 300 individuals:
Sensitivity = 601100 = 0.6 or 60%
Specificity = 1801200 = 0.9 or 90%
-
LR + = 0.6/(1 0.9) = 6
LR - = (1 - 0.6)lO.g = 0.44
The positive predictive value is 60/(60 + 20) = 0.75 or 75% (i.e. 75% of those who test
positive actually have the disease in this sample)
The prevalence of the disease in this sample is ((60 + 40)1(100 -t: 200)) = 0.33 or 33%
If a particular patient had a prior odds of 1.5 of having the disease (meaning that he or she
is 1.5 times more likely to have the disease than not to have it) tlien 1.512.5 (or 6O0/0) of
patients of this type will have the disease). The posterior odds of the patient having the
disease will thus be determined by the result of the screening test:
If the test is positive (LR +) then the odds of having the disease will be 1.5 x 6 = 9
If the test is negative (LR -), the odds will be 1.5 x 0.44 = 0.66
Note that, as expected, the odds of having the disease rise if the test is positive and fall if
the test is negative.
A posterior odds of 9 means that the patient is nine times more likely to have the disease
than not which equates to a probability of 9110 or 0.9 (as opposed to 0.6 before testing).
A posterior odds of 0.66 equates to a probability of 0.6611.66, or 0.4 (as opposed to 0.6
before testing).
Essential Revision Notes in P;7edic?tric-sfor the MRCPCH 2nd Fdition
7. FURTHER READING
Bland M. 1987. An Introduction to Medical Research Oxford, Oxford Medical Publications,
Kirkwood BR. 1988. Essentials of Medical Statistics. Cambridge, Blackwell Scientific
Publications.
Altman DG. 1991. Practical Statistics for Medical Research. Chapman and Hall.
Armitage P, Berry G. 1987. Statistical Methods in Medical Research. Cambridge, Blackwell
Scientific Publications.
Chapter 24
Surgery
Merrill McHoney, Vivien McNamara and Robert Wheeler
CONTENTS
Neonatal Surgery
4. Intestinal atresia
4.1 Duodenal obstruction
4.2 Jejunoiieal atresia
4.3 Colonic atresia
4.4 Pyloric atresia
5. Malrotation
6. Meconium ileus
7. Hirschsprung disease
8. Anorectal malformations
8.1 Imperforate anus
9. Necrotizing enterocolitis
10. Biliary atresia
11. ~ n t k r i o rwall defects
1 1 . 1 Gastroschisis
11.2 Abdominal Compartment Syndrome
11.3 Exomphalos
Essential Revision Notes in Paedinfrics tor the MRCPCH 2170' Edition
Diagnosis
Antenatal scan - polyhydramnios, absent gastric bubble, distended upper oesophagus
(interrupted foetal swallowing)
After birth - excessive salivation, choking because of aspiration after every feed,
respiratory distress with or without cyanotic episodes. Other associated anomalies are
seen in 30-50%
Confirmation - failure to pass a large-bore (10 French scale) nasogastric tube (with
chest X-ray to demonstrate that the nasogastric tube is not coiled in the oesophagus)
+I- bronchoscopy at surgery to confirm location of lower pouch fistula and to exclude
upper pouch fistula and laryngeal cleft
Contrast swallow is not indicated (risk of aspiration)
Essential Revision Notes in Paediatrics f i r the MRCPCH 2nd Edition
2
Management
Stop feeds and aspirate upper pouch
Respiratory support as required - avoid bag and mask ventilation to reduce gastric
distension
Replogle tube - sited in the proximal pouch - double-lumen gastric tube (with side
holes) placed on low-pressure continuous suction preventing suction of the intestinal
mucosa against the tube. Larger lumen requires flushing with 1-2 ml saline to prevent
blockage with tenacious secretions
Antibiotics if evidence of pulmonary aspiration
Minimal handling - reduces air swallowing from crying
Echocardiogram - ideally before surgery, especially if infant is cyanotic, there is
significant cardiac murmur or infant requires cardiac support. May have duct-dependent
lesion requiring prostaglandin El infusion and early cardiac opinion. Repair the
oesophageal atresiahracheo-oesophageal fistula when stable
Renal ultrasound - if urine is passed, this can be delayed until after surgery
Spinal ultrasound - to exclude cord tethering (will be asymptomatic in the neonatal
period)
Karyotype - if infant is dysmorphic or has other system anomalies
Parental counselling
Emergency ligation of fistula - seen in the premature neonate with respiratory distress
syndrome
+ Common anatomy (OA + TOF) - right thoracotomy, ligation of the fistula and primary
end-to-end anastomosis of OA with early extubation. Trans-anastomotic tube passed for
feeding. A 'tightf anastomosis may require a period of paralysis and ventilation
+ Long-gap - may require complex and staged procedures
Complications
Anastomotic leak
Recurrent fistula
Stricture (at anastomosis)
Tracheomalacia
Gastro-oesophageal reflux
Abnormal oesophageal motility
Missed upper pouch fistula
Reflex bradycardia +I- respiratory arrest - vagal stimulation from a distending food
bolus
Chylothorax
Surgery
Outcome
a Overall survival is 85-95%
a Highest risk - birth weight < 1500 g, severe associated anomalies, major congenital
heart defect, ventilator dependency
Clinical presentation
May have clinical suspicion from antenatal ultrasound - proximal bowel dilatation,
'double bubble', echogenic bowel loops (meconium ileus), polyhydramnios
Most present shortly after birth with abdominal distension (delayed in distal obstruction),
large nasogastric aspirate (>50 ml initial volume), bilious vomiting, delayed passage of
meconium (>24 h)
Premature neonate - delayed passage of meconium expected, bilious nasogastric
aspirate may be the result of intestinal immaturity or sepsis
Passage of flatus will exclude an atresia
Common causes
Malrotation with volvulus
Duodenal atresia, stenosis, extrinsic compression
Jejunoilealatresia, or stenosis
Meconium ileus (simple, complicated)
Meconium plug syndrome
Hirschsprung disease
Ileus secondary to sepsis, paralysis/ventilation/medication
Inguinal hernia (incarcerated)
Anorectal malformation
Radiological diagnosis
Abdominal X-ray
Proximal obstruction - a few dilated loops, mainly in the upper abdomen
Distal - numerous throughout most of abdomen (paucity of rectal gas suggests
distal colonic or rectal obstruction)
Essentid Revision Notes in Paediatrics tilt-the MRCPCH 2nd Edition
Partial obstruction will allow some distal gas, often mixed with meconium
Inspect for peritoneal/scrotal calcification (meconium peritonitis/prenatal perforation)
Water-soluble lower gastrointestinal contrast - to distinguish distal bowel obstruction
(Hirschsprung disease, ileal atresia, meconium ileus/plug)
Water-soluble upper gastrointestinal contrast - to investigate intestinal rotation
abnormalities
General management
Nasogastric tube and gastric decompression
Replace nasogastric losses with 0.9% NaCl with KCI, ml for ml
Intravenous fluid replacement
Consider rectal decompression or washout after surgical consultation/review
Broad-spectrum antibiotics if there is suspicion of intestinal ischaemia (red/shiny/
oedematous abdominal wal I, abdominal tenderness, absent bowel sounds, metabolic
acidosis) or perforation
Megacystis-microcolon-intestinalhypoperistalsis syndrome
A rare, usually fatal, condition with degenerative smooth muscle changes in the bowel and
renal tract. Abdominal distension from lax abdominal muscles and a dilated bladder.
Incomplete intestinal rotation, microcolon (barium enema) with poor peristalsis. Ultrasound
demonstrates hydronephrosis and megacystis (differentiate from Hirschsprung disease).
4. INTESTINAL ATRESIA
Development of the intestine is completed by 10 weeks gestation,' foregut, midgut and
hindgut forming with their respective blood supplies (coeliac, s~periormesenteric and
inferior mesenteric arteries). Liver and pancreas arise from the developing duodenum.
Duodenal -failed vacuolization and recanalization of the developing duodenum
during weeks 8 to10 of gestation. Greater association with other major anomalies and
development anomalies of the pancreashiliary tree
Jejunoileal/colonic- follows a late intrauterine mesenteric vascular event with sterile
ischaemia of the bowel (resorbed). Associated with abdominal/mechanical abnormalities
(gastroschisis, mucoviscidosis in meconium ileus, with volvulus +/- cystic fibrosis,
volvulus secondary to malrotation)
Relative frequency -jejunal > duodenal > ileal > colonic > pyloric
More proximal atresia - earlier vomiting, less abdominal distension
Distal atresia - delayed presentation of vomiting, more abdominal distension, greater
fluid and electrolyte abnormality
Abdominal X-ray - number of dilated bowel loops suggests the approximate level of
atresia
A neonate with an intestinal atresia (as opposed to other causes of intestinal obstruction)
will fail to pass any flatus, even after rectal examination
Note: The presence of a few dilated bowel loops is suggestive of a proximal small bowel I
atresia. It may however represent an infant with little distal midgut following a major
intrauterine mesenteric vascular event which may be incompatible with life and only
1
!
identified at surgery. A
i
4.1 Duodenal obstruction
Incidence is 1 in 2500 live births
Intrinsic obstruction - atresia, stenosis, web
Extrinsic obstruction - annular pancreas, malrotation, pre-duodenal portal vein
50% are associated with other anomalies - cardiac, genitourinary, anorectal, OA +/-
TOF, malrotation, congenital diaphragmatic hernia, vertebral
30-40% are associated with trisomy 21
80% are periampullary (bilious vomiting), 20% pre-ampullary (non-bilious vomiting)
Prenatal diagnosis
Polyhydramnios in up to 75% '1 I
Intrauterine growth restriction, premature delivery in up to 50%
Dilated stomach and proximal duodenum ('double bubble') on antenatal ultrasound
Features suggesting trisomy 2 1 (nuchal translucency)
I
I
Post-natal diagnosis I
Index of suspicion - trisomy 21, oesophageal atresia
Vomiting - especially bilious, initial nasogastric aspirate > 20 ml with no other obvious
cause
Abdominal X-ray - 'double bubble'
Caution - suggestive 'double bubble' with some distal gas may be duodenal stenosis or
bifid biliary duct but must exclude malrotation +/- volvulus (see below).
Medical management
Nasogastric insertion for gastric decompression, intravenous volume replacement
Assess for other anomalies +/- karyotype if dysmorphic
Surgical care
Laparotomy - primary repair (duodenoduodenostomy +I- duodenal tapering)
Post-operative nasogastric replacement - initial aspirate volume may be high (100-
150 ml/day), until duodenal stasis is resolved. Replace ml for ml with 0.9% NaCl (with
added KCI)
Complications
Related to co-morbid pathology - cardiac, chromosomal
Prolonged bilious aspirates because of poor motility from delayed duodenal peristalsis
tor the MRCPCH 2nd Edition
Essenfi,l/ Revision Notes in t-??ec~icilric~
Post-natal presentation
Persistent bilious vomiting
Abdominal distension - most marked with distal atresia, visible bowel loops, fluid and
electrolyte disturbance
Meconium - varies from normal colour to grey plugs of mucus
Radiology
Dilated bowel loops - number of loops suggests level of atresia (proximal versus distal)
Note: In the neonate, large and small bowel are indistinguishable on X-ray because
of the poor development of the haustral folds and valvulae conniventes
Abdominal calcification - meconium peritonitis secondary to an intrauterine
perforation
Medical management
Nasogastric tube insertion for gastric decompression, volume replacement
Cardiorespiratory support as required
surgery
Laparotomy - assessment of bowel length and viability, identification of all atresias,
and other pathology, primary anastomosis (more than one may be required) +/-
proximal stoma
Complications
Anastomotic leak
Stricture formation
Nutritional - vitamin BI2and bile salt absorption affected from loss of terminal ileum
Short bowel syndrome - following catastrophic small bowel loss, the survival prognosis
depends partly on the presence of the ileocaecal valve (30 cm with, 50 cm without). The
premature neonate has a greater capacity for functional adaptation
Surgery
5. MALROTATION
Interference with the normal return of the fetal intestine into the abdominal cavity.
Present within the first week (55%), or by one month (80%) with only sporadic cases
thereafter
May exist with other abnormalities - exomphalos, gastroschisis, diaphragmatic hernia,
cardiac anomalies associated with visceral heterotaxy
Small bowel predominantly in the right abdomen
The narrow mesentery is prone to kinking, and in the event of a volvulus, the entire
midgut blood supply may be compromised, bowel infarction may occur in 6 h and that
gut will be lost
Radiology
Gas pattern on plain abdominal X-ray may be normal
Signs of proximal intestinal obstruction +/- asymmetric and/or sparse distal gas pattern
Failure of the duodenojejunal junction to cross the midline on upper gastrointestinal
contrast and lie to the left of the spine
'Corkscrew' sign if small bowel volvulus is present
Barium enema may show caecumlappendix in the right hypochondrium - an
unreliable sign alone as the normal neonatal colon is mobile
Caution - bilious vomiting mandates an urgent water-soluble upper gastrointestinal
contrast study at any time of the day/night (even if the infant is well, without abdominal
distension or tenderness, with a 'normal' plain abdominal X-ray and with normal
biochemistry/haematology profiles). Clinical deterioration with abdominal tenderness,
cardiorespiratory collapse, metabolic and lactic acidosis, upper/lower gastronitestinal
bleeding is a late sign of compromised bowel and impending death. This is a life-
threatening emergency.
Surgery
Adequate resuscitation
Nasogastric decompression, fluid, broad-spectrum antibiotics
Essential Revision Notes it1 R?edi;7tric-stor the MMKCPCH 2nd Ecfiticm
6. MECONIUM ILEUS
Incidence of 1 in 1000 to 2000 live births
80-90% will have cystic fibrosis but only 15% of infants with cystic fibrosis will present
with meconium ileus
Thick mucus and viscid meconium, lower lactase/sucrase levels, more albumin and less
pancreatic enzyme
Obstruction of the distended meconium-filled terminal ileum. Small, unused colon,
inspissated pellets of colourless mucus
Complications occur in 5Ooh - antenatal volvulus of the distended ileum with atresia,
meconium peritonitis or pseudocyst formation
Antenatal perforation is sterile, post-natal perforation is complicated by bacterial
contamination and systemic sepsis
Diagnosis
Uncomplicated - abdominal distension, bilious vomiting, failure to pass meconium,
'doughy' mass on palpation within 24-48 h of birth
Complicated - abdominal wall erythema, oedema, meconium staining - suggests
prenatal perforation
Cystic fibrosis screen
Simple - proximal bowel dilatation, few air-filled loops, meconium mottling ('soap
bubble', 'ground glass') often in the right lower quadrant
Complicated - calcification (extravasation of meconium into the peritoneal cavity),
massive bowel dilatation (atresia), displaced bowel loops (pseudocyst), ascites
Water-soluble contrast enema - barium is contraindicated in case of existing
perforation
Alternative - N-acetylcysteine (Mucomyst) by nasogastric tube or per rectum (breaks
down disulphide bridges in tenacious meconium)
Caution - gastrograffin is hyperosmolar and draws fluid into the terminal ileum from the
intravascular space, softening the meconium. Adequate fluid resuscitation is vital before
and during use to prevent potentially catastrophic cardiovascular collapse.
Complications
With cystic fibrosis, 1-year survival is 75-90%
Late complications - distal intestinal obstruction syndrome (1O0/0), appendicitis (5°/0),
intussusception (2%), rectal prolapse (10-30%)
7. HIRSCHSPRUNG DISEASE
Absence of ganglion cells in the myenteric plexus of the most distal bowel; male incidence
greater than female. Occurs in 1 in 5000 births.
Gene on chromosome 10, RET proto-oncogene
Long-segment Hirschsprung disease is familial (4-7%) with equal sex incidence
Associated with trisomy 21 (5-1 5% reports vary between 2-1 5% have Downs), high
frequency of other congenital abnormalities, including multiple endocrine neoplasia
Transition zone in the rectosigmoid junction is most common (> 75%)
Total colonic/small bowel involvement (5-1 0%) - poor prognosis
Presentation
Usually presents in infancy - poor feeding, abdominal distension, delayed passage of
meconium, bilious vomiting
Radiological evidence of distal intestinal obstruction with absence of rectal gas
Explosive decompression following rectal examination of gas excludes atresia)
First presentation may be with acute enterocolitis (red, tender, shiny abdomen) +/-
severe systemic collapse. Diarrhoea is offensive +I - or ischaemic mucosa. May
blood
require emergency defunctioning colostomy
Enterocolotis can occur pre- or post-surgery, associated with Clostridium diffcile
enterotoxin
Initial management
Nil-by-mouth, intravenous fluids, correction of electrolyte abnormalities, high colonic
washouts to decompress the bowel (feeding tube, not balloon catheter)
Fluid resuscitation + broad-spectrum antibiotics if presenting with enterocolitis
Poor result - usually technical but may suggest long segment disease
Diagnosis
Contrast enema - identify transition zone, exclude other pathology
Definitive test is suction rectal biopsy for histology
Essential Revision Notes in Paediatrics for the MRCPCH 2nd Edition
2
Surgery
Duhamel pull-through - excision of the involved colon, anastomosis with innervated
proximal bowel (propulsion), small part of involved rectum remains (sensation and
sphincter innervation). Other options are available
Still have risk of enterocolitis following surgery (treated as above)
Outcome
lncidence of from enterocolitis: 5-25%, increased in trisomy 21 (29-54O/0), associated
cardiac defects, total colonic involvement (15-25%). Overall mortality from
enterocolitis: 5-2 5%
Surgical management for anastomotic leak, pelvic abscess, intestinal obstruction
Medical management of soiling, constipation, frequent loose stools
8. ANORECTAL MALFORMATIONS
8.1 Imperforate anus
lncidence of 1 in 4000 to 5000 live births
Association with maternal diabetes
Male (60%) - most commonly imperforate anus with rectourethral fistula
Female (40%) - most commonly imperforate anus with rectovestibular fistula
Imperforate anus without a fistula is uncommon (5%)
Associated defects are common
Presentation
Clinical examination
Failure to pass meconium, abdominal distension, bilious vomiting (late sign)
Passage of meconium or bubbles per urethralvagina or meconium staining beneath
perineal skin
Neuropathic bladder if anorectal malformation is not suspected
Following identification of other VACTERL anomalies (vertebral, anal, cardiac, tracheal,
oeophageal, renal and limb)
Initial management
Nil-by-mouth, intravenous, nasogastric decompression (passage of tube will exclude
OA/TOF).
Systematic examination, chest/abdomen/sacral X-ray, echocardiogram, renal ultrasound,
spinal ultrasound (exclude cord tethering), +/- karyotype
Prophylactic antibiotics until communication with renal tract is excluded (trimethoprim)
Invertogram to assess level of rectal atresia (lateral shoot through, infant prone over a
foam wedge, buttock elevated with a radio-opaque marker at the anal position). Thick
meconium within distal bowel or straining (crying) will provide inaccurate results
Surgery
Sigmoid loop colostomy usually within 48 h
Distal loopagram and micturating cystourethrogram to identify anatomy of rectum and
communication with urinary tract (position of fistula) +I- vesicoureteric reflux
Posterior sagittal anorectoplasty most commonly indicated
Various surgical options - may require complex staged procedures, urogenital surgery,
dilatation of new anus, medical management of bowel control (including enema)
Aim for colostomy closure. May be refashioned for protracted soiling (patient request)
Outcome
Dependent on level of lesion, sacral development (S3, 4 and 5 required for urinary
continence) and associated anomalies
Low lesion - constipation (4O0/0), soiling (1 5%), diarrhoea (5%)
High lesion - constipation (35%), soiling (5S0/0), diarrhoea (12%)
9. NECROTIZING ENTEROCOLITIS
Pathological response of the immature gastrointestinal tract to perinatal or post-natal injury.
Usually seen in the first 2-3 weeks of life. Rapid and early introduction of non-breast-milk
feeds, hyperosmolar feeds and bacterial infection are important aetiological factors. Progres-
sive intestinal mucosal ischaemia, most commonly affecting the caecum, ascending colon
and terminal ileum but can affect the entire intestinal tract.
Risk factors
Prematurity
Intrauterine growth restriction
Antepartum haemorrhage
Perinatal asphyxia (absent or reversed end-diastolic umbilical wave from)
Respiratory distress syndrome
Umbilical artery catheterization
Polycythaemia
Patent ductus arteriosus
Premature rupture of membranes
Sepsis
a Upper abdominal lucency, especially over the liver (anteroposterior supine film, vertical
beam projection)
Medical management
Neonatal intensive care unit-continuous positive airway pressure is avoided in cases of
pneumatosis and/or perforation
Stop enteral feeds for 7-1 4 days (depending on severity of illness)
Intravenous antibiotics (broad-spectrum, including metronidazole; consult local unit
policy)
Adequate intravenous analgesia
Total parenteral nutrition
Nasogastric tube, on free drainage with hourly aspiration and volume replacement
Remove umbilical lines
Regular abdominal X-rays to exclude perforation or the development of a fixed loop
Consideration of contrast studies - assessment of possible strictures (intolerance of
increasing feed volume, intestinal obstruction, or recurrent bacterial translocation
following clinical recovery)
Complications
Recurrence (10% of cases consider Hirschsprung disease)
Perforation in 20-30%
Overwhelming sepsis
Disseminated intravascular coagulation
Stricture formation - up to 20%
Short-bowel syndrome (following extensive surgical resection)
Laaulose intolerance - > 0.5% faecal reducing substances significant
Surgical management
Indications - pneumoperitoneum, failure of maximal medical management, stricture
formation, fixed loop +/- palpable mass
Insertion of a peritoneal drain - may be life-saving for a tense pneumoperitoneum
compromising ventilation
Laparotomy - allows diagnosis to be confirmed, extent of disease to be assessed and
peritoneal toilet to be performed and abscess cavities drained
Localized resection with primary anastomosis
Proximal diversion stoma +/- bowel resection
Stoma formation - ileostomy or colostomy depending on extent/location of necrotizing
enterocolitis
May require more than one procedure, including stoma closure and stricture resection
Investigations
Liver function tests (often normal enzymes with conjugated hyperbilirubinaemia),
clotting
Ultrasound (may be normal, gall bladder may be absent)
Radionuclide Tc-99m iminodiacetic acid ( 9 9 ~ DA) c - ~scan (unimpaired hepatic uptake
of isotope but failure of excretion into the duodenum after 24 h)
Liver biopsy
Laparotomy - operative cholangiography.
Treatment
Hepatoportoenterostomy (Kasai procedure)
Aim for surgery before the infant is 60 days old
Ursodeoxycholic acid to promote bile secretion, fat-soluble vitamin supplementation
Post-operatively - high risk of cholecystitis (prompt treatment with intravenous
antibiotics)
Fat malabsorption, cirrhosis, liver failure
Liver transplantation may be indicated
Caroli's disease
Autosomal recessive, congenital cystic dilatation of the intrahepatic ducts
Recurrent acute cholangitis, biliary lithiasis, risk of cholangiocarcinoma
, Herniation of bowel without a covering sac, stomach, occasionally bladder, but never
I the liver
Intestinal atresia is common, occurring in approximately 20% of cases. Short bowel may
complicate outcome
Rarely associated with lethal chromosomal or major structural abnormalities
Can be confused with a ruptured exomphalos
Management at delivery
Wrap cling-film around entire trunk, covering exposed bowel and ensure infant is well
supported in the midline to reduce temperature and fluid evaporative losses
Large-bore nasogastric tube, intravenous fluids above normal rate
Regular visual assessment of bowel viability if closure is delayed, and during neonatal
transfer
Surgical management
Undertaken promptly after delivery. May require staged surgical repair
Total parenteral nutrition and trophic milk via nasogastric tube
Delay in establishing feeds is related to poor intestinal motility - bilious NG aspirates,
abdominal distension, failure to pass changed stool
Repair of atresia is present when possible
Outcome
Morbidity is related to short bowel
10% risk of necrotizing enterocolitis
Prognosis is usually good
11.3 Exomphalos
Failure of closure of the abdomen at the umbilical ring
Incidence is 1 in 5000 to 1 in 10,000 live births, trend is decreasing (partly related to
termination of pregnancy following identification of other lethal structural or
chromosomal abnormalities)
40-70% have associated abnormalities - chromosomal (trisomies 13, 18 and 21),
cardiac (25%), genitourinary, gastrointestinal, craniofacial, pulmonary hypoplasia
Syndromic associations - Beckwith-Wiedemann, prune belly syndrome and pentalogy
of Cantrell
Antenatal karyotype analysis should be advocated, along with a more detailed anomaly
Surgery
scan. Parental counselling in cases with severe associated abnormalities may include
elective termination
Management at delivery
Leave cord length long
Cover exomphalos with cling-film, as per gastroschisis (reduce temperaturelfluid
evaporative loss)
Support contents in the midline (vertically tie the umbilical cord to the overhead heater
or incubator)
Assess bowel colour through sac (initially transparent), look for blood (hepatic trauma),
avoid sac rupture
Nasogastric decompression, intravenous fluid/electrolyte resuscitation, temperature as
per gastroschisis
Clinical assessment - dysmorphic features (especially midline defects), karyotype, chest
X-ray, echocardiacogram, renal ultrasound
Early and regular blood glucose measurements (Beckwith-Wiedemann syndrome)
Early surgical involvement
Surgery
Aim for reduction of abdominal contents and complete closure
May require staged procedures
Massive exomphalos (especially with small abdominal cavity) or infants with multiple
abnormalities may be managed conservatively. Topical application of saline, to allow
eschar formation and skin overgrowth. Delayed surgical management of massive ventral
hernia some years later
Meticulous fluid management
Outcome
Associated defects or chromosomal abnormalities have a major influence on survival
3S0/0 mortality, three times that of gastroschisis
Poor prognostic factors - gestational age < 25 weeks at diagnosis, structural cardiac
abnormality, chromosomal abnormality, polyhydramnios, contralateral lung-to-thoracic
transverse area ratio < 0.5, contralateral lung-to-head circumference ratio < 0.62, left
ventricular hypoplasia
Pentalogy of Cantrell
A rare defect resulting from a severe mesodermal fusion failure
Comprises - diaphragmatic hernia (retrosternal defect), lower sternal defect, pericardial
defect, major cardiac anomaly and epigastric exomphalos
Differential diagnosis
Congenital cystic adenomatoid malformation
Lung sequestration
Cystic lesions (bronchogenic, thymic, neuroenteric, duplication)
Diaphragm eventration
Post-natal diagnosis
Absence of visible diaphragm
Bowel loops seen in the chest
Tip of nasogastric tube in the chest (only if stomach herniated)
Absence of bowel loops within abdomen
Contralateral mediastinal shift
Small contralateral lung
Resuscitation at birth
Avoid bag and mask positive-pressure ventilation (minimize visceral distension)
Prompt endotracheal intubation in the delivery room for respiratory distress
Replogle or wide-bore nasogastric tube insertion (will need to be passed beyond the
usual distance)
Chest X-ray to confirm diagnosis, nasogastric tube position and exclude other diagnoses
(congenital cystic adenomatoid malformation, pulmonary sequestration)
Medical management
Minimal stimulation with consideration of paralysis
Abnormal pulmonary vascular reactivity produces reduced lung perfusion, pulmonary
hypertension, right-to-left shunting through the foramen ovale, ductus arteriosus and
intrapulmonary vessels
Surfactant used in some centres
Maintain preductal oxygen saturations at 85-90%
Minimal ventilation pressures to reduce barotrauma. Iatrogenic injury from ventilation
strategies may be significant and should be minimized
Volume resuscitation and vasopressors (dopamine and dobutamine) often required
Pulmonary vasodilatation with inhaled nitric oxide
Surgery
Surgical management
Stabilization with medical treatment takes priority
Operative repair includes reduction of the herniated viscera into the abdominal cavity
Closure of the diaphragmatic defect: direct suture +I- a prosthetic patch
Diaphragm agenesis may require more extensive surgical intervention
Complications
Continued medical management of pulmonary hypoplasia
Thoracic wall deformities with growth
Detachment of prosthetic patch: may require further surgery
Macroglossia
Localized - haemangioma, lymphangioma
Generalized - hypothyroidism, Beckwith-Wiedemann syndrome (check blood glucose)
May require surgical reduction
Presentation
Some diagnosed antenatally on ultrasound
Usually within a few hours of birth (50%) with severe respiratory distress
Chest asymmetry, hyperresonant
May be asymptomatic at birth, with symptoms by 6 months
Radiology
Left upper lobe (42%), right upper lobe (21°/0), right mid-lobe (35%),rare in lower lobes
Hyperlucent overexpanded lung
Herniation of emphysematous segmenthng across midline (anterior to mediastinum)
Mediastinal shift
Compression/atelectasis of adjacent lung/lobes
Depression of ipsilateral diaphragm
Ventilation-perfusion scan may confirm absent perfusion/ventilation in severe cases
Management
Mild cases - conservative, regular review with chest X-ray
Echocardiogram
Most require lobectomy - may be required urgently for life-threatening respiratory
insufficiency. Emphysematous lobe may bulge out of the operative field
Follow-up
After lobectomy, no significant functional impairment
Asymptomatic overdistended lobes do not impair development of normal lung
Radiology
Chest and abdominal X-ray will help to distinguish between a congenital cystic
adenomatoid malformation and diaphragmatic hernia (demonstrate normal intestinal gas
pattern in the former but not the latter)
Early plain films may be radio-opaque (delayed clearance of lung fluid)
Air-filled cystic spaces, adjacent lung compression, subtle changes (appear normal)
Computed tomography (CT) scan - precise anatomical location and extent of disease
(see below)
Management
Most will be sufficiently stable for complete pre-operative assessment (X-rays and CT)
Symptomatic - elective lobectomy
Asymptomatic - controversial
Radiology
Require CT or magnetic resonance imaging (MRI) to identifyllocate abnormal arterial
supply
Essential Revision Notes in Pacdiafric-s t i ~ fr1 - r ~MRCPCH 2nd Eclition
Management
* Thoracotomy and resection, taking care with identification of blood supply (which is
often large)
Surgery advocated for risk - infection, malignancy
Outcome is related to associated anomalies
14.1 Teratoma
Embryonal neoplasm derived from the germ layers (ectoderm, mesoderm, endoderm)
Most common in paraxial or midline location - sacrococcygeal (45 -64%), mediastinal
(10°/~), gonadal (10-35%), retroperitoneal (5%), cervical (5%), presaual (5%
Solid, cystic or mixed
80% benign, 20% malignant
Diagnosis
Antenatal - ultrasound imaging, elevated serum a-fetoproteinlhuman P-chorionic
gonadotrophin (see below)
Poor prognosis - polyhydramnios, placentomegaly, gestational age < 30 weeks
Late presentation - features of urinary or intestinal obstruction, lower limb neurology or
ma1ignancy
Imaging - plain X-ray, MRI, CT
Surgery
a-fetoprotein
Normally produced by the fetal liver, also by yolk sac tumour elements. Plot serum levels
against a nomogram (levels fall rapidly following birth). Levels should fall to normal
following successful resection. Elevated levels may suggest malignancy. Rising levels
indicate recurrence.
Complications
Placentomegaly
Hydrops
Cardiac failure
Malpresentation, premature rupture of membranes, cord prolapse, placental abruption,
shoulder dystocia
Massive bleeding
Surgery
Resection (<2 months at latest) - may require combined abdominal and perineal
approach. Technically difficult. Requires excision of coccyx
Follow-up with 3-monthly tumour markers, clinical assessment (PR (rectal examination))
+I-further imaging
Greatest risk of malignant change - surgery after 2 months, incompleie excision,
immature elements on histology
Less severe defects may not be apparent at birth, cutaneous stigmata (pigmentation
anomalies, excess hair, lipoma, dermal sinus)
Obvious open lesion - skin defect, cord may be protected by pia arachnoid, or there
may be an open neural tube defect (exposed neural plate)
Many are associated with central nervous system abnormalities (hydrocephalus)
Essential Re\,/ision Notes in Paec/i,~trics ihr the kIKCYCH 2 1 7 ~ I Eclition
'
Assessment
Level of lesion (cervical, thoracic, lumbar, sacral - most will be lumbosacral), and size
Neurological deficit - motor and sensory level, spontaneous limb movement, posture.
Always begin sensory assessment from 'abnormal to normal' area
Bladderlbowel function - appearance and sensation of perineum; rectal prolapse,
absent natal cleft (paralysis of pelvic floorlsphincters)
Hydrocephalus - bulging anterior fontanelle, persistent metopic suture, suture diastasis,
setting-sun eyes, frontal bossing, enlarging head circumference (crossing percentile
curves), +I -
Arnold-Chiari malformation (see below)
Orthopaedic deformities - spine (kyphoscoliosis), hips (congenital dislocation), feet
(talipes)
Other abnormalities - sacral agenesis (partial/complete), cord tethering, renal tract
anomalies (hypospadias, horseshoe kidney, exstrophy), congenital heart disease,
anorectal malformation, craniofacial anomalies
Neurology level
13 - legs totally paralysed
14/15 - flexed hip, extended knee, no other movement
S1 - movement of the hip and knee, foot can dorsiflex but not plantarflex
S2IS3 - normal leg movements, still doubly incontinent
Immediate management
Prone positioning (with attention to prevent faecal soiling of exposed neural tissue)
Cover exposed neural tissue with cling-film (wrapped around trunk)
Broad-spectrum antibiotics
Intermittent urinary catheterization
Surserv
Formal closure of defect with reconstruction of anatomical layers
Ventricular shunt for hydrocephalus
Delayed orthopaedic procedures may be required
Clean intermittent catheterization +I -
bladder augmentation procedures
Outcome
Poor prognosis with severe hydrocephalus, severe kyphosis, thoracolumbar lesions, asso-
ciated malformations, poor social support
Meningitis and ventriculitis (10-1 5%) requires prompt treatment
Hydrocephalus - thoracolumbar lesion (95%), lumbosacral (60%)
Ambulation - dependent on level of lesion, orthopaedic abnormalities, intellect.
Thoracic and lumbar (few achieve independence), sacral (most), lumbosacral (many can
walk with calipers but may choose a wheelchair for ease)
Lumbosacral: with clean intermittent catheterization, nearly 90% remain continent
Intellectual development: dependent on level, up to 40% have IQ impairment
16. MISCELLANEOUS CONDITIONS
6 Antenatal torsion
Presentation
Non-tender, discoloured scrotal swelling, usually unilateral
Differential diagnosis - hydrocoele, traumatic haematoma (breech delivery),
incarcerated inguinal hernia (associated with a thickened cord), lesion secondary to
patent processus vaginalis (meconium, intraperitoneal bleeding) infection, gonadal
neoplasm
Investigations
Abdominal X-ray may be helpful - identification of scrotal contents via patent
processus vaginalis (air within a herniated bowel loop), meconium (antenatal intestinal
perforation)
Ultrasound - distinguish solid from cystic masses. Useful if concerned about a possible
tumour
Management
Testis is considered non-viable at the time of presentation
Most will not remove ischaemic testis but will elect for early fixation of the contralateral
side
4
3s
General Paediatric Surgery
17. MEAD AND NECK SURGERY
1 Ranula
A mucous retention cyst of the sublingual salivary gland caused by partial obstruction of
the duct
Presents clinically as soft, occasionally tense, clear swelling on the floor of the mouth
Can increase in size after first appearing
Usually symptomless, although they can be painful
Treatment consists of marsupialization of the cyst by incising the cyst wall and suturing
the edges open; thereby draining the obstructed gland. Only very occasionally is
excision required
Neck
Axilla
Chest
Abdomina
Can be identified antenatally
Present clinically as a brilliantly trans-illuminable multi-cystic swelling
Usually soft
If infected they can become tense, red and painful; occasionally progressing to abscess
formation
Can also cause symptoms by exerting pressure on adjacent structures (e.g. dysphagia,
stridor, respiratory compromise)
Surgery
Differential diagnosis
Includes haemangiomas, lipomas, dermoid cysts and mixed lesions. Lymphangiomas are
rarely of a 'pure' pathology; commonly they are combined with vascular or fatty
elements
Ultrasound used to confirm the diagnosis and assist with identification of macrocystic
and microcystic varieties
Occasionally CT scan is required to define extent large lesion and anatomic
relationships
Treatment options
Conservative management has become the aim - commonly after initial presentation
and increase in size these lesions undergo involution; this is also common after infection
Sclerotherapy - the most common agent is OK-432, which is a streptococcus-derived
antigen. It is more successful in predominantly macrocystic lesions. Causes an acute
inflammatory reaction (with acute swelling and symptoms) that causes involution but
may have an adverse, temporary effect on contiguous structures (e.g. stridor).
Surgical excision is occasionally required for larger lesions or those that do not respond
to other modalities of treatment.
Thyroglossal cyst
Thyroid gland develops as a diverticulum at the foramen caecum and descends to its
cervical location in fetal life. Path is marked by the thyroglossal tract. Persistence of part
or the entire tract leads to thyroglossal duct and cyst
Presents as a midline swelling between the tongue and infra-hyoid region. Moves with
swallowing and protrusion of the tongue, although this sign is relatively insensitive
Ultrasound is indicated to identify a normal thyroid gland, and to confirm the diagnosis
Surgical excision includes excision of the cyst, along with the tract (and central portion
of the hyoid bone), all the way to the base of the tongue
Investigations
Usually include an ultrasound to confirm the diagnosis and extent of the lesion
MRI or CT scans may be required for lesions in some sites
Angiography may assist in the anatomical definition of arteriovenous malformations
Treatment
Conservative management - sufficient for most haemangiomas as they resolve,
arteriovenous malformations that cause no symptoms can be treated conservatively
Compression therapy - can be used for accessible lesions and may accelerate
involution of haemangiomas
Sclerotherapy - used for symptomatic lesions; multiple treatments may be required
Interferon-a - shown by some series to be of benefit in haemangiomas that are resistant
to other modalities of treatment. Treatment is required over a few months
Surgical excision - used for lesions that give rise to complications and do not respond
to conservative or other modalities of treatment
Laser therapy - used for some superficial lesions that are disfiguring
Embolization - used in cases in which a large feeding vessel can be identified and
accessed. Particularly useful in cases with cardiac failure
Poland's syndrome
Unknown aetiology
Characterized by hypoplasia or aplasia of the pectoralis major muscle and one or more
of the following: hypoplasia or aplasia of the breast or nipple, aplasia of ribs, or
syndactylyhradydactyly
Sternal clefts
Occur in isolation or associated with other syndromes, the most common being
Cantrell's pentalogy (sternal cleft, omphalocele, pericardial and cardiac defects, and
diaphragmatic hernia)
Supraumbilicalhernia
Less common than umbilical hernia
Defect is sited above the cicatrix, therefore elliptical and points downwards
Do not resolve and therefore require operative closure
Epigastric hernia
Present as intermittent swellings usually midway between the umbilicus and the
xiphisternum
Although present from birth, usually present in school-age children, often with
symptoms of abdominal pain (sometimes caused by strangulation of fat in the defect)
The defect is often difficult to define
Surgical correction is advised
Inguinal hernia
A congenital abnormality caused by persistence of the patent processus vaginalis, a
peritoneal tube along the path of testicular descent into the scrotum
Surgery
Incidence in general population is 1-2%; ten times more common in boys and in
premature infants
Rare association of inguinal hernia in girls with complete androgen insensitivity
syndrome; girls presenting with inguinal hernia should have their chromosomes checked
Present as intermittent swellings in groin which may reach the scrotum
Irreducibility for prolonged periods can lead to obstruction (abdominal pain, distension
. and vomiting) and eventually strangulation (hard, tender swelling)
Elective repair advised
Patients who present with an irreducible hernia require hernia reduction and delayed
repair after the resultant oedema has settled, this generally involves a 24- to 48-h
hospitalization and repair before discharge
Repair consists of reduction of the contents of the hernia, and ligation of the patent
processus through a groin incision
' Hydroceles
Identical to inguinal hernia in aetiology
Usually present as symptomless fluid-filled swellings of the scrotum that are
transilluminable, and are variably reducible
Occasionally present as tense swellings during an acute illness
Unusual variety is a hydrocele confined to a portion of the cord only (encysted
hydrocele)
Most hydroceles (unlike hernias) resolve without surgery in the first few years of life.
Surgery is indicated if they fail to resolve
19.3 Intussusception
Telescoping of one part of the intestine into the other
Peak incidence between 4 months and 1 year
Most cases are 'idiopathic' ileocolic intussusception; enlarged Peyer's patches are
believed to be causative in most of these cases
In 5-1 0% there is a pathological lead point - Meckel's diverticulum, duplication cyst,
polyp, haemangioma, or a bleeding point in Henoch-Schonlein purpura; may present
with recurrent intussusception
Classical triad of symptoms (but not present in all patients):
Abdominal pain (and drawing up of legs)
Bleeding per rectum (red currant jelly stools)
Palpable mass
Vomiting, constipation or diarrhoea may be present and may predate the occurrence of
intussusception
Complete obstruction may be present; but is usually late in the presentation
Patients can present in extremis, with signs of shock and sepsis
Management - careful attention to primary resuscitation and fluid management
Children can need up to 40 ml/kg fluid resuscitation
Triple antibiotics should be started when the diagnosis is suspected
Nasogastric decompression required if there are signs of obstruction
Ultrasound scan confirms diagnosis, with the appearance of the typical target lesion of
the telescoping bowel
Doppler assessment can identify blood flow, or lack of it, in the bowel wall
Plain abdominal X-ray may reveal signs of obstruction and a soft tissue mass may be
seen
Air enema under radiological control used to reduce the intussusception - with a
success rate of around 85%; contraindicated if there are signs of perforation
Laparotomy indicated for signs of peritonitis, perforation or a failed air enema
19.4 Appendicitis
Acute appendicitis is one of the most common paediatric surgical emergencies
Incidence increases with increasing age, but sometimes seen in children as young as 2
Presentation in the younger child can be atypical and the diagnosis difficult
Typical history is of colicky central abdominal pain shifting to right iliac fossa, followed
by vomiting that is usually non-bilious
Characterized by low-grade fever and mild tachycardia; may be fetor
Localized tenderness in the right iliac fossa; localized percussion tenderness may also
be present
Advanced cases may be septic, with hypovolaemia and marked fever
May be overt peritonitis to suggest perforation
History in atypical cases may mimic urinary tract infection, with dysuria, frequency and
fever
Diarrhoea may be the prominent symptom, especially with a pelvic appendix
Differential diagnoses
Urinary tract infection
Gastroenteritis
Mesenteric adenitis
Pancreatitis
Meckel's diverticulitis
Viral illness
Respiratpry tract infection
Diabetic ketoacidosis
Investigations
Urinalysis to rule out urinary tract infection - urgent microscopy if urinalysis is positive,
as a pelvic appendix can give rise to white cells in the urine
In obvious cases no investigation required. Raised white blood cells and elevated C-
reactive protein are often present, but are not specific
Ultrasound scan can confirm the diagnosis in some cases that are not clear cut. The
typical finding is a dilated, non-compressible appendix. There may be some free fluid in
the right iliac fossa. However, a negative ultrasound does not rule out appendicitis
Repeated examination and careful observation are the most useful tools in doubtful
cases
Management
Appendicectomy should be performed as soon as possible - by traditional right iliac
fossa incision or laparoscopically
One dose of preoperative antibiotics is given; the postoperative antibiotic regimen will
be dictated by the operative findings
Essential Revision Notes in Pnediatrics for the MRCPCH 2nd Eclition
.
Investigations
Urinalysis and/or midstream urine should be performed to rule out infection
Ultrasound Doppler of the testis is sometimes entertained, but is seldom helpful in
doubtful cases; the torsion may also be intermittent
Urgent surgical exploration is required to confirm the diagnosis and save the testis
19.8 Phimosis
Defined as narrowing of the preputial ring that prevents retraction of the foreskin. At
birth the foreskin is usually non-retractile (physiological), this regresses with age
Percentage of boys with retractile foreskin by age - newborn' infants, 4%; 1 -year-old
boys, 50%; 4-year-old boys, 90%
Physiological phimosis is not an indication for circumcision
Pathological phimosis may rarely be a primary and congenital anomaly but is much
more commonly secondary to repeated attacks of infection that cause scarring
Difficulty with voiding and ballooning of the prepuce are commonest reasons for
referrals, though recurrent bacterial infections (balanoposthitis)may also occur
Usual infecting organism is Staphylococcus sp. - flucloxacillin or co-amoxiclav is
usually therapeutic
Chronic inflammation may lead to a rigid, fibrous foreskin
Can also be the result of balanitis xerotica obliterans. In this condition, equivalent to
lichen sclerosis atrophicus, the foreskin is thickened, inflamed, scarred and unyielding.
Circumcision is perfomed in these cases
Underlying urethral meatal stenosis is an underlying abnormality, and must be looked
for in these boys
19.9 Hypospadias
Hypospadias is an abnormality in which the urethral meatus is situated proximal to the
tip of the penis on its ventral aspect
Anatomically it is described by the position on the meatus as either:
Glanular
Coronal
Penile
Peno-scrota1
Perineal
Along with the abnormality of the position of the meatus there is often a degree of
deficient ventral development resulting in curvature of the penis (chordee)
A hooded foreskin is also evidence of a ventral deficiency in penile development
Incidence is around 1 :300 live births
Aetiology unknown in most cases - seen in conditions associated with deficient
testosterone secretion or responsiveness (intersex disorders)
Hypospadias with undescended testis should be investigated as potential cases of
ambiguous genitalia
Severe forms of hypospadias (e.g. peno-scrota1 and perineal) are associated with renal
tract (and occasionally other systems) anomalies
Surgical correction includes correction of any chordee, tubularization of appropriate
tissue to create a new urethra and skin cover. Tissues used to create the urethra include:
Native urethral plate
Prepucial skin (hence circumcision is contraindicated in patients with hypospadias)
Buccal or bladder mucosa
Postoperative complications include infection, wound dehiscence, meatal stenosis and
fistula formation